CN111479502A - Continuous automatic regulating system - Google Patents

Abstract

An apparatus for assessing intracranial biological impedance in a patient's head and assessing brain autoregulation includes a headset, a transmission and reception module, a processing and communication module, and at least one registration feature for registering the headset with the patient's head. The headset includes a housing containing control circuitry and a display on the housing. The transmission and reception module includes at least one reception antenna and at least two transmission antennas. The processing and communication module is configured to measure a phase shift in intracranial bioimpedance by measuring a phase shift in radio frequency signals transmitted by the at least two transmit antennas and received in the at least one receive antenna.

Description

Continuous automatic regulating system

This application is filed as a PCT international patent application on 12/11/2018 and claims priority benefit of U.S. non-provisional patent application serial No.15/810,762 filed on 13/11/2017, the entire disclosure of which is incorporated herein by reference in its entirety.

Cross Reference to Related Applications

This application is a partial continuation of U.S. patent application sequence No.15/635,986 entitled "Continuous flow Monitoring" filed on 28.6.2017, No.15/635,986 is a partial continuation of U.S. patent application sequence No.15/410,838 entitled "Difference of flow Volume Change" filed on 20.1.2017, No.15/410,838 is a partial continuation of U.S. patent application sequence No.7 entitled "Detection and Analysis of porous Varying currents L Using Magnetic Signals" filed on 3.9.2015, No.14/844,681 is a partial continuation of U.S. patent application sequence No.14/690,985 filed on 2015 20.20.18, No.14/690,985 is a partial continuation of U.S. patent application sequence No. 6855 filed on 2015.12.3, No. 9.19 is a partial continuation of U.S. patent application sequence No. for Detection and trend in fluids "filed on 2014.4.42.S. and No. 9.S. 14.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.s.

Technical Field

The present application relates to non-invasive, diagnostic, medical devices, systems and methods. More particularly, some embodiments of the present disclosure relate to devices, systems, and methods for monitoring changes in fluids in the brain or other parts of the body using volume-integrated phase-shift spectroscopy (VIPS).

Background

In many different medical environments, it would be advantageous to be able to detect changes in the composition and distribution of bodily fluids in a non-invasive manner. For example, monitoring changes in intracranial fluid content or distribution in Intensive Care Unit (ICU) patients is often critical. Standard care for these patients includes invasive monitors that require drilling a hole in the skull and inserting a probe, such as an intracranial pressure (ICP) monitor or microdialysis or "licox" probe, for measuring chemical changes in fluids in the brain. There is currently no continuous, non-invasive measurement technique available for detecting changes in cerebral fluid, such as changes that occur with bleeding or edema. Furthermore, many brain injuries are not severe enough to warrant drilling holes in the skull for invasive monitoring. Thus, for many patients with brain damage, no continuous monitoring technique can be used to alert clinical personnel when edema or hemorrhage may increase deleteriously. Instead, these patients are typically observed by a caregiver through clinical neurological examinations and cannot respond to a doctor or nurse until a change in fluid composition or distribution in the brain results in an observable impairment of brain function. In other words, there is currently no way to self-monitor intracranial fluid changes, and thus the ability to compensate for such changes is limited.

Volume-integrated phase-shift spectroscopy (VIPS) has previously been proposed for diagnosing cerebral fluid abnormalities. (VIPS may alternatively be referred to by other acronyms, such as magnetic induction phase shift spectroscopy (MIPS)), the proposed device has been patented and promising scientific research of prototype devices is described in the literature. For example, Rubinsky et al describe the use of VIPS for this purpose in U.S. patent nos. 7,638,341, 7,910,374, and 8,101,421, the disclosures of which are incorporated herein in their entirety (referred to herein as the "Rubinsky patent"). Additional details of the use and design of VIPS devices are described in U.S. patent 8,731,636 to Wyeth et al, which is incorporated herein in its entirety. However, no practical, mass-produced medical device based on VIPS technology has emerged to provide the benefits of such devices to clinicians specializing in brain therapy or other medical fields.

Therefore, a continuous, non-invasive measurement device and method for detecting intracranial fluid changes, such as changes due to hemorrhage or edema, is highly desirable. Ideally, such medical devices and methods would provide improved performance, usability, and manufacturability compared to currently available devices. Ideally, the devices and methods would be non-invasive or less invasive, and they would provide continuous monitoring of patient fluid changes over time. It would also be desirable if the apparatus and method could be used (or adapted to be used) to detect fluid changes in the brain and other areas of the body. Embodiments described in this application address at least some of these goals.

Disclosure of Invention

In one aspect of the present disclosure, a method for measuring intracranial bio-impedance in a patient's head to aid in detecting automatic adjustment of intracranial fluid may first involve securing a volume-integrated phase-shift spectroscopy (VIPS) device to the patient's head. The VIPS device may then be used to measure intracranial bio-impedance by measuring, at one or more frequencies, a phase shift between a magnetic field transmitted from a transmitter on one side of the VIPS device and a magnetic field received by a receiver on the other side of the VIPS device. Next, the method involves detecting, using a processor in the VIPS device, an automatic adjustment in the intracranial bioimpedance. In this specification, the term "phase shift" may be used in this application to indicate a phase shift between a transmitter and a receiver or any of a number of other signal changes and/or frequencies between a transmitter and a receiver, such as, but not limited to, phase shifts, currents, voltages, amplitudes, attenuations, and other signal changes resulting from the transfer of radio frequency energy through biological tissue. In any event, where the meaning of "phase shift" is not clear in this disclosure, the broader definition set forth is that intended.

In some embodiments, measuring the intracranial bioimpedance involves measuring a baseline phase shift of the intracranial bioimpedance at a later time and measuring at least a second phase shift of the intracranial bioimpedance. In such embodiments, detecting the autoregulation and/or intracranial compliance may involve identifying, with the processor, a change between the baseline phase shift and the second phase shift. The method may also involve defining a threshold corresponding to the autoregulation and/or intracranial compliance, wherein detecting the autoregulation and/or intracranial compliance involves identifying, with the processor, that a change between the baseline phase shift and the second phase shift meets or exceeds the threshold. The method may also involve defining an indicator based on a threshold. In some embodiments, the indicator may be one or more mathematical formulas, or may be based on a mathematical formula involving a phase shift across multiple frequencies or in only one frequency. In various embodiments, the identified changes may include changes in intracranial fluid, intracranial soft tissue, or both.

In some embodiments, measuring intracranial bio-impedance involves measuring a first phase shift through a left half of the patient's head and measuring a second phase shift through a right half of the patient's head (when referring herein to the patient's head or two halves of the intracranial space, these two halves generally refer to the right half and the left half, respectively, which are on opposite sides of a sagittal plane of the patient's head.) detecting autoregulation and/or intracranial compliance may involve identifying, with a processor, a difference between the first phase shift and the second phase shift that corresponds to an asymmetry between the left half and the right half of the patient's head.

In one embodiment, the method involves measuring bioimpedance asymmetry. In such an embodiment, an index (or "formula") may be used to measure the asymmetry, where the index is a function of the phase shift at a plurality of frequencies. The indicator is applied to the signals from the left transmitter to the receiver and from the right transmitter to the receiver and a percentage difference between the left indicator and the right indicator is calculated. The asymmetry can be shown as a percentage value, e.g. 0% asymmetry is fully symmetric, whereas 50% asymmetry means that the difference between the right and left indices divided by the average of the two is 50%.

Optionally, the method may further involve displaying an indicator on a display of the VIPS device to indicate the autoregulation and/or intracranial compliance response. The method may also involve raising an alert on the VIPS device for a predetermined response associated with the anomaly. In some embodiments, detecting an abnormality involves detecting a cerebral vascular resistance that may impair cerebral autoregulation in the brain of the patient. Such a method may also optionally involve measuring intracranial fluid after stimulation (such as drug administration) has occurred.

In some embodiments, detecting autoregulation and/or intracranial compliance includes detecting that a hemorrhagic stroke has occurred in the brain of the patient and the effect of the stroke on brain compliance/autoregulation. The method may further comprise identifying a hemisphere of the patient's brain in which the abnormality is located. In some embodiments, measuring the phase shift involves measuring intracranial fluid and any intracranial solid tissue between the transmitter and the receiver. In some embodiments, measuring intracranial fluid volume involves monitoring fluid volume over time by making multiple phase shift measurements to detect changes in intracranial fluid over time.

Securing the VIPS device to the patient's head may involve registering the VIPS device to the patient's head by bringing two support arms of a headgear of the VIPS device into contact with the patient's head just above the patient's ears. Optionally, registering the VIPS device to the patient's head may also involve contacting the nose bridge of the headset with the patient's nose. In some embodiments, the nose piece is adjustable and/or can be replaced with a differently sized nose piece. The method may also involve removing the VIPS device from the patient's head, securing the VIPS device back onto the patient's head (where securing involves re-registering the VIPS device to the patient's head), and repeating the measuring and determining steps.

In another aspect of the present disclosure, a method for measuring intracranial fluid in a head of a patient after stimulation of brain perfusion pressure in the brain of the patient may involve: securing the VIPS device to the head of the patient; measuring intracranial fluid of the VIPS device by measuring, at one or more frequencies, a phase shift between a magnetic field transmitted from a transmitter on one side of the VIPS device and a magnetic field received at a receiver on the other side of the VIPS device; and characterizing the brain's autoregulatory responsiveness with a processor.

In some embodiments, measuring intracranial fluid may involve measuring a first phase shift before stimulation and measuring a second phase shift after stimulation. The determining step may include measuring a change in intracranial fluid before and after the stimulation, which corresponds to a difference between the first and second phase shifts. Measuring intracranial fluid may include comparing a first bioimpedance in a left hemisphere of a patient's brain to a second bioimpedance in a right hemisphere of the patient's brain. Optionally, the method may further comprise comparing the cerebral autoregulation of the two hemispheres of the brain. In some embodiments, measuring intracranial fluid may include monitoring fluid volume over time to detect changes in intracranial fluid. In some embodiments, the stimulus may be an administered medication and/or a blood pressure cuff applied to the limb.

In another aspect of the present disclosure, a volume-integrated phase-shift spectroscopy (VIPS) apparatus for measuring intracranial fluid in a head of a patient may include a frame comprising: a front portion including a housing having a display; two arms extending from opposite ends of the front portion; and two encircling ends configured to encircle the back of the patient's head and over the ears. The VIPS apparatus further includes: at least one registration feature coupled with the frame to facilitate registration of the VIPS device with the patient's head; at least one receiver housed within the housing; a first transmitter in one of the two surrounding ends of the frame; a second transmitter in the other of the two looped ends of the frame, wherein the first and second transmitters and the at least one receiver are configured to measure at least one of a plurality of phase shifts or a plurality of amplitudes in the intracranial fluid; and a processor in the housing configured to receive data from the at least one receiver and process the data to generate display data descriptive of the intracranial fluid for display on a display of the housing of the VIPS device.

In some embodiments, the processor is configured to determine the presence of an occlusion of a blood vessel supplying the brain or a hemorrhagic stroke based on data received from the at least one receiver. In some embodiments, the processor is configured to determine whether an abnormality is present in the intracranial fluid based on data from the at least one receiver that meets or exceeds a predefined threshold. In some embodiments, the processor-generated display data may include a processor-generated indicator value. For example, the indicator value may be determined by data from the receiver meeting, exceeding, or falling below a predefined threshold. In some embodiments, the processor may be further configured to generate an indicator for alerting the user when the data from the at least one receiver meets, exceeds, or falls below a predefined threshold.

In some embodiments, the registration device includes two support arms extending from the frame to help support the device on the patient's head by resting at the junction of the patient's ears with the patient's head. For example, the two support arms may be rigid and the position of each of the two support arms relative to the frame may be adjustable. The registration device may alternatively or additionally include a nose bridge configured to rest on the nose of the patient to help support the device on the patient's head. For example, the nose piece may be detachable and configured to be replaced by a differently sized nose piece to adjust the fit of the device and/or it may be adjustable in size or position to adjust the fit of the device.

In some embodiments, the device is configured to detect at least two different fluid volumes, wherein one of the different fluid volumes comprises a first fluid volume in the right hemisphere of the brain and another of the different fluid volumes comprises a second fluid volume. The device may optionally include a power cable plug on the frame for connecting the device to a power source. The device may also optionally include at least one control button on the frame for controlling at least one function of the device. Each of the two arms of the device may comprise a flexible portion. The device may further include an accelerometer coupled to the frame for detecting movement of the patient, wherein the processor is configured to filter out the movement of the patient from the data received by the receiver. In some embodiments, the accelerometer may indicate the orientation of the device relative to gravity in order to record or alert the user as to the patient's head position, e.g., whether the patient's head is tilted to one side or the other.

In another aspect of the present disclosure, a method for measuring changes in intracranial fluid volume in a head of a patient may involve: securing the VIPS device to the head of the patient; measuring the fluid volume with a VIPS apparatus; and measuring the periodic change in amplitude of the fluid volume. In some embodiments, the method may further comprise measuring a periodic change in amplitude over time. The method may further comprise measuring the rate of periodic variation of the amplitude over time. In some embodiments, the method further comprises determining that a stroke has occurred in the brain of the patient based at least in part on the measurements. Some embodiments also relate to determining the hemisphere of the brain of a patient who has suffered a stroke. Such embodiments may also include determining whether the stroke is a hemorrhagic stroke or an ischemic stroke based on the measurement. In some embodiments, measuring the volume of fluid involves comparing a first volume of fluid in one hemisphere of the patient's brain to a second volume of fluid in another hemisphere of the patient's brain. In some embodiments, the patient may be receiving cardiopulmonary resuscitation and the method may further involve determining a rate of chest compressions based on the measurements.

In another aspect of the present disclosure, a volume-integrated phase-shift spectroscopy (VIPS) apparatus for measuring intracranial fluid volume in a patient's head may include a headband configured to be mounted circumferentially around the patient's head, a VIPS receiver attached to a front portion of the headband, circuitry attached to the headband and the VIPS receiver, a first VIPS transmitter attached to the headband separate from the VIPS receiver, and a second VIPS transmitter attached to the headband separate from the VIPS receiver and the first VIPS transmitter, wherein the first and second VIPS transmitters and the VIPS receiver are configured to measure a plurality of phase shifts and/or a plurality of amplitudes of the fluid volume in the patient's head. The device also includes a processor coupled with the headband and the circuitry and configured to determine that the plurality of phase shifts and/or the plurality of amplitudes are indicative of an occlusion of the blood vessel.

In some embodiments, the device is configured to detect at least two different fluid volumes, wherein one of the fluid volumes is a first fluid volume in the right hemisphere of the brain and another of the fluid volumes is a second fluid volume in the left hemisphere of the brain. In other embodiments, the apparatus may be configured to detect a first bulk fluid volume at a first time and a second bulk fluid volume at a second time, and the processor is configured to compare the first bulk fluid volume to the second bulk fluid volume.

Some embodiments may also include an accelerometer coupled to the headgear for detecting movement of the patient. The headband may also optionally include a stabilizer. For example, the stabilizer may be an adhesive. In some embodiments, the circuitry includes a flexible circuit coupled to the VIPS receiver, the first and second VIPS transmitters, and the processor. In some embodiments, the first and second VIPS transmitters are movable along the headband. In some embodiments, the VIPS receiver is movable along the headband. Some embodiments include at least one additional VIPS receiver attached to the headband. The device may further include at least a third VIPS transmitter attached to the headband.

These and other aspects and embodiments are described in further detail below with reference to the figures.

Drawings

FIG. 1 is a block diagram of a system for monitoring fluid changes in a body according to one embodiment;

FIG. 1A is a perspective view of a patient headgear used in the system of FIG. 1 according to one embodiment;

FIG. 1B is an exploded perspective view of a patient headgear used in the system of FIG. 1 according to an alternative embodiment;

2A-2F illustrate various embodiments of transmitter transducers and receiver sensors used in the system of FIG. 1;

FIG. 3 is a circuit diagram of a phase shift detection device according to one embodiment;

FIG. 4 is a simplified logic diagram of a waveform averager processor for use in the system of FIG. 1, according to one embodiment;

FIG. 5 is a simplified logic diagram of a phase shift measurement processor used in the system of FIG. 1 according to one embodiment;

FIG. 6 is a flowchart of operations used in the system of FIG. 1, according to one embodiment;

FIG. 7 is a block diagram of a system for monitoring fluid changes in a body corresponding to cardiac signals, according to one embodiment;

FIG. 8 is an isometric view of a system for monitoring fluid changes according to an embodiment, the system including a temporary stabilizer;

FIG. 9 is a system diagram of a system for monitoring fluid changes in a body according to an alternative embodiment;

FIG. 10A is a left isometric view of a patient wearing a headgear of the system of FIG. 9;

FIG. 10B is a front view of the patient wearing the headgear of FIG. 10A;

FIG. 10C is a right isometric view of a patient wearing the headgear of FIG. 10A;

FIG. 11 is a front isometric view of a system for monitoring fluid changes in a body according to another embodiment;

FIG. 12 is a graph illustrating calibrated phase shift measurements as a function of time according to one embodiment;

FIG. 13 is a graph illustrating the change in phase shift readings over time during application of a eustachian tube insufflation (valsalva) protocol according to one embodiment;

FIG. 14A is a perspective view of a headset for monitoring fluid changes in a body according to an alternative embodiment;

14B and 14C are top and bottom perspective views, respectively, of an alternative embodiment of a headset for monitoring fluid changes in a body;

FIG. 15 is a graph illustrating measurement of patient cerebral fluid volume over time after performing a cerebrovascular occlusion treatment;

FIG. 16 is a side view of a patient's head with a headgear device in place to monitor fluid changes in the body, according to one embodiment;

FIG. 17 is a schematic top view of a patient's head with transmitters and receivers positioned around the head as one example of a headgear or headband for monitoring fluid changes in the body, according to an alternative embodiment;

FIG. 18 is a block diagram of modular device interconnectivity for a fluid monitoring system according to an embodiment;

FIG. 19 is a diagram of a transmission module for a fluid monitoring device according to one embodiment;

FIG. 20 is a diagram of a receiver module for a fluid monitoring device according to one embodiment;

21A and 21B are schematic diagrams illustrating a system sequence in an interrogator/transponder portion of a fluid monitoring device according to one embodiment;

FIG. 22 is a block diagram of an interrogator module according to one embodiment; and

FIG. 23 is a block diagram of a transponder module according to one embodiment.

Detailed Description

Certain details are set forth below to provide a sufficient understanding of certain embodiments of the disclosure. However, some embodiments of the disclosure may be practiced without these specific details. Moreover, the particular embodiments of the present disclosure are provided by way of example and should not be used to limit the scope of the present disclosure to those particular embodiments. In some instances, well-known circuits, control signals, timing protocols, and software operations have not been shown in detail to avoid unnecessarily complicating the description.

Overall system architecture

FIG. 1 is a block diagram of one embodiment of a system 100 that may be used to detect fluid changes in the human brain. While the present description often focuses on using the system 100 to detect fluid changes in the brain, this or alternative embodiments of the system 100 may be used to detect/monitor fluid changes in any other part of the body. Accordingly, the exemplary descriptions provided herein for the brain should not be construed as limiting the scope of the invention as set forth in the claims.

In some examples, the system 100 may include a laptop computer 102 or other computing device, a processing unit 104, and a patient headset 106. the system 100 may be controlled, for example, by a Windows L-based overview language program running on the laptop computer 102. the program generates a Graphical User Interface (GUI) that is displayed on the screen of the laptop computer 102. after the headset 106 is placed on the patient, a clinician operating the system 100 may initiate monitoring through mouse controls, where the headset 106 may resemble an elastic headband or bandage.

The laptop computer 102, which may be an external computer relative to the patient headset 106, may have a USB serial link to the processing unit 104. This USB link may be electrically isolated to meet applicable medical device requirements. The processing unit 104 may derive power from a standard universal AC line power connection consistent with international standards. All internal electronics of the processing unit 104 may be powered by a medical grade low voltage DC power supply, which complies with applicable standards for patient isolation, line-to-neutral, chassis and patient leakage, and earth-to-ground continuity, EMI susceptibility and emissions, as well as other standard medical equipment requirements.

The laptop 102 may initiate phase-shift data collection and record the data, along with other relevant data and state information, in a file on the hard drive of the laptop 102.

A GUI on the laptop 102 may control the operation of the system 100 and may include controls and status indications that guide the clinician through the installation of the patient headgear 106 and preliminary self-testing of the entire system 100. If the self-test passes, the clinician is instructed to begin monitoring. During monitoring, phase shift angle versus frequency data will be collected from the USB interface and appropriate status and alarm methods applied to the data. If additional action or emergency response is indicated, the clinician may be notified. The data of the phase shift versus frequency and additional state information are recorded in the laptop 102 for later reference. "sanity checking" of data and other built-in test features may run continuously in the background, and if a fault is encountered, various severity levels will generate an alert or interrupt the operation of the system 100.

In some examples and as shown in fig. 1, the architecture of the hardware and firmware in the processing unit 104 and the patient headset 106 may be optimized to achieve the desired phase measurement accuracy and stability while using a minimum number of custom electronic components. For example, in one embodiment and referring to FIG. 1, system 100 may include several highly integrated small off-the-shelf components. The system 100 may include three Field Programmable Gate Arrays (FPGAs) 110, 112, 114 in the processing unit 104, which are programmed with appropriate firmware. One FPGA110 can synthesize a time-varying signal to provide to a transmitter (which may alternatively be referred to as a transmitter) 120 to generate a magnetic field, a second FPGA112 can collect and average digital samples of the transmitted and received magnetic fields, and a third FPGA 114 can measure a phase shift between the transmitted and received signals representative of the transmitted and received magnetic fields.

A microcontroller 118 may also be included in the processing unit 104 and may supervise the actions of the three FPGAs 110, 112, 114 and communicate with the laptop 102 (e.g., by communicating phase data results). The microcontroller 118 may also provide an interface between the external laptop 102 (via the electrically isolated USB interface) and the FPGAs 110, 112, 114 for real-time signal processing of data from the headset 106. The microcontroller 118 may also perform other miscellaneous functions, such as interfacing with basic user controls, including power-up, initiation of data collection, setting of the frequency synthesizer 110, internal temperature monitoring, power supply monitoring, and other system status monitoring and fault detection tasks.

In one embodiment, the processing unit 104 may include an off-the-shelf electronic signal generator (such as Techtronix arbitrary waveform generator model 3252), and a digital oscilloscope (such as L eCry model 44 xi).

The architecture of the system 100 shown in fig. 1 may be relatively flexible, allowing for improvements in all phases of data collection, data processing, and data interpretation (e.g., clinical alerts) through relatively simple software or firmware modifications. The FPGAs 110, 112, 114 can effectively act as parallel processors to enable data collection and processing to occur in near real time. Thus, the amount of phase data transmitted to laptop 102 via microcontroller 118 and archived for later reference may be reduced, thereby requiring less computing time on laptop 102 to process the data. This in turn may free the laptop 102 to check data consistency and apply the methods necessary to alert the clinician that corrective action needs to be taken.

While the processing unit 104 in fig. 1 has been illustrated and described as a relatively flexible embodiment, in other examples, the diagnostic system 100 may be an embedded system with custom electronic components specifically designed for use in the diagnostic system 100. For example, one or more analog-to-digital (a-to-D) converters may be located in the processing unit 104, which may be physically separate and apart from the headset 106, or may be integral with the headset 106 (e.g., in the custom system 100, the headset 106 may include all electronics and processing equipment needed to capture and process the phase shift information). Also, the functions performed by three FPGAs can be combined into one FPGA. In general, any suitable architecture may be used.

Returning again to fig. 1, the system 100 may also include a headset 106 having a transmission module (such as one or more transmitters 120 and one or more receivers 124), the details of which are explained in more detail below. In one example, the headset 106 includes a single transmitter 120 and a single receiver 124, while in other examples, the headset 106 includes multiple transmitters 120 and/or multiple receivers 124. For example, the headset 106 may include one transmitter 120 and two receivers 124. If multiple receivers 124 are placed at different locations on the patient's head, they may allow the clinician to triangulate the location of fluid changes (e.g., intracerebral hemorrhage from a blood vessel or tumor) and/or image the bioimpedance of the patient's brain. In other examples, the headset 106 may include multiple transmitters 120 that may generate magnetic fields of different or similar frequencies. If different frequencies are used, the single or multiple receivers 124 may be able to distinguish between the frequencies of several transmissions, for example to further distinguish the type of fluid change. As discussed in more detail below, other types of transmission characteristics (such as time transmission, waveform, frequency, attenuation, amplitude, and/or variations in additional waves) may be used to identify a particular transmitter for a particular signal.

In some examples, in addition to positioning the receiver 124 elsewhere on the patient's head, additional receivers may be positioned on the same side of the patient's head as the transmitter 120 (e.g., the receiver may be concentric with the transmitter 120, or may circumscribe the transmitter 120, or may be placed in a separate plane from the transmitter 120) in order to obtain a measurement of the transmitted magnetic field from the transmitter (not shown in fig. 1). In other examples, the emitted magnetic field may be sampled from the transmitter 120 in another manner, such as by measuring a current and/or voltage present on the transmitter 120. In some examples and with reference to fig. 1, the patient headset 106 includes a/ D converters 122, 126 for one or more of the transmitter(s) 120 and/or receiver(s) 124 proximate to the respective transmitter(s) 120 and/or receiver(s) 124 themselves-e.g., in some examples, the a/D converters may be located on the same printed circuit board as the respective transmitter(s) 120 or receiver(s) 124.

However, in other examples, the analog signals are not converted to digital signals until after passing through one or more coaxial cables (or other transmission lines) connected to a separate processing unit (e.g., processing unit 104 shown in fig. 1). In these examples, various techniques may be employed to reduce cross-coupling between, for example, a coaxial cable carrying a signal indicative of a transmitted magnetic field from transmitter 120 and a coaxial cable carrying a signal indicative of a measured magnetic field from receiver 124. For example, a relatively flexible RF-316 double shielded cable may be used to increase the isolation between two cables, or in other examples, a triple shielded cable may be used. As another option, a highly flexible PVC or silicone tube may be provided around the coaxial cable from the receiver 124 and/or transmitter 120.

Referring again to the headset 106 shown in fig. 1, for repeatable readings, it may be important for the transmitter 120 and receiver 124 not to move during operation of the system 100, as such movement may introduce errors in the phase shift measurements. To overcome such errors, in some examples, the transmitter 120 and receiver 124 may be mounted in a rigid manner, such as in a device similar to a helmet 140, an example of the helmet 140 being shown in fig. 1A. The helmet 140 may provide the necessary support and rigidity to ensure that the transmitter 120 and receiver 124 remain stationary relative to each other and relative to the patient's head. However, such a helmet 140 may be uncomfortable or impractical for use on a patient when the patient is lying down. Also, it is not practical in some clinical situations to have the patient wear the helmet 140 as desired for several days.

Thus, in an alternative embodiment, and referring to fig. 1B, a headgear 129 (such as an elastic band 129) is used to hold the transmitter 120 and receiver 124 against the patient's head. The transmitter 120 and receiver 124 may be mounted on the headgear 129, for example, by securing them within pockets of the headgear 129 or using stitches, rivets or other fasteners. The transmitter 120 and receiver 124 may be spaced a fixed distance from the skin surface by incorporating a non-conductive spacing material 127, such as plastic or fabric. The spacers 127 may be used for the purpose of maintaining a fixed distance between the transmitter 120 and receiver 124 and the skin, for example, to reduce variability in capacitance between the transmitter 120/receiver 124 and the skin. In some embodiments, the spacer 127 may be, for example, a plastic acrylic disc. Rubber, medical adhesive, or other materials may also or alternatively be used for the spacer 127, and may be placed at the skin interface surface of the transmitter 120 and receiver 124 to help prevent them from moving during use.

In some embodiments, the headgear 129 may be placed on the patient's head across the forehead and around the back of the head; or in other configurations a different belt or other device may be placed, including around the patient's chest, arms, or legs. In other words, any suitable positioning device may be used to properly position the transmitter 120 and receiver 124 near the region of the patient's body under investigation, the headgear 106, 129 and headband 129 described herein being merely examples. Additional features, such as chin straps or overhead connections, may be added to the headgear 129 to provide additional stability and to provide features on which to mount additional transmitters 120 or receivers 124. Since patients often lie on the pillow, a convenient location for electrical components and cable terminations may be the overhead. For example, a bridge from a point near each ear may be created so that the electronics can be mounted overhead, away from the surface on which the patient may lie. Lightweight, low profile components can be used to maximize comfort and minimize the tendency of the headgear to move on the patient's head after it is in place.

In headgear 129 designs, the headband 129 may be made of elastic, rubber, acrylic, latex, or other flexible material, and may be elastic or inelastic. The headgear 129 may be made of inexpensive materials, and thus the headgear may be a disposable component of the system. Alternatively, the headgear 129 may be reusable. If it is reusable, the belt 129 may be washable so that it can be cleaned between patients, or periodically for the same patient. The washable material may include plastic, rubber, silicone, fabric, or other materials. The headset 106 may also include mounting means for securing electronic components and routing cables to prevent them from interfering with the patient or clinical personnel.

In some embodiments, including those using a headband 129, to reduce relative motion between the transmitter 120/receiver 124 and the patient, one or more stabilizing agents 128 may be used. The stabilizing agent 128 may be custom molded to the patient's body to hold the transmitter 120 and/or receiver 124 in place. As an example of a stabilizer 128, a trained clinician may use a low melting point plastic to mount the transmitter 120/receiver 124, similar to an orthopedic casting made of the same material. Other customizable shaped materials and methods may be used, such as materials that polymerize over time, or materials that activate by heat or chemical reaction (such as materials used to make orthopedic casts or splints).

Referring now to the exploded view of fig. 1B, the operation of one embodiment using the headgear 129 will be described, but it will be understood that a similar strap 129 may be used to monitor fluid changes in other parts of the body, such as a bandage tied to a leg or arm. Each transmitter 120/receiver 124 may first be coupled to a respective spacer 127 by, for example, screws or other fasteners such as glue. The transmitter 120 and corresponding spacer 127 may then be positioned on the patient's head, and a stabilizing agent 128 may be positioned around the transmitter 120/spacer 127 to stabilize the transmitter and help prevent movement. The stabilizer 128 may need to be immersed in water or otherwise prepared for use prior to being placed around the transmitter 120/spacer 127. Once the stabilizer 128 has fixed the transmitter 120/spacer 127, another stabilizer 128 may be used in a similar manner to stabilize the receiver 124 and spacer 127. The stabilizing agent 128 may cure or dry out to perform a stabilizing function. A headgear (such as a headband 129) may then be wrapped around the stabilizer 128 and the transmitter 120/spacer 127 and the receiver 124/spacer 127. However, in some embodiments, instead of using a stabilizer, a headband 129 may be used to directly position the receiver 124/spacer 127 and transmitter 120/spacer 128 on the patient's head. In still other embodiments, and as mentioned above, the headband 129 may include pockets for the transmitter 120 and receiver 124, with the material of the headband 129 itself acting as a spacer. Also, in some embodiments, the headgear 129 may have a non-slip material applied to the inside of the headgear 129 to help prevent the headgear 129 from slipping on the patient's head.

Other examples of headgear 129 may also be used. Fig. 8 illustrates an isometric view of an example of the headgear 129. In this embodiment, the headgear 129 may be substantially similar to the headgear 129 shown in fig. 1B. However, in this example, the stabilizer 800 may be included in the headgear 129. In addition, the headgear 129 may include a flexible circuit 802 or other wiring mechanism that may extend between the processing unit 104 and the transmitters and receivers 120, 124. The headgear 129 may also include securing elements 804, such as headgear, elastic, etc., that may flex and/or stretch to secure the headgear 129 about the patient's head.

The stabilizing agent 800 temporarily secures the headgear 129 on the user's head (or other desired location), but may allow the headgear 129 to be removed when monitoring is no longer desired. Stabilizer 800 may generally be a skin compatible adhesive. The stabilizing agent 800 may be a double-sided adhesive, where one side may be secured to the headgear 129 (such as to the flexible circuit 802 or the fixation element 804) and the other side may be secured to the patient's head. As another example, the stabilizer 800 may be an adhesive, such as glue or another similar fluid or gel having adhesive properties. As a specific example, the stabilizer 800 may be a hydrogel.

In embodiments that include the stabilizing agent 800, the stabilizing agent 800 stabilizes and locks various components of the headgear 129 to specific locations on the patient's body. This helps to ensure accurate readings because the electronics (e.g., transmitter and receiver) and circuitry 802 can maintain substantially the same orientation and position even if the patient moves. Additionally, the stabilizing agent 800 may also help prevent deformation of the electronics because the flexible extensions of the transmitter and receiver (e.g., the flexible circuit 802) may be shaped to bend or wrap around in one dimension of the patient's head (or other monitored area) but not substantially bend or stretch in the other dimension. As one example, the lateral position of the transmitter and receiver 120,124 (i.e., front to back) and the flexible circuit 802 may remain stable when pressed against the surface of the patient's head.

Various embodiments include mechanical mechanisms for determining proper placement, alignment, and attachment to specific locations on the patient's body. For example, the helmet 140 in fig. 1A, the headband 129 in fig. 1B, the headgear 906 of fig. 9, and the headgear 950 of fig. 11. These mechanisms help to ensure placement accuracy and repeatability, which in turn helps to ensure accuracy and precision of readings. Further improvements in mechanical stability and repeatability can be enhanced by sensors detecting and monitoring the point or series of contacts with the patient's body. For example, sensors may be placed on the arms 962 of the headgear 950 of fig. 11 such that they detect when the arms 962 are in contact with the location where the scalp meets the patient's ears. Additionally or alternatively, a sensor can be positioned to detect when the back of the lens 960 or the top inner edge of the frame is in the correct position on the forehead. Further, one or more sensors may monitor the continuous optimal placement of the headgear during the measurement sequence. If the headgear is removed from the desired location at any time, the one or more sensors will send a signal to the processing unit 104, which processing unit 104 can in turn inform the user to correct the placement of the headgear and/or identify the measured data as being undesirable due to the placement. A non-exhaustive list of sensor types that may be used in these embodiments includes impedance, capacitance, conductivity, optics, heat, and distance.

Another example of a system for detecting a volume of fluid in a body will now be discussed. Fig. 9 is a diagram of a system 900 for detecting a volume of a fluid. Fig. 10A-10C illustrate various views of a headgear 906 of a patient worn system 900. Referring to fig. 9-10C, the system 900 may include a headset 906 or support structure, a processing unit 104 having a network/communication interface for communicating with one or more external devices, one or more transmitters/receivers 124, and a computing device 902. The computing device 902 may communicate with the headset 906 and/or the processing unit 904 via the network 920. The network 920 may be, for example, WiFi, bluetooth, wireless, etc., and in many embodiments may be wireless to allow data to be transmitted from the processing unit 904 and the headset 906 to the computing device 902 without the need for cables, etc. In these embodiments, the computing device 902 may be external to the headset 906 in that the computing device may be a stand-alone device that communicates with the headset 906 via a wireless communication pathway. In other embodiments, the networking interface may communicate with an external computer and/or network via one or more wired pathways.

The computing device 902 may be substantially similar to the computer 102 of fig. 1. In some embodiments, the computing device 902 may be portable to allow an attending physician to more easily transport the computing device 902 between different patients. However, in embodiments where portability may not be required, the computing device 902 may be substantially any other type of computer, such as, but not limited to, a server, a desktop computer, a workstation, and the like. It should be noted that computing device 902, processing unit 904, and/or headset 906 may include networking interface components that provide a communication pathway from each respective device to network 920.

Referring to fig. 10A-10C, the headgear 906 will now be discussed in more detail. The headgear 906 in this example includes a processing unit 904 and transmitter/ receivers 120, 124. The integration of the processing unit 904 and transmitter/receivers 120,124 onto the signal device allows the sensing unit to be more portable, easier to place on the patient, and enhances the mobility of the patient while wearing the device. Furthermore, as discussed in more detail above, in embodiments where the processing unit 904 may do most of the processing of data near the transmitter/receivers 120,124, the risk of errors is reduced and the signal-to-noise ratio may also be reduced.

In one embodiment, the headgear 906 includes a front support structure or frame 910 that defines the front of the sensing device. The anterior support structure 910 may support the processing unit 904 and define a frame for two lenses, e.g., for the left and right eyes of a patient. In embodiments where no lenses are required, such as when the patient does not need to wear glasses or have other eye protection, the lenses may be omitted to provide clarity to the user. The front support structure 910 may vary as desired based on the size and configuration of the processing unit 904.

With continued reference to fig. 10A-10C, the headgear 906 may also include two arms 912 extending from each end of the front support structure 910. The arm 912 is configured to wrap around the head 930 of the patient and be supported over and/or on the ear 912 of the patient. The arm 912 may include a contoured portion that better fits the patient's head 930 and/or ear 912, and may also help hold the device in place on the patient's head 930. The headgear 906 may be adjustable, and in some embodiments may include a securing strap 922 connected to an end of each arm 912. The securing strap 922 is configured to tighten around the patient's head 930 and secure the headgear 906 in place. For example, a fastener or other device may selectively adjust the length of the securing strap 922 and help secure it around the head 930.

As discussed above, in this example, the headgear 906 is configured to be portable and the transmission module (e.g., transmitter/receiver 120, 124) is connected to the headgear 906. In one example, such as the example shown in fig. 10A-10C, the transmitter/receivers 120,124 may be connected to the arms 912 of the frame so that when the headgear 906 is placed on the patient's head 930, the transmitter and receivers 120,124 will be positioned opposite each other and oriented to receive and transmit signals through the user's head 930. The transmitter and receiver are configured to communicate with each other and are positioned to transmit or receive signals, respectively, to a corresponding device.

The transmitter/receivers 120,124 or transmission modules may communicate with and receive power from the processing unit 904. For example, a plurality of connection lines 934 may extend from the processing unit 904 and electrically connect the transmitter/receivers 120,124 to the processing unit 904. The connection lines 934 may transmit power from a power source, such as a battery received within a battery slot 936 on the processing unit 904, as well as data and/or signals from the processing unit 904. Further, the transmitters and receivers 120,124 can transmit data to the processing unit 904, and the processing unit 904 can then transmit data to the computing device 902. For example, receiver 124 may transmit the received signal to processing unit 904, and processing unit 904 may then process the signal and transmit the data to computing device 902 via network 920.

It should be understood that the arrangement and configuration of the headgear 906 and the processing unit 904 may be varied as desired. For example, in another example, the communication lines 934 may be omitted or incorporated into a frame or support structure of the headgear 906. Fig. 11 is an isometric view of another example of a headgear 906. Referring to fig. 11, in this example, the headgear 950 may be substantially similar to the headgear 906 shown in fig. 10A-10C, but the communication wires 934 may be incorporated into the material and/or structure of the frame 910. Further, in this example, the headgear 920 may include a lens 960 in the front support structure, which may be modified based on the needs of the patient. Arms 962 of headgear 950 may extend from each end of frame 910 and are configured to support transmitter/receivers 120,124 thereon. Further, in this example, the third transmitter/receiver 120,124 may be configured on the back side of 904 adjacent the forehead. As can be appreciated, the processing unit 904 may be smaller and centered on the frame 910, which provides better mobility for the patient while wearing the headgear 906. Moreover, because the processing unit 904 is significantly smaller, it may be able to better remain in place and more accurately transmit data to and from the computing device 902 and/or the transmitter/ receivers 120, 124.

In some embodiments, the processing element 904 or unit is configured to provide transmission data corresponding to one or more received magnetic field data received by the transmitter/receiver to a networking interface, which in turn transmits the transmission data to the external computing device 902. In these embodiments, the processing element 904 may convert analog data received from the transmitter and receiver to digital data before transmitting the data to the external computing device 902. This allows data transfer speeds between the headset and the computing device 902 to be increased and more reliable.

In various embodiments, the devices and methods described herein may be used for fluid measurements (often fluid change measurements) in all parts of the body and for a variety of medical diagnostic applications. In various embodiments, the configuration of the emitter and detector (which may alternatively be referred to as a receiver) coils may be modified to suit the body and/or region of the diagnostic application involved. For example, for applications involving a limb (such as an arm), or where it may be more important to measure fluid content at a shallow depth in tissue, the transmitter coil and detector coil may be placed on the same side of the subject tissue. A coplanar arrangement may be suitable. Since the coils can be separated by a shorter distance, the received signal strength can be much greater and the size of the coils can be reduced. In various alternative embodiments, coils may be in a side-by-side coplanar arrangement or a concentric coplanar arrangement using coils having different diameters. In some embodiments, it may be more appropriate to place the plane of the coil at a small angle to conform to the shape of the body part under study.

With various examples of the described system, a method of operating the system will now be described in more detail. Referring now to FIG. 6, one example of the operation of the system 100 will now be briefly described, it being understood that the various operations shown in FIG. 6 will be described in greater detail below, and that various alternative methods and modes of operation will also be described below. Beginning with operation 501, the system 100 is powered up and performs a self test. If the system 100 fails the test, a stop or failure indicator is displayed on the laptop 102 in operation 502. If the system 100 passes the power-on self test, operation moves to operation 504. Also, throughout the operation of the system 100, the continuous status monitor may run in operation 503 and if the status monitor determines that the system 100 is malfunctioning, the system may display a stop or failure indicator in operation 502.

Once the system 100 self-tests by power-up and operation has moved to operation 504, the frequency synthesizing FPGA110 can be initialized and begin providing transmit signals to the transmitter 120 in operation 504. In operation 505, the waveform averager FPGA112 may begin collecting and averaging waveforms (e.g., fluid data) from the transmitter 120 and the receiver 124. The averaged waveform may be provided to the phase shift measurement FPGA 114, which may determine the phase shift between the transmitter 120 and receiver 124 waveforms beginning at operation 506 and calculate the final phase calculation of interest in operation 507. The phase calculation may be provided to the laptop 102 in operation 508. At any time after operation 505, the frequency synthesizer FPGA110 may provide another frequency to the transmitter 120, and the process may repeat for the next frequency. Multiple frequencies can be transmitted from the transmitter 120 and the subsequent phase shift calculated. For example, the frequency synthesizing FPGA110 may provide the next frequency in the repeated operation 504 while the phase shift measuring FPGA 114 measures the phase shift from the waveform of the previous frequency, or the frequency synthesizing FPGA may not provide the second frequency until the phase calculation has been provided to the laptop in operation 508. In alternative embodiments, the transmitter may transmit a single frequency and harmonic frequencies simultaneously, or by using multiple frequency generators, for later separation using techniques such as Fast Fourier Transforms (FFTs). Transmitting multiple frequencies simultaneously may be advantageous for noise cancellation, motion suppression, and other purposes.

Transmitter(s) and receiver(s)

One range of electromagnetic frequencies suitable for the inductive phase shift measurement based system 100 for cerebral fluid diagnostics is in the Radio Frequency (RF) range of about 20MHz to 300MHz, but other frequencies may be used, such as between 1MHz and 500MHz, between 3MHz and 300MHz, and so on. The selected frequency may provide a relatively low absorption in human tissue, a good signal with respect to noise factors, such as capacitive coupling and signal line crosstalk, and ease of accurate phase measurements.

Previously, some examples of transmitters (and corresponding receivers) that emit (and sense) magnetic fields in these frequency ranges were constructed from a thin inductive coil of several circular turns placed so that the plane of the coil was parallel to the circumference of the head. The coils of these previous transmitters and receivers have a diameter of 10cm or more and 5 turns or more. However, these relatively large transmitter and receiver coils are bulky and have resonance in the frequency range of interest for VIPS detection of fluids in the human brain. When a transmitter or receiver coil is operated at a frequency close to one of its natural resonant frequencies, the measured phase shift may depend to a large extent on the magnitude of the parasitic capacitance of the coil itself, and very small variations and/or environmental effects due to motion of either coil may cause large changes in the phase shift, resulting in unacceptable noise in the measurement of the phase shift.

Thus, in some embodiments of the present disclosure, the lowest natural resonant frequency of the transmitter 120 and/or receiver 124 may be higher than the expected frequency of the magnetic field to be transmitted. In some examples, the transmitter 120 may include a coil as a magnetic field generator or transducer. For symmetry considerations, this same or similar coil may act as a magnetic field sensor in the receiver 124. In either case, the first self-resonant frequency generally increases as the coil diameter and number of turns (i.e., loops) decreases. The limitation is therefore that for a coil with a single loop, the loop has a very small diameter. However, as the diameter of the ring decreases, the magnetic flux intercepted by the ring will decrease by a factor equal to the diameter squared ratio. Also, the induced voltage in the loop decreases, resulting in a smaller signal from the loop in the receiver 124 acting as a magnetic field sensor. Therefore, there is a practical limit to diameter reduction. However, in some embodiments, an additional increase in self-resonant frequency may be achieved by using transmission line technology in the construction of the transmitter 120/receiver 124.

An alternative to using coils designed for a relatively constant phase shift over a wide bandwidth is to add external reactive components in a series-parallel network to tune out the phase shift at a single frequency or a small number of discrete frequencies. This concept works best if an approximation of each frequency is known and the number of discrete frequencies is small before the entire system is designed. Phase shift tuning can be automated and controlled by software using switched or motor driven adjustable components. An advantage of tuning to a constant phase shift is that it provides more freedom in selecting the size and shape of the coil. Using larger coils may increase the detected signal strength and provide a field shape that optimally matches the brain or other body part being sampled.

In one embodiment, referring to fig. 2A, a single loop 250 having a high self-resonant frequency and an associated stable phase response below the self-resonant frequency may be constructed using a shielded transmission line, such as a coaxial cable, buried stripline on a printed circuit board, shielded twisted pair, twinaxial cable, or triaxial cable. . The loop 250 may be used as a magnetic field generator in the transmitter 120 or as a magnetic field sensor in the receiver 124. The shielded transmission line may comprise a first conductor as a shield 251, which at least partially encloses a second conductor. The first conductor or shield 251 may be grounded and may form a faraday cage around the second conductor. The second conductor may provide an output signal in response to the changing magnetic field, and due to the faraday cage, the second conductor may be shielded from external electrostatic influences and capacitive coupling. For example, in one embodiment, a single loop 250 of buried striplines may be sandwiched between two ground planes in a printed circuit board. A plurality of vias may extend between the two ground planes, the spacing of the vias being determined by the wavelength of the electromagnetic field to be transmitted and/or received, and the vias together with the two ground planes form an effective electrostatic or faraday cage around the buried stripline loop 250. In other embodiments, other types of transmission lines with external shielding (such as coaxial cables) may be used to form a faraday cage to reduce external electrostatic effects on the ring 250.

In a single loop 250 embodiment of the transmitter 120 or receiver 124, the voltage of the loop 250 may not be in phase with the current of the loop 250 due to the inductive nature of the single loop 250. This phase error may be detected and accounted for during initialization of the diagnostic system 100, as described below. However, in some embodiments of a single transmitter loop 250, and referring to fig. 2B, a balun 254 may be added to eliminate the need to correct for such phase errors. In still other embodiments, and referring to FIG. 2C, a second separate, smaller, concentric ring 260 is used to sense the transmitted magnetic field and provide a current representative of the magnetic field to the A/D converter. In some examples, the second concentric transmitter ring 260 may be the same size as the corresponding receiver ring (e.g., in the receiver 124) in order to have a proportional signal and good uniformity between them, while in other examples, the receiver ring may be larger than the second concentric transmitter ring 260 in order to be more sensitive to the received magnetic field. In those transmitters 120 having a second concentric transmitter ring 260, and referring to fig. 2D, a balun 264 may also be used on this second concentric ring 260 to balance the sensed voltage and current. Further, for the single turn receiver loop 250, a balun 254 may be similarly added to balance its performance, similar to that shown for the transmitter cable in fig. 2B.

Referring now to fig. 2E, in another embodiment, the transmission line concept may be extended from building a single loop, single ended device to building a dual loop 270, which may be double ended or "balanced," for use as the receiver 124 (or symmetrically for use as the balanced transmitter 120). In fig. 2E, four conductive (e.g., copper) layers 271, 272, 273, 274 may be formed on the printed circuit board as shown, with a tri-layer dielectric material (not shown in fig. 2E) coupled between the four conductive layers 271, 272, 273, 274 when vertically stacked. The top layer 271 and the bottom layer 274 may be grounded, thereby forming an electrical shield. Furthermore, there may be small linear discontinuities 271A, 274a in both the top layer 271 and the bottom layer 274, so that the ground planes 271, 274 do not function like additional shorted turns. Between the top ground plane 271 and the bottom ground plane 274, a + ring 273 and a-ring 272 may be located, and leads from both rings 272, 273 are coupled to balanced amplifiers (not shown in fig. 2E). In some examples, + ring 273 and-ring 272 may be center tapped. The inner diameter of the two rings 272, 273 may be about 1 inch and may be slightly larger than the inner diameter of the circular voids in the two ground planes 271, 274. In some embodiments, the thickness and dielectric constant of the dielectric material, the width and thickness of the conductive material forming the rings 272, 273, the spacing of the ground planes 271, 274, and so forth may be selected such that the dual ring 270 has an impedance of approximately 50 ohms in order to match the transmission line to which it is to be coupled. In this manner, the self-resonant frequency of dual-loop structure 270 may be greater than 200MHz in some examples.

Still referring to fig. 2E, for the dual ring 270 used as a magnetic field sensor in the receiver 124, external noise coupling into the system 100 from environmental changes in the magnetic field due to environmental EMI sources or motion near conductors or magnetic materials may be reduced due to common mode rejection of the differential amplifier to which the two rings 272, 273 are coupled. Thus, when used as a receiver 124, a differential amplifier coupled to the loops 272, 273 may allow the diameter of the loops 272, 273 to be reduced while maintaining the output signal level at an appropriate level for transmission to the remote processing unit 104 (e.g., for systems where one or more a/D converters are not located directly in the headset 106). In some embodiments, the amplifier power gain may be approximately 40 db. Low cost wide bandwidth amplifiers providing a gain of 40db for the power level of interest are readily available from commercial suppliers in small packages with negligible phase shift variation over the frequency range of 20MHz to 200 MHz.

Referring to fig. 2F, as suggested, the dual ring 270 of the receiver 124 for balancing has a similar application as the transmitter 120 that generates the magnetic field. The method for constructing the balance of the transmitter 120 may result in common mode cancellation of noise in the transmitted magnetic field due to the opposite winding directions of the dual rings, thereby reducing noise in the transmitted magnetic field that may otherwise be generated due to electrostatic or magnetic pickup from environmental factors.

Still referring to fig. 2E and 2F, in some embodiments, the two rings 272, 273 can be formed in different planes, or in other embodiments, the two rings can be fabricated in the same plane with concentric circular strip line traces (thereby reducing the number of layers required to fabricate the printed circuit board). Such a concentric design may be used for the transmitter 120 and/or the receiver 124.

Also, referring to any of fig. 2A through 2F, in examples where analog-to-digital conversion is not performed near the transmitter 120 or receiver 124, a resistive attenuator may be added to the printed circuit board and a surface-mounted resistor mounted therein to help reduce cross-coupling of the transmitter signal to the receiver signal in the cable through which the analog signal is transmitted, which may help improve the accuracy and stability of the phase measurement. The on-board attenuator may be significantly reduced in size and cost as compared to bulky discrete modular attenuators. Also, continuing with the example in which analog-to-digital conversion is not performed near the transmitter 120 or receiver 124, still referring to any of fig. 2A through 2F, one or more amplifiers may be provided to amplify the signals from the transmitter 120 and/or receiver 124 in order to reduce attenuation of the signals through the cable to the external analog-to- digital converters 122, 126. Still continuing with the example in which analog-to-digital conversion is not performed near the transmitter 120 or receiver 124, the voltages on the transmitter and receiver may be in phase with the currents on the respective transmitter and receiver, since the "balanced" transmitter and receiver shown in fig. 2E and 2F terminate in the 50ohm characteristic impedance of the coaxial line.

Referring now to fig. 3, an alternative design may include an amplifier 256 on the same printed circuit board as the ring 250. Including the amplifier 256 on the same printed circuit board as the loop 250 (e.g., for use as the receiver 124) may help increase the signal-to-noise ratio, which may be particularly useful for embodiments where analog-to-digital conversion is done away from the headset 106. Amplifier 256 may also be used in embodiments where analog-to-digital conversion of signals is performed near loop 250. As mentioned above, a balun may also be included on the printed circuit board between the loop 250 and the amplifier 256, which may help cause the coils to operate in a "balanced" mode. In balanced mode, capacitively coupled electromagnetic interference pickup or motion induced signal level fluctuations may be reduced or cancelled out, as they are typically equally coupled into the negative and positive leads of a balanced differential signal.

Initialization: aerial scanning to remove fixed phase errors

As suggested above, in some examples, the diagnostic system 100 may be initialized to calibrate the transmitter 120 alone, calibrate the receiver 124 alone, calibrate the transmitter 120 and receiver 124 to each other, and calibrate with other associated electronics, and so forth. For example, variations in the length of the leads and amplifier time delays in the signal paths from the transmitter 120 and receiver 124 may be detected during initialization and removed from the signal during signal processing to prevent fixed offset errors in the data. Also, any phase shift between the (measured) voltage and current in the single turn ring 250 can be detected.

In one embodiment, the initialization may be an "over the air scan" in which the transmitter(s) 120 and receiver(s) 124 are positioned such that only air is located between them, and the transmitter(s) 120 and receiver(s) 124 are positioned such that if they are placed on the head of an average patient, they are as far apart as possible. Once spaced, phase shift data is collected for different frequency ranges (as the errors may be constant across different frequencies or vary between different frequencies), and any phase shift errors of the system 100 may then be corrected during signal processing using the collected aerial scan values (e.g., by subtracting them from values obtained during operation of the system 100). Initialization may occur when the a/ D converters 122, 126 are in close proximity to the transmitter 120 and receiver 124 in the headset 106, when the a/ D converters 122, 126 are external to the headset 106, and so on.

Drive and sample signal generation

As mentioned above, because the phase shift caused by various tissue types and body fluids may vary with frequency, the diagnostic system 100 collects phase shift data for transmitted time-varying magnetic fields at multiple frequencies. The diagnostic system 100 shown in fig. 1 provides a flexible frequency synthesizer 100 within the processing unit 104, although in other embodiments the frequency synthesizer 110 may be provided in, for example, the headset 106. In some examples, this frequency synthesizer 110 may have a minimum 1MHz resolution in the range of about 20MHz to 200MHz (or alternatively, about 20MHz to 300MHz or about 10MHz to 300MHz or any of a number of other suitable ranges). The selectable frequency can be obtained from a single stable crystal controlled clock oscillator using standard digital phase locked loop techniques. As described above, the digital portion of the synthesizer 110 may be implemented in one of the FPGAs 110 in the processing unit 104. The synthesizer 110 may generate a substantially square wave clock signal for generating a magnetic field in the transmitter 120 as well as a sampling signal. In some embodiments, the sampling signal may be slightly offset in frequency (e.g., 10KHz) from the signal that generates the magnetic field. In some embodiments, the square wave signal used to generate the magnetic field may be amplified to correct its level, and may also be filtered to eliminate higher harmonics and achieve a low distortion sine wave at one or more fundamental frequencies.

In other cases, it may be advantageous to emphasize harmonics of the fundamental frequency when computing the phase using frequency domain techniques such as FFT processing of time domain data. For these embodiments, additional circuitry may be added after the fundamental synthesizer to make the rise time or fall time of the square wave or pulse waveform faster, thereby increasing the relative amplitude and number of higher harmonics. As mentioned previously, this embodiment allows for the generation of frequency "combs" with a single RF burst, and the processing of the captured time domain data from the emitter and detector using fourier techniques to produce simultaneous time dependent phase difference data sets for each frequency in the "comb". Capturing phase data from multiple frequencies simultaneously may yield significant advantages for separating desired information about a patient's cerebral fluid from motion artifacts or other effects that may affect a single scan of the frequencies, where the phase data for each frequency is measured at different times. In this case, sampling each frequency at different times introduces noise that may be difficult to detect or remove.

Since the signal used to generate the magnetic field is typically periodic, it may not be necessary to use a sampling frequency many times greater than the frequency of that signal to capture phase information from a single period of the waveform, but an undersampling technique may be employed in some examples. Undersampling is similar to heterodyne (heterodyning) techniques used in modern radios, where most of the amplifier gain and audio or video signal demodulation is performed at the much lower Intermediate Frequency (IF) stage of the electronics. In effect, undersampling allows the system to collect the same or similar number of sample points over a longer period of time without disturbing the phase information of the signal.

The use of undersampling may eliminate the need for high speed a/D converters (which are expensive and may involve many different wired connections) that would otherwise be required to capture enough phase samples from a single cycle of the waveform to accurately measure the phase angle. If lower speed A/D converters can be used, it is commercially and physically feasible to locate the A/ D converters 122, 126 near the transmitter 120 and receiver 124 loops 250, 270, as described above.

Thus, in some embodiments, one or both of the transmitted and received magnetic field signals may be undersampled (e.g., one sample or less per cycle), so samples taken over a much longer time interval may be used to capture an average record of the waveform than one cycle. To accomplish undersampling, the transmit signal and the sampled signal may be derived from a common clock signal, where the sampled signal is offset from the transmit signal frequency (or subharmonic frequency) by exactly a small amount. If the offset is, for example, 10KHz from the first harmonic frequency of the transmit signal, the result after a period of 100 seconds will be a valid picture of one cycle of the repeating transmit waveform with f/10000 individual samples. For a transmit signal frequency of 100MHz and a sampling frequency of 100.010MHz, 10000 undersampled individual samples of a single cycle of the transmit waveform are spaced at a resolution of 360/10000 or.036 degrees. As an alternative to undersampling, frequency conversion using standard non-linear mixing techniques prior to the a/ D converters 122, 126 may also be employed.

In other examples, the frequency of the magnetic field generator signal and the frequency of the sampling signal may be otherwise related, an example of which is described below with reference to frequency domain signal processing techniques. In still other examples, the sampling frequency may be relatively constant (e.g., 210MHz, while the generation frequency may vary over a wide range).

Converting transmitted and received analog signals into digital data

In some embodiments, the electronic phase shift measurement between the transmit and receive signals may be performed using analog signal processing techniques, while in other examples, the phase shift measurement may be performed after converting analog data to digital data by one or more a/ D converters 122, 126, as described above. The digital waveform may then be processed to obtain associated phase shift information. Processing digital data rather than analog data may facilitate sampling and averaging many cycles of a waveform, for example, to reduce the effects of random noise and even to reduce non-random periodic noise such as AC line pick-up at frequencies approaching 60Hz with appropriate techniques. Also, after reducing noise in the waveform data, many methods, such as correlation, may be employed to obtain accurate phase measurements using digital signal processing.

In some examples of the diagnostic system 100 described herein, a/D conversion of both transmitted and received signals is performed as close as practicable to the point of generation and/or detection of the magnetic field. For example, the A/D conversion may be performed in the headset 106 by miniaturized, single-chip, A/ D converters 122, 126 located integrally with printed circuits containing the transmitter 120 and receiver 124, respectively. For example, in one example, the a/D converter 122 for the transmitter 120 may differentially sample the voltage across the balanced output of the transmitter 120. For example, an a/D converter 126 for the receiver 124 may be located at the output of a wide bandwidth signal amplifier coupled to the receiver 124. By locating the a/ D converters 122, 126 on the headset 106 rather than in the remote processing unit 104 (but this may be the case in other embodiments described herein), it may be possible to reduce or eliminate the effects of phase shifts associated with motion, bending, or environmental changes on the cables carrying the analog signals to the a/ D converters 122, 126. Other sources of error that may be reduced or eliminated include standing wave resonances related to the cable length due to small impedance mismatches at the terminals, and cross-coupling between the transmit and receive signals on the interconnecting cables, which can generate phase errors due to waveform distortion. To achieve similar advantages in embodiments where the a/ D converters 122, 126 are not located near the transmitter 120 and receiver 124, a single cable may be used to carry the sampled signal to the transmitter and receiver a/ D converters 122, 126 in the processing unit 104, and/or in some embodiments, a high quality semi-rigid cable may be used between the two a/ D converters 122, 126.

Integrated operation and pipeline

Referring again to fig. 1, waveform data may be captured for both the transmitted and received magnetic fields (which may be undersampled in some embodiments), and the captured waveforms may be processed at least partially in real-time (or substantially real-time). As described herein, one FPGA112 can average the data of each of the two waveforms over many cycles to reduce noise. Another FPGA 114 can then use correlation techniques to perform phase shift measurements using the averaged waveform data. In some embodiments, pipelining may be used to speed up data throughput in order to collect phase data over multiple frequency samples. Transmitter 120 may generate a time-varying magnetic field at a first desired frequency, and waveform averager FPGA112 may perform the necessary number of waveform averages at this first frequency.

After the averager FPGA112 collects and averages all sample data points from the transmitter 120 and receiver 124, it can be passed to the phase shift measurement FPGA 114. In some embodiments, only a single transmit frequency is used in diagnosing fluid changes in the patient, but in other embodiments, multiple different transmit frequencies within a desired spectral range may be generated and corresponding data collected. In those embodiments having multiple transmit frequencies, the phase determination of a first transmit frequency may be made in the phase shift measurement FPGA 114 (using data acquired during the first transmit frequency), while the frequency synthesizer FPGA110 causes the transmitter 120 to generate a magnetic field having a second desired frequency of the spectral sweep, and the waveform data from the second transmit frequency is averaged (and thus pipelined) by the waveform averager FPGA 112. In other embodiments, the waveform averaging one transmit frequency may occur substantially simultaneously with recording multiple samples of the second frequency. In general, many different types of pipelining may be used (e.g., two or more portions of signal generation, acquisition, and data processing are performed substantially simultaneously). However, in other embodiments, there may not be any pipeline, and the diagnostic system 100 may transmit, collect, average, and process all data related to a single transmit frequency before moving to the second transmit frequency.

Regardless of whether pipelining is used, the process of using different transmit frequencies for any number of transmit frequencies may be repeated with a desired spectral frequency sweep, and the process of using different transmit frequencies may also be repeated for one or more frequencies within the spectral sweep. In some examples, the phase shift calculated for each frequency may be transmitted directly from the phase shift measurement FPGA 114 to the laptop 102.

Signal processing-averaging

Due to the relatively small size of the transmitter 120 and receiver 124, and the relatively low power of the transmitted magnetic field (which is low power, among other reasons, particularly due to the need to protect the patient from excessive exposure to RF radiation, and to minimize electromagnetic field emissions from the system 100), the magnetic field measured at the transmitter 120 and/or receiver 124 may have a relatively large amount of noise compared to its relatively small amplitude. The noise may include input thermal noise of the amplifier, background noise from EMI pickup, and the like. In some embodiments, noise may contribute a significant proportion to the phase shift measurement relative to the actual phase shift. For example, a 1ml fluid change may correspond to a.3 degree phase shift, and thus, if the noise in the transmit and receive signals is a significant fraction of the expected phase shift, or even exceeds the expected phase shift, the noise may render the data unacceptable.

To reduce noise, in some embodiments, the diagnostic system 100 described herein may sample many cycles of the transmitted and received magnetic field (e.g., many times 10000 samples, such as 32000 samples), and may average the individual samples to substantially reduce random noise or filter specific frequencies. In some examples, the total sampling time interval may be extended to approximately an integer multiple of one 60Hz AC power cycle in order to reduce the effects of electromagnetic interference pickup associated with 60 Hz. As explained below, these waveforms may be averaged by any suitable averaging technique, including multiplying them by each other in the time domain, as well as other frequency domain averaging techniques.

Referring now to fig. 4, one embodiment 300 of a simplified logic diagram of the waveform averager FPGA112 is shown, of course, in other embodiments, custom circuitry may be employed to average the data, which may be located in the headset 106, the processing unit 104, the laptop 102, or another suitable location, however, fig. 4 illustrates one example of logic that may be implemented in the waveform averager FPGA112 to average the transmitted waveform samples after having been digitized by an a/D converter similar logic 300 may be used to average the received waveform samples after having been digitized the input to the waveform averager FPGA112 may be a low voltage differential signal (L VDS) type format from an a/D converter in order to reduce the wiring required between the a/D converter and the waveform averager FPGA112 in the L VDS format, the words of digital data representing individual waveform data points may first be converted from parallel data to serial data per each by the deserialization logic described below.

The logic shown in fig. 4 includes a synchronous serial-in, parallel-out shift register 301 clocked by the data transfer clock from the a/D converter. The parallel data words are then transferred into a memory buffer 302 of sufficient capacity to process the maximum number of individual waveform samples required to make up one complete cycle of the transmitted waveform. The adder 303 may be used to accumulate the sum of all waveform samples in the memory buffer 302 when the data word leaves the register 301 or after the memory buffer 302 is completely filled. The word size (in bits) of each waveform sum memory location can accommodate the expected maximum number without overflow. For example, a 12-bit resolution a/D converter and 4096 waveform sums require a memory word size of 24 bits. After accumulating the sum of the expected number of waveforms in the waveform memory for the transmitted signal samples (and similarly summing the receiver signal samples in the waveform averager separately), the memory contents of the two waveforms are serially transferred to the phase shift measurement FPGA 114. In some examples, it may not be necessary to divide by the number of averaged waveforms, as only the relative amplitudes of the data points in the averaged waveforms may be relevant in the next step of the process. Because of this, an appropriate number of least significant bits can also be deleted from each averaged waveform data point without significantly affecting the accuracy of the overall phase shift determination.

Signal processing-determining phase shift

Referring now to fig. 5, phase shift measurement FPGA 114 may also contain two rotation shift registers 401, 402, a multiplier 403, and an adder 404. It may also include logic configured to calculate a sum of products of respective transmit and receive averaged waveform data points with an adjustable phase shift between the two waveforms. The FPGA can be used to find the phase shift where the sum of products is closest to zero and the slope of the sum of products with respect to the phase shift is also negative.

Consider having a frequency f and a phase shift

The following trigonometric identity of the product of two sinusoids:

Sin u sin v＝1/2[cos(u-v)-cos(u+v)]wherein

And v 2uft (equation 1)

1/2[ cos (4>) -cos (27t (2F) t + (4)) ] (equation 2)

The first term of the product is a DC term that depends only on the phase shift. The second term is another sine wave of twice the frequency, which averages to zero over one complete cycle of the original frequency. Note that when the phase angle is

At +90 ° or-90 °, the first term (cosine wave) is also zero. Furthermore, the slope of the product with respect to the change in phase angle

For the

Is negative, and is at

Is positive.

Through iteration, the FPGA can determine_n0ffsetWherein the transmitted wave and the received wave are closest to a +90 ° phase shift. For the_n0ffsetN of one sample and one complete 360 DEG waveform_tThe offset of one sample, then the phase shift is calculated using the following equation:

phase shift of 90 ° + (n)₀ffset/n_t) 360 ° (equation 3)

The resolution determined may be limited to the number of samples (resolution 360 °/nt). If this resolution is not sufficient to achieve the required measurement accuracy, interpolation can be used to find_n0ffsetThe fractional value of (c), where the sum of the product terms is exactly zero.

Frequency domain signal processing method for phase shift measurement

As explained above (see, e.g., the section on averaging and multiplying waveforms together to obtain phase shifted data), signal processing of the measured and digitized magnetic field traces from the transmitter 120 and receiver 124 may be performed in the time domain. However, in other embodiments, the signal may be processed in the frequency domain using, for example, a Fast Fourier Transform (FFT).

In one embodiment of fourier domain analysis, the signals from the transmitter 120 and receiver 124 are digitized at a relatively high resolution (e.g., 14 bits) at a sampling rate of, for example, about 200 MHz. The a/D converter and data capture electronics may be included in a relatively small printed circuit assembly package. The captured data may be transferred to the laptop 102 via a high speed USB serial link. The time domain processing can then be replaced with frequency domain processing on the laptop 102 to calculate the phase shift between the waveforms.

Once the data is on the laptop 102, an FFT for each of the transmitter and receiver time domain waveforms may be calculated (although in other embodiments, the FFT may be calculated by an FPGA or other processor near the a/D converter). The resulting real and imaginary solutions representing the resistive and reactive frequency domain data may then be converted from cartesian to polar coordinates to produce a frequency domain plot of the amplitude and phase of the waveform. The phase of each waveform may be obtained from a frequency domain plot of the phase of the frequency of interest. If the fundamental frequency is not proportional, then the difference frequency between the sampling frequency and the transmitted wavefield frequency may be used. For example, a sampling frequency of 210MHz produces an FFT in the frequency range 0 to 105MHz, and the fundamental frequency is used for phase shift measurements when the transmitted wavefield frequency is in this range. If the transmitted wavefield frequency is at the higher end of the range, e.g. 105MHz to 315MHz, then the difference frequency is used.

After the FFT is computed for both the transmitted and received wavefield signals, the phase shift for a particular frequency of interest may then be computed from the difference in phase values obtained from the transformed transmitter and receiver waveforms. Note that some sign inversion may be required for the phase information in the respective frequency regions when calculating the shift.

To allow the FFT to be calculated for samples from the transmitter 120 and receiver 124, the frequency used for sampling and the transmitted waveform may be determined to allow coherent sampling such that both the transmitted and received waveforms contain an integer number of complete time segments of the repeating waveform and the number of samples collected for the waveform is an even power of 2. One method for implementing coherent sampling is to select the transmitter and receiver sampling frequencies such that prime/ftransmit is prime 2/freceive. In some embodiments, prime numbers primei and prime2 and the number of samples may be very large, thereby reducing the separation between allowable values of signal frequency (e.g., the tuning resolution may be about 1 Hz). This may be achieved by using digital frequency synthesis techniques, such as by combining a stable frequency source with an appropriate combination of an integer multiplier, integer divider and phase locked loop.

For coherent sampling, the theoretical accuracy of the phase calculation may be limited only by the number of samples of the time domain waveform and the digital resolution of the a/D converter. DC noise and low frequency noise sources (such as 1/f noise) can be inherently rejected by frequency domain processing techniques. The use of coherent sampling also reduces the likelihood that harmonic and intermodulation product frequency components will be located above the target frequency for calculating phase. Furthermore, determining the phase using an FFT frequency domain solution may provide information about the magnitude or amplitude of the measured transmitted and received magnetic fields. The ratio of the amplitude values may be used to determine the attenuation of the transmitted magnetic field, which may be expressed in units of log dB power ratios.

Alternative signal processing in the time domain

As an additional alternative signal processing technique in the time domain, the phase shift measurement may be done via one or more relatively low cost analog phase detectors or by measuring the time delay between the zero crossings of the transmitted and received wavefield signals. For example, the integrated phase detector circuit may include an amplifier that converts the sine wave of the transmitted and received wavefields into a square wave by clipping the sine wave (e.g., with very high gain), and then comparing the clipped/square wave from the transmitter with the wave from the receiver using an analog exclusive-or (XOR) gate, where the pulse width provided by the XOR gate indicates the phase shift between the transmitted and received magnetic fields.

Reducing phase measurement errors due to motion

Among all the factors that cause phase measurement errors, many are motion related, such as patient motion, movement of the transmitter 120, movement of the receiver 124, bending of the connection or transmission cable, and so forth. For example, relative motion between the patient and the transmitter 120/receiver 124 causes the path length and position of the magnetic field lines as they pass through the patient's head to change. Electrically conductive or magnetic objects moving near the transmitter 120 and/or near the receiver 124 may also change the shape of the magnetic field lines as they pass from the transmitter 120 to the receiver 124.

In some embodiments, methods may be deployed to reduce artifacts due to patient movement. These algorithms may, for example, detect statistical changes in the differential phase shift data across the spectrum of frequencies of interest (e.g., from about 30MHz to 300MHz or from about 20MHz to 200MHz), which may not be the result of biological changes, as determined by their rate of change or other characteristics. Thus, this threshold type of approach can be used to eliminate data corrupted by means other than a true biological change.

As another example, attenuation data obtained from the amplitude portion of the FFT process may be utilized in an algorithm by examining its variation across the spectrum to help detect and correct for motion artifacts in the phase shifted data.

As yet another example, an electronic accelerometer may additionally or alternatively be used to detect motion of one or more of the transmitter 120, the receiver 124, the patient, or the transmission cable. In some examples, the accelerometer may be coupled to the same printed circuit board as the transmitter or receiver (e.g., using a MEMS-type accelerometer).

In addition to detecting any motion above a threshold level, it is also possible to check whether there is a relative difference in the relationship between the transmitter/receiver accelerometer data and the patient accelerometer data. For example, small amplitude changes sensed in both the patient and the transmitter/receiver may have little consequence. There will almost always be some patient motion (because, for example, even a comatose patient will breathe). However, larger or uncorrelated accelerometer readings may be used to trigger data rejection or correction. Because individual motion of completely independent objects in the vicinity of the patient may also have motion artifacts in the data, some type of motion detection and correction based on statistical analysis of the phase data may still be required.

Medical diagnostic method for alerting a clinician

The system 100 described herein may be used to measure, among other things, changes in phase shift caused by, for example, changes in fluid content ("intracranial fluid") in a patient's head. In various embodiments, the system 100 may be used to measure anything in a number of things within the intracranial space. For example, in some embodiments, intracranial fluids are measured. In other embodiments, intracranial soft tissue is measured or fluid and soft tissue are measured together. In general, the system 100 may measure the bio-impedance of all tissues across the intracranial space. In the present application, the term "bioimpedance" is used to generally refer to the bioimpedance of intracranial fluids, soft tissues, or both. Methods may be employed to analyze the phase data and determine whether fluid changes represent tissue changes that are plaguing the clinician user. For example, when a patient first arrives at a hospital, baseline readings of the phase shift between the magnetic field transmitted from the transmitter 120 located on one side of the patient's head and the magnetic field received by the receiver 124 located on the other side of the patient's head at one or more frequencies may be recorded. The clinician may then track and trend any significant changes in the measured phase shift that occur during subsequent scans to help understand the clinical condition of the patient, and certain thresholds, patterns, or trends may trigger an alarm. Many methods may be employed and optimized to provide the clinician with the most useful fluid change information. For example, if the phase shifts beyond a certain degree, the system may issue an alarm to alert the clinician that the patient may have clinically significant bleeding or edema. For some conditions, it may be useful to alert the clinician if the rate of change of the phase shift exceeds a threshold.

For example, the phase shift at different frequencies may be a function of different fluid changes, as described in U.S. patent No.7,638,341, which is incorporated by reference herein in its entirety for all purposes. Certain phase shift patterns may be associated with certain clinical conditions. For example, symptoms such as bleeding or edema may be evidenced by an increase in phase angle at one frequency and a concurrent decrease at another frequency. The use of phase shift ratios at different frequencies can provide additional information about the type of fluid and the manner in which it is changed. For example, the ratio of the phase shift at the first frequency to the phase shift at the second frequency may be a good parameter to assess blood content or to separate edema from bleeding or other fluid changes. For example, the phase-shifted frequency response of saline may be different from the phase-shifted frequency response of blood, thus allowing the clinician to separately identify changes in blood and saline content in the patient's brain cavity. In some cases, the effect of the change in the amount of water on the phase shift is relatively small, but the concentration of the electrolyte in the ionic solution may have a more pronounced effect.

The phase shift pattern may also be time dependent. The postulated clinical condition may be characterized by an increase in phase shift over a period of time, then a plateau, and then a return to baseline after some other period of time. Noise factors, such as patient activity, e.g., getting up, eating, drawing blood, or talking to visitors, may cause the phase shift reading to change from baseline. Clinically meaningful fluid changes can be distinguished from noise by examining patterns associated with different activities.

Using a combination of phase shift and/or attenuation data at various frequencies, the ratios or other functions of those phase shifts and/or attenuations and/or time-based methods may be combined and optimized in various embodiments to provide a clinician with a range of useful information about tissue and/or fluid changes. The clinician can then react to the change in tissue by using more specific diagnostic techniques, such as medical imaging to diagnose tissue problems.

In some cases, the therapy may be changed in response to fluid and/or tissue change information. For example, the diagnostic system described herein may monitor fluid changes in a patient that is using a blood diluent to dissolve clots in cerebral arteries. If the system detects intracerebral hemorrhage, the blood diluent may be reduced or stopped to help control the hemorrhage, or other interventions (such as vascular surgery) may be performed to stop the bleeding. As another example, a patient beginning to experience cerebral edema may undergo medical intervention to control or reduce the edema, or may undergo surgery to drain fluid, or even a semi-craniotomy procedure to reduce the intracerebral pressure due to edema.

In some cases, the clinician may use fluid change information to administer drug doses by examining information effectively fed back from the diagnostic system. For example, if mannitol is used to reduce intracerebral pressure by withdrawing water from the brain, a treating clinician can use the diagnostic system described herein to receive feedback on how the patient's brain water changes in response to a drug.

Similarly, drugs for blood pressure management, electrolyte concentration, and other parameters may be administered more effectively when the dosage is controlled in response to feedback from the diagnostic system described herein. For example, intravenous hypertonic or hypotonic saline solutions can be used to control brain sodium concentration. The change in ion concentration may be detected as a phase angle shift or some function of the phase angle shift at one or more frequencies. Such information can be used as feedback to the physician to better manage the patient.

Additional embodiments

One embodiment of a VIPS system for monitoring intracranial/cerebral fluid(s) houses all electronics in the headset 129. The headgear 129 may be configured to image a helmet or hard hat. The rf oscillator may be placed near one or more of the transmitters 120/124, possibly on the same printed circuit board. One oscillator may generate the transmitter signal and another oscillator may be used to generate the sampling signal. As will be discussed later, multiple transmitters or receivers may be used, and it may be desirable to have different oscillators for different transmitters. Thus, multiple oscillators may be used. In another embodiment, the headgear 129 may be configured to image a pair of eyeglasses. One advantage of such an embodiment is that because the device will be mechanically registered to the nose and both ears, the position can be better controlled, making it possible to remove and replace the device with good antenna position repeatability. The antenna may be placed on the temple of the glasses just above and in front of the ear, thereby providing a location approximately in the center of the brain. Antenna placement close to the ear has features close to the mechanical reference point, thus providing good positional repeatability.

In some embodiments, multiple transmitters may be used that transmit frequencies that are offset from each other. For example, three transmitter antennas may be used, and each antenna may transmit a frequency that differs from the other antennas by a few KHz. The frequencies of all three oscillators should be derived from the same stable reference oscillator and digital phase-locked loop synthesis techniques are used to reduce phase errors due to differences in the thermal frequency drift and phase noise of the individual oscillators. One advantage of each transmitter being slightly different in frequency is that the system can then identify and separate the resulting signals from each transmitter, for example, using a Fast Fourier Transform (FFT). Using this technique, all transmitters can be powered on briefly at the same time, and within the same very short time interval, all received phase information for each transmitter/receiver combination can be determined simultaneously using the FFT of the transmitted and received waveforms. This information may allow the system to resolve the location of fluid changes within the tissue and also distinguish from phase changes caused by patient motion, tissue fluid flow or motion of the antenna or field motion generated by moving objects in the environment. For example, such a system may be used to specifically identify the location of a hematoma or the volume of ischemia within a patient's brain.

For medical applications, it may be desirable to transmit signals within the industrial, scientific, and medical radio frequency bands (referred to herein as the "ism band"). However, it may be desirable to design the system to transmit outside this band to reduce the effects of exposure to more ambient radio frequency noise from other devices operating in the ism band.

To improve the robustness of the system against ambient radio frequency noise, the system may detect ambient radio frequency noise during periods when the oscillator is not transmitting any signal. If the noise at certain frequencies is too high, the system may go to generating signals at different frequencies, thereby improving the signal-to-noise ratio. In some applications, it may be desirable to measure phase using spread spectrum techniques in order to spread the electromagnetic interference frequency over a wider frequency range to improve the signal-to-noise ratio. To facilitate changing the frequency, multiple crystals may be installed in the device, and the system may select between the crystals to allow the most appropriate frequency to be selected given the noisy environment. Alternatively, the digital RF frequency synthesizer may have sufficient bandwidth and resolution to facilitate fast frequency synthesis of new frequencies from a single reference crystal oscillator. If necessary, the reference crystal oscillator can be stabilized in an oven to further reduce phase errors caused by temperature fluctuations.

Various wave shapes may be employed when generating the signal. A square wave will provide more power at harmonics of the fundamental frequency. Sine waves and distorted square waves can be used to push more rf power to higher frequencies, or to provide power at various harmonic frequencies. Alternatively, the fundamental and higher frequencies may be added together for additional power at different frequencies. The sampled signal may also require a separate RF frequency for analog-to-digital conversion. For sufficient resolution in the phase measurement, the resolution required at the sampling frequency may also be very high to allow coherent sampling. Digital frequency synthesizers may utilize various combinations of phase locked loop stabilized frequency multipliers and frequency dividers to achieve the high resolution required for coherent sampling while also generating slightly offset frequencies for multiple transmitters. There is a need for a receiver amplifier with high gain and good phase stability. In one embodiment, amplification with about 40dB gain is used. In some embodiments, the receiver amplifier may employ two or more gain stages, for example, 20dB on the antenna and an additional 20dB on the analog-to-digital conversion board.

The analog-to-digital converter may also be included on the same printed circuit board with the transmitter and receiver antennas and any amplifiers suitable for amplifying the signal to an optimal level.

Various high speed cable connections and protocols can be used to transmit data from the helmet to the console. The use of metal cables can cause a source of error by changing the shape of the magnetic field. To avoid this problem, optical fiber cables may be used instead of metal cables.

Data may be wirelessly transmitted from the patient's headgear or helmet to the console using a wireless protocol, such as bluetooth, WiFi, wireless, or other suitable protocol. The transmitted data may be time domain data, or an FFT may be performed by a processor in the headset and then the generated digital data is wirelessly transmitted to the console. The main advantage of using FFT to transmit data in the frequency domain is that the amount of data is reduced, thereby reducing the required data transmission rate. The FFT may be performed by a processing element, such as a Field Programmable Gate Array (FPGA) hardwired to perform the FFT within the helmet. Alternatively, other types of microprocessors (including general purpose microprocessors) may be used to perform the FFT. Because all of these electronics are mounted inside the helmet or other headgear 129, it may be advantageous in some embodiments to minimize the size and power consumption of the components. To further reduce the need for a cable connection to the console, a portable rechargeable battery based power supply system may be included in the helmet.

In one embodiment, the system is designed to take multiple samples continuously or in short bursts per second so that the data can be analyzed to measure the heart rate of the patient, or to provide other useful information. Much like the technique used in pulse oximetry, this technique can help to distinguish arterial blood volume from venous blood volume. In another embodiment, the system may be configured to synchronize with EKG, pulse oximetry, or other cardiac signals. This can provide very accurate timing triggers to measure arterial and venous blood volumes simultaneously with specific portions of the cardiac cycle. Synchronizing the VIPS readings with the external cardiac signal may undersample against heart rhythm, while the VIPS readings may be several seconds apart. By comparing VIPS readings from different portions of the cardiac cycle, a series of VIPS readings may be processed to reconstruct fluid composition changes associated with the heart rhythm, revealing a measure of global perfusion within the brain.

An illustrative system for synchronizing VIPS readings with cardiac signals will now be discussed. It should be understood that the embodiment of fig. 7 may be modified with substantially any type of physiological sensor for detecting changes in a patient's body, and should not be limited to the cardiac signals specifically discussed. Fig. 7 is a block diagram of a system 700 for detecting and monitoring a volume of bodily fluid that occurs as a result of or with a cardiac cycle of a patient. The system 700 of fig. 7 may be substantially similar to the system 100 of fig. 1. However, in the embodiment of fig. 7, system 700 includes a cardiac module 701, which may include a cardiac cycle sensor 702 and a trigger 704. The cardiac cycle sensor 702 can be substantially any type of sensor or combination of sensors that detect electrical activity of the patient's heart. For example, cardiac cycle sensor 702 can be configured to detect polarization and depolarization of cardiac tissue. The cardiac cycle sensor 702 may also be in communication with the processing unit 104, microcontroller 118, or other processing element that may convert various signals into a cardiac waveform or other desired form. In a particular example, the cardiac sensor 702 can be a pressure sensor that detects pressure changes within the patient to detect characteristics of the cardiac cycle. In another example, cardiac sensor 702 may be an acoustic sensor that senses changes in sound to detect characteristics of the cardiac system. The cardiac cycle sensor 702 may be integrally formed with the headset 106 or may be a separate component therefrom.

The trigger 704 may be substantially any type of device that can receive and/or transmit a signal. The trigger 704 may be in electrical communication with the cardiac sensor(s) 702 and may be configured to transmit signals, such as infrared pulses (open air or fiber optics), radio frequency pulses, and/or timed pulses based on radio frequency digital communication, to the processing unit 104 and/or the headset 106.

Using the system 700 of fig. 7, VIPS measurements may be triggered wirelessly or by wire through the trigger 704. For example, based on the detection of a particular cardiac event (e.g., pulse oximetry) or other cardiac signal, the trigger 704 may instruct the processing unit 104 to activate the VIPS reading so that data may be detected and collected at specific portions of the cardiac cycle. In this example, VIPS detection may be based on cardiac events. However, in other embodiments, the detection antenna or wiring on the heart sensor 702 may be sensitive to the VIPS radio transmission frequency and may be configured to be activated by the VIPS in order to capture the instant of each VIPS data acquisition pulse within the EKG record (an enhanced and/or alternative method of ensuring that the VIPS data correlates very accurately with the cardiac cycle data).

With each heartbeat, the volume of arterial, venous, and cerebrospinal fluid in the brain fluctuates, and these changes can yield valuable diagnostic information as detected by VIPS monitoring. In one embodiment, the system is designed to take multiple samples continuously or in short bursts per second so that the data can be analyzed to measure the heart rate of the patient. In another embodiment, the system may be configured to be triggered by and synchronized with EKG, pulse oximetry, or other cardiac signals. This can provide a very accurate timing trigger for measuring fluid conditions including arterial blood volume, venous blood volume, and cerebrospinal fluid volume at one or more specific portions of the cardiac cycle. Much like the technique used in pulse oximetry, this technique can help to distinguish arterial blood volumes from venous blood volumes.

In yet another embodiment, the VIPS measurements are not triggered to synchronize to the EKG or other external cardiac signal, but rather are time-stamped with sufficient accuracy to assign each VIPS measurement to the portion of the cardiac cycle in which it was collected. By comparing VIPS readings at different portions of the cardiac cycle, either by simultaneous acquisition or by subsequent analysis, a series of VIPS readings may be processed to reconstruct fluid composition changes associated with the cardiac cycle. Such analysis of VIPS measurements may reveal measurements of global perfusion within the brain, as well as valuable information for condition diagnosis, such as shunt failure (described in detail later in this specification). These methods (synchronizing or time-based correlation of VIPS readings with external cardiac signals) allow undersampling relative to the heart rhythm such that the interval between individual VIPS readings can be even a few seconds while still providing valuable information about fluid fluctuations associated with the cardiac cycle. Other examples include synchronization with (or isolation of) a ventilation signal, such as a capnography signal.

Various signal processing analysis techniques, including frequency domain methods such as Discrete Fourier Transform (DFT) and Fast Fourier Transform (FFT) analysis, may be applied to VIPS measurements to reveal the frequency distribution of oscillations in the cerebral fluid, which are derived from the patient's heart rhythm. These techniques may be applied to measured VIPS phase and/or amplitude data for multiple radio frequencies, either individually or in combination. Useful combinations for analysis include theoretically and empirically derived formulas that use a weighted combination of VIPS phase and amplitude data to create an index related to blood volume, cerebrospinal fluid, edema, or other relevant fluid characteristics. When an external cardiac signal is available for correlation, the period and frequency of the cardiac cycle will be provided and may be used with processing methods such as applying an average, median or other statistical information to the VIPS measurements for each measured portion of the cardiac cycle and then calculating the difference between the intervals to determine the magnitude of the fluid change associated with the cardiac cycle.

In another embodiment, the system is designed to take multiple samples per second and is configured to generate a signal corresponding to the magnitude of the change in intracranial blood volume caused by each arterial pulse. It is well known in the art of intracranial pressure (ICP) measurement that ICP increases in the diastolic phase of the cardiac cycle and decreases in the systolic phase due to an induced change in intracranial blood volume. Thus, using an ICP monitor, a plethysmogram can be generated that approximately plots the time-varying repetitive fluctuation of intracranial blood volume over time.

In patients with a burr hole (e.g., an intraventricular catheter), the amplitude of ICP changes due to the beating of the heart are significantly attenuated (damp). This is because the pressure pulse is released as the fluid moves back and forth through the conduit. The same decay of the ICP plethysmogram also occurs in patients with intra-ventricular shunts, as is commonly used in chronic hydrocephalus patients. When the shunt is operating properly, the cerebrospinal fluid will move back and forth in the shunt catheter, attenuating the ICP excursion (outflow) during the cardiac cycle. However, when the shunt becomes clogged or otherwise fails, the fluid will not move during the cardiac cycle and the amplitude of the ICP variation increases. The present invention may be configured to monitor changes in blood and cerebrospinal fluid volume caused during the cardiac cycle and detect shunt obstructions or malfunctions.

Once the plethysmogram is generated, there are a number of ways in which this information can be used to help diagnose the condition of the patient. For example, after the heart pressure/volume pulse peaks, the lower portion of the waveform represents a recovery period during which the fluid volume returns to baseline. The time taken from the peak of the cardiac cycle to another subsequent time may provide information about intracranial compliance or intracranial pressure. It may help identify specific characteristics of shunt performance or failure within the ventricle. Ratios, differences and other mathematical relationships of plethysmographic amplitudes at various points in time along the cardiac cycle may be developed to indicate various clinical conditions and physiological parameters.

During the performance of cardiopulmonary resuscitation (CPR), feedback on the effect of cardiac compressions needs to be provided. Currently, there are devices that can measure the displacement distance, which is related to the heart compression and the resulting change in blood volume. However, these devices do not directly measure the effectiveness of pressure to induce blood flow into the brain, which is a major goal of CPR. The invention can be applied to the head of a patient undergoing CPR and direct readings can be taken to detect the amplitude of blood volume changes in the brain during CPR. In this embodiment of the invention, the effectiveness of CPR can be monitored and improved by providing the CPR administrator with direct feedback on the actual change in blood volume at each heart compression.

In addition to using the VIPS technique to generate a plethysmogram of intracranial fluid changes, other techniques may be used to implement the present invention. For example, the plethysmogram may be generated using near infrared spectroscopy (nirs) or by measuring the absorption of light at various wavelengths. For example, pulse oximetry devices typically use two wavelengths of light and rapidly sample the absorption of these wavelengths during the heart pulses to produce a plethysmogram. This can also be done with one wavelength. This type of light absorption technique can be applied to the brain to produce a plethysmogram that can be used to assess shunt malfunction. Those skilled in the art of plethysmography will recognize that plethysmograms of intracranial fluids may be generated by a variety of techniques, and the present invention is not limited to any particular means of generating plethysmograms.

In the field of ICP monitoring, skilled neurologists and other specialists can examine the shape of ICP figures and determine important clinical conditions. At high sampling rates, the plethysmographs produced by the present invention may produce similar curves and may provide clinicians with similar diagnostic information without the use of invasive ICP probes. Information about arterial and venous blood flow and volume, intracranial compliance, edema, CSF volume, and pulsatility can all be obtained from high resolution plethysmograms. In some cases, it may be useful to use VIPS plethysmograms in conjunction with ICP monitors to better understand the clinical condition of a patient, particularly when information about a variety of different fluids is required. This technique can also be used to inform clinicians of intracranial compliance.

In another embodiment, detection of intracranial compliance (such as eustachian tube insufflation manipulation, jugular vein compression, cerebrospinal fluid injection or withdrawal (e.g., using spinal taps), hyperventilation, hypoventilation, or changes in patient position) may be accomplished by examining changes in the volume of one or more intracranial fluids over time or in response to external stimuli. Recovery after initial stimulation may also indicate intracranial compliance and autoregulation. The present invention may be used in conjunction with an ICP monitor to establish a relationship between pressure and volume, and thus provide information about intracranial fluid compliance and automatic adjustment. The present device may be combined with other monitoring techniques such as, but not limited to, ECG, EEG, pulse oximetry, ultrasound, transcranial doppler, and/or infrared SPE endoscopy to correlate intracranial fluid volumes with other physiological parameters that may be useful in diagnosing, managing, or treating disease.

In another embodiment, the present device may be used to detect CSF leaks. For example, patients at risk of CSF leakage, such as patients undergoing epidural anesthesia surgery, may be monitored with current devices, and the devices may alert the attending physician when the volume of CSF changes. Since there is currently no way to detect CSF leaks directly during or after spinal or epidural anesthesia, anesthesiologists are usually left unattended hours or days later before symptoms of the leak become apparent. Since most patients remain prone during the immediate post-operative recovery, they usually wait until the post-operative stand up before any neurological symptoms appear. Due to the depletion of CSF within the skull, the brain will sag due to gravity and lack of normal buoyancy supplied by a sufficient amount of CSF. It is generally assumed that this sagging causes pressure on certain blood vessels supplying the brain, resulting in a severe headache, commonly referred to as "spinal headache". One common treatment for such CSF leakage that is accidentally caused by a dural puncture is to inject the patient's autologous blood into the epidural space near the puncture. This is called a blood patch. Other treatments involve the injection of saline or other fluids into the cavity, or surgical repair of dural tears. With the proper application of the current apparatus, a novel method of treating a patient can be formulated, comprising the steps of: an intracranial fluid monitor is applied to a patient undergoing a procedure that may lead to CSF leakage, CSF leakage is detected, and the leakage is repaired during the same surgical session. Variations of this method may include detecting CSF leaks in a patient using an intracranial fluid monitor, and repairing the leak by leak detection. Alternatively, the intracranial CSF volume of a patient may be measured prior to a procedure that may cause CSF leakage, and a second measurement of the intracranial CSF volume may be taken during or after the procedure, and if a significant decrease is detected, repair may be performed prior to the end of the procedure. Alternatively, the second measurement may be taken at any time after the protocol, and the repair may be performed after the leak is detected.

In another embodiment of the invention, plethysmography is used to detect respiratory rate and volume, heart rate or penile erectile function. For example, the sensors may be designed such that they will adhere to the torso in a manner that detects the extent of chest excursion due to the breathing cycle. Sensors may also be integrated into the armband, headphones, or watch bracelet to monitor changes in blood volume of the underlying tissue, which is then related to the heart and respiratory cycle via mathematical transformations. A sensor attached to the base of the penis can measure the volume change associated with the erectile response.

According to one embodiment, a console of a VIPS system may include custom electronics with a display. A laptop computer or tablet (such as an iPad) may alternatively be used. An advantage of using one of these off-the-shelf computers is that wireless communication capabilities, including bluetooth or WiFi, have been integrated. A custom console comprised of off-the-shelf or custom parts may also be used.

To detect asymmetry (or other symmetrical or asymmetrical features) of the fluid in the brain, multiple transmitters and receivers may be strategically located. The transmitter and receiver may be positioned such that the transmitter transmits through different portions of the patient's bulk tissue, and the receiver is generally positioned opposite the transmitter to receive signals through the tissue. For example, a single transmitter (or receiver) may be positioned on or near the patient's forehead, and two receivers (or transmitters) are spatially separated from each other and may be located on either side of the head, preferably facing backwards, so that a time-varying magnetic field propagates through each hemisphere, or in the case of two transmitters, each time-varying magnetic field is propagated uniquely to a different side of the brain. In this example, the magnetic field received by the receiver (or two magnetic fields received by a single transmitter, in the case where two transmitters are used) will be transmitted substantially through different portions (e.g., the first portion and the second portion) of the overall tissue sample. Depending on the orientation of the transmitter/receiver, there may be some overlap in the tissue portions, but typically the transmitter is arranged to be transmitted through discrete portions of the overall block-packed tissue.

Continuing with this example, a non-uniform signal between two receivers and one transmitter, or between one receiver and two transmitters, may indicate the presence of a stroke or hemorrhage on one side. This is useful because most brain lesions are not located directly in the center of the brain. Thus, detection of asymmetry will indicate a lesion. To identify the signal transmitted from each transmitter, the signal may include transmission characteristics as identifiers, such as synchronization pulses, amplitude or frequency modulation, and/or each transmitter may transmit at a different base frequency or a different sequence of frequencies. For example, the signal transmitted from the first transmitter may have a different frequency than the signal transmitted from the second transmitter. As another example, a signal transmitted from a first transmitter may be shifted in time compared to a signal transmitted from a second transmitter. As yet another example, each or one of the signals may include data bits (e.g., amplitude values, etc.) corresponding to a particular transmitter from which the signal was transmitted.

It is possible to allow a single antenna or coil to act as a transmitter or receiver at different times, thereby creating a transceiver. A switch may be implemented to switch the antenna from the receiver to the transmitter and vice versa. For example, gallium arsenide FET or PIN diode switches may be used. Alternatively, two concentric loop antennas may be positioned on the same printed circuit board or other substrate.

Some of the electronic components may be sensitive to temperature changes when measuring the phase shift. In order to minimize the effect of temperature induced variations, it may be desirable to design the cable from the transmitter to the analog-to-digital converter to be the same length as the cable from the receiver. Adding a compensating resistance or reactance in the form of a series/parallel network of resistors, capacitors and inductors may also minimize the effect of temperature. In addition, heaters or thermoelectric coolers and thermal insulation materials may be used to keep the temperature of the amplifier or other components that are themselves temperature sensitive.

To reduce the effects of the transmit antenna mismatch with the cable delivering the RF transmit signal, a directional coupler may be used to remove cable reflections and provide pure transmit signal samples that may be used for analog-to-digital conversion.

To reduce the sensitivity of the system to movement of people or other objects near the antenna or in the magnetic field, it may be useful to shield the antenna to direct the magnetic field. Various field shaping passive devices formed of ferrites, other magnetic materials, or electrical conductors may be combined with the antenna to best match the field profile to the human brain cavity.

Algorithm

As already described, VIPS devices may capture electrical characteristic data for multiple frequencies. Such data may include a measure of the phase shift between the emitter and the detector and the attenuation of the voltage or current signal. In some embodiments, measurements of phase shift or attenuation will be made between multiple emitters and detectors.

Different biological tissues have varying electrical properties and thus cause different phase shifts and attenuations. By examining the frequency response of the electrical property changes (e.g., phase shift), it is possible to separately examine the volume change of each type of fluid. Because the skull is a rigid and closed volume, changes in volume of different fluids (such as blood, intracellular fluids, extracellular fluids, and cerebrospinal fluids) affect each other because the total fluid volume must remain substantially constant. The fundamental relationship between intracranial pressure and intracranial fluid volume was first published by professors Monro and Kellie for two more centuries ago. Monro and Kellie have established the theory that because the skull is essentially a rigid closed volume, venous outflow of blood from the skull is necessary to allow arterial blood flow into the skull. This phenomenon is also applicable to other intracranial fluids.

Various algorithms may be generated to reliably detect changes in intracranial fluid. The formula may be derived from the phase shift, attenuation, or other electrical parameter of certain fluids at certain frequencies. An equation B (p (fl), a (f2)) which is closely related to intracranial blood volume can be empirically derived. In this example, formula B is a function of the phase shift (p) at a particular frequency (f1) and the attenuation (a) at the same or another frequency f (2). In living patients or animals, as blood volume increases, we expect the volume of cerebrospinal fluid to decrease. Thus, if we derive a formula for cerebrospinal fluid and call it C, then an increase in the ratio of B/C can be a good indicator of venous blood pool or cerebral hemorrhage. As another example, it is well known that as cerebral edema progresses, increasing volumes of intracellular and extracellular fluids push some intracranial blood out of the skull. Thus, if we derive a formula for the cell fluid and call it CF, the ratio of CF/B can be used as a measure to quantify edema. The use of a ratio formula may be particularly helpful in distinguishing noise factors that may affect the numerator and denominator.

Further to this general approach, one of ordinary skill in the art can develop many such algorithms that utilize formulas that are closely related to the location of one or more specific intracranial fluids and/or fluids in the cerebral hemisphere. The relationship between two or more fluids may be represented by a mathematical formula, which may include a ratio, a product, a sum, a difference, or various other mathematical relationships.

The present invention may be used to diagnose conditions such as cerebral hemorrhage or edema. It may also be used to help control the treatment of some of these conditions. For example, the device may be used to measure cellular fluid in brain tissue. In cases of dangerous edema, physicians often use intravenous drugs such as mannitol and hypertonic saline solutions to draw water from the brain. These drugs can be dangerous if not administered properly and in the correct dosage. It would be useful for the attending physician to know how much fluid is removed from the brain tissue. Thus, use of a device such as that described herein would have utility as a therapeutic means of providing feedback to reduce intracranial fluid volume. Another example is the use of such devices to provide a positive measurement of intracranial blood as feedback for the management of drugs that alter blood pressure and flow rate, sometimes used to treat brain-injured patients. Other examples of feedback that may be used with intracranial fluid measurements include: hydration in strenuous exercise (such as running marathon); sodium concentration in strenuous exercise; or treating patients with inappropriate levels of sodium.

While the examples used herein focus on intracranial fluids, algorithms and treatment methods using devices that can distinguish between different types of fluids may also be used in other medical fields. Algorithms and feedback techniques such as those described above can be used to reliably measure the ratio of different types of fluids in other parts of the body. For example, examining fluid accumulation in lung tissue of a congestive heart failure patient may be understood as a change in the ratio of lung fluid to blood in the same region. Lymphedema that typically occurs in a patient's arm after breast cancer surgery can be measured by the ratio of extracellular fluid to blood or muscle tissue volume. As described above, feedback may be used to determine a patient's treatment that affects tissue fluid volume, such as a compression suit for lymphedema or a diuretic for congestive heart failure patients.

Clinical application

During hemodialysis, blood is withdrawn from the patient's vein and substances including sodium and urea are filtered out. The blood-brain barrier prevents these larger molecules, known as osmomolecules, from rapidly leaving the brain. This establishes a concentration gradient that provides an osmotic pressure to draw water across the blood brain barrier into the brain, resulting in brain edema. In extreme cases, this brain edema causes a condition known as dialysis imbalance syndrome, and can be severe enough to cause deterioration of brain function and even permanent brain damage. Partly for this reason, performing dialysis requires an extended period of time, typically about 4 hours. It is believed that many patients can tolerate faster dialysis regimens, but it is difficult to determine which patients can tolerate faster dialysis rates. By monitoring intracranial fluid during dialysis, the VIPS system described herein may enable new dialysis protocols. The steps of such a method would involve placing a fluid monitor on the patient before starting dialysis, initiating dialysis at a relatively fast rate, and examining the patient for signs of cerebral edema. As edema progresses, the dialysis rate may be reduced in response to the fluid readings, customizing the dialysis rate for each patient based on their ability to tolerate the procedure.

For patients with sodium imbalance, the VIPS system described herein may be used to detect changes in sodium levels that may lead to conditions such as hypernatremia and hyponatremia. In patients suspected of having such a condition, the system may be deployed to detect and diagnose the condition, or to assist clinicians in correcting the patient's sodium balance by providing real-time feedback during infusion or drug therapy.

During cardiac surgery, there is a risk that insufficient blood flows to the brain. This may be the result of embolism or insufficient blood circulation or low cerebral blood pressure. An article discussing this problem is "A Review" by Silent Brain experience after cardio Surgery, author: sun et al/Journal of the American College of Cardiology, 2012. The fluid monitor may detect a decrease in blood volume in the brain and may detect ischemia in the brain tissue. Thus, new monitoring techniques may involve placing a fluid monitor (such as the system described herein) on the patient at the beginning of a cardiac surgical procedure and monitoring the patient during the surgical procedure. In the event that the device detects cerebral ischemia or a reduction in cerebral blood volume, the physician may be alerted and may attempt to correct the problem through various clinical means.

The VIPS device may be configured to non-invasively monitor intracranial pressure. It is well known in the neurological arts that intracranial pressure and volume are approximately linearly related when intracranial fluid is properly regulated by the body's own intracranial fluid control system. It has been determined in clinical studies that VIPS devices can detect fluid displacement proportional to a change in pressure.

There is a need to detect ischemia in the gastrointestinal tract, especially in newborns. The VIPS system described herein may be used to detect ischemia by continuous monitoring or transient measurement.

In car accident victims, soccer players, military forces, and other types of head injuries, prevention and detection of head injuries is critical. Accelerometers have been added to football helmets to monitor acceleration due to impact, and companies such as nikker have integrated acceleration detectors into hats. However, accelerometers are, at best, an indirect method of helping to determine the likelihood of a head injury. Movement of the skull in the brain in response to external acceleration forces can lead to concussions or brain damage. VIPS can also be added to helmets, hats, headbands, or applied directly to the head and can detect brain movement within the skull during an impact. This could be used instead of an accelerometer but would be most effective if used with an accelerometer. Monitoring brain movement within the skull with VIPS would provide a better measure of potential brain damage than with an accelerometer alone. Soccer is one application. Crash testing is another application. Vehicle safety studies can greatly benefit from a better understanding of brain movement during an impact (e.g., crash testing with VIPS monitored dummy).

The detection of concussions is important, especially in sports injuries. If a person suffers from a concussion, then a second concussion before the first concussion has not been resolved can cause very severe damage, known as second impact syndrome ("second impact syndrome", by & Ostick, West J emery Med.2009, 2 months; 10(1):6-10.) although concussions and their effects on intracranial fluid are still developing, VIPS can be used to detect early stages of intracranial swelling, hyperemia, venoclysis, bleeding, ischemia, changes in blood flow velocity, or other biological changes affecting the bioimpedance of tissue. With a VIPS device, readings may be taken prior to the race or at some other baseline time, and the readings after the potential injury event compared to the baseline to determine the presence or extent of the injury.

A variety of other medical conditions may be monitored with the VIPS system described herein. Peripheral edema can be caused by a variety of medical conditions. Swelling of the feet and legs is common in congestive heart failure patients. Arm swelling is common when patients develop lymphedema after breast cancer surgery. Swelling of the limbs or other parts of the body following surgery is common. In some types of surgery, there is a risk of ischemia, edema, or venous incorporation of the flap. Compartment syndrome can result when there is insufficient blood flow to muscles and nerves due to increased pressure in the compartment, such as the arm, leg, or any enclosed space in the body. Current devices use minimally invasive devices (involving needles to penetrate tissue and take readings of pressure) to measure compartment syndrome pressure ("acuracy in the medium of complex pressures:. a complex soft breeze common used devices", body & wongwortat, J Bone Joint Surg am.2005 Nov; 87(l l):2415-22.) patients with congestive heart failure or other conditions have pulmonary or pleural effusions. The VIPS apparatus described herein may be used to monitor changes due to any of these or other conditions related to swelling, blood flow, perfusion, and/or other fluid characteristics of the limb and other parts of the body. A baseline reading can be taken and subsequent measurements can be compared to that baseline to monitor and detect changes in, for example, swelling or perfusion of the tissue. Continuous monitoring of swelling may provide feedback for drug treatment to control edema, blood flow, or other clinical parameters.

Dehydration can be a life-threatening medical condition and can occur in athletic activities (such as marathon running) as well as patients suffering from various medical conditions. The VIPS devices described herein may be used to quantify a hydration level of a patient for initial diagnosis, to monitor the effectiveness of therapy, and/or as an alert to patient deterioration.

Fighter pilots and other people experiencing extreme accelerations can sometimes lose consciousness due to sudden liquid transfer in their brains. Similar situations occur in deep sea divers, astronauts, parachutists, and mountain climbers exposed to extreme conditions that may affect their intracranial fluids. The VIPS devices described herein may be mounted within a helmet, or may be attached to a person's head during activities that may expose them to a risk of intracranial fluid changes, which may be monitored in real time. If a dangerous fluid change occurs, the individual or a third party may be alerted to intervene.

Migraine is known to be caused by dilation of blood vessels in and around the brain. Regular or continuous monitoring of intracranial blood volume can be used to diagnose or better understand the physiology of migraine. Migraine sufferers can quantify the effect of various migraine treatments during administration and can use that information as feedback to titrate the medication or adjust the treatment. Periodic monitoring of migraine sufferers (e.g., short VIPS spot check readings taken every night and morning upon waking) will enable individuals to detect characteristic intracranial fluid changes that precede migraine symptoms, thereby facilitating early intervention to more effectively alleviate the symptoms.

Penile plethysmography is commonly used in urology surgery to assess erectile function before and after prostatectomy. Currently, this is typically done via a circumferential strain gauge transducer. VIPS sensors may be used to provide a direct volume measurement of penile filling. Such a device may also be used in an ambulatory setting to assess the cause of erectile dysfunction, i.e., whether physiological or psychological, or to monitor nighttime arousal.

As described above, various methods of detecting bodily fluids (directly or indirectly) using the system 100, 700 may be used. For example, in one approach, asynchronous EKG and VIPS readings may be time stamped and VIPS readings may be segmented according to location in the cardiac cycle for subsequent analysis. As some examples, exemplary analysis includes statistics, such as median or mean values in each interval, and then the difference between the mean values of the intervals related to the diastolic and systolic portions may indicate the degree of fluid exchange.

As another example of a method, a signal processing algorithm (e.g., FFT, DFT) may be applied by the processing unit 104 and/or a computing device (e.g., laptop, desktop, server) to the measured phase, amplitude, and/or weighted combination (such as a computed indicator associated with blood, CSF, etc.). To determine the heart rate (frequency) and/or amplitude of fluid changes associated with the heart cycle.

Physiological monitoring is commonly used in various medical environments to include parameters such as heart rate and respiration rate. While there are currently a variety of methods to derive these values (electrical, optical and other values), the VIPS may also be used to provide data on these vital signs, thereby avoiding the need for additional monitors when the VIPS device has been used for cranial fluid monitoring or as an additional source of the same information. That is, the physiological sensors may be used to directly or indirectly detect one or more characteristics of fluid flow or other conditions within the patient, which may then be used to calibrate or filter data from the VIPS system.

The automatic regulation of intracranial fluids is a complex biological process involving vasodilation, vasoconstriction, movement of cerebrospinal fluid (CSF) between the various compartments of the brain and the spine, and the production of CSF. Patients with a variety of neurological disorders have poor self-regulating abilities, which can lead to increased or decreased intracranial pressure. The VIPS devices described herein may be used to assess autoregulation and intracranial compliance of a particular patient. Tests may be developed to measure fluid changes that occur as a result of protocol or posture changes. For example, the patient may lie flat back down, and the clinician may take fluid volume readings, lift the patient's legs to an elevated position, and measure the fluid changes that occur. Other tests may include intravenous infusion of large amounts of fluid, administration of drugs, and/or moving a patient from a flat position to a vertical position, all of which may cause changes in blood, cerebrospinal fluid, and other fluids in the brain. The results from a particular patient test can be compared to baseline measurements of the same patient performed at different times, or to a database of known normal and pathological responses, to help clinicians better understand patient autoregulation and intracranial compliance status. By better understanding the intracranial fluid function of the patient, the clinician may be able to better select the treatment regimen that is most beneficial to the patient.

A study comparing the recovery of normal cerebrovascular responsiveness (CVR) in subjects following spontaneous manipulation of blood flow to the brain indicates a difference between patients with concussion and healthy subjects. Unlike healthy subjects, people with concussion fail to recover normal CVR after hyperventilation. This condition continues for several days after the concussion. In contrast, in healthy subjects, CVR returns to normal conditions in a much shorter time. Our experiments show that there are measurable changes in a number of measurements of brain electromagnetic properties during tests that affect CVR, such as eustachian tube insufflation manipulation and jugular vein compression. The results show that the return to time and amplitude normality can be accurately detected with the device and method described in this patent application. This illustrates that these devices and methods can be used to assess various diseases (such as concussions) by assessing time and amplitude patterns of deviation from normal features, due to the well-controlled manipulation that produces blood flow.

Experimental examples

This experiment is based on the idea that substantial insight can be found in the response of electromagnetic signals to spontaneous changes in tissue conditions. This results in a more controlled diagnostic method based on electromagnetic measurements of the condition of the biological tissue. In our experiments, spontaneous changes are produced in the interrogated organs or tissues, and diagnosis is made by assessing changes in electromagnetic properties that occur in those organs or tissues in response to the spontaneously produced changes and correlating those changes with spontaneous behavior.

One example of this approach involves concussions, which are an important medical problem in sports medicine. Concussions caused by exercise or mild traumatic brain injury (mTBI) are of increasing interest in sports medicine. Neuropsychological examinations are the primary diagnostic tool for detecting mTBI. However, mTBI also produces physiological effects including heart rate variability and baroreflex sensitivity, cellular metabolism, and decreased cerebral blood flow. Cerebrovascular reactivity (or "cerebrovascular reaction", CVR), which is a measure of cerebrovascular flow, is impaired by brain trauma. Various methods are used to assess CVR. They include hyperventilation, breath-holding, inhalation of carbon dioxide and administration of acetoxazole amide. It has been shown that doppler ultrasound measurements of the carotid artery can be used to monitor changes in CVR, which are then correlated with mTBI and used for diagnosis of the condition. The methods and apparatus described herein provide an alternative means for measuring CVR changes, with practical application in mTBI diagnostics.

This experiment demonstrates that various methods of assessing CVR through spontaneous movement of the body produce changes in the electromagnetic properties of the brain. These characteristics produce distinct features in amplitude and time and can therefore be used with our device for brain diagnostics.

An experimental system: inductance spectrometer

An experimental multi-frequency induction spectrometer was designed and constructed. The system consists of four modules: function generator, transceiver, two channel demodulator and analog-to-digital converter. A personal computer is used to control the system and process the data. The function generator module uses two identical programmable synthesizers (NI 5401 synthesizer, National Instruments, inc., Austin, TX) as oscillators. The first oscillator supplies an excitation signal icos (coet) of about 20mA at pre-programmed steps, ranging from 1 to 10 MHz. The second oscillator generates a modulation signal icos (comt). To generate narrow-band measured voltage signals at a constant low intermediate frequency for processing and demodulation, the difference ω is divided over the entire bandwidth_e-ω_m＝ω₀100(2 pi) remains constant.

The excitation and modulation signals are connected to the transceiver and the dual channel demodulator module, respectively. The transceiver is composed of an excitation coil and an induction coil which are coaxially aligned with each other<i-18 cm with two differential receiver amplifiersAD 8130. Both coils were made of electromagnetic wire AWG32 wound five turns on a cylindrical plastic bobbin with radius r 2 cm. The coil inductance calculated according to faraday's law is about 40 mH. The excitation coil generates a primary oscillating magnetic field. The sensing coil detects the primary magnetic field and its perturbation through the proximal conductive sample. To avoid inductive pick-up, the wire of the coil is wound. The amplifier is connected as a conventional operational amplifier and collects the reference voltage (V) in the drive and sense coils, respectively_ref) And induced voltage (V)_md). The gain of the amplifier is adjusted to obtain a dynamic range of +5V over the entire bandwidth.

The dual-channel demodulator module uses a mixer and narrow bandpass filters to pass information at any excitation and sensing frequency to the same low frequency (ω)₀). This module uses two similar channels to demodulate the reference and sense signals. To avoid additional inductance and stray capacitance in the circuit, the amplifier and dual-channel demodulator circuits are shielded by a metal box and connected to the coil by a short coaxial cable (length less than 0.8 m). Current flows through the shield to minimize any mutual inductance between the circuit and the coil.

The analog-to-digital conversion module digitizes the reference voltage signal and the induced voltage signal at a constant low frequency. A data acquisition card (NI 607IE, National Instruments, inc., Austin, TX) was used as an analog-to-digital converter with a sampling rate of 1.25 mlamples/seg and a resolution of 12 bits.

The phase of the reference and induced voltages was calculated in software over approximately five cycles by an extracted tone function available in L AB VIEW V6.1(National Instruments Inc, Austin, TX.) the phase shift between the reference and induced voltages was estimated as

By averaging the twenty spectra, the signal-to-noise ratio (SNR) (39 dB at 1 MHz) for the phase shift measurement can be improved.

The experimental protocol is as follows:

external jugular vein compression

The two external jugular veins, which are located on both sides of the neck, are one of the main routes of cerebral venous drainage. By applying light pressure to both sides of the neck, the person can inhibit drainage. In doing so, the intracranial fluid volume increases by 20-30 cc. As described in this patent application, the purpose of this experiment was to evaluate the ability of phase-shifting intracranial fluid monitoring devices to detect these changes in blood volume.

Experiments showed that the readings decayed exponentially after jugular release after compression. It was also shown that after the second compression and release, the reading did not return to the original value. This is a typical phenomenon of CVR when metabolism is depleted due to ischemia. This suggests that this approach may provide another technique for assessing CVR and thus concussion.

Referring to fig. 12, the results of this experience are presented in a graph. As shown in fig. 2, the phase shift measurement after calibration is plotted as a function of time, and the increase in phase shift is due to a decrease in venous compression and release. In addition, after the vessel is released, the exponential decay in the reading does not return to the original value. This is a typical phenomenon of CVR when metabolism is depleted due to ischemia, and indicates that the method may provide another technique for assessing CVR and assessing concussion.

Eustachian tube inflation examination method control

Eustachian tube insufflation maneuvers are performed by exhaling moderately forcefully through a closed airway, usually by closing its mouth and pinching its nose while pressing outward, just like a blown-out balloon. Eustachian tube insufflation manipulation the ability of the body to compensate for changes in the amount of blood returned to the heart (preload) and to affect the flow of blood into and out of the head is tested. The circulatory system indicates several physiological functions, including CVR, through the dynamic response of the manipulations. This procedure may also evaluate other conditions. For example, a patient with autonomic dysfunction will have a heart rate and/or blood pressure change that is different than expected for a healthy patient.

Using the apparatus as described herein, the time response to eustachian tube insufflation manipulation was measured. This measurement has several typical aspects of time that can be used for diagnostic purposes. These include the time constant of the increase, the peak, the time constant of the decay of the reading, and the final short and long term values.

Figure 13 illustrates a graph showing the change in displacement readings over time during a eustachian tube insufflation protocol. As shown in fig. 13, the reading has several typical time aspects that can be used for diagnostics, including the time constant of the increase, peak, decay, and final short and long term values of the reading.

Detecting concussion

In humans with concussions, spontaneous manipulation of blood flow in the brain leads to a return of normal CVR, unlike in healthy humans. Several days after a concussion, subjects with concussion were unable to recover normal CVR after being subjected to the hyperventilation test. On the other hand, in healthy subjects, CVR recovers the normal state in a short time. Our experiments show that our extensive measurements of the electromagnetic properties of the brain show that measurable changes are very significant during tests that affect CVR, such as eustachian tube insufflation manipulation and jugular vein compression. The results show that recovery to normal can be accurately detected by our measurements. This demonstrates that our device can be used to assess various diseases (such as concussions) by assessing time and amplitude patterns of deviation from normal features, due to the manipulation that produces good control of blood flow.

Detecting macrovascular occlusion

The effect of occluding one or more cerebral vessels is to reduce or eliminate the flow of oxygenated blood through the occluded arteries, resulting in hypoxia (i.e., insufficient oxygen delivery) of the "downstream" brain tissue, if undetected and therefore untreated, L VOs will cause brain cell death, resulting in persistent brain injury and even death in some cases.

L earlier detection of VO will lead to earlier clinical intervention and therefore can minimize brain cell damage the ability to continuously, non-invasively monitor L VO evidence can eliminate the need to keep the patient awake, can reduce or eliminate the need for hospital staff to perform continuous visual monitoring and interaction with the patient, and can limit the patient's exposure to radiation from multiple CT (computed tomography) scans.

Any of the embodiments of the non-invasive, diagnostic VIPS systems and methods described above may be used to monitor fluid changes in the brain or other parts of the body to detect L VO. in any given L VO, the fluid in the region of the brain affected by L VO may have detectable changes after an occlusion occurs.

Another way to detect L VO is to take only one "snapshot" of the brain using the VIPS system as described herein and compare the blood volume of the right hemisphere of the brain to the blood volume of the left hemisphere of the brain, for example, in the case of L VO appearing on the right side of the brain, the blood on the right side will be less than the blood on the left side, thus indicating that L VO. may be present on the right side this detection method can be performed immediately, and one advantage of this method is that it does not require baseline fluid measurements to be compared.

For example, in some embodiments, these techniques may be used to detect small vessel occlusion or hemorrhagic stroke (such as those caused by rupture of an aneurysm).

Referring now to fig. 15, it may also be important to detect the removal of an occlusion in patient management. After successful recanalization (e.g., mechanical or venous tPa), cerebrovascular reactivity will occur, which will cause fluid changes as blood floods into the depleted arterial vasculature. Over time, fluid in the brain (blood, edema, parenchymal fluid, etc.) will reach homeostasis, providing additional clinical feedback on effectiveness. Again, any of the VIPS systems and methods described herein may be used to detect fluid changes associated with removal of cerebrovascular occlusion. As detailed in this application, the VIPS system may also be used to identify one or more types of fluids in the brain, such as blood, CSF, edema, and the like. Fig. 15 is a chart 680 illustrating one clinical example of using a VIPS system as described herein to monitor a patient undergoing occlusion removal. Using the VIPS system as described herein, each point on the graph represents a snapshot measurement of the volume of fluid in the brain. The first point at the far left and bottom of the graph represents the baseline amplitude. The second point (i.e., the next point to the right from baseline) represents the change in fluid volume measured just after the occlusion removal procedure is performed. Subsequent points moving to the right on the graph represent subsequent VIPS fluid measurements, showing a slower rise in fluid volume followed by a gradual decrease. This is just one example of the manner in which the VIPS system described herein may be used to measure fluid changes after an occlusion removal procedure.

In addition to detecting L VOs, the VIPS systems and methods described herein may also be used to help determine L VOs location in the cerebral vasculature.determining L VOs location (such as in which hemisphere of the brain) may provide important clinical diagnostic feedback for important treatments.for example, a VIPS device having two transmitters and one receiver spatially separated to distinguish fluid changes in a particular region of the brain may be used to detect in which hemisphere fluid changes are present.

Bilateral detection

The ability to detect spatially the changes in fluid in the right and left hemispheres, whether for locating L VOs or for other applications, is critical to the diagnosis and care of the patient.

The VIPS technique has been previously discussed and disclosed as "volume-integrated phase-shift spectroscopy". This technique is based on the principle of spectroscopy, as it generates and directs a spectrum (range) of frequencies towards a part of the body (e.g. the chest or brain) and measures/detects effects (e.g. absorption and propagation phase delays). Electromagnetic radiation is due to substances (e.g., fluids) within the body part. However, in this application, the concept of generating and detecting a single frequency rather than one or more frequency spectrums is disclosed. Furthermore, the acronym VIPS is used as "VIPS technology", "VIPS system" and "VIPS device", for example, VIPS in this context may denote a single frequency or a range of multiple spectra/frequencies.

As described throughout this application, in many embodiments, fluid changes in a body organ or body part, such as the brain, may be measured using VIPS techniques (volume integrated phase shift spectroscopy) using multiple frequencies, phases, and/or amplitudes. Indeed, the focus of the above description is on the use of multiple transmitters and/or receivers in the system, which are often used to distinguish between different types of fluids in a given space. However, in some embodiments, the systems described herein may use only one frequency, phase, or amplitude to make any of a variety of types of measurements. As just mentioned above, plethysmography is a method of measuring organ or whole body volume changes, usually due to changes in blood or air volume. In some embodiments, the systems described herein may use one frequency to measure changes in blood volume in the brain or skull to determine, for example, whether one hemisphere of the brain receives less blood flow than another hemisphere. Similarly, a frequency can be used to measure the overall change in blood flow to the brain. This is merely an example provided to illustrate that while the description herein focuses on using multiple frequencies, phases, and amplitudes, some embodiments may employ only one frequency, phase, and/or amplitude.

Fig. 14A illustrates one embodiment of a headset 600 for a fluid monitoring system, which headset 600 may provide bilateral detection as described above. In various embodiments, the form of the headgear 600 may be similar to any of the previously described embodiments of headgear, such as the headgear 129 of fig. 8, the headgear 906 of fig. 9, 10A-10C, the headgear 950 of fig. 11, and the headgear 650 of fig. 14B and 14C. The features of any of these embodiments may be combined and/or modified in any other embodiment to produce a headgear, head set, headband, helmet, or other wearable device for placement on a patient's head to monitor intracranial fluids and changes thereof. As such, terms such as "headgear," "headband," "helmet," and other similar terms may be used interchangeably throughout this application, and use of a particular one of these terms in describing given conditions should not be construed as limiting the scope of the invention.

By way of this introduction, in the embodiment shown in fig. 14A, the headset 600 (or "headset") includes a frame 605 and transmitter, receiver(s), and electronics (not visible) housed therein. A frame 605 extends from the forward housing 604 around the head on both sides to flexible arms 612, 613 and wrap ends 602, 603 on each side. Each of the surrounding ends 602, 603 contains a transmitter, and each transmitter transmits preferentially through one hemisphere of the brain to one or more receiving antennas located elsewhere within the housing 604 and/or frame 605. The flexible arms 612, 613 and the looped ends 602, 603 are designed to loop around the back of the patient's head to help hold the headgear 600 tightly on the head.

The housing 604 houses control circuitry for the headset 600 and at least one receive antenna. The housing 604 may also include a display 610, on which display 610 any relevant information about the headset 600 may be displayed, such as, but not limited to, on/off indicators, the continuous time of a given measurement, measured values, etc. In some embodiments, the display 610 may provide sufficient information so that the headset 600 may function as a fully self-sufficient stand-alone device that does not require communication with a secondary device such as a computer. Alternatively, such standalone or other embodiments may communicate with desktop computers, laptop computers, tablets, smart phones, etc., wirelessly or via wired connections. The two support arms 608, 609 may also be coupled with the frame 605, and when the headgear 600 is placed on the head, the frame 605 rests on the patient's ears, thereby helping to retain the headgear 600 on the patient's head. Nose piece 606 may also be coupled to frame 605 to provide a surface for headgear 600 to rest on the patient's nose, thereby providing additional stability, as well as a consistent alignment/registration reference for subsequent placement of headgear 600 on the patient. In alternative embodiments, other devices further shown and described above may be used (or modified for use) in bilateral detection.

Fig. 14B and 14C are top and bottom perspective views, respectively, of an alternative embodiment of a headgear 650 having a similar form and many of the same features as the headgear 600 of fig. 14A. Again, the headset 650 includes a frame 655 and transmitter, receiver(s), and electronics (not visible) housed therein. A frame 655 extends from the forward housing 654 on both sides around the head to the flexible arms 662, 663 and the looped ends 652, 653 on each side. Each of the surround terminals 652, 653 contain a transmitter and each transmitter transmits preferentially through one hemisphere of the brain to one or more receiving antennas located elsewhere within the housing 654 and/or frame 655. The housing may again include a display 660. The frame 655 also includes two support arms 658, 659. Nose piece 656 is attached to frame 655. The headset 650 may also include a power cable plug 664 for connection to a power source, for example, to charge batteries contained within the housing 654. The frame 655 may also include one or more control buttons 666 for turning the headset 650 on and off and/or for controlling other functions.

When using either of the two headgear 600, 650, it can often be very important to be able to (1) properly fit the headgear 600, 650 on many different sizes and shapes of head, and (2) register the headgear 600, 650 with the patient's head. For the purposes of this application, registering with the patient's head means only providing some type of mechanism or method that allows the headgear 650, 655 to be placed on the head, removed from the head, and then accurately replaced on the head in the same or nearly the same orientation and position. This registration allows the headgear 600, 650 to be removed and replaced and used multiple times for multiple readings, while maintaining consistency of the readings and not subjecting them to different positioning of the headgear 600, 650 on the head. To address the size issue, the headgear 650, 655 may of course be provided in different sizes. The headgear 650, 655 may also include one or more features to aid in sizing and/or alignment. For example, the headgear 650, 655 may include an adjustable nose piece or a plurality of removable and replaceable nose pieces, such that the nose pieces may be selected to optimally fit a particular patient. The flexible arms 612, 613, 662, 663 may also be adjustable and/or extendable to allow further adjustability. The ear support arms 608, 609, 658, 659 may also aid in registration because they are stable and always sit on top of the patient's ears during donning of the headgear 600, 650. In some embodiments, they may also be adjustable to aid in resizing and/or registration.

Using the headgear 600, 650 or any other headgear or headgear embodiments described herein, one goal of intracranial (or other) fluid monitoring in a patient is often to provide continuous monitoring of the fluid(s) over a relatively long period of time, such as extended ICU dwell time. As such, the headgear 600, 650 may include any of a number of features to make it more wearable, comfortable, and effective over a longer period of time. Indeed, alternative embodiments of the headgear 600, 650 may be significantly smaller, and in some embodiments may be similar to a headband (such as a sports headband). Fig. 16 illustrates one embodiment of a headband 670, the headband 670 being part of an intracranial fluid monitoring system. Again, while terms such as "headgear" and "headband" are often used interchangeably in this application, a headband such as the headband 670 of fig. 16 typically has a form factor that wraps around the head in a circumferential direction. Headgear or headgear (such as that shown in fig. 14A-14C) typically rests on the head and does not wrap around the head all the way around. The headgear and headgear described herein generally resemble a virtual reality goggle or eyeglass frame with the front and arms extending over the ears of the patient. In some embodiments, these embodiments can be made small and easy to wear. Headgear such as headgear 670 may also have additional advantages in terms of wearability, the ability to accommodate different shapes and sizes of different patient heads, the ability to stay in one position on a patient's head for a longer period of time. In general, making VIPS fluid monitoring devices (headgear, headband, or otherwise) smaller and more wear resistant would involve miniaturization of parts, a reduction in the number of parts, or both. In some embodiments, this may result in a modular headband or headgear device.

Referring again to fig. 16, in some embodiments, the headband 670 may include two modules, one of which provides transmission and reception and the other of which provides processing and communication. The transmit and receive module 672 (not visible due to being embedded within the headgear 670) may provide placement and securement of the antenna to the patient's head for spot check (spot check) and/or long term continuous monitoring. A processing module 674 (also embedded in the headband 670) may be attached to the transmit and receive module 672. This embodiment may allow easy placement of the long-term transmitter(s) and receiver antenna(s) without the additional size and weight of the processing module. Furthermore, such an approach may be useful in transporting a patient EMT to a hospital, where the processing module 674 is non-transferable or disposable, but the transmitting and receiving module 672 is transferred with the patient. This transfer provides consistent antenna placement for the patient and allows similar processing and communication devices (modules or otherwise) to be connected.

Another goal of the mechanical design of the headgear 600, 650 or headband 670 is to provide stable and repeatable (if used as a spot check) antenna positioning over all head sizes and shapes (or other body parts in other embodiments). Achieving this goal may involve adding more transmitters and receivers to the device, and/or using new data processing algorithms that compensate for smaller position changes by comparing how the data changes on the various transmitter/receiver pairs. In addition, the analog-to-digital converters on the headband 670 may include more channels being sampled at the same time (e.g., one channel per receiver), more on-head signal processing for FFT, etc., and additional buffering for low data rate transmitted data to the processor or bluetooth interface. Various features and embodiments designed to achieve these objectives are described below, and may be included and combined in any suitable manner in a given embodiment.

Referring now to fig. 17, one embodiment of an antenna placement configuration of the fluid monitoring device 1000 is schematically illustrated from the perspective of the top of the head of a patient P, with the forehead F pointing to the right side of the figure. In this embodiment, four transmitters 1002(X) and three receivers 1004(R) are placed around the fluid monitoring device 1000, and the fluid monitoring device 1000 is positioned on the patient's head, for example, by attaching the transmitters and receivers to the headgear 670 or headgear 600, 650. In this embodiment, the transmitter and receiver may be attached to the headband 670 or the headgear 600, 650 as a reconfigurable module. For example, the illustrated example may be advantageous for use in plethysmography, and the more transmitters 1002 and receivers 1004 are positioned around the patient's head, the more the headband 670 or headgear 600, 650 can triangulate between the transmitters 1002 and receivers 1004 to obtain accurate data.

In some embodiments, the analog-to-digital converter (ADC) in the headset/headband may have four channels (all sampled simultaneously), instead of two. Four channels instead of two should result in a two-fold increase in time domain data. The two additional channels mean that the Fast Fourier Transform (FFT) is now also increased from two to four, and the set of FFT transmitter harmonic bins is also increased from two to four. Thus, the number of FFT interval data points per measurement increases from twenty to eighty. In some embodiments, there may be flexibility to omit some data if the bluetooth command protocol is not required for a particular application.

Another challenge of continuous intracranial fluid monitoring is electrical interference control. One possible solution to this challenge is to focus the critical functions entirely in a dedicated custom Application Specific Integrated Circuit (ASIC) to eliminate signal cross-coupling on PCB traces and reduce radiated emissions and susceptibility. The fluid monitoring system may also include new guidelines for the power system to eliminate ground rings, etc. The system may also include new guidelines for transmitter clock synchronization and transmitter output detection signal interface to the ADC to minimize transmitter/receiver cross-coupling. Other new guidelines for receiver antenna/receiver amplifier design may also be included to minimize antenna-to-receiver amplifier interconnect pickup.

A possible ASIC of the system just described includes an RF clock synthesizer. The system may include four coherent transmitters and one sample frequency from a common reference. The synthesizer may be tunable over a span of several MHz to mitigate interference and/or improve detection of specific cerebral fluids. The transmitter clock synchronization signal may signal at a base frequency of 16X to push this potential interferer out of the received band. Another ASIC candidate has a four-channel simultaneous sampling ADC with a data buffer supporting three receivers and four frequency multiplexed transmitters. It may comprise a 4x4096x16 bit data buffer to simplify the interface with the signal processor. Such an embodiment may allow the use of off-the-shelf microcontrollers or DSPs for FFT and bluetooth interfaces by reducing the clock frequency of data transfer from the ADC. Some embodiments may alternatively include a separate ADC for each receiver, which may have the advantage of significantly reducing cross-coupling. Finally, in some embodiments, another ASIC possibility is to have a transmitter divider/driver. A 16X high frequency clock synchronous divider from the RF clock synthesizer and square wave antenna driver (clock synchronous frequency >9 th harmonic mitigates the receiver's interfering pickup).

Fig. 18 is a block diagram of the modular fluid monitoring apparatus 1000 of fig. 17. Device 1000 may include four transmitters 1002(Xmtrl-Xmtr4), three receivers 1004(Rcvrl-Rcvr3), an RF synthesizer module 1006, a main processing module 1008, and a battery (battery)/central power regulator 1010. In one embodiment, battery/central power regulator 1010 may include a battery, a charger interface, and central power regulator(s) to provide power to other modules. The main processing module 1008 may include a receiver with a 20db350MHz BW amplifier, an ADC, microcontroller, or DSP, and a bluetooth module (or alternatively, some embodiments may have a post-amplifier and digitization in the receiver module), which may be an ASIC or a combination of an ASIC and discrete components. The RF synthesizer module 1006 may include a 10MHz reference crystal, VCO external components, a loop filter cap, and an RF synthesis ASIC. The transmitter module (including the four transmitters 1002) may include a transmitter divider/driver ASIC, an antenna, a field shaping ferrite, and an electrostatic shield. The receiver module (including the three receivers 1004) may include an antenna, an electrostatic shield, and a 20db350MHz preamplifier. Device 1000 may also include interconnections to support reuse of modules in various configurations.

Another challenge in creating a small wearable VIPS fluid monitoring device that can be worn continuously over time is providing a sufficient number of antennas and placement of antennas on the device to make accurate measurements. In one embodiment, the headgear/headband device may include a ferrite beam steering/shaping core to the transmit module to optimize the antenna pattern to reduce reflections at the interface with the patient's head and improve coverage of the entire brain volume or provide directional RF into a particular area. Some embodiments may include electrostatic shielding for the transmit and receive modules to prevent emissions to the rear and sides and reduce sensitivity from external sources. The overall goal is to achieve higher transmission field strength in all important areas of the brain and to reduce the coupling between transmitters and receivers of the desired frequencies through the air around the desired path of the brain. Adding more receivers 1004 and more transmitters 1002 also helps to ensure coverage of all critical parts of the brain.

Fig. 19 illustrates one embodiment of a transmit module 1002 that may be used with the VIPS fluid monitoring headgear/headband described herein. In this embodiment, the emitter module 1002 includes an electrostatic shield.

Fig. 20 illustrates one embodiment of a receiver module that may be used with the VIPS fluid monitoring headgear/headband described herein.

Referring now to fig. 21-23, some embodiments of a VIPS fluid monitoring system may include a basic interrogator/transponder. In such embodiments, and referring to fig. 21A, the interrogator module synthesizes an appropriate, continuous, stable RF frequency signal that is coherent with the second synthesized ADC sample frequency signal, and transmits an amplified burst of this RF signal to the transponder module. The transponder module receives the RF signal bursts from the interrogator module and internally synthesizes its own continuous RF signal, which is at the same frequency and phase locked to the interrogator unit's RF signal bursts. Referring to FIG. 21B, the transponder module then switches to a transmit mode and returns a precisely timed delayed RF signal burst of known amplitude to the master module using an amplified version of its internally synthesized interrogator signal replica. At the same time, the interrogator module has switched to a receive mode, and it amplifies and processes the retransmitted signal from the transponder module. The phase difference between its internal composite signal and the returned signal replica is calculated. The amplitude of the returned signal is also calculated. This data was retained for use in the brain fluid calculation of the monitor. FIG. 22 is a block diagram of an interrogator module according to one embodiment. FIG. 23 is a block diagram of a transponder module according to one embodiment.

In continuous fluid monitoring, a monitoring device is placed on a patient, for example on/around the patient's head, where it is held for a period of time. The processing module initiates a series of measurements during the time the device is parked on the patient. These measurements are essentially serial spot checks performed using a continuous wearable device. The rate and frequency of measurement may be pre-programmed, programmable by a user, predetermined for a given use condition, or some combination thereof. For example, TBI (traumatic brain injury) patients may require one measurement per hour to assess the progression of initial injury and/or SBI (secondary brain injury) that may occur late at night sleep. This device can also be used as a spot check (open, measure, then close) in a headband configuration or other device configuration.

In some embodiments, another optional feature may be to provide one or more adhesive "anchors" for placement on the patient, and then use the anchors to attach the monitoring device to the patient. Such anchors may be similar in form to electrocardiogram (ECG or EKG) "buttons" that are conventionally used to conduct electrical current through the body to measure the electrical activity of the heart. In some embodiments, these adhesive anchors may be used primarily to provide a secure attachment mechanism for attaching the fluid monitoring device to the patient. In embodiments where registration of the device with the patient is important, they may also assist in registering the device with the patient's head. The anchor allows the monitoring device to be snapped and undocked on the patient, repositioning to the same location with each reapplication. Any suitable number of anchors may be used, and the anchors may be located at any suitable location on the head, such as the forehead, temples, or scalp (shaving may be required in some embodiments). In some embodiments, the anchor may be used in conjunction with another medical device to pass current through or measure electrical stimulation of the body.

Similar to the anchor concept, some embodiments may include an adhesive substance on or separate from the monitoring device such that the monitoring device may be adhered to the forehead of the patient using the adhesive/sticky substance. This will help to secure the device in place. The device itself may contain or as an accessory include an adhesive medium that helps secure the headband in place after first placement. The viscous medium may be applied, for example, to the forehead, temples, or a combination thereof.

In other embodiments, alignment, stability, and placement repeatability of the monitoring device may be achieved or enhanced via mechanical attachment placed in the ear canal and/or around the ear. For example, in one embodiment, a transmitter may be placed in one ear canal, a receiver in another ear canal, and VIPS measurements may be taken by the brain while providing mechanical support and alignment for the device. The device may contain data local processing and display and/or transfer to off-site processing devices. Furthermore, in some embodiments, additional transmitters and receivers may be placed around the head in addition to each ear canal (transmitter/receiver) containing an antenna. In some embodiments, the receiver may be positioned in the ear canal and the transmitter positioned around the head, or any combination thereof.

Additionally or alternatively to the above features, some embodiments may involve tattooing or otherwise marking the patient for headgear placement/re-adjustment reference. The monitoring device may provide visual registration for repeated and reliable placement and replacement. This may be accomplished by the clinician placing one or more markers on the patient and using the marker(s) to register the monitoring device to the patient. Such registration may be achieved optically, for example, by a sensor that is part of the device, or alternatively by a device that contains a crosshair for the clinician to visually align the device with the marker(s) placed on the patient.

In some embodiments, regardless of the manner in which the monitoring device is attached to the patient, the device may contain an internal frame that provides mechanical rigidity/stiffness to maintain the antenna in the same position during use. This internal frame may reduce or eliminate any torsional translation between the antennas while allowing flexibility in accommodating various head sizes.

In some embodiments, the monitoring device may include a phased array structure of at least two transmit antennas to adjust the spatial sensitivity of at least one receive antenna in real time and/or between subsequent data acquisitions. Some embodiments may include frequency jitter for detecting a particular source. In such an embodiment, the monitoring device may include multiple transmitters/transceivers, all of which have the exact same frequency. The processing unit may dither one or more of the transmitter/transceiver frequency, phase, and/or amplitude to uniquely identify the receiver antenna (or antennas). In an alternative embodiment, the monitoring device may have multiple transmitters/transceivers, each with a unique frequency. The processing unit may dither one or more of the transmitter/transceiver frequency, phase, and/or amplitude to uniquely identify the receiver antenna (or antennas).

Some embodiments of the monitoring device may include one or more antennas, each tuned to a single unique frequency. For example, the monitoring device may have an antenna to have an optimal response for the transmitting, receiving, or target fluid. These antennas may also be mechanically and/or electrically configured for unique applications. The antenna may be tuned to a specific frequency, constructed with ferrite material to optimize the frequency of RF penetration into the human body, shielded to reduce emissions into and out of the antenna for optimal noise suppression, etc.

In some embodiments, coaxial cables may be incorporated to deliver not only signals, but also power. Conventionally, coaxial cables are used where Radio Frequency (RF) shielding is required to suppress noise from a transmission signal as a center conductor. In VIPS devices, these coaxial cables may be used to transmit frequencies. In some embodiments, the device may be powered (AC/DC) using existing shielding of multiple RF coaxial cables, where one shield may be used for power ground and another shield may be used for power. This will reduce the number of connectors and cables, thereby reducing the size of the monitoring system and more importantly reducing the number of potential sources of radiated and conducted noise.

Other embodiments of the monitoring device may include optical fibers for transmitting digital signals, data communications, clocks, and the like. The use of cable and/or wire conductors in the measurement equipment introduces sources of conductive or radiative noise. These noise sources can present problems in measurement systems with high sensitivity. Thus, some embodiments of the monitoring device may include optical fibers to reduce these noise sources (errors). The use of optical fibers in the monitoring device may also provide greater flexibility to adapt the headband to varying head sizes. Furthermore, optical fibers are not susceptible to triboelectric effects produced by the cable when electrical charge is picked up by touch or bending, which can introduce noise and/or false signals.

In some embodiments, the headgear 600 or headband monitoring device may be comprised of separate self-powered modules, wherein each module includes a transmitter module, a receiver module, and a processing module. Alternatively, power may be provided by a central common power source. In some embodiments, the transmitter module may include an antenna, RF generation, digitization, and communication. The receiver module may include, for example, an antenna, receiver amplification, digitization, and communication. The processing module may control each transmitter/receiver module. The processing module communicates with each module to transmit the frequency (using the transmitter module) and measures the frequency, phase and/or amplitude of the transmitter module with the receiver module. According to alternative embodiments, module communication may be wired or wireless. The module power may be integrated into the module or provided by an external power source. Further, each module may act as a stand-alone module, and all communications may be performed wirelessly (RF for communications). For example, the measurement may be made by a "trigger" pulse sent by the processing module to the transmitter and receiver modules to initiate the scan. The measurement data may then be transmitted via RF back to the processing module, which may either process the data or transmit it to another processing unit. In some embodiments, these data may be uniquely identified for each module and synchronized with a timestamp. If most connections are wireless, various noise sources introduced through wired connections may be reduced or eliminated. The processing unit of the monitoring system may transmit the processed or raw data wirelessly or via a wired connection to a remote computer. Each module or separate transmitter and receiver (or transceiver) may operate in digital, analog, or a mixture of digital and analog modes. A module or an entire device may comprise either discrete circuitry or an ASIC (application specific integrated circuit) which may be digital and/or mixed signal (analog and digital). The ASIC may provide the following advantages: reducing the size and power consumption of the modules, and consistent performance between modules and systems.

In other embodiments, a fluid monitoring device such as a headband device for monitoring intracranial fluids may have separate modules, such as processing, transmission, and reception modules, the headband may also include attachments for specific applications.

In some embodiments, a monitoring device may be used to detect anatomical landmarks. In some applications, the placement of the monitoring device is critical to achieving sensitivity for detecting pathological conditions. Placement repeatability is also important for measurement repeatability during spot checks where the device is removed between readings. For example, in some embodiments, a monitoring device may be used to detect the sinus cavity to ensure that RF signals are being delivered into the brain. The anatomical landmarks may include ear canals, skeletal structures, or any other anatomical feature between the transmitter and receiver antennas that provides repeatable/predictable registration to place the monitoring device on the patient. Detection of these landmarks may be provided by the monitoring device's own RF and/or by other detectors using light or sound in the monitoring system or in the monitoring system.

Some embodiments of the headband monitoring device may use only analog signals, and not digital signals. Such an embodiment may derive a voltage corresponding to the relative amplitude and relative phase between the transmitted and received frequencies. Doing so would eliminate the need to sample the analog transmit and receive frequencies and then digitize and compute an FFT of the source and receive frequencies to extract the VIPS measurements. In this analog version, the voltages would correspond directly to the data of interest, thereby reducing processing overhead and power consumption.

Any of the VIPS systems described herein may incorporate a cellular phone, smart phone, tablet device, or other personal computing device. The cell phone intentionally generates and transmits multiple RFs into the environment for cell tower communication, WiFi and bluetooth. In some embodiments, the VIPS system described in this application may use a cellular phone (or similar device) as the transmitted s) and accessory design to receive these frequencies, thereby providing a personal, convenient spot check VIPS device. The cellular phone may be applied to one side of the body part (e.g., head, torso, arms) and the receiver to the other side. The software application will initiate the measurement and process the data.

Any of the VIPS monitoring devices described herein may incorporate any additional sensors to provide any additional measurements, diagnostics, or parameters to a clinician. For example, the fluid monitoring device may also measure pulse oximetry, patient temperature, respiratory rate, blood pressure, or any combination thereof. Additional devices for measuring these parameters may be integrated into the VIPS fluid monitoring device. These additional parameters/scales may also be used in conjunction with the processing of the VIPS data. For example, a pulse oximeter may be used to identify heart rate and provide a synchronized trigger for blood flow detection.

In some embodiments, the fluid monitoring device may be a stationary device, and the patient may place his or her head (or other body part in other applications) into the device. For example, the monitoring devices may be deployed in a "kiosk" fashion. For example, in one embodiment, the VIPS monitor may be designed as a stationary device, and the patient sits down and places his/her chin on the chin rest to align the patient's head with the transmitter(s) and receiver(s) to take VIPS readings.

Numerous additional aspects and embodiments of the described VIPS fluid monitoring apparatus, systems and methods may be included. The following list is merely exemplary and is not intended to be limiting.

1. A conceptually modular apparatus, each module comprising a transmitter and a receiver, and the apparatus comprising any suitable number of modules

2. Not only containing the drive electronics, but also shielding and "focusing" RF from and into the "module

3. Centralized or distributed methods of system power, control and design

4. Use of multiple frequency or time division multiplexed RF transmitters and multiple RF receivers to capture spatially resolved data to calculate cerebral fluid volume changes

5. Using ferrite cores to optimize transmit antenna shape and orientation

6. Use of electrostatic shields to minimize back and side transmission and reception of stray RF fields to minimize undesirable cross-coupling of transmitter signals to receivers

7. Synchronizing transmitter frequencies from a central location using a fundamental frequency well above a harmonic frequency of interest to eliminate transmitter/receiver cross-coupling

8. Synthesizing a sample frequency and multiple transmitter frequencies that are coherent with a large sample size from a single reference frequency to mitigate reference long term frequency drift and short term stability problems

9. Frequency hopping for EMI (electromagnetic radiation) mitigation and/or optimized fluid detection

10. Headband and module designs accommodate variations in head size and shape through stable and repeatable antenna positioning

11. Headgear and module design accommodates changes in head size and shape during long-term (continuous) monitoring through stable "one-time" positioning

12. Modular approach for easily adapting system configuration to a variety of product types, tasks, complexity levels, costs, etc.

13. Multiple antennas increase position resolution for cerebral fluid volume change detection capability

14. Multiple antennas and new algorithms allow compensation for antenna position changes between two measurements using "triangulation

15. Digitization at each receiver antenna to reduce interference pickup

Detecting and differentiating stroke

While some of the above description focuses on the detection of L VO (large vessel occlusion), the systems and methods described in this application may be used to detect any type of stroke and/or to help diagnose whether a given patient has suffered a stroke.

There are two main categories of stroke: ischemic stroke and hemorrhagic stroke. Ischemic stroke is caused by occlusion or occlusion of an artery, while hemorrhagic stroke is caused by intracranial hemorrhage due to one or more ruptured blood vessels. The clinical route of stroke treatment depends on whether the stroke is ischemic or hemorrhagic. In the case of ischemic stroke, for example, tissue plasminogen activator (tPA) may be used to dissolve the blood clots that cause the stroke, or surgical intervention may be used to mechanically remove the obstruction(s). On the other hand, in the case of hemorrhagic stroke, drugs may be used to reverse blood thinning and promote clotting, or surgical intervention may be required to suture the rupture. These are merely examples of the type of stroke treatment, but they illustrate the fact that: the type of stroke generally determines the type of treatment.

Time is of crucial importance in the treatment of stroke, whichever type of stroke occurs. This is because stroke "starves" the affected areas of oxygenated blood, resulting in brain cell death. If a clinician is able to (1) determine the hemisphere in which the stroke occurred and (2) determine the type of stroke using a non-invasive portable medical device, clinically meaningful data will be provided for a definitive diagnosis more quickly than current methods.

For example, when a stroke victim is attended by an Emergency Medical Technician (EMT), valuable time has passed. Once an EMT arrives, they do not have the medical equipment to determine which type of stroke occurred and therefore they cannot be treated appropriately, such as tPA for ischemic stroke. Further delays are caused by the need to transport the patient to a medical facility. Upon arrival at the facility, the patient will be sent to a Computed Tomography (CT) scan (diagnostic criteria) to determine in which hemisphere and type of stroke occurred. Using this data, the clinician can perform the appropriate treatment. However, if EMTs are able to determine the type of stroke and which hemisphere it occurs in at the time of initial exposure, they can make informed treatment decisions for the patient early. For example, the EMT may know to take the appropriate medication and/or direct the patient to a stroke center instead of the primary hospital. This is a well-known need and some ambulances are now equipped with mobile CT machines to allow diagnosis in ambulances. However, it is expensive and difficult to equip an ambulance with a CT machine.

The non-invasive, diagnostic VIPS systems and methods described above may be used to monitor changes in fluid in the brain to detect the occurrence of a stroke and help distinguish the type of stroke. This technique makes use of the fact that: most strokes occur in only one hemisphere of the brain, and the left and right hemispheres of the brain are separated by a medial longitudinal fissure. In the case of ischemic stroke, the occlusion may block the flow of blood to the tissue, resulting in ischemia of the tissue, or a reduction of blood in the tissue. In the case of hemorrhagic stroke, the blood vessels rupture, allowing blood to flow out of the blood vessels, forming a hematoma. The blood supply downstream of the rupture is also reduced. The VIPS monitor described herein measures fluid volume, volume change from baseline, and plethysmographs caused by the stroke volume of each beat. This VIPS technique is also configured to uniquely measure different volumes in a given region, which provides the ability to detect symmetry, asymmetry, and large volumes.

As described above and with respect to fig. 14, the VIPS technique may be configured to uniquely measure the right and left hemispheres of the brain. For each stroke type, the different frequency responses of phase shift, attenuation, and/or other electrical characteristics may be measured using the VIPS technique described. Algorithms can be used to uniquely identify specific correlations, for example, with changes (increases or decreases) in blood volume and/or changes in plethysmograph response. The ability to distinguish between left and right hemisphere volume changes (symmetry versus asymmetry) can also be incorporated into the algorithm to further enhance the identification of which hemisphere and stroke type. In the case of ischemic stroke, the blood volume in the hemisphere where the stroke occurs is reduced while the blood volume on the other side remains relatively constant. In the case of hemorrhagic stroke, the extravascular blood volume of the hemisphere in which the condition occurs will increase, while the tissue blood volume (intravascular) will decrease, while the opposite side volume remains relatively constant. In both cases, a VIPS monitor may be used to measure a large change in blood based on a baseline measurement and/or asymmetry in hemispherical blood volume to detect the occurrence and/or progression of a stroke. As the blood volume changes, the plethysmograph response will change. For example, when there is a large vessel occlusion (large ischemic stroke), the tissue downstream of the occlusion will not pulsate with the blood in each cardiac cycle, thereby reducing the amplitude of the cardiac plethysmogram measured by the VIPS device in the affected hemisphere. Algorithms employed in such devices can be used to examine the ratio or difference of plethysmograph amplitudes to detect large vessel occlusion and diagnose ischemic stroke.

Although specific embodiments of the disclosure have been described herein for purposes of illustration, various modifications may be made without deviating from the spirit and scope of the disclosure. For example, while the present application includes several examples of monitoring fluid changes in the human brain as one potential application of the systems and methods described herein, the present disclosure finds broad application in many other applications, including monitoring fluid changes in other areas of the human body (e.g., arms, legs, lungs, etc.), monitoring fluid changes in other animals (e.g., sheep, pigs, cows, etc.), and other medical diagnostic environments. For example, fluid changes in the arm may be detected by wrapping the arm in a bandage that includes a transmitter and a receiver.

Some examples of other medical diagnostic environments in which the systems and methods described herein may be used include determining the absolute proportion of a particular fluid, tissue (e.g., muscle, fat, parenchymal organ, etc.), or other solid (e.g., tumor) in a given region of the human body, determining the relative permittivity and/or relative permeability of an object, and so forth. Further clinical applications include a variety of monitoring and diagnostic uses, including internal bleeding detection, distinguishing between different types of fluids (e.g., blood, extracellular fluid, intracellular fluid, etc.), assessing edema, including cerebral edema and lymphedema, and assessing lung fluid accumulation resulting from conditions such as congestive heart failure. All of these applications, as well as more applications, may be addressed by the various embodiments described herein. Thus, the scope of the claims is not limited to the specific examples given herein.

Claims (18)

1. An apparatus for assessing intracranial bio-impedance of a patient's head, the apparatus comprising:

a headgear, comprising:

a housing containing control circuitry; and

a display on the housing, wherein the display is configured to provide sufficient information about intracranial bioimpedance so that a user can operate the device as a self-sufficient, standalone device; and

a transmission and reception module coupled with the headset, the transmission and reception module comprising:

at least one receiving antenna located in the housing; and

at least two transmit antennas coupled with the headset at two different locations to transmit radio frequency signals through the patient's head to the receive antennas;

a processing and communication module coupled with the headset, wherein the processing and communication module is configured to measure a phase shift in intracranial bioimpedance by measuring a phase shift in radio frequency signals transmitted by the at least two transmit antennas and received in the at least one receive antenna; and

at least one registration feature incorporated into or coupled with the headgear for registering the headgear with the patient's head.

2. The apparatus of claim 1, wherein the headset further comprises:

a frame;

two flexible arms attached to the frame, having looped ends, for fitting around the head of a patient;

two support arms attached to the frame for resting the headgear on the patient's ears when placed on the patient's head; and

a nose bridge attached to the frame, wherein the at least one registration feature comprises the nose bridge.

3. The apparatus of claim 1, wherein the headgear comprises a headband.

4. The apparatus of claim 1, wherein the at least one registration apparatus comprises at least one optical sensor coupled with a headset.

5. The device of claim 1, wherein the at least one registration device includes at least one crosshair on the device to allow a user to visually align the device with at least one of a marker placed on the patient's head or an anatomical feature of the patient's head.

6. The apparatus of claim 1, wherein the at least one registration apparatus comprises an internal frame within the headgear that provides mechanical rigidity to the headgear to maintain the at least one receive antenna and the at least one transmit antenna in a fixed position on the patient's head during use of the apparatus.

7. The apparatus of claim 1, wherein the at least one registration apparatus comprises at least one adhesive anchor coupled with a headgear to attach the headgear to the patient's head.

8. The device of claim 1, wherein the display is configured to display at least one type of information selected from a device on/off indication, a continuous time for a given measurement to be performed by the device, and a measured value measured by the device.

9. The apparatus of claim 1, further comprising at least one beamforming means for enhancing the shape and direction of transmissions from the at least two transmit antennas.

10. The apparatus of claim 9, wherein the at least one beamforming member comprises at least one ferrite core.

11. The apparatus of claim 1, further comprising an electrostatic shield for blocking stray radio frequency fields.

12. The apparatus of claim 1, further comprising an analog-to-digital converter coupled to the headset that includes one channel for each of the at least one receive antenna.

13. The apparatus of claim 12, wherein the analog-to-digital converter has four channels that are sampled simultaneously.

14. The apparatus of claim 1, wherein the at least one receive antenna comprises a plurality of receive antennas.

15. The apparatus of claim 14, wherein the at least two transmit antennas comprise three or more transmit antennas.

16. The apparatus of claim 1, further comprising a central power regulator coupled with the headset.

17. The apparatus of claim 1, wherein the processing and communication module comprises:

an analog-to-digital converter;

a microcontroller; and

and a Bluetooth module.

18. The device of claim 1, wherein the device is configured to assess intracranial bio-impedance and assess cerebral autoregulation in a head of a patient.

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