WO2022003360A1

WO2022003360A1 - Acousto-optic apparatus and methods

Info

Publication number: WO2022003360A1
Application number: PCT/GB2021/051676
Authority: WO
Inventors: James Robert DACOMBE
Original assignee: CoMind Technologies Limited
Priority date: 2020-07-01
Filing date: 2021-07-01
Publication date: 2022-01-06
Also published as: GB2596564A; GB202010043D0; GB2596564B

Abstract

The disclosure provides brain tissue acousto-optic apparatus and methods. The apparatus comprises an optical source (201) configured to emit light towards a target volume (250) containing brain tissue of a living subject, an optical detector (202) configured to detect light from the target volume, and an ultrasound source (203) arranged to provide an ultrasound field of spatially varying ultrasound amplitude in the target volume. The ultrasound field is arranged to modify the optical path length of light (212, 214) passing through the target volume (250), and to define a plurality of regions (210a-210f) in the target volume (250), wherein each region (210a-210f) provides a unique modification of the optical path length (212, 214).

Description

Acousto-Optic Apparatus and Methods

Technical Field The present invention relates to apparatus and methods for identifying areas of activation or stimulation in the brain. More particularly the invention relates to an acousto-optic apparatus and methods for producing ultrasound encoded light, and in particular the analysis of optical signals emitted into and detected from brain tissue to acquire information about the path taken by the light through the brain, where the properties of the brain tissue have been modified using an ultrasound field.

Background

The brain is an extremely complex organ, and despite advances in imaging techniques in recent decades, a great deal remains unknown about the specific function of different regions of the brain and how these regions interact to provide the various aspects of brain functionality.

There has also been an increased interest in the use of brain- computer interfaces (BCIs). These devices can obtain signals from the brain for example via imaging or scanning, and the received information can be transformed into computer commands. In addition, such devices may stimulate the neurons in the brain to change their optical properties, thereby modifying the outputted commands. Traditional imaging methods typically fall into one of two categories:

1. Methods such as two-photon imaging or microscopy, and other fluorescence techniques. These methods are only capable of imaging a small area of the brain. As such it is difficult to infer anything meaningful about brain tissue functionality from the information obtained from such techniques, as the scale they operate on is too small.

2. Methods such as functional magnetic resonance imaging (fMRI) and functional near-infrared spectroscopy (fNIRS). These techniques detect changes the magnetic and optical properties of the brain tissue respectively, that are caused due to changes in the blood oxygen level in the tissue. These techniques only achieve a low imaging resolution, meaning that it is difficult to obtain a detailed understanding of the structure and function of each region of the brain. Optical imaging in turbid mediums such as the brain is extremely difficult due to photons which scatter as they propagate through the medium. Photon scattering poses severe constraints on the spatial resolution which can be achieved by these methods. Reducing or monitoring photon scattering is an important barrier to overcome in order to non-invasively achieve a high spatial resolution whilst imaging a highly turbid medium such as the brain. Improved levels of spatial resolution are required to image close to, or at, the single-neuron resolution. Earlier attempts to address these issues, that is, to reduce or monitor the photon scattering, include monitoring the time of flight of a photon from the light source to the detector and utilising computational modelling to predict the path taken by the photon. However, such techniques require an enormous amount of computational power, extremely sensitive sensors and super fast lasers to monitor the time of flight of the photons. This is therefore not a scalable method and is difficult to do efficiently. Another approach which has been taken is Ultrasound-Modulated Optical Imaging, which uses ultrasound waves projected into a known location to compress the medium (in this case, brain tissue). This in turn modulates the photons via a phase shift. The change in phase can then be detected in order to indicate which photons have passed through that specific location where the Ultrasound wave was focused. However, Ultrasound-Modulated Optical Imaging suffers from several problems: Firstly, using a single Ultrasound focal point reduces the area of the brain that can be imaged. In addition, attempting to achieve a high axial resolution can cause heating within the brain and cannot pass through the skull. Existing ultrasound modulation methods are fundamentally limited by the size of the ultrasound focal point, causing the spatial resolution to be capped. Higher frequencies are traditionally needed to create smaller focal points. However these waves cannot pass through the skull and can cause acoustic heating which damages tissue.

Summary of Invention

Aspects and examples of the invention are set out in the appended claims, and may aim to address problems such as those outlined above. Examples of the disclosure aim to provide a localisation technique which may aid in improving spatial resolution in acousto-optic imaging. In particular, examples of the disclosure provide overlapping acoustic waves in order to create a field of varying ultrasound amplitude, specifically comprising multiple acoustic focal points which are smaller than the focal point created by a single acoustic wave. In so doing photons travelling through the field can be encoded with a unique phase shift which can then be decoded at a detector to determine the path taken by light as it travelled through brain tissue. This may aid in achieving a higher axial resolution in brain imaging. In addition, such examples aim to provide a technique which reduces photon scattering in the brain, which may improve the signal-to- noise ratio and further improve spatial resolution.

In an aspect there is provided a brain tissue imaging apparatus comprising an optical source configured to emit light towards a target volume containing brain tissue of a living subject; an optical detector configured to detect light from the target volume; and an ultrasound source arranged to provide an ultrasound field of spatially varying ultrasound amplitude in the target volume; wherein the ultrasound field is arranged to modify the optical path length of light passing through the target volume; and wherein the ultrasound field is arranged to define a plurality of regions in the target volume, wherein each region provides a unique modification of the optical path length.

In another aspect there is provided a method of determining the path taken by light through a volume of tissue, the method comprising: providing an ultrasound field of varying ultrasound amplitude to the tissue to define a plurality of regions within the volume, each region providing a unique modification of the optical path length of light passing through the region based on the local ultrasound amplitude; emitting light into the volume; detecting the light from the volume; determining a phase shift of the detected light; and determining, based on the phase shift, the regions through which the light travelled.

The modification of optical path length may be provided by the local amplitude of the ultrasound field in each region.

The ultrasound field may be provided by the superposition of coherent ultrasound waves emitted by the ultrasound source. The superposition of ultrasound waves in each region may provide the unique modification of the optical path length.

The regions may define a plurality of routes through the target volume, each route comprising a sequence of regions providing a path through which the light can travel from the source to the detector, and the modifications of the optical path length provided by each region may be selected so that each route provides a different total optical path length from all other routes of the plurality of routes.

A plurality of optical sources and/or optical detectors may be provided. The optical source may comprise an array of spatially separated optical sources. The optical detector may comprise an array of spatially separated optical detectors. For example each optical source may have a corresponding optical detector. Such an array may enable a greater section of brain tissue to be imaged. For example at least 5, for example approximately 10 optical sources may be provided. For example at least 5, for example at least 10, for example approximately 20 optical detectors may be provided. Providing an array of optical sources and/or detectors may enable increased spatial resolution, spatial coverage and depth information. The optical source may be a coherent source, for example a laser, e.g. one or more laser diodes. The optical source may have a power of greater than lmW/cm², for example greater than 5mW/cm², for example less than 2010mW/cm², for example around 10mW/cm². The optical source may provide light with various wavelengths. For example a wavelength of between approximately 650nm to 950nm, may be provided. Light of this wavelength may penetrate deeper into the brain and may minimize the amount of scattering that occurs. In particular, light in this range may correspond to the first "optical window" of the body, and may enable the light to penetrate the skull and other head tissue and effectively interact with the brain as desired. In other examples light with other wavelengths may be provided.

The optical detector may comprise a photodiode, for example an avalanche photodiode (APD). This may enable very weak light signals to be detected. The detector may comprise a lock-in detector, for example in combination with an APD. A lock-in amplifier may also be provided, for example in combination with an APD. This may enable noise signals to be removed, and more efficiently detect the emitted and phase modulated light.

The ultrasound source may comprise a plurality of ultrasound-on- chip transducers. Use of ultrasound on-chip transducers may reduce at least one of the cost, size and weight of the apparatus. The transducers may be configured, e.g. programmed, to provide the ultrasound field, e.g. to produce a desired sound wave shape.

The ultrasound source may comprise a phase conjugate lens in conjunction with a single element transducer.

The plurality of ultrasound-on-chip transducers may be arranged in at least one group, wherein each group of transducers provide a plurality of ultrasound waves having a single frequency and amplitude. The at least one group of transducers may comprise a first group and a second group; wherein the first group provides a plurality of ultrasound waves having a first frequency and a first amplitude; and wherein the second group provides a plurality of ultrasound waves having a second frequency and a second amplitude.

The ultrasound source may comprise an acoustic hologram plate. The acoustic hologram plate may be 3D printed. The hologram plate may be arranged to change the shape of a generated sound wave to provide the ultrasound field. The ultrasound field may have a frequency of less than 1.5 MHz, for example less than 1MHz. Frequencies in this range may avoid heating occurring within brain and other human tissue, and may avoid being distorted by tissue such as the skull. The ultrasound may have a frequency of between 0.3MHz and 0.4MHz. As well as avoiding the above effects, ultrasound of this frequency may avoid causing neural stimulation which can distort the detected light signal. Ultrasound of this frequency may therefore provide a good level of propagation into the brain as well as a high focussing ability. Alternative ultrasound frequencies may be provided in other environments, for example if a portion of skull of the subject was absent or removed, or if a different area of the body is to be analysed.

The optical source may be configured to provide the emitted light as a train of pulses.

The apparatus may further comprise a path determiner, configured to determine through which regions of the field the pulse train passed, based on the difference between the phase of the emitted pulse train and the phase of the detected pulse train.

The path determiner may be configured to extract, from the detected pulse train, a signal indicating activation of tissue within the volume. The signal indicating activation of tissue may be extracted using a stimulus signal corresponding to a stimulus provided to the subject. The path determiner may be configured to extract, from the detected pulse train, signals which are synchronised with the stimulus signal. The signals that are synchronised with the stimulus may comprise signals that are at least one of time locked and phase locked with the stimulus signal. Extracting signals which are synchronised with the stimulus may comprise determining phase information using quadrature detection.

The present disclosure may provide a headset comprising the apparatus.

Brief Description of Figures

Embodiments of the disclosure will now be described with reference to the accompanying drawings, in which:

Figure 1 shows a subject wearing a headset for detecting optical signals from the brain; Figure 2 shows a schematic diagram of an apparatus which may be incorporated into the headset of Figure 1;

Figure 3 shows a schematic diagram of a controller for providing and obtaining signals from an apparatus such as that shown in Figure 2; Figure 4 gives a flow diagram which illustrates a process which may be performed by the apparatus;

Figure 5 gives a flow diagram which illustrates another process which may be performed by the apparatus;

Figure 6 gives a flow diagram which illustrates another process which may be performed by the apparatus.

In the drawings like reference numerals are used to indicate like elements. Detailed Description

Described herein are methods and apparatus for providing an ultrasound field within an area of brain tissue, the field may provide discrete regions of differing ultrasound amplitude, for example so that the field has the form of a mesh in that area of brain tissue. The ultrasound in each discrete region of the mesh may modify the optical properties of the tissue in that discrete region according to the ultrasound amplitude in that region.

By measuring the phase shift of light which has passed through the area of tissue, the sections of the field through which the light has travelled can be determined. This may enable improved localisation of brain activity.

Figure 1 shows a subject 100 whose brain is to be analysed. The subject 100 is wearing a headset 102, which, as is described in more detail below, comprises acoustic and optical components. The headset 102 may substantially surround the brain of the subject 100, or may be placed against a specified area of the brain such as the visual cortex and/or the motor cortex and so forth.

The headset 102 is connected to a controller 104 by at least one output 106 and at least one input 108. The controller 104 is configured to communicate with the headset 102 via the output 106 and the input 108, in particular the headset is configured to provide and obtain signals to and from the headset via the output 106 and the input 108 respectively. For example, the controller 102 may control optical and ultrasound sources in the headset 102 and obtain optical signals from a detector in the headset 102, as explained in more detail below.

Figure 2 gives a schematic view of an example of an acousto-optic apparatus 200 which may be provided within a headset, such as a headset 102 shown in Figure 1. The acousto-optic apparatus 200 comprises an optical source 201, which is configured to emit photons 212, 214, into a target area 250 of the subject's brain. In particular the optical source is a coherent source such as a laser e.g. a laser diode.. The optical source may have a power of around 10mW/cm², and a wavelength of between 650nm and 950nm.The optical source 201 is electrically connected to a controller 300. For example, the controller may send signals to the optical source 201 to control the emission of light into the target area.

The emitted photons 212, 214 travel through the area of the brain 250 and are detected at an optical detector 202. The detector 202 is also electrically connected to the controller 300, and is configured to send signals to the controller based on the detected light. The detector 202 may be a photodiode, for example an avalanche photodiode (APD). The distance between the optical source 201 and the optical detector 201 may vary depending on the depth of tissue to be analysed. Although only a single optical source 201 and optical detector

202 are shown in Figure 2, it will be appreciated that an array of spatially separated sources and/or detectors could be provided, in order to analyse a greater area of brain tissue. For example an array of multiple sources and/or detectors could be provided. For example, approximately 10 optical sources, e.g. laser diodes, could be provided in an array, and/or approximately 20 detectors could be provided in an array. In other examples, for example where the target area of the brain is larger, greater numbers of sources and detectors can be provided. In some examples each optical source has a corresponding optical detector.

As the light travels through the target area 250 it encounters brain tissue which modulates the phase of the emitted light. In particular the phase of the light is modulated because of the refractive index and scattering properties of the tissue through which the light travels. The extent of this phase shift can be determined at the controller 300 based on comparing the signal from the detector 202, and the signal which characterises the light emitted at the optical source 201.

The optical properties of the tissue, that is, the refractive index and scattering properties, within the target area 250 can be modified using acoustic waves. When ultrasound is focused on a medium such as the human brain it causes a periodic compression and rarefaction of the tissue which has two main optical effects. Firstly, it causes a modification of the refractive index of that specific piece of tissue. Secondly, it causes a modification of the position of the optical scattering sites. Photons that travel through or near to the ultrasound focus then accumulate a phase modulation through these two effects.

To achieve this the apparatus 200 further comprises an ultrasound source 203. The ultrasound source 203 emits ultrasound waves, for example having a frequency of less than 1 MHz which together provide an ultrasound field of varying intensity within the target areas 250. For example the ultrasound source 203 may be configured to provide ultrasound waves which have a frequency of between 0.3MHz and 0.4MHz. In particular the ultrasound source is configured to provide the ultrasound field as a lattice or mesh, comprising discrete regions of substantially constant ultrasound amplitude (i.e. focal points) 210a-f. In some examples each region may have a length and/or width between approximately 100 microns and 1 millimetre, for example approximately 500 microns. Each of the regions 210a-f have a particular ultrasound amplitude, which thus each provide a unique phase and frequency shift to photons which pass through that region (e.g. the light undergoes a Doppler shift). In passing through several regions between the optical source 201 and detector 202, a photon will thus accumulate a particular total phase modulation based on the region of the field through which it passes. In doing so the light becomes be encoded or 'tagged' with a particular phase shift. This phase shift can be decoded by the controller once the photons have reached the detector 202. For example as shown in

Figure 2, a first photon 212 passes through regions 210a, 210f,

210e, and 210d before reaching the detector, and therefore is tagged with a specific accumulated phase modulation, whereas a second photon 214 passes through regions 210a, 210b, 210c, 210d, and is therefore tagged with a different accumulated phase modulation. The ultrasound source 203 is configured to provide a field where each region has an amplitude such that every path through a particular set of regions of the field causes a unique phase shift. The controller 300 can then decode the phase modulation to determine a particular path taken by the passed through the field - in particular to determine through which regions of the field the light passed. The ultrasound source 203 may comprise an ultrasound transducer, for example an on-chip ultrasound transducer. For example the ultrasound source may be provided by an array of ultrasound transducers, such as capacitive micromachined ultrasonic transducers (CMUT) and/or Piezoelectric Micromachined Ultrasonic Transducers (PMUT). For example between 2000 and 4000 transducers may be provided in such an array.

Alternatively, or additionally, the ultrasound source may comprise an acoustic hologram generator. For example, the sound waves can be shaped using acoustic holograms in conjunction with at least one transducer, e.g. an on-chip transducer. The use of an on-chip transducer may help to reduce the cost size and weight of the apparatus. Such examples may utilise an acoustic lens, (which for example may be 3D printed) to create acoustic hologram. For example, the lens may be created based on a predetermined phase map which shapes an acoustic wave from a transducer into the desired shape of the ultrasound field. This phase map is designed to diffract the acoustic wave to form a predesigned acoustic pattern, such as a lattice (mesh) shape as shown in Figure 2, and also to modulate the amplitude and phase of the ultrasound wave.

The above described ultrasound field may be provided and/or modified based on the physical, acoustic and/or optical properties of the different tissue types that may be present between the source and the detector, for example skin, aponeurosis, periosteum, skull, meninges including dura mater, arachnoid mater, pia mater, subarachnoid space and cerebrospinal fluid. For example, the ultrasound field may be provided taking into account the width, density, scattering properties, absorption properties of these different tissue types, based on standard e.g. typical or known values, to provide an ultrasound field with regions which provide unique optical phase shifts. Alternatively or additionally, the above properties may be determined for a particular subject based on obtained data, e.g. via a scan of the subject's head tissue, e.g. a Magnetic Resonance Imaging (MRI) scan. In some examples such as that shown in Figure 2, linear arrays can be produced at different angles which intersect to provide the mesh/lattice field. For example, Figure 2 shows a linear array at 60 degrees from the left side, 90 degrees from the centre and 120 degrees from the right side causing the beams to cross when in the target area of the brain 250. Further such linear arrays could be added in other examples to create a mesh with a greater number of regions of unique amplitude. As described above each unique region causes unique phase changes when light passes through it.

In some examples several transducers, e.g. silicon transducer, can be grouped together to create a wave. For example, around 100 silicon transducers could be grouped together to create a wave. In such an example each group of silicon transducers can produce three linear waves at the same frequency and amplitude, one which is perpendicular to the transducer (90 degrees), one which is on a 60 degree angle from the transducer and one which is on a 120 degree angle from the transducer, such as is shown in Figure 2. This is then repeated for each group of 100 silicon transducers, with each group providing a wave of different frequency and amplitude, where the frequency and amplitude of each group is assigned in order to provide unique phase shifts for each region when the waves are combined.

Figure 3 shows a schematic view of a controller 300, such as may be used as part of the apparatus described above with reference to Figure 2. The controller 300 comprises an optical source output 302 which is arranged to communicate with an optical source such as the one described above. In particular the optical source output 302 is configured to provide signals, e.g. control signals to the optical source. The optical source output 302 is also connected to a processor 304 and is arranged to receive signals from the processor. The optical source output 302 is therefore configured to provide signals from the processor 304 to the optical source. For example, as described in more detail below the optical source output is configured to provide control signals from the processor to the optical source, for example to control the on-off time and pulse width of the optical source.

The processor 302 comprises a path determiner 314, configured to determine, based on the signal obtained from the detector input 306. This is described in more detail below. The controller further comprises a detector input 306. The detector input 306 is arranged to communicate with, for example obtain signals from, an optical detector such as the one described above. The detector input 306 is also arranged in communication with the processor 304, such that the detector input 306 is configured to obtain signals from a detector and provide them to the processor 304. In examples where an array of detectors is provided, the detector input is configured to obtain signals from each detector and provide them to the processor.

The controller 300 further comprises an ultrasound output 308 which is arranged to communicate with an ultrasound source such as the one described above. In particular the ultrasound source output 308 is configured to provide signals, e.g. control signals to the ultrasound source. The ultrasound source output 308 is also connected to the processor 304 and is arranged to receive signals from the processor. The ultrasound output 308 is therefore configured to provide control signals from the processor 304 to the ultrasound source, for example to control the on-off times and amplitude of one or more ultrasound transducers.

The controller 300 further comprises a reference unit 310, which is also arranged to communicate to the processor 304. The processor 304 is configured to obtain, from the reference unit 310, one or more reference signals. The path determiner 314 is configured to compare the one or more reference signals with the signal obtained from the detector input 306. For example, the timing and or the phase of the detected signal may be compared with that of the output signal. The path determiner 314 is configured determine, based on this comparison, the area of the ultrasound field and therefore the areas of the brain through which light passed. The path determiner 314 may further be able to identify areas of stimulation in the brain based on the comparison of the detected signal with a reference signal. Examples of such processes are described in more detail below. In certain applications, the optical source output 302 may be connected to the reference unit 310, instead of or in addition to the processor 304. For example, the reference signal may be based on the signal provided to the optical source, and/or it may be based on a signal characterising a stimulus applied to a subject, as discussed in more detail below. The controller also comprises a memory unit 312, arranged in communication with the processor 304. The memory unit 312 stores data which defines an association between a determined phase shift and a path taken by the light. For example, the data may correspond to that used to design the map of the field provided by the ultrasound source. The memory unit 312 may store the relationship in the form of a look-up table, which identifies, for each detected phase shift, a corresponding unique sequence of regions of the field that the light passed through. The path determiner 314 is thus able to obtain from the memory unit 312 an indication of the route taken by the light, based on the determined phase shift. The processor 304 is also configured to provide data to the memory 312, for example data corresponding to the signals from the detector input 306, so that such data can be stored in the memory 312.

Figure 4 shows a flow diagram of a general method 400 which may be performed by an apparatus such as that described above with reference to Figures 2 and 3, to determine the path taken by light through an ultrasound field. Firstly, an ultrasound field of varying amplitude, for example as described above in relation to Figure 2, is applied 401 to an area of brain tissue, to provide the change in optical properties of the tissue as described above. Secondly, light is emitted 402 into the brain tissue, e.g. from an optical source. After passing through the target area, including brain tissue, the light is detected 403 at a detector. Based on the detected light the phase shift of the light is determined 404, e.g. by a controller. This phase shift may be determined based on a comparison of the detected light with that of a reference signal - for example the reference signal may be the output signal for the optical source. Based on this determined phase shift, the regions of the ultrasound field through which light travelled is determined, by obtaining data indicating the relationship between a phase shift and a series of regions in the ultrasound field.

Figure 5 shows a flow diagram of a specific example of a method 500 which may be used to determine the path that light has taken through the ultrasound field. In a first step 501 an ultrasound field of varying amplitude is provided within the tissue of the target area of the brain. In particular, as discussed above, a field is provided which has regions of unique ultrasound amplitude, and which provides unique total phase shifts for each combination of regions through which light could pass as it travels through the field. Light is then emitted 502 into the target volume which contains brain tissue. In particular the light is emitted as a train of pulses. This pulse train is then detected 503 after having passed through the target volume. The detected pulse train is then compared 504 with a reference signal, which in this case is the pulse train emitted into the target volume. In particular, the delay between the emitted pulse train and detected pulse train is calculated, and, based on this delay a total phase shift for the light is determined 505. Based on this determined phase shift, the regions of the ultrasound field through which the light passed can be determined 506 because, as described above, each possible sequence of regions of the field through which the light could pass provides a unique total phase shift. In some examples, the time of flight taken for the light to travel between the source and detector can be measured, for example with nanosecond resolution. In so doing, light which arrives at the detector before or after a certain time can be filtered out from the detected signal. For example, if photons have taken a time shorter than a first time 'c' (depending on the distance between the source and the detector) to arrive at the detector, this indicates that they have only passed through the skull and haven't reached the brain tissue that is to be analysed. Similarly, if photons have taken a time longer than a second time 'y' to reach the detector, this may indicate that the photon has scattered too much and will deteriorate the signal. These photons can therefore be filtered out of the detected signal to reduce noise - i.e. increase the signal-to noise ratio and improve spatial resolution. In other examples light may be detected using a time-gated system, which filters the useful signal into different time-gates depending on the time of flight of the specific photons, to further enhance this effect. Figure 6 shows a flow diagram of an example method 600 which can be used, in conjunction with the method of localisation described in Figure 5, to determine an area of stimulation in the brain. In particular, a stimulus, such as a sequence of flashes of light that are shone into the subject's eyes, can be applied to a subject and the optical response of the brain tissue measured. Such a sequence of flashes may cause a corresponding sequence of activation in the brain of the subject, which changes the optical properties (e.g. refractive index, scattering properties) of the brain tissue in a particular area of the brain. Alternatively, the stimulus could be an auditory or tactile stimulus, which similarly causes changes in the optical properties of brain tissue in a particular area. The changes in optical properties of the brain caused by this stimulation can be detected using the apparatus described above. In particular, the stimulus applied to the subject, and the corresponding tissue response can both be characterised by a signal, (the stimulus signal) and, by comparing the detected signal with the applied stimulus signal, brain stimulation can be detected. By using this information in conjunction with the localisation method described above, the location of stimulation within the target volume can be determined.

In the first step 601 a stimulus such as a sequence of flashes is applied to a subject. In the next step 602, the localisation method, such as described above with reference to Figure 5 is performed. Because of the application of the stimulus, the light signal detected is based on the emitted light, the ultrasound field, and also the applied stimulus, and thus the detected light signal is encoded with a phase shift based on the ultrasound field, and also based on the applied stimulus. In the next step 603, a signal synchronised with the stimulus signal can be extracted from the detected signal. For example, these signals may be time locked and/or phase locked with the stimulus signal, and may be extracted, if present, using the stimulus signal as a reference signal. For example, the controller may be configured to obtain the detected signal (from the detector), and the stimulus signal (e.g. from the reference unit) and attempt extract the stimulus signal from the detected signal. This extraction processes may comprise determining phase information of the detected signal using quadrature detection. If a stimulus signal can be extracted from the detected signal, this indicates that activation occurred in response to the stimulus in the area of the brain the light passed through. Therefore, by using the localisation information obtained from the detected signal based on the ultrasound field, the location of this activation inside the brain can be determined to a high resolution. For example, with a single detector the activation can be narrowed down to a particular area within the set of regions it has been determined that light travelled. Where an array of optical sources and detectors are provided, the stimulus signal can be attempted to be extracted from each detected signal, and based on which of the detected signals the stimulus signal can be extracted from, the location of activation can be further pinpointed. The methods and apparatus described may therefore enable greater resolution in brain imaging and in determining, mapping or imaging the areas of the brain which may be stimulated.

It will be appreciated by the skilled addressee in the context of the present disclosure that the methods and apparatus described herein may be implemented in custom built hardware logical processing units such as electronics to generate the various outputs which may be used to control the apparatus. One example of such a system is described above, but it will be appreciated that the division of functionality between different parts of that system is merely exemplary and the functionality of one or more of the parts of the system described with reference to the figures may be shared with other parts of that system, or integrated into a single element. It will also be appreciated that controllers may also comprise programmable processors, so the control scheme and apparatus described above, may also be implemented in a suitably programmed processor of any controller 300. One example of suitable programming is computer readable instructions which program such a processor to perform the methods described above. Accordingly, in some examples of the disclosure, one or more memory elements can store data and/or program instructions used to implement the operations described herein. Embodiments of the disclosure provide tangible, non- transitory storage media comprising program instructions operable to program a processor to perform any one or more of the methods described and/or claimed herein and/or to provide data processing apparatus as described and/or claimed herein.

The function of one or more of the elements shown in the drawings may be further subdivided, and/or distributed throughout apparatus of the disclosure. In some embodiments the function of one or more elements shown in the drawings may be integrated into a single functional unit. Such functional units (e.g. one or more features of the controller 300, such as the processor and its components) may be implemented with fixed logic such as assemblies of logic gates or programmable logic such as software and/or computer program instructions executed by a processor. Mixtures of software and hardware may also be used. Any kind of programmable logic can also be used, examples of suitable programmable logic include programmable processors, programmable digital logic (e.g., a field programmable gate array (FPGA), an erasable programmable read only memory (EPROM), an electrically erasable programmable read only memory (EEPROM)), an application specific integrated circuit, ASIC, or any other kind of digital logic, software, code, electronic instructions, flash memory, optical disks, CD-ROMs, DVD ROMs, magnetic or optical cards, other types of machine-readable mediums suitable for storing electronic instructions, or any suitable combination thereof.

It will be appreciated from the discussion above that the embodiments shown in the Figures are merely exemplary, and include features which may be generalised, removed or replaced as described herein and as set out in the claims. With reference to the drawings in general, it will be appreciated that schematic functional block diagrams are used to indicate functionality of systems and apparatus described herein. It will be appreciated however that the functionality need not be divided in this way, and should not be taken to imply any particular structure of hardware other than that described and claimed below. The function of one or more of the elements shown in the drawings may be further subdivided, and/or distributed throughout apparatus of the disclosure. In some embodiments the function of one or more elements shown in the drawings may be integrated into a single functional unit. The above embodiments are to be understood as illustrative examples. Further embodiments are envisaged. It is to be understood that any feature described in relation to any one embodiment may be used alone, or in combination with other features described, and may also be used in combination with one or more features of any other of the embodiments, or any combination of any other of the embodiments. Furthermore, equivalents and modifications not described above may also be employed without departing from the scope of the invention, which is defined in the accompanying claims.

Claims

CLAIMS:

1. A brain tissue acousto-optic apparatus comprising: an optical source configured to emit light towards a target volume containing brain tissue of a living subject; an optical detector configured to detect light from the target volume; an ultrasound source arranged to provide an ultrasound field of spatially varying ultrasound amplitude in the target volume; wherein the ultrasound field is arranged to modify the optical path length of light passing through the target volume; and wherein the ultrasound field is arranged to define a plurality of regions in the target volume, wherein each region provides a unique modification of the optical path length.

2. The apparatus of claim 1, wherein the modification of optical path length is provided by the local amplitude of the ultrasound field in each region.

3. The apparatus of claim 1 or 2, wherein the ultrasound field is provided by the superposition of coherent ultrasound waves emitted by the ultrasound source.

4. The apparatus of claim 3 wherein the superposition of ultrasound waves in each region provides the unique modification of the optical path length.

5. The apparatus of any preceding claim, wherein the regions define a plurality of routes through the target volume each route comprising a sequence of regions providing a path through which the light can travel from the source to the detector, and the modifications of the optical path length provided by each region are selected so that each route provides a different total optical path length from all other routes of the plurality of routes.

6. The apparatus of any preceding claim, wherein the optical source comprises an array of spatially separated optical sources; and/or wherein the optical detector comprises an array of spatially separated optical detectors.

7. The apparatus of any preceding claim, wherein the ultrasound source comprises a plurality of ultrasound-on-chip transducers.

8. The apparatus of claim 7 wherein the plurality of ultrasound-on-chip transducers are arranged in at least one group, wherein each group of transducers provide a plurality of ultrasound waves having a single frequency and amplitude.

9. The apparatus of claim 8 wherein the at least one group of transducers comprises a first group and a second group; wherein the first group provides a plurality of ultrasound waves having a first frequency and a first amplitude; and wherein the second group provides a plurality of ultrasound waves having a second frequency and a second amplitude.

10. The apparatus of any preceding claim wherein the ultrasound source comprises an acoustic hologram plate.

11. The apparatus of claim 10 wherein the acoustic hologram plate is 3D printed.

12. The apparatus of any preceding claim wherein the ultra-sound has a frequency of less than 1.5 MHz.

13. The apparatus of any preceding claim, wherein the optical source is configured to provide the emitted light as a train of pulses.

14. The apparatus of claim 13, further comprising a path determiner, configured to determine through which regions of the field the pulse train passed, based on the difference between the phase of the emitted pulse train and the phase of the detected pulse train.

15. The apparatus of claim 14, wherein the path determiner is configured to extract, from the detected pulse train, a signal indicating activation of tissue within the volume.

16. The apparatus of claim 15, wherein the signal indicating activation of tissue is extracted using a stimulus signal corresponding to a stimulus provided to the subject.

17. The apparatus of claim 16, wherein the path determiner is configured to extract, from the detected pulse train, signals which are synchronised with the stimulus signal.

18. The apparatus of claim 17, wherein signals that are synchronised with the stimulus comprise signals that are at least one of time locked and phase locked with the stimulus signal.

19. The apparatus of claim 17 or 18, wherein extracting signals which are synchronised with the stimulus comprises determining phase information using quadrature detection.

20. A wearable headset comprising the apparatus of any preceding claim.

21. A method of determining the path taken by light through a volume of tissue, the method comprising: providing an ultrasound field of varying ultrasound amplitude to the tissue to define a plurality of regions within the volume, each region providing a unique modification of the optical path length of light passing through the region based on the local ultrasound amplitude; emitting light into the volume; detecting the light from the volume; determining a phase shift of the detected light; and determining, based on the phase shift, the regions through which the light travelled.