CN114199405B - Temperature measuring method and system based on GRE (GRE) image and magnetic nanoparticles - Google Patents

Temperature measuring method and system based on GRE (GRE) image and magnetic nanoparticles Download PDF

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CN114199405B
CN114199405B CN202111423713.5A CN202111423713A CN114199405B CN 114199405 B CN114199405 B CN 114199405B CN 202111423713 A CN202111423713 A CN 202111423713A CN 114199405 B CN114199405 B CN 114199405B
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王帅
彭浩
刘文中
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Huazhong University of Science and Technology
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    • G01MEASURING; TESTING
    • G01KMEASURING TEMPERATURE; MEASURING QUANTITY OF HEAT; THERMALLY-SENSITIVE ELEMENTS NOT OTHERWISE PROVIDED FOR
    • G01K7/00Measuring temperature based on the use of electric or magnetic elements directly sensitive to heat ; Power supply therefor, e.g. using thermoelectric elements
    • G01K7/36Measuring temperature based on the use of electric or magnetic elements directly sensitive to heat ; Power supply therefor, e.g. using thermoelectric elements using magnetic elements, e.g. magnets, coils
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N24/00Investigating or analyzing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects
    • G01N24/08Investigating or analyzing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects by using nuclear magnetic resonance
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A90/00Technologies having an indirect contribution to adaptation to climate change
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Abstract

The invention discloses a temperature measuring method and a system based on GRE images and magnetic nanoparticles, which belong to the technical field of nano material testing and comprise the following steps: guiding the magnetic nanoparticles into an object to be detected to obtain a sample to be detected, and acquiring GRE images of the sample to be detected at a plurality of TE (time evolution) times at a known temperature as reference images at corresponding TE times; the plurality of TE times comprises a predetermined target TE time; at a target moment, obtaining GRE images of a sample to be detected at multiple TE time, calculating image phase difference delta phi and image amplitude change of the sample to be detected at each TE time, and fitting T2 relaxation time; establishing a model according to a corresponding relation f (C, T) of the phase difference and the magnetic nanoparticle concentration and the temperature, and a corresponding relation g (C, T) of T2 relaxation time and the magnetic nanoparticle concentration and the temperature, wherein the corresponding relation f (C, T) is calibrated in advance:
Figure DDA0003378298290000011
and solving the concentration C and the temperature T of the magnetic nanoparticles, and taking the T as the temperature of the object to be detected. The invention can improve the precision and speed of temperature measurement.

Description

Temperature measuring method and system based on GRE (GRE) image and magnetic nanoparticles
Technical Field
The invention belongs to the technical field of nano material testing, and particularly relates to a temperature measuring method and system based on GRE images and magnetic nanoparticles.
Background
Temperature is an important characteristic of life activities, and cell activities including division, metabolism, gene expression and the like are accompanied by temperature changes, so that sensing the 'thermal events' on a cell level is helpful for mastering energy changes in the cell activities, and the method has important significance for drug targeting and tumor thermotherapy. However, due to the "sealing" of living bodies, how to non-invasively and accurately perceptually measure these "thermal events" becomes a leading topic and key challenge in life medicine.
In recent years, magnetic temperature measurement methods have been considered as one of the most promising approaches in the field of temperature imaging due to their good penetration. Magnetic Nanoparticles (MNPs), such as iron oxide nanoparticles, have great potential for development due to their excellent magneto-temperature properties. In 2009, Weaver et al used the ratio of the magnitude of the fifth and third harmonics of the ac magnetization of magnetic nanoparticles to make the temperature measurement error reach 0.3K. From 2011, a professor team in Liu text systematically studies the mechanism of magnetic nanoparticle temperature measurement, including the excitation mode of a magnetic field and the construction of a temperature measurement model, and finally realizes the temperature measurement under multiple scenes.
In the patent application publication No. CN 110687152 a, a magnetic method and apparatus for monitoring activity and temperature of a moving object are disclosed, and the related technical solution is specifically: performing primary nuclear magnetic resonance imaging on a detected body to obtain a primary nuclear magnetic resonance spectrum image containing resonance frequency and spectrum half-height width information; laying magnetic nano particles in a detected body until the magnetic nano particles reach a target position and reach an equilibrium state; after a plurality of activity cycles of the measured body, carrying out nuclear magnetic resonance imaging on the measured body again to obtain a nuclear magnetic resonance spectrum image; obtaining concentration information and temperature information of the magnetic nanoparticles according to the correlation between the variation of the resonance frequency and the full width at half maximum of the spectrum of the two imaging and the concentration and the temperature of the magnetic nanoparticles; and repeating the two steps to obtain the change condition of the concentration and the temperature of the magnetic nanoparticles along with time, thereby realizing the monitoring of the activity of the tested body.
The above patent application document can obtain the correlation between the variation of the resonance frequency and the full width at half maximum of the spectrum and the concentration and the temperature of the magnetic nanoparticles by using the magnetic nanoparticles as the sensor, and has high spatial resolution and temperature resolution. However, since the spectral image is actually a curve, the imaging resolution is low, which affects the accuracy of temperature measurement; moreover, the imaging speed of the spectrum image is slow, and the temperature of the object to be measured may change in real time during the actual temperature measurement, so that the temperature may have changed greatly during the scanning process, which may affect the accuracy of the temperature measurement on one hand, and on the other hand, the real-time temperature measurement cannot be realized. In addition, the spectral image can only image one sample at a time, the field drift can not be corrected by using a constant temperature reference object in long-time measurement, and a temperature insensitive substance needs to be added into the sample as an internal reference, which can greatly increase the difficulty of subsequent data processing.
Disclosure of Invention
Aiming at the defects and the improvement requirement of the prior art, the invention provides a temperature measurement method and a temperature measurement system based on GRE images and magnetic nanoparticles, and aims to improve the accuracy and speed of temperature measurement.
To achieve the above object, according to one aspect of the present invention, there is provided a temperature measurement method based on GRE images and magnetic nanoparticles, comprising:
introducing the magnetic nanoparticles into an object to be detected to obtain a sample to be detected, and acquiring GRE images of the sample to be detected at a plurality of TE (time evolution) times at a known temperature to serve as reference images at corresponding TE times; the plurality of TE times comprises a predetermined target TE time;
at a target moment, obtaining GRE images of a sample to be detected at multiple TE time, calculating image phase difference delta phi and image amplitude change of the sample to be detected at each TE time, and fitting T2 relaxation time according to the image amplitude change;
establishing a model according to a corresponding relation f (C, T) between the phase difference and the magnetic nanoparticle concentration and the temperature, and a corresponding relation g (C, T) between T2 x relaxation time and the magnetic nanoparticle concentration and the temperature, wherein the corresponding relations are calibrated in advance:
Figure BDA0003378298270000031
and solving the concentration C and the temperature T of the magnetic nanoparticles according to the established model, and taking the temperature T as the temperature of the object to be detected.
The method combines magnetic nanoparticles with magnetic resonance imaging, calibrates the corresponding relation between phase difference related to a GRE image and the concentration and temperature of the magnetic nanoparticles and the corresponding relation between T2 relaxation time and the concentration and temperature of the magnetic nanoparticles in advance, and obtains the GRE image of a sample at different TE time after the magnetic nanoparticles are introduced into a body to be measured based on the corresponding calibration result, namely, the concentration and temperature of the magnetic nanoparticles in the sample can be solved and obtained at the same time, wherein the temperature is also the temperature of the body to be measured; the GRE (gradient Recall echo) image is a two-dimensional image, has high resolution and high imaging speed, can quickly acquire the GRE image of a sample at a target moment needing temperature measurement, improves the temperature measurement speed, ensures that the acquired image is the image at the target moment, and effectively improves the temperature measurement precision.
Furthermore, the correspondence f (C, T) between the phase difference and the magnetic nanoparticle concentration and the temperature, and the correspondence g (C, T) between the relaxation time T2 and the magnetic nanoparticle concentration and the temperature are calibrated in a manner that includes:
(S1) preparing magnetic nanoparticle solutions with different concentrations in advance to serve as samples to be calibrated;
(S2) simultaneously placing all samples to be calibrated in pure water having a temperature higher than the maximum temperature of the object to be measured, and placing the samples in a coil for receiving magnetic resonance signals;
(S3) after the samples to be calibrated and the pure water reach thermal equilibrium, measuring the temperature of the pure water in real time and measuring images corresponding to the temperature points by utilizing a GRE sequence; the GRE sequence sets a plurality of TE times;
(S4) taking the temperature of each sample to be calibrated and pure water when the samples to be calibrated and the pure water reach thermal equilibrium as a reference temperature, taking a GRE image at the reference temperature as a reference GRE image, calculating the image phase difference and the image amplitude change of each object to be calibrated at each TE time according to the GRE image and the reference GRE image at each temperature point, and fitting the T2 relaxation time corresponding to each sample to be calibrated according to the image amplitude change;
(S5) according to the calculation result of (S4), fitting to obtain a corresponding relation g (C, T) of T2 x relaxation time, magnetic nanoparticle concentration and temperature and a corresponding relation f (C, T) of phase difference, magnetic nanoparticle concentration and temperature at each TE time, taking the corresponding relation as a calibration result at the corresponding TE time, and calculating a corresponding temperature measurement error;
(S5) taking the TE time corresponding to the calibration result with the minimum temperature measurement error as the target TE time, and taking the calibration result corresponding to the TE time as the final calibration result.
The magnetic nano particles and the magnetic resonance imaging are combined, a plurality of samples can be imaged at the same time, and the calibration efficiency is high; the TE time is the echo time of the GRE sequence scanning image, T2 relaxation time of the sample can be obtained according to the amplitude values of the GRE sequence scanning image under a plurality of TEs, and T2 contains magnetic field nonuniformity information and can reflect the magnetic susceptibility of the magnetic nanoparticles; the optimal TE time cannot be directly determined at the initial time of calibration, a plurality of different TE times are set, T2 relaxation time is fitted by using imaging results of the plurality of TE times, calibration is respectively carried out on each TE time, the TE time which enables the temperature measurement error to be minimum is selected from the TE times, the TE time is used as the target TE time in actual measurement, and the calibration result corresponding to the target TE time is used as the calibration result used in the actual measurement, so that the temperature measurement error can be minimized, and the accuracy of the temperature measurement is further improved.
Further, the step (S2) further includes: placing a constant temperature reference object beside the pure water, and placing the constant temperature reference object into a coil, so that each GRE image acquired in the step (S3) simultaneously comprises the pure water and the constant temperature reference object;
in step (S4), at any one of the temperature points T 0 Optional sample C to be calibrated 0 At any TE time TE 0 The following image phase difference calculation method includes:
according to temperature point T 0 TE time TE 0 GRE image and TE time TE of 0 Respectively calculating the samples C to be calibrated according to the reference GRE images 0 Subtracting the second phase difference from the first phase difference to obtain a sample C to be calibrated 0 At temperature point T 0 TE time TE 0 The phase difference of the images.
In the calibration process, the related temperature change experiment, namely the process that the sample and pure water are subjected to heat exchange and are changed to room temperature together after reaching heat balance, needs longer time, the stability of the system is not ensured, and the situation of magnetic field drift may exist, and the magnetic field drift further causes phase fluctuation, thereby influencing the result of temperature measurement based on phase difference; the constant temperature reference object is arranged outside the sample to be calibrated, the phase difference of the constant temperature reference object at different temperature measuring points can be used for reflecting the phase fluctuation, and the phase fluctuation is subtracted from the calculated real-time phase difference, so that the phase fluctuation caused by magnetic field drift can be calibrated, and the temperature measurement precision is further improved.
Further, the constant temperature reference is a water mold.
Further, the particle size of the magnetic nanoparticles is not more than 20 nm; the magnetic nanoparticles with the particle size of less than 20nm are of a single domain structure and show superparamagnetism, and when the particle size is more than 20nm, the magnetic nanoparticles can have a multi-domain structure, so that a model becomes complicated; the invention uses magnetic nano particles with the particle size not more than 20nm, has good temperature sensitivity and simple model, and is beneficial to improving the temperature measurement precision and the measurement efficiency.
Furthermore, the particle size range of the magnetic nanoparticles is 5-20 nm; for magnetic nanoparticles with different particle diameters, the temperature sensitivity is different, and with the increase of a main magnetic field, the temperature sensitivity of particles with small particle diameter is better, but the preparation concentration of the magnetic nanoparticles with too small particle diameter is higher; in the invention, the particle size range of the magnetic nanoparticles is 5-20 nm, and the magnetic nanoparticles are easy to obtain while ensuring good temperature sensitivity and simple model.
Further, the magnetic nanoparticles are Fe 2 O 3
According to another aspect of the present invention, there is provided a temperature measurement system based on GRE images and magnetic nanoparticles, comprising: the device comprises a preprocessing module, a magnetic resonance imaging device, a control module and a data processing module;
the pretreatment module is used for introducing the magnetic nanoparticles into an object to be detected to obtain a sample to be detected;
the magnetic resonance imaging device is used for scanning images through the GRE sequence to obtain GRE images;
the control module is used for acquiring GRE images of a sample to be detected at a plurality of TE (time evolution) times by using magnetic resonance imaging equipment at a known temperature; the plurality of TE times comprises a predetermined target TE time;
the control module is also used for acquiring GRE images of the sample to be detected at a plurality of TE (time-of-arrival) times by using the magnetic resonance imaging equipment at a target moment and triggering the data processing module;
a data processing module to: calculating the image phase difference delta phi and the image amplitude change of the sample to be detected at each TE time according to the GRE image and the reference image acquired at the target time, and fitting T2 relaxation time according to the image amplitude change; establishing a model according to a corresponding relation f (C, T) of the phase difference and the magnetic nanoparticle concentration and the temperature, and a corresponding relation g (C, T) of T2 relaxation time and the magnetic nanoparticle concentration and the temperature, wherein the corresponding relation f (C, T) is calibrated in advance:
Figure BDA0003378298270000061
and solving the concentration C and the temperature T of the magnetic nanoparticles according to the established model, and taking the temperature T as the temperature of the object to be detected.
Generally, by the above technical solution conceived by the present invention, the following beneficial effects can be obtained:
(1) the invention combines magnetic resonance imaging and magnetic nano-particle temperature measurement, the magnetic nano-particle has excellent magnetic-temperature characteristic, is non-toxic and harmless, has small enough volume, can be used as a reliable temperature sensitive element, can effectively realize the visualization of an object to be measured by the magnetic resonance imaging, and has higher imaging speed and larger imaging range compared with a wave spectrum by GRE sequence scanning, therefore, the invention can greatly improve the spatial resolution and the temperature resolution of the magnetic nano-particle and effectively improve the precision and the speed of the temperature measurement.
(2) The invention combines magnetic resonance imaging and magnetic nano particles to measure the temperature, can simultaneously image all samples to be calibrated each time in the calibration process, and has higher calibration efficiency.
(3) In the calibration process, the constant-temperature reference object is used for correcting phase fluctuation caused by magnetic field drift, so that the temperature measurement precision can be further improved.
Drawings
FIG. 1 is a schematic diagram of a GRE image and magnetic nanoparticle-based temperature measurement method provided by an embodiment of the invention;
fig. 2 is a GRE image of magnetic nanoparticle samples at the same temperature at different concentrations and different TE times according to an embodiment of the present invention;
FIG. 3 is a GRE image of magnetic nano-samples of different concentrations and different temperatures at the same TE time according to an embodiment of the present invention;
fig. 4 is a relationship between a phase of a GRE image of a magnetic nano sample according to temperature and concentration provided by an embodiment of the present invention;
fig. 5 is a graph showing the relationship between the relaxation time T2 of the magnetic nano sample GRE image according to the temperature and the concentration;
fig. 6 is a temperature error graph obtained by inversion using experimental data according to an embodiment of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention. In addition, the technical features involved in the embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.
In the present application, the terms "first," "second," and the like (if any) in the description and the drawings are used for distinguishing between similar elements and not necessarily for describing a particular sequential or chronological order.
Before explaining the technical scheme of the invention in detail, the following brief description is made on the relevant theoretical analysis:
after magnetic nano particles are introduced and an excitation magnetic field is applied, the magnetic nano particles are magnetized, so that a local magnetic field of magnetic resonance imaging is influenced, and a result of the magnetic resonance imaging is further influenced; the magnetic nano particles have good magnetic-temperature characteristics, so the magnetic nano particles can be used as reliable temperature sensitive elements;
the GRE scanning imaging is carried out on a sample containing magnetic nanoparticles, the amplitude and the phase of an obtained GRE image both contain the magnetization intensity information of the magnetic nanoparticles, the magnetization response of superparamagnetic magnetic nanoparticles conforms to a Langmuir function, and the expression is as follows:
Figure BDA0003378298270000081
wherein M represents magnetization, C represents magnetic nanoparticle concentration, and M s Saturation magnetization, V is particle volume, μ 0 Is vacuum permeability, H is AC excitation magnetic field, k B Boltzmann constant, T is the absolute temperature of the magnetic nanoparticles;
according to the expression, the magnetization intensity is related to parameters such as particle concentration, temperature, particle size and the like; the relaxation time T2 of the sample can be obtained according to the amplitude values of the GRE image under a plurality of TEs, and T2 contains the information of magnetic field nonuniformity, which can reflect the magnetic susceptibility of the magnetic nanoparticles; the GRE image phase is related to the chemical shift of protons and is also affected by the magnetic field inhomogeneity, so the relationship between T2 and image phase and magnetic nanoparticle concentration and temperature can be used to model:
Figure BDA0003378298270000082
wherein, Δ Φ is phase variation, T2 is T2 relaxation time, α is undetermined temperature coefficient related to sample concentration, γ is magnetic rotation ratio, B is 0 Is the main magnetic field, TE is the echo time (TE time), T ref For reference temperature, T2 is transverse relaxation time, T2 and M are both concentration and temperature related parameters;
from the above formula, Δ Φ is related to sample concentration, temperature and TE time, and T2 is related to sample concentration and temperature; under the given TE time, as long as the amplitude and the phase change of the GRE image of the magnetic nano sample are known, the concentration and the temperature of the magnetic nano particles can be solved simultaneously by utilizing T2 and the phase difference, and the temperature is also the temperature of the object to be measured; the above equation can be simplified as:
Figure BDA0003378298270000083
wherein f (C, T) and g (C, T) respectively represent the phase difference and the correspondence between T2 relaxation time and the magnetic nanoparticle concentration and temperature, and T2 relaxation time and the correspondence between magnetic nanoparticle concentration and temperature;
based on the analysis, after the corresponding relations f (C, T) and g (C, T) are obtained through calibration, the magnetic nanoparticles are introduced into the object to be measured, different GRE images are obtained, the phase difference and T2 × relaxation time are calculated, the concentration and temperature of the magnetic nanoparticles in the object to be measured can be obtained through simultaneous solving, and the solved temperature is the temperature of the object to be measured.
Compared with the traditional temperature measurement method based on nuclear magnetic resonance spectrum images and magnetic nanoparticles, the GRE sequence scanning has higher imaging speed and larger imaging range relative to the spectrum, and simultaneously, the phase information and the T2 relaxation time are utilized to measure the temperature and the concentration, so that the spatial resolution and the temperature resolution of the magnetic nanoparticles can be greatly improved, and the precision and the speed of temperature measurement are effectively improved.
The following are examples.
Example 1:
a temperature measurement method based on GRE images and magnetic nanoparticles, as shown in fig. 1, includes: a calibration process performed in advance, and a process of performing temperature measurement based on the calibration result.
The calibration process is that the corresponding relation f (C, T) of the phase difference and the magnetic nanoparticle concentration and temperature, and the corresponding relation g (C, T) of T2X relaxation time and the magnetic nanoparticle concentration and temperature;
optionally, the magnetic nanoparticles used in this embodiment are Fe 2 O 3 The magnetic nano particles are stable in property, non-toxic and harmless;
in order to calibrate f (C, T) and g (C, T) accurately, a plurality of samples with different concentrations need to be prepared for measurement; for convenience of description, the following only takes four concentrations of the sample to be calibrated in the concentration range of 0.025-0.1mg/mL as an example, and the specific calibration process is explained; the concentrations of the four samples to be calibrated are respectively as follows: 0.025mg/ml, 0.05mg/ml, 0.075mg/ml, 0.1 mg/ml;
in this embodiment, the corresponding relationship f (C, T) between the phase difference and the magnetic nanoparticle concentration and temperature, and the corresponding relationship g (C, T) between T2 × relaxation time and the magnetic nanoparticle concentration and temperature are calibrated in the following manner:
(S1) preparing magnetic nanoparticle solutions with different concentrations in advance to serve as samples to be calibrated;
considering that the temperature sensitivity of the phase of the GRE image is different when the particle diameter and the concentration of the magnetic nanoparticles are different, the temperature sensitivity of the particles with small particle diameter is better along with the increase of the main magnetic field; the magnetic nanoparticles with the diameter within the range of less than 20nm are of a single domain structure and show superparamagnetism, and when the particle diameter is more than 20nm, the magnetic nanoparticles can have a multi-domain structure, and a model can become complicated, so that the particle diameter of the selected magnetic nanoparticles does not exceed 20 nm; further considering that the preparation process requirement is high when the particle size is too small, in order to ensure good temperature sensitivity and simple model and simultaneously ensure easy acquisition of the magnetic nanoparticles, the particle size range of the selected magnetic nanoparticles is preferably 5-20 nm;
optionally, in this embodiment, the magnetic resonance imaging device used is uMR790 manufactured by joint radiography medical science, the main magnetic field is 3T, and specifically, magnetic nanoparticles with a particle size of 5nm are selected as the temperature-sensitive particles;
(S2) simultaneously placing all samples to be calibrated in pure water having a temperature higher than the maximum temperature of the object to be measured, and placing the samples in a head coil for receiving magnetic resonance signals;
considering that magnetic field drift may occur in the subsequent measurement process to cause phase fluctuation, as a preferred embodiment, a room temperature water model is further provided as a reference in this embodiment in addition to pure water, and during the calibration process, the temperature of the water model is kept constant at room temperature and is used as a reference to calibrate the phase fluctuation caused by the field drift; the room temperature water mold and pure water are placed in the head coil together;
it should be noted that the room temperature water mold is only an alternative embodiment and should not be construed as the only limitation of the present invention; to calibrate for phase fluctuations, in other embodiments of the invention, other constant temperature references may be used;
in order to reduce the signal-to-noise ratio as much as possible, the head coil selected in this embodiment is selected as little as possible under the condition that the sample and the water model are ensured to be put in simultaneously;
in the embodiment, after the pure water soaked with the sample to be calibrated and the room temperature water model are placed in a coil, the coil is placed in an imaging area of magnetic resonance imaging equipment, and subsequent GRE sequence scanning is carried out;
(S3) after the samples to be calibrated and the pure water reach thermal equilibrium, measuring the temperature of the pure water in real time and measuring images corresponding to the temperature points by utilizing a GRE sequence; the GRE sequence sets a plurality of TE times;
the temperature of the sample is different from that of pure water, so that time is required for heat exchange to reach thermal equilibrium; the sample, the pure water and the water mold shake after entering the bed, artifacts may appear in immediate imaging, so that the sample, the pure water and the water mold need to be kept still for a period of time, and measurement is performed after the liquid is stable;
in the embodiment, images are scanned through the GRE sequence, and meanwhile, the temperature of pure water in the cooling process is monitored in real time by using an optical fiber thermometer; cooling pure water and a sample from 39 ℃ to 18 ℃;
setting a plurality of TE time, on one hand, in order to obtain T2 relaxation time according to the fitting of imaging results under different TE time, on the other hand, in consideration of the fact that the optimal TE time cannot be directly determined at the initial time of calibration, setting a plurality of different TE time, respectively calibrating each TE time, selecting the TE time which enables the temperature measurement error to be minimum from the TE time, taking the TE time as the target TE time in actual measurement, and taking the calibration result corresponding to the target TE time as the calibration result used in the actual measurement, so that the temperature measurement error can be minimized, and the accuracy of the temperature measurement is further improved;
optionally, in this embodiment, when performing GRE imaging by using a magnetic resonance apparatus, the TR time of a GRE sequence is set to 25ms, the scan interval is 150s, and the set TE times are respectively 3.06ms, 4.59ms, 6.04ms, 10ms, 14ms, and 20 ms;
(S4) taking the temperature of each sample to be calibrated and the pure water when the samples to be calibrated and the pure water reach thermal equilibrium as a reference temperature, taking a GRE image at the reference temperature as a reference GRE image, calculating the image phase difference and the image amplitude change of each object to be calibrated at each TE time according to the GRE image and the reference GRE image at each temperature point, and fitting the T2 relaxation time corresponding to each sample to be calibrated according to the image amplitude change;
in the step (S4) of the present embodiment, for any one temperature point T 0 Optional sample C to be calibrated 0 At any TE time TE 0 The following image phase difference calculation method includes:
according to temperature point T 0 TE time TE 0 GRE image and TE time TE of 0 Respectively calculating the samples C to be calibrated according to the reference GRE images 0 Subtracting the second phase difference from the first phase difference between the first phase difference in the two GRE images and the second phase difference of the water model in the two GRE images to obtain a sample C to be calibrated 0 At temperature point T 0 TE time TE 0 A lower image phase difference;
because the phase change of the corresponding images of the water model at different moments reflects the phase fluctuation, the phase fluctuation is subtracted from the image phase difference calculated by the sample, and the phase fluctuation caused by the magnetic field drift can be calibrated;
(S5) according to the calculation result of (S4), fitting to obtain a corresponding relation g (C, T) of T2 x relaxation time, magnetic nanoparticle concentration and temperature and a corresponding relation f (C, T) of phase difference, magnetic nanoparticle concentration and temperature at each TE time, taking the corresponding relation as a calibration result at the corresponding TE time, and calculating a corresponding temperature measurement error;
FIG. 2 is a GRE image of magnetic nanoparticle samples at different concentrations and different TE times at the same temperature; FIG. 3 is a GRE image of magnetic nano-samples at different concentrations and different temperatures at the same TE time; FIG. 4 is a graph showing the phase change of a magnetic nano sample with the temperature and concentration of the sample; FIG. 5 is a graph of magnetic nanosample T2 as a function of sample temperature and concentration; FIG. 6 is the Root Mean Square Error (RMSE) of temperature; as can be seen from the experimental results shown in fig. 6, in the present embodiment, the measurement accuracy of the temperature can be better than 0.1K.
According to the root mean square error RMSE of the temperature measurement at different TE time, the TE time with the minimum error can be selected as the target TE time in the actual measurement, and in the actual temperature measurement, the temperature calculation is carried out based on the calibration result at the target TE time.
Based on f (C, T) and g (C, T) obtained by calibration in the above calibration process, the specific process for measuring the temperature in this embodiment includes:
introducing the magnetic nanoparticles into an object to be detected to obtain a sample to be detected, and acquiring GRE images of the sample to be detected at a plurality of TE (time evolution) times at a known temperature to serve as reference images at corresponding TE times; the plurality of TE times comprises a predetermined target TE time; the known temperature can be measured by other means such as optical fiber, thermocouple, thermal resistor, etc.;
at a target moment, obtaining GRE images of a sample to be detected at multiple TE time, calculating image phase difference delta phi and image amplitude change of the sample to be detected at each TE time, and fitting T2 relaxation time according to the image amplitude change;
establishing a model according to a corresponding relation f (C, T) of the phase difference and the magnetic nanoparticle concentration and the temperature, and a corresponding relation g (C, T) of T2 relaxation time and the magnetic nanoparticle concentration and the temperature, wherein the corresponding relation f (C, T) is calibrated in advance:
Figure BDA0003378298270000121
and solving the concentration C and the temperature T of the magnetic nanoparticles according to the established model, and taking the temperature T as the temperature of the object to be detected.
In summary, in this embodiment, magnetic nanoparticles are combined with magnetic resonance imaging, the correspondence between the phase difference and the magnetic nanoparticle concentration and temperature related to a GRE image and the correspondence between T2 × relaxation time and the magnetic nanoparticle concentration and temperature are calibrated in advance, and based on the corresponding calibration result, after the magnetic nanoparticles are introduced into the body to be measured, GRE images of the sample at different TE times are obtained, i.e., the concentration and temperature of the magnetic nanoparticles in the sample can be solved at the same time, and the temperature is also the temperature of the object to be measured; the GRE image is a two-dimensional image, the resolution ratio is high, the imaging speed is high, the GRE image of the sample can be quickly obtained at the target time needing temperature measurement, the temperature measurement speed is improved, the measured temperature can accurately reflect the temperature of the object to be measured at the target time, and the temperature measurement precision is effectively improved.
Example 2:
a GRE image and magnetic nanoparticle based temperature measurement system comprising: the device comprises a preprocessing module, a magnetic resonance imaging device, a control module and a data processing module;
the pretreatment module is used for introducing the magnetic nanoparticles into an object to be detected to obtain a sample to be detected;
the magnetic resonance imaging device is used for scanning images through the GRE sequence to obtain GRE images;
the control module is used for acquiring GRE images of a sample to be detected at a plurality of TE (time evolution) times by using magnetic resonance imaging equipment at a known temperature; the plurality of TE times comprises a predetermined target TE time;
the control module is also used for acquiring GRE images of the sample to be detected at a plurality of TE time by using the magnetic resonance imaging equipment at the target moment and triggering the data processing module;
a data processing module to: calculating the image phase difference delta phi and the image amplitude change of the sample to be detected at each TE time according to the GRE image and the reference image acquired at the target time, and fitting T2 relaxation time according to the image amplitude change; establishing a model according to a corresponding relation f (C, T) of the phase difference and the magnetic nanoparticle concentration and the temperature, and a corresponding relation g (C, T) of T2 relaxation time and the magnetic nanoparticle concentration and the temperature, wherein the corresponding relation f (C, T) is calibrated in advance:
Figure BDA0003378298270000131
solving the concentration C and the temperature T of the magnetic nanoparticles according to the established model, and taking the temperature T as the temperature of the object to be detected;
in this embodiment, the specific implementation of each module and the calibration manner of f (C, T) and g (C, T) may refer to the description in the above method embodiment, and will not be repeated here.
It should be noted that, the temperature measurement system based on the GRE image and the magnetic nanoparticles provided in this embodiment can improve the accuracy and speed of temperature measurement, and meanwhile, the magnetic nanoparticles have stable properties, are non-toxic and harmless, have a small volume compared with other paramagnetic particles, and can exist in vivo for a long time, thereby meeting clinical requirements; the magnetic resonance imaging equipment is very effective for visualizing the internal organs and tissues of the living body, and is expected to realize high-resolution detection and imaging of the body temperature under the condition of not damaging the object to be detected.
It will be understood by those skilled in the art that the foregoing is only an exemplary embodiment of the present invention, and is not intended to limit the invention to the particular forms disclosed, since various modifications, substitutions and improvements within the spirit and scope of the invention are possible and within the scope of the appended claims.

Claims (8)

1. A temperature measurement method based on GRE images and magnetic nanoparticles is characterized by comprising the following steps:
introducing the magnetic nanoparticles into an object to be detected to obtain a sample to be detected, and acquiring GRE images of the sample to be detected at a plurality of TE (time evolution) times at a known temperature to serve as reference images at corresponding TE times; the plurality of TE times comprises a predetermined target TE time;
at a target moment, acquiring GRE images of the sample to be detected at the plurality of TE time, calculating image phase difference delta phi and image amplitude change of the sample to be detected at each TE time, and fitting T2 relaxation time according to the image amplitude change;
establishing a model according to a corresponding relation f (C, T) of the phase difference and the magnetic nanoparticle concentration and the temperature, and a corresponding relation g (C, T) of T2 relaxation time and the magnetic nanoparticle concentration and the temperature, wherein the corresponding relation f (C, T) is calibrated in advance:
Figure FDA0003717451870000011
and solving the concentration C and the temperature T of the magnetic nano particles according to the established model, and taking the temperature T as the temperature of the object to be detected.
2. The GRE image and magnetic nanoparticle-based temperature measurement method of claim 1, wherein said phase difference versus magnetic nanoparticle concentration and temperature correspondence f (C, T), and said T2 relaxation time versus magnetic nanoparticle concentration and temperature correspondence g (C, T), are calibrated in a manner comprising:
(S1) preparing magnetic nanoparticle solutions with different concentrations in advance to serve as samples to be calibrated;
(S2) simultaneously placing all samples to be calibrated in pure water having a temperature higher than the maximum temperature of the object to be measured, and placing the samples in a coil for receiving magnetic resonance signals;
(S3) after the samples to be calibrated and the pure water reach thermal equilibrium, measuring the temperature of the pure water in real time and measuring GRE images corresponding to the temperature points by utilizing the GRE sequence; the GRE sequence sets a plurality of TE times;
(S4) taking the temperature of each sample to be calibrated and the pure water when the samples to be calibrated and the pure water reach thermal equilibrium as a reference temperature, taking a GRE image at the reference temperature as a reference GRE image, calculating the image phase difference and the image amplitude change of each object to be calibrated at each TE time according to the GRE image and the reference GRE image at each temperature point, and fitting the T2 relaxation time corresponding to each sample to be calibrated according to the image amplitude change;
(S5) according to the calculation result of (S4), fitting to obtain a corresponding relation g (C, T) of T2 x relaxation time, magnetic nanoparticle concentration and temperature and a corresponding relation f (C, T) of phase difference, magnetic nanoparticle concentration and temperature at each TE time, taking the corresponding relation as a calibration result at the corresponding TE time, and calculating a corresponding temperature measurement error;
(S5) taking the TE time corresponding to the calibration result with the minimum temperature measurement error as the target TE time, and taking the calibration result corresponding to the TE time as the final calibration result.
3. The GRE image and magnetic nanoparticle-based temperature measurement method of claim 2,
the step (S2) further includes: placing a constant temperature reference beside the pure water, and placing the constant temperature reference into the coil, so that each GRE image acquired in the step (S3) simultaneously comprises the pure water and the constant temperature reference;
in the step (S4), the temperature is set to any one of the temperature points T 0 Optional sample C to be calibrated 0 At any TE time TE 0 The following image phase difference calculation method includes:
according to temperature point T 0 TE time TE 0 GRE image and TE time TE of 0 Respectively calculating the samples C to be calibrated according to the reference GRE images 0 Subtracting the second phase difference from the first phase difference to obtain the sample C to be calibrated 0 At temperature point T 0 TE time TE 0 The phase difference of the images.
4. The GRE image and magnetic nanoparticle-based temperature measurement method of claim 3, wherein the constant temperature reference is a water phantom.
5. The GRE image and magnetic nanoparticle-based temperature measurement method according to any one of claims 1 to 4, wherein the magnetic nanoparticles have a particle size of not more than 20 nm.
6. The GRE image and magnetic nanoparticle-based temperature measurement method according to claim 5, wherein the magnetic nanoparticles have a particle size in the range of 5-20 nm.
7. The GRE image and magnetic nanoparticle-based temperature measurement method according to any one of claims 1 to 4, wherein the magnetic nanoparticles are Fe 2 O 3
8. A temperature measurement system based on GRE images and magnetic nanoparticles, comprising: the device comprises a preprocessing module, a magnetic resonance imaging device, a control module and a data processing module;
the pretreatment module is used for introducing the magnetic nanoparticles into an object to be detected to obtain a sample to be detected;
the magnetic resonance imaging equipment is used for scanning images through a GRE sequence to obtain a GRE image;
the control module is used for acquiring GRE images of the sample to be detected at a plurality of TE (time evolution) times by using the magnetic resonance imaging equipment at a known temperature; the plurality of TE times comprises a predetermined target TE time;
the control module is further configured to acquire GRE images of the sample to be measured at the multiple TE times by using the magnetic resonance imaging device at a target time, and trigger the data processing module;
the data processing module is used for: calculating the image phase difference delta phi and the image amplitude change of the sample to be detected at each TE time according to the GRE image and the reference image acquired at the target time, and fitting T2 relaxation time according to the image amplitude change; establishing a model according to a corresponding relation f (C, T) of the phase difference and the magnetic nanoparticle concentration and the temperature, and a corresponding relation g (C, T) of T2 relaxation time and the magnetic nanoparticle concentration and the temperature, wherein the corresponding relation f (C, T) is calibrated in advance:
Figure FDA0003717451870000031
and solving the concentration C and the temperature T of the magnetic nano particles according to the established model, and taking the temperature T as the temperature of the object to be detected.
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