CN114099991B

CN114099991B - System for synchronously performing transcranial ultrasonic stimulation and near-infrared brain function imaging

Info

Publication number: CN114099991B
Application number: CN202111480058.7A
Authority: CN
Inventors: 任李源; 孙俊峰; 童善保
Original assignee: Shanghai Jiaotong University
Current assignee: Shanghai Jiaotong University
Priority date: 2021-12-06
Filing date: 2021-12-06
Publication date: 2023-01-24
Anticipated expiration: 2041-12-06
Also published as: CN114099991A

Abstract

The present application provides a system for simultaneous transcranial ultrasound stimulation and near-infrared brain function imaging, comprising: the near infrared-ultrasonic coupler is provided with an ultrasonic transducer which is used for generating focused ultrasonic waves required by transcranial ultrasonic stimulation; the near-infrared brain function imaging device comprises a near-infrared blood oxygen data acquisition unit, and the near-infrared blood oxygen data acquisition unit is integrated at the far end of the near-infrared-ultrasonic coupler, so that the near-infrared brain function imaging device synchronously acquires near-infrared blood oxygen data of an ultrasonically stimulated part; the near-infrared blood oxygen data acquisition unit comprises a light source module and a photoelectric detector module, wherein the light source module is used for emitting multi-wavelength near-infrared light waves, and the photoelectric detector module is used for receiving near-infrared light wave signals. The system can simultaneously perform transcranial ultrasound stimulation and detect neural activity at the stimulated site.

Description

System for synchronously performing transcranial ultrasonic stimulation and near-infrared brain function imaging

Technical Field

The invention relates to the field of nerve regulation and brain function detection, in particular to a system for synchronously performing transcranial ultrasonic stimulation and near-infrared brain function imaging.

Background

Transcranial Ultrasound Stimulation (TUS) is a technique that uses low frequency focused ultrasound of specific parameters to stimulate specific nerves or functional areas within the brain to achieve modulation of cranial nerve activity. In animal experimental studies, transcranial ultrasound stimulation may be detected by electrodes implanted or affixed to the cerebral cortex, as well as by optical imaging through a craniotomy or by functional magnetic resonance imaging. However, in the study of human brain, considering that the implantation of electrodes or the operation of craniotomy is required, the detection of the neural regulation effect of transcranial ultrasonic stimulation is mainly detected by performing electroencephalogram experiments in the baseline stage before ultrasonic stimulation and after ultrasonic stimulation, or by functional magnetic resonance imaging, or by multiple behavioral experiments of a subject. However, these detection methods have limitations, and the electroencephalogram experiments before and after the ultrasonic stimulation cannot synchronously obtain the immediate neuromodulation effect of the ultrasonic stimulation, the time resolution of the functional magnetic resonance imaging is low, and the neuromodulation effect detection with high time resolution cannot be provided, and the cost of the functional magnetic resonance imaging is high, and the ultrasonic stimulation system is required to perform the magnetic resonance compatible design. And when the transcranial ultrasonic stimulation device is used, the ultrasonic wave needs to maintain lower sound intensity loss on a conduction path, and extra devices on the conduction path are reduced as much as possible. This makes it impossible to simply integrate the existing brain function testing device with the transcranial ultrasound stimulation system, and it is inconvenient to simultaneously observe the instant effect of the ultrasound stimulation on the brain activity. In general, in the research of human brain, the neuromodulation effect stimulated by transcranial ultrasonic still lacks synchronous, non-invasive, convenient and quantitative neuromodulation effect detection technology and device.

Compared with the existing mature nerve regulation and control technologies such as Transcranial Magnetic Stimulation (TMS) and the like, the development of the Transcranial Ultrasonic Stimulation (TUS) technology is still in an early stage, parameters of transcranial ultrasonic nerve regulation and control need further experimental testing and optimization, a related experimental paradigm is not mature, the regulation and control effect of transcranial ultrasonic stimulation still needs further research, and particularly, a non-invasive, convenient and fast technology and method capable of synchronously detecting the nerve regulation and control effect of transcranial ultrasonic on human brain stimulation are lacked. Therefore, it is necessary to develop a neural activity and brain function detection technology and device specially used for transcranial ultrasonic stimulation, so as to provide real-time and convenient regulation and control effect detection for the transcranial ultrasonic stimulation and meet the requirements of brain science research and clinical treatment.

Compared with the current main technical means of brain function detection, such as functional magnetic resonance imaging (fMRI), positron Emission Tomography (PET), and the like, the near infrared brain function spectral imaging (fNIRS) based on the near infrared spectrum has the excellent characteristics of convenience, portability, wide applicability, timely response, and the like, and is widely applied to brain science research. As a non-invasive optical monitoring means, the near infrared spectrum technology is more and more popular in application range, and is a convenient and efficient brain function detection means.

The existing non-invasive human cranial nerve activity detection technologies mainly comprise electroencephalogram (EEG), magnetoencephalogram (MEG), functional magnetic resonance imaging (fMRI) and near-infrared brain functional spectral imaging (fNIRS), and the technologies respectively have advantages and disadvantages. When the transcranial ultrasonic nerve regulation and control effect detection is carried out, the conductive paste needs to be coated between the brain electrode and the scalp for recording brain electricity, the size of the brain electrode is large, the size of the ultrasonic transducer is also large, the ultrasonic coupling agent needs to be coated between the transducer and the scalp (air does not exist between the scalp and the transducer, attenuation in the ultrasonic wave propagation process is reduced), and therefore the ultrasonic transducer used for emitting ultrasonic waves cannot be superposed on the brain electrode (the spatial position is overlapped), and therefore the nerve activity of a brain area directly stimulated by the ultrasonic waves cannot be synchronously detected. When the magnetoencephalogram and the functional magnetic resonance imaging are used for synchronously detecting transcranial ultrasonic stimulation, a transcranial ultrasonic stimulation system is required to be specially designed in a magnetic compatibility mode, and the magnetoencephalogram system and an ultrasonic transducer have the problem of spatial overlapping; meanwhile, the magnetoencephalogram and the functional magnetic resonance imaging equipment are huge, expensive, high in operation and maintenance cost and not portable. Compared with these technologies, near-infrared brain function spectral imaging has the advantages of economy, portability, low requirements on use environment and the like, and has been widely used for brain function research.

The existing near-infrared brain function spectral imaging technology and system do not consider the requirement of synchronously detecting the neural activity at the brain region stimulated by transcranial ultrasonic, and the technology and system capable of synchronously detecting the neural regulation effect stimulated by the transcranial ultrasonic are lacked. And the prior art has no structural design aiming at synchronous detection of transcranial ultrasonic stimulation, when the near-infrared brain function spectral imaging and the transcranial ultrasonic stimulation are used cooperatively, because the stimulated part of the transcranial ultrasonic is superposed with the detection part of the near-infrared brain function spectral imaging, and the structure volumes of a common near-infrared light source and a detector are too large, the ultrasonic conduction is easily influenced, so that the neural regulation effect of the transcranial ultrasonic stimulation cannot be synchronously detected.

In addition, the transcranial ultrasonic stimulation needs to apply a rated ultrasonic sound intensity to a target point of a designated brain region and avoid the influence on other brain regions as much as possible, so that an ultrasonic sound field is required to have certain symmetry and focusing property, the focus position of the sound field is clear, and the practical application is convenient. If the common infrared light source is directly arranged at the bottom of the ultrasonic transducer, the problems of focus offset of a sound field, near-field waveform distortion, loss of symmetry of the sound field, weakening of sound field concentration, reduction of effective intensity of the sound field and the like easily occur, and further the use of a transcranial ultrasonic system is seriously influenced. Therefore, the necessary structural design of the fNIRS device and the ultrasound transducer working synchronously is required to ensure the effectiveness of the ultrasound stimulation.

When the transcranial ultrasonic stimulation system sends a trigger pulse signal, the near-infrared brain function spectral imaging system is required to record and analyze the waveform at the corresponding moment, and the synchronization function in the prior art can only realize that the near-infrared brain function spectral imaging system and other systems start or stop working at the same time, lacks the function of marking the stimulation moment and performing further analysis, and does not match the requirements of a software algorithm level and the transcranial ultrasonic stimulation system. Externally, the existing near-infrared brain function imaging equipment adopts a relatively large photoelectric probe, and the structure is too heavy, so that the detection part cannot be flexibly adjusted. The existing photoelectric measuring head part can also influence the effective conduction of ultrasonic waves and is difficult to work with a transcranial ultrasonic system. In terms of system functions, external device synchronization modules equipped in the existing near-infrared brain function imaging device only have simple and easy functions of simple synchronous acquisition starting, synchronous acquisition stopping and the like. The inability to identify the more complex stimulation pulse sequences in transcranial ultrasound stimulation systems is difficult to use for the simultaneous detection of the neuromodulation effects of transcranial ultrasound stimulation.

Therefore, there is an urgent need in the art to develop a system for simultaneously performing transcranial ultrasound stimulation and near-infrared brain function imaging, which is capable of combining transcranial ultrasound stimulation with near-infrared brain function imaging, and performing transcranial ultrasound stimulation and simultaneously detecting the neuromodulation effect of the transcranial ultrasound stimulation in real time.

Disclosure of Invention

The system can combine transcranial ultrasonic stimulation and near-infrared brain function imaging, can perform transcranial ultrasonic stimulation, and can synchronously detect the nerve regulation effect of the transcranial ultrasonic stimulation in real time.

The present application provides a system for simultaneous transcranial ultrasound stimulation and near-infrared brain function imaging, comprising:

the near infrared-ultrasonic coupler is provided with an ultrasonic transducer which is used for generating focused ultrasonic waves required by transcranial ultrasonic stimulation;

the near-infrared brain function imaging device comprises a near-infrared blood oxygen data acquisition unit, and the near-infrared blood oxygen data acquisition unit is integrated at the far end of the near-infrared-ultrasonic coupler, so that the near-infrared brain function imaging device synchronously acquires near-infrared blood oxygen data of an ultrasonically stimulated part; the near-infrared blood oxygen data acquisition unit comprises a light source module and a photoelectric detector module, wherein the light source module is used for emitting multi-wavelength near-infrared light waves, and the photoelectric detector module is used for receiving near-infrared light wave signals.

In another preferred example, the light source module is disposed below the ultrasonic transducer, and the photodetector module is disposed around the light source module.

In another preferred example, a polymer ultrasonic conducting medium is installed at a far end of an ultrasonic transducer in the near infrared-ultrasonic coupler, the near infrared-ultrasonic coupler includes a coupler far end surface, the light source module is arranged at a geometric center of the coupler far end surface, the light source module is in close contact with the polymer ultrasonic conducting medium, and the photodetector module is arranged around the light source module.

In another preferred example, the light source module is disposed on the lower surface of the polymer ultrasonic conductive medium.

In another preferred embodiment, the lower housing distal surface is annular.

In another preferred example, the near infrared-ultrasonic coupler includes a near infrared-ultrasonic coupler lower case forming a first internal space in which the ultrasonic transducer is installed, the photodetector module includes a plurality of photodetecting devices, and the near infrared-ultrasonic coupler lower case includes a plurality of photodetecting mounting holes in which the plurality of photodetecting devices are mounted.

In another preferred example, the plurality of photodetecting mounting holes are disposed at the distal end of the lower housing of the near infrared-ultrasonic coupler.

In another preferred example, the light source module comprises three miniature semiconductor infrared lasers with different wavelengths.

In another preferred example, the photoelectric detection device includes a photoelectric measurement head, the photoelectric measurement head includes a photoelectric detector and a near-infrared filtering polarizer, the near-infrared filtering polarizer is disposed below the photoelectric detector, and the near-infrared polarizer is configured to filter interference light waves other than the near-infrared detection light waves.

In another preferred example, the exterior of the photoelectric measuring head is provided with a plurality of groups of ring-mounted buckling grooves for adjusting the telescopic length of the photoelectric measuring head during installation.

In another preferred example, the near infrared-ultrasonic coupler further includes a near infrared-ultrasonic coupler upper housing, and the ultrasonic transducer is fixed on the near infrared-ultrasonic coupler upper housing.

In another preferred example, the near infrared blood oxygen data collecting unit further includes a light source fixing rod configured to support the light source module, the light source fixing rod is disposed on the distal end surface of the coupler and is connected to the lower housing of the near infrared-ultrasonic coupler.

In another preferred example, the number of the photodetection mounting holes is 4 and the photodetection device is mounted in each photodetection mounting hole, and the included angle between the central lines of two adjacent photodetection devices is 90 °.

In another preferred example, the number of the light source fixing rods is 3, and the included angle between the longitudinal axes of two adjacent light source fixing rods is 120 °.

In another preferred example, the minimum included angle between the longitudinal axis of the light source fixing rod and the connecting line of the light source module and the photoelectric detection device is θ, wherein θ is in the range of 7 ° to 15 °.

In another preferred embodiment, θ > 8.5 °.

In another preferred embodiment, θ is 15 °.

In another preferred embodiment, the width of the cross section of the light source fixing rod is L ₁ ，L ₁ Less than half the wavelength of the ultrasonic waves generated by the ultrasonic transducer.

In another preferred embodiment, the diameter of the light source module is d ₂ ，d ₂ Less than the wavelength of the ultrasonic waves.

In another preferred example, the system further comprises a transcranial ultrasound stimulation device for synchronously generating the ultrasound stimulation signals.

In another preferred example, the diameter of the light source module is between 1.35mm and 5.5mm, and the diameter of the light detector module is between 3mm and 8.5 mm.

In another preferred example, the system further comprises an upper computer system in communication with the near-infrared brain function imaging device and in communication with the transcranial ultrasound stimulation device, the upper computer system being configured to control the transcranial ultrasound stimulation device and the near-infrared brain function imaging device.

In another preferred example, the near-infrared brain function imaging device further comprises a near-infrared blood oxygen data processing unit, and the near-infrared blood oxygen data processing unit is configured to acquire and process the data acquired by the near-infrared blood oxygen data acquisition unit, and is used in cooperation with a transcranial ultrasound stimulation device which synchronously generates an ultrasound stimulation signal.

In another preferred embodiment, the upper computer system is in communication connection with the near infrared blood oxygen data processing unit.

In another preferred example, the near infrared blood oxygen data processing unit comprises a signal conditioning module, a multi-path A/D sampling module, an MCU main control board module and a direct frequency synthesis module; the signal conditioning module is used for processing the detection signal of the photoelectric detector module, filtering out an irrelevant noise signal and demodulating the signal; the multi-path A/D sampling module is used for receiving the signal of the signal conditioning module and performing analog-to-digital conversion; the MCU main control board module is used for controlling the lower computer circuit, receiving and analyzing the near infrared signal sampling data transmitted by the multi-path A/D sampling module and simultaneously communicating with the upper computer system; the direct frequency synthesis module is used for sending out driving signals with different frequencies by frequency division multiplexing and providing reference signals for the signal conditioning module.

In another preferred embodiment, the near infrared blood oxygen data acquisition unit further includes an LED driving control module, the LED driving control module is configured to control a constant current source for driving an LED to adjust the brightness of the light source module, and the LED driving control module is further in communication connection with the direct frequency synthesis module.

In another preferred embodiment, the signal conditioning module includes a signal preprocessing module and a double phase-locked amplifier module; the signal preprocessing module comprises a secondary filter circuit and an isolation amplifying circuit and is used for filtering noises such as ambient light noise, power frequency interference and the like.

In another preferred embodiment, the dual lock-in amplifier module utilizes a lock-in amplification technique to synchronously demodulate the frequency-division multiplexing signal of the photodetector, and simultaneously filter out noise irrelevant to the original physiological signal.

In another preferred embodiment, the upper computer system integrates near-infrared imaging map analysis software based on transcranial ultrasonic stimulation, can perform functions of real-time recording of multi-channel near-infrared data, signal preprocessing, data statistics, drawing of visual near-infrared brain topographic maps and the like under various different ultrasonic stimulation parameters, can display transcranial ultrasonic stimulation time and parameters in a near-infrared brain imaging map in real time, and performs comprehensive analysis according to multi-channel map changes and transcranial ultrasonic stimulation parameters.

It is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments. Not to be reiterated herein, but to the extent of space.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below. It is to be understood that the drawings in the following description are merely exemplary embodiments of the invention and that one skilled in the art may, without any inventive step, derive other embodiments from these drawings.

FIG. 1 is a block diagram of a system for simultaneous transcranial ultrasound stimulation and near-infrared brain function imaging according to an embodiment of the present application;

FIG. 2 is a schematic diagram of an external structure of a near infrared-ultrasonic coupler according to an embodiment of the present application;

FIG. 3 is a schematic diagram of an internal structure of a near infrared-ultrasonic coupler according to an embodiment of the present application;

FIG. 4 is a top view of a near infrared-ultrasonic coupler according to an embodiment of the present application;

FIG. 5 is a top view of a near infrared-ultrasonic coupler with sizing according to an embodiment of the present application;

fig. 6 is an external schematic view of an optoelectronic probe according to one embodiment of the present application;

fig. 7 is a schematic view of the interior of an optoelectronic probe according to one embodiment of the present application;

fig. 8a to 8b are respectively a light source fixing bar sectional width L of a near infrared-ultrasonic coupler according to a first embodiment (example 1) of the present application ₁ Test charts of the cross section and the longitudinal section of the ultrasonic sound field when =0.5 mm;

fig. 8c to 8d are sectional widths L of a light source fixing bar of a near infrared-ultrasonic coupler according to a first embodiment (example 1) of the present application, respectively ₁ Test charts of the cross section and the longitudinal section of the ultrasonic sound field when =1.5 mm;

FIGS. 8e-8f are diagrams, respectivelyIs a light source fixing rod cross-sectional width L of the near infrared-ultrasonic coupler according to the first embodiment (example 1) of the present application ₁ Test charts of the cross section and the longitudinal section of the ultrasonic sound field when =2.5 mm;

FIGS. 9a-9b are respectively the light source diameters d of the NIR-ultrasonic coupler according to a second embodiment (example 2) of the present application ₂ Test patterns of the cross section and the longitudinal section of the ultrasonic sound field when the diameter is 1.5 mm;

FIGS. 9c-9d are respectively the light source diameters d of the NIR-ultrasonic coupler according to a second embodiment (example 2) of the present application ₂ Test patterns of the cross section and the longitudinal section of the ultrasonic sound field when the diameter is not less than 6 mm;

fig. 10a is a layout diagram of the number of light source fixing bars of the near infrared-ultrasonic coupler according to the third embodiment (example 3) of the present application being 4;

FIGS. 10b-10c are cross-sectional and longitudinal sectional test views, respectively, of the ultrasonic field of the near-IR-ultrasonic coupler of FIG. 10a with the light source fixing rods arranged;

FIG. 11 is a schematic illustration of ultrasonic sound field parameters according to an embodiment of the present application.

In the drawings, the designations are as follows:

upper shell of 1-near infrared-ultrasonic coupler

Lower shell of 2-near infrared-ultrasonic coupler

21-coupler lower inner shell

22-coupler lower outer shell

3-polymer gasket

4-ultrasonic transducer

5-high molecular ultrasonic conducting medium

6-Cable fixing port

7-photoelectric detection mounting hole

8-infrared laser mounting hole

9-transducer fixing groove

10-light source fixing rod

101-first light source fixing rod

102-second light source fixing rod

103-third light source fixing rod

11-photoelectric probe

111-photoelectric probe shell

112-photoelectric detector

113-near infrared polarizing plate

L ₁ Light source fixing bar cross-sectional width

d ₁ -ultrasonic transducer diameter

d ₂ Diameter of light source

d ₃ Source-source detector distance

Minimum deflection angle between theta-light source fixing rod and light source-detector

S-bottom ultrasound occlusion area ratio

Lambda-ultrasonic wave length

Detailed Description

The inventor develops a system for synchronously performing transcranial ultrasonic stimulation and near-infrared brain function imaging for the first time through extensive and intensive research, and the system can synchronously perform transcranial ultrasonic stimulation and detect nerve activity of a stimulated part based on near-infrared brain function spectrum imaging and transcranial ultrasonic stimulation technologies. The system designs a novel near infrared-ultrasonic coupler, the coupler improves a sound guide material medium by integrating a miniature near infrared light source and a detector, reduces the loss of ultrasound in conduction to the maximum extent, ensures the symmetry and the focusing of an ultrasonic sound field, realizes synchronous real-time acquisition of near infrared spectrum data at a transcranial ultrasonic stimulation target point, and provides a new tool for the transcranial ultrasonic stimulation technology in brain function and research and clinical application.

Term(s)

As used herein, "distal" refers to the end of the housing on the coupler distal to the site to be stimulated, and "proximal" refers to the end of the housing on the coupler distal to the site to be stimulated.

As used herein, "transcranial ultrasound stimulation system" and "transcranial ultrasound stimulation apparatus" are used interchangeably.

As used herein, "near infrared blood oxygen data acquisition unit" and "infrared blood oxygen data acquisition unit" are used interchangeably.

Transcranial ultrasonic stimulation Technology (TUS)

Transcranial Ultrasound Stimulation (TUS) is a technique for stimulating specific nerves or functional regions inside the brain using low-intensity low-frequency focused ultrasound to modulate cranial nerve activity, and has the advantages of no wound, large stimulation depth, high spatial resolution, and the like, compared with other nerve modulation techniques.

Near infrared brain function spectral imaging (fNIRS)

fNIRS uses mainly the absorption spectral characteristics of hemoglobin in the near infrared band to calculate hemodynamic parameters, i.e. the change in the concentration of oxygenated hemoglobin (HbO) and reduced hemoglobin (HbR), and then performs analytical studies on brain functional activities. fNIRS usually uses near-infrared light (650-900 nm) with two or more wavelengths to detect the diffused light that is emitted after the incident light passes through the scalp and skull to reach the cerebral cortex and is absorbed and scattered by the brain tissue. Because HbO and HbR, which reflect the metabolic and hemodynamic characteristics of brain tissue, are the main absorbers in the near-infrared light band, and the 650-900nm near-infrared light can penetrate relatively deep tissues before being absorbed, the spatial distribution of the changes in the concentration of HbO and HbR in the cerebral cortex can be reduced by spatially resolved measurement of diffuse light before and after stress.

Phase-locked amplification technique

The lock-in amplifier technology is considered as a method for effectively removing signal interference when weak light is detected. In a spectrum detection system, a light source modulated by a specific frequency is used, so that the light intensity of a useful signal is very weak after passing through a detected object, and strong environmental noise is mixed, and a phase-locked amplifier is usually used for extracting the useful signal in the detection of the weak signal. Usually, weak useful signals are mixed with noise and have mutual incoherence on frequency, and the lock-in amplifier separates the useful signals from the noise by using reference signals which have cross correlation with the measured signals and are not correlated with the noise signals, and realizes signal demodulation.

Detection principle of phase-locked amplifier

The signal channel sends an original signal accompanied with noise to a phase sensitive detector after primary pretreatment including blocking, filtering, amplifying and the like; meanwhile, the reference channel provides a reference signal with the same frequency as the input signal to the phase sensitive detector; the phase sensitive detector is used for multiplying the signal input by the signal channel and the signal of the reference channel to obtain the sum frequency and difference frequency components of the signals of the signal channel and the reference channel, and then the high-frequency signal component is filtered under the action of low-pass filtering to obtain a useful signal to be detected. In conclusion, the phase-locked amplification technology is applied to near-infrared brain function imaging (fNIRS), so that the overall signal-to-noise ratio of the equipment can be effectively improved, and more accurate detection is realized.

Transcranial ultrasonic stimulation device

In the present application, a transcranial ultrasound stimulation device is used for generating the ultrasound stimulation signal, which may be a conventional transcranial ultrasound stimulation device.

The transcranial ultrasonic stimulation device and the near-infrared brain function imaging device work simultaneously, so that the nerve activity of the stimulated part is detected while transcranial ultrasonic stimulation is performed.

Near-infrared brain function imaging device

The near-infrared brain function imaging device comprises a near-infrared blood oxygen data acquisition unit, wherein the near-infrared blood oxygen data acquisition unit is integrated at the far end of the near-infrared-ultrasonic coupler, so that the near-infrared brain function imaging device synchronously acquires near-infrared blood oxygen data of an ultrasonically stimulated part; the near-infrared blood oxygen data acquisition unit comprises a light source module and a photoelectric detector module, wherein the light source module is used for emitting multi-wavelength near-infrared light waves, and the photoelectric detector module is used for receiving near-infrared light wave signals;

the near-infrared brain function imaging device further comprises a near-infrared blood oxygen data processing unit, wherein the near-infrared blood oxygen data processing unit is configured to acquire data acquired by the near-infrared blood oxygen data acquisition unit, process the data and simultaneously cooperate with a transcranial ultrasonic stimulation device which synchronously generates ultrasonic stimulation signals for use.

The near infrared blood oxygen data processing unit comprises a signal conditioning module, a multi-path A/D sampling module, an MCU main control board module and a direct frequency synthesis module; the signal conditioning module is used for processing the detection signal of the photoelectric detector module, filtering out an irrelevant noise signal and demodulating the signal; the multi-path A/D sampling module is used for receiving the signal of the signal conditioning module and performing analog-to-digital conversion; the MCU main control board module is used for controlling the lower computer circuit, receiving and analyzing the near infrared signal sampling data transmitted by the multi-path A/D sampling module and simultaneously communicating with the upper computer system; the direct frequency synthesis module is used for sending out driving signals with different frequencies by frequency division multiplexing and providing reference signals for the signal conditioning module.

The near infrared blood oxygen data acquisition unit further comprises an LED driving control module, the LED driving control module is used for controlling and driving a constant current source of the LED to realize the adjustment of the brightness of the light source module, and the LED driving control module is further in communication connection with the direct frequency synthesis module.

The terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. Without further limitation, the use of the verb "comprise a" to define an element does not exclude the presence of another, same element in a process, method, article, or apparatus that comprises the element. In the present patent application, if it is mentioned that a certain action is executed according to a certain element, it means that the action is executed according to at least the element, and two cases are included: performing the action based only on the element, and performing the action based on the element and other elements. The expression of a plurality of, a plurality of and the like includes 2, 2 and more than 2, more than 2 and more than 2. It should be noted that, in the present patent application, relational terms such as first and second, and the like are used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions.

In the present invention, all the directional indications (such as up, down, left, right, front, rear, etc.) are used only to explain the relative positional relationship between the respective members, the motion situation, etc. in a certain posture (as shown in the drawing), and if the certain posture is changed, the directional indication is changed accordingly.

The invention has the main advantages that:

(a) The system for synchronously performing transcranial ultrasonic stimulation and near-infrared brain function imaging can monitor the brain blood oxygen change in the transcranial ultrasonic stimulation process in real time, and a synchronous analysis system is integrated on software, so that an effective tool is provided for further researching the instant regulation and control effect of transcranial ultrasonic stimulation;

(b) The near infrared-ultrasonic coupler integrated structure design of the system for synchronously performing transcranial ultrasonic stimulation and near infrared brain function imaging adopts the improved sound conduction high polymer material, realizes that transcranial ultrasonic equipment and near infrared imaging equipment work at the same target point, can prevent ultrasonic sound field deformation, focus position offset and sound intensity attenuation, and reduces the influence of the ultrasonic sound field on ultrasound to the minimum;

(c) The near infrared-ultrasonic coupler of the system for synchronously performing transcranial ultrasonic stimulation and near infrared brain function imaging integrates the miniature near infrared light source and the miniature near infrared detector, improves a sound guide material medium, reduces the loss of ultrasound in conduction to the maximum extent, ensures the symmetry and the focusing property of an ultrasonic sound field, realizes synchronous real-time acquisition of near infrared spectrum data at a transcranial ultrasonic stimulation target point, and provides a new tool for the transcranial ultrasonic stimulation technology in brain function research and clinical application;

(d) The ultrasonic transducer of the near infrared-ultrasonic coupler and the integrated light source, the photoelectric detector device and the light source fixing rod are reasonably arranged in structure, the ultrasonic sound field can meet the use requirement after the coupler is additionally installed, the effective ultrasonic sound intensity can be maintained at the near infrared detection point, the sound beam shape maintains better focusing performance, the ultrasonic focus position is close to the position without the coupler when the coupler is additionally installed, and the effect that the ultrasonic stimulation is not influenced after the near infrared detection function is additionally installed by the coupler is realized.

(e) The system for synchronously performing transcranial ultrasonic stimulation and near-infrared brain function imaging adopts the light source frequency division multiplexing and multi-channel signal phase-locked demodulation technologies, realizes light intensity measurement when multiple light sources are simultaneously excited, overcomes the defects of long time of multi-light source time division multiplexing measurement and errors generated by channel switching, and improves the time resolution of the whole system.

In the following description, numerous technical details are set forth in order to provide a better understanding of the present application. However, it will be understood by those skilled in the art that the technical solutions claimed in the present application may be implemented without these technical details and with various changes and modifications based on the following embodiments.

The system for synchronously performing transcranial ultrasonic stimulation and near-infrared brain function imaging can be a multi-channel imaging system, namely a plurality of light sources and a plurality of photoelectric detection devices, and can comprise an integrated design of a plurality of ultrasonic transducers and an infrared acquisition unit, so that transcranial ultrasonic stimulation and synchronous near-infrared brain function imaging are performed on a plurality of areas of a brain. The following technical details only describe the integrated design of one ultrasonic transducer and an infrared acquisition unit; the integrated design of the multiple ultrasonic transducers and the infrared acquisition unit, the integrated design of the single or multiple ultrasonic transducers and the infrared acquisition unit, and the design of the multi-channel near-infrared brain function imaging system can be obtained by referring to the description of the embodiment, and are not described again.

1. Near infrared-ultrasonic coupler

Referring to fig. 2, the system for synchronously performing transcranial ultrasonic stimulation and near-infrared brain function imaging comprises: the near-infrared-ultrasonic brain function imaging device comprises a near-infrared-ultrasonic coupler 100 and a near-infrared brain function imaging device, wherein the near-infrared-ultrasonic coupler 100 is provided with an ultrasonic transducer 4, and the ultrasonic transducer 4 is used for generating focused ultrasonic waves required by transcranial ultrasonic stimulation;

the near-infrared brain function imaging device comprises a near-infrared blood oxygen data acquisition unit, wherein the near-infrared blood oxygen data acquisition unit is integrated at the far end of the near-infrared-ultrasonic coupler 100, so that the near-infrared brain function imaging device synchronously acquires the near-infrared blood oxygen data of the part stimulated by the ultrasonic wave; the near-infrared blood oxygen data acquisition unit comprises a light source module and a photoelectric detector module, wherein the light source module is used for emitting multi-wavelength near-infrared light waves, and the photoelectric detector module is used for receiving near-infrared light wave signals. In one embodiment, the near infrared-ultrasonic coupler is provided with at least one near infrared light source mounting hole for mounting a light source module below the mounting position of the ultrasonic transducer 4, and the photoelectric detector module is arranged around the light source module. In an embodiment, a polymer ultrasound conducting medium is installed at a far end of the ultrasound transducer 4 in the near infrared-ultrasound coupler 100, the near infrared-ultrasound coupler 100 further includes a coupler far end surface, the light source module is disposed on a geometric center of the coupler far end surface, and the light source module is in close contact with the polymer ultrasound conducting medium, and the photodetector module is disposed around the light source module.

According to an embodiment of the present application, as shown in fig. 3 and 4, the near infrared-ultrasonic coupler 100 is generally cylindrical, the near infrared-ultrasonic coupler 100 includes an upper near infrared-ultrasonic coupler housing 1 and a lower near infrared-ultrasonic coupler housing 2, and the upper near infrared-ultrasonic coupler housing 1 is fixed to the lower near infrared-ultrasonic coupler housing 2 by a screw structure; the near infrared-ultrasonic coupler 100 includes a coupler distal end surface;

the lower shell 2 of the near infrared-ultrasonic coupler forms a first internal space, the ultrasonic transducer 4 is installed in the first internal space, the upper shell 1 of the near infrared-ultrasonic coupler is fixed with the ultrasonic transducer 4 through a transducer fixing groove 9, the near end of the ultrasonic transducer 4 is fixed on the upper shell 1 of the near infrared-ultrasonic coupler, and the far end of the ultrasonic transducer 4 is provided with (the bottom of the ultrasonic transducer is tightly attached with) a high-molecular ultrasonic conducting medium 5 for realizing low-loss conduction of ultrasonic;

the near-infrared-ultrasonic coupler lower shell 2 comprises a near-infrared-ultrasonic coupler lower shell 2, wherein the bottom (far end) of the near-infrared-ultrasonic coupler lower shell 2 is provided with 4 photoelectric

detection mounting holes

7 and 1 near-infrared light source mounting hole 8, the near-infrared light source mounting hole 8 is used for mounting a light source module, is arranged in the geometric center of the surface of the far end of the coupler and is tightly contacted with the high-molecular ultrasonic conducting medium 5; 4 photoelectric detection mounting holes 7 are uniformly distributed around the 1 near-infrared light

source mounting hole

8, and 4 photoelectric detection devices of a photoelectric detection module are respectively mounted in the 4 photoelectric detection mounting holes 7; the included angle between the central lines of two adjacent photoelectric detection mounting holes 7 is 90 degrees, namely the included angle between the central lines of two adjacent photoelectric detection devices is 90 degrees. The diameter of the light source module is between 1.35mm and 5.5mm, and the diameter of the light detector module is between 3mm and 8.5 mm. The selection of the diameter of the light source (i.e., the diameter of the near-infrared light source mounting hole 8) and the number of the photodetecting devices will be described in detail with the test results below.

The bottom of the lower shell 2 of the near infrared-ultrasonic coupler is wrapped with a polymer light-insulating liner 3; the lower near infrared-ultrasonic coupler shell 2 comprises a lower coupler inner shell 21, a lower coupler outer shell 22 and a cable fixing port 6, a second

inner space

23,4 photoelectric detection mounting holes 7 are formed in the lower coupler inner shell 21 and the lower coupler outer shell 22 and are arranged on the lower near infrared-ultrasonic coupler shell 2, so that a photoelectric detection device is arranged in the second inner space 23 and comprises a photoelectric detection head 11, and the photoelectric detection head 11 comprises a photoelectric detector 112; the cable of the photodetector 112 is fixed at the cable fixing port 6 through the second inner space 23 (cavity structure) of the lower case 2.

As shown in fig. 4 and 5, the blood oxygen data collecting unit further comprises a light source fixing rod 10, which is disposed on the distal end surface of the coupler and is used for supporting the light source, and the light source fixing rod is connected with the lower shell of the near infrared-ultrasonic coupler. The light source fixing rod is internally provided with a conductive wire to provide power for the light source 8 fixed by the light source fixing rod. In this embodiment, the number of the light source fixing rods is 3, which are respectively the first light source fixing rod, the second light source fixing rod and the third light source fixing rod, and the included angle between the longitudinal axes of two adjacent light source fixing rods is 120 °. In one embodiment, the minimum angle between the longitudinal axes of the first, second and third light source fixing bars and the line connecting the light source module and the light detecting device is θ (since it is a symmetrical relationship, it is assumed in fig. 5 that the angle between the first light source fixing bar and the line connecting the light source module and the light detecting device adjacent thereto is labeled θ), where θ may be between 7 ° and 15 °; preferably, θ > 8.5 °, more preferably, θ is 15 °, and an angle is formed between the light source fixing rod and the light source-detector connecting line so as to maintain a certain sound field intensity on the light source-detector connecting line, the power source, the photoelectric detection device and the light source fixing rod are arranged to achieve effective detection of the fNIRS signal and reduce interference of the fixing rod on the fNIRS signal, and the setting of θ is described in detail with test results in the following.

The width of the cross section of the light source fixing rod is L ₁ ，L ₁ I.e. correspondingly the light source fixing bar 10 has an influence on the ultrasound field of transcranial ultrasound stimulation on the base ultrasound occlusion area, preferably L ₁ The selection of the width of the cross section of the light source fixing rod, which is less than half the wavelength of the ultrasonic waves generated by the ultrasonic transducer, will be explained in detail in the following with experimental test results.

In an embodiment, as shown in fig. 6 and 7, the photodetector module includes a plurality of photodetecting devices, each photodetecting device includes a photodetecting head 11, and a photodetecting head 11 providing a photodetecting mounting hole mounted on the coupler, the photodetecting head mounting hole 7 and the photodetecting head 11 are mounted by using a snap-fit structure, as shown in fig. 7, the photodetecting head 11 includes a casing 111 of the photodetecting head, a photodetector 112, and a near-infrared polarizer 113, the casing 111 of the photodetecting head has a plurality of sets of snap-fit grooves mounted around and capable of adjusting the telescopic length of the photodetecting head when mounted, the near-infrared polarizer 113 is mounted at the bottom of the casing 111 of the photodetecting head to filter out other interfering light waves except for the near-infrared detecting signal; preferably, the photodetector 112 is a SiPM silicon photomultiplier sensor, which enables the acquisition of near infrared signals.

In a preferred embodiment, the present application proposes a design of a near infrared-ultrasonic coupler that can reduce ultrasonic conduction loss to the maximum extent, does not affect a near infrared detection optical path, and maintains a high detection signal-to-noise ratio according to actual sound field tests and near infrared test results. As shown in fig. 4 and 5, fig. 4 is a top view of a near infrared-ultrasonic coupler according to an embodiment of the present application; FIG. 5 is a top view of a near infrared-ultrasonic coupler with sizing according to an embodiment of the present application; fig. 5 shows a reasonable structure of a three-light-source fixing rod, the coupler structure can maintain the symmetry of a sound field to a certain extent, the ultrasonic conduction loss is low, the sound field required by transcranial stimulation can be conducted, and meanwhile, a certain sound intensity is maintained in a near-infrared detection area on a light source-photoelectric detector connecting line, and specific parameters of the coupler structure meet the following table:

TABLE 1 near-IR-ULTRASONIC COUPLER PARAMETERS TABLE

Through practical tests, the coupler structure meeting the requirements of the upper table can meet the sound field data shown in the table 2, and the sound beam can meet certain symmetry and focusing performance, so that the effectiveness of ultrasonic stimulation is ensured. The sound field parameters in table 2 are shown in fig. 11.

Table 2 sound field parameter table satisfied by the preferred embodiment

In practical tests, when the coupler parameters do not meet the requirements of the table 1, the ultrasonic sound field data in the table 2 are difficult to meet, the sound field is asymmetric, and the ultrasonic sound intensity and the focusing performance are difficult to meet the requirements.

Based on the application scene of the synergistic use of the transcranial ultrasonic stimulation and the near-infrared brain function imaging device, the measuring head for the near-infrared brain function imaging can be simply improved, for example, the distance between a light source for the near-infrared brain function imaging and a photoelectric detector is increased, so that an ultrasonic transducer structure can be accommodated between the light source and the photoelectric detector, and the problem of position coincidence of the ultrasonic transducer and the photoelectric detector is solved.

However, in the above technical solution, along with the increase of the distance between the light source and the photodetector, the detection precision is inevitably further reduced, and further, the requirement of high-precision detection is not sufficiently satisfied.

2. Experiment under different near infrared-ultrasonic coupler structural designs

In order to ensure the effectiveness of ultrasonic stimulation and synchronously acquire near infrared spectrum data at a transcranial ultrasonic stimulation target point in real time, the applicant hopes that a sound field formed by a designed near infrared-ultrasonic coupler keeps certain symmetry on the cross section, and the focus position cannot deviate from the central point of the far end of the coupler too far; meanwhile, the longitudinal section of the sound field needs to keep spindle-shaped sound field distribution, the focal distance is close to that of the sound field without the coupler, and the half-height width of the longitudinal section sound beam meets the requirement. The applicant has carried out a great deal of structural design and experiments on the structural arrangement of the light source module, the light source detector module and the light source fixing rod in the near infrared-ultrasonic coupler, so as to obtain the optimal structural arrangement shown in table 1, and some embodiments are as follows.

Example 1

Referring to fig. 5, in the present embodiment, the light source is disposed at the geometric center of the far end surface of the near infrared-ultrasonic coupler, 4 light source detection devices are disposed around the light source, and the included angle between the center lines of two adjacent photoelectric detection devices is 90 °; the 3 light source fixing rods are used for supporting the light source modules, the included angle between the longitudinal axes of every two adjacent light source fixing rods is 120 degrees, and the specific sizes of the light source, the photoelectric detection device and the light source fixing rods are shown in table 3.

Referring to fig. 8a to 8f, the inventors studied and analyzed the light source fixing bar cross-sectional width L of the near infrared-ultrasonic coupler ₁ The effect on the ultrasonic testing; the following tests were performed, the test conditions are shown in Table 3.

Table 3: test conditions

The test results were as follows:

FIGS. 8a-8f show different light source fixing rod sectionsTesting the cross section and the longitudinal section of the ultrasonic field under the face width; wherein, fig. 8a to 8b are respectively a light source fixing bar sectional width L of the near infrared-ultrasonic coupler according to embodiment 1 of the present application ₁ Test patterns of the cross section and the longitudinal section of the ultrasonic sound field when the diameter is 0.5 mm; FIGS. 8c to 8d are sectional widths L of the light source fixing bar of the near-infrared-ultrasonic coupler according to embodiment 1 of the present application, respectively ₁ Test charts of the cross section and the longitudinal section of the ultrasonic sound field when =1.5 mm; FIGS. 8e to 8f are respectively a light source fixing bar sectional width L of the near infrared-ultrasonic coupler according to embodiment 1 of the present application ₁ Test patterns of the cross section and the longitudinal section of the ultrasonic sound field when the diameter is 2.5 mm;

referring to FIGS. 8a and 8b, when L is ₁ =0.5 mm: sound intensity at focus I _SPPA ＝8.221W/cm ² Focal length: 43.51mm;

see fig. 8c and 8d, when L is ₁ =1.5 mm; sound intensity at focus I _SPPA ＝7.151W/cm ² Focal length: 49.52mm;

see FIGS. 8e and 8f, when L is ₁ =2.5 mm; sound intensity at focus I _SPPA ＝2.345W/cm ² Focal length: 64.45mm;

from the above results and FIGS. 8a-8f, it is concluded that: in this example, when L ₁ When the wave length is less than lambda/2 =1.5mm, the influence of the bottom structure of the coupler on a sound field is small; if the value is larger than the above value, the symmetry of the sound field is weakened, and the attenuation of the sound field intensity is larger.

Because the ultrasonic stimulation needs to apply stimulation with rated intensity on a target point of the cortex at a specified depth, the proper focal distance is required for an ultrasonic sound field, the shape of the sound field presents a symmetrical spindle shape, and the focality of the sound field is kept. And L is ₁ There is a large influence on the sound field distribution.

Thus, the cross-sectional width L of the holder for fixing the light source (three light source fixing bars) ₁ Less than the wavelength of the acoustic wave is required, and preferably less than half the wavelength of the acoustic wave. For the 0.5MHz ultrasonic transducer employed in this embodiment, L ₁ Preferably less than 1.5 mm.

Example 2

Referring to FIGS. 9a-9d, example 2 and exampleExcept that the light source fixing lever cross section L of embodiment 2 ₁ Is 1.5mm, in the present example, the inventors studied and analyzed the influence of the light source diameter of the near infrared-ultrasonic coupler on the ultrasonic test; and the following tests were performed: the test conditions are shown in Table 4.

Table 4: test conditions

Referring to FIGS. 9a and 9b, when d ₂ Acoustic intensity at focus I =1.5mm _SPPA ＝8.458W/cm ² Focal length: 41.51mm;

referring to FIGS. 8c and 8d, when d is reached ₂ Acoustic intensity at focus I =3mm _SPPA ＝7.151W/cm ² Focal length: 49.52mm; note that: tests under this parameter are listed in the examples, so reference is made here to the graphs of FIGS. 8c-8 d;

referring to FIGS. 9c and 9d, when d is reached ₂ =6mm, sound intensity at focus I _SPPA ＝1.151W/cm ² Focal length: 64.48mm;

from the above results and FIGS. 9a-9d, it is concluded that: d ₂ <When the thickness is 3mm, the influence on the sound field is small, if the thickness is larger than the value, the symmetry of the sound field is weakened, and the attenuation of the intensity of the sound field is large. According to the experimental test results, in the coupler structure design, the diameter d of the central light source ₂ Preferably less than 3mm.

In combination with the above experimental test results, we can state in the application that the diameter d of the light source is the designed structure ₂ Should be smaller than the wavelength of the sound waves. For the 0.5MHz ultrasonic transducer used only in this embodiment, d ₂ Preferably less than 3mm.

Example 3

In the embodiment, the inventor researches and analyzes the influence of the number of fixing rods of the near infrared-ultrasonic coupler on the ultrasonic test; and the following tests were performed:

(1) And (3) testing conditions are as follows:

d ₁ ＝30mm，d ₂ ＝3mm，L ₁ ＝1.5mm，d ₃ =17mm, θ =15 °, S =9.59%, wherein reference numerals refer to descriptions in table 1, wherein an arrangement of the light source, the light source fixing lever, and the light source detecting device is as shown in fig. 5, which is the same as that of embodiment 1, and it is noted that experiments under the parameters have been listed in embodiment 1, so reference is made to fig. 8c-8d herein;

see FIGS. 8c-8d, sound intensity I at focus _SPPA ＝7.151W/cm ² Focal length: 49.52mm.

(2) Referring to fig. 10a to 10c, the arrangement of the light source fixing bars 10 is as shown in fig. 10a, wherein the number of the light source fixing bars is 4, the angle between the longitudinal axes of two adjacent fixing bars is 90 °, and the angle between the center lines of two adjacent light source detecting devices is 90 °.

And (3) testing conditions are as follows:

L ₁ ＝1.5mm d ₁ ＝30mm，d ₂ ＝3mm，d ₃ =17mm, s =12.46%, wherein the reference numerals refer to the description of table 1.

Referring to FIGS. 10b-10c, sound intensity I at focus _SPPA ＝4.451W/cm ² Focal length: 62.43mm.

The results of (1) and (2) above and FIGS. 8c-8d, 10a-10c lead to the conclusion that: as the number of the fixed rods of the light source is increased, the ratio of the bottom shielding area is increased, the focus position is gradually back, and the sound intensity at the focus is obviously reduced.

Example 4

The included angle between the light source fixing rod and the connecting line of the light source-light source detection device is used for keeping certain sound field intensity on the connecting line of the light source-detector. In order to enable the sound intensity of the near infrared-ultrasonic coupler to keep more than 80% of the original sound intensity (the coupler is not provided with an integrated light source and a light detector), the inventor researches and analyzes the influence of a light source fixing rod of the near infrared-ultrasonic coupler and the minimum deflection angle (included angle) of the light source-detector on ultrasonic testing; and the following tests were performed:

(1) And (3) testing conditions: detecting the sound intensity at a designated point by adopting a structure that a fixed rod is superposed with a connecting line of a light source and a detector to obtain the sound intensity of the detection point, and simultaneously testing the maximum sound intensity value (focus sound intensity) in a sound field;

wherein d is ₁ ＝30mm，d ₂ ＝3mm，d ₃ ＝17mm；

When the light source-light source detector connecting lines are coincident, and L is more than or equal to 1.3mm ₁ When the thickness is less than or equal to 2mm, the sound field close to the position (28.5 mm) of the light source fixing rod has certain attenuation, the sound field change is small at the focus position, and the sound field result is shown in the table 5:

table 5:

L ₁ (mm)	detecting the sound intensity (W/cm) ² )	Focal point sound intensity (W/cm) ² )	Focal position (m)
				1.3	3.524	8.542	43.51
1.5	1.524	7.151	49.52
				2.0	0.425	6.451	54.37

Therefore, when L is used ₁ When the thickness is not less than 1.5mm, a certain deflection angle is required to exist between the light source fixing rod and the connection line of the light source detector and the light source detector, so that the influence of the fixing rod on the stimulation target point is reduced

(2) And (3) testing conditions: detecting the sound intensity at a designated point by adopting a structure that an included angle exists between a fixed rod and a light source-detector connecting line, wherein d ₁ ＝30mm，d ₂ ＝3mm，d ₃ =17mm, sound field results see table 6.

TABLE 6

θ	Detecting the sound intensity (W/cm) ² )	Focal point sound intensity (W/cm) ² )	Focal position (mm)
				6°	3.415	8.264	48.97
8.5°	5.347	8.355	48.97
				11°	6.813	8.542	48.97

The conclusion is drawn from the test results of example 4 under the (1) and (2) test conditions: because fNIRS is to detect the change of blood oxygen on the connection line between the light source and the detector, when the ultrasonic stimulation and fNIRS work together, the connection line between the light source of fNIRS and the detector needs to maintain a certain ultrasonic intensity, the above test shows that the position of the light source fixing rod can affect the ultrasonic sound intensity on the connection line between the light source and the detector, when the included angle existing between the fixing rod and the connection line between the light source and the detector is more than 8.5 degrees, the sound intensity value of the detection point can meet the required requirement, and the included angle is 15 degrees, which is the optimal included angle designed by the three crossed fixing rods in fig. 5.

3. System for synchronously performing transcranial ultrasonic stimulation and near-infrared brain function imaging

Referring to fig. 1, the system for synchronously performing transcranial ultrasonic stimulation and near-infrared brain function imaging provided by the application is an integrated system for performing transcranial ultrasonic stimulation and near-infrared brain function imaging, which can synchronously perform transcranial ultrasonic stimulation and detect nerve activity of a stimulated part. The system can monitor the change condition of brain function information such as brain blood oxygen content, blood vessel volume and the like under the transcranial ultrasonic stimulation system in real time by utilizing infrared while the transcranial ultrasonic device works, performs functional imaging and synchronously detects the nerve activity of the part stimulated by the transcranial ultrasonic.

Structurally, the system realizes the integrated design of an ultrasonic transducer and an infrared acquisition unit of a transcranial ultrasonic stimulation system, and can realize the acquisition of brain near-infrared light imaging information without influencing ultrasonic stimulation conduction. The system controls the distribution of an ultrasonic stimulation sequence, the acquisition of brain near infrared light imaging information, and the time stamp and the stimulation type mark of the ultrasonic stimulation sequence on the acquired near infrared light imaging data through upper computer software. In actual use, the system can flexibly adjust the position of the ultrasonic and infrared integrated ultrasonic transducer to detect brain function information of different brain targets, and the use efficiency of the system is greatly improved.

The system for synchronously performing transcranial ultrasonic stimulation and near-infrared brain function imaging comprises the near-infrared-ultrasonic coupler, a transcranial ultrasonic stimulation device and a near-infrared brain function imaging device working in cooperation with the transcranial ultrasonic stimulation, wherein the near-infrared-ultrasonic coupler is provided with an ultrasonic transducer and the near-infrared brain function imaging device, and the near-infrared brain function imaging device comprises a near-infrared blood oxygen data acquisition unit and a near-infrared blood oxygen data processing unit.

The near-infrared blood oxygen data acquisition unit is integrated at the far end of the near-infrared-ultrasonic coupler, so that the near-infrared brain function imaging device synchronously acquires the near-infrared blood oxygen data of the part which is ultrasonically stimulated; the near infrared blood oxygen data processing unit is configured to acquire the data acquired by the near infrared blood oxygen data acquisition unit and process the data, and is matched with a transcranial ultrasonic stimulation device which synchronously generates an ultrasonic stimulation signal for use.

The near infrared blood oxygen data acquisition unit comprises a light source part (a light source module), a detector part (a photoelectric detector module) and a light source drive control module part; the near infrared blood oxygen data processing unit comprises a signal conditioning module part, a multi-channel signal sampling part, a main control board part and a computer part.

The light source part comprises 660nm,780nm and 850nm miniature semiconductor infrared lasers with different wavelengths, and drivers with each wavelength are driven by square wave signals with different modulation frequencies sent by the light source driving control module, so that the frequency division multiplexing of the LED light source is realized, and the overall sampling rate of the system is effectively improved. The light source part integrates lasers with three wavelengths, and miniaturization is realized structurally so as to reduce the influence of the size of the lasers on transcranial ultrasonic conduction.

The light source driving control module is composed of a plurality of groups of independent driving control chips and provides adjustable current driving for the plurality of paths of LED light sources, and each group of lasers with different wavelengths is provided with an independent driving control circuit so as to realize the independent control of each laser. The light source is driven in a frequency division multiplexing mode, namely, each laser is driven by a driving signal with different frequency. The light source driving control module works by receiving a driving signal sent by the direct frequency synthesis module, can feed back the working state of the light source in real time, and has the functions of multi-path gating, light power detection, output power and current regulation, overcurrent protection, low power consumption mode and the like.

The photoelectric detector part comprises a plurality of groups of high-performance silicon photomultiplier (SiPM) photoelectric detector units which are distributed around the ultrasonic coupler so as to detect the blood oxygen change condition of the ultrasonic stimulation part. The silicon photomultiplier (SiPM) has picosecond-level rapid response capability and higher time resolution, has the characteristics that a solid detector is insensitive to a magnetic field and can resist high-strength mechanical impact, and is suitable for a use scene working with an ultrasonic system. The photoelectric detector part integrates a primary amplifying circuit and a silicon photomultiplier tube, and can realize the detection of weak illumination information.

The signal conditioning module comprises two parts of signal preprocessing and a double phase-locked amplifier, and the signal preprocessing module comprises a secondary filter circuit and an isolated amplifying circuit. And the signal preprocessing part is used for filtering noises such as ambient light noise, power frequency interference and the like. The biphase phase-locked amplifier calculates a plurality of photoelectric voltage signals led out by the signal preprocessing module and a reference signal sent by the main control board by utilizing a phase-locked amplifying technology, realizes synchronous demodulation of the frequency division multiplexing signals of the photoelectric detector, and simultaneously filters noise irrelevant to the original physiological signals.

The multi-path A/D sampling module can realize analog-to-digital conversion with high sampling rate, and the signals synchronously demodulated by the two-phase lock-in amplifier are sent to the multi-path A/D sampling module for analog-to-digital conversion and finally sent to the main control board to be calculated to obtain a blood oxygen saturation area, thereby realizing brain function imaging.

The direct frequency synthesis module can generate high-precision square wave driving signals with different frequencies and duty ratios and transmit the square wave driving signals to the LED driving control module, and generate phase-orthogonal reference signals and transmit the phase-orthogonal reference signals to the signal conditioning module. The direct frequency synthesis module has a multi-channel signal independent regulation function, can communicate with a main control board by utilizing an I2C bus, and regulates output signals.

The main control board part is responsible for the whole system and time sequence control of the lower computer and can provide control signals for the direct frequency synthesis module so as to realize the gating control of the multi-path light source. And calculating the blood oxygen saturation degree by analyzing the data converted by the multi-path A/D sampling module, and transmitting the waveform information to a computer system. The main control board is controlled by the upper computer system, and can realize the cooperative work with the transcranial ultrasonic stimulation system.

The upper computer system can control the main control board and the transcranial ultrasonic stimulation system. The cooperative work of the near-infrared imaging system and the transcranial ultrasonic stimulation system can be realized through the upper computer system. The upper computer system can adjust the transcranial ultrasonic stimulation parameters such as the stimulation intensity, the pulse duration, the pulse frequency, the pulse duty ratio, the pulse number and the like in real time according to the requirements. The upper computer system can realize real-time communication of the main control board part, and further realize control of the multi-channel near-infrared light source and the detector. The upper computer system can draw a multi-channel brain blood oxygen change map in a real-time image form, identify the time when the transcranial ultrasonic system generates ultrasonic stimulation in the near-infrared imaging data, and reflect the change condition of the brain blood oxygen under the ultrasonic stimulation in an image form.

The transcranial ultrasonic stimulation system is controlled by an upper computer system, can send pulse ultrasonic with parameters specified by the upper computer system through an ultrasonic transducer, and is conducted through a near infrared-ultrasonic coupler to stimulate different areas of the cerebral cortex, so that a corresponding nerve regulation function is realized.

As a further implementation mode, the upper computer integrates a near-infrared imaging map analysis software system based on transcranial ultrasonic stimulation. The imaging atlas analysis system can perform real-time recording, signal preprocessing, data statistics, parameter comparison analysis, waveform spectrum analysis, drawing of a visual near-infrared brain topographic map and other functions of multi-channel near-infrared data under various different ultrasonic stimulation parameters, so that a user can conveniently analyze and process the near-infrared atlas.

As a further embodiment, the present invention contemplates a coupler suitable for both near infrared detection and transcranial ultrasound stimulation. The coupler integrates an ultrasound transducer, an ultrasound conductive medium, a near infrared light source, and a photodetector. The ultrasonic wave can be transmitted almost without loss by improving the internal structure of the coupler and using the improved polymer composite material as an ultrasonic conducting medium, and the sound guide material is used as a pad to contact the head. The sound guide composite material is used as a protective sleeve of the photoelectric detector, the good light impermeability of the sound guide composite material can effectively reduce the interference of an external light source, the near infrared light radiation energy in the protective sleeve is concentrated, and a better detection effect is realized.

All documents mentioned in this application are to be considered as being incorporated in their entirety into the disclosure of this application so as to be subject to modification as necessary. Further, it is understood that various changes or modifications may be made to the present application by those skilled in the art after reading the above disclosure of the present application, and such equivalents are also within the scope of the present application as claimed.

Claims

1. A system for simultaneously performing transcranial ultrasound stimulation and near-infrared brain function imaging, comprising:

the near-infrared brain function imaging device comprises a near-infrared blood oxygen data acquisition unit, and the near-infrared blood oxygen data acquisition unit is integrated at the far end of the near-infrared-ultrasonic coupler, so that the near-infrared brain function imaging device synchronously acquires near-infrared blood oxygen data of an ultrasonically stimulated part; the near-infrared blood oxygen data acquisition unit comprises a light source module and a photoelectric detector module, wherein the light source module is used for emitting multi-wavelength near-infrared light waves, and the photoelectric detector module is used for receiving near-infrared light wave signals;

a polymer ultrasonic conduction medium is mounted at the far end of an ultrasonic transducer in the near infrared-ultrasonic coupler, the near infrared-ultrasonic coupler comprises a coupler far end surface, the light source module is arranged at the geometric center of the coupler far end surface, and the light source module is in close contact with the polymer ultrasonic conduction medium;

the near infrared blood oxygen data acquisition unit further comprises a light source fixing rod configured to support the light source module, the light source fixing rod is arranged on the far end surface of the coupler and is connected with the near infrared-ultrasonic coupler lower shell;

the width of the cross section of the light source fixing rod is L ₁ ，L ₁ Less than the wavelength of the ultrasonic waves generated by the ultrasonic transducer;

the diameter of the light source module is d ₂ ，d ₂ Less than the wavelength of the ultrasonic waves;

the light source module is arranged on the lower surface of the high-molecular ultrasonic conducting medium;

the near infrared-ultrasonic coupler comprises a near infrared-ultrasonic coupler lower shell forming a first inner space, the ultrasonic transducer is installed in the first inner space, the photoelectric detector module comprises a plurality of photoelectric detection devices, and the near infrared-ultrasonic coupler lower shell comprises a plurality of photoelectric detection installation holes for installing the photoelectric detection devices;

the photoelectric detection mounting holes are arranged at the far end of the lower shell of the near infrared-ultrasonic coupler.

2. The system of claim 1, wherein the number of the photo detection mounting holes is 4 and a photo detection device is mounted in each photo detection mounting hole, and an angle between center lines of two adjacent photo detection devices is 90 °.

3. The system of claim 2, wherein the number of light source fixing bars is 3, and the included angle between the longitudinal axes of two adjacent light source fixing bars is 120 °.

4. The system of claim 3, wherein a minimum angle between a longitudinal axis of the light source fixing rod and a line connecting both the light source module and the photodetecting device is θ, wherein θ is in a range of 7 ° -15 °.

5. The system of claim 1, wherein the light source module is between 1.35mm and 5.5mm in diameter and the photodetector module is between 3mm and 8.5mm in diameter.

6. The system of claim 1, further comprising a host computer system communicatively coupled to the near-infrared brain function imaging device and further communicatively coupled to a transcranial ultrasound stimulation device, the host computer system configured to control the transcranial ultrasound stimulation device and the near-infrared brain function imaging device.

7. The system of claim 6, wherein said near-infrared brain function imaging device further comprises a near-infrared blood oxygen data processing unit configured to acquire and process data acquired by said near-infrared blood oxygen data acquisition unit while being used in conjunction with a transcranial ultrasound stimulation device that synchronously generates ultrasound stimulation signals.

8. The system of claim 7, wherein said host computer system is communicatively coupled to said near infrared blood oxygen data processing unit.

9. The system of claim 8, wherein said near infrared blood oxygen data processing unit comprises a signal conditioning module, a multi-channel a/D sampling module, an MCU master control board module, and a direct frequency synthesis module; the signal conditioning module is used for processing the detection signal of the photoelectric detector module, filtering an irrelevant noise signal from the detection signal and demodulating the signal; the multi-path A/D sampling module is used for receiving the signal of the signal conditioning module and performing analog-to-digital conversion; the MCU main control board module is used for controlling the lower computer circuit, receiving and analyzing the near infrared signal sampling data transmitted by the multi-path A/D sampling module and simultaneously communicating with the upper computer system; the direct frequency synthesis module is used for sending out driving signals with different frequencies through frequency division multiplexing and providing reference signals for the signal conditioning module.

10. The system of claim 9, wherein said near infrared blood oxygen data collecting unit further comprises an LED driving control module, said LED driving control module is used for controlling a constant current source for driving the LED to adjust the brightness of the light source module, said LED driving control module is further connected to said direct frequency synthesizing module in a communication manner.

11. The system of claim 10, wherein the signal conditioning module comprises a signal pre-processing module and a dual phase-locked amplifier module; the signal preprocessing module comprises a secondary filter circuit and an isolation amplifying circuit and is used for filtering ambient light noise and power frequency interference noise.

12. The system of claim 11, wherein the dual lock-in amplifier module synchronously demodulates the photodetector frequency division multiplexed signal using lock-in amplification while filtering out noise not related to the original physiological signal.

13. The system of claim 12, wherein the upper computer system integrates a near infrared imaging atlas analysis software based on transcranial ultrasonic stimulation, can record multichannel near infrared data in real time under various different ultrasonic stimulation parameters, preprocess signals, count data, draw a visual near infrared brain topographic function, display transcranial ultrasonic stimulation time and parameters in the near infrared brain imaging atlas in real time, and perform comprehensive analysis according to multichannel atlas changes and transcranial ultrasonic stimulation parameters.

14. The system of claim 1, further comprising a transcranial ultrasound stimulation device for synchronized generation of ultrasound stimulation signals.