WO2016101487A1 - 一种超声深部脑刺激方法及系统 - Google Patents

一种超声深部脑刺激方法及系统 Download PDF

Info

Publication number
WO2016101487A1
WO2016101487A1 PCT/CN2015/078373 CN2015078373W WO2016101487A1 WO 2016101487 A1 WO2016101487 A1 WO 2016101487A1 CN 2015078373 W CN2015078373 W CN 2015078373W WO 2016101487 A1 WO2016101487 A1 WO 2016101487A1
Authority
WO
WIPO (PCT)
Prior art keywords
ultrasonic
ultrasound
brain stimulation
deep brain
transducer array
Prior art date
Application number
PCT/CN2015/078373
Other languages
English (en)
French (fr)
Inventor
郑海荣
牛丽丽
王丛知
钱明
肖杨
孟龙
Original Assignee
中国科学院深圳先进技术研究院
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 中国科学院深圳先进技术研究院 filed Critical 中国科学院深圳先进技术研究院
Publication of WO2016101487A1 publication Critical patent/WO2016101487A1/zh
Priority to US15/630,623 priority Critical patent/US11253730B2/en

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy
    • A61N7/02—Localised ultrasound hyperthermia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0033—Features or image-related aspects of imaging apparatus classified in A61B5/00, e.g. for MRI, optical tomography or impedance tomography apparatus; arrangements of imaging apparatus in a room
    • A61B5/0036—Features or image-related aspects of imaging apparatus classified in A61B5/00, e.g. for MRI, optical tomography or impedance tomography apparatus; arrangements of imaging apparatus in a room including treatment, e.g., using an implantable medical device, ablating, ventilating
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0033—Features or image-related aspects of imaging apparatus classified in A61B5/00, e.g. for MRI, optical tomography or impedance tomography apparatus; arrangements of imaging apparatus in a room
    • A61B5/004—Features or image-related aspects of imaging apparatus classified in A61B5/00, e.g. for MRI, optical tomography or impedance tomography apparatus; arrangements of imaging apparatus in a room adapted for image acquisition of a particular organ or body part
    • A61B5/0042—Features or image-related aspects of imaging apparatus classified in A61B5/00, e.g. for MRI, optical tomography or impedance tomography apparatus; arrangements of imaging apparatus in a room adapted for image acquisition of a particular organ or body part for the brain
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/05—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves 
    • A61B5/055—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves  involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A61B5/316—Modalities, i.e. specific diagnostic methods
    • A61B5/369—Electroencephalography [EEG]
    • A61B5/377—Electroencephalography [EEG] using evoked responses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/72—Signal processing specially adapted for physiological signals or for diagnostic purposes
    • A61B5/7235—Details of waveform analysis
    • A61B5/7239—Details of waveform analysis using differentiation including higher order derivatives
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H50/00—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics
    • G16H50/50—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for simulation or modelling of medical disorders
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16Z—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS, NOT OTHERWISE PROVIDED FOR
    • G16Z99/00—Subject matter not provided for in other main groups of this subclass
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/02—Details of sensors specially adapted for in-vivo measurements
    • A61B2562/0209—Special features of electrodes classified in A61B5/24, A61B5/25, A61B5/283, A61B5/291, A61B5/296, A61B5/053
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/04—Arrangements of multiple sensors of the same type
    • A61B2562/046—Arrangements of multiple sensors of the same type in a matrix array
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy
    • A61N2007/0004—Applications of ultrasound therapy
    • A61N2007/0021—Neural system treatment
    • A61N2007/0026—Stimulation of nerve tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy
    • A61N2007/0052—Ultrasound therapy using the same transducer for therapy and imaging
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy
    • A61N2007/0073—Ultrasound therapy using multiple frequencies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy
    • A61N2007/0082—Scanning transducers

Definitions

  • the present invention relates to ultrasonic brain stimulation techniques, and more particularly to an ultrasonic deep brain stimulation method and system.
  • the nervous system is the system that plays a leading role in the body.
  • the central nervous system mediates the generation of advanced functions such as emotion, attention, learning, and memory, and participates in the generation of feelings and the initiation of random movement.
  • Neurons are functional units in which the nervous system plays a variety of functions. Neurons form networks through synapses, communicate with each other, transmit information, and form systems of sense and movement. Each system can be divided into several subsystems, such as feelings.
  • the function of vision, smell, hearing, taste and body surface touch, etc. depends on different types of neural circuits formed by precise connections between cells in different parts of the nervous system.
  • the neural circuit is a bridge between molecular function and overall behavioral function. The study of specific functional neural circuits is helpful for understanding the formation and modification of neural circuits, information coding, processing and processing, and their relationship with behavior. A deeper understanding of how the brain works.
  • DBS Deep brain stimulation
  • Cerebral pacemaker is a new treatment combining neurological disease surgery with electronic technology.
  • Stereotactic surgery is used to implant the microelectrode into the brain target of the patient, and the abnormal function of the target cell is inhibited by controlled electrical stimulation to achieve the purpose of effectively interfering with the disease (see Chinese Patent CN 102470247 A, CN 102762253 A4) .
  • This technology is currently the only technology that can directly contact the deep brain and interfere with brain activity and treat brain diseases. Since it was first used for tremor control in 1987, more than 100,000 patients worldwide have implanted DBS devices.
  • refractory brain diseases such as depression, Parkinson's disease, refractory epilepsy, dystonia, stubbornness Solid pain and the like provide an effective new intervention method [Halpem CH, Samadani U, Litt B, et a1. Deep brain stimulation for epilepsy. Neurotherapeutics, 2008, 5(1): 59-67.].
  • Transcranial direct current stimulatioin and transcranial magnetic stimulation (TMS) are painless and non-invasive detection and treatment techniques.
  • the former changes the depolarization or hyperpolarization direction of the neuronal membrane potential on the surface of the brain through two saline-soaked scalp-attached electrodes to change the cortical excitability of spontaneous neuronal activity [CN] 202538169 U].
  • the TMS generates a magnetic field perpendicular to the plane of the coil by a momentary, high-voltage pulse generated by a magnetic coil placed on the scalp, passing through the scalp and skull almost without attenuation, reaching deep tissues of the brain and generating an induced current that causes the nerve cells to depolarize. And produce an evoked potential.
  • Modes of single-pulse, double-pulse, and repetitive transcranial magnetic stimulation are used to regulate the excitatory or inhibitory properties of nerve cells, thereby regulating the function of the cortex (see Chinese Patent CN 102462892 A and US Pat. No. 6,827,681 B2 and Kirton A, Chen R, Friefeld).
  • the Drug Delivery Pump achieves neuromodulation by direct administration of the pump device at a precise location (see US Pat. No. 6,609,030 B1). Since the drug acts directly on the part, the dosage is effectively reduced, and side effects are reduced. Long-term use of baclofen through the implanted pump sheath has become the basic method for the treatment of refractory spinal cord or sputum originating from the brain. Optogenetics are a powerful tool for exploring neural circuits (see Chinese Patent No. CN 102283145 A and US Pat. No. 20140142664 A1). The basic principle is that the opsin gene plus a specific promoter is introduced into a specific neuron group by viral transfection, and the physiological activity of the neuron is changed by light stimulation of different parameters, thereby realizing the regulation of the adjacent neural pathway.
  • Transcranial ultrasound neuromodulation is a new non-invasive brain stimulation technique in recent years. It stimulates or inhibits the central nervous system of the stimulation site through different intensities, frequencies, pulse repetition frequencies, pulse widths, and durations. Reversible change in regulation (see U.S. Patent No. US20130197401, US20110092800). Recently, the Arizona State University team demonstrated low-frequency, low-pressure ultrasound-induced neuromodulation through mouse brain horse-horse test, and also proposed a possible regulatory mechanism, that is, ultrasound affects voltage-gated sodium and calcium channels [Tyler WJ, Tufail Y, Finsterwald M, Tauchmann ML, Olson EJ, et al.
  • brain stimulation changes the activity of voltage-gated channels, depletion of neurotransmitters, which hinders the transmission of synaptic information, suppresses the output of nerve signals around the electrodes, and exerts a functional impairment effect on the stimulated nuclei; Stimulation acts on the axon terminal that is synaptic to the neurons surrounding the electrode, indirectly regulating the output of the neural signal, which in turn alters the pathological neural network function.
  • DBS is an invasive technique.
  • the device and surgery are expensive.
  • There are certain risks such as surgical complications, target tolerance, rejection, etc.
  • the life of the battery is 4-5 years. After the battery is exhausted, the battery must be replaced again.
  • Internal stimulators causing greater pain and financial burden to users, have largely limited the popularity of DBS.
  • the non-invasive tDCS and TMS technologies require higher operator and experimental conditions. The results are affected by factors such as the frequency of treatment, the location of stimulation, the duration of stimulation, the severity of the disease, and the drug treatment. The evaluation of efficacy is still controversial.
  • Transcranial ultrasound neuromodulation technology uses low-frequency and low-pressure ultrasound to achieve cranial nerve regulation, but the current ultrasound regulation device is simple, single-point regulation, and the mechanism of ultrasound neuromodulation is still unclear.
  • the invention provides an ultrasonic deep brain stimulation method and device, which can enter the deep brain region through the skull without non-invasiveness, and obtain an optimal ultrasound emission sequence required for transmitting transcranial focused ultrasound.
  • the present invention provides an ultrasonic deep brain stimulation method, and the ultrasonic deep brain stimulation method includes:
  • the three-dimensional digital model of the ultrasound transducer array, the structure, density and acoustic parameters of the skull and brain tissue, the structure, density and acoustic parameters of the ultrasound transducer array are first generated Ultrasound emission sequence;
  • the ultrasonic transducer array is controlled to emit ultrasonic waves according to the first ultrasonic emission sequence, and the ultrasonic nerve brain stimulation is performed on the brain nerve nuclei to be stimulated.
  • the ultrasonic deep brain stimulation method further comprises: selecting a position of one or more brain nerve nuclei to be stimulated, and in the head three-dimensional digital model, the brain to be stimulated The position of the nerve nuclei is located.
  • the three-dimensional digital model of the ultrasound transducer array, the structure, density, and acoustic parameters of the skull and brain tissue, the structure, density of the ultrasound transducer array, according to the three-dimensional digital model of the head And the acoustic parameters generate a first ultrasound transmission sequence, including:
  • simulating a voltage signal of the ultrasound transducer array includes:
  • the ultrasonic deep brain stimulation method further comprises: adjusting a virtual three-dimensional digital model of the head and a virtual space position of the three-dimensional digital model of the ultrasound transducer array according to an actual spatial position.
  • the ultrasonic deep brain stimulation method further comprises: estimating an acoustic parameter of the head according to the structure and density of the skull and brain tissue.
  • the ultrasonic deep brain stimulation method further includes:
  • the ultrasonic transducer array is controlled to emit ultrasonic waves according to the second ultrasonic transmission sequence, and the ultrasonic nerve brain stimulation is performed on the brain nerve nuclei to be stimulated.
  • the ultrasonic deep brain stimulation method further comprises: acquiring an acoustic field focus position and shape after the ultrasound craniotomy by using an imaging sequence of the magnetic resonance imaging system, according to the sound field focus position and shape and the head A three-dimensional digital model that adjusts the first ultrasound emission sequence or the second ultrasound emission sequence to change the position and shape of the ultrasound focus focus.
  • the ultrasound deep brain stimulation results are acquired using magnetic resonance functional imaging techniques, and the ultrasound focus position is fine tuned based on the ultrasound deep brain stimulation results.
  • the medical imaging of the animal or human head to generate image data includes: performing a three-dimensional magnetic resonance imaging scan and a three-dimensional CT imaging scan on the animal or human head to generate image data.
  • establishing a three-dimensional digital model of the head according to the image data comprises: performing three-dimensional reconstruction and registration of the image data to establish an animal or a human body including a skull, a brain tissue structure, a density, and an acoustic parameter.
  • the three-dimensional digital model of the head comprises: performing three-dimensional reconstruction and registration of the image data to establish an animal or a human body including a skull, a brain tissue structure, a density, and an acoustic parameter.
  • a virtual sound source is placed at one or more locations where focusing is desired, and the propagation state of the ultrasonic waves emitted by the virtual sound source in the three-dimensional digital model of the head is simulated, including: Placing a virtual sound source at one or more locations, and simulating the ultrasonic waves emitted by the virtual sound source in a three-dimensional digital model of the head using a linear wave equation, a nonlinear wave equation, a finite time difference method, or a k-space virtual spectrum method The state of propagation.
  • the shape of the ultrasound transducer array comprises: a flat plate, a spherical surface, and a curved surface, while the ultrasound transducer array is compatible with a magnetic resonance imaging system.
  • the imaging sequence is an imaging sequence that observes tissue displacement produced by the ultrasound sound field, or an imaging sequence that observes temperature changes produced by the ultrasound sound field.
  • the manner in which the ultrasonic nerve brain stimulation is performed on the brain nerve nuclei to be stimulated includes: a pulse mode, a multi-cycle mode, and a coding mode.
  • the present invention provides an ultrasonic deep brain stimulation method, and the ultrasonic deep brain stimulation method includes:
  • the ultrasonic transducer array is controlled to emit ultrasonic waves according to the ultrasonic emission sequence, and ultrasonic brain brain stimulation is performed on the brain nerve nuclei to be stimulated.
  • the ultrasonic deep brain stimulation method further comprises: selecting a position of one or more brain nerve nuclei to be stimulated, and in the head three-dimensional digital model, the brain to be stimulated The position of the nerve nuclei is located.
  • the three-dimensional digital model of the head is input into a 3D printer to generate an ultrasound transmission sequence, including:
  • the ultrasonic transducer array receives ultrasonic waves emitted by a sound source placed at a position to be focused, and generates a voltage signal according to the ultrasonic waves;
  • a time inversion of the voltage signal is performed to generate a time inversion signal as the ultrasound transmission sequence.
  • the ultrasound deep brain stimulation results are acquired using magnetic resonance functional imaging techniques, and the ultrasound focus position is fine tuned based on the ultrasound deep brain stimulation results.
  • the ultrasonic deep brain stimulation method further comprises: acquiring an acoustic field focus position and shape after the ultrasound craniotomy by using an imaging sequence of the magnetic resonance imaging system, according to the sound field focus position and shape and the head A three-dimensional digital model that adjusts the ultrasound emission sequence to change the position and shape of the ultrasound focus focus.
  • the ultrasound deep brain stimulation results are acquired using magnetic resonance functional imaging techniques, and the ultrasound focus position is fine tuned based on the ultrasound deep brain stimulation results.
  • the medical imaging of the animal or human head to generate image data includes: performing a three-dimensional magnetic resonance imaging scan and a three-dimensional CT imaging scan on the animal or human head to generate image data.
  • establishing a three-dimensional digital model of the head according to the image data comprises: performing three-dimensional reconstruction and registration of the image data to establish an animal or a human body including a skull, a brain tissue structure, a density, and an acoustic parameter.
  • the three-dimensional digital model of the head comprises: performing three-dimensional reconstruction and registration of the image data to establish an animal or a human body including a skull, a brain tissue structure, a density, and an acoustic parameter.
  • the shape of the ultrasound transducer array comprises: a flat plate, a spherical surface, and a curved surface, while the ultrasound transducer array is compatible with a magnetic resonance imaging system.
  • the manner in which the ultrasonic nerve brain stimulation is performed on the brain nerve nuclei to be stimulated includes: a pulse mode, a multi-cycle mode, and a coding mode.
  • the present invention provides an ultrasonic deep brain stimulation system, which comprises: medical imaging equipment, MRI system, ultrasonic transmission/reception control system, main control computer, MRI control system and power management a system; the master computer is connected to the medical imaging device, an ultrasound transmitting/receiving control system, and an MRI control system; the MRI system is connected to the MRI control system; the MRI system is internally provided with an ultrasound transducer array and a head a fixing and positioning device for fixing a head, the ultrasonic transducer array being disposed around the head fixing and positioning device, and connecting the ultrasonic transmitting/receiving control system ;
  • the medical imaging device is configured to capture a head image, and reconstruct a three-dimensional digital model of the head according to the head image;
  • the master computer establishes a three-dimensional digital model of the ultrasound transducer array according to the structure, density and acoustic parameter information of the ultrasound transducer array, and according to the three-dimensional digital model of the head and the ultrasound transducer array Generating a sequence of ultrasound emissions from the three-dimensional digital model, and then issuing an ultrasound deep brain stimulation command to the ultrasound transmit/receive control system;
  • the ultrasonic transmitting/receiving control system receives the ultrasonic deep brain stimulation instruction, and controls the ultrasonic transducer array to emit ultrasonic waves according to the ultrasonic emission sequence to a brain nucleus to be stimulated according to the ultrasonic deep brain stimulation instruction Implement ultrasound brain stimulation;
  • the MRI control system controls the MRI system to monitor the actual position and shape of the ultrasound focus point in real time, and adjust the ultrasound transmission sequence according to frequency, pulse duration, pulse length, pulse repetition frequency, and intensity.
  • the ultrasonic deep brain stimulation system further comprises: a 3D printer, a sink, and a sound source;
  • the 3D printer is configured to print a skull model according to the three-dimensional digital model of the head
  • the sink is placed in the skull model and the ultrasound transducer array
  • the sound source is placed in a position to be focused for emitting ultrasonic waves to the array of ultrasonic transducers placed in the water tank.
  • the shape of the ultrasound transducer array comprises: a flat plate, a spherical surface, and a curved surface.
  • Ultrasound deep brain stimulation systems and methods provide high spatial resolution (1 ⁇ 2mm), can enter the deep brain region through the skull without non-invasive.
  • Ultrasound time inversion method can be used to obtain the optimal ultrasound emission sequence required for transcranial focused ultrasound, and the actual position and shape of the ultrasound focus point can be monitored in real time by the magnetic resonance imaging system, and the transmission sequence (frequency, pulse) can be adjusted according to the time situation. Duration, pulse length, pulse repetition frequency, intensity, etc., to achieve targeted area regulation.
  • the spatial resolution for a given electromagnet TMS is fixed. For tDCS, only the position, type, current amplitude and duration of the stimulation of the electrode can be varied.
  • the use of different ultrasound emission sequences can be used to study the mechanism of ultrasound neuromodulation (acoustic radiation force, acoustic flow, shock wave, cavitation effect, etc.).
  • FIG. 1 is a flow chart of an ultrasonic deep brain stimulation method according to an embodiment of the present invention
  • FIG. 2 is a flowchart of a method for generating an ultrasound transmission sequence according to an embodiment of the present invention
  • FIG. 3 is a flowchart of a focus area elimination processing method according to an embodiment of the present invention.
  • FIG. 5 is a flowchart of a method for generating an ultrasound transmission sequence according to another embodiment of the present invention.
  • FIG. 6 is a schematic structural view of an ultrasonic deep brain stimulation system according to an embodiment of the present invention.
  • FIG. 7A and FIG. 7B are schematic diagrams showing simulation results of a method for realizing a desired ultrasound transmission sequence for cranial focusing according to an embodiment of the present invention.
  • the present invention provides an ultrasonic deep brain stimulation method, and the ultrasonic deep brain stimulation method includes:
  • S101 Perform medical imaging on an animal or a human head to generate image data
  • S103 Establish a three-dimensional digital model of the ultrasound transducer array according to the structure, density, and acoustic parameter information of the ultrasound transducer array;
  • S104 According to the three-dimensional digital model of the head, the three-dimensional digital model of the ultrasound transducer array, the structure, density and acoustic parameters of the skull and brain tissue, the structure, density and acoustic parameter generation of the ultrasound transducer array First ultrasonic emission sequence;
  • S105 Control the ultrasound transducer array to emit ultrasonic waves according to the first ultrasound transmission sequence, and perform ultrasonic brain stimulation on the brain nerve nuclei to be stimulated.
  • the present invention first establishes a three-dimensional digital model of the head and a three-dimensional digital model of the ultrasound transducer array, and obtains an ultrasound transmission sequence according to the three-dimensional digital model of the head and the three-dimensional digital model of the ultrasound transducer array.
  • ultrasound brain stimulation can be performed on the brain nucleus to be stimulated.
  • the deep brain region can be entered through the skull non-invasively, and the optimal ultrasound emission sequence required for transmitting the transcranial focused ultrasound can be obtained.
  • the three-dimensional magnetic resonance imaging scan and the three-dimensional CT imaging scan of the head or the animal that needs to perform ultrasonic deep brain stimulation can be performed by using the medical imaging device to obtain image data, and the obtained image data is three-dimensionally reconstructed. And registration, establish a three-dimensional digital model of the animal or human head including the skull, brain tissue structure, density and acoustic parameters, and then import the three-digit model of the head into the host computer.
  • any other medical imaging device capable of imaging the head may be imaged and the image is fused to the head three-dimensional digital model.
  • the method of the present invention is not limited thereto.
  • the ultrasonic deep brain stimulation method shown in FIG. 1 further includes: selecting a position of one or more brain nerve nuclei to be stimulated, and in the three-dimensional digital model of the head, the to-be-stimulated The location of the brain's nucleus is located. This step may be performed after S102 and before S105, and the present invention does not specifically limit the order relationship with S103 and S104.
  • the ultrasonic time reversal simulation software can be installed in the main control computer, and then the three-dimensional digital model of the ultrasonic transducer array obtained in S102 and S103, the structure, density and acoustic parameters of the skull and brain tissue, ultrasound The structure, density and acoustic parameters of the transducer array are input to an ultrasonic time inversion simulation software.
  • S201 Adjusting a virtual three-dimensional digital model of the head and a virtual space position of the three-dimensional digital model of the ultrasonic transducer array according to the actual spatial position, and the virtual space of the three-dimensional digital model of the head and the three-dimensional digital model of the ultrasonic transducer array The position is adjusted in place according to the actual spatial position desired.
  • S202 Place a virtual sound source at one or more locations that need to be focused, and simulate a propagation state of the ultrasonic waves emitted by the virtual sound source in the three-dimensional digital model of the head.
  • S203 Simulating a voltage signal of the ultrasonic transducer array when the ultrasonic wave propagates to a virtual space location where the ultrasound transducer array is located.
  • the sound intensity signal of the simulated ultrasonic wave on the surface of the ultrasonic transducer array is simulated when the ultrasonic wave propagates to the virtual space position where the ultrasonic transducer array is located (the virtual space position after the position is adjusted according to the actual spatial position desired)
  • the sound pressure signal according to the sound intensity signal and the sound pressure signal and the piezoelectric conversion parameter of the ultrasonic transducer array, the voltage signal of the ultrasonic transducer array is simulated, that is, the sound intensity signal and the sound pressure signal are simulated by the ultrasonic transducer. Piezoelectrically converted voltage signal.
  • S204 Perform time inversion on the voltage signal to generate a first time inversion signal as the first ultrasound transmission sequence.
  • the time reversal performed by the voltage signal is a time-inverted sequence, and the method may be referred to as a time inversion method.
  • the voltage signal is flipped in time series and then used to excite the ultrasound transducer array, and the generated ultrasound is focused at one or more locations in which the virtual sound source is placed in S202. Therefore, by the ultrasonic time inversion simulation software, the present invention can obtain an ultrasound emission sequence required to stimulate a designated brain nucleus, which can complete cranial focusing.
  • the head of an animal or a person who needs to perform ultrasonic deep brain stimulation is first fixed at a specified position in the magnetic resonance imaging system by using a head fixing and positioning device, and the ultrasonic transducer array is also in advance.
  • the designed location is fixed.
  • the ultrasound transducer array is controlled by the ultrasound transmitting/receiving control system by an instruction from the host computer to perform ultrasound transmission in accordance with the ultrasound transmission sequence.
  • the method for performing the ultrasonic brain stimulation of the brain nucleus to be stimulated includes: a pulse mode, a multi-cycle mode, and a coding mode, and the present invention is not limited thereto.
  • the focus area for these undesired stimuli can be eliminated by the following method:
  • S302 Perform phase inversion on the second time inversion signal to generate an inversion signal.
  • S304 Control the ultrasound transducer array to emit ultrasonic waves according to the second ultrasound transmission sequence, and perform ultrasonic brain stimulation on the brain nerve nuclei to be stimulated.
  • the accuracy, effectiveness, and safety of targeted neuromodulation can be further improved by the method illustrated in FIG.
  • the imaging sequence of the magnetic resonance imaging system may be utilized (special Imaging sequence) obtaining the position and shape of the sound field focus after the ultrasound is craniotomy, adjusting the first ultrasound emission sequence or the second ultrasound emission sequence according to the measured position and shape of the sound field focus, and adjusting the position of the ultrasound focus focus And shape to meet the requirements of ultrasound deep brain stimulation.
  • the imaging sequence can be an imaging sequence that observes the tissue displacement produced by the ultrasound sound field, or an imaging sequence that observes temperature changes produced by the ultrasound sound field.
  • the ultrasonic deep brain stimulation result (stimulus effect) can also be obtained by using magnetic resonance functional imaging technology, and the stimulation effect is observed and analyzed, and the ultrasonic focus position is finely adjusted.
  • magnetic resonance brain function imaging includes, but is not limited to, other methods such as electroencephalography and ultrasound brain function imaging.
  • the above ultrasonic time inversion software is used to simulate the algorithms used for ultrasonic propagation, including but not limited to linear wave equations, nonlinear wave equations, finite time difference methods, k-space virtual spectrum methods, and the like. That is, when S202 is specifically implemented, after the virtual sound source is placed at one or more positions that need to be focused, the virtual sound source can be simulated by using a linear wave equation, a nonlinear wave equation, a finite-time difference method, or a k-space virtual spectrum method. The propagation state of the emitted ultrasonic waves in the three-dimensional digital model of the head.
  • the shape of the ultrasound transducer array used in the ultrasonic deep brain stimulation method of the present invention may include a variety of shapes such as a flat plate, a spherical surface, and a curved surface, while the ultrasonic transducer array is compatible with the magnetic resonance imaging system.
  • an embodiment of the present invention provides an ultrasonic deep brain stimulation method, and the ultrasonic deep brain stimulation method includes:
  • S401 Perform medical imaging on an animal or a human head to generate image data
  • S403 input the three-dimensional digital model of the head into a 3D printer to generate an ultrasound transmission sequence.
  • S404 Control the ultrasound transducer array to emit ultrasonic waves according to the ultrasound transmission sequence, and perform ultrasonic brain stimulation on the brain nerve nuclei to be stimulated.
  • the present invention first establishes a three-dimensional digital model of the head, inputs a three-dimensional digital model of the head into a 3D printer, and generates an ultrasonic transmission sequence, by which the brain nerve nuclei to be stimulated can be implemented. Ultrasound brain stimulation. Through the above procedure, the optimal ultrasound emission sequence required for transmitting transcranial focused ultrasound can be obtained.
  • a three-dimensional magnetic resonance imaging scan and a three-dimensional CT imaging scan of the head of an animal or a person who needs ultrasonic deep brain stimulation may be performed by using a medical imaging device to obtain image data, and the obtained image data is reconstructed in three dimensions. And registration, establish a three-dimensional digital model of the animal or human head including the skull, brain tissue structure, density and acoustic parameters, and then import the three-digit model of the head into the host computer.
  • any other medical imaging device capable of imaging the head may be imaged and the image is fused to the head three-dimensional digital model.
  • the method of the present invention is not limited thereto.
  • the ultrasonic deep brain stimulation method shown in FIG. 4 further includes: selecting a position of one or more brain nerve nuclei to be stimulated, and in the head three-dimensional digital model, the to-be-stimulated The location of the brain's nucleus is located. This step may be performed after S102 and before S104, and the present invention does not specifically limit its sequential relationship with S103.
  • the present invention can obtain the structure and density of the skull and brain tissue, and then calculate the acoustic parameters of the head according to the structure and density of the skull and brain tissue, including but not limited to the speed of sound, attenuation coefficient.
  • S501 Input a 3D digital model of the head into a 3D printer to obtain a skull model.
  • the 3D digital model of the head needs to be input into the 3D printer, and the skull is reproduced according to the same size and structure using the 3D printed material with acoustic properties similar to the skull to obtain a skull model.
  • the ultrasonic transducer array receives ultrasonic waves emitted by a sound source placed at a position to be focused, and generates a voltage signal according to the ultrasonic waves.
  • the ultrasonic transducer array or the hydrophone is placed as a sound source at a position where the focus is required, and the ultrasonic wave emitted by the sound source is transmitted to the position of the ultrasonic transducer array, and is received by the ultrasonic transducer array. And after piezoelectric conversion, a series of voltage signals are obtained.
  • S504 Perform time inversion on the voltage signal to generate a time inversion signal as the ultrasound transmission sequence.
  • the voltage signal is collected by the ultrasonic transmitting/receiving control system, and the ultrasonic transmitting/receiving control system converts the voltage signal into a digital signal, and then performs time inversion to excite the ultrasonic transducer array to generate
  • the ultrasound will be focused at the location where the sound source is placed. Therefore, compared with the ultrasonic deep brain stimulation method shown in FIG. 1, the ultrasonic deep brain stimulation method shown in FIG. 4 can also obtain the ultrasound required to stimulate the designated brain nucleus and complete the cranial focusing.
  • the firing sequence is specifically implemented.
  • the time reversal performed by the above voltage signal is a time-inverted sequence, which may be referred to as a time inversion method.
  • the head of the animal or the person who needs to perform ultrasonic deep brain stimulation is first fixed at a specified position in the magnetic resonance imaging system by using the head fixing and positioning device, and the ultrasonic transducer array is also pre-arranged.
  • the designed location is fixed.
  • the ultrasound transducer array is controlled by the ultrasound transmitting/receiving control system by an instruction from the host computer to perform ultrasound transmission in accordance with the ultrasound transmission sequence.
  • the method for performing the ultrasonic brain stimulation of the brain nucleus to be stimulated includes: a pulse mode, a multi-cycle mode, and a coding mode, and the present invention is not limited thereto.
  • the ultrasonic deep brain stimulation result (stimulus effect) can also be obtained by using magnetic resonance functional imaging technology, and the stimulation effect is observed and analyzed, and the ultrasonic focus position is finely adjusted.
  • magnetic resonance brain function imaging includes, but is not limited to, other methods such as electroencephalography and ultrasound brain function imaging.
  • the imaging sequence (special imaging sequence) of the magnetic resonance imaging system can be used to obtain the ultrasonic transmission. Focus position and shape of the sound field behind the skull, according to the measured position and shape of the sound field, combined with the three-dimensional digital model of the head, adjust the ultrasound emission sequence, and change the position and shape of the focus of the ultrasound focus to meet the requirements of ultrasonic deep brain stimulation.
  • the imaging sequence can be an imaging sequence that observes the tissue displacement produced by the ultrasound sound field, or an imaging sequence that observes temperature changes produced by the ultrasound sound field.
  • the shape of the ultrasound transducer array used in the ultrasonic deep brain stimulation method shown in FIG. 4 may include a variety of shapes such as a flat plate, a spherical surface, and a curved surface, while the ultrasonic transducer array is compatible with the magnetic resonance imaging system.
  • an embodiment of the present invention provides an ultrasonic deep brain stimulation system, which includes: a medical imaging device 601, an MRI system 602, an ultrasound transmission/reception control system 603, and a main control computer 604.
  • the power management system 606 provides power to the medical imaging device 601, the MRI system 602, the ultrasound transmit/receive control system 603, the host computer 604, and the MRI control system 605.
  • the main control computer 604 is connected to the medical imaging device 601, the ultrasonic transmission/reception control system 603, and the MRI control system 605.
  • the MRI system 602 is coupled to the MRI control system 605.
  • the MRI system 602 is internally provided with an ultrasound transducer array 607, a head fixation and positioning device 608 for securing the head, and an ultrasound transducer array 607 disposed at the head fixation and positioning device 608. Surrounding, and connecting the ultrasonic transmission/reception control system 603.
  • the medical imaging device 601 is used to capture a head image of a person or an animal, and reconstruct a three-dimensional digital model of the head from the image of the head of the person or animal. Specifically, the medical imaging device 601 performs three-dimensional magnetic resonance imaging scanning and three-dimensional CT imaging scanning on the animal or the person who needs to perform ultrasonic deep brain stimulation, obtains image data, and performs three-dimensional reconstruction and registration on the obtained image data. A three-dimensional digital model of the animal or human head including the skull, brain tissue structure, density, and acoustic parameters is established, and the head three-digit model is then imported into the host computer 604.
  • the main control computer 604 can obtain the structure and density of the skull and brain tissue according to the three-dimensional digital model of the head, and then calculate the acoustic parameters of the head according to the structure and density of the skull and brain tissue, including but not limited to sound speed and attenuation. coefficient.
  • the host computer 604 can also establish a three-dimensional digital model of the ultrasound transducer array based on the structural shape and acoustic parameter information of the ultrasound transducer array.
  • the main control computer 604 is equipped with ultrasonic time inversion simulation software, which inputs the three-dimensional digital model of the ultrasonic transducer array, the structure, density and acoustic parameters of the skull and brain tissue, the structure, density and acoustic parameters of the ultrasonic transducer array.
  • ultrasonic time inversion simulation software To the ultrasonic time inversion simulation software, the ultrasonic emission sequence is obtained as follows:
  • the propagation state of the emitted ultrasonic waves in the three-dimensional digital model of the head simulating the sound intensity signal and the sound pressure signal of the ultrasonic wave on the surface of the ultrasonic transducer array when the ultrasonic wave propagates to the virtual space position where the ultrasonic transducer array is located,
  • the voltage signal of the ultrasonic transducer array is simulated based on the sound intensity signal and the sound pressure signal and the piezoelectric conversion parameters of the ultrasound transducer array.
  • Time-reversing the voltage signal to generate a first time inversion signal as an ultrasound transmission sequence The voltage signal is flipped in time sequence and then used to excite the ultrasound transducer array, and the resulting ultrasound is focused at one or more locations where the virtual sound source is placed.
  • the host computer 604 After obtaining the ultrasound transmission sequence, the host computer 604 issues an ultrasound deep brain stimulation command to the ultrasound transmission/reception control system 603.
  • the ultrasonic transmitting/receiving control system 603 receives the ultrasonic deep brain stimulation command, and controls the ultrasonic transducer array to perform ultrasonic brain stimulation according to the ultrasonic emission sequence to emit ultrasonic waves to the brain nucleus to be stimulated according to the ultrasonic deep brain stimulation instruction.
  • the MRI control system 605 controls the MRI system 602 to monitor the actual position and shape of the ultrasound focus point in real time, and the ultrasound emission sequence can be adjusted based on frequency, pulse duration, pulse length, pulse repetition frequency, and intensity.
  • the ultrasonic deep brain stimulation system shown in Figure 6 includes a 3D printer, a sink, and a sound source, not shown.
  • the 3D printer is configured to print a skull model according to the three-dimensional digital model of the head, the sink is placed in the position to be focused for placing the ultrasonic transducer in the sink due to the placement of the skull model and the ultrasound transducer array
  • the array emits ultrasonic waves.
  • the MRI system 602 employs a radio frequency coil 609 and a gradient coil 610.
  • RF subsystems RF coils
  • fast parallel imaging techniques based on multi-channel RF transmission and reception are required.
  • gradient subsystem gradient coil
  • the shape of the ultrasonic transducer array includes: a flat plate, a spherical surface, a curved surface, and the like, and the invention is not limited thereto.
  • the ultrasonic deep brain stimulation method shown in FIG. 1 and FIG. 4 can be used for the ultrasonic deep brain stimulation system, and the ultrasonic deep brain stimulation method shown in FIG. 1 does not require a 3D printer and a water tank, and the ultrasonic deep brain shown in FIG.
  • the stimulation method requires a 3D printer and a sink.
  • the invention provides a new safe and effective non-invasive ultrasonic deep brain stimulation method and system, which can realize fixed-point specific neural network regulation, multi-point network neural regulation and physical mechanism research of neuromodulation, and contribute to the development of central nervous system diseases.
  • Potential therapies also provide powerful new tools for exploring normal human brain function, understanding cognition, decision-making and thinking, and accurately mastering neural circuit activities. Therefore, ultrasonic deep brain stimulation methods and systems are expected to become important scientific instruments for neuroscience and brain disease research.
  • the ultrasonic deep brain stimulation system of the invention can be compatible with the MRI imaging system, and uses fMRI to monitor ultrasonic neuromodulation information (focus, structural function, Bold signal, etc.) in real time, and simultaneously realize fixed-point specific neural network regulation, multi-point network neural regulation, and further To achieve the regulation and regulation mechanism (acoustic radiation force, sound flow, shock wave, cavitation effect, etc.) of ultrasound neural regulation on neural circuits.
  • the ultrasonic deep brain stimulation method and system of the invention can realize the physical mechanism of ultrasonic neuromodulation: realize different neuromodulation functions by adjusting ultrasonic parameters (frequency, PRF, intensity, pulse duration, etc.) Degree of stimulation or inhibition of nerve excitability, through neural regulation to achieve the desired body or emotional response, to produce targeted therapeutic effects on different neurological diseases, etc.)
  • the ultrasonic deep brain stimulation method and system of the invention can realize individualized and specific neurological regulation: the same neurological disease may be different even in different patients, and a single neuromodulation measure cannot be fully applied, and the present invention integrates magnetic resonance , CT and other medical image information, establish a personalized three-dimensional digital model of the head to guide the neural control process (positioning and navigation, etc.), and use various functional medical imaging methods to observe, evaluate and adjust the control effect, so it can be achieved Individualized and specific neuromodulation of the patient.
  • the ultrasonic deep brain stimulation method and system of the invention can realize multi-point loop level regulation: the method of using the ultrasonic time inversion principle to obtain the ultrasound emission sequence for achieving cranial focusing, and the innovative method can realize multiple pairs on the neural circuit Simultaneous or sequential stimulation of key nodes, or simultaneous or sequential stimulation of a continuous area of the entire neural circuit.
  • the ultrasonic deep brain stimulation method and system of the invention can realize precise control of the nerve regulation stimulation range: since the time inversion method still forms a certain intensity sound field distribution in the undesired focus area, the above undesired stimulation area can be adopted by the above method First, placing the virtual sound source to obtain the time inversion signal, and then injecting the negative phase to invert the ultrasonic signal, and eliminating the sound field intensity in the region, can further improve the accuracy, effectiveness and safety of the targeted neural regulation. .
  • the ultrasonic deep brain stimulation system of the invention can realize the hardware scale far beyond the common ultrasonic imaging equipment, can realize the transmission and reception of 10,000 channels of ultrasonic signals, each channel is independently controlled, and the breakthrough is completed by using arbitrary waveform excitation excitation. Time reversal of ultrasound signals.
  • the invention is based on the characteristics of the ultrasonic focus positioning technology of magnetic resonance imaging, and the 1D imaging technique can avoid the macroscopic motion causing interference to the displacement monitoring; the motion sensitive gradient should be synchronized with the ultrasonic action, and the motion sensitive gradient can be added in any direction in the space; The accuracy of the graph is proportional to the image signal to noise ratio.
  • the invention adopts magnetic resonance image guiding and non-invasive temperature measuring technology to determine the precision of ultrasonic deep brain stimulation and regulation effect.
  • the present invention uses a fast parallel imaging technique based on multi-channel RF transmission and reception for a radio frequency subsystem (radio frequency coil).
  • radio frequency subsystem radio frequency coil
  • it is necessary to significantly increase the gradient strength and gradient rise rate relative to the clinical system, while having good stability and low noise.
  • the ultrasonic deep brain stimulation method and system of the present invention can provide a high spatial resolution (1 to 2 mm), and can enter the deep brain region through the skull without creation.
  • Ultrasound time inversion method can be used to obtain the optimal ultrasound emission sequence required for transcranial focused ultrasound, and real-time monitoring of ultrasound focus by magnetic resonance imaging system Actual position and shape, adjust the transmission sequence (frequency, pulse duration, pulse length, pulse repetition frequency, intensity, etc.) according to the time situation to achieve the regulation of the target area.
  • the present invention obtains a simulation experiment of a method for realizing the ultrasonic emission sequence required for craniotomy by using ultrasonic time inversion software in a two-dimensional plane.
  • the experimental results are shown in FIG. 7A and FIG. 7B.
  • the small dot at (0, 40) in FIG. 7A is the initial position of the virtual sound source, and FIG. 7B is the ultrasonic focusing effect realized by the time inversion method; It is a 1024 array linear array ultrasonic transducer array.
  • FIG. 7B is a skull model reconstructed from the CT scan image, and the acoustic parameters of the head are estimated according to the structure and density of the skull and brain tissue, and then imported into the simulation software to set the corresponding node of the two-dimensional plane.
  • the corresponding value From the simulation results, although the lateral and longitudinal dimensions of the ultrasound focus point are increased after the time-reversal emission, the energy is mostly concentrated in the expected position, which can satisfy the precise point stimulation and ensure other surrounding areas. A double request that is less affected. As long as the method is extended from a two-dimensional plane to a three-dimensional digital model, the needs of the present invention are met.
  • mice after anesthesia the top of the skull was depilated and fixed to the brain stereotaxic instrument.
  • the ultrasound transducer array is accurately positioned by the brain stereotaxic instrument and radiates pulsed ultrasound to the motor cortex proximate the skull. Ultrasound stimulation can simultaneously induce the limb's action response in mice.
  • embodiments of the present invention can be provided as a method, system, or computer program product. Accordingly, the present invention may take the form of an entirely hardware embodiment, an entirely software embodiment, or a combination of software and hardware. Moreover, the invention can take the form of a computer program product embodied on one or more computer-usable storage media (including but not limited to disk storage, CD-ROM, optical storage, etc.) including computer usable program code.
  • computer-usable storage media including but not limited to disk storage, CD-ROM, optical storage, etc.
  • the computer program instructions can also be stored in a computer readable memory that can direct a computer or other programmable data processing device to operate in a particular manner, such that the instructions stored in the computer readable memory produce an article of manufacture comprising the instruction device.
  • the apparatus implements the functions specified in one or more blocks of a flow or a flow and/or block diagram of the flowchart.
  • These computer program instructions can also be loaded onto a computer or other programmable data processing device such that a series of operational steps are performed on a computer or other programmable device to produce computer-implemented processing for execution on a computer or other programmable device.
  • the instructions provide steps for implementing the functions specified in one or more of the flow or in a block or blocks of a flow diagram.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Biomedical Technology (AREA)
  • Medical Informatics (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Molecular Biology (AREA)
  • Surgery (AREA)
  • Biophysics (AREA)
  • Radiology & Medical Imaging (AREA)
  • Psychiatry (AREA)
  • High Energy & Nuclear Physics (AREA)
  • Databases & Information Systems (AREA)
  • Physiology (AREA)
  • Computer Vision & Pattern Recognition (AREA)
  • Signal Processing (AREA)
  • Data Mining & Analysis (AREA)
  • Artificial Intelligence (AREA)
  • Epidemiology (AREA)
  • Primary Health Care (AREA)
  • Neurology (AREA)
  • Psychology (AREA)
  • Magnetic Resonance Imaging Apparatus (AREA)
  • Surgical Instruments (AREA)

Abstract

一种超声深部脑刺激方法及系统，所述的超声深部脑刺激方法包括：对动物或人的头部进行医学成像，生成图像数据；根据所述图像数据建立头部三维数字模型；根据超声换能器阵列（607）的结构、密度及声学参数信息建立超声换能器阵列（607）的三维数字模型；根据所述头部三维数字模型，所述超声换能器阵列（607）的三维数字模型，颅骨和脑组织的结构、密度及声学参数，所述超声换能器阵列（607）的结构、密度及声学参数生成第一超声发射序列；控制所述超声换能器阵列（607）按照所述第一超声发射序列发射超声波，对待刺激的脑部神经核团实施超声深脑刺激。通过所述方法及系统，超声可以无创穿过颅骨聚焦于深脑区域。利用不同的超声发射序列，可以实现超声神经调控，并可对其作用机制进行研究。

Description

一种超声深部脑刺激方法及系统 技术领域
本发明是关于超声脑刺激技术，特别是关于一种超声深部脑刺激方法及系统。
背景技术
随着社会老龄化和日渐加深的心理压力等因素的影响，世界范围内包括帕金森病、肌张力失常、强迫症、抑郁症、癫痫等神经精神疾病患者的数量急剧增加，目前全球患者已逾五亿六千万。德国的科学家报道了电刺激下犬的大脑皮层可引发特定的躯体反应。这一重大发现，在此后的一个世纪催生了大脑电刺激、磁刺激、神经植入等系列干预技术，极大促进了人们对脑皮层功能定位的认识和脑疾病研究仪器的研发，并开启了情感、记忆、认知等脑功能调控和心理、精神疾病干预治疗的新篇章。
神经系统是机体内起主导作用的系统。中枢神经系统介导情绪、注意、学习、记忆等高级功能的产生，参与感觉的产生以及随意运动的发起。神经元是神经系统发挥多种功能的功能单位，神经元之间通过突触形成网络，彼此联络，传递信息，形成感觉、运动等系统，每个系统又可分为若干子系统，如感觉中的视觉、嗅觉、听觉、味觉及体表触觉等，其功能的实施依赖于不同类型、处于神经系统不同部位细胞之间精准联系而形成的神经环路。神经环路是联系分子细胞功能与整体行为功能之间的桥梁，特定功能神经环路的研究有利于理解神经环路的形成与修饰，信息编码、加工与处理，以及其与行为间关系，从而可更深层次了解脑的工作原理。
神经调控是研究神经环路的一种有效手段，脑深部电刺激(Deep brain stimulation,DBS)，亦称“脑起搏器”，是一种神经系统疾病外科与电子技术相结合的新疗法，采用立体定向手术，将微电极植入患者的脑内靶点，通过可控的电刺激抑制靶点细胞的异常功能，达到有效干预疾病的目的(参见中国专利CN 102470247 A，CN 102762253 A4】)。该技术是目前唯一能够与大脑深部直接接触并干预大脑活动、治疗大脑疾病的技术手段，自1987年首次被用于震颤的控制以来，全世界共有超过10万名患者植入了DBS装置，为众多难治性的脑疾病如抑郁症、帕金森病、难治性癫痫、肌张力失调、顽 固性疼痛等提供了一种有效的新型干预方法【Halpem CH,Samadani U,Litt B,et a1.Deep brain stimulation for epilepsy.Neurotherapeutics,2008,5(1)：59-67.】。
经颅直流电刺激(transcranial direct current stimulatioin,tDCS)和经颅磁刺激(transcranial magnetic stimulation,TMS)等技术是无痛无创的检测和治疗技术。前者经由两个盐水浸湿的头皮贴附电极片向颅内特定区域输入恒定电流，改变大脑表面神经元膜电位的去极化或超极化方向，从而改变自发神经活动的皮质兴奋性【CN 202538169 U】。TMS由放置于头皮上的磁性线圈产生的瞬时、高伏脉冲产生一个垂直于线圈平面的磁场域，几乎无衰减地通过头皮和颅骨，到达大脑的深部组织并产生感应电流，使神经细胞去极化并产生诱发电位。通过单脉冲、双脉冲和重复经颅磁刺激等模式，调控神经细胞的兴奋或抑制特性，从而调节皮层的功能(参见中国专利CN 102462892 A及美国专利US 6827681 B2以及Kirton A,Chen R,Friefeld S,Gunraj C,Pontigon A-M,et al.(2008)Contralesional repetitive transcranial magnetic stimulation for chronic hemiparesis in subcortical paediatric stroke:a randomised trial.The Lancet Neurology 7:507-513.)。两种技术均用于评价神经电生理传导通路，以及抑郁症、癫痫、中风、精神分裂症、自闭症等疾病的神经康复治疗。
微量药物泵技术(Drug Delivery Pump)通过在精确位置植入泵装置直接给药的手段来实现神经调控(参见美国专利US 6609030 B1)。由于药物直接作用到局部，有效减少了用药剂量，减少了副作用。长期通过植入泵鞘内使用巴氯芬已经成为治疗难治性脊髓或者大脑起源的痉挛的基本方法。光感基因神经调控(Optogenetics)是探索神经环路的有力工具(参见中国专利CN 102283145 A及美国专利US 20140142664 A1)。其基本原理是将视蛋白基因加上特异启动子通过病毒转染导入特定的神经元类群，并通过不同参数的光刺激，来改变该神经元的生理活动，从而实现所属神经通路的调控。
经颅超声神经调控是近年来出现的无创性脑刺激新技术，通过不同的强度、频率、脉冲重复频率、脉冲宽度、持续时间使刺激部位的中枢神经产生刺激或抑制效应，对神经功能产生双向调节的可逆性变化(参见美国专利US20130197401，US20110092800)。最近，亚利桑那州立大学小组通过小鼠脑海马片实验证明了低频低压超声波诱发神经调控，而且也提出可能的调控机制，即超声波影响电压门控的钠离子和钙离子通道【Tyler WJ,Tufail Y,Finsterwald M,Tauchmann ML,Olson EJ,et al.(2008)Remote excitation of neuronal circuits using low-intensity,low-frequency ultrasound.PLoS One 3:e3511.】。后来，该小组首次通过活体动物实验证明了利用低频低压超声波实现 神经调控【Tufail Y,Matyushov A,Baldwin N,Tauchmann ML,Georges J,et al.(2010)Transcranial pulsed ultrasound stimulates intact brain circuits.Neuron 66:681-694.】。弗吉尼亚理工大学Carilion研究所的Legon Wynn等将低频低压超声波直接作用于脑部特定区域，能增强人们对触觉的分辨能力。这项发现第一次证明了低强度、经颅聚焦超声波能调节人类脑活动，提高觉察能力【Legon W,Sato TF,Opitz A,Mueller J,Barbour A,et al.(2014)Transcranial focused ultrasound modulates the activity of primary somatosensory cortexin humans.Nature neuroscience 17:322-329.】。
尽管上述脑刺激和神经调控技术的临床或科学实验效果已得到肯定，但其作用机制尚不清楚。目前认为脑刺激改变了电压门控通道的活性，神经递质耗竭，从而阻碍了突触信息的传递，阻抑了电极周围的神经信号输出，对所刺激的核团产生了功能性损毁效应；刺激作用于与电极周围神经元有突触联系的轴突终末，间接调节神经信号的输出，进而改变了病理性神经网络功能。
上述各种脑刺激装置仍存在多方面的局限性和技术挑战。例如，DBS是有创技术，装置和手术费用昂贵，存在一定的手术并发症、靶点耐受、排斥反应等风险，供电电池寿命为4-5年，电池耗尽后必须再次手术更换电池或者内部刺激器，给使用者造成更大的痛苦和经济负担，在很大程度上限制了DBS的普及。无创的tDCS和TMS技术外对操作者和实验条件要求较高，结果受治疗频率、刺激部位、刺激持续的时间、病情严重程度、药物治疗情况等因素影响，疗效评价尚有争议。光感基因神经调控存在局限性，如采用宽场刺激模式，虽可激活或抑制神经元，但它会把整个动物样品或整个神经环路激活，无法实现特定细胞或一群细胞选择性光刺激激活；如采用基于扫描镜、声光偏转器、发光二极管阵列、空间光调制器、液晶或微反射镜技术，虽可实现高时空分辨率的刺激激活细胞，但通常必须结合倒置或正置荧光显微镜上，只适用于培养细胞、脑切片的光刺激激活，存在光刺激范围小，不适合研究大的神经网络和调控活体动物的行为活动。这些限制了光感基因神经调控技术在神经环路研究中的应用。此外，上述装置与MRI的兼容性问题尚未妥善解决。
经颅超声神经调控技术利用低频低压超声波实现了脑神经调控作用，但目前的超声调控装置简单，单点调控，而且目前超声神经调控的机制还不明确。
发明内容
本发明提供一种超声深部脑刺激方法及装置，以无创穿过颅骨进入深脑区域，获得发射穿颅聚焦超声所需要的最优超声发射序列。
为了实现上述目的，本发明提供一种超声深部脑刺激方法，所述的超声深部脑刺激方法包括：
对动物或人的头部进行医学成像，生成图像数据；
根据所述图像数据建立头部三维数字模型；
根据超声换能器阵列的结构、密度及声学参数信息建立超声换能器阵列的三维数字模型；
根据所述头部三维数字模型，所述超声换能器阵列的三维数字模型，颅骨和脑组织的结构、密度及声学参数，所述超声换能器阵列的结构、密度及声学参数生成第一超声发射序列；
控制所述超声换能器阵列按照所述第一超声发射序列发射超声波，对待刺激的脑部神经核团实施超声神脑刺激。
在一实施例中，所述的超声深部脑刺激方法还包括：选择一个或多个待刺激的脑部神经核团的位置，并在所述头部三维数字模型对所述待刺激的脑部神经核团的位置进行定位。
在一实施例中，根据所述头部三维数字模型，所述超声换能器阵列的三维数字模型，颅骨和脑组织的结构、密度及声学参数，所述超声换能器阵列的结构、密度及声学参数生成第一超声发射序列，包括：
在需要聚焦的一个或多个位置放置虚拟声源，并仿真所述虚拟声源所发出的超声波在所述头部三维数字模型中的传播状态；
当所述超声波传播到所述超声换能器阵列所处的虚拟空间位置时，仿真所述超声换能器阵列的电压信号；
对所述电压信号进行时间反演，生成第一时间反演信号，作为所述第一超声发射序列。
在一实施例中，当所述超声波传播到所述超声换能器阵列所处的虚拟空间位置时，仿真所述超声换能器阵列的电压信号，包括：
仿真所述超声波在超声换能器阵列表面的声强信号和声压信号，根据所述声强信号和声压信号以及所述超声换能器阵列的压电转换参数仿真出所述超声换能器阵列的电压信号。
在一实施例中，所述的超声深部脑刺激方法还包括：根据实际空间位置对所述头部三维数字模型及所述超声换能器阵列的三维数字模型的虚拟空间位置进行调整。
在一实施例中，所述的超声深部脑刺激方法还包括：根据所述颅骨和脑组织的结构及密度推算头部的声学参数。
在一实施例中，所述的超声深部脑刺激方法还包括：
在无需刺激的聚焦区域放置所述虚拟声源，得到第二时间反演信号；
对所述第二时间反演信号进行相位反转，生成反转信号；
将所述反转信号与所述第以时间反演信号合并，作为第二超声发射序列；
控制所述超声换能器阵列按照所述第二超声发射序列发射超声波，对待刺激的脑部神经核团实施超声神脑刺激。
在一实施例中，所述的超声深部脑刺激方法还包括：利用磁共振成像系统的成像序列获取超声穿颅后的声场焦点位置和形状，根据所述声场焦点位置和形状及所述头部三维数字模型，调整所述第一超声发射序列或第二超声发射序列，改变超声聚焦焦点的位置和形状。
在一实施例中，利用磁共振功能成像技术获取超声深脑刺激结果，根据所述超声深脑刺激结果对超声聚焦位置进行微调。
在一实施例中，所述对动物或人的头部进行医学成像，生成图像数据，包括：对动物或人的头部进行三维磁共振成像扫描及三维CT成像扫描，生成图像数据。
在一实施例中，根据所述图像数据建立头部三维数字模型，包括：将所述图像数据进行三维重建和配准，建立动物或人的包括其颅骨和脑部组织结构、密度及声学参数的所述头部三维数字模型。
在一实施例中，在需要聚焦的一个或多个位置放置虚拟声源，并仿真所述虚拟声源所发出的超声波在所述头部三维数字模型中的传播状态，包括：在需要聚焦的一个或多个位置放置虚拟声源，并利用线性波动方程、非线性波动方程、有限时间差分法或k空间虚拟频谱法仿真所述虚拟声源所发出的超声波在所述头部三维数字模型中的传播状态。
在一实施例中，所述超声换能器阵列的形状包括：平板、球面及弧面，同时所述超声换能器阵列与磁共振成像系统兼容。
在一实施例中，所述成像序列为观察超声声场所产生的组织位移的成像序列，或观察超声声场所产生的温度变化的成像序列。
在一实施例中，对待刺激的脑部神经核团实施超声神脑刺激的方式包括：脉冲方式、多周期方式及编码方式。
为了实现上述目的，本发明提供了一种超声深部脑刺激方法，所述的超声深部脑刺激方法包括：
对动物或人的头部进行医学成像，生成图像数据；
根据所述图像数据建立头部三维数字模型；
将所述头部三维数字模型输入3D打印机，生成超声发射序列；
控制所述超声换能器阵列按照所述超声发射序列发射超声波，对待刺激的脑部神经核团实施超声神脑刺激。
在一实施例中，所述的超声深部脑刺激方法还包括：选择一个或多个待刺激的脑部神经核团的位置，并在所述头部三维数字模型对所述待刺激的脑部神经核团的位置进行定位。
在一实施例中，将所述头部三维数字模型输入3D打印机，生成超声发射序列，包括：
将头部三维数字模型输入3D打印机，获得颅骨模型；
将超声换能器阵列及所述颅骨模型放入一水槽中；
所述超声换能器阵列接收放置在需聚焦位置的声源发出的超声波，根据所述超声波生成电压信号；
对所述电压信号进行时间反演，生成时间反演信号，作为所述超声发射序列。
在一实施例中，利用磁共振功能成像技术获取超声深脑刺激结果，根据所述超声深脑刺激结果对超声聚焦位置进行微调。
在一实施例中，所述的超声深部脑刺激方法还包括：利用磁共振成像系统的成像序列获取超声穿颅后的声场焦点位置和形状，根据所述声场焦点位置和形状及所述头部三维数字模型，调整所述超声发射序列，改变超声聚焦焦点的位置和形状。
在一实施例中，利用磁共振功能成像技术获取超声深脑刺激结果，根据所述超声深脑刺激结果对超声聚焦位置进行微调。
在一实施例中，所述对动物或人的头部进行医学成像，生成图像数据，包括：对动物或人的头部进行三维磁共振成像扫描及三维CT成像扫描，生成图像数据。
在一实施例中，根据所述图像数据建立头部三维数字模型，包括：将所述图像数据进行三维重建和配准，建立动物或人的包括其颅骨和脑部组织结构、密度及声学参数的所述头部三维数字模型。
在一实施例中，所述超声换能器阵列的形状包括：平板、球面及弧面，同时所述超声换能器阵列与磁共振成像系统兼容。
在一实施例中，对待刺激的脑部神经核团实施超声神脑刺激的方式包括：脉冲方式、多周期方式及编码方式。
为了实现上述目的，本发明提供一种超声深部脑刺激系统，所述的超声深部脑刺激系统包括：医学影像设备、MRI系统、超声发射/接收控制系统、主控计算机、MRI控制系统及电源管理系统；所述的主控计算机连接所述的医学影像设备、超声发射/接收控制系统及MRI控制系统；MRI系统连接所述MRI控制系统；所述MRI系统内部设有超声换能器阵列、头部固定和定位装置，所述头部固定和定位装置用于固定头部，所述超声换能器阵列设置在所述头部固定和定位装置的周围，并连接所述超声发射/接收控制系统；
所述的医学影像设备用于拍摄头部图像，并根据所述头部图像重建出头部三维数字模型；
所述的主控计算机，根据超声换能器阵列的结构、密度及声学参数信息建立超声换能器阵列的三维数字模型，并根据所述头部三维数字模型及所述超声换能器阵列的三维数字模型生成超声发射序列，然后向所述超声发射/接收控制系统发出超声深脑刺激指令；
所述超声发射/接收控制系统接收所述超声深脑刺激指令，根据所述超声深脑刺激指令控制所述超声换能器阵列按照所述超声发射序列向待刺激的脑部神经核团发射超声波实施超声神脑刺激；
所述MRI控制系统控制所述MRI系统实时监测超声聚焦点的实际位置和形状，根据频率、脉冲持续时间、脉冲长度、脉冲重复频率及强度调整所述超声发射序列。
在一实施例中，所述的超声深部脑刺激还系统包括：3D打印机、水槽及声源；
所述3D打印机用于根据所述头部三维数字模型打印出颅骨模型；
所述水槽由于放置所述颅骨模型及超声换能器阵列；
所述声源放置在待聚焦位置，用于向放置于所述水槽中所述超声换能器阵列发出超声波。
在一实施例中，所述超声换能器阵列的形状包括：平板、球面及弧面。
超声深脑刺激的系统与方法提供较高的空间分辨率(1～2mm)，可以无创穿过颅骨进入深脑区域。利用超声时间反演方法可以获得发射穿颅聚焦超声所需要的最优超声发射序列，并通过磁共振成像系统实时监测超声聚焦点的实际位置和形状，根据时间情况来调整发射序列(频率、脉冲持续时间、脉冲长度、脉冲重复频率、强度等)，实现对靶向区域调控。而对于一个给定的电磁铁TMS的空间分辨率是固定的。对于tDCS，仅仅电极的位置、类型、电流振幅和刺激持续时间能够改变。另外，利用不同的超声发射序列可以实现超声神经调控作用机制(声辐射力、声流、shock wave、空化效应等)研究。
附图说明
为了更清楚地说明本发明实施例或现有技术中的技术方案，下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本发明的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动性的前提下，还可以根据这些附图获得其他的附图。
图1为本发明实施例的超声深部脑刺激方法流程图；
图2为本发明实施例的超声发射序列的生成方法流程图；
图3为本发明实施例的聚焦区域消除处理方法流程图；
图4为本发明另一实施例的超声深部脑刺激方法；
图5为本发明另一实施例的超声发射序列的生成方法流程图；
图6为本发明实施例的超声深部脑刺激系统结构示意图；
图7A及图7B为本发明实施例实现穿颅聚焦所需超声发射序列的方法的仿真实验结果示意图。
具体实施方式
下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
如图1所示，本发明提供一种超声深部脑刺激方法，所述的超声深部脑刺激方法包括：
S101：对动物或人的头部进行医学成像，生成图像数据；
S102：根据所述图像数据建立头部三维数字模型；
S103：根据超声换能器阵列的结构、密度及声学参数信息建立超声换能器阵列的三维数字模型；
S104：根据所述头部三维数字模型，所述超声换能器阵列的三维数字模型，颅骨和脑组织的结构、密度及声学参数，所述超声换能器阵列的结构、密度及声学参数生成第一超声发射序列；
S105：控制所述超声换能器阵列按照所述第一超声发射序列发射超声波，对待刺激的脑部神经核团实施超声神脑刺激。
由图1所示的流程可知，本发明首先建立头部三维数字模型及超声换能器阵列的三维数字模型，根据头部三维数字模型及超声换能器阵列的三维数字模型得到超声发射序列，利用该超声发射序列，可以对待刺激的脑部神经核团实施超声神脑刺激。通过上述流程，可以无创穿过颅骨进入深脑区域，获得发射穿颅聚焦超声所需要的最优超声发射序列。
S101及S102具体实施时，可以利用医学影像设备对需要进行超声深脑刺激的动物或人进行头部三维磁共振成像扫描和三维CT成像扫描，得到图像数据，并将获得的图像数据进行三维重建和配准，建立起动物或人的包括颅骨和脑部组织结构、密度及声学参数的头部三维数字模型，然后将该头部三位数字模型导入主控计算机。
在另一实施例中，除了头部三维磁共振成像扫描和三维CT成像扫描方法，也可以采用其他任何可对头部进行成像的医学影像设备进行成像，并将图像融合到头部三维数字模型中的方法，本发明不以此为限。
在一实施例中，图1所示的超声深部脑刺激方法还包括：选择一个或多个待刺激的脑部神经核团的位置，并在所述头部三维数字模型对所述待刺激的脑部神经核团的位置进行定位。该步骤只要在S102之后并在S105之前进行即可，本发明并不具体限定其与S103及S104的顺序关系。
在S104之前，需要根据S102得到的头部三维数字模型，得到颅骨和脑组织的结构及密度，然后根据颅骨和脑组织的结构及密度推算头部的声学参数，该声学参数包括但不限于声速、衰减系数。
S104具体实施之前，可以在主控计算机中安装超声时间反演仿真软件，然后将S102及S103中得到的超声换能器阵列的三维数字模型，颅骨和脑组织的结构、密度及声学参数，超声换能器阵列的结构、密度及声学参数输入到超声时间反演仿真软件。
如图2所示，S104具体实施时，包括如下步骤：
S201：根据实际空间位置对头部三维数字模型及所述超声换能器阵列的三维数字模型的虚拟空间位置进行调整，将头部三维数字模型及超声换能器阵列的三维数字模型的虚拟空间位置按照所希望采用的实际空间位置调整到位。
S202：在需要聚焦的一个或多个位置放置虚拟声源，并仿真所述虚拟声源所发出的超声波在所述头部三维数字模型中的传播状态。
S203：当所述超声波传播到所述超声换能器阵列所处的虚拟空间位置时，仿真所述超声换能器阵列的电压信号。具体地，当超声波传播到超声换能器阵列所处的虚拟空间位置(按照所希望采用的实际空间位置调整到位后的虚拟空间位置)时，仿真超声波在超声换能器阵列表面的声强信号和声压信号，根据声强信号和声压信号以及超声换能器阵列的压电转换参数仿真出超声换能器阵列的电压信号，即将声强信号和声压信号仿真出超声换能器经过压电转换后的电压信号。
S204：对所述电压信号进行时间反演，生成第一时间反演信号，作为所述第一超声发射序列。
具体地，该电压信号进行的时间反演为按时间前后顺序的翻转，该方法可以称为时间反演方法。该电压信号按时间前后顺序翻转后，再用来激励超声换能器阵列，所产生的超声波会在S202中放置虚拟声源的一个或多个位置聚焦。因此，通过该超声时间反演仿真软件，本发明可以得到刺激指定的脑部神经核团所需要的，能够完成穿颅聚焦的超声发射序列。
S105具体实施时，首先要将需要进行超声深脑刺激的动物或人的头部，利用头部固定和定位装置固定在磁共振成像系统中的指定位置，同时将超声换能器阵列也按照预先设计好的位置固定好。通过主控计算机发出指令，利用超声发射/接收控制系统控制超声换能器阵列，按照超声发射序列进行超声发射。
上述对待刺激的脑部神经核团实施超声神脑刺激的方式包括：脉冲方式、多周期方式及编码方式等，本发明不以此为限。
此外，由于上述的时间反演方法会在非期望聚焦区域形成一定强度的声场分布，对这些不希望刺激的聚焦区域，如图3所示，可以通过如下方法进行消除处理：
S301：在无需刺激的聚焦区域放置虚拟声源，得到第二时间反演信号；
S302：对所述第二时间反演信号进行相位反转，生成反转信号；
S303：将所述反转信号与所述第以时间反演信号合并，作为第二超声发射序列；
S304：控制所述超声换能器阵列按照所述第二超声发射序列发射超声波，对待刺激的脑部神经核团实施超声神脑刺激。
通过图3所示的方法，可以进一步提高靶向神经调控的准确性、有效性和安全性。
按照第一超声发射序列或第二超声发射序列进行超声发射时，可能会出现聚焦焦点的位置发生偏移和形状发生变化的情况，为了解决该问题，可以利用磁共振成像系统的成像序列(特殊成像序列)获取超声穿颅后的声场焦点位置和形状，根据实测的声场焦点位置和形状，结合头部三维数字模型，调整第一超声发射序列或第二超声发射序列，改变超声聚焦焦点的位置和形状，使其满足超声深脑刺激的要求。该成像序列可以为观察超声声场所产生的组织位移的成像序列，或观察超声声场所产生的温度变化的成像序列。
S105之后，还可以利用磁共振功能成像技术获取超声深脑刺激结果(刺激效果)，对该刺激效果进行观测及分析，对超声聚焦位置进行微调。除了对刺激效果进行观测和评估的方法，磁共振脑功能成像外，还包括但不限于脑电图、超声脑功能成像等其他方法。
上述的超声时间反演软件用来仿真超声波传播所使用的算法，包括但不限于线性波动方程、非线性波动方程、有限时间差分法、k空间虚拟频谱法等。即S202具体实施时，在需要聚焦的一个或多个位置放置虚拟声源之后，可以并利用线性波动方程、非线性波动方程、有限时间差分法或k空间虚拟频谱法仿真所述虚拟声源所发出的超声波在所述头部三维数字模型中的传播状态。
本发明的超声深部脑刺激方法中使用的超声换能器阵列的形状可以包括很多种，如：平板、球面及弧面等，同时超声换能器阵列与磁共振成像系统能够兼容。
如图4所示，本发明实施例提供一种超声深部脑刺激方法，所述的超声深部脑刺激方法包括：
S401：对动物或人的头部进行医学成像，生成图像数据；
S402：根据所述图像数据建立头部三维数字模型；
S403：将所述头部三维数字模型输入3D打印机，生成超声发射序列；
S404：控制所述超声换能器阵列按照所述超声发射序列发射超声波，对待刺激的脑部神经核团实施超声神脑刺激。
由图4所示的流程可知，本发明首先建立头部三维数字模型，将头部三维数字模型输入3D打印机，生成超声发射序列，利用该超声发射序列，可以对待刺激的脑部神经核团实施超声神脑刺激。通过上述流程，可以获得发射穿颅聚焦超声所需要的最优超声发射序列。
S401及S402具体实施时，可以利用医学影像设备对需要进行超声深脑刺激的动物或人进行头部三维磁共振成像扫描和三维CT成像扫描，得到图像数据，并将获得的图像数据进行三维重建和配准，建立起动物或人的包括颅骨和脑部组织结构、密度及声学参数的头部三维数字模型，然后将该头部三位数字模型导入主控计算机。
在另一实施例中，除了头部三维磁共振成像扫描和三维CT成像扫描方法，也可以采用其他任何可对头部进行成像的医学影像设备进行成像，并将图像融合到头部三维数字模型中的方法，本发明不以此为限。
在一实施例中，图4所示的超声深部脑刺激方法还包括：选择一个或多个待刺激的脑部神经核团的位置，并在所述头部三维数字模型对所述待刺激的脑部神经核团的位置进行定位。该步骤只要在S102之后并在S104之前进行即可，本发明并不具体限定其与S103的顺序关系。
利用S102得到的头部三维数字模型，本发明可以得到颅骨和脑组织的结构及密度，然后根据颅骨和脑组织的结构及密度推算头部的声学参数，该声学参数包括但不限于声速、衰减系数。
如图5所示，S403具体实施时，包括：
S501：将头部三维数字模型输入3D打印机，获得颅骨模型。
具体实施时，需要将头部三维数字模型输入3D打印机，利用声学属性与颅骨相似的3D打印材料，将颅骨按照同样的尺寸和结构复制出来，获得一个颅骨模型。
S502：将超声换能器阵列及所述颅骨模型放入一水槽中。
S503：所述超声换能器阵列接收放置在需聚焦位置的声源发出的超声波，根据所述超声波生成电压信号。
S503具体实施时，在需要聚焦的位置放置超声换能器阵列或水听器作为声源，声源所发出的超声波传播到超声换能器阵列所处位置时，被超声换能器阵列接收，并经过压电转换后得到一系列电压信号。
S504：对所述电压信号进行时间反演，生成时间反演信号，作为所述超声发射序列。
S504具体实施时，该电压信号被超声发射/接收控制系统采集，超声发射/接收控制系统将该电压信号转换为数字信号，再进行时间反演后，用来激励超声换能器阵列，所产生的超声波会在上述放置声源的位置聚焦。因此，与图1所示的超声深部脑刺激方法相比，通过图4所示的超声深部脑刺激方法，也可以得到刺激指定的脑部神经核团所需要的，能够完成穿颅聚焦的超声发射序列。
上述电压信号进行的时间反演为按时间前后顺序的翻转，该方法可以称为时间反演方法。
S404具体实施时，首先要将需要进行超声深脑刺激的动物或人的头部，利用头部固定和定位装置固定在磁共振成像系统中的指定位置，同时将超声换能器阵列也按照预先设计好的位置固定好。通过主控计算机发出指令，利用超声发射/接收控制系统控制超声换能器阵列，按照超声发射序列进行超声发射。
上述对待刺激的脑部神经核团实施超声神脑刺激的方式包括：脉冲方式、多周期方式及编码方式等，本发明不以此为限。
S404之后，还可以利用磁共振功能成像技术获取超声深脑刺激结果(刺激效果)，对该刺激效果进行观测及分析，对超声聚焦位置进行微调。除了对刺激效果进行观测和评估的方法，磁共振脑功能成像外，还包括但不限于脑电图、超声脑功能成像等其他方法。
按照S404的超声发射序列进行超声发射时，可能会出现聚焦焦点的位置发生偏移和形状发生变化的情况，为了解决该问题，可以利用磁共振成像系统的成像序列(特殊成像序列)获取超声穿颅后的声场焦点位置和形状，根据实测的声场焦点位置和形状，结合头部三维数字模型，调整超声发射序列，改变超声聚焦焦点的位置和形状，使其满足超声深脑刺激的要求。该成像序列可以为观察超声声场所产生的组织位移的成像序列，或观察超声声场所产生的温度变化的成像序列。
图4所示的超声深部脑刺激方法中使用的超声换能器阵列的形状可以包括很多种，如：平板、球面及弧面等，同时超声换能器阵列与磁共振成像系统能够兼容。
如图6所示，本发明实施例提供一种超声深部脑刺激系统，所述的超声深部脑刺激系统包括：医学影像设备601、MRI系统602、超声发射/接收控制系统603、主控计算机604、MRI控制系统605及电源管理系统606。
电源管理系统606为医学影像设备601、MRI系统602、超声发射/接收控制系统603、主控计算机604及MRI控制系统605供电。
主控计算机604连接医学影像设备601、超声发射/接收控制系统603及MRI控制系统605，MRI系统602连接MRI控制系统605。
MRI系统602内部设有超声换能器阵列607、头部固定和定位装置608，头部固定和定位装置608用于固定头部，超声换能器阵列607设置在头部固定和定位装置608的周围，并连接超声发射/接收控制系统603。
医学影像设备601用于拍摄人或动物的头部图像，并根据人或动物的头部图像重建出头部三维数字模型。具体地，利用医学影像设备601对需要进行超声深脑刺激的动物或人进行头部三维磁共振成像扫描和三维CT成像扫描，得到图像数据，并将获得的图像数据进行三维重建和配准，建立起动物或人的包括颅骨和脑部组织结构、密度及声学参数的头部三维数字模型，然后将该头部三位数字模型导入主控计算机604。
主控计算机604可以根据该头部三维数字模型，得到颅骨和脑组织的结构及密度，然后根据颅骨和脑组织的结构及密度推算头部的声学参数，该声学参数包括但不限于声速、衰减系数。
主控计算机604还可以根据超声换能器阵列的结构形状和声学参数信息，建立超声换能器阵列的三维数字模型。
主控计算机604中安装有超声时间反演仿真软件，将超声换能器阵列的三维数字模型，颅骨和脑组织的结构、密度及声学参数，超声换能器阵列的结构、密度及声学参数输入到超声时间反演仿真软件，得到超声发射序列具体如下：
根据实际空间位置对头部三维数字模型及所述超声换能器阵列的三维数字模型的虚拟空间位置进行调整，在需要聚焦的一个或多个位置放置虚拟声源，并仿真所述虚拟声源所发出的超声波在头部三维数字模型中的传播状态，当超声波传播到超声换能器阵列所处的虚拟空间位置时，仿真超声波在超声换能器阵列表面的声强信号和声压信号，根据声强信号和声压信号以及超声换能器阵列的压电转换参数仿真出超声换能器阵列的电压信号。对所述电压信号进行时间反演，生成第一时间反演信号，作为超声发射序列。该电压信号按时间前后顺序翻转后，再用来激励超声换能器阵列，所产生的超声波会在放置虚拟声源的一个或多个位置聚焦。
得到该超声发射序列之后，主控计算机604向超声发射/接收控制系统603发出超声深脑刺激指令。
超声发射/接收控制系统603接收该超声深脑刺激指令，根据该超声深脑刺激指令控制超声换能器阵列按照超声发射序列向待刺激的脑部神经核团发射超声波实施超声神脑刺激。
MRI控制系统605控制MRI系统602实时监测超声聚焦点的实际位置和形状，根据频率、脉冲持续时间、脉冲长度、脉冲重复频率及强度，可以调整超声发射序列。
在一实施例中，图6中所示的超声深部脑刺激还系统包括：3D打印机、水槽及声源，图中未示出。3D打印机用于根据所述头部三维数字模型打印出颅骨模型，水槽由于放置所述颅骨模型及超声换能器阵列，声源放置在待聚焦位置，用于向放置于水槽中超声换能器阵列发出超声波。
MRI系统602采用了射频线圈609及梯度线圈610。对于射频子系统(射频线圈)，需要用到基于多通道射频发射和接收的快速并行成像技术。对于梯度子系统(梯度线圈)，相对于临床系统需要显著提高其梯度强度、梯度上升率，同时具有良好的稳定性和较低的噪声。
在一实施例中，超声换能器阵列的形状包括：平板、球面及弧面等，本发明不以此为限。
图1及图4所示的超声深部脑刺激方法均可以用于该超声深部脑刺激系统，图1所示的超声深部脑刺激方法无需用到3D打印机及水槽，图4所示的超声深部脑刺激方法需要用到3D打印机及水槽。
本发明提出一种新的安全有效、非入侵超声深脑刺激方法及系统，可以实现定点特异性神经网络调控、多点网络神经调控以及神经调控的物理机制研究，有助于开发中枢神经疾病的潜在疗法，也为探索正常人脑功能，理解认知、决策与思维、精确掌握神经环路活动带来了强有力的新工具。因此，超声深脑刺激方法及系统有望成为神经科学和脑疾病研究的重要科学仪器。
本发明的超声深脑刺激系统可以与MRI成像系统兼容，利用fMRI实时监测超声神经调控信息(焦点、结构功能、Bold信号等)，同时实现定点特异性神经网络调控、多点网络神经调控，进一步实现超声神经调控对神经回路的调控作用及调控机制(声辐射力、声流、shock wave、空化效应等)研究。
本发明超声深脑刺激方法及系统可以实现超声神经调控物理机制研究：通过调整超声参数(频率、PRF、强度、脉冲持续时间等)实现不同的神经调控功能(实现不同程 度的刺激或抑制神经兴奋性，通过神经调控实现所期望的人体身体或情绪上的不同反应，对不同的神经性疾病产生针对性的治疗效果等).
本发明超声深脑刺激方法及系统可以实现个性化特异性神经调控：同一种神经性疾病即使在不同患者身上也会有所差别，单一的神经调控措施并不能全部适用，本发明通过整合磁共振、CT等医学影像信息，建立个性化的头部三维数字模型指导神经调控过程(定位和导航等)，并利用各种功能性医学影像方法对调控效果进行观测、评估和调节，因此可以实现对患者的个性化特异性神经调控。
本发明超声深脑刺激方法及系统可以实现多点环路水平调控：所使用的利用超声时间反演原理获得实现穿颅聚焦的超声发射序列的方法，创新性的可以实现对神经环路上多个关键节点的同时或先后刺激，或者对整个神经环路实现一片连续区域上的同时或先后刺激。
本发明的超声深脑刺激方法及系统可以实现精确控制神经调控刺激范围：由于时间反演方法依然会在非期望聚焦区域形成一定强度的声场分布，对这些不希望刺激的区域，可以通过上述方法，先放置虚拟声源以得到时间反演信号，再发射负相位的时间反演超声信号，对该区域的声场强度进行消除处理，可以进一步提高靶向神经调控的准确性、有效性和安全性。
本发明的超声深脑刺激系统可以实现拥有远远超过常见超声成像设备的硬件规模，可实现1万通道超声信号的发射和接收，每个通道独立控制，且突破性的采用任意波形激励发射完成对超声信号的时间反演。
本发明基于磁共振成像的超声焦点定位技术特点，使用1维成像技术，可以避免宏观运动对位移监测造成干扰；运动敏感梯度要与超声作用同步，运动敏感梯度可以加在空间中任意方向；位移图精度正比于图像信噪比。
本发明采用磁共振图像引导和无创温度测量技术，决定了超声深脑刺激与调控效果的精度。本发明对于射频子系统(射频线圈)，用到了基于多通道射频发射和接收的快速并行成像技术。对于梯度子系统(梯度线圈)，相对于临床系统需要显著提高其梯度强度、梯度上升率，同时具有良好的稳定性和较低的噪声。
综上所述，本发明的超声深脑刺激方法及系统，可以提供较高的空间分辨率(1～2mm)，可以无创穿过颅骨进入深脑区域。利用超声时间反演方法可以获得发射穿颅聚焦超声所需要的最优超声发射序列，并通过磁共振成像系统实时监测超声聚焦点的 实际位置和形状，根据时间情况来调整发射序列(频率、脉冲持续时间、脉冲长度、脉冲重复频率、强度等)，实现对靶向区域调控。
本发明在二维平面中利用超声时间反演软件获得了实现穿颅聚焦所需超声发射序列的方法的仿真实验。实验结果如图7A及图7B所示，图7A中(0，40)处的小圆点为虚拟声源的初始位置，图7B为利用时间反演方法仿真实现的超声聚焦效果；图上边框为1024阵元线阵超声换能器阵列。图7A及图7B中灰色部分为由CT扫描图像重建出的颅骨模型，并根据颅骨和脑组织的结构及密度推算头部的声学参数，然后导入仿真软件中设置为二维平面对应计算节点的相应数值。从仿真结果看，尽管经过时间反演发射后，超声聚焦点的横向和纵向尺寸都比原声源尺寸有所增加，但能量大部分依然集中在预计位置，可以满足精确定点刺激和保证周围其他区域受到较小影响的双重要求。只要将该方法从二维平面扩展到三维空间数字模型中，即可满足本发明的需要。
在超声刺激小鼠颅脑诱导动作响应的实验方面：麻醉后的小鼠，头颅顶部去毛，固定于脑立体定位仪。超声换能器阵列由脑立体定位仪精确定位，并贴近颅骨向运动皮层辐射脉冲超声。超声的刺激，能同步诱发小鼠产生肢体动作响应。
本领域内的技术人员应明白，本发明的实施例可提供为方法、系统、或计算机程序产品。因此，本发明可采用完全硬件实施例、完全软件实施例、或结合软件和硬件方面的实施例的形式。而且，本发明可采用在一个或多个其中包含有计算机可用程序代码的计算机可用存储介质(包括但不限于磁盘存储器、CD-ROM、光学存储器等)上实施的计算机程序产品的形式。
本发明是参照根据本发明实施例的方法、设备(系统)、和计算机程序产品的流程图和/或方框图来描述的。应理解可由计算机程序指令实现流程图和/或方框图中的每一流程和/或方框、以及流程图和/或方框图中的流程和/或方框的结合。可提供这些计算机程序指令到通用计算机、专用计算机、嵌入式处理机或其他可编程数据处理设备的处理器以产生一个机器，使得通过计算机或其他可编程数据处理设备的处理器执行的指令产生用于实现在流程图一个流程或多个流程和/或方框图一个方框或多个方框中指定的功能的装置。
这些计算机程序指令也可存储在能引导计算机或其他可编程数据处理设备以特定方式工作的计算机可读存储器中，使得存储在该计算机可读存储器中的指令产生包括指令装置的制造品，该指令装置实现在流程图一个流程或多个流程和/或方框图一个方框或多个方框中指定的功能。
这些计算机程序指令也可装载到计算机或其他可编程数据处理设备上，使得在计算机或其他可编程设备上执行一系列操作步骤以产生计算机实现的处理，从而在计算机或其他可编程设备上执行的指令提供用于实现在流程图一个流程或多个流程和/或方框图一个方框或多个方框中指定的功能的步骤。
本发明中应用了具体实施例对本发明的原理及实施方式进行了阐述，以上实施例的说明只是用于帮助理解本发明的方法及其核心思想；同时，对于本领域的一般技术人员，依据本发明的思想，在具体实施方式及应用范围上均会有改变之处，综上所述，本说明书内容不应理解为对本发明的限制。

Claims (28)

  1. 一种超声深部脑刺激方法，其特征在于，所述的超声深部脑刺激方法包括：
    对动物或人的头部进行医学成像，生成图像数据；
    根据所述图像数据建立头部三维数字模型；
    根据超声换能器阵列的结构、密度及声学参数信息建立超声换能器阵列的三维数字模型；
    根据所述头部三维数字模型，所述超声换能器阵列的三维数字模型，颅骨和脑组织的结构、密度及声学参数，所述超声换能器阵列的结构、密度及声学参数生成第一超声发射序列；
    控制所述超声换能器阵列按照所述第一超声发射序列发射超声波，对待刺激的脑部神经核团实施超声神脑刺激。
  2. 根据权利要求1所述的超声深部脑刺激方法，其特征在于，所述的超声深部脑刺激方法还包括：选择一个或多个待刺激的脑部神经核团的位置，并在所述头部三维数字模型对所述待刺激的脑部神经核团的位置进行定位。
  3. 根据权利要求1所述的超声深部脑刺激方法，其特征在于，根据所述头部三维数字模型，所述超声换能器阵列的三维数字模型，颅骨和脑组织的结构、密度及声学参数，所述超声换能器阵列的结构、密度及声学参数生成第一超声发射序列，包括：
    在需要聚焦的一个或多个位置放置虚拟声源，并仿真所述虚拟声源所发出的超声波在所述头部三维数字模型中的传播状态；
    当所述超声波传播到所述超声换能器阵列所处的虚拟空间位置时，仿真所述超声换能器阵列的电压信号；
    对所述电压信号进行时间反演，生成第一时间反演信号，作为所述第一超声发射序列。
  4. 根据权利要求3所述的超声深部脑刺激方法，其特征在于，当所述超声波传播到所述超声换能器阵列所处的虚拟空间位置时，仿真所述超声换能器阵列的电压信号，包括：
    仿真所述超声波在超声换能器阵列表面的声强信号和声压信号，根据所述声强信号和声压信号以及所述超声换能器阵列的压电转换参数仿真出所述超声换能器阵列的电压信号。
  5. 根据权利要求4所述的超声深部脑刺激方法，其特征在于，所述的超声深部脑刺激方法还包括：根据实际空间位置对所述头部三维数字模型及所述超声换能器阵列的三维数字模型的虚拟空间位置进行调整。
  6. 根据权利要求5所述的超声深部脑刺激方法，其特征在于，所述的超声深部脑刺激方法还包括：根据所述颅骨和脑组织的结构及密度推算头部的声学参数。
  7. 根据权利要求6所述的超声深部脑刺激方法，其特征在于，所述的超声深部脑刺激方法还包括：
    在无需刺激的聚焦区域放置所述虚拟声源，得到第二时间反演信号；
    对所述第二时间反演信号进行相位反转，生成反转信号；
    将所述反转信号与所述第以时间反演信号合并，作为第二超声发射序列；
    控制所述超声换能器阵列按照所述第二超声发射序列发射超声波，对待刺激的脑部神经核团实施超声神脑刺激。
  8. 根据权利要求7所述的超声深部脑刺激方法，其特征在于，所述的超声深部脑刺激方法还包括：利用磁共振成像系统的成像序列获取超声穿颅后的声场焦点位置和形状，根据所述声场焦点位置和形状及所述头部三维数字模型，调整所述第一超声发射序列或第二超声发射序列，改变超声聚焦焦点的位置和形状。
  9. 根据权利要求8所述的超声深部脑刺激方法，其特征在于，利用磁共振功能成像技术获取超声深脑刺激结果，根据所述超声深脑刺激结果对超声聚焦位置进行微调。
  10. 根据权利要求1-9中任一项所述的超声深部脑刺激方法，其特征在于，所述对动物或人的头部进行医学成像，生成图像数据，包括：对动物或人的头部进行三维磁共振成像扫描及三维CT成像扫描，生成图像数据。
  11. 根据权利要求10所述的超声深部脑刺激方法，其特征在于，根据所述图像数据建立头部三维数字模型，包括：将所述图像数据进行三维重建和配准，建立动物或人的包括其颅骨和脑部组织结构、密度及声学参数的所述头部三维数字模型。
  12. 根据权利要求1-9中任一项所述的超声深部脑刺激方法，其特征在于，在需要聚焦的一个或多个位置放置虚拟声源，并仿真所述虚拟声源所发出的超声波在所述头部三维数字模型中的传播状态，包括：在需要聚焦的一个或多个位置放置虚拟声源，并利用线性波动方程、非线性波动方程、有限时间差分法或k空间虚拟频谱法仿真所述虚拟声源所发出的超声波在所述头部三维数字模型中的传播状态。
  13. 根据权利要求1-9中任一项所述的超声深部脑刺激方法，其特征在于，所述超声换能器阵列的形状包括：平板、球面及弧面，同时所述超声换能器阵列与磁共振成像系统兼容。
  14. 根据权利要求8所述的超声深部脑刺激方法，其特征在于，所述成像序列为观察超声声场所产生的组织位移的成像序列，或观察超声声场所产生的温度变化的成像序列。
  15. 根据权利要求1-9中任一项所述的超声深部脑刺激方法，其特征在于，对待刺激的脑部神经核团实施超声神脑刺激的方式包括：脉冲方式、多周期方式及编码方式。
  16. 一种超声深部脑刺激方法，其特征在于，所述的超声深部脑刺激方法包括：
    对动物或人的头部进行医学成像，生成图像数据；
    根据所述图像数据建立头部三维数字模型；
    将所述头部三维数字模型输入3D打印机，生成超声发射序列；
    控制所述超声换能器阵列按照所述超声发射序列发射超声波，对待刺激的脑部神经核团实施超声神脑刺激。
  17. 根据权利要求16所述的超声深部脑刺激方法，其特征在于，所述的超声深部脑刺激方法还包括：选择一个或多个待刺激的脑部神经核团的位置，并在所述头部三维数字模型对所述待刺激的脑部神经核团的位置进行定位。
  18. 根据权利要求16所述的超声深部脑刺激方法，其特征在于，将所述头部三维数字模型输入3D打印机，生成超声发射序列，包括：
    将头部三维数字模型输入3D打印机，获得颅骨模型；
    将超声换能器阵列及所述颅骨模型放入一水槽中；
    所述超声换能器阵列接收放置在需聚焦位置的声源发出的超声波，根据所述超声波生成电压信号；
    对所述电压信号进行时间反演，生成时间反演信号，作为所述超声发射序列。
  19. 根据权利要求16所述的超声深部脑刺激方法，其特征在于，利用磁共振功能成像技术获取超声深脑刺激结果，根据所述超声深脑刺激结果对超声聚焦位置进行微调。
  20. 根据权利要求19所述的超声深部脑刺激方法，其特征在于，所述的超声深部脑刺激方法还包括：利用磁共振成像系统的成像序列获取超声穿颅后的声场焦点位置和形状，根据所述声场焦点位置和形状及所述头部三维数字模型，调整所述超声发射序列，改变超声聚焦焦点的位置和形状。
  21. 根据权利要求20所述的超声深部脑刺激方法，其特征在于，利用磁共振功能成像技术获取超声深脑刺激结果，根据所述超声深脑刺激结果对超声聚焦位置进行微调。
  22. 根据权利要求16-21中任一项所述的超声深部脑刺激方法，其特征在于，所述对动物或人的头部进行医学成像，生成图像数据，包括：对动物或人的头部进行三维磁共振成像扫描及三维CT成像扫描，生成图像数据。
  23. 根据权利要求22所述的超声深部脑刺激方法，其特征在于，根据所述图像数据建立头部三维数字模型，包括：将所述图像数据进行三维重建和配准，建立动物或人的包括其颅骨和脑部组织结构、密度及声学参数的所述头部三维数字模型。
  24. 根据权利要求16-21中任一项所述的超声深部脑刺激方法，其特征在于，所述超声换能器阵列的形状包括：平板、球面及弧面，同时所述超声换能器阵列与磁共振成像系统兼容。
  25. 根据权利要求16-21中任一项所述的超声深部脑刺激方法，其特征在于，对待刺激的脑部神经核团实施超声神脑刺激的方式包括：脉冲方式、多周期方式及编码方式。
  26. 一种超声深部脑刺激系统，其特征在于，所述的超声深部脑刺激系统包括：医学影像设备、MRI系统、超声发射/接收控制系统、主控计算机、MRI控制系统及电源管理系统；所述的主控计算机连接所述的医学影像设备、超声发射/接收控制系统及MRI控制系统；MRI系统连接所述MRI控制系统；所述MRI系统内部设有超声换能器阵列、头部固定和定位装置，所述头部固定和定位装置用于固定头部，所述超声换能器阵列设置在所述头部固定和定位装置的周围，并连接所述超声发射/接收控制系统；
    所述的医学影像设备用于拍摄头部图像，并根据所述头部图像重建出头部三维数字模型；
    所述的主控计算机，根据超声换能器阵列的结构、密度及声学参数信息建立超声换能器阵列的三维数字模型，并根据所述头部三维数字模型及所述超声换能器阵列的三维数字模型生成超声发射序列，然后向所述超声发射/接收控制系统发出超声深脑刺激指令；
    所述超声发射/接收控制系统接收所述超声深脑刺激指令，根据所述超声深脑刺激指令控制所述超声换能器阵列按照所述超声发射序列向待刺激的脑部神经核团发射超声波实施超声神脑刺激；
    所述MRI控制系统控制所述MRI系统实时监测超声聚焦点的实际位置和形状，根据频率、脉冲持续时间、脉冲长度、脉冲重复频率及强度调整所述超声发射序列。
  27. 根据权利要求26所述的超声深部脑刺激系统，其特征在于，所述的超声深部脑刺激还系统包括：3D打印机、水槽及声源；
    所述3D打印机用于根据所述头部三维数字模型打印出颅骨模型；
    所述水槽由于放置所述颅骨模型及超声换能器阵列；
    所述声源放置在待聚焦位置，用于向放置于所述水槽中所述超声换能器阵列发出超声波。
  28. 根据权利要求27所述的超声深部脑刺激系统，其特征在于，所述超声换能器阵列的形状包括：平板、球面及弧面，同时所述超声换能器阵列与磁共振成像系统兼容。
PCT/CN2015/078373 2014-12-26 2015-05-06 一种超声深部脑刺激方法及系统 WO2016101487A1 (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US15/630,623 US11253730B2 (en) 2014-12-26 2017-06-22 Ultrasound deep brain stimulation method and system

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201410829230.9 2014-12-26
CN201410829230.9A CN104548390B (zh) 2014-12-26 2014-12-26 一种获得用于发射穿颅聚焦超声的超声发射序列的方法及系统

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US15/630,623 Continuation US11253730B2 (en) 2014-12-26 2017-06-22 Ultrasound deep brain stimulation method and system

Publications (1)

Publication Number Publication Date
WO2016101487A1 true WO2016101487A1 (zh) 2016-06-30

Family

ID=53066129

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2015/078373 WO2016101487A1 (zh) 2014-12-26 2015-05-06 一种超声深部脑刺激方法及系统

Country Status (3)

Country Link
US (1) US11253730B2 (zh)
CN (1) CN104548390B (zh)
WO (1) WO2016101487A1 (zh)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110786853A (zh) * 2018-08-03 2020-02-14 中国科学院上海生命科学研究院 一种用于磁共振成像的小鼠头部固定装置及其固定方法
EP3607991A4 (en) * 2017-04-01 2021-01-13 Shenzhen Institutes of Advanced Technology SYSTEM AND METHOD FOR MANIPULATING PARTICLES BASED ON TIME REVERSE TECHNOLOGY

Families Citing this family (50)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104548390B (zh) * 2014-12-26 2018-03-23 中国科学院深圳先进技术研究院 一种获得用于发射穿颅聚焦超声的超声发射序列的方法及系统
CN104545919B (zh) * 2014-12-31 2017-05-10 中国科学院深圳先进技术研究院 一种超声穿颅聚焦的方法
CN104826243B (zh) * 2015-05-15 2018-02-27 深圳先进技术研究院 一种超声刺激神经组织的装置
CN104887185A (zh) * 2015-06-12 2015-09-09 冯明臣 脑部重症患者治疗装置
WO2017035767A1 (zh) * 2015-09-01 2017-03-09 中国科学院深圳先进技术研究院 声敏感离子通道遗传操作方法及系统
EP3363497B1 (en) 2015-10-15 2023-12-27 National Yang-Ming University Ultrasound stimulation helmet
CN105536156A (zh) * 2015-12-25 2016-05-04 中国科学院深圳先进技术研究院 一种基于大规模面阵元的超声脑刺激或调控方法及装置
JP6832958B2 (ja) * 2016-02-23 2021-02-24 サニーブルック リサーチ インスティテュート 診断的経頭蓋手順および治療的経頭蓋手順のための患者個体別ヘッドセット
CN105999569B (zh) * 2016-05-04 2019-03-12 中国科学院深圳先进技术研究院 一种多阵元换能器的阵元选择装置、方法和超声刺激系统
CN106039601A (zh) * 2016-05-31 2016-10-26 深圳先进技术研究院 磁兼容超声刺激系统
CN105944244B (zh) * 2016-05-31 2019-01-04 深圳先进技术研究院 超声刺激系统
GB2557915B (en) * 2016-12-16 2020-06-10 Calderon Agudo Oscar Method of and apparatus for non invasive medical imaging using waveform inversion
CN108245314A (zh) 2016-12-28 2018-07-06 中国科学院深圳先进技术研究院 用于进行听觉恢复治疗的超声波的生成装置
CN110997066B (zh) * 2017-06-21 2022-08-05 香港理工大学 用于超声脊髓刺激的设备和方法
US10987016B2 (en) * 2017-08-23 2021-04-27 The Boeing Company Visualization system for deep brain stimulation
CN109718481A (zh) * 2017-10-31 2019-05-07 深圳先进技术研究院 治疗成瘾性疾病的超声神经调控系统、方法及存储介质
FI127922B (en) 2017-11-14 2019-05-31 Altum Tech Oy Method for cleaning a device
CN108310687A (zh) * 2018-03-13 2018-07-24 重庆医科大学 一种聚焦超声声场的在线检测方法
CN108593766B (zh) * 2018-04-28 2020-12-25 中国人民解放军陆军军医大学第三附属医院（野战外科研究所） 一种低频脉冲超声激活神经元的成像装置及操作方法
CN108888266B (zh) * 2018-05-28 2021-05-14 中国医学科学院生物医学工程研究所 降低tms电磁脉冲对大鼠运动诱发电位影响的工频滤除方法
CN108744273B (zh) * 2018-05-29 2020-04-28 西安交通大学 一种针对神经环路的经颅无创深部脑双焦点刺激系统和方法
CN109011228B (zh) * 2018-09-06 2019-08-16 西安交通大学 一种高空间分辨率超声神经调控方法及系统
US20200085409A1 (en) * 2018-09-17 2020-03-19 Javier Grinfeld Ultrasound focusing utilizing a 3d-printed skull replica
DK180231B1 (en) * 2018-10-31 2020-08-28 Synaptic Aps Method of establishing a brain status indication parameter and system therefor
CN109200471B (zh) * 2018-11-07 2024-10-15 清华大学 Dbs手术定位头架及其制造方法
CA3122104A1 (en) * 2018-12-13 2020-06-18 Liminal Sciences, Inc. Systems and methods for a wearable device for treating a health condition using ultrasound stimulation
CN113613708A (zh) * 2019-01-23 2021-11-05 香港理工大学 可植入装置上使用一个或多个超声换能器的瞄准能量传输方法
CN109771855A (zh) * 2019-03-04 2019-05-21 武汉市中创悟空生命科技有限公司 基于多模成像的超声调控神经组织的装置及方法
US11998297B2 (en) 2019-03-25 2024-06-04 Creaholic S.A. Treatment parameters for acoustic wave stimulation
EP3946589A1 (en) 2019-03-25 2022-02-09 Creaholic S.A. Treatment devices for acoustic wave stimulation
CN109893784A (zh) * 2019-04-19 2019-06-18 深圳先进技术研究院 一种实现超声穿颅聚焦的方法以及电子设备
WO2020211076A1 (zh) * 2019-04-19 2020-10-22 深圳先进技术研究院 一种实现超声穿颅聚焦的方法以及电子设备
CN110160517B (zh) * 2019-05-22 2021-03-16 上海交通大学 一种超声换能器的实时导航方法及系统
CN110292359B (zh) * 2019-07-09 2021-01-08 浙江大学 一种无标记全光学神经调控与成像的方法与装置
WO2021012178A1 (zh) * 2019-07-23 2021-01-28 深圳先进技术研究院 一种神经调控装置及方法
CN110477917A (zh) * 2019-08-13 2019-11-22 深圳先进技术研究院 脑内淋巴管刺激系统、方法及控制装置
WO2021056342A1 (zh) * 2019-09-26 2021-04-01 深圳先进技术研究院 一种神经调控结果预测方法、装置及终端设备
WO2021097674A1 (zh) * 2019-11-19 2021-05-27 深圳先进技术研究院 一种血脑屏障通透性调控装置、方法及存储介质
CN111001099A (zh) * 2019-12-31 2020-04-14 深圳市神经科学研究院 超声刺激人类语言神经中枢的系统
CN111135484A (zh) * 2020-01-14 2020-05-12 中国人民解放军总医院 一种用于诊治脑病的磁共振引导聚焦超声能量预测方法
CN111494816A (zh) * 2020-02-28 2020-08-07 南北兄弟药业投资有限公司 一种超声精准自适应聚焦系统和方法
WO2021253236A1 (zh) * 2020-06-16 2021-12-23 中国科学院深圳先进技术研究院 超声聚焦控制方法、装置、电子设备及存储介质
CN111938628B (zh) * 2020-09-01 2024-01-23 天津大学 一种基于经颅聚焦超声刺激的脑电源信号检测装置
CN112568870B (zh) * 2020-12-10 2024-05-28 中国科学院深圳先进技术研究院 光声成像设备及驱动装置
WO2023039283A1 (en) 2021-09-13 2023-03-16 Rourk Christopher J Deep brain sensing and stimulation probe
CN116266484A (zh) * 2021-12-18 2023-06-20 中国科学院深圳先进技术研究院 全息超声跨颅与神经环路调控系统及其设计方法
US20240009486A1 (en) * 2022-07-06 2024-01-11 X Development Llc Quantitative method for target and dose tracking in response to transcranial neuro-modulation
US20240008847A1 (en) * 2022-07-06 2024-01-11 X Development Llc Ultrasound for neuro-imaging and neuro-modulation device in a single device
WO2024108566A1 (zh) * 2022-11-25 2024-05-30 中国科学院深圳先进技术研究院 一种超声换能器、在体转染系统及其应用
CN118079257A (zh) * 2022-11-25 2024-05-28 中国科学院深圳先进技术研究院 一种变频超声调控装置

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101663013A (zh) * 2007-05-02 2010-03-03 霜鸟良雄 脑神经系统疾病预防装置
US20110092800A1 (en) * 2002-04-30 2011-04-21 Seung-Schik Yoo Methods for modifying electrical currents in neuronal circuits
CN102149428A (zh) * 2008-07-14 2011-08-10 代理并代表亚利桑那州立大学的亚利桑那董事会 使用超声用于调节细胞活性的方法和装置
US20120283604A1 (en) * 2011-05-08 2012-11-08 Mishelevich David J Ultrasound neuromodulation treatment of movement disorders, including motor tremor, tourette's syndrome, and epilepsy
CN103028202A (zh) * 2012-12-26 2013-04-10 上海交通大学 经颅超声刺激修复脑神经功能的装置及方法
US20130197401A1 (en) * 2011-12-30 2013-08-01 Tomo Sato Optimization of ultrasound waveform characteristics for transcranial ultrasound neuromodulation
CN103432691A (zh) * 2013-08-13 2013-12-11 北京师范大学 一种经颅超声脑调控的方法与装置
CN104548390A (zh) * 2014-12-26 2015-04-29 中国科学院深圳先进技术研究院 一种超声深部脑刺激方法及系统

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5038787A (en) * 1988-08-10 1991-08-13 The Board Of Regents, The University Of Texas System Method and apparatus for analyzing material properties using reflected ultrasound
US6609030B1 (en) 2000-02-24 2003-08-19 Electrocore Techniques, Llc Method of treating psychiatric diseases by neuromodulation within the dorsomedial thalamus
EP1273320B1 (de) 2001-06-28 2005-04-27 BrainLAB AG Vorrichtung für transcraniale magnetische Stimulation
FR2843874B1 (fr) * 2002-08-28 2004-11-05 Centre Nat Rech Scient Procede non invasif pour obtenir un champ predetermine d'ondes acoustiques dans un milieu sensiblement homogene masque par une barriere osseuse, procede d'imagerie, et dispositif pour la mise en oeuvre de ces procedes
JP4630127B2 (ja) * 2005-05-17 2011-02-09 株式会社日立製作所 超音波診断治療装置
WO2009012290A1 (en) * 2007-07-16 2009-01-22 Indiana University Research And Technology Corporation Anatomically realistic three dimensional phantoms for imaging
BRPI1015422A2 (pt) 2009-07-30 2016-04-19 Sapiens Steering Brain Stimulation Bv sistema para estimulação cerebral profunda, métodos para determinar amplitudes, para aplicar uma distribuição espacial de amplitudes e produto de programa de computador.
EP2515762A4 (en) * 2009-12-22 2014-04-09 Univ Columbia PLANNING SYSTEM FOR TARGETING TISSUE STRUCTURES WITH ULTRASOUND
CN102762253A (zh) 2010-02-12 2012-10-31 沙皮恩斯脑部刺激控制有限公司 用于为深部脑刺激确定设置的方法和系统
CN102462892B (zh) 2010-11-09 2014-01-01 首都医科大学附属北京安定医院 头戴式位置可调经颅磁刺激器
CN102283145A (zh) 2011-06-08 2011-12-21 芜湖旺龙渔业有限责任公司 中华绒螯蟹强化培育和育肥技术
CN202538169U (zh) 2012-02-24 2012-11-21 江苏苏云医疗器材有限公司 一种经颅直流电刺激仪
WO2013152035A1 (en) * 2012-04-02 2013-10-10 Neurotrek, Inc. Device and methods for targeting of transcranial ultrasound neuromodulation by automated transcranial doppler imaging
CN104736068B (zh) * 2012-10-19 2018-02-23 皇家飞利浦有限公司 用于紧急医疗服务的超声波头部框架
WO2014081971A1 (en) 2012-11-21 2014-05-30 Roukes Michael L Highly multiplexed optogenetic neural stimulation using integrated optical technologies

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110092800A1 (en) * 2002-04-30 2011-04-21 Seung-Schik Yoo Methods for modifying electrical currents in neuronal circuits
CN101663013A (zh) * 2007-05-02 2010-03-03 霜鸟良雄 脑神经系统疾病预防装置
CN102149428A (zh) * 2008-07-14 2011-08-10 代理并代表亚利桑那州立大学的亚利桑那董事会 使用超声用于调节细胞活性的方法和装置
US20120283604A1 (en) * 2011-05-08 2012-11-08 Mishelevich David J Ultrasound neuromodulation treatment of movement disorders, including motor tremor, tourette's syndrome, and epilepsy
US20130197401A1 (en) * 2011-12-30 2013-08-01 Tomo Sato Optimization of ultrasound waveform characteristics for transcranial ultrasound neuromodulation
CN103028202A (zh) * 2012-12-26 2013-04-10 上海交通大学 经颅超声刺激修复脑神经功能的装置及方法
CN103432691A (zh) * 2013-08-13 2013-12-11 北京师范大学 一种经颅超声脑调控的方法与装置
CN104548390A (zh) * 2014-12-26 2015-04-29 中国科学院深圳先进技术研究院 一种超声深部脑刺激方法及系统

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3607991A4 (en) * 2017-04-01 2021-01-13 Shenzhen Institutes of Advanced Technology SYSTEM AND METHOD FOR MANIPULATING PARTICLES BASED ON TIME REVERSE TECHNOLOGY
CN110786853A (zh) * 2018-08-03 2020-02-14 中国科学院上海生命科学研究院 一种用于磁共振成像的小鼠头部固定装置及其固定方法
CN110786853B (zh) * 2018-08-03 2024-02-23 中国科学院脑科学与智能技术卓越创新中心 一种用于磁共振成像的小鼠头部固定装置及其固定方法

Also Published As

Publication number Publication date
US11253730B2 (en) 2022-02-22
CN104548390A (zh) 2015-04-29
US20170291044A1 (en) 2017-10-12
CN104548390B (zh) 2018-03-23

Similar Documents

Publication Publication Date Title
WO2016101487A1 (zh) 一种超声深部脑刺激方法及系统
Fomenko et al. Low-intensity ultrasound neuromodulation: an overview of mechanisms and emerging human applications
Bergmann et al. Inferring causality from noninvasive brain stimulation in cognitive neuroscience
Blackmore et al. Ultrasound neuromodulation: a review of results, mechanisms and safety
Fomenko et al. Systematic examination of low-intensity ultrasound parameters on human motor cortex excitability and behavior
Naor et al. Ultrasonic neuromodulation
King et al. Effective parameters for ultrasound-induced in vivo neurostimulation
Tufail et al. Ultrasonic neuromodulation by brain stimulation with transcranial ultrasound
AU2016293999A1 (en) Method and system for improving stimulation of excitable tissue
Cadoni et al. Ectopic expression of a mechanosensitive channel confers spatiotemporal resolution to ultrasound stimulations of neurons for visual restoration
Pouget et al. Neuronavigated repetitive transcranial ultrasound stimulation induces long-lasting and reversible effects on oculomotor performance in non-human primates
WO2017107230A1 (zh) 一种基于大规模面阵元的超声脑刺激或调控方法及装置
US11020617B2 (en) Methods and systems for peripheral nerve modulation using non ablative focused ultrasound with electromyography (EMG) monitoring
Bao et al. Personalized depth‐specific neuromodulation of the human primary motor cortex via ultrasound
US20200147415A1 (en) Methods and systems for selective modulation of motor neuronal activity in the peripheral nervous system
Yang et al. Transcranial ultrasound stimulation: a possible therapeutic approach to epilepsy
Yuan et al. Closed-loop transcranial ultrasound stimulation with a fuzzy controller for modulation of motor response and neural activity of mice
Cadoni et al. Sonogenetic stimulation of the brain at a spatiotemporal resolution suitable for vision restoration
Chen et al. Advances and challenges in transcranial magnetic stimulation (TMS) research on motor systems
Sanguinetti et al. 32 Human Brain Stimulation with Transcranial Ultrasound
CN116266484A (zh) 全息超声跨颅与神经环路调控系统及其设计方法
Wagner et al. Novel methods of transcranial stimulation: electrosonic stimulation
Hesselink et al. Investigating the impact of skull vibrations on motor responses to focused ultrasound neuromodulation in small rodents and methods to mitigate them
WO2017035767A1 (zh) 声敏感离子通道遗传操作方法及系统
Machado et al. Low Intensity Focused Ultrasound Modulation of Neural Circuits Activity

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 15871563

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

32PN Ep: public notification in the ep bulletin as address of the adressee cannot be established

Free format text: NOTING OF LOSS OF RIGHTS PURSUANT TO RULE 112(1) EPC (EPO FORM 1205 DATED 03.11.2017)

122 Ep: pct application non-entry in european phase

Ref document number: 15871563

Country of ref document: EP

Kind code of ref document: A1