WO2024058498A1 - Système ultrasonore focalisé non invasif de faible intensité pour stimulation cérébrale profonde - Google Patents

Système ultrasonore focalisé non invasif de faible intensité pour stimulation cérébrale profonde Download PDF

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Publication number
WO2024058498A1
WO2024058498A1 PCT/KR2023/013480 KR2023013480W WO2024058498A1 WO 2024058498 A1 WO2024058498 A1 WO 2024058498A1 KR 2023013480 W KR2023013480 W KR 2023013480W WO 2024058498 A1 WO2024058498 A1 WO 2024058498A1
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low
transducer
intensity
deep brain
brain stimulation
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PCT/KR2023/013480
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English (en)
Korean (ko)
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조남규
윤귀홍
오정훈
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주식회사 뉴로소나
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Publication of WO2024058498A1 publication Critical patent/WO2024058498A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • 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
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy

Definitions

  • the present invention relates to an ultrasound system, and more particularly, to a low-intensity non-invasive focused ultrasound system for deep brain stimulation.
  • Ultrasound is a sound wave with a frequency greater than the audible frequency (16 Hz to 20 kHz), and is widely used in existing clinical trials by being applied to ultrasonic medical imaging devices, high-intensity focused ultrasound surgery devices, and ultrasound tumor treatment devices.
  • DLPFC Dorsolateral Prefrontal Cortex
  • CC Cingulate Cortex
  • NAcc Nucleus Accumbens
  • TMS transcranial magnetic stimulation
  • TMS transcranial magnetic stimulation
  • the present invention was devised to solve the above problems, and the problem to be solved by the present invention is to provide a low-intensity non-invasive focused type for deep brain stimulation that can alleviate symptoms by stimulating the deep brain of patients with depression. It provides an ultrasonic system.
  • a pulse bundle 150 consisting of pulses 160 of a first frequency is generated by ultrasonic waves 120 with a low intensity of ISPPA (Intensity Spatial Peak Pulse Average) 50 W/cm 2 or less. and an ultrasonic generator 200 that forms and outputs a second frequency with a pulse bundle 150;
  • a transducer (110) connected to the ultrasonic generator and irradiating ultrasonic waves by contacting the head (130);
  • an image display means for displaying the simulation results based on the output signal of the transducer 110 by superimposing them on the MRI image 100 of the head 130.
  • the transducer 110 can be operated while viewing the simulation results.
  • a low-intensity non-invasive focused ultrasound device for deep brain stimulation is provided.
  • the low intensity is ISPPA 14 W/cm 2 or less.
  • the first frequency is 10 to 10,000 Hz
  • the second frequency is 1.4 to 10 Hz.
  • the ultrasonic waves are in the low frequency band of 240 to 260 kHz.
  • the output signals of the transducer 110 are the current and voltage signals of the transducer 110.
  • the transducer 110 forms a focus of 10 mm or less (preferably 3 to 7 mm) with 90% of the focused energy at a distance of 20 to 40 mm from the surface of the transducer 110.
  • the ultrasonic generator 200 operates in the range of 60 seconds to 3,600 seconds.
  • the object of the present invention as described above is another category, a method of stimulating the deep brain using the above-described ultrasonic device, wherein the ultrasonic generator 200 has a low intensity of ISPPA (Intensity Spatial Peak Pulse Average) 50 W/cm 2 or less. And generating a pulse bundle 150 consisting of pulses 160 of a first frequency using ultrasonic waves 120 in a low frequency band of 240 to 260 KHz, and forming and outputting a second frequency using the pulse bundle 150.
  • ISPPA Intensity Spatial Peak Pulse Average
  • the transducer 110 irradiates ultrasonic waves to the head 130, so that 90% of the focused energy forms a focus of 10 mm or less at a distance of 20 to 40 mm from the surface of the transducer 110;
  • the symptoms of depression patients who have not seen any effect from transcranial magnetic stimulation can be alleviated by stimulating the deep brain area with ultrasound.
  • TMS transcranial magnetic stimulation
  • the focused ultrasound according to the present invention safely stimulates the left dorsolateral prefrontal cortex (DLPFC) area of the cerebrum, which can serve as a scientific basis for its use in the treatment of major depressive disorder.
  • DLPFC dorsolateral prefrontal cortex
  • Figure 1 is an example of simulation results for a low-intensity non-invasive focused ultrasound system and MRI images for deep brain stimulation according to the present invention
  • Figure 2 is a waveform diagram of an ultrasonic system according to the present invention.
  • first and second are used to distinguish one component from another component, and the scope of rights should not be limited by these terms.
  • a first component may be named a second component, and similarly, the second component may also be named a first component.
  • first component may be named a second component, and similarly, the second component may also be named a first component.
  • second component When a component is referred to as being “connected” to another component, it should be understood that it may be directly connected to the other component, but that other components may also exist in between.
  • a component when a component is referred to as being “directly connected” to another component, it should be understood that there are no other components in between.
  • other expressions that describe the relationship between components such as "between” and “immediately between” or “neighboring” and “directly neighboring” should be interpreted similarly.
  • Figure 1 is an example of simulation results for a low-intensity non-invasive focused ultrasound system and MRI images for deep brain stimulation according to the present invention.
  • the ultrasonic generator 200 is connected to the transducer 110, and the transducer 110 radiates ultrasonic waves 120 to the head 130.
  • the image may be an MRI (Magnetic Resonance Imaging) image (100) or a CT (Computed Tomography) image.
  • a dedicated program (simulation program) on the computer simulates and displays the intensity of the ultrasonic waves 120 based on the voltage and current signals of the transducer 110.
  • the ultrasound 120 irradiated into the brain is indicated by the ultrasound range of the transducer 110.
  • the ultrasound 40 is displayed as a cone or rectangle, and the inside of the rectangle changes in gradation from red to blue depending on the intensity.
  • the length and direction of the cone-shaped ultrasonic wave 120 indicate the limit and direction of the ultrasonic wave 120, the red color inside can be the place where the ultrasonic intensity is the strongest, and the blue color can be the place where the ultrasonic intensity is the lowest. Accordingly, the therapist (operator) can operate the transducer 110 while viewing the simulation results (feedback effect).
  • the ultrasonic generator 200 generates focused ultrasonic waves.
  • the ultrasonic generator 200 can change an electrical waveform into a mechanical waveform using a piezoelectric material, and when the piezoelectric material is operated in a degassed medium (e.g., degassed water), an ultrasonic pressure shock waveform of 20 kHz or more is generated. It can be converted to .
  • This shock wave is generated from the piezoelectric material arranged in a hemispherical shape and is concentrated at a location corresponding to the radius of curvature (ROC) of the hemispherical circumference.
  • a degassed medium e.g., degassed water
  • the intensity of the ultrasound 120 uses a low intensity of 50 W/cm 2 or less, and according to the standards of the Food and Drug Administration (hereinafter referred to as the Food and Drug Administration), the ultrasound applies an effective intensity of less than 3 W/cm 2 and does not cause heat or cavity ( It can be used within the range where cavitation phenomenon does not occur.
  • the ultrasound stimulation to be used is a pressure sound wave type, and is provided at a frequency in the low-frequency band of 240 to 260 kHz (preferably 250 kHz), rather than the high-frequency ultrasound used in existing diagnostic ultrasound machines, so it can penetrate the skull and reach deep areas of the brain.
  • the focus can be positioned up to
  • the size (focus area) affected by the ultrasonic waves 120 is deep from the surface of the transducer 110, at a distance of 20 to 40 mm (preferably 30 mm), and 90% of the focused energy is at a focus of 10 mm or less (preferably Preferably 3 to 7 mm, more preferably 5 to 6 mm). Since this focal area is a sphere or oval-shaped cone (shaped like a grain of rice), detailed functional control of a specific area is possible. Additionally, it can be used within a range that does not exceed the Mechanical Safety Index of 1.9. Additionally, the core area can be selected in the range of 40 to 70 mm depending on the disease.
  • FIG. 2 is a waveform diagram of an ultrasonic system according to the present invention.
  • a pulse 160 is formed using an ultrasonic waveform of 250 kHz.
  • the frequency of pulse 160 is 10 to 10,000 Hz.
  • the single tone width (TBD) of the pulse 160 is 0.1 to 100 ms, and the duty cycle can be adjusted in the range of 1 to 100%.
  • the pulse bundle 150 is composed of regular pulses 160, and the frequency of the pulse bundle 150 is 1.4 to 10 Hz.
  • the width (SD) of the pulse bundle (sonic processing, 150) is set to 10 to 3,000 ms.
  • the period (SI) of the pulse bundle (sonic wave processing, 150) is set to 10 to 7,000 ms.
  • the total ultrasonic time (T/T) can be appropriately selected within the range of 60 seconds to 3,600 seconds. If it is less than 60 seconds, the effect of stimulation is minimal, and if it exceeds 3,600 seconds, excessive stimulation may cause excitement or side effects.
  • image data is generated by taking an MRI image 100 and a CT image of the human head 130.
  • patients with major depressive disorder who exhibit mild or more major depressive episodes without psychotic features are selected.
  • the DSM-5 major depressive disorder diagnostic criteria must meet at least 5 of the 9 items below and must include at least one of 1. and 2.
  • [Table 1] is a table showing the change in suicide ideation scale score (SSI) after 4 weeks compared to the baseline (mlTT).
  • the present invention relates to an ultrasound system, and more particularly, to a low-intensity non-invasive focused ultrasound system for deep brain stimulation.
  • T/T Total ultrasonic treatment time (Treatment Time)
  • PRP Pulse Repetition Period
  • PRF Pulse Repetition Frequency.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Physics & Mathematics (AREA)
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Abstract

La présente invention concerne un système ultrasonore et, plus particulièrement, un système ultrasonore focalisé non invasif de faible intensité destiné à une stimulation cérébrale profonde. À cet effet, est fourni un dispositif ultrasonore focalisé non invasif de faible intensité destiné à une stimulation cérébrale profonde, comprenant : un générateur d'ultrasons (200) de faible intensité ayant une intensité moyenne d'impulsion de crête spatiale (ISPPA) de 50 W/cm2 ou moins, qui génère, au moyen d'ondes ultrasonores (120), un faisceau d'impulsions (150) comprenant des impulsions (160) d'une première fréquence, forme des impulsions d'une seconde fréquence à partir du faisceau d'impulsions (150), et délivre celles-ci ; un transducteur (110), qui est connecté au générateur d'ultrasons et vient en contact avec une tête (130) pour émettre les ondes ultrasonores ; et un moyen d'affichage d'image destiné à afficher un résultat de simulation sur la base du signal de sortie provenant du transducteur (110) par superposition de celui-ci sur une image IRM (100) de la tête (130), et ainsi la présente invention permet de faire fonctionner le transducteur (110) tout en visualisant le résultat de la simulation.
PCT/KR2023/013480 2022-09-14 2023-09-08 Système ultrasonore focalisé non invasif de faible intensité pour stimulation cérébrale profonde WO2024058498A1 (fr)

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KR1020220115788A KR102549663B1 (ko) 2022-09-14 2022-09-14 뇌 심부 자극을 위한 저강도 비침습 집속형 초음파 시스템
KR10-2022-0115788 2022-09-14

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KR102549663B1 (ko) * 2022-09-14 2023-06-30 주식회사 뉴로소나 뇌 심부 자극을 위한 저강도 비침습 집속형 초음파 시스템

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KR20220009927A (ko) * 2020-07-16 2022-01-25 주식회사 딥슨바이오 초음파를 조사하여 동적 압력에 의한 부피유동을 유도함으로써, 뇌 림프계의 노폐물 배출 촉진을 위한 초음파장치
US20220062661A1 (en) * 2009-11-04 2022-03-03 Arizona Board Of Regents On Behalf Of Arizona State University Devices and methods for modulating brain activity
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KR101428547B1 (ko) 2013-05-13 2014-08-11 주식회사 웨이전스 우울증 치료, 스트레스 해소 및 집중력 향상을 위한 헤드 셋

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US20220062661A1 (en) * 2009-11-04 2022-03-03 Arizona Board Of Regents On Behalf Of Arizona State University Devices and methods for modulating brain activity
KR20190097165A (ko) * 2016-12-22 2019-08-20 서니브룩 리서치 인스티튜트 경두개 초음파 치료 및 영상화 절차 수행을 위한 시스템 및 방법
KR20190047251A (ko) * 2017-10-27 2019-05-08 (주)헬스허브 초음파 안내하의 뇌 치료용 플랫폼
KR20210033926A (ko) * 2019-09-19 2021-03-29 기초과학연구원 세타-버스트 초음파를 이용한 신경 가소성 조절 장치 및 조절방법
KR20220009927A (ko) * 2020-07-16 2022-01-25 주식회사 딥슨바이오 초음파를 조사하여 동적 압력에 의한 부피유동을 유도함으로써, 뇌 림프계의 노폐물 배출 촉진을 위한 초음파장치
KR102549663B1 (ko) * 2022-09-14 2023-06-30 주식회사 뉴로소나 뇌 심부 자극을 위한 저강도 비침습 집속형 초음파 시스템

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