Focused ultrasound processing system for opening and monitoring blood-brain barrier and ultrasound control method of focused ultrasound processing system for opening and monitoring blood-brain barrier

Abstract

A focused ultrasound processing system for opening and monitoring a blood-brain barrier according to an embodiment of the present invention may include: at least one piezoelectric element having a single structure; and a driving module for providing an electrical signal so as to cause ultrasound energy having at least one resonant frequency among a plurality of resonant frequencies to be output by the at least one piezoelectric element.

Description

Focused ultrasound processing system for opening and monitoring the blood-brain barrier and ultrasound control method of the focused ultrasound processing system for opening and monitoring the blood-brain barrier

[0001] The present invention relates to a focused ultrasound processing system for opening and monitoring the blood-brain barrier and an ultrasound control method of the focused ultrasound processing system for opening and monitoring the blood-brain barrier.

[0002] The present invention was supported by the Ministry of Health and Welfare's Drug Delivery Therapy Technology Development Project (Project Unique Number: 1465040354, Project Number: HI23C0344000023, Research Project Title: Development of Brain Drug Delivery Technology Using Externally Attached Ultrasound and Drug Carrier, Project Management Agency: Korea Health Industry Development Institute, Project Executing Agency: Newmus Co., Ltd., Research Period: 2023.04.01 ~ 2027.12.31, Contribution Rate: 50%) and the Ministry of SMEs and Startups' Startup Growth Technology Development (R&D) (Project Unique Number: 1425179650, Project Number: 00261874, Research Project Title: Development of Patient-tailored Blood-brain Barrier Control Multi-channel Focused Ultrasound Equipment, Project Management Agency: Small and Medium Business Technology Information Promotion Agency, Project Executing Agency: Newmus Co., Ltd., Research Period: 2023.06.01 ~ This is derived from research conducted as part of the "2026.05.31 (Contribution rate: 50%)" project. Meanwhile, the Korean government has no financial interest in any aspect of the present invention.

[0003] The blood-brain barrier (BBB) ​​is a physiological barrier that exists within the cerebral blood vessels to separate and protect the brain and central nervous system. This barrier separates the nerve cells within the brain from the blood.

[0004] Meanwhile, the inability of brain-disease therapeutics to sufficiently penetrate the brain due to the blood-brain barrier is a significant issue associated with many neurological and medical challenges. While the blood-brain barrier serves to protect and keep the brain safe by separating blood and brain tissue, it also hinders the effective delivery of therapeutics.

[0005] Recently, various technologies have been developed and studied to deliver brain disease treatments through the blood-brain barrier, but there are various limitations, such as limited or temporary effects, safety issues, and difficulties in precise targeting.

[0006] Therefore, there is a need for a technology that not only efficiently and safely controls the opening of the blood-brain barrier, but also monitors the entire process to overcome the aforementioned problems and effectively deliver brain disease treatments into the brain.

[0007] The technical problem to be solved by the present invention is to open the blood-brain barrier by outputting (or irradiating) ultrasonic energy having one resonance frequency among the resonance frequencies of a plurality of ultrasonic piezoelectric elements.

[0008] In addition, the technical problem to be solved by the present invention is to monitor in real time the degree of opening of the blood-brain barrier (or the location and behavior of the acoustic cavitation generating substance) and the location of focus of the ultrasonic energy (or the location in the brain where opening of the blood-brain barrier occurs) by receiving an acoustic cavitation signal from a target to which ultrasonic energy is output (or irradiated).

[0009] In addition, the technical problem to be solved by the present invention is to obtain an image of the skull of a subject by outputting ultrasonic energy having one of the resonance frequencies of a plurality of ultrasonic piezoelectric elements throughout the entire opening cycle of the blood-brain barrier.

[0010] A focused ultrasound processing system for opening and monitoring the blood-brain barrier according to one embodiment of the present invention may include at least one piezoelectric element having a single structure; and a driving module that provides an electric signal so that ultrasonic energy having one resonant frequency among a plurality of resonant frequencies or ultrasonic energy having at least two or more resonant frequencies is output by the at least one piezoelectric element.

[0011] Additionally, the at least one piezoelectric element according to one embodiment of the present invention may be configured such that the member interacting with the ultrasonic energy is made of a single or multiple materials.

[0012] Additionally, the at least one piezoelectric element according to one embodiment of the present invention can output the ultrasonic energy to the target object or the acoustic cavitation generating material administered to the target object.

[0013] Additionally, the at least one piezoelectric element according to one embodiment of the present invention can receive an acoustic cavitation signal reflected from the object or generated due to an acoustic cavitation phenomenon of the acoustic cavitation generating material.

[0014] Additionally, the plurality of resonant frequencies according to one embodiment of the present invention may include a first resonant frequency; and a second resonant frequency that is a lower frequency value than the first resonant frequency.

[0015] In addition, the focused ultrasound processing system for opening and monitoring the blood-brain barrier according to one embodiment of the present invention may further include a judgment module for analyzing the acoustic cavitation signal to generate an image of the object or to determine the location or behavior of the acoustic cavitation-generating substance.

[0016] In addition, the judgment module according to one embodiment of the present invention can generate the image by analyzing the acoustic cavity signal generated when the first ultrasonic energy having the first resonant frequency is reflected from the object.

[0017] In addition, the judgment module according to one embodiment of the present invention can generate the image by measuring TOF (Time Of Flight), which is a period between the time point at which the first ultrasonic energy is output by the at least one piezoelectric element and the time point at which the acoustic cavitation signal is detected.

[0018] Additionally, the at least one piezoelectric element according to one embodiment of the present invention can open the object by outputting second ultrasonic energy having the second resonant frequency.

[0019] Additionally, according to one embodiment of the present invention, the target object may be a blood-brain barrier, and the acoustic cavitation generating material may be a microbubble located near the target object.

[0020] In addition, the judgment module according to one embodiment of the present invention extracts a frequency component corresponding to a value of n / 2 of the second resonance frequency from the acoustic cavity signal to judge the behavior of the acoustic cavity generating material, and n may be a natural number other than 2.

[0021] In addition, the judgment module according to one embodiment of the present invention can determine the location of the acoustic cavitation-generating material by analyzing the acoustic cavitation signal generated by the second ultrasonic energy having the second resonance frequency.

[0022] In addition, each of the at least one piezoelectric elements according to one embodiment of the present invention,

[0023] At least two or more functions may be performed among a first function for generating an image of the object by outputting the ultrasonic energy; a second function for opening the object by outputting the ultrasonic energy; a third function for analyzing the acoustic cavitation signal to determine the behavior of the acoustic cavitation-generating substance; and a fourth function for simultaneously determining the location and behavior of the acoustic cavitation-generating substance by analyzing the acoustic cavitation signal.

[0024] In addition, in an ultrasound control method of a focused ultrasound processing system for opening and monitoring the blood-brain barrier, driven by at least one processor according to one embodiment of the present invention, the method may include: providing an electric signal so that ultrasound energy having at least one resonant frequency among a plurality of resonant frequencies is output by the at least one processor; and receiving the electric signal by the at least one processor and outputting the ultrasound energy having the resonant frequency to a subject and an acoustic cavitation-generating material administered to the subject.

[0025] In addition, the present invention may include a computer-readable recording medium having recorded thereon a program for executing an ultrasound control method of a focused ultrasound processing system for opening and monitoring the blood-brain barrier according to one embodiment of the present invention.

[0026] A focused ultrasound processing system for opening and monitoring the blood-brain barrier and a control method for the focused ultrasound processing system for opening and monitoring the blood-brain barrier according to one embodiment of the present invention can obtain an image of the skull by utilizing the resonance frequency of a high-frequency region of a single-structure piezoelectric element.

[0027] In addition, the focused ultrasound processing system for opening and monitoring the blood-brain barrier and the control method of the focused ultrasound processing system for opening and monitoring the blood-brain barrier according to one embodiment of the present invention can open the blood-brain barrier by utilizing the resonance frequency of the low-frequency region of a single-structure piezoelectric element.

[0028] In addition, the focused ultrasound processing system for opening and monitoring the blood-brain barrier and the control method for the focused ultrasound processing system for opening and monitoring the blood-brain barrier according to one embodiment of the present invention can determine and monitor the focused location of the ultrasound energy (or the location of the brain where the blood-brain barrier opening occurs) and the degree of opening of the blood-brain barrier (or the location and behavior of the acoustic cavitation-generating substance) by analyzing the acoustic cavitation signal generated by the ultrasound energy in real time.

[0029] FIG. 1 is a drawing of a focused ultrasound processing system for opening and monitoring the blood-brain barrier according to one embodiment of the present invention.

[0030] FIG. 2 is a diagram of the frequency domain of a single piezoelectric element according to one embodiment of the present invention.

[0031] FIG. 3 is an example of a process for obtaining an image of a skull by utilizing a resonant frequency in a high-frequency range according to one embodiment of the present invention.

[0032] FIG. 4 is another example of a process for obtaining an image of a skull by utilizing a resonant frequency in a high-frequency range according to one embodiment of the present invention.

[0033] FIG. 5 is a diagram of a piezoelectric element brain target position adjustment based on image bonding according to one embodiment of the present invention.

[0034] Figure 6 is a drawing of a process for monitoring the location and behavior of the cerebral blood barrier opening and acoustic cavitation generating material using the ultrasonic energy of Figure 2.

[0035] FIG. 7 is a flowchart of an ultrasound control method of a focused ultrasound processing system for opening and monitoring the blood-brain barrier according to one embodiment of the present invention.

[0036] Hereinafter, various embodiments of the present invention will be described in detail with reference to the attached drawings so that those skilled in the art can easily implement the invention. The present invention may be implemented in various different forms and is not limited to the embodiments described herein.

[0037] To clearly explain the present invention, irrelevant parts have been omitted, and the same reference numerals are used to designate identical or similar components throughout the specification. Accordingly, the reference numerals described above may also be used in other drawings.

[0038] Additionally, the sizes and thicknesses of each component shown in the drawings are arbitrarily shown for convenience of explanation, and thus the present invention is not necessarily limited to what is shown. In order to clearly express multiple layers and regions in the drawings, the thicknesses may be exaggerated.

[0039] Additionally, the expression "same" in the description may mean "substantially the same." That is, the degree of similarity may be such that a person of ordinary skill would be convinced that the two are identical. Other expressions may also omit the word "substantially."

[0040] In addition, when a part in the description is said to 'include' a certain component, this does not mean that other components are excluded, but rather that other components can be included, unless specifically stated otherwise. The '~ unit' used in this specification refers to a unit that processes at least one function or operation, and may mean, for example, software, an FPGA, or a hardware component. The function provided by the '~ unit' may be performed separately by multiple components, or may be integrated with other additional components. The '~ unit' in this specification is not necessarily limited to software or hardware, and may be configured to be located in an addressable storage medium, or may be configured to reproduce one or more processors. Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings.

[0041]

[0042] FIG. 1 is a drawing of a focused ultrasound processing system for opening and monitoring the blood-brain barrier according to one embodiment of the present invention.

[0043] A focused ultrasound processing system (1) for opening and monitoring the blood-brain barrier according to one embodiment of the present invention may include a focused ultrasound processing device (10), a driving module (20), and a judgment module (30).

[0044] However, it is obvious that the focused ultrasound processing system (1) for opening and monitoring the blood-brain barrier may be composed of fewer or more components than the components shown in Fig. 1.

[0045] For example, a focused ultrasound processing system (1) for opening and monitoring the blood-brain barrier may further include a power supply unit (not shown) for providing power, an output time control unit (not shown) for setting or controlling the output time of focused ultrasound energy, a matching circuit (resonant circuit, not shown) for setting the resonant frequency so that focused ultrasound energy having an arbitrary resonant (or, center) frequency set by a user is output, and a display unit (or, display device, not shown) for visually confirming the frequency analysis results.

[0046] Each of the above-mentioned focused ultrasonic processing device (10), driving module (20), and judgment module (30) may be configured with at least one processor or may be driven by the processor.

[0047] The focused ultrasound processing device (10) may be in the form of a helmet, but the present invention is not limited thereto. That is, the focused ultrasound processing device (10) may be manufactured in various forms that can surround the head (or skull) of the subject.

[0048] The focused ultrasound processing device (10) may be equipped with at least one piezoelectric element (11, see FIGS. 2A and 2B). At this time, at least one piezoelectric element (11) may be installed on the inner surface (or lower surface) of the focused ultrasound processing device (10) facing the head (or skull) of the subject.

[0049] At least one piezoelectric element (11) may be arranged on the lower surface of the focused ultrasonic processing device (1) at a predetermined interval from each other. At this time, the arrangement structure of the piezoelectric elements (11) may vary. For example, at least one piezoelectric element may be arranged radially with respect to the center of the focused ultrasonic processing device (1).

[0050] At least one piezoelectric element (11) may be configured as a single structure (see Fig. 2b). That is, the piezoelectric element (11) may be a single element formed of only one structure, rather than being configured by combining different separate elements.

[0051] The piezoelectric element (11) may be composed of quartz, a ceramic material (e.g., lead zironate titanate (or lead zironate titanate, PZT), a polymer material, etc.), but the present invention is not limited thereto.

[0052] The piezoelectric element (11) may be composed of at least one of the materials described above, which interacts with the ultrasonic energy (or focused ultrasonic energy) described below. For example, the piezoelectric element (11) may be composed of any one of the materials described above, or may be composed of a material in which at least two of the materials described above are mixed.

[0053] At least one piezoelectric element (11) can output ultrasonic energy to at least one of a target object and an acoustic cavitation generating material based on an electric signal provided from a driving module (20) described later.

[0054] Specifically, as described below, the acoustic cavitation generating material may be located in the vicinity of a target object (e.g., blood-brain barrier), so that ultrasonic energy output from at least one piezoelectric element (11) may reach not only the target object but also the acoustic cavitation generating material.

[0055] In addition, each of at least one piezoelectric element (11) can receive (or detect) an acoustic cavitation signal (hereinafter referred to as an acoustic signal) generated due to an acoustic cavitation phenomenon of the acoustic cavitation generating material.

[0056] Specifically, the subject may be pre-injected with an acoustic cavitation-generating agent (e.g., microbubbles). The microbubbles, which are acoustic cavitation-generating agents, may be positioned near the blood-brain barrier (BBB) ​​after being injected into the subject.

[0057] Each of the at least one piezoelectric element (11) can output ultrasonic energy toward a target of the subject (e.g., the blood-brain barrier) and at least one of the pre-injected microbubbles based on an electrical signal.

[0058] Microbubbles supplied with ultrasonic energy can generate acoustic signals due to acoustic cavitation, and at least one piezoelectric element (11) can each receive (or detect) the acoustic signals.

[0059] The driving module (20) can provide an electric signal so that ultrasonic energy having at least one resonant frequency among a plurality of resonant frequencies is output simultaneously or sequentially by at least one piezoelectric element (11).

[0060] At this time, the plurality of resonant frequencies may include a first resonant frequency (or a resonant frequency in a high-frequency range) and a second resonant frequency (or a resonant frequency in a low-frequency range) that is a lower frequency value than the first resonant frequency. At this time, the frequency values ​​of the first resonant frequency and the second resonant frequency may be variously set in advance by the user.

[0061] The drive module (20) can provide an electric signal to at least one piezoelectric element (11) so that the piezoelectric element (11) simultaneously or sequentially outputs ultrasonic energy having at least one resonant frequency among the first resonant frequency and the second resonant frequency according to a user's setting or preset conditions.

[0062] For example, the driving module (20) can provide an electric signal (hereinafter referred to as a first electric signal) to a predetermined arbitrary piezoelectric element (11), and the piezoelectric element (11) can output ultrasonic energy (hereinafter referred to as first ultrasonic energy) having a first resonant frequency based on the first electric signal to at least one of the target object and the acoustic cavitation generating material.

[0063] Alternatively, the driving module (20) can provide an electrical signal (hereinafter referred to as a second electrical signal) to any piezoelectric element (11), and the piezoelectric element (11) can output ultrasonic energy (hereinafter referred to as a second electrical signal) having a second resonant frequency based on the second electrical signal to at least one of the target object (or the blood-brain barrier) and the acoustic cavitation generating material.

[0064] Alternatively, the drive module (20) can provide an electric signal to any or a plurality of piezoelectric elements (11), and the piezoelectric elements (11) can simultaneously or sequentially output first ultrasonic energy having a first resonant frequency and ultrasonic energy having a second resonant frequency to at least one of the target object and the acoustic cavitation generating material based on the electric signal.

[0065] At this time, the subject (or blood-brain barrier) receiving the second ultrasound energy may be opened. Opening the blood-brain barrier allows the desired drug to enter the brain.

[0066] The judgment module (30) can analyze the acoustic signal to generate an image of the target object or determine the location of focus of the ultrasonic energy (or the location of the brain where the opening of the blood-brain barrier occurs, or the current location or behavior of the acoustic cavitation generating substance, or the degree of opening of the blood-brain barrier).

[0067] Specifically, the judgment module (30) can analyze an acoustic signal generated when first ultrasonic energy having a first resonant frequency is reflected from an object to generate an image (e.g., an image of the skull of the object).

[0068] At this time, the judgment module (30) can generate an image by measuring the TOF (Time Of Flight), which is the period between the time when the first ultrasonic energy is output by at least one piezoelectric element (11) and the time when it is reflected and returned and detected.

[0069] Alternatively, the judgment module (30) can analyze an acoustic signal generated when second ultrasonic energy having a second resonance frequency is reflected from the target object to determine the location of focus of the ultrasonic energy (or the location of the brain where the opening of the blood-brain barrier occurs, or the current location or behavior of the acoustic cavitation-generating substance, or the degree of opening of the blood-brain barrier).

[0070] Specifically, the judgment module (30) can judge the behavior of an acoustic cavitation-generating substance by extracting frequency components (i.e., sub-harmonics components, harmonics components, and ultra-harmonics components) corresponding to a value of n / 2 times the second resonance frequency (where n is a natural number other than 2) from an acoustic signal.

[0071] The behavior of acoustic cavitation-generating substances refers to the size, shape, and thickness of microbubbles that vibrate due to ultrasonic energy, and the degree of opening of the blood-brain barrier can be inferred (or determined) from the behavior of acoustic cavitation-generating substances.

[0072] Alternatively, the judgment module (30) can analyze (or Passive Acoustic Mapping (PAM)) multiple acoustic signals detected from multiple piezoelectric elements (11) to determine the location (or current location) of the acoustic cavitation generating material.

[0073] Meanwhile, each of the at least one piezoelectric element (11) described above can simultaneously or sequentially perform at least two or more functions among a first function for generating an image of an object by outputting ultrasonic energy, a second function for opening the blood-brain barrier by outputting ultrasonic energy, a third function for analyzing an acoustic signal to determine the behavior of an acoustic cavitation-generating substance, and a fourth function for simultaneously determining the location and behavior of an acoustic cavitation-generating substance by analyzing an acoustic signal.

[0074] For example, any piezoelectric element (11) can simultaneously or sequentially perform a first function of outputting ultrasonic energy to the skull of a subject to obtain an image of the skull and a third function of analyzing an acoustic signal received from an acoustic cavitation-generating substance to determine the behavior of the acoustic cavitation-generating substance.

[0075] Alternatively, any piezoelectric element (11) may simultaneously or sequentially perform a second function of outputting ultrasonic energy to the blood-brain barrier to open the blood-brain barrier and a fourth function of analyzing an acoustic signal received from the acoustic cavitation-generating substance to simultaneously determine the location and behavior of the acoustic cavitation-generating substance.

[0076]

[0077] FIG. 2 is a diagram of the frequency domain of a single piezoelectric element according to one embodiment of the present invention.

[0078] Fig. 2a is a view of the bottom surface of a focused ultrasonic processing device (10). Fig. 2b is a perspective view of a piezoelectric element. Fig. 2c is a graph of the frequency range utilized in at least one piezoelectric element (11) provided in a connected ultrasonic processing device (10).

[0079] Referring to Fig. 2a, a hole may be formed at the center of the focused ultrasonic processing device (10). At this time, at least one piezoelectric element (11) may be spaced apart from each other at a predetermined interval with the hole as the center and may be arranged radially.

[0080] As described above in Fig. 1, the piezoelectric element (11) may be composed of a single material or multiple materials (e.g., composite materials having different densities) that interact with ultrasonic energy.

[0081] Although the piezoelectric element (11) is illustrated in the form of a cylinder in FIG. 2b, the present invention is not limited thereto. That is, the piezoelectric element (11) may be formed into various three-dimensional shapes capable of interacting with ultrasonic energy.

[0082] Additionally, each of the plurality of piezoelectric elements (11) can perform at least two of the first to fourth functions described above in Fig. 1. This can be preset by the user.

[0083] The driving module (20) can provide a first electrical signal to a piezoelectric element (11) that is preset (or designated) to perform a first function. At this time, the piezoelectric element (11) can output first ultrasonic energy having a first resonant frequency (approximately 3000 kHz) among the frequency ranges shown in FIG. 2c to the target object.

[0084] Alternatively, the driving module (20) may provide a second electrical signal to a piezoelectric element (11) preset (or designated) to perform a second function. At this time, the piezoelectric element (11) may output second ultrasonic energy having a second resonant frequency (approximately 250 kHz) in the frequency range shown in FIG. 2b to at least one of the target object (or the blood-brain barrier) and the acoustic cavitation generating material.

[0085] Meanwhile, the piezoelectric element (11) set to perform the third function can receive an acoustic signal generated by an acoustic cavitation-generating substance and provide it to the judgment module (30). The judgment module (30) can analyze a frequency component (125 kHz, 375 kHz, ...) corresponding to a value of n / 2 times (i.e., f2*n / 2, n=1,3,5...) of the second resonant frequency (250 kHz, f2) in the acoustic signal and a frequency component (500 kHz, 750 kHz, ...) corresponding to a value of f2*n (n=2,3,4...) to determine the behavior of the acoustic cavitation-generating substance.

[0086] A plurality of piezoelectric elements (11) set to perform the fourth function can receive a plurality of acoustic signals generated by an acoustic cavitation-generating substance and provide them to a judgment module (30). The judgment module (30) can perform passive acoustic mapping based on the plurality of acoustic signals and simultaneously determine the location and behavior of the acoustic cavitation-generating substance.

[0087]

[0088] FIG. 3 is an example of a process for obtaining an image of a skull by utilizing a resonant frequency in a high-frequency range according to one embodiment of the present invention.

[0089] Referring to Fig. 3a, a focused ultrasound processing device (10) of the present invention may be mounted on the head of the subject. At this time, a medium that facilitates the transmission of focused ultrasound energy may be positioned between at least one piezoelectric element (11) and the head of the subject.

[0090] For example, the medium may be water, but the present invention is not limited thereto. That is, a material capable of minimizing the attenuation of ultrasonic energy may be used instead of water.

[0091] Referring to FIG. 1, FIG. 3a and FIG. 3b together, in order to obtain a skull image of a target object, the driving module (20) can provide a first electrical signal to at least one piezoelectric element (11) performing a first function.

[0092] The piezoelectric element (11) can output first ultrasonic energy (solid line in FIGS. 3a and 3b) having a first resonant frequency (about 3000 kHz) toward the skull of the target object based on the first electrical signal.

[0093] The first ultrasonic energy can be output from the piezoelectric element (11) and reach the surface of the skull of the subject, and can be reflected from the surface of the skull (Fig. 3a) and returned to the piezoelectric element (11).

[0094] At this time, the judgment module (30) can generate an image of the skull (or, B-mode (Brightness-mode) image, see FIG. 3c) by measuring the TOF, which is the period between the point in time when the first ultrasonic energy is output from the piezoelectric element (11) and the point in time when the first ultrasonic energy reflected from the surface of the skull is detected.

[0095] The judgment module (30) can generate an image of the skull through the above process, and the user can visually confirm the image through a display unit (or display device), etc.

[0096]

[0097] FIG. 4 is another example of a process for obtaining an image of a skull by utilizing a resonant frequency in a high-frequency range according to one embodiment of the present invention.

[0098] Referring to FIG. 4, unlike FIG. 3, a skull image of a subject can be obtained by moving the position of at least one piezoelectric element (11) provided in a focused ultrasound processing device (10).

[0099] Specifically, in cases where it is difficult to obtain an image of the entire skull of a subject using only at least one piezoelectric element (11) provided in the focused ultrasound processing device (10) due to limitations such as the area of ​​the focused ultrasound processing device (10), a segmented image of the skull can be obtained and then the images can be synthesized (or superimposed) to obtain an image of the entire skull.

[0100] For example, at least one piezoelectric element (11) installed at a first position of a focused ultrasound processing device (10) can output first ultrasonic energy having a first resonant frequency toward a first region of the skull (first output in FIG. 4).

[0101] The piezoelectric element (11) receives the first ultrasonic energy reflected and returned from the surface of the first region of the skull, and the judgment module (30) can generate an image of the first region of the skull using the TOF described above in FIG. 3.

[0102] At least one piezoelectric element (11) can be moved to a second position of the focused ultrasonic processing device (10) by a mobile device installed in the focused ultrasonic processing device (10) or by a user's operation.

[0103] At least one moved piezoelectric element (11) can output first ultrasonic energy having a first resonant frequency toward a second region of the skull (secondary output in FIG. 4).

[0104] The piezoelectric element (11) receives the first ultrasonic energy reflected and returned from the surface of the second region of the skull, and the judgment module (30) can generate an image of the second region of the skull using the TOF described above in FIG. 3.

[0105] At least one piezoelectric element (11) can be moved to a third position of the focused ultrasonic processing device (10) by a mobile device installed in the focused ultrasonic processing device (10) or by a user's operation.

[0106] At least one moved piezoelectric element (11) can output first ultrasonic energy having a first resonant frequency toward a third region of the skull (third output in FIG. 4).

[0107] The piezoelectric element (11) receives the first ultrasonic energy reflected and returned from the surface of the third region of the skull, and the judgment module (30) can generate an image of the third region of the skull using the TOF described above in FIG. 3.

[0108] The judgment module (30) can obtain an image of the entire overlapping skull by synthesizing the images of the first to third regions of the skull generated through the above-described process.

[0109] Meanwhile, although a two-dimensional image of the skull is illustrated in FIG. 4, the present invention is not limited thereto. That is, the shape of the skull may be three-dimensional, and it goes without saying that the judgment module (30) can generate a three-dimensional image of the entire skull through the above-described process.

[0110]

[0111] FIG. 5 is a diagram of a piezoelectric element brain target position adjustment based on image bonding according to one embodiment of the present invention.

[0112] An MRI image (or CT image) of the subject may be stored in a database (not shown). That is, an MRI image (or CT image) of the subject may be acquired on-site using an MRI device (or CT device, not shown), and the image may be stored in a database.

[0113] The judgment module (30) can move the focused ultrasound processing device (10) using the images of the skull part or the entire skull described above in FIGS. 3 and 4 and the MRI images (or CT images) pre-stored in the database, thereby adjusting the brain target location where the ultrasound energy is focused.

[0114] Specifically, the judgment module (30) can compare and analyze images of a part or the entire skull and pre-stored MRI images (or CT images) through an image stitching process.

[0115] For example, the judgment module (30) can obtain the current three-dimensional coordinate values ​​(X, Y, Z) of the focused ultrasound processing device (10) at which the skulls are maximally matched (or the point at which the error rate between images (or the image stitching error rate) is the lowest) through comparative analysis based on the image stitching process, and the coordinate values ​​(Xf, Yf, Zf) of the focused point of the ultrasound energy output from the focused ultrasound processing device (10) located at the corresponding three-dimensional coordinate values ​​(X, Y, Z).

[0116] A mobile device (e.g., a robotic arm) can adjust the position of the focused ultrasonic processing device (10) based on the current three-dimensional coordinate values ​​(X, Y, Z) of the acquired focused ultrasonic processing device (10) and move it to a position of new three-dimensional coordinate values ​​(X1, Y1, Z1).

[0117] The mobile device can consider the brain lesion target location coordinate values ​​(X1f, Y1f, Z1f) obtained from the MRI image (or CT image), and can adjust the location of the focused ultrasound processing device (10) from the current 3D coordinate values ​​(X, Y, Z) to new 3D coordinate values ​​(X1, Y1, Z1) so that the coordinate values ​​(Xf, Yf, Zf) of the current focused point of ultrasound energy are located at the brain lesion target location coordinate values ​​(X1f, Y1f, Z1f).

[0118] At this time, the sound field characteristic prior data of the focused ultrasonic processing device (10) can be used. Specifically, the sound field characteristic prior data means data on different focusing characteristics of the ultrasonic energy output according to the position of the focused ultrasonic processing device (10) based on the skull of the target object (e.g., installation position, installation angle, etc.), such as the position of the focus point where the ultrasonic energy output from at least one piezoelectric element (11) included in the focused ultrasonic processing device (10) is fused and focused, the width of the focus point, the length of the focus point, etc.

[0119] The sound field characteristic prior data for each position of the focused ultrasound processing device (10) based on the skull of the target object may be stored in advance in a database, and a mobile device (e.g., a robotic arm) may use the sound field characteristic prior data to move the focused ultrasound processing device (10) or adjust the position of at least one piezoelectric element (11) so that the ultrasonic energy can be effectively focused on the target focused position (X1f, Y1f, Z1f).

[0120] Specifically, the mobile device can move the focused ultrasound processing device (10) or adjust the position of at least one piezoelectric element (11) (e.g., forward or backward placement of the piezoelectric element (11)) by utilizing the sound field characteristic pre-data together so that the ultrasound energy can be focused on the target focus position (or target focus point) determined through clinical analysis (or MRI image).

[0121] The process of moving the focused ultrasonic processing device (10) or adjusting the position of at least one piezoelectric element (11) may include the process of moving or rotating at least one piezoelectric element (11) by the moving device.

[0122] Alternatively, the process may include increasing or decreasing the distance of the focused ultrasound treatment device (10) relative to the surface of the skull by the moving equipment.

[0123] Alternatively, the process may include moving at least one piezoelectric element (11) included in the focused ultrasound processing device (10) by the moving device so that the at least one piezoelectric element (11) moves closer to or further away from the surface of the skull.

[0124] Through the above-described process, ultrasonic energy can be focused on a brain lesion target, and the judgment module (30) can obtain new three-dimensional coordinate values ​​(X1, Y1, Z1) and three-dimensional target focus point (or brain lesion target point (X1f, Y1f, Z1f)) of the adjusted focused ultrasound processing device (10) through the above-described process.

[0125]

[0126] Figure 6 is a drawing of a process for monitoring the location and behavior of acoustic cavitation-generating substances and opening of the blood-brain barrier using ultrasonic energy of Figure 2.

[0127] Referring to FIG. 2 and FIG. 6A together, at least one piezoelectric element (11) performing a first function based on a first electrical signal provided from a driving module (20) can output a pulse (A) of ultrasonic energy of a first resonant frequency (3000 kHz) in a high frequency range.

[0128] At least one piezoelectric element (11) can detect a pulse (B) of ultrasonic energy reflected from the skull of the subject and returned. At this time, the time interval between the point in time when the pulse (A) is output from the at least one piezoelectric element (11) and the point in time when the pulse (B) is detected by the piezoelectric element (11) may be several milliseconds.

[0129] The judgment module (30) can generate an image of the skull by measuring the TOF, which is the time interval (several ms) between the point in time when the pulse (A) is output from at least one piezoelectric element (11) and the point in time when the pulse (B) is detected by the piezoelectric element (11).

[0130] Meanwhile, although the pulses (A, B) have been described as being used to generate an image of the skull of a subject, the present invention is not limited thereto. That is, the pulses (A, B) may also be used in the image stitching process with the MRI image (or CT image) described above in FIG. 5.

[0131] Referring to FIG. 2 and FIG. 6b together, at least one piezoelectric element (11) performing a second function based on a second electrical signal provided from a driving module (20) can output a pulse (C) of ultrasonic energy of a second resonant frequency (250 kHz) in a low-frequency region.

[0132] A pulse (C) of ultrasound energy can be output toward the blood-brain barrier of a desired brain tissue of a subject, and the blood-brain barrier can be opened due to the pulse (C) of ultrasound energy.

[0133] At this time, since the acoustic cavitation-generating substance (microbubble) can be located not only at the blood-brain barrier but also near the blood-brain barrier, the output ultrasonic energy can be applied to (or reach) the acoustic cavitation-generating substance as well as the blood-brain barrier.

[0134] Acoustic cavitation-generating materials can experience resonance due to pulses of ultrasonic energy (C) and can emit acoustic signals (D) to the outside due to the acoustic cavitation phenomenon.

[0135] The piezoelectric element (11) performing the third function can detect an acoustic signal (D) emitted from an acoustic cavity generating material, and the judgment module (30) can analyze the acoustic signal (D) in real time.

[0136] The judgment module (30) can determine the behavior of the acoustic cavitation-generating material by analyzing the frequency components (125 kHz, 375 kHz, kHz) corresponding to the value of n / 2 times (i.e., f2*n / 2, n=1, 3, 5, kHz) of the second resonant frequency (250 kHz, f2) in the acoustic signal (D) and the frequency components (500 kHz, 750 kHz, kHz) corresponding to the value of n times (i.e., f2*n, n=2, 3, 4, kHz) of the second resonant frequency (250 kHz, f2).

[0137] That is, as described above in FIGS. 6A and 6B, the present invention outputs ultrasonic energy to the blood-brain barrier and the acoustic cavitation-generating substance, and simultaneously analyzes the acoustic signal generated from the acoustic cavitation-generating substance to analyze the behavior (e.g., intensity of the behavior) of the acoustic cavitation-generating substance, thereby making it possible to determine whether the opening of the blood-brain barrier is performed appropriately and safely.

[0138] In addition, the judgment module (30) can perform Passive Acoustic Mapping (PAM) by analyzing a plurality of acoustic signals (D) detected by at least one piezoelectric element (11) (or a plurality of piezoelectric elements (11)) performing the fourth function, and simultaneously judge (or monitor) the location and behavior of an acoustic cavitation-generating substance.

[0139] The above process may be repeated for a pulse repetition frequency (PRF) of 1 Hz, but the present invention is not limited thereto. That is, the above process may be repeated for various periods of time set by the user.

[0140] As described above, the focused ultrasound processing system (1) for opening and monitoring the blood-brain barrier of the present invention can open the blood-brain barrier by utilizing low-frequency based ultrasound energy with optimized skull penetration efficiency, and can also acquire an image of the skull by utilizing high-frequency based ultrasound energy during the ultrasound energy output process and adjust the position of the focused ultrasound processing device (10) or control the piezoelectric element (11) in real time through image stitching, thereby irradiating ultrasound energy to a desired lesion.

[0141] That is, the present invention can obtain an image of the skull by utilizing ultrasonic energy having a high resonance frequency, and adjust the position (or installation position or installation angle, etc.) of the focused ultrasound processing device (10) to be suitable for the irradiation of ultrasonic energy, and can open the blood-brain barrier by utilizing ultrasonic energy having a low resonance frequency, thereby allowing a desired drug to easily and safely move into the brain.

[0142] In addition, it is possible to infer the degree of opening of the blood-brain barrier in real time by analyzing the acoustic signal generated by the acoustic cavitation-generating substance located near the blood-brain barrier in real time, and it is also possible to determine the current location of the acoustic cavitation-generating substance to confirm or monitor whether the ultrasound energy is properly focused.

[0143]

[0144] FIG. 7 is a flowchart of an ultrasound control method of a focused ultrasound processing system for opening and monitoring the blood-brain barrier according to one embodiment of the present invention.

[0145] In step (S1), MRI images or CT images can be acquired.

[0146] Specifically, the judgment module (30) can upload an MRI image or CT image of a subject pre-stored in a database.

[0147] In step (S2), a skull image can be acquired based on high frequency.

[0148] Specifically, a focused ultrasound processing device (10) may be pre-mounted on the head of the object. The driving module (20) may provide a first electrical signal to at least one piezoelectric element (11) pre-designated to perform a first function.

[0149] The ultrasonic processing device (10) can output first ultrasonic energy having a first resonant frequency (about 3000 kHz) toward the skull of the target object based on the first electrical signal.

[0150] The first ultrasonic energy can be output from the piezoelectric element (11) and reach the surface of the skull of the target object, and can be reflected from the surface of the skull and returned to the piezoelectric element (11).

[0151] At this time, the judgment module (30) can obtain an image of the skull by measuring the TOF, which is the period between the time when the first ultrasonic energy is output from the piezoelectric element (11) and the time when the first ultrasonic energy reflected from the surface of the skull and returned is detected.

[0152] The images can be spliced ​​in step (S3).

[0153] Specifically, the judgment module (30) can perform image stitching by comparing and analyzing the MRI image or CT image of the object acquired in step (S1) and the image of the skull acquired in step (S2).

[0154] In step (S4), it can be determined whether the image stitching error rate is xmm or less.

[0155] Specifically, the judgment module (30) can determine whether the image stitching error rate between the MRI image or CT image of the object acquired in step (S1) and the image of the skull acquired in step (S2) is less than or equal to a preset x mm.

[0156] If the image stitching error rate exceeds the preset x mm, the process returns to step (S3), and the skull image acquired in step (S2) may be adjusted (e.g., rotated) and image stitched again with the MRI image or CT image of the object acquired in step (S1). This may be repeatedly performed until the image stitching error rate becomes less than or equal to the preset x mm.

[0157] In step (S5), the current position coordinate value of the focused ultrasonic processing device and the current position coordinate value of the focused point can be derived.

[0158] Specifically, when the image stitching error rate is less than or equal to a preset x mm (i.e., the point where the error rate between images is the lowest or when image stitching is completed), the judgment module (30) can obtain the current three-dimensional coordinate values ​​(X, Y, Z) of the focused ultrasound processing device (10) mounted on the target object.

[0159] In addition, the judgment module (30) can obtain the focus point coordinate values ​​(Xf, Yf, Zf) of the ultrasonic energy output at the current location based on the current three-dimensional coordinate values ​​(X, Y, Z) of the acquired focused ultrasonic processing device (10) as described above in FIG. 5 (i.e., by utilizing sound field characteristic dictionary data).

[0160] As described above in FIG. 5, the mobile device can additionally utilize sound field characteristic prior data to move the focused ultrasonic processing device (10) or adjust the position of at least one piezoelectric element (11) to obtain new three-dimensional coordinate values ​​(X1, Y1, Z1) of the adjusted focused ultrasonic processing device (10) and new three-dimensional target focus point coordinate values ​​(Xf1, Yf1, Zf1) of ultrasonic energy.

[0161] In step (S6), ultrasound energy can be output to the brain lesion target.

[0162] That is, at the current three-dimensional coordinate values ​​(X1, Y1, Z1) of the focused ultrasound processing device (10) obtained in step (S5), second ultrasonic energy having a second resonance frequency (about 250 kHz) of low frequency can be output from at least one piezoelectric element (11) toward a target object (e.g., brain lesion target).

[0163] Specifically, the driving module (20) can provide a second electrical signal to a piezoelectric element (11) preset to perform a second function. At this time, the focused ultrasound processing device (10) can output second ultrasonic energy having a second resonant frequency (approximately, 250 kHz) to the cerebral blood vessel barrier and microbubbles located near the cerebral blood vessel barrier.

[0164] The blood-brain barrier can be opened at step (S7).

[0165] Specifically, the second ultrasonic energy output from at least one piezoelectric element (11) can reach the blood-brain barrier and the microbubbles located nearby, thereby opening the blood-brain barrier.

[0166] In step (S8), the opening of the blood-brain barrier can be analyzed based on the acoustic signal.

[0167] Specifically, the piezoelectric element (11) set to perform the third function can receive an acoustic signal generated by an acoustic cavity generating material, which can be provided to the judgment module (30).

[0168] The judgment module (30) can determine the behavior of the acoustic cavitation generating material by analyzing the frequency components (125 kHz, 375 kHz, ...) corresponding to the value of n / 2 (i.e., f2*n / 2, n=1,3,5...) of the second resonant frequency (250 kHz, f2) in the acoustic signal and the frequency components (500 kHz, 750 kHz, ...) corresponding to the value of f2*n (n=2,3,4...).

[0169] If the behavior of the acoustic cavitation-generating material is judged to be such that the microbubbles are about to break, and if it goes beyond opening the blood-brain barrier and causes damage to surrounding tissue cells, the intensity of the ultrasound energy can be reduced.

[0170] Alternatively, a plurality of piezoelectric elements (11) set to perform the fourth function can receive a plurality of acoustic signals generated by an acoustic cavitation-generating substance and provide them to a judgment module (30). The judgment module (30) can perform Passive Acoustic Mapping (PAM) based on the plurality of acoustic signals and simultaneously determine the location and behavior of the acoustic cavitation-generating substance.

[0171] Through this, it is possible to monitor whether the ultrasonic energy is focused at the desired location as a result of determining the location of the acoustic cavitation generating material, and if it is not focused at the desired location, the location of the piezoelectric element can be adjusted as in step (S6).

[0172] In step (S9), it is possible to determine whether the error rate is less than ymm using an image based on Passive Acoustic Mapping (PAM).

[0173] Specifically, the judgment module (30) can acquire a PAM image based on the Passive Acoustic Mapping performed in step (S8). In addition, the judgment module (30) can determine whether the error rate of the PAM image is ymm or less.

[0174] If the error rate of the PAM image exceeds ymm, the position of the focal point of the ultrasonic energy output from the current position of the focused ultrasonic processing device (10) and the position of the brain lesion target do not properly match, so the process returns to step (S6) to reset the coordinate values ​​of the focal point of the ultrasonic energy output from the focused ultrasonic processing device (10), and the ultrasonic energy can be output again.

[0175] Steps (S6 to S9) can be repeated until the error rate of the PAM image is ymm or less, and the focus of the ultrasound energy can be reset in real time during the process of opening the blood-brain barrier using ultrasound energy. This can improve the accuracy of opening the blood-brain barrier.

[0176] The method for resetting the focus of ultrasonic energy may utilize the previously stored sound field characteristic dictionary data, but the present invention is not limited thereto.

[0177] It can be determined whether the preset time has been met in step (S10).

[0178] Specifically, if the error rate of the PAM image in step (S9) is ymm or less, the position of the focal point of the ultrasound energy output from the current position of the focused ultrasound processing device (10) and the position of the brain lesion target are properly matched, so the judgment module (30) can determine whether a preset time (e.g., treatment time) has been met. The preset time can be variously set by the user.

[0179] If the preset time is not met, the process returns to step (S7) and the blood-brain barrier opening can be re-performed using low frequency. That is, steps (S7 to S10) can be repeated until the preset time is met.

[0180] The output of ultrasonic energy can be terminated at step (S11).

[0181] Specifically, the output of ultrasound energy can be terminated when a preset time (e.g., treatment time) has been met.

[0182]

[0183] The drawings and detailed description of the invention described so far are merely illustrative of the present invention and are used solely for the purpose of explaining the present invention and are not intended to limit the scope of the invention as defined in the claims. Therefore, those skilled in the art will understand that various modifications and equivalent embodiments are possible. Accordingly, the true technical protection scope of the present invention should be determined by the technical spirit of the appended claims.

[0184] The embodiments described above may be implemented using hardware components, software components, and / or a combination of hardware components and software components. For example, the devices, methods, and components described in the embodiments may be implemented using one or more general-purpose computers or special-purpose computers, such as, for example, a processor, a controller, an arithmetic logic unit (ALU), a digital signal processor, a microcomputer, a field programmable gate array (FPGA), a programmable logic unit (PLU), a microprocessor, or any other device capable of executing instructions and responding to them.

[0185] A processing device can execute an operating system and one or more software applications running on the operating system. Furthermore, the processing device can access, store, manipulate, process, and generate data in response to the execution of the software. For ease of understanding, the processing device is sometimes described as being used singly. However, those skilled in the art will understand that the processing device can include multiple processing elements and / or multiple types of processing elements.

[0186] For example, a processing unit may include multiple processors, or a processor and a controller. Other processing configurations, such as parallel processors, are also possible. Software may include computer programs, code, instructions, or a combination of one or more of these, and may configure a processing unit to perform a desired operation or command the processing unit, either independently or collectively.

[0187] Software and / or data may be embodied in any type of machine, component, physical device, virtual equipment, computer storage medium, or device for interpretation by a processing device or for providing instructions or data to the processing device. The software may be distributed across networked computer systems and stored or executed in a distributed manner. The software and data may be stored on one or more computer-readable recording media.

[0188] The method according to the embodiment may be implemented in the form of program commands that can be executed by various computer means and recorded on a computer-readable medium. The computer-readable medium may include program commands, data files, data structures, etc., either singly or in combination. The program commands recorded on the medium may be those specifically designed and configured for the embodiment or may be known and usable by those skilled in the art of computer software.

[0189] Examples of computer-readable recording media include magnetic media such as hard disks, floppy disks, and magnetic tapes; optical media such as CDROMs and DVDs; and hardware devices specifically configured to store and execute program instructions, such as ROMs, RAMs, and flash memories. Examples of program instructions include not only machine language codes such as those generated by a compiler, but also high-level language codes that can be executed by a computer using an interpreter or the like. The hardware devices described above may be configured to operate as one or more software modules to perform the operations of the embodiments, and vice versa.

[0190] Although the embodiments have been described with limited examples and drawings, those skilled in the art will appreciate that various modifications and variations can be made based on the above teachings. For example, appropriate results can be achieved even if the described techniques are performed in a different order than described, and / or components of the described systems, structures, devices, circuits, etc. are combined or combined in a different manner than described, or are replaced or substituted with other components or equivalents. Therefore, other implementations, other embodiments, and equivalents of the claims also fall within the scope of the claims described below.

Claims

1. At least one piezoelectric element composed of a single structure; and A driving module that provides an electric signal so that ultrasonic energy having one resonant frequency among a plurality of resonant frequencies or ultrasonic energy having at least two or more resonant frequencies is output by at least one piezoelectric element, A focused ultrasound treatment system for blood-brain barrier opening and monitoring.

2. In paragraph 1, The at least one piezoelectric element is composed of a single or multiple materials that interact with the ultrasonic energy. A focused ultrasound treatment system for blood-brain barrier opening and monitoring.

3. In paragraph 1, wherein said at least one piezoelectric element outputs said ultrasonic energy to a target object or an acoustic cavitation generating material administered to said target object, A focused ultrasound treatment system for blood-brain barrier opening and monitoring.

4. In paragraph 3, The at least one piezoelectric element receives an acoustic cavitation signal reflected from the object or generated due to an acoustic cavitation phenomenon of the acoustic cavitation generating material. A focused ultrasound treatment system for blood-brain barrier opening and monitoring.

5. In paragraph 4, The above multiple resonant frequencies are, first resonant frequency; and including a second resonant frequency which is a lower frequency value than the first resonant frequency, A focused ultrasound treatment system for blood-brain barrier opening and monitoring.

6. In paragraph 5, The above focused ultrasound treatment system for opening and monitoring the blood-brain barrier is: Further comprising a judgment module for analyzing the acoustic cavitation signal to generate an image of the object or to determine the location or behavior of the acoustic cavitation generating material. A focused ultrasound treatment system for blood-brain barrier opening and monitoring.

7. In paragraph 6, The above judgment module, The first ultrasonic energy having the first resonant frequency is reflected from the object, and the acoustic cavity signal is analyzed to generate the image. A focused ultrasound treatment system for blood-brain barrier opening and monitoring.

8. In paragraph 7, The above judgment module, Generating the image by measuring the time of flight (TOF), which is the period between the time at which the first ultrasonic energy is output by the at least one piezoelectric element and the time at which the acoustic cavitation signal is detected. A focused ultrasound treatment system for blood-brain barrier opening and monitoring.

9. In paragraph 5, At least one piezoelectric element, Opening the object by outputting a second ultrasonic energy having the second resonant frequency, A focused ultrasound treatment system for blood-brain barrier opening and monitoring.

10. In paragraph 9, The above target is the blood-brain barrier and the acoustic cavitation generating material is a microbubble located near the target. A focused ultrasound treatment system for blood-brain barrier opening and monitoring.

11. In paragraph 6, The above judgment module, The behavior of the acoustic cavitation-generating material is determined by extracting a frequency component corresponding to the value of n / 2 of the second resonance frequency from the above acoustic cavitation signal, and n is a natural number other than 2. A focused ultrasound treatment system for blood-brain barrier opening and monitoring.

12. In paragraph 6, The above judgment module, By analyzing the acoustic cavitation signal generated by the second ultrasonic energy having the second resonant frequency, the location of the acoustic cavitation generating material is determined. A focused ultrasound treatment system for blood-brain barrier opening and monitoring.

13. In paragraph 6, Each of the above at least one piezoelectric element, A first function for generating an image of the object by outputting the ultrasonic energy; A second function for opening the object by outputting the ultrasonic energy; A third function for analyzing the above acoustic cavitation signal to determine the behavior of the acoustic cavitation-generating substance; and Performing at least two of the fourth functions for simultaneously determining the location and behavior of the acoustic cavitation generating material by analyzing the above acoustic cavitation signal. A focused ultrasound treatment system for blood-brain barrier opening and monitoring.

14. In an ultrasound control method of a focused ultrasound processing system for opening and monitoring the blood-brain barrier driven by at least one processor, providing an electrical signal so that ultrasonic energy having at least one resonant frequency among a plurality of resonant frequencies is output by at least one processor; and A step of receiving the electric signal by the at least one processor and outputting the ultrasonic energy having the resonant frequency to the target object and the acoustic cavitation generating material administered to the target object, Ultrasonic control method of a focused ultrasound treatment system for opening and monitoring the blood-brain barrier.

15. A computer-readable recording medium having recorded thereon a program for executing an ultrasound control method of a focused ultrasound processing system for opening and monitoring the blood-brain barrier in Article 14.

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