Ultrasonic signal processing device and method therefor

Abstract

Disclosed are an ultrasonic signal processing device and a method therefor. According to the present invention, a destructive histotripsy ultrasonic signal is output to a central region of an affected area through a first transducer, and a non-destructive focused ultrasonic signal is output to a peripheral region of the affected area through a second transducer, thereby minimizing side effects of destructive methods while locally fragmenting tissue.

Description

Ultrasonic signal processing device and method

[0001] The present invention relates to diagnostic and therapeutic technologies using ultrasound, and more specifically, to image scanning and therapeutic technologies using focused ultrasound (FUS).

[0002] Ultrasound signals can be used to treat tissues such as cancer, tumors, and lesions. Ultrasound therapy is a method of treating lesions by outputting ultrasound signals to the lesions in the human body. Compared to general surgical procedures or chemotherapy, ultrasound therapy causes less trauma to the patient and enables non-invasive treatment. Its applications are diverse, including liver cancer, bone sarcoma, breast cancer, pancreatic cancer, kidney cancer, soft tissue tumors, and pelvic tumors.

[0003] Focused Ultrasound (FUS) signals can be used to treat tissues such as cancer, tumors, and lesions. Development of FUS-based treatments has primarily focused on thermal ablation, which utilizes thermal effects to thermally cauterize tissues. However, thermal ablation can cause thermal damage to surrounding tissues and pain.

[0004] According to one embodiment, in a technology using focused ultrasound, an ultrasound signal processing device and a method are proposed that can locally fragment tissue while minimizing the side effects of the fragmentation method by combining a fragmentation histotripsy method and a non-histotripsy method.

[0005] An ultrasonic signal processing device according to one embodiment includes a first transducer that outputs a fragmentary histotriptic ultrasonic signal in a central area of ​​a lesion, a second transducer that outputs a non-fragmentary focused ultrasonic signal in a peripheral area of ​​a lesion, and a processor that controls the first transducer and the second transducer to output the histotriptic ultrasonic signal and the focused ultrasonic signal.

[0006] The first transducer and the second transducer can sequentially and repeatedly output an ultrasonic signal during fragmentation histotripping and a non-fragmentation focused ultrasonic signal.

[0007] During histotrip, the ultrasonic signal can have an intensity of 40 MPa or more.

[0008] The focused ultrasound signal can be a high-intensity focused ultrasound signal having an intensity of 10 MPa or less.

[0009] Focused ultrasound signals can be ultrasound signals that induce cavitation in tissues using mechanical effects.

[0010] The processor can first identify a bubble cloud generated in the tissue by the histotrip ultrasound signal output by the first transducer, and if the bubble cloud is identified, control the second transducer to output a non-destructive focused ultrasound signal.

[0011] The processor can confirm bubble clouds generated in tissue by ultrasound signals during histotrips through imaging, or detect and confirm cavitation signals generated when bubble clouds form and collapse.

[0012] When an ultrasonic signal processing device creates temporary micro-pores in tissue through cavitation generated in the tissue by non-disruptive focused ultrasound signals, a pre-injected drug can be delivered to the tissue through the created micro-pores.

[0013] The processor can determine therapeutic parameters to maximize the non-local far-range immune response effect of the first transducer and the mechanical effect of the second transducer, and control the first transducer and the second transducer to output to the tissue through histotripsy ultrasound signals and focused ultrasound signals having the determined therapeutic parameters.

[0014] The processor can control the output ratio of the ultrasonic signals of the first transducer and the second transducer.

[0015] An ultrasonic signal processing method using an ultrasonic signal processing device according to another embodiment includes the steps of: outputting a fragmentary histotriplic ultrasonic signal to a central region of a lesion through a first transducer; and outputting a non-fragmentary focused ultrasonic signal to a peripheral region of a lesion through a second transducer.

[0016] In the step of outputting an ultrasonic signal during fragmentation histotrip and the step of outputting a non-fragmentation focused ultrasonic signal, the ultrasonic signal during fragmentation histotrip and the non-fragmentation focused ultrasonic signal can be sequentially and repeatedly output.

[0017] During histotrip, the ultrasonic signal can have an intensity of 40 MPa or more.

[0018] The focused ultrasound signal can be a high-intensity focused ultrasound signal having an intensity of 10 MPa or less.

[0019] Focused ultrasound signals can be ultrasound signals that induce cavitation in tissues using mechanical effects.

[0020] The ultrasound signal processing method may further include a step of confirming a bubble cloud generated in the tissue by the ultrasound signal during histotrip, and in the step of generating a non-destructive focused ultrasound signal, if a bubble cloud is confirmed, a non-destructive focused ultrasound signal may be output to a peripheral area of ​​the affected area secondarily.

[0021] In the step of confirming the bubble cloud, the bubble cloud generated in the tissue by the ultrasound signal during histotrip can be confirmed through imaging, or the cavitation signal generated when the bubble cloud forms and collapses can be detected.

[0022] The ultrasonic signal processing method may further include the step of temporarily creating micropores in the tissue through cavitation generated in the tissue by a non-disruptive focused ultrasonic signal, and the step of delivering a pre-injected drug to the tissue through the created micropores.

[0023] The ultrasound signal processing method may further include the step of determining therapeutic parameters to maximize the non-local far-range immune response effect of the first transducer and the mechanical effect of the second transducer, and controlling the first transducer and the second transducer to output to the tissue through a histotripsy ultrasound signal and a focused ultrasound signal having the determined therapeutic parameters.

[0024] The ultrasonic signal processing method may further include the step of controlling the output ratio of the ultrasonic signals of the first transducer and the second transducer.

[0025] The present invention combines a fragmentary histotripsy method and a non-fragmentary method to locally fragment tissue while minimizing the side effects of the fragmentary method.

[0026] The present invention can induce an abscopal immune response effect resulting from tumor tissue fragmentation through ultrasound signal output during fragmentation histotripsy.

[0027] The present invention can safely deliver drugs to tissues by utilizing the mechanical effect of non-disruptive focused ultrasound signals.

[0028] FIG. 1 is a diagram illustrating the configuration of an ultrasonic signal processing device according to one embodiment of the present invention.

[0029] FIG. 2 is a diagram illustrating the flow of an ultrasonic signal processing method according to an embodiment of the present invention.

[0030] FIGS. 3 and 4 are drawings illustrating the structure of a therapeutic transducer according to various embodiments of the present invention.

[0031] FIG. 5 is a diagram illustrating a treatment sequence according to one embodiment of the present invention.

[0032] The advantages and features of the present invention and the methods for achieving them will become clear by referring to the embodiments described below in detail together with the accompanying drawings. However, the present invention is not limited to the embodiments disclosed below but can be implemented in various different forms. These embodiments are provided merely to ensure that the disclosure of the present invention is complete and to fully inform those skilled in the art of the scope of the invention, and the present invention is defined only by the scope of the claims. Throughout the specification, the same reference numerals refer to the same components.

[0033] In describing the embodiments of the present invention, if it is determined that a detailed description of known functions or configurations may unnecessarily obscure the essence of the invention, such detailed description will be omitted. Furthermore, the terms described below are defined to reflect the functions in the embodiments of the present invention, and these may vary depending on the intentions or conventions of the user or operator. Therefore, their definitions should be based on the content throughout this specification.

[0034] Hereinafter, embodiments of the present invention will be described in detail with reference to the attached drawings. However, the embodiments of the present invention exemplified below may be modified in various different forms, and the scope of the present invention is not limited to the embodiments described below. The embodiments of the present invention are provided to more completely explain the present invention to those skilled in the art to which this invention pertains.

[0035] FIG. 1 is a diagram illustrating the configuration of an ultrasonic signal processing device according to one embodiment of the present invention.

[0036] The ultrasonic signal processing device (1) can minimize the side effects of the fragmentation method by using a fragmentation method in the central area of ​​the affected area and a non-fragmentation method in the peripheral area of ​​the affected area. For example, the ultrasonic signal processing device (1) first outputs a histotrip ultrasound signal of high intensity (e.g., 40 MPa or more) toward the central area of ​​the affected area to generate a bubble cloud, and secondarily outputs a focused ultrasound signal of low intensity (e.g., 10 MPa or less) toward the peripheral area of ​​the affected area. At this time, the high-intensity histotrip ultrasound signal is applied to the central area of ​​the affected area, and the low-intensity focused ultrasound signal is applied to the peripheral area of ​​the affected area. The focused ultrasound signal may be an ultrasound signal that generates cavitation in tissue using a mechanical effect. The focused ultrasound signal may be a High Intensity Focused Ultrasound (HIFU) signal. The peripheral area may be the edge area of ​​the central area of ​​the affected area. Alternatively, the peripheral area may be the entire area of ​​the affected site, including the central area. In this case, the boundary margin may be 5 mm or more. The boundary margin refers to the safe distance between the central area of ​​the tumor and the peripheral area of ​​the tumor.

[0037] Hereinafter, with reference to FIG. 1, the configuration of an ultrasonic signal processing device (1) having the aforementioned features will be described.

[0038] Referring to FIG. 1, the ultrasonic signal processing device (1) includes a processor (100), a therapeutic ultrasonic pulse generator (101), a diagnostic ultrasonic pulse generator (102), an ultrasonic treatment head (103), an image generator (108), a mechanical drive unit (109), a positioning arm (110), an input unit (111), a display unit (112), a storage unit (113), and a cavitation sensor (114). The ultrasonic treatment head (103) may include a first transducer (104), a second transducer (105), an image transducer (106), and a beam steering unit (107).

[0039] The treatment ultrasound pulse generator (101) generates a pulse-shaped driving signal having a predetermined pulse repetition frequency (PRF, hereinafter referred to as 'PRF') and duty cycle, and transmits it to the first transducer (104) and the second transducer (105).

[0040] The first transducer (104) and the second transducer (105) convert an electrical waveform, which is a driving signal received from the therapeutic ultrasound pulse generator (101), into an ultrasound signal and output the converted ultrasound signal to the tissue.

[0041] The first transducer (104) outputs an ultrasonic signal during histotrip in the central area of ​​the affected area. The ultrasonic signal during histotrip can have a high intensity of 40 MPa or more. The fragmentation method using the ultrasonic signal during histotrip is a non-heating method, and is a method of treating biological tissue by generating a bubble cloud in the central area of ​​the affected area, and by the generated bubble cloud being created, expanded, and collapsed, thereby fragmenting the central area of ​​the affected area.

[0042] The Histotripsy method allows for precise tissue targeting because it operates only in the central region of the affected area where the ultrasound signal is concentrated. The Histotripsy method can fragment tissues, such as tumors, using only ultrasound signals without surgical incision.

[0043] The first transducer (104) can induce an abscopal immune response effect through tissue fragmentation, such as of a tumor, via ultrasound signals during histotrip. The abscopal immune response is an important immunological phenomenon in which local treatment induces an immune response in distant tumors. This effect can be further enhanced through the combination of immunotherapy and ultrasound therapy in tumor treatment, and can present new possibilities for the treatment of metastatic cancer.

[0044] The second transducer (105) outputs a focused ultrasound signal to the peripheral area of ​​the affected area. The focused ultrasound signal may be a high-intensity focused ultrasound signal having a low intensity of 10 MPa or less. The focused ultrasound signal may be an ultrasound signal that causes cavitation in tissue using mechanical effects. The peripheral area may be the edge area of ​​the central area of ​​the affected area. Or the peripheral area may be the entire area of ​​the affected area including the central area of ​​the affected area.

[0045] The drug delivery effect can be improved through the focused ultrasound signal for mechanical effect that the second transducer (105) outputs to the surrounding area.

[0046] One drug delivery technology utilizing focused ultrasound involves a method that induces thermal vasodilation. However, this method carries a high risk of causing thermal damage to surrounding tissues or major organs. Furthermore, if tissues are thermally degenerated, the penetration efficacy of therapeutic agents, such as anticancer drugs, decreases. Another drug delivery technology using focused ultrasound involves delivering drugs by inducing cavitation within microbubbles through the application of mechanical force. However, this method has the limitation of requiring the use of microbubbles. Additionally, commercially available microbubbles are inefficient due to their low stability and short duration.

[0047] To solve the aforementioned problems, the second transducer (105) uses a safe, non-thermal, non-histotripsy method and a method that does not use microbubbles. For example, the second transducer (105) creates temporary micropores (sonoporation) in the tissue by inducing cavitation in the tissue without microbubbles using the mechanical effect of focused ultrasound. At this time, drugs are delivered through the micropores in the tissue using the acoustic streaming effect. The drugs include, for example, chemical therapeutic agents, gene therapy agents, biopharmaceuticals, and genetic materials. The drugs are injected through the blood vessels in the body using a syringe or similar device before the focused ultrasound is transmitted, and when micropores are created, the drugs present in the blood vessels are delivered to the tissue through the micropores. When a focused ultrasound signal is irradiated into the body without microbubbles, the occurrence of cavitation can be confirmed through the cavitation sensor (114).

[0048] The ultrasonic signal processing device (1) can sequentially and repeatedly output an ultrasonic signal during a fragmentation histotrip of the first transducer (104) and a non-fragmentation focused ultrasonic signal of the second transducer (105).

[0049] The image transducer (106) outputs an image ultrasound signal into the tissue and receives an ultrasound echo signal reflected from the tissue in accordance with an electrical signal of a short pulse, which is a driving signal received from the diagnostic ultrasound pulse generator (102). The image transducer (106) receives the ultrasound echo signal and transmits it to the processor (100) until the next pulse is generated.

[0050] The image transducer (106) may be configured with a piezoelectric element or the like embedded in a cylindrical casing. The image transducer (106) may be a phased array imaging transducer.

[0051] The ultrasonic treatment head (103) may have a structure in which an image transducer (106) is located in the center and a first transducer (104) and a second transducer (105) are arranged in the periphery. The first transducer (104) and the second transducer (105) may have an integrated array structure.

[0052] The ultrasonic signal processing device (1) can perform drug delivery using the focused ultrasonic signal of the second transducer (105) and simultaneously obtain a diagnostic image using the image ultrasonic signal of the image transducer (106).

[0053] The beam steering unit (107) performs transmission beam focusing or reception beam focusing of an ultrasonic signal through mechanical and / or electronic beam steering. At this time, the beam steering unit (107) can vary the ultrasonic focusing area by steering the beam direction. The beam steering unit (107) can perform hybrid beam steering in which mechanical steering and electronic steering are combined. The beam steering unit (107) can utilize a multi-channel array structure of a first transducer (104) and a second transducer (105) for mechanical and / or electronic beam steering.

[0054] The image generation unit (108) processes the ultrasonic echo signal received from the image transducer (106) and generates an ultrasonic image based on the processed received signal. The generated ultrasonic image can be displayed on a screen through the display unit (112). For signal processing, the image generation unit (108) may include a low-noise amplifier (LNA) and an analog-to-digital converter (ADC).

[0055] The mechanical drive unit (109) drives the beam steering unit (107) so that the beam steering unit (106) can mechanically beam stir the first transducer (104), the second transducer (105), and the image transducer (106).

[0056] The positioning arm (110) can move the ultrasonic treatment head (103), including the first transducer (104), the second transducer (105), and the image transducer (106), so that the ultrasonic treatment head (103) is positioned accurately and stably at the target. To this end, the positioning arm (110) may include a mechanism for tilting and rotating. The positioning arm (110) may tilt or rotate the first transducer (104), the second transducer (105), or the image transducer (106) individually, and may tilt or rotate the ultrasonic treatment head (103), including the first transducer (104), the second transducer (105), and the image transducer (106). To this end, the positioning arm (110) may have three or more degrees of freedom.

[0057] The input unit (111) receives a user operation signal. To this end, the input unit (111) may include a user interface. The display unit (112) outputs an ultrasound image. The storage unit (113) stores the received signal and stores information necessary for the operation of the processor (100). The storage unit (113) stores information necessary for signal analysis by the processor (100) or stores information analyzed through the processor (100).

[0058] The processor (100) can first identify a bubble cloud generated in the tissue by the ultrasonic signal during histotripping output by the first transducer (104), and if the bubble cloud is identified, it can secondarily control the second transducer (105) to output a non-fragmentary focused ultrasonic signal. The processor (100) can identify the bubble cloud generated in the tissue by the ultrasonic signal during histotripping through an image generated by the image generation unit (108), or identify the cavitation signal generated when the bubble cloud is formed and collapses by detecting it through the cavitation sensor (114).

[0059] The processor (100) controls the ultrasound signal output of the first transducer (104), the second transducer (105), and the image transducer (106). At this time, the processor (100) determines treatment parameters to maximize the non-local far-range immune response effect of the ultrasound signal during histotrip of the first transducer (104) and the mechanical effect of the second transducer (105), and controls the first transducer (104) and the second transducer (105) to transmit to the tissue through the ultrasound signal during histotrip and the focused ultrasound signal having the determined treatment parameters. The treatment parameters may be acoustic pressure, waveform, output time, frequency, duty cycle, etc.

[0060] The processor (100) can control the output ratio of the ultrasonic signals of the first transducer (104) and the second transducer (105). For example, the output ratio of the ultrasonic signal during histotrip of the first transducer (104) and the output ratio of the focused ultrasonic signal of the second transducer (105) can each be controlled within a sum of output ratios of 1 (100%).

[0061] The cavitation sensor (114) can detect a cavitation signal caused by a bubble cloud generated in the tissue by an ultrasonic signal during histotrip of the first transducer (104). The cavitation sensor (114) can detect a cavitation signal generated in the tissue by a focused ultrasonic signal of the second transducer (105). The processor (100) can analyze the detected cavitation signal to confirm the effect of the ultrasonic signal.

[0062] FIG. 2 is a diagram illustrating the flow of an ultrasonic signal processing method according to one embodiment of the present invention.

[0063] Referring to FIGS. 1 and FIGS. 2, first, a drug is injected into the body through blood vessels, etc. A syringe, etc., may be used for the drug injection method.

[0064] The ultrasonic signal processing device (1) primarily outputs a fragmentation histotrip ultrasonic signal to the central area of ​​the affected area through the first transducer (104) (S210). The histotrip ultrasonic signal can have an intensity of 40 MPa or more.

[0065] Next, the ultrasonic signal processing device (1) checks for bubble clouds generated in the tissue by the ultrasonic signal during histotrip (S220).

[0066] In the step of confirming the bubble cloud (S220), the ultrasonic signal processing device (1) can confirm the bubble cloud generated in the tissue by the ultrasonic signal during histotrip through an image, or detect and confirm the cavitation signal generated when the bubble cloud is formed and collapses.

[0067] Next, when the ultrasonic signal processing device (1) confirms a bubble cloud, it outputs a non-destructive focused ultrasonic signal to the surrounding area of ​​the affected area through the second transducer (105) in a secondary manner (S230). The focused ultrasonic signal may be a high-intensity focused ultrasonic signal having an intensity of 10 MPa or less. The focused ultrasonic signal may be an ultrasonic signal that causes cavitation in tissue using mechanical effects. The surrounding area may be the edge area of ​​the central area of ​​the affected area. Or, the surrounding area may be the entire area of ​​the affected area including the central area of ​​the affected area.

[0068] The ultrasonic signal processing device (1) can determine treatment parameters to maximize the non-local far-range immune response effect of the first transducer (104) and the mechanical effect of the second transducer (105), and control the first transducer (104) and the second transducer (105) to output to the tissue through histotripsy ultrasonic signals and focused ultrasonic signals having the determined treatment parameters.

[0069] The ultrasonic signal processing device (1) can control the output ratio of the ultrasonic signals of the first transducer (104) and the second transducer (105).

[0070] Next, the ultrasonic signal processing device (1) can temporarily create micro-holes in the tissue through cavitation generated in the tissue by a non-destructive focused ultrasonic signal (S240).

[0071] Next, the injected drug can be delivered to the tissue through the generated micropores (S250).

[0072] FIGS. 3 and 4 are drawings illustrating the structure of a therapeutic transducer according to various embodiments of the present invention.

[0073] The first transducer (104) and the second transducer (105) may be an integrated array structure, wherein the array structure may be an annular array in which the first transducer (104) and the second transducer (105) are in an annular shape as shown in FIGS. 3 and 4, or a random array in which they are arranged in a random shape.

[0074] FIG. 5 is a diagram illustrating a treatment sequence according to one embodiment of the present invention.

[0075] Referring to FIGS. 1 and 5, the ultrasonic signal processing device (1) can sequentially and repeatedly output a fragmentary histotriptic ultrasonic signal and a non-fragmentary focused ultrasonic signal. For example, the ultrasonic signal processing device (1) can first output a fragmentary histotriptic ultrasonic signal (510) to the central area of ​​the affected area through the first transducer (104), and secondarily output a non-fragmentary focused ultrasonic signal (520) to the peripheral area of ​​the affected area through the second transducer (105).

[0076] The present invention has been described above with reference to its embodiments. Those skilled in the art will understand that the invention may be implemented in modified forms without departing from the essential characteristics of the invention. Therefore, the disclosed embodiments should be considered in an illustrative rather than a restrictive sense. The scope of the invention is defined by the claims, not by the foregoing description, and all variations within the scope of the claims should be interpreted as being included in the invention.

Claims

1. A first transducer that outputs an ultrasonic signal upon fragmentation histotrip in the central region of the affected area; A second transducer that outputs a non-fragmentary focused ultrasound signal to the surrounding area of ​​the affected area; and A processor that controls a first transducer and a second transducer to output an ultrasonic signal and a focused ultrasonic signal during histotrip; An ultrasonic signal processing device characterized by including 2. In claim 1, the first transducer and the second transducer are An ultrasonic signal processing device characterized by sequentially and repeatedly outputting a fragmentation histotriptic ultrasonic signal and a non-fragmentation focused ultrasonic signal.

3. In Paragraph 1, An ultrasonic signal processing device characterized by the ultrasonic signal having an intensity of 40 MPa or more during histotrip.

4. In Paragraph 1, An ultrasonic signal processing device characterized in that the focused ultrasonic signal is a high-intensity focused ultrasonic signal having an intensity of 10 MPa or less.

5. In Paragraph 1, An ultrasound signal processing device characterized by the fact that the focused ultrasound signal is an ultrasound signal that generates cavitation in tissue using mechanical effects.

6. In claim 1, the processor First, check the bubble cloud generated in the tissue by the ultrasound signal during histotrip output from the first transducer, and An ultrasonic signal processing device characterized by controlling a second transducer to output a non-fragmentary focused ultrasonic signal when a bubble cloud is detected.

7. In Clause 6, the processor Ultrasonic signal processing device characterized by confirming bubble clouds generated in tissue by ultrasound signals during histotrips through imaging, or detecting and confirming cavitation signals generated when bubble clouds are formed and collapse.

8. In claim 1, the ultrasonic signal processing device An ultrasonic signal processing device characterized by the creation of temporary micro-holes in tissue through cavitation generated in tissue by a non-destructive focused ultrasound signal, through which a previously injected drug is delivered to the tissue.

9. In claim 1, the processor An ultrasound signal processing device characterized by determining therapeutic parameters to maximize the non-local far-range immune response effect of a first transducer and the mechanical effect of a second transducer, and controlling the first transducer and the second transducer to output to tissues through histotrip ultrasound signals and focused ultrasound signals having the determined therapeutic parameters.

10. In claim 1, the processor Ultrasonic signal processing device characterized by controlling the output ratio of ultrasonic signals of a first transducer and a second transducer.

11. In a method for processing ultrasonic signals using an ultrasonic signal processing device, A step of outputting an ultrasonic signal during fragmentation histotrip in the central region of the affected area through a first transducer; and A step of outputting a non-fragmentary focused ultrasound signal to the surrounding area of ​​the affected area through a second transducer; Ultrasonic signal processing method characterized by including 12. In Paragraph 11, The steps of outputting an ultrasonic signal during fragmentation histotrip and outputting a non-fragmentation focused ultrasonic signal are: An ultrasonic signal processing method characterized by sequentially and repeatedly outputting a fragmentation histotripsy ultrasonic signal and a non-fragmentation focused ultrasonic signal.

13. In Paragraph 11, Ultrasonic signal processing method characterized by the ultrasonic signal having an intensity of 40 MPa or more during histotrip.

14. In Paragraph 11, An ultrasonic signal processing method characterized in that the focused ultrasonic signal is a high-intensity focused ultrasonic signal having an intensity of 10 MPa or less.

15. In Paragraph 11, An ultrasound signal processing method characterized in that the focused ultrasound signal is an ultrasound signal that generates cavitation in tissue using mechanical effects.

16. In claim 11, the ultrasonic signal processing method The method further includes the step of identifying a bubble cloud generated in the tissue by an ultrasound signal during histotrip; and The step of generating a non-fragmentary focused ultrasound signal An ultrasonic signal processing method characterized by outputting a non-fragmentary focused ultrasonic signal to the surrounding area of ​​the affected area secondarily when a bubble cloud is confirmed.

17. In Clause 16, the step of verifying the bubble cloud Ultrasound signal processing method characterized by confirming, through imaging, bubble clouds generated in tissue by ultrasound signals during histotrip, or detecting and confirming cavitation signals generated when bubble clouds are formed and collapse.

18. In claim 11, the ultrasonic signal processing method A step of creating temporary micro-holes in the tissue through cavitation generated in the tissue by a non-destructive focused ultrasound signal; and A step in which a drug injected earlier is delivered to the tissue through the micropores created above; Ultrasonic signal processing method characterized by further including 19. In claim 11, the ultrasonic signal processing method A step of determining therapeutic parameters to maximize the non-local distant immune response effect of the first transducer and the mechanical effect of the second transducer, and controlling the first transducer and the second transducer to output to the tissue through a histotripsy ultrasound signal and a focused ultrasound signal having the determined therapeutic parameters; Ultrasonic signal processing method characterized by further including 20. In claim 11, the ultrasonic signal processing method A step of controlling the output ratio of the ultrasonic signals of the first transducer and the second transducer; Ultrasonic signal processing method characterized by further including

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