Focused ultrasound processing device and drug delivery method using same

Abstract

Disclosed are a focused ultrasound processing device and a drug delivery method using same. A drug delivery method according to one embodiment comprises the steps of: determining a treatment parameter for a mechanical effect of focused ultrasound; transmitting focused ultrasound having the determined treatment parameter to tissue through a focused ultrasound transducer; generating cavitation in the tissue without microbubbles by using the mechanical effect of the transmitted focused ultrasound; temporarily generating fine holes in the tissue through the generated cavitation; and delivering a pre-injected drug through the generated fine holes.

Description

Focused ultrasound treatment device and drug delivery method using the same

[0001] The present invention relates to a diagnostic and therapeutic technique using ultrasound, and more particularly, to an image scanning and therapeutic technique using focused ultrasound (FUS).

[0002] Ultrasound signals can be used to treat biological tissues such as cancer, tumors, and lesions. Ultrasound therapy involves applying ultrasound signals to lesions in the body to treat them. Compared to conventional surgery or chemotherapy, ultrasound therapy causes less trauma to the patient and offers non-invasive treatment. Its applications include a variety of conditions, 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. Treatments using FUS have primarily focused on thermal ablation, which utilizes thermal effects to thermally ablate tissue. However, thermal ablation can cause thermal damage and pain to surrounding tissue.

[0004] According to one embodiment, in drug delivery using focused ultrasound, a focused ultrasound treatment device and a drug delivery method using the same are proposed, which can safely deliver a drug to a living tissue non-thermally and non-histotripsy without using microbubbles.

[0005] A drug delivery method according to one embodiment includes the steps of determining treatment parameters for a mechanical effect of focused ultrasound, transmitting focused ultrasound having the determined treatment parameters to a tissue through a focused ultrasound transducer, generating cavitation in the tissue by the transmitted focused ultrasound, temporarily generating micro-holes in the tissue through the generated cavitation, and delivering a pre-injected drug to the tissue through the generated micro-holes.

[0006] At the stage of determining treatment parameters, the intensity of focused ultrasound can be determined as 1.0 to 3.0 kW / cm2.

[0007] In the step of determining treatment parameters, the frequency of focused ultrasound can be determined as 0.5 to 3.0 MHz.

[0008] In the step of determining the treatment parameters, the duty cycle of the focused ultrasound can be determined to be 10% or less.

[0009] In the step of generating cavitation, stable cavitation in which bubbles vibrate and inertial cavitation in which bubbles collapse can be generated by synchronizing the bubbles generated by the focused ultrasound and the focused ultrasound.

[0010] The drug delivery method may further include a step of detecting a cavitation signal caused by a cavitation phenomenon occurring in a tissue by the transmitted focused ultrasound through a cavitation sensor, and a step of analyzing the detected cavitation signal to confirm the mechanical effect of the focused ultrasound.

[0011] In the step of confirming the mechanical effect of the focused ultrasound, it is confirmed whether a stable cavitation signal and an inertial cavitation signal are detected from the detected cavitation signal, and if two cavitation signals are detected, it can be determined that a mechanical effect has occurred.

[0012] The drug delivery method may further include a step of adjusting treatment parameters of focused ultrasound based on the results of cavitation signal analysis, and a step of transmitting focused ultrasound with the adjusted treatment parameters to a tissue through a focused ultrasound transducer.

[0013] The drug delivery method may further include a step of steering the direction of a beam of focused ultrasound to be transmitted.

[0014] In the step of steering the direction of the beam, at least one of mechanical beam steering and electrical beam steering through a multi-channel array can be performed.

[0015] The drug delivery method may further include a step of controlling the position of the ultrasound treatment head via a positioning arm.

[0016] The drug delivery method may further include a step of outputting an image ultrasound signal to a tissue through an image transducer, receiving an ultrasound echo signal reflected from the tissue, a step of processing the received ultrasound echo signal to generate an ultrasound image signal, and a step of analyzing the generated ultrasound image signal to confirm the mechanical effect of the focused ultrasound.

[0017] According to another embodiment, a focused ultrasound treatment device includes a focused ultrasound transducer that transmits focused ultrasound to a tissue, and a processor that determines treatment parameters for a mechanical effect of the focused ultrasound, transmits focused ultrasound with the determined treatment parameters to the tissue through the focused ultrasound transducer, generates cavitation in the tissue without microbubbles using the mechanical effect of the transmitted focused ultrasound, and temporarily creates microholes through the generated cavitation, so that an injected drug is delivered to the tissue through the generated microholes.

[0018] According to a focused ultrasound treatment device and a drug delivery method using the same according to one embodiment, by using the mechanical effect of focused ultrasound, a drug can be delivered to a living tissue in a safe, non-thermal, non-histotripsy manner, and in a manner that does not use microbubbles.

[0019] FIG. 1 is a diagram illustrating the configuration of a focused ultrasound treatment device for drug delivery according to one embodiment of the present invention;

[0020] Figure 2 is a diagram illustrating a flow of a drug delivery method according to one embodiment of the present invention;

[0021] FIG. 3 is a drawing illustrating sonoporation using cavitation according to one embodiment of the present invention.

[0022] FIG. 4 is a diagram illustrating a cavitation signal according to an embodiment of the present invention;

[0023] FIG. 5 is a diagram illustrating an example of beam steering of a focused ultrasonic transducer according to one embodiment of the present invention.

[0024] The advantages and features of the present invention, and the methods for achieving them, will become clearer with reference to the embodiments described in detail below together with the accompanying drawings. However, the present invention is not limited to the embodiments disclosed below and may be implemented in various different forms. These embodiments are provided only 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. Like reference numerals designate like elements throughout the specification.

[0025] In describing embodiments of the present invention, if it is determined that a specific description of a known function or configuration may unnecessarily obscure the gist of the present invention, such detailed description will be omitted. The terms described below are terms defined to reflect functions in embodiments of the present invention, and these may vary depending on the intention or custom of the user or operator. Therefore, the definitions should be made based on the contents throughout this specification.

[0026] Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings. However, the embodiments of the present invention exemplified below may be modified in various other 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 fully explain the present invention to those skilled in the art.

[0027] FIG. 1 is a diagram illustrating the configuration of a focused ultrasound treatment device for drug delivery according to one embodiment of the present invention.

[0028] One drug delivery technique utilizing focused ultrasound involves thermally inducing vasodilation. However, this method carries a high risk of causing thermal damage to surrounding tissues and major organs. Furthermore, thermal tissue denaturation reduces the penetration effectiveness of therapeutic agents such as anticancer drugs.

[0029] Another drug delivery technique utilizing focused ultrasound involves applying mechanical force to microbubbles, inducing cavitation within the microbubbles to deliver the drug. However, this method has limitations, requiring the use of microbubbles. Furthermore, commercially available microbubbles have low stability and short duration, making them inefficient.

[0030] To solve the above-described problems, a focused ultrasound treatment device (1) according to one embodiment uses a safe, non-thermal, non-histotripsy method and a method that does not use microbubbles. For example, the focused ultrasound treatment device (1) temporarily creates microholes in the tissue by inducing cavitation in the tissue inside the body without microbubbles by utilizing the mechanical effect of focused ultrasound (sonoporation). Then, the focused ultrasound treatment device (1) uses the acoustic streaming effect to deliver drugs between the microholes. Drugs include, for example, chemical therapeutic agents, gene therapeutic agents, biopharmaceuticals, and genetic materials. The drug is injected through blood vessels inside the body using a syringe or the like before transmitting focused ultrasound, and when microholes are created, the drug existing in the blood vessels is delivered to the tissue through the microholes. The focused ultrasound may be high intensity focused ultrasound (HIFU). Even when focused ultrasound is irradiated into the body without microbubbles, cavitation can be confirmed to occur using a cavitation sensor (see Fig. 4).

[0031] High-intensity focused ultrasound can cause gas molecules dissolved in a biofluid to assemble, forming gaseous bubbles. Alternatively, activated liquid molecules within the liquid itself, generated when the fluid pressure drops below its saturated vapor pressure due to high-intensity focused ultrasound, can assemble, forming vaporous bubbles.

[0032] The phenomenon in which the bubbles created in this way vibrate in sync with the focused ultrasound is called "stable cavitation." In addition, the phenomenon in which the bubbles collapse is called "inertial cavitation." Stable cavitation creates a fluid flow (acoustic stream) around the bubble, which generates shear force against the vessel wall and creates a gap. In inertial cavitation, when the bubble collapses, the fluid creates a microjet, and the microjet creates microholes. The phenomenon in which microholes are created in cells and tissues due to this cavitation phenomenon is called sonoporation. Cavitation refers to the process in which small bubbles are formed due to the action of negative and positive pressure caused by pressure changes within the tissue when focused ultrasound reaches the tissue, and these bubbles grow to their maximum size and then burst repeatedly, destroying the cells within the tissue. Cavitation can cause shocks when bubbles vibrate (stable cavitation) or collapse (inertial cavitation).

[0033] Hereinafter, the configuration of a focused ultrasonic processing device (1) having the above-described characteristics will be described with reference to FIG. 1.

[0034] Referring to FIG. 1, a focused ultrasound treatment device (1) includes a processor (100), a focused ultrasound pulse generator (101), a diagnostic ultrasound pulse generator (102), an ultrasound treatment head (103), an image generation unit (107), a mechanical driving unit (108), a positioning arm unit (109), an input unit (110), a display unit (111), a storage unit (112), and a cavitation sensor (113). The ultrasound treatment head (103) may include a focused ultrasound transducer (104), an image transducer (105), and a beam steering unit (106).

[0035] The focused ultrasonic pulse generator (101) generates a pulse-shaped driving signal having a pulse repetition frequency (PRF, hereinafter referred to as 'PRF') and a duty cycle, and transmits the signal to the focused ultrasonic transducer (104).

[0036] The focused ultrasound transducer (104) converts the electrical waveform, which is a driving signal received from the focused ultrasound pulse generator (101), into focused ultrasound and outputs the converted focused ultrasound to the tissue. At this time, the focused ultrasound may have an intensity of 1.0 to 3.0 kW / cm2, a frequency of 0.5 to 3.0 MHz, and a duty cycle of 10% or less. The duty cycle is a numerical value that represents the ratio of the time that the signal is on in one period of the signal, expressed as a percentage.

[0037] The focused ultrasound transducer (104) may have a focused ultrasound radiation surface. The focused ultrasound transducer (104) generates focused ultrasound and focuses it on a treatment area. The focused ultrasound transducer (104) may have a multi-channel array structure composed of a plurality of units. In this case, the multi-channel array structure may be an annular array in which a plurality of treatment transducers are in an annular shape, or a random array in which the treatment transducers are arranged in a random shape.

[0038] The image transducer (105) outputs an image ultrasound signal into the tissue in response to a short pulse electrical signal, which is a driving signal received from the diagnostic ultrasound pulse generator (102), and receives an ultrasound echo signal reflected from the tissue. The image transducer (105) receives the ultrasound echo signal until the next pulse is generated and transmits it to the processor (100).

[0039] The image transducer (105) may be configured by having a piezoelectric element or the like built into a cylindrical casing. The image transducer (105) may be a phased array imaging transducer.

[0040] The ultrasound treatment head (103) may have a structure in which an image transducer (105) is positioned at the center and focused ultrasound transducers (104) are arranged at the periphery. However, the structures of the image transducer (105) and the focused ultrasound transducer (104) are not limited to this and can be modified in various ways.

[0041] A focused ultrasound treatment device (1) according to one embodiment can perform drug delivery using focused ultrasound of a focused ultrasound transducer (104) and simultaneously obtain a diagnostic image using image ultrasound of an image transducer (105).

[0042] The beam steering unit (106) performs transmission beam focusing or reception beam focusing of ultrasonic waves through mechanical and / or electronic beam steering. At this time, the beam steering unit (106) can vary the ultrasonic focusing area by steering the beam direction. The beam steering unit (106) can perform hybrid beam steering that combines mechanical steering and electronic steering. The beam steering unit (106) can utilize a multi-channel array structure of focused ultrasonic transducers (104) for mechanical and / or electronic beam steering. An example of beam steering of the beam steering unit (106) will be described below with reference to FIG. 5.

[0043] The image generation unit (107) processes the ultrasonic echo signal received from the image transducer (105) 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 (111). For signal processing, the image generation unit (107) may include a low noise amplifier (LNA) and an analog to digital converter (ADC).

[0044] The mechanical driving unit (108) drives the beam steering unit (106) so that the beam steering unit (106) can mechanically steer the focused ultrasound transducer (104) and the image transducer (105).

[0045] The positioning arm (109) can move the ultrasound treatment head (103) including the focused ultrasound transducer (104) and the image transducer (105) so that the ultrasound treatment head (103) is accurately and stably positioned on the target. For this purpose, the positioning arm (109) can include a mechanism for tilting and rotating. The positioning arm (109) can individually tilt or rotate the focused ultrasound transducer (104) or the image transducer (105), and can tilt or rotate the ultrasound treatment head (103) including the focused ultrasound transducer (104) and the image transducer (105). For this purpose, the positioning arm (109) can have three or more degrees of freedom.

[0046] The input unit (110) receives a user operation signal. For this purpose, the input unit (110) may include a user interface. The display unit (111) outputs an ultrasound image. The storage unit (112) stores the received signal and stores information necessary for the operation of the processor (100). The storage unit (112) stores information necessary for signal analysis of the processor (100) or stores information analyzed by the processor (100).

[0047] The processor (100) determines treatment parameters for the mechanical effect of focused ultrasound and controls the focused ultrasound transducer (104) to transmit focused ultrasound with the determined treatment parameters to the tissue. At this time, the mechanical effect of the transmitted focused ultrasound is utilized to generate cavitation in the tissue without microbubbles, and the generated cavitation temporarily creates microholes. Subsequently, the injected drug is delivered to the tissue through the generated microholes.

[0048] The cavitation sensor (113) detects a cavitation signal generated by a cavitation phenomenon in the tissue using focused ultrasound. The cavitation signal is used to confirm the mechanical effect of the focused ultrasound for generating cavitation in the tissue without microbubbles. The processor (100) can analyze the cavitation signal detected through the cavitation sensor (113) to confirm the mechanical effect of the focused ultrasound. At this time, the processor (110) can determine whether a stable cavitation signal and an inertial cavitation signal are detected from the detected cavitation signal, and if two cavitation signals are detected, it can be determined that a mechanical effect has occurred. An example of cavitation signal analysis will be described below with reference to FIG. 4.

[0049] The processor (100) can adjust the parameters of the focused ultrasound according to the results of the cavitation signal analysis. For example, the processor (100) can compare the cavitation detection value with a predetermined cavitation threshold value, and if the cavitation detection value is higher than the predetermined cavitation threshold value, the processor (100) can adjust the parameters of the focused ultrasound so that the cavitation detection value is lowered. In addition, the processor (100) can compare the cavitation detection value with a predetermined cavitation threshold value, and if the cavitation detection value is lower than the predetermined cavitation threshold value, the processor can adjust the parameters of the focused ultrasound so that the cavitation detection value is higher than the cavitation threshold value. The setting values ​​of the cavitation limit value and the cavitation threshold value can be set according to the type of biological tissue and the characteristics of the focused ultrasound, and can also be set by receiving a user operation signal.

[0050] The processor (100) can determine the parameters of the focused ultrasound so that the focused ultrasound does not generate a shock wave scattering effect within the biological tissue. The shock wave scattering effect occurs due to the interaction between the bubble and the focused ultrasound. In this case, the shock is generated at a point other than the focal point, causing damage to the biological tissue area that is not desired to be removed. Therefore, the processor (100) can determine the parameters of the focused ultrasound so that this shock wave scattering effect does not occur.

[0051] Parameters of focused ultrasound may include acoustic pressure, waveform, output time, frequency, duty cycle, etc. The intensity and pressure of the focused ultrasound can be controlled by adjusting the focused ultrasound parameters.

[0052] The processor (100) can determine focused ultrasound parameters to maximize the mechanical effect of the focused ultrasound. For example, the processor (100) controls the focused ultrasound to output a focused ultrasound having a predetermined first frequency through the focused ultrasound transducer (104), and compares a cavitation detection value with a predetermined cavitation threshold value. Then, if the cavitation detection value is higher than the cavitation threshold value, the processor (100) adjusts the frequency of the focused ultrasound from the first frequency to a second frequency. Then, the processor (100) can control the focused ultrasound to output the adjusted second frequency through the focused ultrasound transducer (104).

[0053] The processor (100) can confirm the mechanical effect of the focused ultrasound by analyzing the ultrasonic image generated by the image generating unit (107). For example, the processor (100) confirms the image brightness value of the focus area within the first frequency range of the first cycle by analyzing the image signal during the first cycle. At this time, it is confirmed whether the image brightness value of the focus area is within a predetermined cavitation image brightness range. At this time, the processor (100) can determine that the mechanical effect has occurred if the image brightness value is within a predetermined image brightness range. Furthermore, the processor (100) can also adjust the parameters of the focused ultrasound according to the results of the ultrasonic image signal analysis.

[0054] FIG. 2 is a diagram illustrating a flow of a drug delivery method according to one embodiment of the present invention.

[0055] Referring to Figures 1 and 2, first, a drug is injected into the body through blood vessels, etc. of the human body. A syringe, etc. may be used as a method for injecting the drug.

[0056] The focused ultrasound treatment device (1) determines treatment parameters for the mechanical effect of focused ultrasound (210). The focused ultrasound may have an intensity of 1.0 to 3.0 kW / cm2, a frequency of 0.5 to 3.0 MHz, and a duty cycle of 10% or less.

[0057] Next, the focused ultrasound treatment device (1) transmits focused ultrasound with determined treatment parameters to the tissue through the focused ultrasound transducer (220).

[0058] Next, the focused ultrasound treatment device (1) uses the mechanical effect of the transmitted focused ultrasound to generate cavitation in the tissue without microbubbles (230).

[0059] Next, the focused ultrasonic treatment device (1) temporarily creates micro-holes in the tissue through the generated cavitation (240).

[0060] Next, the focused ultrasound treatment device (1) delivers the pre-injected drug to the tissue through the created micro-holes (250).

[0061] Furthermore, the focused ultrasound treatment device (1) can detect a cavitation signal caused by a cavitation phenomenon occurring in a tissue by the transmitted focused ultrasound through a cavitation sensor (113), and analyze the detected cavitation signal to confirm the mechanical effect of the focused ultrasound. For example, the focused ultrasound treatment device (1) can determine whether a stable cavitation signal and an inertial cavitation signal are detected from the detected cavitation signal, and if two cavitation signals are detected, it can be determined that a mechanical effect has occurred.

[0062] A focused ultrasound treatment device (1) can adjust the treatment parameters of focused ultrasound according to the results of cavitation signal analysis, and transmit focused ultrasound with the adjusted treatment parameters to the tissue through a focused ultrasound transducer.

[0063] A focused ultrasound processing device (1) can steer the direction of a beam of focused ultrasound to be transmitted. At this time, the focused ultrasound processing device (1) can perform at least one of mechanical beam steering and electrical beam steering through a multi-channel array.

[0064] The focused ultrasound treatment device (1) can control the position of the ultrasound treatment head (103) through a positioning arm having three or more degrees of freedom.

[0065] The focused ultrasound processing device (1) can analyze the ultrasound image generated through the image generating unit (107) to confirm the mechanical effect of the focused ultrasound.

[0066] FIG. 3 is a drawing illustrating sonoporation using cavitation according to one embodiment of the present invention.

[0067] Referring to FIGS. 1 and 3, sonoporation occurs, in which micro-holes are created in cells and tissues, due to the capillary phenomenon. For example, as illustrated in FIG. 3, when focused ultrasound (310) is transmitted through a focused ultrasound transducer, cavitation occurs, in which bubbles (330) are formed in the tissue without microbubbles, due to the mechanical effect of the transmitted focused ultrasound (310). Subsequently, micro-holes (340) are temporarily created in the tissue due to the cavitation. Subsequently, a drug (320) previously injected into the body passes through the blood vessels and is delivered to the tissue through the micro-holes (340).

[0068] FIG. 4 is a diagram illustrating a cavitation signal according to one embodiment of the present invention.

[0069] More specifically, (a) shows a cavitation signal obtained from a low intensity excitation at a frequency of 1.1 MHz, and (b) shows a cavitation signal obtained from a high intensity excitation at a frequency of 1.1 MHz.

[0070] Referring to FIGS. 1 and 4, the mechanical effect of focused ultrasound can be confirmed through the cavitation signal.

[0071] Stable cavitation is associated with harmonic signals: Hamonics (nf0), Sub-Harmonics (1 / 2f0), and Ultra-Harmonics ((2n+1) / 2f0), while inertial cavitation occurs in the form of broadband noise. f0 is the fundamental frequency.

[0072] Inertial cavitation occurs alongside stable cavitation signals, as stable cavitation evolves into inertial cavitation. Because each bubble in a bubble cluster grows at a different rate, stable cavitation always occurs alongside inertial cavitation.

[0073] FIG. 5 is a diagram illustrating an example of beam steering of a focused ultrasonic transducer according to one embodiment of the present invention.

[0074] In more detail, (a) is a drawing illustrating a focused ultrasound transducer having a multi-channel array structure, (b) is a drawing illustrating a mechanical beam steering appearance of the focused ultrasound transducer, (c) is a drawing illustrating an electrical beam steering appearance of the focused ultrasound transducer, and (d) is a drawing illustrating a hybrid beam steering appearance combining mechanical beam steering and electrical beam steering of the focused ultrasound transducer.

[0075] Referring to FIGS. 1 and 5, the focused ultrasound transducer (104) may be a multi-channel array structure composed of a plurality of units. At this time, the multi-channel array structure may be an annular array in the form of a plurality of treatment transducers in an annular shape, or a random array in which the treatment transducers are arranged in a random shape.

[0076] The focused ultrasound transducer (104) can perform at least one of mechanical beam steering and electrical beam steering through a multi-channel array. For example, as illustrated in (b), mechanical beam steering of the focused ultrasound transducer (104) can be performed. As another example, as illustrated in (c), electrical beam steering of the focused ultrasound transducer (104) can be performed. As yet another example, as illustrated in (d), hybrid beam steering that combines mechanical beam steering and electrical beam steering of the focused ultrasound transducer (104) can be performed.

[0077] The present invention has been described above, focusing on specific embodiments thereof. Those skilled in the art will appreciate that variations and modifications can be made without departing from the essential characteristics of the invention. Therefore, the disclosed embodiments should be considered illustrative rather than limiting. The scope of the present invention is set forth in the claims, not the foregoing description, and all differences within the scope equivalent thereto should be construed as being encompassed by the present invention.

Claims

1. In a drug delivery method using a focused ultrasound treatment device, Step of determining treatment parameters for the mechanical effect of focused ultrasound; A step of transmitting focused ultrasound with the above-determined treatment parameters to a tissue through a focused ultrasound transducer; A step of generating cavitation in tissue without microbubbles by utilizing the mechanical effect of the transmitted focused ultrasound; A step of temporarily creating micro holes in the tissue through the above-mentioned generated cavitation; and A step in which the injected drug is delivered to the tissue through the micro-holes created above; A drug delivery method comprising:

2. In paragraph 1, the step of determining the treatment parameters is A drug delivery method characterized by determining the intensity of focused ultrasound to be 1.0 to 3.0 kW / cm2.

3. In paragraph 1, the step of determining the treatment parameters is A drug delivery method characterized by determining the frequency of focused ultrasound to be 0.5 to 3.0 MHz.

4. In paragraph 1, the step of determining the treatment parameters is A drug delivery method characterized in that the duty cycle of focused ultrasound is determined to be 10% or less.

5. In paragraph 1, the step of generating cavitation is A drug delivery method characterized by generating stable cavitation in which bubbles vibrate and inertial cavitation in which bubbles collapse by synchronizing focused ultrasound with bubbles generated by focused ultrasound.

6. In paragraph 1, the drug delivery method is A step of detecting a cavitation signal caused by a cavitation phenomenon occurring in a tissue by transmitted focused ultrasound through a cavitation sensor; and A step of analyzing the above-detected cavitation signal to confirm the mechanical effect of the focused ultrasound; A drug delivery method characterized by further comprising:

7. In paragraph 6, the step of confirming the mechanical effect of focused ultrasound A drug delivery method characterized in that it is determined that a mechanical effect has occurred by checking whether a stable cavitation signal and an inertial cavitation signal are detected from a detected cavitation signal and, if two cavitation signals are detected, 8. In paragraph 6, the drug delivery method is A step of adjusting the treatment parameters of focused ultrasound according to the results of cavitation signal analysis; and A step of transmitting focused ultrasound with the above-described adjusted treatment parameters to a tissue through a focused ultrasound transducer; A drug delivery method characterized by further comprising:

9. In paragraph 1, the drug delivery method is A step of steering the direction of a beam of focused ultrasound to be transmitted; A drug delivery method characterized by further comprising:

10. In the 9th paragraph, the step of steering the direction of the beam A drug delivery method characterized by performing at least one of mechanical beam steering and electrical beam steering through a multichannel array.

11. In paragraph 1, the drug delivery method is A step of controlling the position of the ultrasonic treatment head through the positioning arm; A drug delivery method characterized by further comprising:

12. In paragraph 1, the drug delivery method is A step of outputting an image ultrasound signal to a tissue through an image transducer and receiving an ultrasound echo signal reflected from the tissue; A step of generating an ultrasonic image signal by signal processing a received ultrasonic echo signal; and A step of analyzing the generated ultrasonic image signal to confirm the mechanical effect of focused ultrasound; A drug delivery method characterized by further comprising:

13. A focused ultrasound transducer that transmits focused ultrasound to the tissue; and A processor for determining treatment parameters for a mechanical effect of focused ultrasound, transmitting focused ultrasound with the determined treatment parameters to a tissue through the focused ultrasound transducer, generating cavitation in the tissue without microbubbles by utilizing the mechanical effect of the transmitted focused ultrasound, and temporarily generating microholes through the generated cavitation, such that an injected drug is delivered to the tissue through the generated microholes; A focused ultrasonic processing device characterized by including a .

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