Ultrasonic treatment device for cardiac disease

Abstract

To provide an ultrasonic treatment device for a cardiac disease, capable of irradiating the whole heart with an ultrasonic wave.SOLUTION: An ultrasonic treatment device includes: at least two ultrasonic transducers that transmit and receive an ultrasonic wave; and a holding part that controls irradiation of an ultrasonic beam from the at least two ultrasonic transducers and holds the ultrasonic transducers. At least two ultrasonic transducers perform irradiation of the ultrasonic beam such that the whole heart is irradiated with the ultrasonic wave of the irradiation.SELECTED DRAWING: Figure 4

Description

Technical Field

[0001] The present invention relates to an ultrasonic treatment device for heart diseases.

Background Art

[0002] With the aging of society, the prevalence of diseases in the cardiovascular field, especially heart diseases such as angina pectoris, heart failure, and arrhythmia, continues to increase.

[0003] A global rapid increase in the number of heart failure patients, called the "heart failure pandemic," has become a serious problem in the cardiovascular field. The number of elderly heart failure patients (estimated number of new-onset heart failure cases in the population aged 65 and over in Japan) in 2015 was reported to be 290,000 (Non-Patent Document 1). In particular, heart failure with preserved ejection fraction (HFpEF), which mainly affects the elderly and is caused by a decrease in diastolic function while maintaining systolic function, has become a problem. In an epidemiological study conducted by the present inventors, currently, more than 50% of chronic heart failure patients are HFpEF patients (Non-Patent Document 2). HFpEF patients are prone to acute exacerbation of heart failure even under mild stress, repeatedly undergo hospitalization and discharge several times a year, have a reduced quality of life, a poor prognosis, and are a cause of increased medical costs. Although effective drug treatments have been developed for heart failure with reduced ejection fraction (HFrEF), there is no effective treatment for HFpEF, and thus the development of a safe and effective treatment for HFpEF is eagerly awaited.

[0004] In addition, the number of patients with angina pectoris (excluding hypertensive ischemic heart disease) in Japan is said to be 720,000 per year (from the number of ischemic heart disease patients in the 2018 White Paper on Health, Labour and Welfare). Existing treatments such as drug therapy for temporary symptom improvement such as nitroglycerin, and revascularization aimed at radical cure by percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) exist. However, about 40% of severe angina patients still have chest symptoms after PCI or CABG, and they continue to require continuous drug therapy, with a poor quality of life and a prognosis of 2 to 5 years. There are virtually no treatment options for severe angina patients who have not improved with radical treatment by revascularization, and the unmet needs are great.

[0005] Furthermore, pulmonary arterial hypertension (PAH) affects only 2,587 patients (in 2013, the Center for Rare Diseases Information). However, it is a refractory disease (designated intractable disease 86) in which the vascular endothelium and vascular smooth muscle of the pulmonary artery wall grow abnormally and disorderly, narrowing the pulmonary artery lumen to complete occlusion, increasing pulmonary vascular resistance, raising pulmonary artery pressure, and ultimately causing right heart failure due to chronic pressure load, leading to the death of the patient (5-year survival rate: approximately 50%). PAH is classified into (1) idiopathic PAH, (2) hereditary PAH, (3) drug-induced PAH, (4) PAH associated with collagen disease, (5) PAH associated with HIV infection, (6) PAH associated with portal hypertension, (7) PAH associated with congenital heart disease, and (8) PAH associated with schistosomiasis. In all cases, the cause of onset has not been elucidated, and it has been designated as an "intractable disease". As treatments, three types of drugs that dilate the pulmonary artery and suppress growth (prostaglandin I2 preparations, endothelin receptor antagonists, and phosphodiesterase 5 inhibitors that enhance the action of nitric oxide NO) have been approved, but their effectiveness is not sufficient, and as a refractory disease with a poor prognosis, the development of new treatment methods is awaited.

[0006] In 1917, P. Langevin invented the world's first practical ultrasonic transducer, and since then, ultrasonic waves have been used in both medical diagnosis and treatment (Non-Patent Document 3).

[0007] In ultrasonic medical diagnosis, an ultrasonic transducer that transmits and receives ultrasonic waves is closely attached to the body surface, and ultrasonic waves reflected by an internal object such as an organ are received. The distance to the object is calculated from the time it takes for the reflected wave to reach the ultrasonic transducer, and the object is imaged using this principle.

[0008] As the first successful examples of the clinical application of ultrasonic diagnosis, the detection of brain tumors by H.T. Ballantine in 1950 (Non-Patent Document 4) and the detection of gallstones by G.D. Ludwig (Non-Patent Document 5) can be cited. In the 1950s, imaging of the breast, breast cancer, heart, blood vessels, tomography of the heart and eyes, and blood flow measurement by ultrasonic Doppler were reported. In the 1960s, D.W. Baker proposed the pulsed Doppler method (Non-Patent Document 6) to replace the classical continuous wave Doppler method, and the era of the practical application of ultrasonic diagnosis began in earnest. In the 1970s, research on scanning methods and the like was conducted to achieve more accurate imaging. Since the 1980s, benefiting from digital signal processing, ultrasonic diagnostic technology has continued to develop by leaps and bounds.

[0009] In ultrasonic therapy, a method of irradiating strong ultrasonic waves from outside the body and concentrating energy on a target site inside the body to remove blood clots, crush stones, and destroy cancerous tissues is the mainstream, and many reports have also been made on the pain relief effect.

[0010] In 1939, R. Pohlman et al. fabricated an ultrasonic therapy device and reported its effect of reducing sciatica pain (Non-Patent Document 7). Subsequently, reports continued on tissue destruction by focused ultrasonic waves by L.G. Lynn et al. in 1942 (Non-Patent Document 8), the effect of ultrasonic irradiation on diseased parts such as arthritis, post-traumatic sequelae, and neuralgia and the analgesic and motor function recovery effects by Okada et al. in 1952 (Non-Patent Document 9), and the effectiveness of stone crushing by focused ultrasonic waves by W.D. Mulvancy in 1953 (Non-Patent Document 10).

[0011] In the latter half of the 1980s, studies began on new clinical applications of ultrasound, such as hyperthermia treatment for cancer using focused ultrasound and enhancement of drug effects using low-intensity ultrasound. Among these, the development of treatment technology using high-intensity focused ultrasound (HIFU) has been active in recent years because it does not require an incision, causes no tissue invasion like surgery, and places little physical burden on the body.

[0012] Low-intensity pulsed ultrasound (LIPUS) technology was also commercialized by Teijin Pharma as the SAFES (registered trademark) exogen (registered trademark) for ultrasonic fracture treatment devices in the latter half of the 1990s and has become widespread as a treatment technology that can shorten the fracture healing period of the forearm bone, upper arm bone, thigh bone, lower leg bone, and collarbone by approximately 40%. This treatment device irradiates a fracture site of about the same diameter with a flat vibrator of about 30 mm in diameter. Since it is for the treatment of bones relatively close to the surface such as the feet and hands, it is a treatment device specialized for fractures at a limited site at the targeted position. Since the mechanism of action is said to be "promotion of bone healing by physical stimulation," the expansion of indications has not progressed.

[0013] In 2000, based on Mariotto's presentation at a conference (Non-Patent Document 11) stating that the expression of endothelial nitric oxide synthase is enhanced by irradiating human cultured umbilical vein endothelial cells (HUVECs) with shock waves, the inventors of the present invention began working on an approach to activate the self-healing ability using shock waves. In 2004, they discovered that when low-energy shock waves were irradiated onto cultured human umbilical vein endothelial cells (HUVECs), the expression of vascular endothelial growth factor (VEGF) was enhanced (Non-Patent Document 12). Subsequently, the inventors found that enhanced expression of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) induces angiogenesis and anti-inflammatory effects. In 2006, they started developing a low-output extracorporeal shock wave therapy device dedicated to treating heart diseases and advanced the co-development with Storz of Switzerland, contributing to the treatment of angina pectoris. However, the shock wave therapy device applied to the heart had the problems of (1) somewhat complicated alignment of irradiation (risk of lung injury) and (2) long treatment time (heartbeat synchronization). To solve these problems, a treatment device using low-output pulsed wave ultrasound was developed, which has the advantages of (1) easy alignment of irradiation (no injury to the lungs) and (2) shortening of the treatment time.

[0014] In 2010, in basic research using human cultured umbilical vein endothelial cells (HUVECs), the inventors irradiated standing waves of ultrasonic waves, but found that the expression of VEGF was not enhanced. Then, with the idea of irradiating ultrasonic waves in chunks like shock waves, they irradiated HUVECs with chunks of different wave numbers such as 1 wave, 16 waves, 32 waves, 48 waves, and 64 waves of the transmitted wave frequency of ultrasonic waves and compared the VEGF expression levels. As a result, they found that LIPUS irradiation with a chunk of 32 waves particularly enhanced the expression of VEGF (Non-Patent Document 13).

[0015] The inventors of the present invention clarified that the expression mechanism of eNOS and VEGF brought about by LIPUS is a mechanotransduction mechanism via physical stimulation of caveolin-1 (Figure 1, Non-Patent Document 14), indicating the possibility of expanding the indications of LIPUS beyond fracture treatment.

[0016] First, the inventors considered angina pectoris (ischemic heart disease), a heart disease, as a new application expansion of LIPUS.

[0017] As past attempts to treat the heart by ultrasonic irradiation, there are: a method of administering a drug to a local target area such as myocardium and enhancing the absorption of substances into cells by vibrational energy from ultrasonic irradiation (Patent Document 1); in HIFU treatment, a treatment device equipped with a movement tracking method synchronized with the heartbeat of the heart (Patent Document 2); an ultrasonic treatment device equipped with an ultrasonic transducer for image acquisition at the innermost of an annular array oscillator and irradiating focused ultrasonic waves for treatment from the annular array ultrasonic transducer while confirming the treatment position in real time with a tomographic image (Patent Document 3); an ultrasonic device for sonic thrombolysis treatment capable of both ultrasonic imaging and cardiac sonic thrombolysis treatment (Patent Document 4).

[0018] In a non-clinical trial using myocardial infarction model mice, when the inventors compared the microvessel density, the expressions of VEGF and eNOS between the LIPUS irradiation group and the control group, it was confirmed that in the LIPUS irradiation group, all of them were significantly increased or enhanced compared to the control group, and the cardiac function indexes such as LVEF were also significantly improved (Non-Patent Document 15).

[0019] Next, in a non-clinical trial using pigs with a chronic myocardial ischemia model, when the inventors compared the density of microvessels, the expressions of VEGF and eNOS between the LIPUS irradiation group and the control group, it was shown that in the LIPUS irradiation group, all of them were significantly increased or enhanced compared to the control group, and the cardiac function indexes such as LVEF were also significantly improved. Also, when comparing the ischemic site and the non-ischemic site, it was found that in the ischemic site (pathological tissue), the density of microvessels, the expressions of VEGF and eNOS were enhanced, but there was no change in the non-ischemic site (normal tissue), indicating that LIPUS acts specifically on the pathological condition (ischemic site) (Non-Patent Documents 16, Patent Documents 5, 6).

[0020] The inventors also examined the expansion of the indication to heart failure with preserved ejection fraction (HFpEF). In a non-clinical trial using an HFpEF mouse model, improvement in diastolic function was observed in terms of echocardiogram, pressure-volume curve, and pressure measurement. Therapeutic effects were confirmed in terms of myocardial cross-sectional area, interstitial fibrosis, treadmill running distance (exercise tolerance), and blood BNP level. It was shown that the mechanism underlying the improvement in myocardial diastolic function and fibrosis of the left ventricle was due to the activation of the NO-sGC-cGMP-PKG pathway (Figure 2, Non-Patent Document 17).

[0021] The inventors also examined the expansion of the indication to pulmonary arterial hypertension (PAH). In a non-clinical trial using a right heart failure model animal (pulmonary artery banding (PAB) mouse model), the eNOS-NO-sGC-cGMP-PKG pathway was activated by LIPUS treatment (Figure 3), and a significant improvement in right ventricular function was observed in the LIPUS treatment group by echocardiogram (Non-Patent Document 18).

Prior Art Documents

Patent Documents

[0022]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Patent Document 5

Patent Document 6

Non-Patent Documents

[0023]

Non-Patent Document 1

Non-Patent Document 2

Non-Patent Document 3

Non-Patent Document 4

Non-Patent Document 5

Non-Patent Document 6

Non-Patent Document 7

Non-Patent Document 8

Non-Patent Document 9

Non-Patent Document 10

Non-Patent Document 11

Non-Patent Document 12

Non-Patent Document 13

Non-Patent Document 14

Non-Patent Document 15

Non-Patent Document 16

Non-Patent Document 17

Non-Patent Document 18

Summary of the Invention

Problems to be Solved by the Invention

[0024] The inventors of the present invention have found that the irradiation region of the LIPUS irradiation device using the element arrays (such as convex type and sector type) of the conventional ultrasonic treatment device and the ultrasonic transducers described in Patent Documents 1 and 2 above is limited to the tomographic plane scanned by the focused ultrasonic beam. In cases where multi-branch lesions spread throughout the coronary arteries, such as severe angina pectoris, cases of left ventricular diastolic dysfunction such as HFpEF, and cases accompanied by right heart failure such as PAH, regions where ultrasonic waves are not irradiated are likely to occur, and it may be difficult to obtain a sufficient therapeutic effect. In this case, although it is possible to increase the irradiation region by increasing the tomographic planes to be irradiated with ultrasonic waves, there is a problem that the treatment time becomes longer and the burden on the patient and the operator increases due to the increase in the tomographic planes.

[0025] The present invention has been made in view of the above problems, and an object thereof is to provide an ultrasonic treatment device capable of irradiating the entire heart with LIPUS, which is used for the treatment of heart diseases such as HFpEF, PAH, and angina pectoris.

Means for Solving the Problems

[0026] As a result of intensive studies to solve the above problems, the inventors of the present invention have found that by using at least two ultrasonic transducers capable of irradiating a non-focused ultrasonic beam (diffused beam), one ultrasonic transducer irradiates the ultrasonic beam from a parasternal approach, and another ultrasonic transducer irradiates the ultrasonic beam from an apical approach through the intercostal space, it is possible to irradiate the entire heart with LIPUS and perform the treatment of various heart diseases such as HFpEF.

[0027] The present invention is based on such new findings, and relates to an ultrasonic treatment device used in the above treatment method, and includes the following inventions. [1] An ultrasonic treatment device for treating heart diseases, comprising: at least two ultrasonic transducers for irradiating a non-focused ultrasonic beam to the heart; a transmission unit for controlling the irradiation of the non-focused ultrasonic beam from the at least two ultrasonic transducers; A holder for holding the at least two ultrasonic transducers at a predetermined position, comprising, The transmission unit controls the ultrasonic transducer so as to sequentially irradiate the non-focused ultrasonic waves, The holder can detachably hold the at least two ultrasonic transducers, and holds one of the at least two ultrasonic transducers at a position where a non-focused ultrasonic beam including a long-axis cross-sectional view of the left margin of the sternum by a parasternal approach can be irradiated to the heart, and holds another one of the at least two ultrasonic transducers at a position where a non-focused ultrasonic beam including an apical long-axis tomographic view by an apical approach from between the ribs can be irradiated to the heart. An ultrasonic treatment apparatus. [2] The transmission unit controls the at least two ultrasonic transducers so as to continuously irradiate the non-focused ultrasonic waves for 1 minute to 80 minutes, wherein the transmission frequency (Transmit Frequency) is 0.1 to 3 MHz, the number of cycles is composed of non-consecutive waves of 1 to 64 cycles, and the pulse repetition time (Pulse Repetition Time; PRT) is 0.25 to 2.56 ms. The ultrasonic treatment apparatus of [1]. [3] The ultrasonic treatment apparatus of [2], wherein the transmission frequency of the non-focused ultrasonic wave is 0.5 to 1.875 MHz. [4] The ultrasonic treatment apparatus of [2], wherein the number of cycles of the non-focused ultrasonic wave is 32 cycles. [5] The ultrasonic treatment apparatus of [1], wherein the at least two ultrasonic transducers have a convex-shaped vibrator surface. [6] The ultrasonic treatment apparatus of [1], wherein the at least two ultrasonic transducers have an acoustic lens on the vibrator surface. [7] The ultrasonic treatment apparatus of [1], wherein the at least two ultrasonic transducers can switch between irradiation of a non-focused ultrasonic beam and irradiation of a focused ultrasonic beam. [8] The ultrasonic treatment apparatus of [7], wherein the at least two ultrasonic transducers are provided with a detachable acoustic lens. [9] The ultrasonic treatment device according to [7], wherein the plurality of ultrasonic transducers include vibrating elements arranged in a large number two-dimensionally.

[10] The ultrasonic treatment device according to [7], further comprising an image forming unit that, after the at least two ultrasonic transducers irradiate a focused ultrasonic beam, obtains an ultrasonic reception signal from a treatment region as waveform information by the transmission / reception means, and the image forming unit forms image data for creating B-mode tomographic image data from the waveform information.

[11] The ultrasonic treatment device according to [1], wherein the at least two ultrasonic transducers have a vibrator surface with a size of 8 mm to 20 mm.

Advantages of the Invention

[0028] According to the present invention, a new ultrasonic treatment device capable of irradiating the entire heart with ultrasonic waves is provided. According to the present invention, ultrasonic waves can be irradiated to the entire heart including the ventricles and atria, and efficient treatment can be performed even in cases where multiple branch lesions spread throughout the heart. Further, according to the present invention, irradiation with ultrasonic waves can promote the production of endothelial nitric oxide synthase (eNOS) and the enhancement of vascular endothelial growth factor (VEGF), promote an increase in blood flow in myocardial tissue and angiogenesis, and enhance the therapeutic effect on ischemic tissue.

Brief Description of the Drawings

[0029]

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DETAILED DESCRIPTION OF THE INVENTION

[0030] Hereinafter, the present invention will be described with reference to the drawings. In the present invention, the "ultrasonic treatment apparatus" means a treatment apparatus that irradiates "LIPUS".

[0031] The ultrasonic treatment device of the present invention is a device for treating heart diseases, and at least two ultrasonic transducers that irradiate the heart with non-focused ultrasonic beams (diffused beams), a transmission unit that controls the irradiation of the ultrasonic beams from the ultrasonic transducers, a holder that holds the at least two ultrasonic transducers at predetermined positions, and are provided, characterized in that the plurality of ultrasonic transducers sequentially irradiate ultrasonic beams so that the irradiated ultrasonic waves irradiate the entire heart.

[0032] The ultrasonic treatment device of the present invention is suitable for the treatment of heart diseases including ischemic heart diseases such as angina pectoris, myocardial infarction, and microvascular angina (MVA), heart failure such as heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF), cardiomyopathies such as hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), pulmonary arterial hypertension (PAH), pressure load heart diseases such as hypertensive heart disease, and secondary cardiomyopathies such as cardiac amyloidosis and Fabry disease.

[0033] Fig. 4 shows a schematic diagram of the overall configuration of a typical embodiment of the ultrasonic treatment device of the present invention. The ultrasonic treatment device 2 of the present invention includes two ultrasonic transducers 1 capable of irradiating non-focused ultrasonic beams (diffused beams). The ultrasonic transducer includes one vibrating element that irradiates ultrasonic waves or a vibrator in which a plurality of vibrating elements are arranged, and a convex scanning type, a sector scanning type, a linear scanning type, a two-dimensional array type arranged in a matrix, etc. can be appropriately used.

[0034] The ultrasonic transducer 1 receives a transmission signal for irradiating ultrasonic waves from the transmission unit 3, converts it into ultrasonic waves by the ultrasonic transducer 1, and irradiates a non-focused ultrasonic beam (diffused beam) from the vibrator surface to the entire region of the heart. The ultrasonic transducer 1 is held at a predetermined position using a holder (not shown). One irradiates the entire heart with a non-focused ultrasonic beam in the long-axis cross-sectional direction of the left sternal border from the third or fourth intercostal space of the left sternal border or the vicinity thereof (parasternal approach). Another irradiates the entire heart with ultrasonic waves with a non-focused ultrasonic beam in the long-axis tomographic plane direction of the apex from the intercostal space (apex) where the apical beat is felt below the nipple. Therefore, both ventricles and both atria of the heart are irradiated with ultrasonic waves.

[0035] The transmission unit 3 outputs a transmission signal for the ultrasonic transducer 1 to irradiate ultrasonic waves and controls the ultrasonic transducer 1. The transmission unit 3 generates a transmission signal for irradiating ultrasonic waves based on the transmission frequency, wave number, and PRT of the ultrasonic waves set by the control unit 4.

[0036] The control unit 4 controls the entire ultrasonic treatment device 2. The control unit 4 outputs a transmission control signal for controlling the transmission frequency, wave number, PRT of the ultrasonic waves irradiated from the ultrasonic transducer 1, switching between a plurality of ultrasonic transducers, etc. to the transmission unit 3.

[0037] The operation unit 5 receives an operation from the user, and the received instruction is output to the control unit 4 and reflected in the control within the ultrasonic treatment device 2.

[0038] The transmission unit 3 is realized by hardware such as an FPGA, a processor, and an electric circuit, for example. Also, the operation unit 5 is composed of at least a part of, for example, a touch panel, a keyboard, a trackball, switches, etc. The control unit 4 is composed of hardware such as a microprocessor and a personal computer, and the function of the control unit 4 is realized by the cooperation of the hardware and software (program) that defines its operation.

[0039] Fig. 5 shows a schematic diagram of a typical embodiment of an ultrasonic transducer that irradiates a non-focused ultrasonic beam (diffused beam) in the present invention. The ultrasonic transducer 1 is composed of a vibrator (not shown) in which one or a plurality of vibrating elements for irradiating ultrasonic waves are arranged, a cable 10 connected to a transmission unit (not shown), and a vibrator surface protection film 8 that covers the vibrator surface 9 which is the ultrasonic irradiation surface. The vibrator surface 9 has a convex curved surface in order to irradiate a non-focused ultrasonic beam (diffused beam). The convex curved surface can be formed by making the ultrasonic irradiation surface into a convex curved surface shape or arranging a plurality of vibrating elements in a convex curved surface shape. By making the ultrasonic irradiation surface into a convex curved surface shape, a non-focused ultrasonic beam (diffused beam) can be efficiently irradiated. In this specification, the "non-focused ultrasonic beam" or "diffused beam" means an ultrasonic beam that diffuses without focusing on a single point or a single line. In the present invention, as shown in Fig. 7 (image of irradiation by the apical approach), in order to irradiate ultrasonic waves from between the ribs and irradiate the entire heart with ultrasonic waves, it is preferable that the non-focused ultrasonic beam diffuses in an inverse taper shape in which the diameter gradually increases in the radial direction. The angle at which the inclined surface of the non-focused ultrasonic beam having an increasing diameter in the inverse taper shape spreads is preferably 50° to 100°, and more preferably 60° to 90°. Since the vibrator surface 9 irradiates ultrasonic waves from between the ribs, its size is preferably 8 mm to 20 mm at the longest part (diameter if the surface is circular). The vibrator surface protection film 8 is adhered or attached to the vibrator surface 9, and prevents damage to the vibrator surface due to collision with an object around the treatment device, and may be any as long as it does not prevent the irradiation of the non-focused ultrasonic beam from the ultrasonic transducer, and is composed of a thin film made of a material such as resin (Noryl resin, polyacetal, ionomer resin, urethane resin, etc.).

[0040] FIG. 6 shows a schematic diagram of another exemplary embodiment of an ultrasonic transducer that irradiates a non-focused ultrasonic beam (diffused beam) in the present invention. The ultrasonic transducer 1 includes a vibrator (not shown) in which one or a plurality of vibration elements for transmitting and receiving ultrasonic waves are arranged, a cable 10 connected to a transmitter (not shown), and an acoustic lens 11 attached to a vibrator surface 9' which is an ultrasonic irradiation surface. The acoustic lens 11 is provided to diffuse the ultrasonic waves generated from the vibrator and irradiate them as a non-focused ultrasonic beam (diffused beam). The acoustic lens 11 may be made of a material (for example, ABS, Pebax) capable of propagating ultrasonic waves at a speed higher than the speed of sound of the ultrasonic waves generated from the vibrator. Thereby, the ultrasonic beam can be spread over a wide angle without being focused.

[0041] FIG. 8 shows a schematic diagram of the overall configuration of another exemplary embodiment of the ultrasonic treatment apparatus of the present invention. The ultrasonic treatment apparatus 22 of the present invention includes two or a plurality of ultrasonic transducers 21. The ultrasonic transducer 21 is a sector scanning type array probe capable of irradiating a non-focused ultrasonic beam (diffused beam), and may include an acoustic lens adapter which is a detachable acoustic lens.

[0042] The ultrasonic treatment apparatus 22 has an ultrasonic treatment function and an ultrasonic diagnostic function, and the ultrasonic transducer 21 can transmit and receive diagnostic ultrasonic waves and therapeutic ultrasonic waves. The ultrasonic transducer 21 may include a vibrator capable of transmitting and receiving both diagnostic ultrasonic waves and therapeutic ultrasonic waves, or may separately include vibrators for transmitting and receiving each of them.

[0043] The ultrasonic transducer 21 is held in a predetermined position using a holder (not shown), receives an electrical signal for irradiating ultrasonic waves from the transmitting and receiving unit 23, converts it into ultrasonic waves with a vibrator, and irradiates a non-focused ultrasonic beam (diffused beam), which is therapeutic ultrasonic waves, from the vibrator surface to a treatment area (for example, the heart, etc.) during the treatment mode. On the other hand, during the diagnostic mode, a focused ultrasonic beam, which is diagnostic ultrasonic waves, is irradiated from the vibrator surface to the treatment area (for example, the heart, etc.). The ultrasonic transducer 21 also receives a reflected wave from the treatment area after irradiation, converts it into a received signal with a vibrator, and outputs it to the transmitting and receiving unit 23.

[0044] The transmitting and receiving unit 23 outputs a transmission signal for irradiating an ultrasonic beam to the vibrator included in the ultrasonic transducer 21 to control the ultrasonic transducer 21. The transmitting and receiving unit 23 generates a transmission signal for irradiating an ultrasonic beam based on the transmission frequency, wave number, and PRT of ultrasonic waves during the treatment mode or the diagnostic mode set by the control unit 26. Further, the transmitting and receiving unit 23 obtains a received signal by performing processes such as coherent addition processing on the electrical signal obtained from the vibrator included in the ultrasonic transducer 21, uses it as waveform information, outputs it to the waveform forming unit 24 during the treatment mode, and outputs it to the image forming unit 212 during the diagnostic mode.

[0045] The waveform forming unit 24 generates image data from the waveform information input from the transmitting and receiving unit 23 and outputs it to the display unit 25.

[0046] The image forming unit 212 performs signal processing for creating B-mode tomographic image data from the waveform information input from the transmitting and receiving unit 23, then changes it into image data and outputs it to the display unit 25.

[0047] The display unit 25 displays the received signal of ultrasonic waves based on the image data input from the waveform forming unit 24, and displays a B-mode tomographic image based on the image data input from the image forming unit 28.

[0048] The control unit 26 controls the entire ultrasonic treatment device 22. The control unit 26 outputs a transmission / reception control signal to the transmission / reception unit 23 to control the transmission frequency, frequency, PRT, switching information between a plurality of ultrasonic transducers, transmission / reception switching information, etc. of the ultrasonic waves irradiated from the ultrasonic transducer 21 during the treatment mode or the diagnosis mode. Further, the control unit 26 outputs a waveform display control signal to the waveform forming unit 24, outputs an image display control signal to the image forming unit 212, and further outputs a display control signal to the display unit 25.

[0049] The operation unit 27 receives an operation from the user, and the received instruction is output to the control unit 26 and reflected in the control within the ultrasonic treatment device 22.

[0050] The transmission / reception unit 23, the waveform forming unit 24, and the image forming unit 212 are each realized by hardware such as, for example, an FPGA, a processor, an electric circuit, etc. Further, the display unit 25 is realized by, for example, a liquid crystal display or the like. Also, the operation unit 27 is composed of at least a part of, for example, a touch panel, a keyboard, a trackball, switches, etc. The control unit 26 is composed of hardware such as a microprocessor or a personal computer, and the function of the control unit 26 is realized by the cooperation of the hardware and software (program) that defines its operation.

[0051] FIG. 9 shows a schematic diagram of a typical embodiment of a sector scanning type one-dimensional array type ultrasonic transducer that irradiates an unfocused ultrasonic beam (diffused beam) as the ultrasonic transducer used in the ultrasonic treatment apparatus described in FIG. 8. The ultrasonic transducer 21 is composed of a vibrator (not shown) in which a plurality of vibration elements for transmitting and receiving ultrasonic waves are arranged, a cable 210 connected to a transmitting and receiving unit (not shown), a vibrator surface 29 that is an ultrasonic irradiation surface, and an acoustic lens adapter 211 that is a detachable acoustic lens. In the diagnostic mode (left side of FIG. 9), the acoustic lens adapter 211 is not attached, and the irradiation timing of each vibration element arranged on the vibrator surface 29 is controlled by the transmitting and receiving unit to irradiate a focused ultrasonic beam that is diagnostic ultrasonic waves. On the other hand, in the treatment mode (right side of FIG. 9), the acoustic lens adapter 211 is attached to the vibrator surface 29, and the irradiation timing of each vibration element arranged on the vibrator surface 29 is controlled by the transmitting and receiving unit to irradiate an unfocused ultrasonic beam (diffused beam) that is therapeutic ultrasonic waves.

[0052] FIG. 10 shows a schematic diagram of a typical embodiment of a sector scanning type two-dimensional array type ultrasonic transducer that irradiates an unfocused ultrasonic beam (diffused beam) as the ultrasonic transducer used in the ultrasonic treatment apparatus described in FIG. 8. The ultrasonic transducer 21' is composed of vibration elements 213 arranged two-dimensionally in a large number on a vibrator surface 29', a cable 210' connected to a transmitting and receiving unit (not shown), and the vibrator surface 29' that is an ultrasonic irradiation surface. In the diagnostic mode, the irradiation timing of each vibration element arranged on the vibrator surface is controlled by the transmitting and receiving unit to irradiate a focused ultrasonic beam that is diagnostic ultrasonic waves (not shown). On the other hand, in the treatment mode (right side of FIG. 10), the irradiation timing of each vibration element arranged on the vibrator surface 29' is controlled by the transmitting and receiving unit to irradiate an unfocused ultrasonic beam (diffused beam) that is therapeutic ultrasonic waves.

[0053] FIG. 11 shows a schematic diagram of an example of the arrangement of ultrasonic transducers for irradiating the entire heart with ultrasonic waves in a typical embodiment of a treatment method using the ultrasonic treatment apparatus of the present invention. In the present invention, two ultrasonic transducers are arranged at separate positions to irradiate a non-focused ultrasonic beam (diffused beam), thereby realizing ultrasonic irradiation over a wide range, preferably the entire heart. As illustrated in FIG. 11, one ultrasonic transducer irradiates a non-focused ultrasonic beam (diffused beam) including a long-axis cross-section of the left margin of the sternum by a parasternal approach, and another ultrasonic transducer irradiates a non-focused ultrasonic beam including an apical long-axis tomographic plane by an apical approach from the intercostal space. Thereby, ultrasonic irradiation over a wide range, preferably the entire heart including the ventricles and atria, can be achieved. When using three or more ultrasonic transducers, in addition to the above positions, each ultrasonic transducer can be separately arranged at a plurality of positions selected from the apex, suprasternal notch, left parasternal margin (long axis and short axis), subxiphoid approach, and other approaches well known in the art.

[0054] In the treatment method, an ultrasonic transducer is placed at a predetermined position and a holder for fixing it is used. Fig. 12 shows an example of a typical holder in the ultrasonic treatment device of the present invention. However, the form of the holder only needs to be able to place and fix the ultrasonic transducer at a predetermined position, and is not particularly limited to this form. The holder shown in Fig. 12 is composed of a chest belt and an ultrasonic transducer fixing belt. The chest belt is wound around the patient's chest so that the ultrasonic transducer installation window of the chest belt matches the target fixing position. Next, the ultrasonic transducer is placed in this ultrasonic transducer installation window, and the transducer is fixed with the ultrasonic transducer fixing belt. Similarly, other ultrasonic transducers are also placed and fixed at predetermined positions. In a typical embodiment using the ultrasonic treatment device of the present invention, the ultrasonic transducer installation window of the chest belt is aligned with the left edge of the sternum and the chest belt is wound around the chest (at this time, it is wound so that the belt does not cover the vicinity of the apical approach). Next, the ultrasonic transducer is placed in the ultrasonic transducer installation window, and the ultrasonic transducer is fixed with the ultrasonic transducer fixing belt. Further, using another chest belt, the ultrasonic transducer installation window of it is aligned with the position of the apical approach and wound around the chest. Next, another ultrasonic transducer is placed in the ultrasonic transducer installation window, and the ultrasonic transducer is fixed with the ultrasonic transducer fixing belt. Thereby, two ultrasonic transducers can be respectively placed and fixed by the parasternal approach and the apical approach.

[0055] Also, in the treatment method, in order to efficiently transmit ultrasonic waves and suppress the heat generation of the patient tissue at the contact part with the ultrasonic transducer, a gel (also called echo gel, echo jelly, etc.) may be appropriately applied to the vibrating surface of the ultrasonic transducer and / or the patient part where the ultrasonic transducer is placed.

[0056] In the treatment method using the ultrasonic treatment device of the present invention, the transmission frequency (Frequency) of the non-focused ultrasonic beam can be appropriately set in the range of 0.1 to 3 MHz, preferably 0.5 to 1.875 MHz. By irradiating ultrasonic waves at this frequency range, the tissue at the irradiation site can be effectively vibrated, promoting the enhancement of eNOS expression, angiogenesis, etc., and the effectiveness of the treatment can be obtained.

[0057] Also, in the present invention, the non-focused ultrasonic beam is a non-continuous wave, and the number of cycles can be appropriately set in the range of 1 to 64 cycles. For example, it can be 1 cycle, 16 cycles, 32 cycles, 48 cycles, 64 cycles, etc., preferably 16 to 48 cycles, and more preferably 32 cycles. Here, the number of cycles of ultrasonic waves indicates the number of waves of the transmitted wave within the width from the start of ultrasonic irradiation to the stop of ultrasonic irradiation. By setting the number of cycles of ultrasonic waves to about 32 cycles, the expression of factors related to angiogenesis (such as VEGF) can be particularly enhanced (Patent No. 6653172, PLOS ONE, August 2014, Volume 9, Issue 8), and the effectiveness of the treatment can be obtained.

[0058] In the present invention, a plurality of ultrasonic transducers are used to irradiate non-focused ultrasonic beams from different locations, thereby achieving ultrasonic irradiation over a wide range, preferably the entire heart. In the present invention, from the viewpoint of safety, more specifically, from the viewpoint of suppressing the overlapping irradiation of ultrasonic waves from a plurality of locations onto the heart and the transmission of excessive ultrasonic energy, non-focused ultrasonic waves are sequentially irradiated among the plurality of ultrasonic transducers. In the present invention, "sequentially irradiating non-focused ultrasonic waves among a plurality of ultrasonic transducers" means that first, among the plurality of ultrasonic transducers, an ultrasonic wave is generated by a certain ultrasonic transducer, and during that time, no ultrasonic wave is generated by the other ultrasonic transducers. Next, an ultrasonic wave is generated by another ultrasonic transducer, and during that time, no ultrasonic wave is generated by the other ultrasonic transducers... That is, among the plurality of ultrasonic transducers, only one ultrasonic transducer generates an ultrasonic wave in the same time period. In other words, it means that ultrasonic waves are not generated simultaneously from two or more transducers. In the present invention, the interval between non-focused ultrasonic irradiations by a plurality of ultrasonic transducers can be represented by PRT, and it is preferably set appropriately in the range of 0.25 to 2.56 ms. By setting PRT within this range in the present invention, before the next non-focused ultrasonic energy irradiation, the irradiated ultrasonic wave attenuates (preferably attenuates to about 1 / 100), and excessive ultrasonic stimulation due to the overlapping of ultrasonic energy in the irradiation region can be avoided or reduced. However, when the irradiation regions of non-focused ultrasonic waves do not overlap among the plurality of ultrasonic transducers, simultaneous irradiation is also possible.

[0059] The irradiation conditions of these non-focused ultrasonic beams are controlled by a control unit via a transmission unit.

[0060] In the treatment method using the ultrasonic treatment device of the present invention, the treatment time by irradiation of non-focused ultrasonic energy can be appropriately determined according to factors such as the patient's symptoms and the irradiation conditions of the non-focused ultrasonic beam. The irradiation time per treatment can be appropriately determined preferably in the range of 1 to 80 minutes, more preferably 15 to 25 minutes, and particularly preferably 20 minutes. Further, the number of irradiations of non-focused ultrasonic energy per day (i.e., the number of irradiations in the treatment per day) can be performed multiple times and is not particularly limited. As the treatment per day, for example, it can be appropriately set in the range of 1 to 4 times, preferably 2 to 3 times, and more preferably 3 times. Each time can be performed with an appropriate interval and is not particularly limited, but it is preferable to perform it with an interval of at least 5 minutes or more. The treatment method of the present invention can be continuously performed at an appropriate frequency as long as there are no harmful events or the like.

[0061] In addition, as the focused ultrasonic beam for diagnosis, the same level as the ultrasonic wave used for diagnosis by a generally known ultrasonic diagnostic device can be used.

[0062] As described above, the present invention has been described based on the drawings showing specific embodiments, but it is obvious that the present invention is not limited to these embodiments. For example, the number of ultrasonic transducers may be two as described in FIGS. 4, 8, etc., or may be more than that (for example, 3, 4, 5, etc.). The connection between the ultrasonic transducer and the transmission unit may be wired or wireless as described in FIGS. 4, 8, etc. Further, the shape of the ultrasonic transducer, particularly the shape of the vibrator surface which is the ultrasonic irradiation surface, only needs to be able to irradiate ultrasonic waves in all directions, and may be circular as described in FIGS. 5, 6, etc., or may be substantially circular, substantially elliptical, polygonal (triangle, quadrilateral (square, rectangle, parallelogram, trapezoid, etc.), pentagon, hexagon, heptagon, octagon, etc.). The present invention includes various modified forms without departing from its essence.

Explanation of Reference Numerals

[0063] 1, 21, 21' Ultrasonic transducer 2. 22 Ultrasonic therapy device 3. 23 Transceiver unit 24 Waveform generation unit 25 Display unit 4. 26 Control unit 5. 27 Operation unit 8 Transducer surface protective film 9, 9’, 29, 29’ Transducer surface 10, 210, 210’ Cable 11 Acoustic lens 211 Acoustic lens adapter 212 Image formation unit 213 Vibration element

Claims

1. An ultrasonic treatment device for treating heart diseases, comprising: at least two ultrasonic transducers for irradiating the heart with non-focused ultrasonic beams; a transmission unit for controlling the irradiation of non-focused ultrasonic beams from the at least two ultrasonic transducers; a holder for holding the at least two ultrasonic transducers at a predetermined position; The ultrasonic treatment device is characterized in that: the transmission unit controls the ultrasonic transducers to sequentially irradiate the non-focused ultrasonic waves; the holder is detachable from the at least two ultrasonic transducers, and holds one of the at least two ultrasonic transducers at a position where a non-focused ultrasonic beam including a long-axis cross-section of the left margin of the sternum by a parasternal approach can irradiate the heart, and holds another one of the at least two ultrasonic transducers at a position where a non-focused ultrasonic beam including an apical long-axis tomographic plane by an apical approach from the intercostal space can irradiate the heart.

2. The transmission unit controls the at least two ultrasonic transducers to continuously irradiate the non-focused ultrasonic waves for 1 minute to 80 minutes, wherein the transmission frequency (Frequency) of the non-focused ultrasonic waves is 0.1 to 3 MHz, the non-focused ultrasonic waves are composed of discontinuous waves with a cycle number of 1 to 64 cycles, and the pulse repetition time is 0.25 to 2.56 ms. The ultrasonic treatment device according to Claim 1.

3. The ultrasonic treatment device according to Claim 2, wherein the transmission frequency of the non-focused ultrasonic waves is 0.5 to 1.875 MHz.

4. The ultrasonic treatment device according to Claim 2, wherein the cycle number of the non-focused ultrasonic waves is 32 cycles.

5. The ultrasonic treatment device according to Claim 1, wherein the at least two ultrasonic transducers have a convex-shaped vibrator surface.

6. The ultrasonic treatment device according to Claim 1, wherein the at least two ultrasonic transducers have an acoustic lens on the vibrator surface.

7. The ultrasonic treatment device according to Claim 1, wherein the at least two ultrasonic transducers are capable of switching between irradiation of non-focused ultrasonic beams and irradiation of focused ultrasonic beams.

8. The ultrasonic treatment device according to Claim 7, wherein the at least two ultrasonic transducers are provided with detachable acoustic lenses.

9. The ultrasonic treatment apparatus according to claim 7, wherein the at least two ultrasonic transducers include vibration elements arranged in a two-dimensional array in a large number.

10. The ultrasonic treatment apparatus according to claim 7, further comprising an image forming unit configured to obtain, as waveform information, an ultrasonic reception signal from a treatment region after the at least two ultrasonic transducers irradiate a focused ultrasonic beam, wherein the image forming unit creates B-mode tomographic image data from the waveform information to form image data.

11. The ultrasonic treatment apparatus according to claim 1, wherein the at least two ultrasonic transducers have a vibrator surface with a size of 8 mm to 20 mm.

Images