NL2025628A - Low-intensity Focused Ultrasonic Blasting System Guided by Ultrahigh-field Magnetic Resonance - Google Patents

Low-intensity Focused Ultrasonic Blasting System Guided by Ultrahigh-field Magnetic Resonance Download PDF

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Publication number
NL2025628A
NL2025628A NL2025628A NL2025628A NL2025628A NL 2025628 A NL2025628 A NL 2025628A NL 2025628 A NL2025628 A NL 2025628A NL 2025628 A NL2025628 A NL 2025628A NL 2025628 A NL2025628 A NL 2025628A
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magnetic resonance
blasting
ultrasonic
ultrasonic transducer
low
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NL2025628A
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Dutch (nl)
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NL2025628B1 (en
Inventor
Sun Xilin
Wang Kai
Yang Jie
Li Yingbo
Li Haoxiang
Wu Lina
Yang Lili
Miao Shuang
Jiang Ying
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Univ Harbin Medical
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/05—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves 
    • A61B5/055—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves  involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
    • A61B90/36—Image-producing devices or illumination devices not otherwise provided for
    • A61B90/37—Surgical systems with images on a monitor during operation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
    • A61B90/50—Supports for surgical instruments, e.g. articulated arms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
    • A61B90/36—Image-producing devices or illumination devices not otherwise provided for
    • A61B90/37—Surgical systems with images on a monitor during operation
    • A61B2090/374—NMR or MRI
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy
    • A61N2007/0004—Applications of ultrasound therapy
    • A61N2007/0021—Neural system treatment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy
    • A61N2007/0004—Applications of ultrasound therapy
    • A61N2007/0021—Neural system treatment
    • A61N2007/0026—Stimulation of nerve tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy
    • A61N2007/0056—Beam shaping elements

Abstract

The present invention relates to a low-intensity focused ultrasonic blasting system guided by ultrahigh-field magnetic resonance, including a 9.4 T magnetic resonance device and a low- intensity focused ultrasonic blasting device; the 9.4 T magnetic resonance device includes a main 5 magnet, a small animal bed, a magnetic resonance coil and a monitor, the low-intensity focused ultrasonic blasting device includes an ultrasonic transducer, an ultrasonic nerve stimulator and a fixing device capable of enabling the ultrasonic transducer to perform fixed-point blasting. The device provided by the present invention allows a fixed-point blasting position of an ultrasonic transducer not to be limited by an upper part of a small animal bed and a space in a magnetic 10 resonance coil, has a less interference to a magnetic resonance device, and exerts the effect of a magnetic resonance imaging device fully, thus achieving a better blasting effect.

Description

Low-intensity Focused Ultrasonic Blasting System Guided by Ultrahigh-field Magnetic Resonance
FIELD OF TECHNOLOGY The present invention belongs to the technical field of medical appliances, and relates to a focused ultrasonic blasting system and in particular to a low-intensity focused ultrasonic blasting system guided by ultrahigh-field magnetic resonance.
BACKGROUND ART Lung cancer has the highest prevalence and death rates. In recent vears, the diagnosis-treatment integrated research for tumors has drawn wide attentions. It is indicated by a great number of researches that anoxia of solid tumors 1s attributed to rapid proliferation of tumor cells and incomplete vascular development, thus causing anoxic relevant drug resistance and failures in cancer treatment. Perfluocarbon (PFC) is widely applied to inflammation imaging, cell tracking and drug release owing to its good biocompatibility and unique oxygen carrying capacity. A third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) AZD9291 drug can target T790M mutant tumors more effectively and 1s used in treatment of non-small cell lung cancers. Hence, the PFC is combined with the AZD9291 drug together to intravenously deliver to target tissues for treatment. However, the insufficient drug delivery is the main reason for treatment failures. As an effective form for energy delivery, ultrasonic waves play a huge role in ultrasonic mediated oxygen release and drug delivery. Additionally, one important application of ultrasonic waves in biology and medicine is a magnetic resonance imaging device which may obtain a magnetic resonance signal selectively by applying an appropriate gradient to a magnetic field, and processes information to obtain tissue characteristics of each point for tissue imaging. The obtained magnetic resonance image has a very high tissue resolution capability and can be very easy to distinguish normal tissues and tumor tissues, and obtain stereoscopic data within a certain volume. The magnetic resonance imaging device may image some part of a human body or even the whole body and thus is very suitable for the use of monitoring in low-intensity focused ultrasonic blasting. Presently, the research statuses and shortages of the ultrasonic blasting systems are mainly embodied in the followings: In-vivo nanoprobe molecular imaging and ultrasonic blasting processes mainly lie in: PFC drug-loading oxygen-carrying molecular imaging nanoprobes reach to target tissues via intravenous injection. and may be used for °F magnetic resonance imaging owing to its high fluorine content and good biocompatibility and stability. Then, use ultrasonic irradiation with certain energy, the PFC drug-loading oxygen-carrying molecular imaging nanoprobes are blasted at the target tissues and release the carried oxygen and drug. Monitored with 9.4 T small animal magnetic resonance, the probes achieve on-demand, accurate and quantitative controlled release, improve efficacy and action time of the drug and reduce toxicities and side effects. Meanwhile, a cavitation effect generated bymicrobubble blasting can accelerate blood circulation of local capillary, improve permeability of cell membranes, and promote drug uptake by the target tissues to achieve the purpose of target treatment. At last, the effect of the positioned delivery and quantitative controlled release drug is evaluated by means of technical means of a magnetic resonance instrument.
However, to achieve the purposes of blasting the PFC drug-loading oxygen-carrying molecular imaging nanoprobes in real time and monitoring the nanoprobes in real time, it is necessary to combing a magnetic resonance molecular imaging device and an ultrasonic microbubble trigger device organically and this is a key technical problem. At present, there is no special magnetic resonance mediated low-intensity focused ultrasonic device for real-time blasting and real-time imaging at home and abroad. The existing devices mainly use a current commercially-available diagnostic ultrasonic instrument for in-vitro blasting and then for magnetic resonance imaging and monitoring. Although ultrasonic irradiation, microbubble blasting and targeted release can be realized, the PFC drug-loading oxvgen-carryng molecular imaging nanoprobes cannot be blasted in real time and monitored in real time via the magnetic resonance.
SUMMARY A technical problem to be solved by the present invention is to provide, for the above shortages of the prior art, a low-intensity focused ultrasonic blasting system guided by ultrahigh-field magnetic resonance and integrated with diagnosis, blasting, monitoring and effectiveness evaluation, which is referred to as an "MR-LIFU system". The system is not limited by an upper part of a small animal bed and a space in a magnetic resonance coil, and has a less interference to a magnetic resonance device.
Technical solutions adopted to solve the technical problem of the present inventionis a low- intensity focused ultrasonic blasting system guided by ultrahigh-field magnetic resonance which includes: a 9.4 T magnetic resonance device and a low-intensity focused ultrasonic blasting device.
The 9.4 T magnetic resonance device includes a main magnet, a magnetic resonance coil, a small animal bed disposed in the magnetic resonance coil and a monitor and the small animal bed is located at a central line of the magnetic resonance device.
The low-intensity focused ultrasonic blasting device includes an ultrasonic transducer of which a diameter of a focal core in a biological focal region for focusing a tumor site is in a range of 0.1-6 mm, an ultrasonic nerve stimulator and a fixing device capable of enabling the ultrasonic transducer to perform fixed-point blasting; and the ultrasonic transducer is located at a naked-mouse tumor site of the animal bed.
In the above solutions, the ultrasonic transducer further includes a collimator device connected thereon and filled with de-aerated water.
The collimator device is located at the naked-mouse tumor site, and provided with an arched fixing device thereon; the ultrasonic transducer is fixed in the fixing device; the fixing device 1sconnected to a fixing bandage capable of being fixed to the small animal bed of the magnetic resonance device, and a self-adhesive buckle capable of being bonded with each other is arranged on surfaces of two bandages. The collimator device is of a conical open structure.
The fixing device can fix the ultrasonic transducer at a tumor position of a naked mouse, and has a less interference to the magnetic resonance device to fully exert the effect of a magnetic resonance imaging device, so the ultrasonic transducer can perform an accurate fixed-point blasting operation.
Preferably, the ultrasonic transducer has a diameter of the focal core in the range of 0.1-6 mm in the biological focal regionWhen the ultrasonic transducer is manufactured, by means of controlling main parameters of the ultrasonic transducer such as a focal length and a frequency, and then verify with a focal region test and an in-vitro experiment to determine that the diameter of the focal core in the biological focal region of the ultrasonic transducer is in the range of 0.1-6 mm.
During whole blasting process, an ultrasonic transducer fixing device is independent of the small animal bed and the magnetic resonance coil, is fixed to the small animal bed via the fixing bandage, and thus greatly reduces the interference of the ultrasonic blasting device to a magnetic field of the magnetic resonance device. The present invention makes a full use of a structure and a function of the magnetic resonance device, and allows an energy applying region of the ultrasonic transducer and an imaging monitoring region of the magnetic resonance device to cross in a blasting target region, to achieve a very good blasting effect.
In the present invention, the ultrasonic transducer and the ultrasonic nerve stimulator are respectively located inside and outside a magnet. The ultrasonic transducer has a focal length of 6 mm and a diameter of 15 mm, which is matched with an acceptable range of the tumor of the naked mouse. The ultrasonic nerve stimulator has a focusing ultrasonic trigger unit that is used to output a certain energy and frequency and can allow a microbubble to blast in a targeted manner, and the energy and the frequency are respectively in a range of 0-136 W and 0.5-5 MHz. The microbubble carries oxygen and a drug. The microbubble is delivered in a focused ultrasonic positioning manner, and the microbubble is blasted in a targeted manner to release the carried oxygen and the drug.
The monitoring device includes a magnetic resonance coil. The small animal bed and the 9.4 T magnetic resonance main magnet are combined into a whole.
The present invention has the following beneficial effects: 1. the low-intensity focused ultrasonic blasting system integrated with diagnosis and treatment and mediated by the ultrahigh-field magnetic resonance merges magnetic resonance molecular imaging and ultrasonic blasting functions, realizes real-time fixed-point blasting and real-time efficacy monitoring purposes, and has a certain chemosensitization effect. 2. With the addition of a body coil, the body coil receives magnetic resonance imaging information and display a blasting site of a naked mouse, and can more accurately monitor an image in a two-dimensional scanning target region of a focal core in blasting.
The present invention is further described below in detail in combination with the embodiments and the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a structural block diagram of the present invention.
Fig. 2 is a side structural schematic diagram of the present invention.
Fig. 3 is a front structural schematic diagram of the present invention.
Fig. 4 is a structural schematic diagram of a low-intensity focused ultrasonic blasting device.
Fig. 5 is a structural schematic diagram of an ultrasonic transducer fixing device.
Fig. 6 is a top expanded structural schematic diagram of Fig. 5.
DETAILED DESCRIPTION OF THE EMBODIMENTS Referring to Figs. 1-6, names of the parts are as follows: 1-9.4 T magnetic resonance device, 2- main magnet, 3- monitor, 4-small animal bed, 5-magnetic resonance coil (body coil), 6-ultrasonic transducer, 7-ultrasonic nerve stimulator, 8-matching plate, 9-fixing device, 10-naked-mouse tumor site, 11-collimator device, 12-fixing bondage, and 13-self-adhesive buckle.
Referring to Figs. 1-6, a low-intensity focused ultrasonic blasting system guided by ultrahigh- field magnetic resonance includes: a 9.4 T magnetic resonance device 1 and a low-intensity focused ultrasonic blasting device.
The 9.4 T magnetic resonance device 1 includes a main magnet 2, a magnetic resonance coil 5, a small animal bed 4 disposed in the magnetic resonance coil 5 and a monitor 3, and the small animal bed 4 is located at a central line of the magnetic resonance device 1.
The low-intensity focused ultrasonic blasting device includes an ultrasonic transducer 6 of which a diameter of a focal core in a biological focal region for focusing a tumor site is in a range of 0.1-6 mm, an ultrasonic nerve stimulator 7 and a fixing device 9 (which allows the ultrasonic transducer 6 to be fixed on a tumor of a naked mouse) capable of enabling the ultrasonic transducer 6 to perform fixed-point blasting; and the ultrasonic transducer 6 is located at a naked-mouse tumor site 10 of the animal bed.
Referring to Fig. 2. in the magnetic resonance device, an imaging information receiving unit for receiving magnetic resonance imaging information is provided on the magnetic resonance bed, and the imaging information receiving unit is sequentially connected to an information processing unit and the monitor 3.
Referring to Fig. 4, a collimator device 11 is connected in front of the ultrasonic transducer 6.
The collimator device 11 is filled with de-aerated water. The de-aerated water serves as a medium for ultrasonic propagation and is used for cooling heat produced during ultrasonic blasting. The ultrasonic transducer 6 is located behind the collimator device 11.
The collimator device 11 is of a conical open structure. In order to reduce an influence of a movement of the blasting device to the blasting in the target region, the fixing device 9 may further be installed above the ultrasonic transducer 6. The fixing device 9 and the ultrasonic transducer 6 are jointly fixed on the small animal bed 4 (see Fig. 3).
5 The ultrasonic transducer 6 has a diameter of a focal core in a range of 0.1-6 mm in a biological focal region and a working frequency of 0.5-5 MHz. Certainly, with appropriate adjustment, a phase control transducer may also serve as a wave source for emitting an ultrasonic wave.
During blasting, a focal core focuses and blasts a target tissue, a two-dimensional imaging functional part of the 9.4 T magnetic resonance device 1 is used to monitor a two-dimensional image ma blasting process with the focal core, and the monitor 3 displays the two-dimensional image to an operator.
Referring to Fig. 3, in order to guarantee the safety in two-dimensional scanning blasting of the focal core and improve the clarity of image information collected by the magnetic resonance, the body coil 5 for receiving imaging information of the magnetic resonance device is installed at a periphery ofthe naked mouse in the small animal bed 4. The body coil 5 is fixed at the periphery of the small animal bed 4 and connected to the imaging information receiving unit of the magnetic resonance device, and is of a circular shape. As the body coil 5 receives the magnetic resonance imaging information and may display a blasting site of the naked mouse, it can more accurately monitor an image in a two-dimensional scanning target region of the focal core.
Except for the body coil 5, no change is made to the magnetic resonance imaging device. The imaging information receiving unit, the information processing unit and the monitorare all existing components of the magnetic resonance imaging device.
A working process is as follows: first of all, under the control of a control unit of a small animal bed 4, a naked mouse on the small animal bed 4 is delivered to a magnetic resonance pore, with a tumor site of the naked mouse located in a magnetic resonance imaging region; a body coil 5 is used to receive magnetic resonance imaging information and transmit the received information to an imaging information receiving unit on the magnetic resonance bed; and finally, the imaging information receiving unit transmits the information to an information processing unit for processing; and upon the processing of the information processing unit, a two-dimensional image established for a lesion in need of being blasted is displayed to an operator by a monitor 3; and then, under the control of a blasting device, a focal core of an ultrasonic transducer 6 and the lesion in the blasting target region are overlapped in a magnetic resonance volume region; and under the driving of a drive circuit (not shown in the figure), the ultrasonic transducer 6 emits an ultrasonic wave, and the focal core part is used to scan and blast the lesion in the treatment target region. As a diameter (0.1-6 mm) of the focal core is smaller than a diameter (2-5 mm) of a magnetic resonance single-layer imaging section, when a blasting process is monitored by the magnetic resonance, just need to establish the two-
dimensional image of the target, and display the established two-dimensional image to the operator via the monitor 3. In this embodiment, the focal core is used to blast the tumor site 10 of the naked mouse.
Thefocused intensity of the focal core is excellent in a whole biological focal region, and the energydegradation on an outer edge of the focal core is very steep and has a characteristic of a “knife”. Therefore, the low-intensity focused ultrasonic blasting system used in this embodiment may be applied to various complex blasting treatments.

Claims (4)

ConclusiesConclusions 1. Een gefocusseerd ultrasoon straalsysteem met lage intensiteit geleid door ultrahoog-veld magnetische resonantie. omvattende: een 9.4 T magnetische resonantie-inrichting (1) en een gefocusseerde ultrasone straalinrichting met lage intensiteit. waarbij de 9.4 T magnetische resonantie-inrichting (1) een hoofdmagneet (2), een magnetische resonantiespoel (5). een kleinedierenbed (4) geplaatst in de magnetische resonantiespoel (5) en een display (3) omvat, en het kleinedierenbed (4) zich op een centrale lijn van de magnetische resonantie-inrichting bevindt (1); en de gefocusseerde ultrasone straalinrichting met lage intensiteit een ultrasone transducer (6) omvat, waarvan een diameter van een focale kern in een biologisch focaal gebied voor focusseren van een tumorplaats binnen een bereik van 0.1-6 mm is, een ultrasone zenuwstimulator (7) en een fixeerinrichting (9) in staat om de ultrasone transducer (6) een vast-puntstraling uit te laten voeren; en de ultrasone transducer (6) is geplaatst op een naakte muis-tumorplaats (10) van het dierenbed.1. A focused, low-intensity ultrasonic beam system guided by ultra-high-field magnetic resonance. comprising: a 9.4 T magnetic resonance device (1) and a focused low intensity ultrasonic beam device. wherein the 9.4 T magnetic resonance device (1) has a main magnet (2), a magnetic resonance coil (5). a small animal bed (4) placed in the magnetic resonance coil (5) and comprising a display (3), and the small animal bed (4) located on a central line of the magnetic resonance device (1); and the focused low intensity ultrasonic beam device comprises an ultrasonic transducer (6), a focal core diameter of which is in a biologically focal region for focusing a tumor site within a range of 0.1-6 mm, an ultrasonic nerve stimulator (7) and a fixing device (9) capable of causing the ultrasonic transducer (6) to output a fixed point radiation; and the ultrasonic transducer (6) is placed on a naked mouse tumor site (10) of the animal bed. 2. Het gefocusseerde ultrasone straalsysteem met lage intensiteit geleid door de ultra-hoog veld magnetische resonantie volgens claim 1, waarbij de ultrasone transducer (6) verder een collimatorinrichting (11) omvat, die daarop is aangesloten en gevuld is met ontlucht water.The focused, low intensity ultrasonic beam system guided by the ultra-high field magnetic resonance according to claim 1, wherein the ultrasonic transducer (6) further comprises a collimator device (11) connected thereto and filled with deaerated water. 3. Het gefocusseerde ultrasone straalsysteem met lage intensiteit geleid door de ultra-hoog veld magnetische resonantie volgens claim 2, waarbij de collimatorinrichting (11) is geplaatst op de naakte muis-tumorplaats (10) en voorzien is van een gebogen fixeerinrichting (9) daarop; de ultrasone transducer (6) is vastgemaakt in de fixeermrichting (9): de fixeerinrichting (9) is verbonden met een fixatieband (12) die kan worden vastgemaakt aan het kleinedierenbed van de magnetische resonantie-inrichting, en een zelfklevende sluiting (13) die met elkaar kan worden verbonden, is aangebracht op oppervlakken van twee banden (12).The focused, low intensity ultrasonic beam system guided by the ultra-high field magnetic resonance according to claim 2, wherein the collimator device (11) is placed on the nude mouse tumor site (10) and includes a curved fixer (9) thereon ; the ultrasonic transducer (6) is attached in the fixing direction (9): the fixing device (9) is connected with a fixing band (12) which can be attached to the small animal bed of the magnetic resonance device, and a self-adhesive closure (13) which can be joined together, is mounted on surfaces of two belts (12). 4. Het gefocusseerde ultrasone straalsysteem met lage intensiteit geleid door de ultra-hoog veld magnetische resonantie volgens claim 2, waarbij de collimatorinrichting (11) een conische open structuur heeft.The focused, low intensity ultrasonic beam system guided by the ultra-high field magnetic resonance according to claim 2, wherein the collimator device (11) has a conical open structure.
NL2025628A 2019-07-30 2020-05-20 Low-intensity Focused Ultrasonic Blasting System Guided by Ultrahigh-field Magnetic Resonance NL2025628B1 (en)

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