WO2009122650A1 - 超音波照射装置 - Google Patents
超音波照射装置 Download PDFInfo
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- WO2009122650A1 WO2009122650A1 PCT/JP2009/000723 JP2009000723W WO2009122650A1 WO 2009122650 A1 WO2009122650 A1 WO 2009122650A1 JP 2009000723 W JP2009000723 W JP 2009000723W WO 2009122650 A1 WO2009122650 A1 WO 2009122650A1
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Definitions
- the present invention relates to an ultrasonic irradiation method and irradiation apparatus for diagnosis / treatment using a phase change type ultrasonic contrast agent.
- Diagnostic imaging modalities such as X-ray CT, MRI, and ultrasonic diagnostic equipment have long become essential tools in the medical field. These are images of differences in CT values, spin relaxation times, and acoustic impedances in vivo, and these differences in physical properties exclusively reflect the structure (form) of the body. Called. On the other hand, what performs imaging of a part which is structurally different even in the same structure is called “functional imaging”. Among these functional imaging, in particular, molecular biological information, that is, visualization of the existence state of biological constituent molecules such as proteins, amino acids, or nucleic acids is often called “molecular imaging”.
- Molecular imaging is one of the research areas that is currently attracting the most attention because it is expected to be applied to elucidation of life phenomena such as development and differentiation and diagnosis and treatment of diseases.
- a “molecular probe” that is a substance having a structure with selectivity for biological molecules is often used.
- a structure that can be detected by some physical means is added to the molecular probe.
- Non-Patent Document 1 describes an example of a molecular probe for targeting a tumor. Peptides, antibodies, etc. are the main molecular probes.
- Positron Emission Topography (PET) devices and optical imaging devices are examples of imaging devices that are almost specialized for such molecular imaging, and the former is a tool for classifying the extent and stage of progression of clinical tumors. The latter is widely used as a non-invasive pharmacokinetic analysis tool using small animals for drug development and the like.
- PET Positron Emission Topography
- optical imaging devices are examples of imaging devices that are almost specialized for such molecular imaging, and the former is a tool for classifying the extent and stage of progression of clinical tumors. The latter is widely used as a non-invasive pharmacokinetic analysis tool using small animals for drug development and the like.
- modalities such as MRI and ultrasound used for existing morphological imaging.
- the system using ultrasonic waves is 1) excellent in real time, 2) small in size and has few restrictions on use in the operating room, and 3) can be used not only as a diagnostic tool but also as a therapeutic tool. Because it has features that do not exist in modality, it is expected as an integrated diagnosis and treatment tool
- ultrasound as a therapeutic tool can be treated with extremely low invasiveness due to site selectivity by irradiation of convergent ultrasound from a site away from the affected area.
- heat coagulation treatment which causes tissue coagulation necrosis that raises the target site to a protein denaturation temperature (about 65 ° C.) or higher in a short time of 1 minute or less. It is called HIFU treatment because it is treatment using high intensity focused ultrasound (HIFU) of 1 kW / cm 2 or higher.
- Non-Patent Document 2 it has been experimentally confirmed that the presence of microbubbles in the system increases the apparent ultrasonic energy absorption coefficient when irradiated with ultrasonic waves. . If the microbubbles can be localized only at the site to be treated, this phenomenon can be used to selectively heat only the target site.
- the heat coagulation action of the target part is enhanced by ultrasonic irradiation with the intensity for normal heat coagulation on the order of kW / cm2, or the purpose is to use an ultrasonic intensity lower than that of normal heat coagulation treatment.
- a treatment method is also conceivable in which the heat coagulation action is caused only at the site and the heat coagulation effect is hardly produced at other sites.
- microbubbles can only exist in blood vessels due to size restrictions, and it is difficult to make high concentrations in blood vessels with a small peripheral flow rate. It is difficult to localize to.
- the action of (acoustic) cavitation can be cited as an ultrasonic biological action involving microbubbles.
- Cavitation is originally a phenomenon in which bubble nuclei are generated by ultrasonic waves, and the bubbles grow and compressively break.
- the presence of microbubbles in the system is equivalent to skipping the beginning of the cavitation process and reaching the stage where bubbles have grown, and by irradiating ultrasonic waves in that state, the cores necessary for cavitation generation One step of generation can be omitted. Since generation of bubble nuclei can be omitted in this way, it is known that when microbubbles exist, the acoustic intensity required for cavitation generation decreases as shown in, for example, [Non-Patent Document 3].
- Patent Document 1 It is known that biological action occurs due to the effect of a chemical substance called a sonochemically active substance as shown in FIG. In particular, cell death and tissue destruction at the site where cavitation is generated is expected to be applied for treatment.
- Non-patent Document 4 a drug that is a nano-sized droplet at the time of administration to a living body and that causes a phase change by ultrasonic irradiation to generate microbubbles is used as an ultrasound diagnostic contrast Use as an agent is being studied. Since nano-sized droplets are smaller than microbubbles, they can be leaked from blood vessels into tissues such as tumors or accumulated in peripheral blood vessels at a high concentration. In addition, tissue selectivity can be provided by using the molecular imaging technique of adding the molecular probe described above. By using such a phase change type contrast agent, ultrasonic contrast with high tissue selectivity becomes possible.
- the microbubbles generated after the phase change promote the heating and coagulation action in the vicinity where the self exists, so that the phase change occurs only at the target part, thereby preventing the ultrasonic heating action.
- a highly sensitive site can be obtained, which makes it possible in principle to construct an integrated site-selective diagnosis and treatment system by phase change and subsequent ultrasonic heat coagulation treatment.
- phase change ultrasound sequence and the treatment ultrasound sequence are independent from each other, and the phase change ultrasound produces a therapeutic effect.
- phase change ultrasonic wave if a therapeutic effect is produced by the phase change ultrasonic wave, the part not originally targeted for treatment is treated due to the misalignment of the phase change ultrasonic wave. Since the phase-change ultrasonic waves use shorter pulses than the therapeutic waves, it is unlikely that a therapeutic effect requiring energy storage will be obtained by the phase-change ultrasonic waves. Therefore, it becomes more problematic that the phase change occurs secondarily by the therapeutic ultrasonic waves.
- Patent Document 2 discloses a device that performs integrated imaging of a target site using a phase-change contrast agent and treatment following the contrast imaging. As a result, if the phase change occurs secondarily, the selectivity of the treatment site decreases.
- the nanoparticle phase-change contrast agent enables tissue-selective ultrasound contrast, but when using the usual irradiation method, it is secondary by subsequent therapeutic ultrasound irradiation.
- the phase change occurs, there is a problem that the selectivity of the treatment site is not ensured.
- the problem is particularly serious because the ultrasonic intensity is higher in a portion closer to the ultrasonic irradiation source than the focal point.
- An object of the present invention is to provide a safe ultrasonic irradiation apparatus that can efficiently perform an imaging with a phase change type ultrasonic contrast agent and that does not cause a secondary phase change by therapeutic ultrasonic waves.
- the inventors compared the ultrasonic characteristics necessary for diagnosis, that is, the generation of microbubbles by the phase change of nanodroplets, and the ultrasonic characteristics necessary for treatment, that is, heat coagulation treatment, and controlled them so that they do not interfere with each other.
- ultrasonic waves are an energy source for accumulating heat energy in the body, and absorption of ultrasonic energy by a living body is closely related to a therapeutic effect.
- the magnitude of ultrasonic energy per unit time is calculated using sound velocity c, medium density ⁇ , and sound pressure amplitude p. p 2 / ( ⁇ ⁇ c) Therefore, only absolute sound pressure is involved, not positive or negative pressure.
- the phase change was mainly defined by the maximum value of the negative pressure of the ultrasonic wave to be irradiated.
- the ultrasonic negative pressure PNM is required for the constants k 1 , k 2 , and the frequency f.
- PNM k 1 -k 2 ⁇ f (F> 1 MHz and f ⁇ 10 MHz). This relational expression was obtained from the following experimental results.
- the present invention is an ultrasonic irradiation apparatus that irradiates a subject to which a contrast agent that changes phase from a liquid to a gas by ultrasonic irradiation is administered.
- An ultrasonic transmission / reception unit that transmits ultrasonic waves to the subject and receives ultrasonic waves from the subject, and the first ultrasonic wave has a higher frequency and a maximum negative pressure value than the second ultrasonic wave. It is high or equivalent, that is, it is not less than the maximum negative pressure value of the second ultrasonic wave.
- diagnosis and treatment can be performed while keeping the ultrasonic intensity required in combination with the phase change type ultrasound contrast agent to the minimum necessary level, particularly diagnosis (phase change). Interference between medical and therapeutic ultrasound can be prevented. These effects can provide a safe diagnosis / treatment technique.
- the figure which shows an experimental system The figure which shows the relationship of the ratio of the ultrasonic maximum negative pressure required to produce the phase change of the nano droplet in water, and the maximum negative pressure and the maximum positive pressure.
- the sample-phase-change convergent ultrasonic wave generating transducer 7 has a diameter of 40 mm and an F number of 1, and is designed to be able to simultaneously irradiate ultrasonic waves of any frequency of 1 MHz + 2 MHz, 2 MHz + 4 MHz, or 3 MHz + 6 MHz.
- the sample 4 is held at the focal point of the transducer 7 by the ultrasonic diagnostic apparatus probe 8 for phase change observation.
- the phase change ultrasonic signal generator 10 and the amplifier 11 are used to irradiate the ultrasonic wave for phase change from the ultrasonic transducer 7 for 5 seconds, and the echo intensity from the sample before and after the irradiation. It is judged that a phase change has occurred when the value changes more than twice.
- the ultrasonic pressure is measured with an underwater microphone having a diameter of 0.5 mm.
- the method for preparing the nanodroplets used is shown below. The following ingredients were added together and homogenized for 1 minute at 9500 rpm at ice temperature in an ULTRA-TURRAX T25 (Janke & Knukel, Staufen Germany) with the slow addition of 20 ml of distilled water.
- the emulsion obtained by homogenization is subjected to high-pressure emulsification treatment at 20 MPa in Emulsiflex-C5 (Avestin, Ottawa Canada) for 2 minutes and filtered through a 0.4 micron membrane filter.
- a substantially transparent microemulsion was obtained by the above treatment. It was confirmed by LB-550 (Horiba, Tokyo) that 98% or more of the obtained microemulsion had a diameter of 200 nm or less.
- An example of the results is shown in FIG.
- the magnitude of the maximum negative pressure required for the phase change varies depending on the frequency, and the phase change occurs at the lowest maximum negative pressure in the case of 3 MHz + 6 MHz having the highest frequency. It can be seen that the lower the frequency used, the higher the maximum negative pressure required. Even if the ratio between the maximum positive pressure and the maximum negative pressure is changed, the maximum negative pressure necessary for the phase change is hardly changed.
- FIG. 3 shows the results of examining the effect of the ultrasonic frequency used for the phase change on the phase change threshold using the experimental system of FIG. In this examination, the single frequency of 2 MHz, 4 MHz, and 6 MHz is used. From the figure, it can be seen that the maximum negative pressure required for the phase change is lower as the ultrasonic frequency is higher, and is lower as the frequency is higher.
- the change in the maximum ultrasonic negative pressure necessary for the phase change when the ratio between the positive pressure and the negative pressure is changed is examined.
- the sample holder 4 was replaced with a mouse holder, and verification using an animal was performed.
- the mouse used for this verification has been about 2 weeks since the Colon 26 experimental tumor was implanted subcutaneously, and the tumor diameter was about 15 mm.
- the focal point of the ultrasonic transducer 7 for phase change was set to a depth of 5 mm from the surface of the mouse tumor, and the maximum ultrasonic negative pressure required for the phase change was measured in the same manner as in Test Example 1.
- FIG. 5 shows the results of examining the effect of the ultrasonic frequency used for the phase change on the phase change threshold.
- the single frequency of 2 MHz, 4 MHz, and 6 MHz is used. From the figure, it can be seen that the maximum negative pressure required for the phase change is lower as the ultrasonic frequency is higher, and is lower as the frequency is higher.
- the ultrasonic irradiation time required for the phase change is generally several micro to milliseconds, and when viewed from the time scale of several to several tens of seconds required for heating and coagulation, it is considered to be almost a pulse. Therefore, when the phase change is caused, an ultrasonic pulse having a frequency as high as possible and having a maximum negative pressure value is used, and the heat coagulation treatment after the phase change is lower than when the phase change is caused. It is possible to realize an ultrasonic irradiation sequence with less interaction between the phase change and the heat coagulation treatment by using an ultrasonic pulse having a lower maximum negative pressure value than that when generating a phase change at a frequency. all right.
- FIG. 6 shows the frequency on the horizontal axis and the maximum negative pressure value on the vertical axis. 3 and 5, it can be seen that there is a region (phase change possible region) in which a phase change determined from the frequency and the maximum negative pressure value can occur.
- the ultrasonic condition A is a point that exists in this phase changeable region, and the ultrasonic condition B has the same maximum negative pressure value as the ultrasonic condition A and the ultrasonic frequency is low, and therefore, from the phase changeable region. Slip off. Since the ultrasonic condition C has the same frequency as the ultrasonic condition B and the maximum negative pressure value is smaller, the ultrasonic condition C deviates from the phase changeable region further than the ultrasonic condition B.
- the present invention was reached based on the above examination results.
- a means for irradiating the target region with phase change ultrasonic waves an image processing unit for generating an ultrasonic diagnostic image indicating the generation state of microbubbles due to the phase change, an ultrasonic diagnostic image
- a means for controlling the irradiation condition of the ultrasonic wave for performing the heat coagulation treatment based on the confirmation of the generation of the microbubbles using.
- the control of ultrasonic irradiation conditions is based on the confirmation of the generation of microbubbles and has a maximum negative pressure value that is substantially the same as the maximum ultrasonic negative pressure value required for phase change and is used for phase change. It can be an ultrasonic wave having a lower frequency.
- the ultrasonic intensity may be increased and the phase change ultrasonic wave may be further irradiated.
- the frequency of ultrasonic waves for phase change is preferably approximately 1 MHz or more because phase change occurs at a lower ultrasonic negative pressure as the frequency is higher. Since the absorption rate is approximately proportional to the ultrasonic frequency and reaches only the body surface due to attenuation at a frequency of 10 MHz, a frequency of about 10 MHz or less is practical. For this reason, the ultrasonic frequency for phase change in the present invention is preferably about 1 MHz to 10 MHz.
- the ultrasonic irradiation apparatus of the present embodiment includes a phase change ultrasonic transmission unit 14, a phase change detection ultrasonic transmission / reception unit 15, and a therapeutic ultrasonic transmission unit 16 that are arranged through the acoustic coupling material 13 with respect to the treatment target 12.
- the phase change ultrasonic transmitter 14 has a single frequency selected from the range of 1 to 10 MHz, a basic frequency selected from the range of 1 to 5 MHz, and a frequency that is twice the basic frequency. It is configured to be able to irradiate ultrasonic waves in a range where the negative pressure is generally greater than 0.1 MPa and lower than 10 MPa. As shown in FIGS. 3 and 5, the frequency of the ultrasonic wave for phase change is preferably about 1 MHz or more because the higher the frequency is, the lower the negative ultrasonic pressure is.
- the absorption rate in the body is approximately proportional to the ultrasonic frequency and reaches only the body surface due to attenuation at a frequency of 10 MHz, so a frequency of about 10 MHz or less is practical.
- the ultrasonic frequency for phase change in the present invention is preferably about 1 MHz to 10 MHz.
- the sound wave preferably has a higher sound pressure than a normal diagnostic apparatus. For this reason, it is generally desirable to use a negative pressure of 0.1 MPa or more. Considering the safety of the living body, it is preferable that the negative pressure does not exceed 10 MPa.
- the phase change detection ultrasonic transmission / reception unit 15 is configured to transmit and receive ultrasonic waves having a frequency of about 2 to 10 MHz and an acoustic intensity of time average intensity of 0.72 W / cm 2 or less, which can be used in a normal ultrasonic diagnostic apparatus.
- the therapeutic ultrasound transmitter 16 is a single frequency selected from the range of 0.5 to 10 MHz or a basic frequency selected from the range of 0.5 to 5 MHz and the basis for performing treatment by the heating action of ultrasound. It is configured to irradiate ultrasonic waves having a frequency twice that of the frequency, and the acoustic intensity can be an arbitrary value selected from the range of 100 to 5000 W / cm 2 .
- phase change of the phase change type ultrasonic contrast agent in the treatment site 12 caused by the ultrasonic irradiation from the phase change ultrasonic transmission unit 14 is detected based on the reception signal of the phase change detection ultrasonic transmission / reception unit 15; This is performed after confirming that the contrast agent is present at the treatment site by image processing using the phase change quantitative signal processing unit 19.
- Ultrasound irradiation from the therapeutic ultrasound transmitter 16 is controlled to obtain such a phase change quantitative signal.
- the phase change quantification signal processing unit 19 processes a signal for image processing for quantifying changes in the intensity and frequency components of the ultrasonic echo signal accompanying the phase change of the contrast agent.
- pre-phase change signal recording unit for holding the ultrasonic echo signal before the phase change ultrasonic irradiation, and for holding the ultrasonic echo signal during or after the phase change ultrasonic irradiation.
- the signal recording unit after phase change can be used to form a calculation unit that obtains a difference between specific frequency components between signals held in each recording unit.
- the therapeutic ultrasound condition calculation unit 20 is based on the ultrasound irradiation conditions in which the phase change generation at the target site quantified by the phase change quantification signal processing unit 19 exceeds a preset value, An operation for determining the conditions for ultrasonic irradiation is performed.
- the ultrasonic irradiation apparatus of the present embodiment it is possible to perform phase change / treatment without interference between the ultrasonic irradiation conditions that cause phase change and the ultrasonic irradiation conditions used for treatment.
- the following procedure is possible.
- an ultrasonic tomographic image near the treatment site 1 is acquired by the phase change detection ultrasonic wave transmitting / receiving unit 4.
- an ultrasonic tomographic image is obtained by the phase change detecting ultrasonic wave transmitting / receiving unit 4, while the phase change ultrasonic wave of 5 MHz maximum negative pressure 3 MPa is obtained from the phase change ultrasonic irradiation unit 3 (10 (Wave ⁇ 50) is synchronized with the phase change detection ultrasonic transmission / reception unit 4 and is irradiated while scanning the substantially the same plane as the ultrasonic tomogram by the phase change detection ultrasonic transmission / reception unit 4 or a part of the plane.
- the image processing unit 9 When it is confirmed by the image processing unit 9 that the echo intensity at the phase change detecting ultrasonic transmission / reception unit 14 has increased to a predetermined level (for example, more than twice or a threshold value) due to the phase change of the contrast agent
- a predetermined level for example, more than twice or a threshold value
- the frequency, maximum negative pressure, wave number, total irradiation time, etc. of the irradiation ultrasonic wave are notified to the therapeutic ultrasonic condition calculation unit 20 as a phase change ultrasonic condition. If the increase in echo intensity in the phase change detection ultrasonic wave transmitting / receiving unit 4 does not exceed a predetermined value, the maximum negative pressure is increased by a predetermined rate (for example, 10%) and the phase change Repeat sonication.
- a predetermined rate for example, 10%
- the therapeutic ultrasound condition calculation unit 20 is used for heat treatment suitable for the treatment calculated from the irradiation conditions of the phase change ultrasound. Calculation of ultrasonic irradiation conditions. This calculation is for performing irradiation with high acoustic intensity so as not to make the maximum negative pressure larger than the phase change ultrasonic wave. That is, the acoustic intensity is adjusted while making the maximum negative pressure of the therapeutic ultrasonic wave smaller than the negative pressure of the phase change ultrasonic wave.
- the frequency is set to 1/2 or less and the maximum negative pressure is substantially the same as that of the phase change ultrasonic wave.
- the threshold required for the phase change is increased by about 1 MPa or more, and the treatment time can be reduced by not reducing the maximum negative pressure value. It will be shortened.
- an ultrasonic wave whose frequency is 1/2 or less and the maximum negative pressure is substantially the same as that of the phase change ultrasonic wave.
- Waveform in which ultrasonic waves with substantially the same pressure are added at the target site so that the phase difference is 5 / 4 ⁇ to 7 / 4 ⁇ (maximum negative pressure is almost the same as phase change ultrasound and maximum positive pressure is Larger than the phase change) can be used.
- This calculation uses the fact that phase change occurs depending on the maximum negative pressure value, whereas heat coagulation treatment depends on the absolute maximum sound pressure value, and the maximum negative pressure value decreases.
- the maximum positive pressure value is high, the phase change hardly occurs during the treatment and the treatment time is shortened.
- a 1 / 2n frequency component (n: a natural number of 3 or more) can be used.
- the phase change occurs depending on the maximum negative pressure value
- the heat coagulation treatment uses the fact that it occurs depending on the absolute maximum sound pressure value, and the frequency used is low. Therefore, therapeutic ultrasonic waves can reach the deep part. Since the maximum positive pressure value is high while the maximum negative pressure value is lowered, the phase change hardly occurs during the treatment, the treatment time is shortened, and the deep treatment can be easily performed.
- 0.1 ml of a nanodroplet was administered to a mouse at a stage where a Colon26 experimental tumor was implanted subcutaneously and grown to a diameter of 20 mm.
- the phase changes at a maximum negative pressure of 3 MPa (4 waves, 48 times / second, 5 seconds), and when heated at a frequency of 3 MHz maximum negative pressure of 3 MPa for 20 seconds, the temperature rises 5 mm before the focus diameter.
- Measurements were taken with a 0.1 mm K-type thermocouple to determine the maximum temperature rise.
- An example of the results is shown in FIG.
- the results of treatment at a frequency of 6 MHz and a maximum negative pressure of 3 MPa are also shown.
- 6MHz the temperature rise is about 65% of the focus at the part 5mm before the focus, whereas when 3MHz is used, it is about 20%, compared to the case of 6MHz. It is clear that the temperature rise occurs selectively at the focal point.
- the frequency of the therapeutic ultrasonic wave is halved for phase change, the maximum negative pressure is made substantially the same as that for phase change, and 1 of phase change frequency is superimposed by changing the phase difference.
- 0.1 ml of a nanodroplet was administered to a mouse at a stage in which a Colon 26 experimental tumor was implanted subcutaneously and grown to a diameter of 20 mm, and 15 minutes after administration of a nanodroplet, a frequency of 8 MHz was used as a phase change ultrasonic wave.
- Phase change at maximum negative pressure 3MPa (4 waves, 48 times / second, 5 seconds)
- the temperature rise 5 mm before the focal point was measured with a K-type thermocouple having a diameter of 0.1 mm to obtain the maximum temperature rise.
- SYMBOLS 1 Resin water tank 2 Deaerated water set to 37 degreeC 3 Sample enclosed tube 4 Sample 5 Tube end fixing clip 6 Sample fixture 7 Convergent ultrasonic wave generation transducer 8 for phase change observation Ultrasonic diagnostic device probe for phase change observation DESCRIPTION OF SYMBOLS 9 Ultrasonic diagnostic apparatus 10 Phase change ultrasonic signal generator 11 Amplifier 12 Treatment object 13 Acoustic coupling agent 14 Phase change ultrasonic transmitter 15 Phase change detection ultrasonic transmitter / receiver 16 Treatment ultrasonic transmitter 17 Phase change Ultrasound control unit 18 Treatment ultrasonic control unit 19 Phase change quantification signal processing unit 20 Treatment ultrasonic condition calculation unit 21 Image processing unit 22 Input unit / drawing unit.
Abstract
Description
p2/(ρ・c)
と表されるため、絶対音圧のみが関与し、圧力の正負にはよらない。照射時間が体内の熱拡散より短い場合(概ね数分間)は投与された超音波エネルギがほぼ全て熱エネルギに変換されると考えられるため、超音波照射による温度上昇は、音速c、媒質密度ρ、音圧振幅pおよび照射時間tを用いて、
p2/(ρ・c) ・t
とあらわすことができる。このため、照射時間が体内の熱拡散よりも短い場合には、照射時間tを長くすることで、振幅が低い場合でも加熱凝固治療効果を得ることが可能となる。
これに対し、前者の相変化に関しては、主に照射する超音波の負圧の最大値により相変化が規定されることがわかった。相変化を生じるのに必要は超音波の負圧PNMは、定数k1、k2、周波数fに対し、
PNM = k1―k2×f
の関係にあることがわかった(f>1MHz、かつf<10MHz)。この関係式は、以下の実験結果により得られた。
PNM = k1―k2×f
の関係にあることがわかった(f>1MHz、かつf<10MHz)。この関係式は、以下の実験結果により得られたものである。
用いたナノ液滴の調製方法を以下に示す。以下の成分を一緒に添加し、そして20mlの蒸留水をゆっくり添加しながら、ULTRA-TURRAX T25(Janke&Knukel、Staufen Germany)中にて9500rpmで氷温にて1分間ホモジナイズした。
グリセロール 2.0g
α―トコフェロール 0.02g
コレステロール 0.1g
レシチン 1.0g
パーフルオロペンタン 0.1g
パーフルオロヘプタン 0.1g
ホモジナイズにより得られたエマルションを、Emulsiflex-C5(Avestin、Ottawa Canada)中で20MPaにて高圧乳化処理を2分間行い、0.4ミクロンのメンブレンフィルターによりろ過する。以上の処理によりほぼ透明のミクロエマルションを得た。得られたマイクロエマルションの98%以上が200nm以下の直径を有することがLB-550(堀場製作所、東京)にて確認できた。
結果の一例を図2に示す。周波数により相変化に必要な最大負圧の大きさは変化し、周波数の最も高い3MHz+6MHzの場合に最も低い最大負圧で相変化が生じている。用いた周波数が低いほど、より高い値の最大負圧が必要であることがわかる。なお、最大正圧と最大負圧との比率を変化させても相変化に必要な最大負圧はほとんど変化していない。
2 37℃に設定された脱気水
3 サンプル封入チューブ
4 サンプル
5 チューブ端固定クリップ
6 サンプル固定具
7 サンプル相変化用収束超音波発生用トランスデューサ
8 相変化観察用超音波診断装置プローブ
9 超音波診断装置
10 相変化超音波信号発生装置
11 増幅器
12 治療対象
13 音響カップリング剤
14 相変化用超音波送信部
15 相変化検出用超音波送受信部
16 治療用超音波送信部
17 相変化用超音波制御部
18 治療用超音波制御部
19 相変化定量用信号処理部
20 治療用超音波条件演算部
21 画像処理部
22 入力部・描画部。
Claims (11)
- 超音波照射により液体から気体への相変化をする造影剤を投与された被検体に対して超音波を照射する超音波照射装置であって、
第1超音波及び第2超音波を前記被検体に送信し、かつ前記被検体から超音波を受信する超音波送受信部と、
前記第1超音波は前記第2超音波よりも、周波数が高く、かつ最大負圧値が前記第2超音波の最大負圧値以上であることを特徴とする超音波照射装置。 - 前記第1超音波は造影剤相変化用超音波であり、前記第2超音波は治療用超音波であることを特徴とする請求項1に記載の超音波照射装置。
- 前記超音波送受信部が受信した信号に基づいて、前記第2超音波の照射条件を演算する第2超音波条件演算部をさらに有することを特徴とする請求項1に記載の超音波照射装置。
- 前記超音波送受信部は、前記第2超音波について、最大負圧を前記第1超音波の負圧より小さくすることを特徴とする請求項1に記載の超音波照射装置。
- 前記超音波送受信部は、前記第2超音波について、最大負圧を前記第1超音波の負圧より小さくしながら音響強度を調節することを特徴とする請求項1に記載の超音波照射装置。
- 前記超音波送受信部の受信信号に基づいて前記相変化を確認するための画像を生成する画像処理部をさらに有することを特徴とする請求項1に記載の超音波照射装置。
- 前記画像の確認に基づいて、前記第2超音波の照射条件を演算する第2超音波条件演算部をさらに有することを特徴とする請求項6に記載の超音波照射装置。
- 前記超音波送受信部は、前記第2超音波について、前記第1超音波の周波数1/2以下の周波数とすることを特徴とする請求項1に記載の超音波照射装置。
- 前記超音波送受信部は、前記第2超音波について、周波数を前記第1超音波の周波数の1/2以下としてかつ最大負圧を前記第1超音波と実質的に同一とすることを特徴とする請求項1に記載の超音波照射装置。
- 前記超音波送受信部は、前記第1超音波の周波数を1MHz以上10MHz以下とすることを特
徴とする請求項1に記載の超音波照射装置。 - 前記超音波送受信部は、前記第2超音波について、前記第1超音波の周波数の1/2以下の音波と前記第1超音波の周波数の1/2n(n:1以上の整数)の音波との合成波とすることを特徴とする請求項1に記載の超音波照射装置。
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Cited By (4)
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WO2011125991A1 (ja) * | 2010-04-09 | 2011-10-13 | 株式会社日立製作所 | 超音波診断治療装置 |
JP2014148470A (ja) * | 2013-01-31 | 2014-08-21 | Olympus Corp | 造影剤とその製造方法および製造キット |
WO2015186651A1 (ja) * | 2014-06-05 | 2015-12-10 | 株式会社 日立メディコ | 超音波治療装置及び超音波治療システム |
JP2018059785A (ja) * | 2016-10-04 | 2018-04-12 | 国立大学法人東北大学 | 微細気泡の含有判定方法及び微細気泡の含有判定装置 |
Families Citing this family (2)
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JP4279328B2 (ja) * | 2007-05-07 | 2009-06-17 | 株式会社日立製作所 | 超音波撮像システム |
WO2018158805A1 (ja) * | 2017-02-28 | 2018-09-07 | オリンパス株式会社 | 超音波医療装置 |
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- 2009-02-20 CN CN2009801117113A patent/CN101980667B/zh not_active Expired - Fee Related
- 2009-02-20 WO PCT/JP2009/000723 patent/WO2009122650A1/ja active Application Filing
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WO2011125991A1 (ja) * | 2010-04-09 | 2011-10-13 | 株式会社日立製作所 | 超音波診断治療装置 |
CN102834068A (zh) * | 2010-04-09 | 2012-12-19 | 株式会社日立制作所 | 超声波诊断治疗装置 |
JPWO2011125991A1 (ja) * | 2010-04-09 | 2013-07-11 | 株式会社日立製作所 | 超音波診断治療装置 |
JP5735488B2 (ja) * | 2010-04-09 | 2015-06-17 | 株式会社日立製作所 | 超音波診断治療装置 |
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JPWO2015186651A1 (ja) * | 2014-06-05 | 2017-04-20 | 株式会社日立製作所 | 超音波治療装置及び超音波治療システム |
JP2018059785A (ja) * | 2016-10-04 | 2018-04-12 | 国立大学法人東北大学 | 微細気泡の含有判定方法及び微細気泡の含有判定装置 |
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CN101980667B (zh) | 2012-08-15 |
JPWO2009122650A1 (ja) | 2011-07-28 |
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