JP2006149872A - System and method for introducing medication - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a medication introducing system for efficiently performing reliable medication introduction which is not affected by a blood circulation state in a part to be treated, etc, and to provide a medication introducing method. <P>SOLUTION: Ultrasonic contrast agent (labeling agent) which is administered to the part to be treatment together with a medication such as a gene is broken by the radiation of ultrasonic wave for introduction. When the medication is introduced to the part to be treated by the breakage, a pixel value comparing part 7 of the medication introducing system 100 compares a predetermined threshold with the pixel value of a radiation position in monitoring image data, which is generated by a monitoring image data generating part 21 before and after the radiation of the ultrasonic wave for introduction relative to the prescribed radiation position set by a radiation plan establishing part 6. A radiation control part 8 controls the radiation of the ultrasonic wave for introduction relative to the radiation position, based on reflux information or breakage information of the ultrasonic wave contrast agent at the radiation position which is reflected by the comparison result. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a drug introduction system and a drug introduction method for introducing a drug into a cell or tissue by using an introduced energy wave.

  In the field of treatment, a minimally invasive treatment called MIT (Minimally Invasive Treatment) has recently attracted attention. Conventional MIT includes interventional treatment using balloon catheters and stents for patients with ischemic brain disease and heart disease. However, these diseases caused by arteriosclerosis have a high recurrence rate, and it is difficult to repeatedly perform the same treatment on the recurrent portion. For such problems, gene transfer therapy that can improve ischemic symptoms by suppressing recurrence or by creating new blood vessels in completely infarcted tissues has attracted attention. . For example, gene therapy that promotes angiogenesis by introducing an angiogenic factor has already been effective for diseases of extremities that have become ischemic or necrotic due to diabetes.

  On the other hand, by introducing an angiogenesis inhibitory factor having an effect opposite to that of an angiogenic factor into tumor cells, it is possible to inhibit the growth of tumor blood vessels and suppress tumor growth. As a new treatment method for such a malignant tumor, gene therapy in which a gene is extracted into a tumor cell and treated is being studied.

  In order to introduce a gene into a cell, a technique for temporarily increasing the permeability of the cell membrane is necessary. As a technique, a method using a virus infectivity, a chemical method such as a liposome, Physical methods such as microinjection, gene gun, electroporation, ultrasound, and laser are being studied. In particular, gene introduction into a tumor cell by a physical method such as ultrasound has a great advantage that a target local tissue can be limited.

  The gene transfer method using ultrasonic waves initially utilizes a phenomenon (sonoporation phenomenon) in which transient pores are generated in the cell membrane by cavitation that occurs when ultrasonic waves are applied to cellular tissues. Thus, methods for introducing genes have been studied. On the other hand, recently, in order to further improve the introduction efficiency, an ultrasonic contrast agent composed of microbubbles is administered to the living body, and the sonoporation phenomenon of the microjet that occurs when the ultrasonic contrast agent is crushed by ultrasonic irradiation. A method for gene transfer is being studied. According to this method, it is possible to introduce a gene with relatively low power ultrasonic energy, so that damage to normal tissue can be reduced (see, for example, Non-Patent Document 1).

  In the gene introduction method using the above-mentioned contrast agent, a contrast agent (microbubble) containing a gene that forms a new protein when it enters the cell nucleus or added to the surface is administered into the tumor tissue, and this tumor Genes are removed by sonicating the tissue to disrupt the microbubbles. And the taken-out gene is introduce | transduced in a cell through the hole of the cell membrane produced | generated at the time of crushing a microbubble. In this case, a method for improving the treatment accuracy by monitoring that the ultrasound contrast agent injected from the veins of the limbs of the patient has reached the treatment target site using ultrasound image data has been proposed (for example, patents). Reference 1).

On the other hand, introduction of a molecular imaging method for the purpose of confirming the effect of gene transfer is being studied. The molecular imaging method uses light and X-rays to visualize cells and molecules in the micro to nano order, and indirectly images the behavior of molecules based on the introduction of drugs into the molecule and metabolism. In the former, a fluorescence microscope or an X-ray microscope is used as the former, and a medical image diagnostic apparatus such as a nuclear medicine apparatus or an MRI apparatus is used as the latter. For example, in a nuclear medicine apparatus, imaging of a metabolic function is possible by combining a radionuclide labeled with a target molecule with a contrast agent or a drug. On the other hand, imaging technology for angiogenesis using ultrasonic diagnostic equipment, X-ray diagnostic equipment, and MRI equipment is also attracting attention. Ultra-early diagnosis based on imaging of neovascularization of cancer, definite diagnosis of cancer, peripheral diagnosis It is expected as a means for early treatment effect determination in angiogenic factor induction treatment for arteriosclerotic embolism.
JP 2000-189521 A Hiroshi Furudate, Yoshinobu Mame “Development of ultrasonic gene transfer”, BME, ME Society of Japan, July 10, 2002, vol16, no7, p. 3-7

  According to the method described in Patent Document 1 described above, it is possible to know the timing at which the ultrasound contrast agent reaches the treatment target site by observing the ultrasound image data for monitoring purposes. There is no means for quantitatively grasping the contrast medium concentration. For this reason, it is impossible to accurately grasp whether or not an ultrasonic contrast agent having a sufficient concentration is accumulated at a predetermined irradiation position when performing ultrasonic irradiation on a treatment target site. In addition, there is no means for accurately grasping the state of crushing of the ultrasonic contrast agent by the irradiated ultrasonic waves. For these reasons, it has been difficult to accurately introduce a drug to a site to be treated.

  The present invention has been made in view of such problems, and its purpose is to promote introduction of a drug by applying an introduction energy wave to a labeled drug administered to a treatment target site together with the drug. An object of the present invention is to provide a drug introduction system and a drug introduction method capable of efficiently performing reliable drug introduction to a treatment target site by performing irradiation energy wave irradiation control based on information on a labeled drug.

  In order to solve the above-mentioned problem, the drug introduction system of the present invention according to claim 1 includes monitoring image data generating means for generating monitoring image data for a treatment target site to which a drug and a labeled drug are administered, and the monitoring An irradiation position setting unit that sets an irradiation position of an introduction energy wave for the purpose of introducing a drug based on information on the treatment target site in image data, and the introduction energy wave with respect to the irradiation position set by the irradiation position setting unit Based on the comparison result by the pixel value comparison means, the pixel value comparison means for comparing the pixel value of the pixel corresponding to the irradiation position of the monitoring image data with a predetermined threshold value, An irradiation control means for controlling irradiation of the introduced energy wave to the irradiation position is provided.

  On the other hand, the drug introduction method of the present invention according to claim 11 is based on a step of generating image data for a treatment target site to which a drug and a labeled drug are administered, and information on the treatment target site in the image data. A step of setting a region of interest, a step of setting an irradiation position of an introduction energy wave for the purpose of drug introduction based on the region of interest, and a step of generating monitoring image data before irradiation of the introduction energy wave with respect to the irradiation position Comparing the pixel value of the pixel corresponding to the irradiation position of the monitoring image data with a predetermined threshold, and irradiating the irradiation position with the introduced energy wave based on the comparison result. It is said.

  The drug introduction method of the present invention according to claim 12 is based on the step of generating image data for a treatment target region to which a drug and a labeled drug are administered, and information on the treatment target region in the image data. A step of setting a region of interest, a step of setting an irradiation position of an introduction energy wave for the purpose of introducing a drug based on the region of interest, a step of irradiating the irradiation energy wave to the irradiation position, and the irradiation Generating monitoring image data after irradiation of the introduced energy wave with respect to the position; comparing a pixel value of a pixel corresponding to the irradiation position of the monitoring image data with a predetermined threshold; and based on the comparison result, It has the step which performs additional irradiation of the introduction energy wave with respect to an irradiation position.

  As described above, according to the present invention, the irradiation energy wave is controlled based on the information of the labeled drug administered together with the drug to the site to be treated, so that it depends on the blood flow state at the site to be treated. It is possible to efficiently and reliably introduce a drug.

  Embodiments of the present invention will be described below with reference to the drawings.

(Device configuration)
A first feature of the embodiment of the present invention is that a drug is introduced into a treatment target site by crushing an ultrasonic contrast agent (labeled drug) administered together with a drug such as a gene to the treatment target site by ultrasonic irradiation. In this case, the above-mentioned drug introduction is performed under the observation of the monitoring image data, and the superposition of the predetermined irradiation position is performed based on the information of the ultrasonic contrast agent reflected in the monitoring image data before or after the introduction of the ultrasonic wave for introduction. It is to control the sonication.

  The second feature of the embodiment of the present invention is that the effect of drug introduction performed on a treatment target site is confirmed by molecular imaging data. In this embodiment, the case where the above-described monitoring image data is generated by the ultrasonic diagnostic apparatus will be described. However, the present invention is not limited to this, and other medical image diagnostic apparatuses may be used.

  An embodiment of the present invention will be described with reference to FIGS. FIG. 1 is a block diagram showing the overall configuration of the drug introduction system in this embodiment, and FIG. 2 is a block diagram showing a specific example of a monitoring image data generation unit and a drug introduction unit provided in this drug introduction system. is there.

  In FIG. 1, a drug introduction system 100 includes a drug introduction unit 1 that irradiates a treatment target site of a patient with ultrasonic waves for the purpose of drug introduction (hereinafter referred to as introduction ultrasonic waves), and a drug introduction time. Monitoring image data generating unit 21 for generating the monitoring image data, molecular imaging data generating unit 22 for generating molecular imaging data for confirming the drug introduction effect, monitoring image data generating unit 21 and molecular imaging data generating unit 22 The position detection unit 3 for detecting the position information of the drug and the position information of the drug introduction unit 1, the monitoring image data, the irradiation position data by the drug introduction unit 1 and the input described later based on the position information obtained by the position detection unit 3 Synthesis of region-of-interest data set by the department, or monitoring image data and molecular imaging data And a data combining unit 4 for the synthesis and the like.

  The drug introduction system 100 includes a region-of-interest data storage unit 5 in which position information of the region of interest is stored, an irradiation plan formulation unit 6 that formulates an irradiation plan based on the region of interest, and a treatment based on the irradiation plan. A pixel value comparison unit 7 for comparing the pixel value of the monitoring image data corresponding to the irradiation position of the introduction ultrasonic wave set in the target region with a preset threshold value (first threshold value and second threshold value); And an irradiation control unit 8 for controlling the irradiation of the introduction ultrasonic wave to the irradiation position based on the comparison result of the pixel value comparison unit 7, and further, the molecular imaging data and the monitoring image data synthesized by the data synthesis unit 4 A display unit 9 for displaying; an input unit 10 for performing input of patient information and setting of a region of interest for monitoring image data; and further, setting of a threshold for pixel value comparison; And a system control unit 11 that collectively controls each unit of the predicate.

  The drug introduction unit 1 supplies an ultrasonic wave irradiation unit 32 for irradiating an ultrasonic wave for introduction for introducing a drug to a treatment target site of the patient, and supplies a drive signal to the ultrasonic wave irradiation unit 32. The drive part 31 to be provided is provided.

  FIG. 2 shows a specific example of the drug introduction unit 1, and the applicator 321 in the ultrasonic irradiation unit 32 of the drug introduction unit 1 is filled with a coupling liquid 323 made of degassed water. Further, a concave or flat piezoelectric vibrator 322 that radiates introduction ultrasonic waves is attached above the applicator 321, and an ultrasonic probe 211 in the monitoring image data generation unit 21 is provided at the center opening thereof. It is mounted so that it can rotate / slide freely.

  On the other hand, a coupling film 324 made of a polymer material having an acoustic impedance substantially equal to that of the coupling liquid 323 is provided at a contact portion of the applicator 321 with the living body 51. Then, the ultrasonic wave for introduction irradiated from the piezoelectric vibrator 322 and the ultrasonic wave for monitoring transmitted / received by the ultrasonic probe 211 are transmitted through the coupling film 324 and the coupling liquid 323 having acoustic characteristics substantially equal to those of the living body 51, It is efficiently transmitted / received to / from the living body 51. The piezoelectric vibrator 322 is configured by two-dimensionally arranging N vibration elements, and the introduction ultrasonic wave radiated from these vibration elements is a predetermined irradiation position set in the treatment target region 55 of the living body 51. Focused on.

  On the other hand, the drive unit 31 of the medicine introduction unit 1 has a function of supplying a drive signal to the N vibration elements in the ultrasonic irradiation unit 32 in order to radiate introduction ultrasonic waves. A burst wave generator 311 for generating a continuous wave (burst wave) of time τ1 based on the supplied control signal, and a delay circuit 312 for giving a predetermined delay phase to the burst wave from the burst wave generator 311; A power amplifier 313 that amplifies the delayed burst wave to a predetermined magnitude based on a control signal from the irradiation control unit 8, and impedance matching is performed to efficiently supply the output of the power amplifier 313 to the piezoelectric vibrator 322. A matching circuit 314 is provided. Note that each of the delay circuit 312, the power amplifier 313, and the matching circuit 314 includes N channels corresponding to the number N of vibration elements of the piezoelectric vibrator 322.

  Based on the control signal from the irradiation control unit 8, the delay circuit 312 described above generates a burst wave to irradiate a desired region with the introduction ultrasonic wave irradiated by the piezoelectric vibrator 322 of the ultrasonic irradiation unit 32. A predetermined delay phase is given to the burst wave output from the generator 311. The delay phase is composed of a delay phase for deflecting the introduction ultrasonic wave in a predetermined direction and a delay phase for focusing the ultrasonic wave for a predetermined distance (focal length). It is uniquely determined by the irradiation position of the introduction ultrasonic wave.

  Next, the configuration of the monitoring image data generation unit 21 having a function of generating ultrasonic image data will be described with reference to the block diagram of FIG.

  The monitoring image data generation unit 21 supplies a transmission signal to the ultrasonic probe 211 that transmits and receives monitoring ultrasonic waves to and from the treatment target portion 55 of the living body 51, and also transmits the ultrasonic probe 211. An image data generation unit 212 that generates monitoring image data based on the received signal obtained from 211 is provided.

  The ultrasonic probe 211 can be the same as that used in normal ultrasonic diagnosis, and particularly prevents the introduction of ultrasonic waves for introduction by the piezoelectric vibrator 322 of the ultrasonic irradiation unit 32. An ultrasonic probe for sector scanning capable of imaging a wide range with a small ultrasonic wave transmitting / receiving surface is preferable. In this embodiment, the sector electronic scanning type ultrasonic probe 211 that electronically controls the transmission / reception direction of the ultrasonic beam to obtain a fan-shaped image region is used, but is not limited thereto. The distal end portion of the ultrasonic probe 211 shown in FIG. 3 has M micro-vibration elements (not shown) arranged one-dimensionally in the X direction. With these micro-vibration elements, an electrical pulse is transmitted as an ultrasonic pulse (transmission). (Ultrasonic wave) and transmitted to the subject 51, and at the time of reception, the ultrasonic reflected wave (received ultrasonic wave) from the subject 51 is converted into an electric signal.

  On the other hand, the image data generation unit 212 generates a drive signal for radiating a transmission ultrasonic wave from the piezoelectric vibrator 322 of the ultrasonic probe 211 to the living body 51 and a reception ultrasonic wave from the living body 51. A receiving unit 42 that receives via the ultrasonic probe 211, a signal processing unit 43 that performs signal processing for generating B-mode data on the received signal, and a B-mode that stores the obtained B-mode data An image data storage unit 44 that generates image data and a scanning control unit 45 that controls the scanning direction of ultrasonic waves in accordance with an instruction signal from the system control unit 11 are provided.

  The transmission unit 41 transmits a rate pulse generator 411 that generates a rate pulse for determining a repetition period of transmission ultrasound to be transmitted to the living body 51, a delay time for focusing the transmission ultrasound, and transmission in a predetermined direction. A transmission delay circuit 412 that emits ultrasonic waves and supplies a delay time for scanning the living body 51 to the rate pulse, a drive signal is generated based on the delayed rate pulse, and the drive signal is output to the ultrasonic probe 211. It has a pulser 413 that supplies the micro-vibration element.

  On the other hand, the receiving unit 42 includes an A / D converter 421 that performs A / D conversion on an M-channel received signal converted into an electrical signal by the micro-vibration element of the ultrasonic probe 211, and a predetermined direction that has been A / D converted. And a reception delay circuit 422 and an adder 423 for phasing and adding received signals from a predetermined depth.

  Each of the transmission delay circuit 412, the pulser 413, the A / D converter 421, and the reception delay circuit 422 described above is composed of M channels corresponding to the number M of micro-vibration elements of the ultrasonic probe 211.

  The signal processing unit 43 includes a logarithmic converter 431 that logarithmically converts the amplitude of a received signal to relatively emphasize a weak signal, and an envelope detector 432 that performs envelope detection on the logarithmically converted received signal. The image data storage unit 44 sequentially stores the B mode data generated by the signal processing unit 43 in units of scanning directions to generate monitoring image data.

  The scanning control unit 45 then transmits a transmission delay circuit 412 of the transmission unit 41 and a reception delay circuit of the reception unit 42 in order to perform ultrasonic transmission / reception in a predetermined scanning direction in the living body in accordance with an instruction signal from the system control unit 11. The delay time of 422 is controlled.

  On the other hand, the molecular imaging data generation unit 22 generates molecular imaging data in order to confirm the drug introduction effect at the treatment target site. The molecular imaging data generation unit 22 is provided with a medical image diagnostic apparatus used for normal clinical diagnosis such as a PET apparatus, an X-ray CT apparatus, and an MRI apparatus. Further, an ultrasonic diagnostic apparatus used as the monitoring image data generation unit 21 may be used in combination.

  Next, the position detection unit 3 in FIG. 1 includes the position information of the ultrasonic probe 211 in the monitoring image data generation unit 21, the position information of the detector in the molecular imaging data generation unit 22, and the superposition of the drug introduction unit 1. The position information of the applicator 321 in the sound wave irradiation unit 32 is detected. For example, a magnetic sensor is attached to each of the above, and position information is detected based on a reception signal from the magnetic sensor. Further, the position detection unit 3 detects the relative position of the irradiation area of the monitoring image data, molecular imaging data, and introduction ultrasonic wave with respect to the patient based on the position information of the ultrasonic probe 211, the detector and the applicator 321.

  Then, the data synthesis unit 4 synthesizes the monitoring image data and the irradiation area data based on the relative position information detected by the position detection unit 3, and further, the monitoring image data on which the irradiation area data is superimposed and the input described later. Synthesis with the region-of-interest data set in the unit 10 is performed. On the other hand, the region-of-interest data storage unit 5 stores the position information of the region of interest set by the operator using the input unit 10 based on the treatment target part of the monitoring image data displayed on the display unit 9.

  Next, the irradiation plan formulation unit 6 is preset in the position information of the region of interest stored in the region of interest data storage unit 5 and the input unit 10 and stored in its own storage circuit via the system control unit 11. A site to be treated based on the number of irradiations n1, irradiation time τ1, irradiation period τ2, irradiation energy, irradiation position interval dx in the horizontal direction (X direction), irradiation position interval dz in the depth direction (Z direction), etc. Develop an ultrasonic irradiation plan for the introduction. At this time, the irradiation position intervals dx and dz are determined based on the beam width in the X direction and the focal depth in the Z direction in the introduction ultrasonic wave.

  4A shows the monitoring image data 82 synthesized by the data synthesis unit 4, the position 83 of the piezoelectric vibrator 322 in the applicator 321 of the ultrasonic irradiation unit 32, and the region of interest 85 set in the input unit 10. As shown, the upper end portion of the monitoring image data 82 corresponding to the distal end portion 81 of the ultrasonic probe 211 is synthesized so as to correspond to the central portion of the piezoelectric vibrator 322 in the applicator 321. The boundary line of the region of interest 85 set so as to surround the region to be treated 84 is synthesized with the monitoring image data 82.

  On the other hand, FIG. 4B schematically shows the irradiation plan of the introduction ultrasonic wave set by the irradiation plan formulation unit 6, and the irradiation plan formulation unit 6 displays the region of interest set in the monitoring image data 82. 85 is divided into a plurality of minute regions formed by the above-described preset irradiation position intervals dx and dz, and the approximate center position of each minute region is set as the irradiation position (for example, C1 to C3) of the introduction ultrasonic waves. Set. Next, the irradiation order of the introduction ultrasonic waves with respect to these irradiation positions C1 to C3 is set in the direction of an arrow, for example. In FIG. 4B, the case where the number of minute regions in the depth direction is one is shown to simplify the following description. However, a plurality of regions can be set.

  Next, FIG. 5 is a time chart showing the irradiation waveform and irradiation order of the introduction ultrasonic waves for the irradiation positions C1 to C3 formulated by the irradiation plan formulation unit 6. In addition, in this figure, although it has shown about the case where the frequency | count n1 of irradiation with respect to the same irradiation position is set to 3 times, it is not limited to this. That is, after setting the focal point of the ultrasonic wave for introduction to the first irradiation position C1 in FIG. 4B and performing irradiation for the irradiation time τ1, the irradiation is stopped for the time τ3 (τ3 = τ2−τ1). In this state, the focal point of the introduced ultrasonic wave is moved to the adjacent irradiation position C2, and irradiation is performed on the irradiation position C2 for the irradiation time τ1. When the irradiation of the irradiation position C3 is completed by the same procedure, the focus of the introduction ultrasonic wave is returned to the irradiation position C1, and the irradiation of the irradiation positions C1 to C3 is repeated at the irradiation cycle τ2, and n1 = for each irradiation position. If irradiation of 3 times is performed, irradiation of the ultrasonic wave for introduction with respect to the treatment object site | part 84 will be once complete | finished. The irradiation plan formulation unit 6 formulates an irradiation plan as shown in FIGS. 4 and 5 based on the region of interest set by the operator.

  Next, the pixel value comparison unit 7 in FIG. 1 includes an arithmetic circuit and a storage circuit (not shown), and the storage circuit includes a first threshold value P1x and a second threshold value supplied from the input unit 10 via the system control unit 11. The threshold value P2x is stored. On the other hand, when the irradiation circuit radiates the introduction ultrasonic wave to the predetermined irradiation position Cn based on the irradiation plan formulated by the irradiation plan formulation unit 6, the calculation circuit calculates the irradiation position of the monitoring image data obtained immediately before the irradiation. A pixel value Pn corresponding to Cn is read from the data synthesis unit 4, and the pixel value Pn is compared with the first threshold value P1x stored in the storage circuit. Similarly, the pixel value comparing unit 7 stores the pixel value Pn corresponding to the irradiation position Cn of the monitoring image data obtained immediately after the introduction ultrasonic wave is irradiated to the irradiation position Cn and the storage. Comparison with the second threshold value P2x stored in the circuit is performed.

  Then, the irradiation control unit 8 supplies a control signal for performing irradiation to the irradiation position Cn to the driving unit 31 of the medicine introduction unit 1 based on the comparison result of the pixel values supplied from the pixel value comparison unit 7.

  Since the above-described pixel value comparison unit 7 and irradiation control unit 8 are the most important parts in this embodiment, the functions and effects of these units will be described in more detail.

  The first condition for introducing an effective drug to the treatment target site is to irradiate the introduction ultrasonic wave when the contrast agent is sufficiently accumulated (refluxed) at the predetermined irradiation position Cn. The second condition is to grasp whether or not the contrast agent is reliably crushed by irradiating this irradiation position Cn with the introduction ultrasonic wave. It is to perform irradiation.

  In contrast to the first condition described above, in this embodiment, the pixel value of the monitoring image data corresponding to the concentration of the contrast agent refluxed to the predetermined irradiation site is monitored, and this pixel value reaches a predetermined size. For example, the ultrasonic wave for introduction is irradiated.

  In FIG. 6A, for example, when the introduction ultrasonic wave is irradiated to the irradiation position C1, the driving unit 31 in the medicine introduction unit 1 controls based on the irradiation plan set by the irradiation plan formulation unit 6. (A-1) is the generation timing of the monitoring image data, (a-2) is the change curve of the pixel value P1 in the pixel corresponding to the irradiation position C1, and (a-3) is The irradiation trigger signal of the irradiation position C1 supplied to the drive part 31 of the chemical | medical agent introduction part 1 from the irradiation control part 8 is shown.

  That is, the introduction ultrasonic wave for the irradiation position C1 is irradiated according to the irradiation trigger signal at time t21, and most of the contrast agent accumulated at the irradiation position C1 is crushed. As the contrast agent is crushed, the pixel value P1 corresponding to the irradiation position C1 of the monitoring image data also decreases rapidly as shown in (a-1). Next, while the introduction ultrasonic waves are irradiated to the irradiation positions C2 and C3, the contrast medium flows back to the irradiation position C1 along with the blood flow from the surrounding blood vessels or tissues. The value P1 also increases gradually. Then, the above-described irradiation plan is formulated so that the next irradiation with respect to the irradiation position C1 is performed at a time point t22 when a sufficient pixel value is reached.

  However, since the irradiation interval [t21 to t22] in this case largely depends on the blood flow state in the treatment target site, it is not desirable to set it strictly in the irradiation plan in consideration of individual differences among patients. For this reason, the above-described pixel value comparison unit 7 in the present embodiment calculates the pixel value P1 of the pixel corresponding to the irradiation position C1 from the monitoring image data obtained at the time t14 immediately before the irradiation timing t22 set in the irradiation plan. Then, the pixel value P1 is compared with the first threshold value P1x stored in its own storage circuit, and the comparison result is supplied to the irradiation control unit 8. Next, the irradiation control unit 8 reads the comparison result supplied from the pixel value comparison unit 7, and when the pixel value P1 is equal to or greater than the first threshold value P1x, the irradiation position C1 is irradiated at time t22 according to the irradiation plan.

  On the other hand, FIG. 6B shows the case of a patient whose contrast medium reflux is particularly slow at the irradiation position C1, and as in FIG. 6A, (b-2) shows the irradiation position. A change curve (b-3) of the pixel value P1 in C1 indicates an irradiation trigger signal at the irradiation position C1 supplied from the irradiation control unit 8 to the driving unit 31.

  That is, the irradiation control unit 8 that has received the comparison result supplied from the pixel value comparison unit 7 has the pixel value P1 of the monitoring image data obtained at time t14 immediately before the irradiation timing t22 set in the irradiation plan as the first value. If the threshold value P1x is not reached, the introduction ultrasonic wave irradiation at time t22 is stopped. If the pixel value P1 at the irradiation position C1 in the monitoring image data (for example, monitoring image data at time t15) obtained subsequently exceeds the threshold value P1x, the irradiation is performed at time t23 after a predetermined time Δτa from time t15. The introduction ultrasonic wave is irradiated to the position C1.

  Next, for the second condition for effective drug introduction to the treatment target site, in this embodiment, monitoring image data obtained immediately after irradiation of the introduction ultrasonic wave to the predetermined irradiation site, When the pixel value P1 at the irradiation position C1 in the monitoring image data is not reduced below the second threshold value P2x set in advance, the introduction ultrasonic wave is irradiated again to the same irradiation position.

  In FIG. 7A, for example, when the introduction ultrasonic wave is irradiated to the irradiation position C1, the driving unit 31 in the medicine introduction unit 1 controls based on the irradiation plan set by the irradiation plan formulation unit 6. (A-1) is the generation timing of the monitoring image data, (a-2) is the change curve of the pixel value P1 at the irradiation position C1, and (a-3) is the irradiation control unit. 8 shows an irradiation trigger signal at the irradiation position C1 supplied from 8 to the drive unit 31.

  Then, as shown in (a-2) of FIG. 7, the pixel value comparison unit 7 obtains at t15 immediately after the introduction ultrasonic wave is irradiated to the irradiation position C1 based on the irradiation trigger signal at time t22. The pixel value P1 of the pixel corresponding to the irradiation position C1 of the obtained monitoring image data is extracted. Next, the pixel value P1 is compared with the second threshold value P2x stored in its own storage circuit, and the comparison result is supplied to the irradiation control unit 8. On the other hand, the irradiation control unit 8 reads the comparison result supplied from the pixel value comparison unit 7, and when the pixel value P1 is less than or equal to the threshold value P2x, the irradiation control unit 8 temporarily ends the irradiation to the irradiation position C1, and introduces the adjacent irradiation position C2. Shift to ultrasonic irradiation.

  On the other hand, FIG. 7B shows a case where the introduction ultrasonic wave is insufficiently irradiated to the irradiation position C1 due to reasons such as body movement, and in the same manner as in FIG. -2) represents a change curve of the pixel value P1 at the irradiation position C1, and (b-3) represents an irradiation trigger signal at the irradiation position C1 supplied from the irradiation control unit 8 to the driving unit 31.

  That is, the irradiation control unit 8 that has received the pixel value comparison result from the pixel value comparison unit 7 has the pixel value P1 of the monitoring image data obtained at time t15 immediately after the irradiation timing t22 greater than the second threshold value P2x. In this case, the irradiation position C1 is irradiated again at time t24, which is a predetermined time Δτb after time t15. Then, when the pixel value P1 of the monitoring image data obtained at time t16 immediately after the irradiation is equal to or less than the threshold value P2x, the process shifts to irradiation for the next irradiation position C2.

  On the other hand, when the pixel value P1 is larger than the threshold value P2x, the irradiation of the introduction ultrasonic wave and the comparison of the pixel value are repeated in the same procedure, and if it is confirmed that the pixel value P1 is less than or equal to the threshold value P2x, Transition to irradiation with respect to the irradiation position C2. Note that the above-described times Δτa and Δτb are set in the initial setting together with the irradiation time τ1 and the like.

  Returning to FIG. 1, the display unit 9 includes a display data generation circuit, a conversion circuit, and a monitor (not shown). The above-described monitoring image data and molecular imaging data stored in the data synthesizer 4 are subjected to scan conversion in the display data generation circuit, and D / A conversion and television format conversion are performed in the conversion circuit for the monitor. Is displayed. In particular, when displaying the monitoring image data, the position information of the applicator 321, the region of interest 85, the position information of the plurality of irradiation positions C1 to C3 set based on the region of interest 85, and various incidental information, etc. It is also possible to display it superimposed on the monitoring image data.

  Next, the input unit 10 is an interactive interface including input devices such as a display panel, a keyboard, a trackball, a mouse, and a selection button on the operation panel. The input unit 10 inputs patient information, selects an image data collection device, and images. Selection of display mode, setting of region of interest, setting of irradiation position interval dx in the horizontal direction (X direction) and irradiation position interval dz in the depth direction (Z direction), irradiation time τ1, irradiation period τ2, time Δτa And .DELTA..tau.b, the number of times of irradiation n1, the irradiation energy, the first threshold value P1x and the second threshold value P2x for the pixel value of the monitoring image data, and the input of various command signals. As the above image display mode, there are display of monitoring image data and molecular imaging data, and an ultrasonic diagnostic apparatus, PET apparatus, CT apparatus, MRI for generating monitoring image data or molecular imaging data as an image data collection apparatus. There are medical image diagnostic apparatuses such as apparatuses.

  The system control unit 11 includes a CPU and a storage circuit (not shown), and input information, setting information, and selection information input from the input unit 10 by an operator are stored in the storage circuit. On the other hand, the CPU performs control of each unit of the drug introduction system 100 and control of the entire system based on the above-described information input from the input unit 10.

(Procedure for introducing drug to the target site)
Next, the procedure for introducing a drug in this embodiment will be described with reference to the flowchart of FIG.

  The operator grasps the position and state of the treatment target site by the pre-treatment diagnosis for the patient. In particular, when performing an image diagnosis on a treatment target site, an ultrasonic diagnostic apparatus, an MRI apparatus, an X-ray CT apparatus, or the like provided in the molecular imaging data generation unit 22 of the drug introduction system 100 may be used. Is possible.

  When the pre-treatment diagnosis is completed, the operator inputs patient information at the input unit 10, then sets the display mode of the monitoring image data as the image display mode, and an image data collection device for generating the monitoring image data As an ultrasonic diagnostic device is selected.

  Further, the operator uses the input unit 10 to set the irradiation position interval dx in the horizontal direction and the irradiation position interval dz in the depth direction, the irradiation time τ1, the times Δτa and Δτb, the number of irradiations n1 with respect to the predetermined irradiation position, and the irradiation energy (burst wave). Amplitude), the first threshold value P1x, the second threshold value P2x, and the like are set for the pixel values of the monitoring image data. The information set at this time is stored in the storage circuit of the system control unit 11, and the irradiation position interval dx and dz, the irradiation time τ1, the number of irradiations n1, the irradiation energy, the time Δτa and Δτb, etc. 6 and the first threshold value P1x and the second threshold value P2x are stored in the storage circuit of the pixel value comparison unit 7 (step S1 in FIG. 8).

  When these initial settings are completed, the ultrasonic probe 211 of the monitoring image data generation unit 21 and the applicator 321 in the ultrasonic irradiation unit 32 of the medicine introduction unit 1 are fixed to the body surface of the patient, and the monitoring image data A command signal for starting generation and display of the command is input.

  The system control unit 11 that has received this command signal supplies an instruction signal for performing ultrasonic transmission / reception in the scanning directions θ1 to θP to the scanning control unit 45 of the monitoring image data generation unit 21, and the scanning control unit 45 In accordance with this instruction signal, the transmission delay time of the transmission unit 41 and the reception delay time of the reception unit 42 are controlled to perform ultrasonic transmission / reception in the scanning directions θ1 to θP. Then, the signal processing unit 43 performs signal processing on the received signal from each scanning direction, saves the obtained B-mode data in the image data storage unit 44, and generates monitoring image data.

  On the other hand, the position detection unit 3 detects relative position information based on the position information of the ultrasonic probe 211 in the monitoring image data generation unit 21 and the position information of the applicator 321 in the ultrasonic irradiation unit 32 of the medicine introduction unit 1. The data synthesizing unit 4 synthesizes the monitoring image data and the irradiation region data of the medicine introduction unit 1 based on the detected relative position information and displays the synthesized data on the monitor of the display unit 9 (step S2 in FIG. 8).

  Next, the operator observes the monitoring image data displayed on the display unit 9, and sets a region of interest for the treatment target region of the monitoring image data using the input device of the input unit 10. Then, the set position information of the region of interest is stored in the region of interest data storage unit 5 (step S3 in FIG. 8).

  Next, the irradiation plan formulation unit 6 reads the position information of the region of interest stored in the region of interest data storage unit 5, and the position information of the region of interest and the irradiation position intervals dx and dz stored in its own storage circuit. Are set to the irradiation positions C1 to C3 of the irradiation plan, and the irradiation time τ1, the irradiation period τ2, and the irradiation waveform and irradiation order of the irradiation plan for these irradiation positions C1 to C3 are stored in its own memory circuit, This is set based on the number of irradiations n1, irradiation energy, etc. (step S4 in FIG. 8).

  If the above-mentioned irradiation plan is formulated, the drug and the ultrasound contrast agent are administered from the patient's upper limb vein, for example (step S5 in FIG. 8), and the arrival of this contrast agent to the treatment target site is monitored. If it confirms by observation, the command signal for starting irradiation of the ultrasonic wave for introduction | transduction with respect to a treatment object site | part will be input from the input part 10 (step S6 of FIG. 8).

  Next, the monitoring image data generation unit 21 generates monitoring image data immediately before the introduction of the introduction ultrasonic wave to the first irradiation position C1 set in the irradiation plan and stores it in the data synthesis unit 4 (FIG. 8). Step S7). In this case, the amplitude of the monitoring ultrasonic wave emitted from the ultrasonic probe 211 to generate monitoring image data and monitoring image data immediately after the introduction ultrasonic wave irradiation, which will be described later, is the ultrasonic contrast at the irradiation position. The power is set low enough that the agent does not break.

  On the other hand, the pixel value comparison unit 7 compares the pixel value P1 of the pixel corresponding to the irradiation position C1 of the monitoring image data with the first threshold value P1x stored in its own storage circuit (step S8 in FIG. 8). The comparison result is supplied to the irradiation control unit 8.

  The irradiation control unit 8 that has received the comparison result from the pixel value comparison unit 7 irradiates the irradiation position C1 with the introduction ultrasonic wave when the pixel value P1 of the monitoring image data is greater than or equal to the first threshold value P1x. (Step S9 in FIG. 8). On the other hand, when the pixel value P1 of the monitoring image data is smaller than the first threshold value P1x, the pixel value P1 corresponding to the irradiation position C1 of the monitoring image data obtained subsequent to the monitoring image data by the same procedure and the above-mentioned The comparison with the threshold value P1x is continued (steps S7 and S8 in FIG. 8). If the pixel value P1 in the new monitoring image data is equal to or greater than the first threshold value P1x, the ultrasonic wave for introduction to the irradiation position C1 is detected. Irradiation is performed (step S9 in FIG. 8).

  Next, the monitoring image data generation unit 21 generates monitoring image data immediately after the irradiation of the introduction ultrasonic wave to the irradiation position C1, and stores the monitoring image data in the data synthesis unit 4 (step S10 in FIG. 8). The value comparison unit 7 compares the pixel value P1 of the pixel corresponding to the irradiation position C1 of the monitoring image data with the second threshold value P2x stored in its own storage circuit (step S11 in FIG. 8). The comparison result is supplied to the irradiation control unit 8.

  Then, in the supplied comparison result, when the pixel value P1 of the monitoring image data is equal to or less than the second threshold value P1x in the supplied comparison result, the irradiation control unit 8 shifts to the irradiation of the introduction ultrasonic wave to the next irradiation position C2 (FIG. 8 steps S7 to S11). On the other hand, if the pixel value P1 of the monitoring image data is larger than the second threshold value P2x, the irradiation of the irradiation position C1 and the comparison between the pixel value P1 of the monitoring image data obtained immediately after the irradiation and the threshold value P2x are repeated. (Steps S9 and S11 in FIG. 8), and if the pixel value P1 becomes smaller than the second threshold value P2x, the irradiation position C2 is irradiated with the introduction ultrasonic wave (Steps S7 to S11 in FIG. 8).

  Then, when the irradiation to the irradiation position C3 is completed by the above-described procedure, the irradiation of the ultrasonic wave for introduction to the treatment target site is temporarily stopped (step S12 in FIG. 8), and the drug introduction effect by the molecular imaging data after a predetermined time elapses. Confirm. When generating molecular imaging data, the operator selects, for example, an MRI apparatus from the available medical imaging diagnostic apparatuses, and observes the gene expression status at the treatment target site by applying molecular imaging means such as Gene Expression Imaging. To confirm the drug introduction effect.

  For the selected MRI apparatus, the position detector 3 detects its position information, and the data synthesizer 4 stores molecular imaging data obtained by the MRI apparatus based on the detected position information and the region-of-interest data storage 5 Are combined with the region-of-interest data stored in the data and displayed on the display unit 9 (step S13 in FIG. 8).

  In the displayed molecular imaging data, for example, the operator observes the drug introduction effect at the treatment target site in the region of interest, and if the drug introduction effect is confirmed in the entire region of the treatment target region, The drug introduction by the irradiation of ultrasonic waves is terminated (step S14 in FIG. 8).

  On the other hand, when a region where the drug introduction effect is insufficient is recognized in the treatment target region, the region of interest is set for the region using the input device of the input unit 10 (step S15 in FIG. 8). Then, the process returns to step S4 in FIG. 8 and the introduction of ultrasonic waves for introduction to the newly set region of interest and the confirmation of the drug introduction effect are repeated (steps S4 to S14 in FIG. 8).

  In the present embodiment described above, when introducing a drug to a treatment target site by crushing an ultrasonic contrast agent administered together with the drug to the treatment target site by irradiation of the introduction ultrasonic wave, irradiation of the introduction ultrasonic wave is performed. Since the introduction of the ultrasound for introduction is controlled based on the reflux state of the ultrasound contrast agent in the monitoring image data obtained immediately before, the ultrasound imaging is always performed without being affected by the blood flow state of the patient. It is possible to irradiate the treatment target site where the agent has reached a predetermined concentration with ultrasonic waves for introduction.

  In addition, since the irradiation of the introduction ultrasonic wave is controlled based on the crushed state of the ultrasonic contrast agent in the monitoring image data obtained immediately after the introduction of the ultrasonic wave for introduction, for example, it is temporarily Even if a state in which the sonic contrast agent is not sufficiently crushed occurs, it is possible to irradiate the optimum introduction ultrasonic wave by additional irradiation without excess or deficiency.

  That is, according to the above-described embodiment, the irradiation of the introduction ultrasonic wave to the predetermined irradiation position is controlled based on the information of the ultrasonic contrast agent reflected in the monitoring image data immediately before or after the introduction of the introduction ultrasonic wave. Therefore, it is possible to efficiently introduce a drug with high accuracy to the treatment target site.

  Further, according to this embodiment, the pixel value of the monitoring image data obtained immediately before and immediately after the introduction of ultrasonic waves for introduction is compared with a preset threshold value, and a predetermined irradiation position is determined based on the comparison result. Since the introduction of ultrasonic waves for introduction is controlled, it is possible to automatically perform accurate control, not only shortening the time required for treatment, but also reducing the burden on the operator and patient. be able to.

  Furthermore, in the above-described embodiment, since the effect of the drug introduction performed on the treatment target site can be confirmed in a short time by the molecular imaging data, the accuracy of the drug introduction can be further improved. It becomes.

  As mentioned above, although the Example of this invention was described, this invention is not limited to the above-mentioned Example, It can be implemented in various deformation | transformation. For example, in the above-described embodiment, the introduction ultrasonic wave is irradiated based on the comparison result between the pixel value P1 of the monitoring image data obtained immediately after the introduction of the ultrasonic wave for introduction to the predetermined irradiation position and the second threshold value P2x. In the control, when the pixel value P1 is larger than the second threshold value P2x, the additional irradiation with respect to the same irradiation position is continuously performed. However, the irradiation position when the pixel value P1 is larger than the second threshold value P2x. The position information Cx is stored, and when the introduction ultrasonic wave irradiation based on a preset irradiation plan is completed, or when the first ultrasonic wave irradiation for a plurality of irradiation positions is completed, the position information is stored. Additional irradiation with respect to the irradiation position of Cx may be performed collectively. In this case, when there are a plurality of irradiation positions that require additional irradiation, the irradiation plan formulation unit 6 formulates a new irradiation plan based on the position information Cx, and performs additional irradiation based on the irradiation plan. Also good. The mapping data of the irradiation position Cx at this time is created and displayed on the display unit 9, whereby the operator can visualize the additional irradiation state of the introduction ultrasonic wave. Furthermore, in this case, it is desirable to display the areas that require additional irradiation, the areas that cannot be irradiated, the irradiated areas, and the like by color.

  On the other hand, although the case where an MRI apparatus is used as the molecular imaging data generation unit 22 in the above-described embodiment has been described, a nuclear medicine apparatus (PET apparatus and SPECT apparatus), an ultrasonic diagnostic apparatus, an X-ray CT apparatus, and an X-ray diagnostic apparatus are used. It may be used. In particular, when a nuclear medicine apparatus is used, it is desirable to administer RI together with a drug or an ultrasound contrast agent to a treatment target site of the patient. Further, as the molecular imaging data, for example, different types of image data such as X-ray CT image data excellent in morphological diagnostic ability and nuclear medicine image data excellent in functional diagnostic ability may be synthesized and used. Furthermore, the above-described molecular imaging data and monitoring image data can be combined and displayed.

  On the other hand, although the case where an ultrasonic contrast agent is used as the labeling agent has been described, other labeling agents may be used. In the above-described embodiment, the number of irradiation positions is three and the number of irradiation times n1 for the predetermined irradiation position is three. However, the present invention is not limited to this.

The block diagram which shows the whole structure of the chemical | medical agent introduction system in the Example of this invention. The block diagram which shows the specific example of the monitoring image data production | generation part in the chemical | medical agent introduction system of the Example, and a chemical | medical agent introduction part. The block diagram which shows the structure of the monitoring image data generation part of the Example. The figure which shows typically the irradiation plan of the ultrasonic wave for introduction in the Example. The time chart which shows the irradiation waveform and irradiation order of the introduction ultrasonic wave in the Example. The figure which shows the irradiation control method based on the monitoring image data before irradiation of the ultrasonic wave for introduction in the Example. The figure which shows the irradiation control method based on the monitoring image data after the irradiation of the ultrasonic wave for introduction in the Example. The flowchart which shows the procedure of the chemical | medical agent introduction | transduction in the Example.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 ... Drug introduction part 3 ... Position detection part 4 ... Data composition part 5 ... Region of interest data storage part 6 ... Irradiation plan formulation part 7 ... Pixel value comparison part 8 ... Irradiation control part 9 ... Display part 10 ... Input part 11 ... System Control unit 21 ... monitoring image data generation unit 22 ... molecular imaging data generation unit 31 ... drive unit 32 ... ultrasonic irradiation unit 100 ... drug introduction system 211 ... ultrasonic probe 212 ... image data generation unit 311 ... burst wave generator 312 ... Delay circuit 313 ... Power amplifier 314 ... Matching circuit 321 ... Applicator 322 ... Piezoelectric vibrator 323 ... Coupling liquid 324 ... Coupling film

Claims (13)

Monitoring image data generating means for generating monitoring image data for a treatment target site to which a drug and a labeled drug are administered;
An irradiation position setting means for setting an irradiation position of an introduction energy wave for the purpose of drug introduction based on information on the treatment target site in the monitoring image data;
Introducing energy wave irradiation means for irradiating the introduction energy wave to the irradiation position set by the irradiation position setting means,
Pixel value comparing means for comparing a pixel value of a pixel corresponding to the irradiation position of the monitoring image data with a predetermined threshold;
A drug introduction system comprising irradiation control means for controlling irradiation of an introduction energy wave to the irradiation position based on a comparison result by the pixel value comparison means.   The pixel value comparison unit compares the pixel value of the monitoring image data generated before irradiation of the introduction energy wave with respect to the irradiation position with a first threshold value, and the irradiation control unit includes the pixel value comparison unit. 2. The drug introduction system according to claim 1, wherein whether or not the introduction energy wave is irradiated with respect to the irradiation position is determined based on a comparison result obtained by.   The irradiation control means irradiates the irradiation energy wave to the irradiation position when the pixel value is equal to or larger than the first threshold value or larger than the first threshold value in the comparison result by the pixel value comparison means. 3. The medicine introduction system according to claim 2, wherein control for controlling the introduction energy wave irradiation means is performed.   The pixel value comparison unit compares the pixel value of the monitoring image data generated after irradiation of the introduction energy wave with respect to the irradiation position with a second threshold value, and the irradiation control unit is based on the pixel value comparison unit 2. The drug introduction system according to claim 1, wherein whether or not additional irradiation of the introduced energy wave to the irradiation position is appropriate is determined based on a comparison result.   The irradiation control means performs additional irradiation of the introduced energy wave on the irradiation position when the pixel value is greater than or equal to the second threshold value or greater than the second threshold value in the comparison result by the pixel value comparison means. 5. The drug introduction system according to claim 4, wherein control for performing is performed on the introduction energy wave irradiation means.   A region-of-interest setting unit, and the irradiation position setting unit sets the irradiation position of the introduced energy wave based on the region of interest set by the region-of-interest setting unit with respect to the treatment target site of the monitoring image data. The drug introduction system according to claim 1.   The drug introduction system according to claim 1, further comprising display means for displaying monitoring image data, wherein the display means displays the comparison result obtained by the pixel value comparison means in a superimposed manner on the monitoring image data.   The labeling agent is an ultrasound contrast agent, and the introduction energy wave irradiation means irradiates the irradiation position of the treatment target site where the ultrasound contrast agent is administered together with the agent, The drug introduction system according to claim 1.   Molecular imaging data generation means, wherein the molecular imaging data generation means generates image data for confirming the drug introduction effect in the treatment target site irradiated with the introduction energy wave by the introduction energy wave irradiation means. The drug introduction system according to claim 1, wherein:   The drug introduction system according to claim 9, wherein the molecular imaging data generation means is at least one of an MRI apparatus, a nuclear medicine apparatus, an X-ray diagnostic apparatus, an X-ray CT apparatus, and an ultrasonic diagnostic apparatus. Generating image data for a site to be treated to which the drug and the labeled drug have been administered;
Setting a region of interest based on information on the treatment site in the image data;
Setting an irradiation position of an introduction energy wave for drug introduction based on the region of interest;
Generating monitoring image data before irradiation of the introduced energy wave to the irradiation position;
Comparing a pixel value of a pixel corresponding to the irradiation position of the monitoring image data with a predetermined threshold;
A method for introducing a medicine, comprising the step of irradiating the irradiation position with an introduction energy wave based on the comparison result Generating image data for a site to be treated to which the drug and the labeled drug have been administered;
Setting a region of interest based on information on the treatment site in the image data;
Setting an irradiation position of an introduction energy wave for drug introduction based on the region of interest;
Irradiating the introduced energy wave to the irradiation position;
Generating monitoring image data after irradiation of the introduced energy wave to the irradiation position;
Comparing a pixel value of a pixel corresponding to the irradiation position of the monitoring image data with a predetermined threshold;
A method for introducing a medicine, comprising the step of performing additional irradiation of an introduction energy wave to the irradiation position based on the comparison result.   The drug introduction method according to claim 11 or 12, further comprising a step of generating molecular imaging data for confirming a drug introduction effect in the treatment target site irradiated with the introduction energy wave.

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