CN1389179A - Acoustodynamic tumor imaging method and device - Google Patents
Acoustodynamic tumor imaging method and device Download PDFInfo
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- CN1389179A CN1389179A CN 02134326 CN02134326A CN1389179A CN 1389179 A CN1389179 A CN 1389179A CN 02134326 CN02134326 CN 02134326 CN 02134326 A CN02134326 A CN 02134326A CN 1389179 A CN1389179 A CN 1389179A
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Abstract
The present invention relates to an acoustic-dynamic imaging method of tumor, which includes: after the acoustic sensing agent is selectively distributed in the tumor tissue, it utilizes the sensitization of ultrasonic wave to produce active oxygen free radical in the tumor tissue; and utilizes chemiluminescent reagent to directly real time convert the active oxygen free radical produced in the course of acoustic sensitization process into photon radiation, on this basis utilzies optical detection technology to make image formation of tumor. Its equipment is formed from ultrasonic wave generation component, photooptical receiving component, A/D converter and computer, said ultrasonic wave generation component is electrically connected with computer, the photooptical receiving component and A/D converter are electrically connected with computer in turn.
Description
Technical field
The present invention relates to medical science and medical apparatus and instruments.A kind of in more detail utilization is to the sound sensitiser in the harmless weak ultrasonic sensitization tumor tissues of organism, and it is luminous to produce the acoustodynamics endogenous, and utilizes the luminous not damaged imaging method of carrying out tumor tissues of this endogenous.
The invention still further relates to and realize the used device of said method.
Background technology
Medically the diagnosis of malignant tumor must depend on the integrated application of clinical diagnosis, instrument diagnoses (as CT, MRI etc.), laboratory (tumor markers, gene test etc.) and pathological diagnosis, and can not make right judgement by certain single means, the diagnosis cost is high, and can't realize the infantile tumour diagnosis.
The Biomedical Photonics imaging technique has to human zero damage, resolution height, can accomplish advantage such as functional imaging that less, biological autofluorescence is disturbed stronger and weak point is a penetration depth.Ultrasonic on the other hand penetration performance in vivo is very good, but can only accomplish the boundary reflection imaging based on ultransonic imaging technique (as B ultrasonic) at present, and resolution is lower.Optical imagery for tumor tissues, the general medicine fluorescence imaging method that adopts induced with laser, because it uses the short excitation source of wavelength, therefore produce can't overcome organize autofluorescence to disturb, problem such as penetration depth is little, will produce the side effect of skin phototoxicity inevitably when utilizing the method in addition, bigger to patient's damage.
Summary of the invention
The object of the present invention is to provide a kind of acoustodynamics formation method of tumor, body is had stronger penetration capacity and optical imagery has high-resolution, undamaged advantage, can not produce radiation injury organism in conjunction with ultrasonic.
Another object of the present invention is to provide a kind of acoustodynamics imaging device of tumor.
The present invention produces reactive oxygen free radical by ultransonic sensibilization after utilizing sound sensitiser optionally to distribute in tumor tissues in tumor tissues; Utilize chemical illuminating reagent directly in real time reactive oxygen free radical in the sound activation process to be converted into photon radiation and come out, on this basis, utilize optical detective technology to carry out the imaging in vivo of tumor.
The acoustodynamics formation method of tumor of the present invention comprises the steps:
---sound sensitiser distributes in tumor tissues, and chemical illuminating reagent distributes in vivo;
---the ultrasonic body that directly acts on, the sound sensitiser in tumor tissues produces reactive oxygen free radical, with the chemical illuminating reagent reaction, produces the acoustodynamics chemiluminescence at the tumor tissues place;
---optical fiber receive module is the signal of telecommunication with luminescent conversion; The signal of telecommunication is a digital signal by analog digital conversion;
---processing digital signal is also carried out image reconstruction, obtains the location drawing picture of tumor tissues.
Described sound sensitiser be meant can be optionally in tumor tissues productive set and can under ultrasonication, produce the material of reactive oxygen free radical.As gallium porphyrin derivant ATX-70 etc.
Described chemical illuminating reagent be meant can be with reactive oxygen free radical generation chemical reaction the luminous and material that can use at body.As sea glimmering fluorescein analog FCLA etc.
Describedly ultrasonicly can continuous sound-field can be, also the pulse sound field can be by general sine signal source through power amplification rear drive ultrasonic transducer generating; Equally distributed sound field can be, also focusing acoustic field can be.
Described optical fiber receive module is the device that is used to survey light.For example CCD take pictures system, light confocal scanning system.Analog digital conversion can realize with general analog-digital converter, the CCD controller that for example image series capture card of National Instruments company production, or Princeton Instruments company is produced.Image reconstruction can for example be realized with the LabVIEW software of NationalInstruments company exploitation or the WINVIEW software of Princeton Instruments company exploitation with general image treatment software in conjunction with computer realization.
The acoustodynamics imaging device of tumor of the present invention is made of ultrasonic generating assembly, optical fiber receive module, analog-digital converter, computer, and ultrasonic generating assembly and computer are electrically connected, and optical fiber receive module, analog-digital converter and computer are electrically connected successively.
Ultrasonic generating assembly can adopt existing ultrasonic generating assembly, is electrically connected by functional generator, power amplifier and ultrasonic transducer and forms.The inventor has designed a kind of ultrasonic transducer that more helps directly acting on organism or tissue and form large tracts of land cylindricality sound field, so that obtain more distinct image, it is a piezoelectric ceramic piece, and two discs are coated with silver conductive film, form two electrodes.It can be driven by the sinusoidal signal after amplifying through power amplifier and produce ultrasonic.A disc of ultrasonic transducer is fixed on the recirculated water box with heat sink glue, but ON cycle water makes transducer refrigeration during work.
Optical fiber receive module is the device that is used to survey light, for example CCD take pictures system, light confocal scanning system.Analog-digital converter can adopt general analog-digital converter, or has other devices of analog-digital conversion function, the CCD controller that for example image series capture card of National Instruments company production, or Princeton Instruments company is produced.
Data processing software is housed in the computer, is used for organism or tissue image and rebuilds and handle.For example use the automated image acquisition process software of the LabVIEW platform development of National Instruments company.
Compared with prior art, the present invention has following advantage:
(1) the inventive method combines and ultrasonic body is had stronger penetration capacity and optical imagery has high-resolution, undamaged advantage, can not produce radiation injury to organism, thus compare with traditional medical imaging diagnosis method have not damaged, advantage that resolution is high;
(2) owing to be the acoustodynamics photon radiation of surveying no autofluorescence background noise in the method, the diagnosis signal to noise ratio is greatly improved.
(3) ultrasonic field penetrates big in tissue and can focus on tumor locus, is a kind of good curing excitaton source.
(4) the porphyrin class sound sensitiser of the no photosensitive effect of application can reduce skin photochemistry toxic side effects.
(5) cost of each assembly of device of the present invention is lower, so the cost of single unit system is also relatively low, again because the structure of this device is comparatively simple, so the production assembling is more or less freely, uses operation also more convenient.
Description of drawings
Fig. 1 is the acoustodynamics imaging device block diagram of tumor of the present invention;
Fig. 2 is the acoustodynamics image of a tumor bearing nude mice;
Fig. 3 is that Fig. 2 figure is superimposed upon resulting image on the same tumor bearing nude mice outline drawing.
The specific embodiment
Below in conjunction with drawings and Examples the present invention is further described.
Fig. 1 shows the structure of the acoustodynamics imaging device of tumor of the present invention, as seen from Figure 1, this device is made up of ultrasonic generating assembly 1, optical fiber receive module 2, analog-digital converter 3, computer 4, and wherein ultrasonic generating assembly 1 is electrically connected by functional generator 1-1, power amplifier 1-2, ultrasonic transducer 1-3 preface successively and constitutes; Optical fiber receive module 2 is connected and composed by take pictures camera lens 2-1 and detector 2-2; Ultrasonic generating assembly 1 is electrically connected with computer 4, and optical fiber receive module 2, analog-digital converter 3 are electrically connected successively with computer 4; 5 is that tested organism (or tissue), 6 is the darkroom.Select for use each member to connect to form this device, wherein: the AFG320 type arbitrary-function generator that functional generator 1-1 selects for use Tektronix company to make; The 2100L molded breadth band power amplifier that power amplifier 1-2 selects for use ENI company to make; Ultrasonic transducer 1-3 is that a diameter is 50mm, the piezoelectric ceramic piece of thick 3mm, and two discs are coated with silver conductive film, draw by lead, form two electrodes, and it can be driven by the sinusoidal signal after amplifying through power amplifier and produce ultrasonic.A disc of ultrasonic transducer is fixed on the recirculated water box with heat sink glue, but during work ON cycle water with the refrigeration transducer; The camera lens 2-1 that takes pictures selects the big digital aperture camera lens (50mm, f/1.2 type) of the Nikon company manufacturing that is applicable to that the low light level is taken for use; Detector 2-2 selects the refrigeration ICCD-576-S/1 type CCD of the enhancement mode of U.S. Princeton Instruments company manufacturing for use; The ST-130 type controller that analog-digital converter 3 selects for use U.S. PrincetonInstruments company to make; Computer 4 is selected Pentium IV microcomputer for use.
Said apparatus is applied to the transplantation tumor nude mice is carried out the imaging diagnostic test.Get one of tumor bearing nude mice, lumbar injection sound sensitiser ATX-70, ATX-70 is in the tumor tissues inner accumulated after 24 hours; Subcutaneous injection FCLA, after 30 minutes, its even diffusion profile.Be placed on the 6 interior ultrasonic transducer 1-3 faces of darkroom record outline drawing as shown in Figure 2 under faint light is shone; Shut the darkroom, producing frequency by the computer regulated functional generator is the sinusoidal signal of 40KHz, is 100W rear drive ultrasonic transducer 1-3 through power amplification, and ultrasonic a little less than producing, the power density of this weak ultrasonic arrival liver organization is about 0.38W/cm
2(ultrasonic to human body safety criterion 23bar far below U.S. FDA is equivalent to 19.32W/cm
2), under weak ultransonic sensibilization, tumor tissues produces the chemiluminescence of acoustodynamics endogenous, detector 2-2 writes down luminous signal 15min and luminous signal is converted into the signal of telecommunication by the camera lens 2-1 that takes pictures, 3 pairs of signals of telecommunication of analog-digital converter carry out analog digital conversion be behind the digital signal with its input computer, in computer, utilize the WINVIEW software of Princeton Instruments company exploitation to carry out image reconstruction and date processing and can obtain as shown in Figure 3 luminescent image.As seen from the figure, the inventive method can be to the tumor tissues imaging, and clear picture, signal to noise ratio are 4.89.
Claims (6)
1, a kind of acoustodynamics formation method of tumor is characterized in that comprising the steps:
---sound sensitiser distributes in tumor tissues, and chemical illuminating reagent distributes in vivo;
---the ultrasonic body that directly acts on, the sound sensitiser in tumor tissues produces reactive oxygen free radical, with the chemical illuminating reagent reaction, produces the acoustodynamics chemiluminescence at the tumor tissues place;
---with luminescent conversion is the signal of telecommunication; The signal of telecommunication is a digital signal by analog digital conversion;
---processing digital signal is also carried out image reconstruction, obtains the location drawing picture of tumor tissues.
2, the acoustodynamics formation method of tumor according to claim 1 is characterized in that described sound sensitiser is gallium porphyrin derivant ATX-70.
3, the acoustodynamics formation method of tumor according to claim 1 and 2 is characterized in that described chemical illuminating reagent is extra large glimmering fluorescein analog FCLA.
4, the acoustodynamics imaging device of the tumor of the method for claim 1 use, it is characterized in that constituting by ultrasonic generating assembly, optical fiber receive module, analog-digital converter, computer, ultrasonic generating assembly and computer are electrically connected, and optical fiber receive module, analog-digital converter and computer are electrically connected successively.
5, the acoustodynamics imaging device of tumor according to claim 4 is characterized in that ultrasonic generating assembly is electrically connected by functional generator, power amplifier and ultrasonic transducer to form.
6, the acoustodynamics imaging device of tumor according to claim 5 is characterized in that described ultrasonic transducer is a piezoelectric ceramic piece, and two discs are coated with silver conductive film, forms two electrodes.
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CN 02134326 CN1389179A (en) | 2002-07-09 | 2002-07-09 | Acoustodynamic tumor imaging method and device |
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CN 02134326 CN1389179A (en) | 2002-07-09 | 2002-07-09 | Acoustodynamic tumor imaging method and device |
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