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CN1735802A - Time discrimination optics imaging method and equipment used for part biological tissues of animal body - Google Patents

Time discrimination optics imaging method and equipment used for part biological tissues of animal body Download PDF

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Publication number
CN1735802A
CN1735802A CN200380108570.2A CN200380108570A CN1735802A CN 1735802 A CN1735802 A CN 1735802A CN 200380108570 A CN200380108570 A CN 200380108570A CN 1735802 A CN1735802 A CN 1735802A
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light
optical
illumination
collection
optics
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威廉·F·朗
伊夫·贝鲁布-洛齐埃
大卫·J·霍尔
劳拉·麦金托什
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ARTEAIDFAN TECHNOLOGY RESEARCH CORP
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ARTEAIDFAN TECHNOLOGY RESEARCH CORP
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Abstract

There is provided a method and system for collecting optical data for use in time resolved optical imaging wherein pulsed light is directionally propagated through free-space optics (24, 26, 28, 29) to impinge on a plurality of illumination at the surface of a biological tissue (14) such as that comprised in small animals. Light re-emitted from the tissue is collected and directionally propagated through free space optics (34, 36, 38) towards a detector (18) to produce time resolved optical signals useful for optical image reconstructions.

Description

The time discrimination optics imaging method and the equipment that are used for part biological tissues of animal body
The cross reference of related application
The application is that the sequence number of submitting on September 22nd, 2003 is No.10/665297, is entitled as the subsequent application of the U.S. Patent application of " time discrimination optics imaging method and the equipment that are used for part biological tissues of animal body "; And according to the regulation of 35 USC § 119 (e), the sequence number that requires on November 11st, 2002 to submit to is No.PCT/IB02/04698, is entitled as the right of priority of the PCT application of " time discrimination optics imaging method and the equipment that are used for biological tissue "; The sequence number that also requires on September 22nd, 2003 to submit to is No.10/665297, is entitled as the right of priority of the U.S. Patent application of " time discrimination optics imaging method and the equipment that are used for part biological tissues of animal body "; And the sequence number that on Dec 12nd, 2002 submitted to is No.60/505352, is entitled as the right of priority of the U.S. Patent application of " time discrimination optics imaging method and the equipment that are used for biological tissue ".
It is 15186-41US that the application relates to agent docket, and sequence number is the common appointment while U.S. Patent application co-pending of No.10/624902, thereby introduces its instructions as a reference.
Technical field
The present invention relates to turbid medium, the biological tissue of animal body part for example, optical imaging field.More particularly, the present invention relates to be used for the collection of the time resolution optical data of optical imagery.
Background of invention
Existing various imaging techniques can be non-invasively in the biological tissue Information Monitoring as the basis of image reconstruction, for example positron emission computerized tomography (PET), magnetic resonance imaging (MRI) and ultrasonic imaging.Recently, the another kind imaging technique that is called optical imagery has become the theme of popular research and business development.
Itself and matter interaction produce signal when light is propagated in object, and optical imagery is analyzed and the information that obtains this signal with regard to being based on.The optical imagery of turbid media can adopt three kinds of different approach to realize, i.e. continuous wave (CW), time domain (TD) and frequency domain (FD).CW is the simplest and the most cheap in three kinds of technology, but the limited space distribution information about the decay of imaging object interior lights can only be provided.TD and FD propagate (FD passes through Fourier transform) by photon and come transmission information in object in required time, thereby be considered to " time resolution ", and can be used for calculating the space distribution of object optical characteristics, for example absorbance and scattering coefficient, with known photon diffusion Equation for Calculating (about the retrospective paper of this theme article referring to Hawrysz and Sevick-Muraca, vol.2 No.5, pp388-417,2000).
Optical imagery receives publicity especially owing to its Noninvasive, and Noninvasive refers under the situation of not damaging biological tissue can obtain internal body information.And whether this technology exists in the sense organ unusually for the monitoring of drug distribution, and the physiologically active figure that perhaps draws in the mammalian body is very useful.
Yet,, hindered the widespread use of optical imaging system because there are some undesirable features in existing system.For example, optical imaging device usually needs to arrive or carry out complex setting from the optical fiber of the light of object being used to transmit.For example people such as the patented claim WO 02/41769 of Ntziachristos and Weissleder and Hillman, Phys.Med.Biol has described this system in 46 (2001) 1117~1130 the article.In these lists of references, the type setting that is used for optical element need be carried out alignment procedures consuming time with target area and the optical fiber that is used for illuminated objects and sensed light signal.Such being arranged on when mammiferous biological tissue carried out imaging especially is a problem.
Easily obtain data, particularly the relative optical element of object is easily located, in the high-throughout application of needs, be even more important, for example in clinical the setting or in the research of adopting such small-sized mammalian such as mouse.In this respect, developed the commercial optical imaging system that is used for the small-sized mammalian imaging.For example, the bioluminescence imaging system by Xenogen company (Biophotonics, vol.9, No.7 pp48-51,2002) exploitation is designed to gather the light that sends from the small-sized mammalian body.Yet this imaging device also has certain shortcoming.For example, need there be bioluminescent molecules in it, and distribution shape spatially is restricted in the body of this molecule, thereby greatly reduces the dirigibility in the imaging process of re-set target zone (ROI).In addition, this technology also is subjected to the restriction of existing light emitting molecule quantity.And this system can not obtain time-resolved data.
For above-mentioned reasons, people are desirable to provide a kind of optical imaging system that is used for imaging turbid media such as biological tissue, and it can obtain time-resolved optical data and have higher flexibility and efficient.
Summary of the invention
According to a broad aspect of the present invention, provide a kind of part biological tissues of animal body time discrimination optics imaging system and method that is used for.The design of the optical element of native system can make light beam directly by air borne, just by the Free Space Optics device, thereby beats on the expection illumination points in the target area (ROI) of organizing.Gather at the collection point place from organizing the light that sends once more, and directly propagate to detecting device by air (being the Free Space Optics device).Light has been cancelled the needs that optical fibre device carried out loaded down with trivial details setting by air borne, makes to have greater flexibility when scanning different ROI.So no longer need animal is directly contacted with optical element, thereby have enough spaces to control or near animal body.
The optical design of this system make illuminating bundle or skin/air interface place reflected light and gather minimum interference between the light, thereby throw light on and light collection by near the air in the site ROI.
In one embodiment, provide a kind of time-resolved optical imaging method, comprise with pulsed light beam with the rayed of one or more wavelength on a plurality of predetermined illumination points of animal body target area.Light beam is by air borne and by utilizing suitable optical element to aim at illumination points.Gather the light of a plurality of predetermined collection point by optical element, wherein the light that comes from the surf zone that has clear profile among the ROI can be optionally gathered in the configuration of this optical element.Then with the photoconduction gathered to detecting device to produce optical signalling, be used for generating optical imagery by reconstruction algorithm.
In another aspect of the present invention, the system of the optical data of using in a kind of acquisition time resolution imaging is provided, comprise that one or more light sources are used to provide the light beam of one or more wavelength, illumination optical device is used for directly propagating described light beam by air, therefore illuminate a plurality of illumination points of the target area of biological tissue in the animal body, thereby light has been injected in the tissue, the optically detecting element is used to be captured in the light the predetermined collection point place of target area launched once more and directly propagates described collection light by air, and time correlation, detecting device was used to detect described collection light.
Optimum system choosing of the present invention is arranged to gather the data that are used for topology or fault imaging.The topology imaging is that constant distance obtains between collection point and the illumination points by keeping.In illumination and collection optics, has synchronous mirror galvanometer to reach the constant distance between illumination points and the detection site.Topographic data acquisition configurations can be used for obtaining the image of 2 dimensions (2D) or 3 dimensions (3D).
The light that fault imaging need send from animal body again in several different acquisitions site/the detection points configurations sampling.Optimum system choosing of the present invention ground provides the removable mirror that can control independently in illumination and collection optics, thereby provides a kind of means in order to obtain the structure of a plurality of illumination points/collection point.
On the other hand, provide a kind of optical imaging method and system that is used for the biological tissue of containing fluorescence molecule.Described tissue can shine with excitation wavelength, and the light that sends once more can be collected and detect in the transmitted wave strong point.This system can also detect described emission wavelength and excitation wavelength.
Description of drawings
By detailed description below in conjunction with accompanying drawing, will more know further aspect of the present invention and advantage, wherein:
Fig. 1 is the embodiment process flow diagram of the inventive method;
Fig. 2 is the embodiment skeleton view of system of the present invention;
Fig. 3 is the system embodiment diagram that comprises a plurality of LASER Light Source;
Fig. 4 has schematically shown the raster scan pattern that throws light in the target area on mammal surface;
Fig. 5 is the embodiment diagram of system of the present invention, and wherein optical element is installed on the carriage that mammal is rotated to obtain to be used for the data of fault imaging; And
Fig. 6 is the embodiment diagram of system of the present invention, and wherein optical element is fixed, and the mammal rotation is to obtain to be used for the data of fault imaging.
Attention is in institute's drawings attached, and same feature is represented with identical Reference numeral.
Embodiment
The present invention relates to the optical imaging field of turbid medium such as part biological tissues of animal body.Although provide relevant example in the following preferred embodiment explanation, be understood that this method also can be used for relatively large animal, particularly laboratory animal for example dog, pig and primate such as the such small-sized mammalian imaging of mouse.
Referring to Fig. 1, the embodiment of the inventive method has roughly been described, be used for being captured in the optical data that time discrimination optics imaging uses.In the step 2, the pulsed light that sends from the light source of selected intensity is directly propagated (promptly by the Free Space Optics device) in air, thereby illuminates a plurality of predetermined illumination points among the ROI of biological tissue in the animal body.Step 4, optionally gather after organizing diffuse reflection from the light that a plurality of collection point are sent, and in step 6, directly relay to detecting device by free space by the Free Space Optics device.In step 8, should gather the optical signalling that light is differentiated with generation time at last with detectors measure.From detect, got rid of selectively from the light that non-sampling site sends.
Use description to gather the system embodiment of optical data now, wherein relate to small-sized mammalian as imageable target, but should be understood that the biological tissue of many types can adopt technology as described herein to do optical imagery.These tissues can be, but be not limited to breast tissue, brain, tumour or the like.
Fig. 2 has represented that system of the present invention is used for the generality diagram of small-sized mammalian imaging.This system comprises the light source 10 that can produce one or more wavelength light beams 12, pass through air, promptly by the Free Space Optics device, directly propagate the illumination optics of this light beam to mammal 14 lip-deep expection illumination points, be used to gather the light 16 that sends again from described mammal and will gather the collection optics that light directly propagates into detecting device 18, be installed in the movably mammal supporting tray 20 on the mobile platform 22, and the computing machine 19 that is used to control described light source, optical device, detecting device and pallet.
Illumination optics device comprises movably catoptron 24, is preferably mirror galvanometer.The angle mirror 26 that light beam is reflected and leads and simultaneously approach with angle θ by this mirror galvanometer, it reflects described light beam to be substantially perpendicular to the direction that is scanned the mammal surface.Should be understood that the deflection meeting of mirror galvanometer changes angle θ and with the different loci on the described thin angle mirror of beam direction, thereby the lip-deep different illumination points of the described mammal of leading.Therefore, the continuous deflection of mirror galvanometer 24 has produced the line scanning that is arranged essentially parallel to described thin angle mirror.Lens 28 optionally are provided and be arranged at mirror galvanometer and thin angle mirror between, make this mirror galvanometer be on the focal length of lens so that telecentric imaging to be provided.Also for example middle density optical filter 29 of optical filter can be arranged between light source and the mirror galvanometer 24 to regulate the intensity of light beam.
In one aspect of the invention, light source is preferably with the luminous variable intensity laser of specific wavelength.In order to produce multi-wavelength's illumination, can use beam of laser device 31, as diode laser, separately with different wavelength luminous (Fig. 3).Can with suitable optical filter for example optical filter 33 and 35 be arranged between light source and the mammal, and launch again between light and the detecting device, be used to select wavelength or regulate light intensity.Converter or dichroic mirror system can be used for continuously or side by side shine this mammal with different wave length.Selectively, also can use an independent multi wave length illuminating source.Under latter event, utilize optical filter, grating or its analog can chosen wavelength range or certain wavelengths, such as is known to the person skilled in the art.
The preferred intensity of light source is allowed the decision of exposure (MPE) limit by the maximum of biological tissue, and it is established by the adjusting situation.Briefly introduce the standard of safety exposure, for example, be used for the American National Standard (ANSI Z 136.1-2000) that laser safety is used.For example, for example concerning the non-invasive imaging of people or small-sized mammalian, should preferably be adjusted in the power of about 200mW or littler for biological tissue with near infrared ray (NIR) emitted laser.
Pallet 20 is carrying this mammal when its imaging.This mammal is preferably anaesthetized in data acquisition, and is minimum so that movability is dropped to.In alternate embodiments, part or whole animal can mechanically fettered to reduce movability.Selectively, can be with the pallet heating to keep this mammiferous body temperature.Pallet can vertically be arranged on the mobile platform 22 with the mammal location in addition, makes it to generate multirow line scanning parallel to each other.Repeat the selected number of times of this multi step format process, to produce raster scanning to target area (ROI).Selectively, can realize this raster scanning by the thin angle mirror 26 of vertical placement.Fig. 3 has represented the raster scan pattern example that carries out on the mammal surface.The user who limits ROI 40 delimit the zone that will scan, and it comprises predetermined illumination points 42.The setting of this optical element also allows to carry out other scan pattern.Be understood that ROI can be made of whole animal body.
The light that sends again from mammal is by the collection optics collection, and this optical device comprises gathers lens 34, and catoptron 36 is preferably mirror galvanometer, and lens 38.Gather the top that lens 34 are positioned at the ROI top and are positioned at thin angle mirror.Mirror 36 with respect to the angle determining positions of incident light and detecting device want sampled collection point because have only part to beat light (corresponding to given collection point) on this mirror with suitable angle reflection arrival detecting device.By this mirror galvanometer of optically-coupled and lens and/or aperture, can improve further the selectivity from the light of given collection point is detected.
Allow the whole setting of light, make to be easy to the location and to control animal body by airborne this optical device.And, because this system does not rely on optical fiber, be not only to control animal by mobile pallet new ROI is entered in the focal length of optical device so can scan a plurality of ROI.Moving of pallet can be carried out outside control by computing machine.
When light was beaten on the animal body surface, part light saw through its skin, and part is reflected at air/skin boundary place.The photon of propagating in this mammalian body has been absorbed with scattering, thereby has formed many photon paths.In biological tissue, when the macromolecular structure that forms inhomogeneous refractive index such as protein, lipid etc. cause scattering,, just can produce light absorption owing to have natural (inherent) or external chromophore.There is not absorbed part light finally leaving this mammal by the diffuse reflection of skin barrier from illumination points different distance place.Should be appreciated that the photon of propagating needs the long time to leave this mammiferous surface in darker tissue.This just provides the basis of time resolution detection optical signal, can select the useful optical signature information of relevant target area by it, so that add in the image reconstruction computing.In the uniform medium of optics, illumination points is relevant with the significant depth of photon average path with the distance between the site that given photon leaves.Therefore distance is big more between the site, and the degree of depth is dark more.And when biological tissue be non-optical when even, illumination points and photon leave the site between distance also can be considered to relevant with the average path degree of depth of photon.
In a preferred embodiment, the employed time resolution method of system of the present invention is time domain (TD).In TD measured, light source was subjected to brief pulse action, detected optical signalling as the function of time with rise time point spread function (TPSF).This light source is preferably the lasing light emitter that can produce the pulse of picosecond range width characteristics.Area detector in the time of can using, for example time grate is amplified CCD (ICCD), single photon counting device time correlation (TCSPC formula), ultrafast semiconductor detector (avalanche type and PIN photodiode), photomultiplier and streak camera.In a preferred embodiment, used the TCSPC device in the system of the present invention.TCSPC formula device can be measured when photon is propagated by illumination optics, tissue and collection optics, and it arrives detecting device institute's time spent.Time measurement provides by being electrically connected on light source and detecting device " clock " circuit.This circuit is known in the field.TCSPC formula device is very sensitive, and advantageously, allows to use lower wattage power supply so that the injury to the scanning tissue is minimized.
In an embodiment of the present invention, utilize system and method for the present invention, the similar attenuation measurement of measurement that can produce and use continuous wave to obtain by integrated TPSF.
By statistics, detection efficiency is promptly produced and aims at the photon numbers in specific illumination site and ratio from the detected photon numbers of given collection point by light source, in particular as light source power and with the function of the illumination points distance of gathering light.The intensity of light source can be adjusted, so that arrive the optimised characteristic that is suitable for detecting device of photon flux of detecting device.In a preferred embodiment, utilized the TCSPC detection system that small-sized mammalian is carried out the TD imaging, it usually need be to the photon detection probability of each illumination light pulse greatly about 1% distortion that causes with the loss of avoiding in instantaneous profile survey owing to electronics idle time, and is such as known to those skilled in the art.Aim at the illumination duration (by the quantity decision of light pulse) of giving anchor point on the mammalian body can change in case provide examining of sufficient amount photon produces appropriate signal, but make the duration short as much as possible to reduce acquisition time.According to the example to the meiofauna imaging, wherein the light transponder pulse frequency of Cai Yonging is 80MHz, and the power that needs to regulate light beam makes per second approximately detect 8 * 105 photons.The selection that should be appreciated that appropriate frequency is a basis, except other factors, particularly, optical element, detecting device, organized by imaging, and the feature of required optical data type.
TPSF can also produce by adopting time grate to amplify charge-coupled image sensor (ICCD).Such detecting device can provide spatial resolution, and it can detect the optical signalling that sends from different collection point simultaneously.In addition, when adopt producing the light source of two or more wavelength, can be divided into the composition wavelength light, aim at the difference of ICCD and detect the position thereby obtain two or more light beams at the light of any given collection point collection.Yet, because the sensitivity of ICCD is less than the TCSPC device, thereby the intensity that should regulate light source, to keep simultaneously can not causing tissue damage.
Consider the low intensity level of this light source, especially under the situation of using the TCSPC device, and the high sensitivity of detecting device, system and mammal can be arranged in the fully sheathed case, and for example box 50.This box is preferably lighttight to prevent any interference of stray light measurement.Can enter the inside of box by door 56.
In order to make up the image of mammalian body region of interest within (ROI), a plurality of illuminations from ROI/detection site obtains optical signalling.Being provided with of this illumination/detection site can change according to rebuilt image type.Following will describing utilizes system and method for the present invention can generate the topological sum faultage image, and all needs different illuminations/detection setting.
Determined the position with respect to the collection point of illumination points before gathering, it is the function of expection imaging depth in the target area.For the imaging surface near skin surface, collection point is positioned near the illumination points, because photon is advanced deeply more, near the probability that photon is launched illumination points again is disconnected low, and vice versa.
Therefore in order to obtain the topological diagram picture, keep the fixed range of collection point and illumination points, so that from essentially identical degree of depth Information Monitoring across ROI.With this constant illumination/detection site distance, the mirror galvanometer that is included in illumination and the collection optics can be finished quick scanning synchronously.
When illumination and the change of collection point order, can obtain layer data, produce a plurality of illuminations like this, thereby obtain the information of different depth collection points distances.Mode deal with data by suitable can generate faultage image.Gather for the tomography optical data, two mirror galvanometers 24 and 26 be preferably independent control so that obtain multiple fluoro data.Therefore when the mirror galvanometer in the illumination optics with photoconduction during to the illumination points of expecting, the mirror galvanometer in the collection optics can be designed at a plurality of different collection point daylighting samples.
In one embodiment, illumination and collection optics are installed in the movable carriage system 52 of moving object rotation (Fig. 5).In this specific embodiments, pallet preferably is " I " shape.This special shape helps that (for example: the data acquisition when trunk) rotating makes animal body cosily supported simultaneously around the target area in illumination and collection optics.With this structure, can make the angular displacement of amplitude be substantially equal to 360 degree.In another embodiment, mammalian body can replace the carriage rotation.Can hold it on the pallet on the pallet by should mammiferous leg tying up.It can rotate 360 ° around the head-tailing axle of health.Be compared to the movable carriage system, this structure design can reduce weight, volume and complicacy.
And in another embodiment, can be when mammal is placed with sitting posture along its head-tailing axle rotation.This animal body is placed on the platform, by supporting its head gently is kept upright in the target area like this.These designs allow animals to carry out the scannings of 360 degree, should be understood that can change optical devices to adapt to different fault tectonics.For example, the mirror 54 in " sitting posture " structure provides a kind of method of direct propagating light easily.
Because the scrambling of animal body profile, a plurality of angle acquisition optical datas around animal body can cause the distance between ROI surface and the collection optics that significant change is arranged.Therefore can adopt autofocus system and be scanned the reconstruction that regional profile improves image by acquisition.In this respect, system can also comprise the means of determining the animal body volume profile.In one embodiment, by determining its volume profile with the laser beam flying animal body that is basically perpendicular to the animal body direction.By gathering animal body surface laser beam image simultaneously, can determine its volume profile with laser path placement video camera at angle.This animal body can scan by mobile pallet.This volume profile that should be understood that so obtain can provide image reconstruction and the spatial information that shows usefulness.
Although the imaging of biological tissue depends on the natural optical characteristics of the interior molecules that the optical contrast is provided, also can introduce foreign molecules so that additional contrast to be provided.In this respect, can use exogenous chromophores and fluorophore.And, can use method and system of the present invention that this contrast preparation is then decomposed in vivo.In a preferred embodiment, thus body in decomposition can carry out obtaining pharmacokinetic data along with time lapse.
Can be arranged to throw light on and detect light with one or more wavelength in the Optical Device And source, as previously described.Can utilize this specific character to carry out the pharmacokinetics of two or more fluorophores and/or chromophore.Particularly, light source can be arranged to throw light on the excitation wavelength of fluorophore with relevant optical device, and detecting device can be arranged to detect light with the emission wavelength of this fluorophore with relevant optical device.
The embodiment of the invention described above is as just showing prominent example.Thereby scope of the present invention is that the claim of passing through to be added limits fully.

Claims (39)

1. a collection is used for the method for the optical data of animal body time discrimination optics imaging, and described force method comprises:
I) optical device by free space will be used for the described animal body location of data acquisition;
Ii) the pulsed light beam that will select intensity by the optical device of free space is directly propagated, thereby with a plurality of predetermined illumination points in the target area of the described animal body of one or more wavelength illumination;
Iii) optionally gather the light that sends from a plurality of predetermined collection point by the optical device of free space;
Iv) described collection light is directly propagated to detecting device by the optical device of free space;
V) with the collection light at one or more wavelength measurement detecting device places to produce time resolution optical signalling to one or more illumination points/detection points configurations; And
Wherein the light that sends from the site of non-predetermined collection point is optionally got rid of from detect.
2. the method for claim 1, wherein said time discrimination optics imaging is time domain (TD) imaging, and wherein the detection optical signal to generate the information of relevant time point spread function (TPSF).
3. method as claimed in claim 2, wherein said measuring process comprise utilizes time correlation single Photoncounting methods to detect described collection light.
4. method as claimed in claim 3, wherein each illumination points is by a plurality of pulse irradiations.
5. method as claimed in claim 4, wherein said illumination step comprise the distortion that the intensity of regulating light beam causes with the loss of avoiding owing to electronics idle time.
6. method as claimed in claim 5, wherein said intensity is regulated by the intensity that changes light source.
7. method as claimed in claim 6 is wherein regulated described intensity with optical filter.
8. as any one method as described in the claim 1-7, wherein detect the described optical signalling of two or more wavelength simultaneously.
9. as any one method as described in the claim 1-7, wherein sequentially detect the described optical signalling of two or more wavelength.
10. as any one method as described in the claim 1-9, wherein said illumination points is the power formula irradiation with raster scanning.
11. as any one method as described in the claim 1-10, wherein said collection point be positioned at the fixing distance of described illumination points to be provided for the optical signalling of topological imaging.
12. method as claimed in claim 11, wherein said distance are about 3mm.
13., wherein gather two or more collection point and be used for each illumination points, to be provided for the optical data of fault imaging as any one method as described in the claim 1-10.
14. method as claimed in claim 13 is wherein gathered two or more collection point at least simultaneously.
15. as any one method as described in the claim 1-14, the detection at wherein different with illumination wavelengths wavelength places is effective.
16. as any one method as described in the claim 1-15, wherein said biological tissue comprises one or more fluorophores, and wherein said detection wavelength is equivalent to the emission wavelength of described one or more fluorophores, and described illumination wavelengths is equivalent to the excitation wavelength of described one or more fluorophores.
17. method as claimed in claim 16 wherein detects described exciting and emission wavelength.
18. as any one method as described in the claim 2-17, wherein integrated described TPSF is to provide attenuation measurement.
19. as any one method as described in the claim 1-18, the optical signalling that wherein comes from a plurality of target areas was gathered in same period.
20. method as claimed in claim 19, wherein said a plurality of target areas comprise the whole body of animal body.
21. as any one method as described in the claim 1-20, wherein said animal body is controllably heated.
22. a collection is used for the system of the optical data of animal body time discrimination optics imaging, described system comprises:
I) one or more light-pulse generators of selected intensity are used for providing light beam with one or more wavelength;
Ii) illumination optical device is used for directly propagating described light beam by the Free Space Optics device, so a plurality of illumination points in irradiating biological organizational goal zone, thereby light is injected in the described animal body;
Ii i) gathers optical element, be used for being captured in the light that the predetermined collection point place of target area launches once more by the Free Space Optics device, make that the light that sends from the site of non-predetermined collection point is optionally got rid of from detect, and directly propagate described collection light by the Free Space Optics device; And
Area detector in the time of iv) is used to detect described collection light.
23. the system as claimed in claim 22, wherein said one or more light sources are the variable intensity light source.
24. system as claimed in claim 23, wherein said variable intensity light source is a laser.
25. as any described system of claim 22-24, wherein said illumination optical device comprises at least one removable mirror, is used for the described a plurality of illumination points of described beam direction.
26. system as claimed in claim 25, wherein said removable mirror is a mirror galvanometer.
27. system as claimed in claim 26 further comprises the thin angle mirror that is positioned at described mirror galvanometer optics downstream.
28. system as claimed in claim 27 wherein is provided with lens between described mirror galvanometer and described thin angle mirror, and with its optically coupling connection so that the telecentric imaging structure to be provided.
29. as any described system of claim 22-28, wherein said collection optical element comprises the lens that are positioned at above-mentioned target area, its focus and described collection point match.
30. system as claimed in claim 29, wherein said collection optical element further comprises mirror galvanometer, is used to detect the collection light to described detecting device.
31. as any described system of claim 30, the mirror galvanometer of wherein said illumination optics and collection optics is synchronous, so that the fixed range between illumination points and each collection point is provided.
32. system as claimed in claim 30, the mirror galvanometer independent regulation of wherein said illumination optics and collection optics is so that provide variable distance between illumination points and each collection point.
33. as any described system of claim 22-32, but wherein said illumination optics, detection optics and light source are the part of the carriage of moving object rotation.
34., further comprise mobile platform as any described system of claim 22-33, be used for pallet is moved in perpendicular to the plane of illuminating bundle, wherein said pallet is used to support animal body.
35. system as claimed in claim 34, wherein said pallet controllably is heated to the temperature that is suitable for described animal body of expection.
36. as any described system of claim 22-35, wherein said detecting device is single photon-counting detector time correlation.
37. as any described system of claim 22-35, wherein said detecting device is time grate ICCD.
38. as any described system of claim 22-37, wherein said animal body, described optical element and described detecting device are included in the closed box.
39. system as claimed in claim 39, wherein said closed box is lighttight.
CN200380108570.2A 2002-11-11 2003-11-10 Time discrimination optics imaging method and equipment used for part biological tissues of animal body Pending CN1735802A (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
IBPCT/IB02/04698 2002-11-11
IB0204698 2002-11-11
US10/317,856 2002-12-12
US60/505,352 2003-09-22

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Cited By (11)

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WO2009006758A1 (en) * 2007-07-10 2009-01-15 Tsinghua University Continuous and dynamical acquisition-type imaging system for small animal induced fluorescence molecule imaging
CN101361651B (en) * 2008-09-19 2010-04-07 清华大学 Fluorescence molecular tomography device
CN102525420A (en) * 2011-12-16 2012-07-04 天津大学 Calibration method for multi-passage time domain fluorescence chromatography imaging system
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CN102525420A (en) * 2011-12-16 2012-07-04 天津大学 Calibration method for multi-passage time domain fluorescence chromatography imaging system
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WO2013185621A1 (en) * 2012-06-14 2013-12-19 南京拓鉒医药科技有限公司 Endotoxin detection systems and detection methods thereof
CN103054557A (en) * 2013-01-08 2013-04-24 白宇 Moire image device
CN103622673A (en) * 2013-11-11 2014-03-12 西安电子科技大学 Autofluorescent fault molecular imaging equipment compatible with magnetic resonance
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