CN101816552A - Imitating CT scanning mode multispectral time domain fluorescence molecular tomography measuring system - Google Patents
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Abstract
The invention relates to the field of small animal molecular imaging, and provides an imitating CT scanning mode multispectral time domain fluorescence molecular tomography measuring system with ultrasensitive and high time-space resolution measurement performances so as to realize the high-quality multi-component multi-parameter imaging function. The imitating CT scanning mode multispectral time domain fluorescence molecular tomography measuring system comprises two picosecond semiconductor lasers, an optical fiber coupler, an incident optical fiber, an imaging cavity, a rotating platform, a receiving optical fiber, a motor driving filter wheel and a detection module, wherein the two picosecond semiconductor lasers and the optical fiber coupler are used for providing wavelength ultrashort laser required, the optical fiber coupler is used for coupling two same-frequency ultrashort laser pulses of different wavelengths into a bundle of laser according to fixed time interval, the incident optical fiber is used for projecting emergent laser of two or one of both picosecond semiconductor lasers onto an object, the imaging cavity and the rotating platform are used for realizing the imitating CT scanning mode, the receiving optical fiber is used for receiving reflective or transmitted laser from the object, and the detection module is used for receiving emergent light passing through corresponding filter pieces. The invention is mainly applied to the molecular imaging of small animals.
Description
Technical field
The present invention relates to the small animal molecule image-forming field, especially, be specifically related to the imitating CT scanning mode multispectral time domain fluorescence molecular tomography measuring system towards the time-domain fluorescent diffusion chromatography system and the time resolution optical chromatography system of small animal molecule image-forming.
Background technology
The molecular imaging qualitative and quantitative research that to be image application method carry out at cell and molecular level the bioprocess under the condition of living organism, be with the generation mechanism of body internal specific molecule, reflect intravital physiology and pathological change process at cell or molecular level by image as image contrast.The advantage of molecular imaging can mainly be summarised as 3 points: one, the molecular image technology can become intuitive image with the process of complexity such as gene expression, bio signal transmission, makes people can understand the mechanism and the feature of disease better on the molecular cell level; Its two, can find variation of the early stage molecular cell of disease and pathological change process; Its three, mechanism and the effect that can on live body, observe medicine or gene therapy continuously.The molecular image technology has continuous, quick, remote, undamaged advantage as a kind of detection method at live body (in vivo), and the 3-D view of molecule in the body or cell more may be provided.It can disclose the early molecule biological property of pathological changes, has promoted the early diagnosis and therapy of disease, has also introduced new notion for clinical diagnosis.
Optical molecular imaging is important molecular image mode, has multiple advantages such as ultra-sensitivity, high specific, real-time and labelling motility concurrently, is particularly suitable for the biomedical basic research based on the toy pathological model.。Especially (Near-Infrared Spectroscopy, NIRS) development is very rapid on biological tissue's imaging in vivo is used for near-infrared spectrum technique.The effect of near infrared light and biological tissue mainly shows as scattering and absorption, wherein in the 600-900nm wavelength band, has tangible irrelevant absorption spectra feature, formed a biological tissue " optical diagnostics window ", (DiffuseOptical Tomography DOT) can obtain the closely-related optical parametric 3-D quantitative information of organizer deep and physiological pathology index to the diffuse optical chromatographic technique of Jian Liing on this basis.Meanwhile, along with of the deepen continuously application of optical molecular iconography in biological study, be based upon combine with specific molecular fluorescent labeling technology optical molecular chromatographic technique on the basis of DOT method and then become the research field of optical molecular imaging forefront, comprise fluorescent chromatographic (Fluorescence Molecular Tomography, FMT) and the archebiosis photosphere analyse (Bioluminescence Tomography, BLT) two kinds of basic mode.FMT is by simultaneous excitation light-fluorescence measurement and fluorescent diffusion chromatography process on exciting light and two wave bands of emitting fluorescence, produce the spatial distribution of the fluorescence parameter of inner special molecular biochemical process intensity of reflection organizer and microenvironment feature thereof, comprise emissivity (fluorescent agent quantum efficiency and absorptance are long-pending) and life-span etc.Difference according to mode of excitation, FMT has three kinds of measurement patterns: time domain (Time Domain, TD), frequency domain (FrequencyDomain, FD) and continuous wave (Continuous Wave, CW), wherein simple and direct in CW mode principle and the realization, and FD and TD mode are expected to realize higher function and index.Though can realize that for the FD mode multiparameter rebuilds simultaneously, but when using this mode in small animal imaging, need the above modulating frequency of 1GHz to reach suitable signal to noise ratio, it is almost nil to exchange amplitude under the so high frequency, the limitation of visible FD mode.Therefore the time domain FMT technology that possesses multiparameter imaging capability and function admirable has obtained to pay attention to widely.Time domain FMT technology is intended to develop high sensitive time resolved detection technique, excite the measurement of lower surface fluorescence transient state " projection " and based on the image inversion algorithm of accurate photon transport model by many " angles ", rebuild the spatial distribution of the inner many fluorescence parameters of specific molecular target of complex organization's body (fluorescent yield and life-span), and the finiteness that remedies spatial sampling quantity by time resolution information realizes the application requirements of FMT with effective raising image quality and detection sensitivity.
(Time-Correlated Single PhotonCounting, TCSPC) technology are a kind of discrete channel measuring techniques with ultra-high sensitive, reasonable time resolution to the existing employing of time domain FMT implementation time correlation single photon meter; Adopt time gated image to strengthen CCD camera (Time-gated Intensifier CCD camera) in addition, it is a kind of measuring technique with high spatial sample rate, but its linearity and dynamic range are not high, and compare the TCSPC technology and do not have advantage yet on sensitivity and temporal resolution.
Summary of the invention
For overcoming the deficiencies in the prior art, remedy the defective of prior art on spatial sampling density, make system with ultra-sensitivity and high time-space resolution measurement performance, realize high-quality multicomponent, multiparameter imaging function then.For achieving the above object, the technical solution used in the present invention is: imitating CT scanning mode multispectral time domain fluorescence molecular tomography measuring system system comprises:
Two the psec semiconductor lasers and the fluorescent probe of required wavelength ultrashort laser are provided, are used to send laser pulse, the wavelength of one of them laser instrument is at the exciting light wave band of fluorescent probe, and another wavelength is at the fluorescence wave band of fluorescent probe;
Be used for the same frequency ultrashort laser pulse of two kinds of different wave lengths was coupled at interval by regular time the fiber coupler of beam of laser;
Be used for two psec semiconductor lasers or the shoot laser of one of them are projected the incident optical of objective body;
Be used to realize the imaging chamber and the rotation platform of imitating CT scanning mode;
Be used to receive from the reflection of objective body or the reception optical fiber of transmission laser;
Be used for the optical filter that filtering or decling phase stress be luminous and realize that the motor that the different performance optical filter switches mutually drives filter wheel;
Be used to receive detection module, comprise: photoelectron counting PMT detector set, 8 passage routing modules, multidimensional time correlation single photon meter TCSPC module by emergent light after the respective filter.
It is respectively corresponding relatively with exciting with emission spectra of different fluorescent dyes that two psec semiconductor laser operation wavelengths and filter set wavelength are provided with, as follows according to the combination that different fluorescent probes carry out:
1) Cy5.5 near infrared fluorescent dye, its peak excitation wavelength is about 670nm, the peak fluorescence wavelength is about 700nm, the wavelength of two psec semiconductor lasers then selecting for use is respectively 670nm and 700nm, there is halfwidth to be spaced apart 10nm in the filter set for 10nm centre wavelength, wave-length coverage is 8 bandpass filters and long pass filter sheet that cutoff wavelength is 690nm of 680-760nm;
2) indocyanine green Indocyanine Green, the ICG near infrared fluorescent dye, its peak excitation wavelength is about 780nm, the peak fluorescence wavelength is about 830nm, the wavelength of two psec semiconductor lasers then selecting for use is respectively 780nm and 830nm, have halfwidth to be spaced apart 10nm for 10nm centre wavelength in the filter set, wave-length coverage is 8 bandpass filters of 790-870nm, and long pass filter sheet that cutoff wavelength is 800nm;
3) Alexa Fluor 750 near infrared fluorescent dyes, its peak excitation wavelength is about 750nm, the peak fluorescence wavelength is about 785nm, the wavelength of two psec semiconductor lasers then selecting for use is respectively 750nm and 785nm, there is halfwidth to be spaced apart 10nm's in the filter set for 10nm centre wavelength, wave-length coverage is 8 bandpass filters of 760-840nm, and the long pass filter sheet that cutoff wavelength is 770m.
Two psec semiconductor lasers are connected to incident optical by a bonder after the optical fiber of different length produces the regular time interval, receive optical fiber and be 8 detection optical fibers or fibre bundle in the isoplanar on incident optical opposite location arrangements, the imaging chamber places on the rotating-/ lifting platform, by the stepped intervals control of the rotating-/ lifting platform anglec of rotation and adjustable height, realize the time discrimination measurement of different spaces sampling density.
8 detection optical fibers or fibre bundle are corresponding to respectively one in 8 the 12 hole filter wheel, a corresponding passage that inserts in 8 PMT sense channels, a hole is a full impregnated in the 12 hole filter wheel, remaining hole is provided with the fluorescent belt pass filter group of long pass filter group of fluorescence and different centre wavelengths respectively, and be used for the neutral density ND attenuator that exciting light detects, be used to carry out the measurement of exciting light, full gloss spectrum fluorescence or multispectral fluorescence signal; 8 PMT detectors insert multidimensional time correlation single photon meter TCSPC module by one 8 passage router.
Two psec semiconductor lasers are correlated with control to realize exporting synchronously the light pulse of same frequency by computer, produce regular time through the optical fiber of different length again and form beam of laser by bonder in the back at interval, to realize measuring the background tissues optical parameter value that obtains under this two wavelength by the DOT before the fluorescence measurement.
The boundary face of incident optical and reception optical fiber and objective body Ω
Certain distance is arranged, be positioned at r
dLuminous flux Γ (the r that the fibre-optical probe of place's reception optical fiber records
d, t) with imaging chamber emissivity
Satisfy following ray theory relation:
System of the present invention adopts optical fiber coupling noncontact mode to realize the measurement of time domain DOT/FMT prototype, and its characteristics are:
1, imaging chamber of the present invention and structure of fiber_optic are inside and outside concentric design, and postanesthetic tumor-bearing mice is vertically put into the imaging chamber with slight extruding during measurement, and fill the gap with optical match liquid.Two are respectively the picosecond pulse laser device that excites with wavelength of fluorescence and are connected to incident optical by a bonder, in the isoplanar on this opposite location arrangements 8 detection optical fibers or fibre bundle are arranged.The imaging chamber places on the rotating-/ lifting platform, stepped intervals control by the anglec of rotation and adjustable height, can realize the time discrimination measurement of different spaces sampling density, the data that obtain can be carried out the monoplane two-dimension image rebuild in groups by Different Plane, or the 3 D stereo reconstruction is carried out in comprehensive utilization.
2, the present invention can realize the multispectral survey technology, outgoing optical fiber inserts 8 PMT sense channels respectively, one 12 hole filter wheel of coupling before each PMT, one of them hole is a full impregnated, remaining hole is provided with the fluorescent belt pass filter group of long pass filter group of fluorescence and different centre wavelengths respectively, and be used for neutral density (ND) attenuator that exciting light detects, can carry out the measurement of exciting light, full gloss spectrum fluorescence or multispectral fluorescence signal.
3, the present invention has adopted single channel multidimensional TCSPC measurement pattern, and 8 PMT detectors insert multidimensional TCSPC module by one 8 passage router, carry out the high speed time discrimination measurement.
4, incident and outgoing optical fiber are the non-cpntact measurement pattern among the present invention, as shown in Figure 6 the boundary face of luminous source optical fiber and detection fiber and objective body Ω
Certain distance is arranged, promptly use optical fiber noncontact mode incentives target body and sensed light signal.Be positioned at r
dLuminous flux Γ (the r that the fibre-optical probe at place records
d, t) with imaging chamber emissivity
Satisfy following ray theory relation:
Wherein r is
Position vector arbitrarily on the surface,
With
Be respectively the unit vector on the normal direction unit vector and fibre-optical probe direction outside the surface, imaging chamber, V (r
d, r) be r point and r
dVisibility function between the point, μ
A0The aerial attenuation quotient of light, R
ARadius for cylindrical target.
5, two of light-source system employings of the present invention are respectively the picosecond pulse laser device that excites with wavelength of fluorescence and are connected to incident optical by a bonder.Two wavelength have regular time at interval during common the use, measure the background tissues optical parameter value that can obtain under this two wavelength by the DOT before the fluorescence measurement.The priori value of background during as the fluorescent chromatographic image reconstruction with this optical parametric can improve the resolution and the quantified precision of fluorescent chromatographic image significantly.
6, non-cpntact measurement pattern of the present invention, not only effective simplified measurement process is got rid of unnecessary systematic error and loaded down with trivial details coupling calibration process, and is made data acquisition become versatile and flexible.Can realize that high-density acquisition and key area emphasize by discrete angle intervals of gated sweep and scope, thereby effectively remedy the deficiency of TCSPC technology on spatial sampling density, make system with ultra-sensitivity and high time-space resolution measurement performance, realize high-quality multicomponent, multiparameter imaging function then.
Description of drawings
Fig. 1 is an imitating CT scanning mode multispectral time domain fluorescence molecular tomography measuring system system block diagram.
The basic structure sketch map of Fig. 2 light-source system.
Fig. 3 motor drives filter wheel and photomultiplier tube group structural representation.
Fig. 4 motor drives optical filter branch sketch map in the filter wheel.
Fig. 5 imaging chamber and scan control scheme sketch map.
Fig. 6 optical fiber non-cpntact measurement pattern chromatography floor map.
The specific embodiment
The contactless pattern of development imitating CT scanning realizes having the meaning of particular importance in the time domain FMT measuring system based on the TCSPC technology: on the one hand, the same with all non-cpntact measurement patterns, it is the simplified measurement process effectively, gets rid of unnecessary systematic error and loaded down with trivial details coupling calibration process; On the other hand, non-contact measurement makes data acquisition become versatile and flexible, can realize that high-density acquisition and key area emphasize by discrete angle intervals of gated sweep and scope, thereby effectively remedy the deficiency of TCSPC technology on spatial sampling density, make system with ultra-sensitivity and high time-space resolution measurement performance, realize high-quality multicomponent, multiparameter imaging function then.
The present invention is an imitating CT scanning mode, i.e. FMT/DOT measuring system under the optical fiber noncontact mode.Fig. 1 is the basic structure of imitating CT scanning mode multispectral time domain fluorescence molecular tomography measuring system system.It is by light-source system 1, incident optical 2, and imaging chamber 3, outgoing optical fiber 4, detection system, computer 11 etc. are partly formed.FMT/DOT measuring process under the concrete optical fiber noncontact mode is described below.
A. when Cy5.5 is fluorescent dye, the measuring process of this system (two optical maser wavelengths that are system are respectively 670nm and 700nm).
1, by before the fluorescence measurement, utilizes two wavelength to carry out the DOT measurement earlier, thereby obtain the background tissues optical parameter value under this two wavelength.The wavelength of excitation wavelength picopulse semiconductor laser 13 is 670nm as shown in Figure 2, and the wavelength of wavelength of fluorescence picopulse semiconductor laser 14 is 700nm.Two laser instrument switches are controlled by related software, and its frequency is identical and receive the synchronizing signal end of multidimensional TCSPC module 10 synchronously by power combiner 12.Two synchronous laser that laser instrument sent are connected to fiber coupler 15 with the optical fiber by different length, and (synchronous signal frequency is elected 40MHZ as, and two wavelength laser pulse intervals are elected 12.5ns as.Because optical fiber internal diameter material is quartzy (refractive index is 1.54), therefore two laser instrument should differ to the fiber lengths of fiber coupler and be about 2.4 meters), thus make two kinds of different wave length laser blend together at interval with a branch of laser emitting to incident optical 2 (core diameter 62.5 μ m) with regular time.
2, incident optical 2 is beaten laser in imaging chamber 3 and (is made by translucent lucite, the about 2-3cm of diameter) on, imaging chamber 3 is inside and outside concentric design with structure of fiber_optic 45 (diameter 4cm) as shown in Figure 5, postanesthetic tumor-bearing mice is vertically put into imaging chamber 3 with slight extruding during measurement, and with optical match liquid filling gap, 101.25 °～258.75 ° the position, isoplanar on this opposite (establishing incident illumination in position, 0 ° of angle) is furnished with 8 outgoing optical fiber 4 (detection optical fibers, core diameter 500 μ m), the angle, space is 22.5 °.The imaging chamber places on the rotating-/ lifting platform 46, and the stepped intervals control by the anglec of rotation and adjustable height realizes imitating CT scanning mode.To survey optical signal by outgoing optical fiber 4 and import detection module.
3,8 outgoing optical fiber 4 insert motor and drive optical filtering wheels 16-23, and motor drives the filter wheel structure as shown in Figure 4, and its mesopore 33 is full impregnated via holes; Hole 34 is the neutral-density filters that decay to 30dB; Hole 35 is the neutral-density filters that decay to 50dB; Before measuring fluorescence, carry out DOT and measure, then drive filter wheel, transfer to the optical signal after suitably being decayed in hole 33/34/35 by filter wheel controller 24 governor motors.
4, the optical signal that as shown in Figure 3 motor is driven the outgoing of optical filtering wheels is sent into the PMT detector 25-32 that has refrigerating function, and the low light level conversion of signals during PMT will test is an electronic pulse signal.8 PMT detectors are linked into multidimensional TCSPC module 10 by 8 passage routing modules 9, electronic impulse to input is counted, and deposit corresponding memory block in by the channel address signal, obtain the temporal extension curve of 8 dual wavelength exciting lights of the test surface outgoing that records from 8 passages.
5, after dual wavelength DOT measured, carrying out the FMT measurement was fluorescence measurement, only opens excitation wavelength picopulse semiconductor laser 13 (wavelength is 670nm).To imaging chamber 3, the stepped intervals control by rotating-/ lifting platform 46 anglecs of rotation and adjustable height realizes imitating CT scanning mode to laser through incident optical 2.Import detection system by outgoing optical fiber 4 again.Drive filter wheel by filter wheel controller 24 governor motors, its mesopore 36 is the long pass filter of 690nm for cut-off frequency; Hole 37-44 is halfwidth is spaced apart 10nm for 10nm centre wavelength 8 bandpass filters (wave-length coverage is 680-760nm); Obtain full gloss spectrum fluorescence or multispectral fluorescence signal by different choice to hole 36-44.Low light level conversion of signals in will testing by PMT again is an electronic pulse signal.8 PMT detectors are linked into multidimensional TCSPC module 10 by 8 passage routing modules 9, electronic impulse to input is counted and is deposited corresponding memory block in by the channel address signal, thereby obtains 8 fluorescence temporal extension curves of the test surface outgoing that records from 8 passages.
6, the each rotation in an imaging chamber angle (generally electing 1 ° as) repeats above-mentioned measuring process, after 360 ° of rotations, by repeating the process of wheel measuring after the step-length of automatically controlled lifting platform stepping (being generally 1mm) again.The generally long 5cm of imaging cylinder, so the stepping scope of lifting platform is greater than 5cm.Be that general available detection data amount is 360 * 50 * 8=144000.Owing to can select more accurate automatically controlled rotation and lifting platform for use, it is not difficult further to improve the spatial discrimination of surveying.
B. when ICG is fluorescent dye, the measuring process of this system (two optical maser wavelengths that are system are respectively 780nm and 830nm).
1, by before the fluorescence measurement, utilizes two wavelength to carry out the DOT measurement earlier, thereby obtain the background tissues optical parameter value under this two wavelength.The wavelength of excitation wavelength picopulse semiconductor laser 13 is 780nm as shown in Figure 2, and the wavelength of wavelength of fluorescence picopulse semiconductor laser 14 is 830nm.Two laser instrument switches are controlled by related software, and its frequency is identical and receive the synchronizing signal end of multidimensional TCSPC module 10 synchronously by power combiner 12.Two synchronous laser that laser instrument sent are connected to fiber coupler 15 with the optical fiber by different length, and (synchronous signal frequency is elected 40MHZ as, and two wavelength laser pulse intervals are elected 12.5ns as.Because optical fiber internal diameter material is quartzy (refractive index is 1.54), therefore two laser instrument should differ to the fiber lengths of fiber coupler and be about 2.4 meters), thus make two kinds of different wave length laser blend together at interval with a branch of laser emitting to incident optical 2 (core diameter 62.5 μ m) with regular time.
2, incident optical 2 is beaten laser in imaging chamber 3 and (is made by translucent lucite, the about 2-3cm of diameter) on, imaging chamber 3 is inside and outside concentric design with structure of fiber_optic 45 (diameter 4cm) as shown in Figure 5, postanesthetic tumor-bearing mice is vertically put into imaging chamber 3 with slight extruding during measurement, and with optical match liquid filling gap, 101.25 °～258.75 ° the position, isoplanar on this opposite (establishing incident illumination in position, 0 ° of angle) is furnished with 8 outgoing optical fiber 4 (detection optical fibers, core diameter 500 μ m), the angle, space is 22.5 °.The imaging chamber places on the rotating-/ lifting platform 46, and the stepped intervals control by the anglec of rotation and adjustable height realizes imitating CT scanning mode.To survey optical signal by outgoing optical fiber 4 and import detection module.
3,8 outgoing optical fiber 4 insert motor and drive optical filtering wheels 16-23, and motor drives the filter wheel structure as shown in Figure 4, and its mesopore 33 is full impregnated via holes; Hole 34 is the neutral-density filters that decay to 30dB; Hole 35 is the neutral-density filters that decay to 50dB; Before measuring fluorescence, carry out DOT and measure, then drive filter wheel, transfer to the optical signal after suitably being decayed in hole 33/34/35 by filter wheel controller 24 governor motors.
4, the optical signal that as shown in Figure 3 motor is driven the outgoing of optical filtering wheels is sent into the PMT detector 25-32 that has refrigerating function, and the low light level conversion of signals during PMT will test is an electronic pulse signal.8 PMT detectors are linked into multidimensional TCSPC module 10 by 8 passage routing modules 9, electronic impulse to input is counted, and deposit corresponding memory block in by the channel address signal, obtain the temporal extension curve of 8 dual wavelength exciting lights of the test surface outgoing that records from 8 passages.
5, after dual wavelength DOT measured, carrying out the FMT measurement was fluorescence measurement, only opens excitation wavelength picopulse semiconductor laser 13 (wavelength is 780nm).To imaging chamber 3, the stepped intervals control by rotating-/ lifting platform 46 anglecs of rotation and adjustable height realizes imitating CT scanning mode to laser through incident optical 2.Import detection system by outgoing optical fiber 4 again.Drive filter wheel by filter wheel controller 24 governor motors, its mesopore 36 is the long pass filter of 800nm for cut-off frequency; Hole 37-44 is halfwidth is spaced apart 10nm for 10nm centre wavelength 8 bandpass filters (wave-length coverage is 790-870nm); Obtain full gloss spectrum fluorescence or multispectral fluorescence signal by different choice to hole 36-44.Low light level conversion of signals in will testing by PMT again is an electronic pulse signal.8 PMT detectors are linked into multidimensional TCSPC module 10 by 8 passage routing modules 9, electronic impulse to input is counted and is deposited corresponding memory block in by the channel address signal, thereby obtains 8 fluorescence temporal extension curves of the test surface outgoing that records from 8 passages.
6, the each rotation in an imaging chamber angle (generally electing 1 ° as) repeats above-mentioned measuring process, after 360 ° of rotations, by repeating the process of wheel measuring after the step-length of automatically controlled lifting platform stepping (being generally 1mm) again.The generally long 5cm of imaging cylinder, so the stepping scope of lifting platform is greater than 5cm.Be that general available detection data amount is 360 * 50 * 8=144000.Owing to can select more accurate automatically controlled rotation and lifting platform for use, it is not difficult further to improve the spatial discrimination of surveying.
C. when Alexa Fluor 750 is fluorescent dye, the measuring process of this system (two optical maser wavelengths that are system are respectively 750nm and 785nm).
1, by before the fluorescence measurement, utilizes two wavelength to carry out the DOT measurement earlier, thereby obtain the background tissues optical parameter value under this two wavelength.The wavelength of excitation wavelength picopulse semiconductor laser 13 is 750nm as shown in Figure 2, and the wavelength of wavelength of fluorescence picopulse semiconductor laser 14 is 785nm.Two laser instrument switches are controlled by related software, and its frequency is identical and receive the synchronizing signal end of multidimensional TCSPC module 10 synchronously by power combiner 12.Two synchronous laser that laser instrument sent are connected to fiber coupler 15 with the optical fiber by different length, and (synchronous signal frequency is elected 40MHZ as, and two wavelength laser pulse intervals are elected 12.5ns as.Because optical fiber internal diameter material is quartzy (refractive index is 1.54), therefore two laser instrument should differ to the fiber lengths of fiber coupler and be about 2.4 meters), thus make two kinds of different wave length laser blend together at interval with a branch of laser emitting to incident optical 2 (core diameter 62.5 μ m) with regular time.
2, incident optical 2 is beaten laser in imaging chamber 3 and (is made by translucent lucite, the about 2-3cm of diameter) on, imaging chamber 3 is inside and outside concentric design with structure of fiber_optic 45 (diameter 4cm) as shown in Figure 5, postanesthetic tumor-bearing mice is vertically put into imaging chamber 3 with slight extruding during measurement, and with optical match liquid filling gap, 101.25 °～258.75 ° the position, isoplanar on this opposite (establishing incident illumination in position, 0 ° of angle) is furnished with 8 outgoing optical fiber 4 (detection optical fibers, core diameter 500 μ m), the angle, space is 22.5 °.The imaging chamber places on the rotating-/ lifting platform 46, and the stepped intervals control by the anglec of rotation and adjustable height realizes imitating CT scanning mode.To survey optical signal by outgoing optical fiber 4 and import detection module.
3,8 outgoing optical fiber 4 insert motor and drive optical filtering wheels 16-23, and motor drives the filter wheel structure as shown in Figure 4, and its mesopore 33 is full impregnated via holes; Hole 34 is the neutral-density filters that decay to 30dB; Hole 35 is the neutral-density filters that decay to 50dB; Before measuring fluorescence, carry out DOT and measure, then drive filter wheel, transfer to the optical signal after suitably being decayed in hole 33/34/35 by filter wheel controller 24 governor motors.
4, the optical signal that as shown in Figure 3 motor is driven the outgoing of optical filtering wheels is sent into the PMT detector 25-32 that has refrigerating function, and the low light level conversion of signals during PMT will test is an electronic pulse signal.8 PMT detectors are linked into multidimensional TCSPC module 10 by 8 passage routing modules 9, electronic impulse to input is counted, and deposit corresponding memory block in by the channel address signal, obtain the temporal extension curve of 8 dual wavelength exciting lights of the test surface outgoing that records from 8 passages.
5, after dual wavelength DOT measured, carrying out the FMT measurement was fluorescence measurement, only opens excitation wavelength picopulse semiconductor laser 13 (wavelength is 750nm).To imaging chamber 3, the stepped intervals control by rotating-/ lifting platform 46 anglecs of rotation and adjustable height realizes imitating CT scanning mode to laser through incident optical 2.Import detection system by outgoing optical fiber 4 again.Drive filter wheel by filter wheel controller 24 governor motors, its mesopore 36 is the long pass filter of 770nm for cut-off frequency; Hole 37-44 is halfwidth is spaced apart 10nm for 10nm centre wavelength 8 bandpass filters (wave-length coverage is 760-840nm); Obtain full gloss spectrum fluorescence or multispectral fluorescence signal by different choice to hole 36-44.Low light level conversion of signals in will testing by PMT again is an electronic pulse signal.8 PMT detectors are linked into multidimensional TCSPC module 10 by 8 passage routing modules 9, electronic impulse to input is counted and is deposited corresponding memory block in by the channel address signal, thereby obtains 8 fluorescence temporal extension curves of the test surface outgoing that records from 8 passages.
6, the each rotation in an imaging chamber angle (generally electing 1 ° as) repeats above-mentioned measuring process, after 360 ° of rotations, by repeating the process of wheel measuring after the step-length of automatically controlled lifting platform stepping (being generally 1mm) again.The generally long 5cm of imaging cylinder, so the stepping scope of lifting platform is greater than 5cm.Be that general available detection data amount is 360 * 50 * 8=144000.Owing to can select more accurate automatically controlled rotation and lifting platform for use, it is not difficult further to improve the spatial discrimination of surveying.
Claims (6)
1. an imitating CT scanning mode multispectral time domain fluorescence molecular tomography measuring system is characterized in that, comprising:
Two the psec semiconductor lasers and the fluorescent probe of required wavelength ultrashort laser are provided, are used to send laser pulse, the wavelength of one of them laser instrument is at the exciting light wave band of fluorescent probe, and another wavelength is at the fluorescence wave band of fluorescent probe;
Be used for the same frequency ultrashort laser pulse of two kinds of different wave lengths was coupled at interval by regular time the fiber coupler of beam of laser;
Be used for two psec semiconductor lasers or the shoot laser of one of them are projected the incident optical of objective body;
Be used to realize the imaging chamber and the rotation platform of imitating CT scanning mode;
Be used to receive from the reflection of objective body or the reception optical fiber of transmission laser;
Be used for the optical filter that filtering or decling phase stress be luminous and realize that the motor that the different performance optical filter switches mutually drives filter wheel;
Be used to receive detection module, comprise: photoelectron counting PMT detector set, 8 passage routing modules, multidimensional time correlation single photon meter TCSPC module by emergent light after the respective filter.
2. according to a kind of imitating CT scanning mode multispectral time domain fluorescence molecular tomography measuring system under the claim 1, it is characterized in that, it is respectively corresponding with exciting with emission spectra of different fluorescent dyes that two psec semiconductor laser operation wavelengths and filter set wavelength are provided with, as follows according to the combination that different fluorescent probes carry out:
1) Cy5.5 near infrared fluorescent dye, its peak excitation wavelength is about 670nm, the peak fluorescence wavelength is about 700nm, the wavelength of two psec semiconductor lasers then selecting for use is respectively 670nm and 700nm, there is halfwidth to be spaced apart 10nm in the filter set for 10nm centre wavelength, wave-length coverage is 8 bandpass filters and long pass filter sheet that cutoff wavelength is 690nm of 680-760nm;
2) indocyanine green Indocyanine Green, the ICG near infrared fluorescent dye, its peak excitation wavelength is about 780nm, the peak fluorescence wavelength is about 830nm, the wavelength of two psec semiconductor lasers then selecting for use is respectively 780nm and 830nm, have halfwidth to be spaced apart 10nm for 10nm centre wavelength in the filter set, wave-length coverage is 8 bandpass filters of 790-870nm, and the long pass filter sheet that cutoff wavelength is 800nm;
3) Alexa Fluor 750 near infrared fluorescent dyes, its peak excitation wavelength is about 750nm, the peak fluorescence wavelength is about 785nm, the wavelength of two psec semiconductor lasers then selecting for use is respectively 750nm and 785nm, there is halfwidth to be spaced apart 10nm in the filter set for 10nm centre wavelength, wave-length coverage is 8 bandpass filters of 760-840nm, and the long pass filter sheet that cutoff wavelength is 770m.
3. according to a kind of imitating CT scanning mode multispectral time domain fluorescence molecular tomography measuring system under the claim 1, it is characterized in that, two psec semiconductor lasers are after the optical fiber of different length produces the regular time interval, be connected to incident optical by a bonder, receive optical fiber and be 8 detection optical fibers or fibre bundle in the isoplanar on incident optical opposite location arrangements, the imaging chamber places on the rotating-/ lifting platform, by the stepped intervals control of the rotating-/ lifting platform anglec of rotation and adjustable height, realize the time discrimination measurement of different spaces sampling density.
4. according to a kind of imitating CT scanning mode multispectral time domain fluorescence molecular tomography measuring system under the claim 3, it is characterized in that, 8 detection optical fibers or fibre bundle are corresponding to respectively one in 8 the 12 hole filter wheel, a corresponding passage that inserts in 8 PMT sense channels, a hole is a full impregnated in the 12 hole filter wheel, remaining hole is provided with the fluorescent belt pass filter group of long pass filter of fluorescence and different centre wavelengths respectively, and be used for the neutral density ND attenuator group that exciting light detects, be used to carry out the measurement of exciting light, full gloss spectrum fluorescence or multispectral fluorescence signal; 8 PMT detectors insert multidimensional time correlation single photon meter TCSPC module by one 8 passage router.
5. according to a kind of imitating CT scanning mode multispectral time domain fluorescence molecular tomography measuring system under the claim 1, it is characterized in that, two psec semiconductor lasers are correlated with control to realize exporting synchronously the light pulse of same frequency by computer, produce regular time through the optical fiber of different length again and form beam of laser by bonder in the back at interval, to realize measuring the background tissues optical parameter value that obtains under this two wavelength by the DOT before the fluorescence measurement.
6. according to a kind of imitating CT scanning mode multispectral time domain fluorescence molecular tomography measuring system under the claim 1, it is characterized in that the boundary face of incident optical and reception optical fiber and objective body Ω
Certain distance is arranged, be positioned at r
dLuminous flux Γ (the r that the fibre-optical probe of place's reception optical fiber records
d, t) with imaging chamber emissivity φ (r,
, t) satisfy following ray theory relation:
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