Development of In Vivo Optical Imaging

Transcript

1 34 12 Vol. 34, No ACTA AUTOMATICA SINICA December, , 2 2.,,.,, R319 Development of In Vivo Optical Imaging LI Hui 1, 2 DAI Ru-Wei 2 Abstract With the emergence of in vivo optical imaging, bioluminescence imaging and fluorescence imaging can be used to non-invasively monitor the activities and responses of cells marked with optical signals in real time, which are considered to be promising tools for tumor detection, gene expression profiling, protein molecular detection, drug receptor localization, drug screening, and therapeutic evaluation. In this paper, the features, imaging systems, and applications of in vivo bioluminescence imaging and in vivo fluorescence imaging have been introduced and compared in detail. The basic theories, application fields, and development of in vivo optical imaging in future are reviewed. Key words In vivo optical imaging, bioluminescence imaging (BLI), fluorescence imaging (FI), (In vivo optical imaging),, (Bioluminescence imaging, BLI) (Fluorescence imaging) [1 2]. (Luciferase) DNA,, (Green fluorescent protein, GFP) (Red fluorescent protein, RFP) [3]., (Charge coupled device camera, CCD camera), Received August 8, 2007; in revised form November 19, 2007 ( ), (20061D ), ( ) Supported by National Natural Science Foundation of China ( ), Research Fund for Beijing Distinguished Specialists (20061D ), Chinese Postdoctoral Science Foundation ( ), and Chinese Academy of Sciences K. C. Wong Postdoctoral Fellowships Department of Education Technology, Capital Normal University, Beijing Key Laboratory of Complex Systems and Intelligence Science, Institute of Automation, Chinese Academy of Sciences, Beijing DOI: /SP.J , [4 8]., (Magnetic resonance imaging, MRI) (Computed tomography, CT) (Ultrasonic imaging) (Positron emission tomography, PET) (Single photon emission computed tomography, SPECT),,. : / ; / ;, ; ;.,. 1 2 ( ) [5, 9],,.,, [4 8].

2 Table 1 (MRI) (CT) (PET) (SPECT) (FRI) (FMT) (BLI) (BLT) 1 Primary uses of different imaging techniques,, 2 Table 2 Parameters of imaging techniques (MRI) m min/h, $$$ (CT) 50 m min $$ 50 m min mm $$ (PET) 1 2 mm min 18F, 11C, 15O $$$ (SPECT) 1 2 mm min 99mTc, 111In $$ (FRI) 1 2 mm s/min < 1 cm, $ (FMT) 1 2 mm s/min < 10 cm $$ (BLI) mm min cm $$ (BLT) mm min cm $$ : $ < 10 ; $$ ; $$$ > 30, , Contag [3] Lux ( ),,. 1997, Fluc, (Luciferin), Mg 2+ ATP,.,.,, [10 11]., ( CCD camera).,, nm., 600 nm,., (Bioluminescent imaging, BLI) (Bioluminescent tomography, BLT)., BLI,.,, [11 12].,, (Xenogen) IVIS. BLT,, [13 15] (

3 12 : 1451 BLT ),., BLT,,. BLT University of Iowa Bioluminescence Tomography Laboratory [16 18] ,,. 1994, Chalfie [19].,, [20]. ( ),,,,.,.,,,., (Fluorescence imaging, FI) (Fluorescence molecular tomography, FMT)., FI,. Xenogen IVIS, nm. (< 5 mm),., ( ) (FMT). ;,,, ( ). FMT [21 22], 2002 Ntziachristos [23] FMT B.,,.,, :, ;,, ;.,,.,,., (Reporter gene)., : Firefly luciferase, Luciferin, ; Renilla luciferase, Coelenterazine,..,,.,.,, : 1) ; 2), ; 3), ; 4),,,., [6, 24 28]. [29] ( 3) :, (BLI BLT),

4 Table 3 3 Comparison of in vivo optical imaging based on luciferase and GFP GFP Milliseconds ( ms) Luciferase Luciferin Minute (10 min),,,, (FI FMT)., : 1), ; 2),,, ; 3) ; 4).,.,,.,,,,, CCD ( ),. 3.2 (BLI BLT), ; (FI FMT),,, 1. University of Iowa Bioluminescence Tomography Laboratory, CCD ( ).,,, CCD.. (a) (a) In vivo fluorescence imaging Fig. 1 1 (b) (b) In vivo bioluminescence imaging Schematics of in vivo optical imaging Xenogen IVIS, CCD (Living imaging)., CCD,,,,.,., (Multispectral imaging) (Time domain optical imaging, TDOI)., ;,,,. 3.3 ( )

5 12 : 1453,., ( ), [30 31] : [D(r) Φ(r, t)] µ a (r)φ(r, t) = 1 Φ(r, t) S(r, t) (1) c t, Φ(r, t) r t ; µ a (r) ; c ; S(r, t) ; D(r) : 1 D(r) = (2) 3[µ a (r) + µ s(r)] µ s(r) = (1 g)µ s (r), g, µ a (r)..., ( ), Cong [32].,,. : ; : Monte Carlo. [33],,,,.,, [34 37] [38 41] ; ( ), ( ). Monte Carlo, [11 12],,,., : 1), ( ); 2) ;,,. CCD,,,,,,. (Perturbation-based method) [42 46] [41, 47 48] (Gradient-based method) [13 15]., Born Rytov Newton, [42 45]. : Cong [46] BLT CCD, Born,.,. Arridge [41], (Method of conjugate gradients, CGD) (Method of steepest descent, SD) (Algebraic reconstruction technique, ART), CGD., UCL BORG (Biomedical Optical Research Group) TOAST (Time-resolved optical absorption and scattering tomography),. Hielscher,. University of Iowa Bioluminescent Tomography Laboratory BLT, Cong [15],,. Lv [13]. : 1),,, ; 2),,,.

6 ; 3),,,,,. 4,, :. 4.1,,. Contag [20],,,,. Yang [49 50],. Jenkins [51],. [49 50, 52 53]. 4.2, AIDS.,,,., [54]. McCaffrey [55], sirna shrna sirna. [56 57] ( ),,,. 4.3,,., Wang [58] (Hematopoietic stem cells, HSC),,, HSC, HSC. Kim [59] (Neural progenitor cell, NPC),,. :,,.,. Paulmurugan [60] Renilla,. 4.4,. ( ),,,. Zhang [61], NO,. GFP [7],

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