Deep tissue optical and optoacoustic molecular imaging technologies for pre-clinical research and drug discovery.

For centuries, biological discoveries were based on optical imaging, in particular microscopy but also several chromophoric assays and photographic approaches. With the recent emergence of methods appropriate for bio-marker in vivo staining, such as bioluminescence, fluorescent molecular probes and proteins, as well as nanoparticle-based targeted agents, significant attention has been shifted toward in vivo interrogations of different dynamic biological processes at the molecular level. This progress has been largely supported by the development of advanced tomographic imaging technologies suitable for obtaining volumetric visualization of bio-marker distributions in small animals at a whole-body or whole-organ scale, an imaging frontier that is not accessible by the existing tissue-sectioning microscopic techniques due to intensive light scattering beyond the depth of a few hundred microns. Major examples of such recently developed optical imaging modalities are reviewed here, including bioluminescence tomography (BLT), fluorescence molecular tomography (FMT), and optical projection tomography (OPT). The pharmaceutical imaging community has quickly appropriated itself of these novel forms of optical imaging, since they come with very compelling advantages, such as quantitative three-dimensional capabilities, direct correlation to the biological cultures, easiness and cost-effectiveness of use, and the use of safe non-ionizing radiation. Some multi-modality approaches, combining light with other imaging modalities such as X-Ray CT or MRI, giving the ability to acquire both an optical contrast reconstruction along with a hi-fidelity anatomical images, are also reviewed. A separate section is devoted to the hybrid imaging techniques based on the optoacoustic phenomenon, such as multispectral optoacoustic tomography (MSOT), which are poised to leverage the traditional contrast and specificity advantages of optical spectrum by delivering an ever powerful set of capabilities, including real-time operation and high spatial resolution, not affected by the scattering nature of biological tissues.

[1]  Zhuang Liu,et al.  Carbon nanotubes as photoacoustic molecular imaging agents in living mice. , 2008, Nature nanotechnology.

[2]  Xavier Intes,et al.  Data subset algorithm for computationally efficient reconstruction of 3-D spectral imaging in diffuse optical tomography. , 2006, Optics express.

[3]  Vasilis Ntziachristos,et al.  Transillumination fluorescence imaging in mice using biocompatible upconverting nanoparticles. , 2009, Optics letters.

[4]  V. Ntziachristos,et al.  Textbook of in vivo imaging in vertebrates , 2006 .

[5]  B. Pogue,et al.  Imaging breast adipose and fibroglandular tissue molecular signatures by using hybrid MRI-guided near-infrared spectral tomography. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[6]  Britton Chance,et al.  Diffuse optical tomography with a priori anatomical information. , 2005 .

[7]  V. Ntziachristos,et al.  Molecular imaging by means of multispectral optoacoustic tomography (MSOT). , 2010, Chemical reviews.

[8]  Vasilis Ntziachristos,et al.  In vivo imaging of Drosophila melanogaster pupae with mesoscopic fluorescence tomography , 2007, Nature Methods.

[9]  R. Weissleder,et al.  Charge-coupled-device based scanner for tomography of fluorescent near-infrared probes in turbid media. , 2002, Medical physics.

[10]  Hamid Dehghani,et al.  In vivo bioluminescence tomography with a blocking-off finite-difference SP3 method and MRI/CT coregistration. , 2009, Medical physics.

[11]  S R Arridge,et al.  Optical tomographic reconstruction in a complex head model using a priori region boundary information. , 1999, Physics in medicine and biology.

[12]  Vasilis Ntziachristos,et al.  Normalized Born ratio for fluorescence optical projection tomography. , 2009, Optics letters.

[13]  Vladimir P Zharov,et al.  Quantum dots as multimodal photoacoustic and photothermal contrast agents. , 2008, Nano letters.

[14]  F. Del Bene,et al.  Optical Sectioning Deep Inside Live Embryos by Selective Plane Illumination Microscopy , 2004, Science.

[15]  Lihong V. Wang,et al.  Photoacoustic tomography of a nanoshell contrast agent in the in vivo rat brain , 2004 .

[16]  B. Pogue,et al.  Image-guided diffuse optical fluorescence tomography implemented with Laplacian-type regularization. , 2007, Optics express.

[17]  B. Pogue,et al.  Near-infrared (NIR) tomography breast image reconstruction with a priori structural information from MRI: algorithm development for reconstructing heterogeneities , 2003 .

[18]  J. Hecksher-Sørensen,et al.  Optical Projection Tomography as a Tool for 3D Microscopy and Gene Expression Studies , 2002, Science.

[19]  Shiwei Wu,et al.  Non-blinking and photostable upconverted luminescence from single lanthanide-doped nanocrystals , 2009, Proceedings of the National Academy of Sciences.

[20]  Liang Song,et al.  Section-illumination photoacoustic microscopy for dynamic 3D imaging of microcirculation in vivo. , 2010, Optics letters.

[21]  Yuting Lin,et al.  Fluorescence diffuse optical tomography with functional and anatomical a priori information: feasibility study , 2007, Physics in medicine and biology.

[22]  Michael Z. Lin,et al.  Mammalian Expression of Infrared Fluorescent Proteins Engineered from a Bacterial Phytochrome , 2009, Science.

[23]  Vasilis Ntziachristos,et al.  Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo , 2008, Proceedings of the National Academy of Sciences.

[24]  Lihong V. Wang,et al.  Noninvasive laser-induced photoacoustic tomography for structural and functional in vivo imaging of the brain , 2003, Nature Biotechnology.

[25]  M. Reddington,et al.  Surface imaging microscopy, an automated method for visualizing whole embryo samples in three dimensions at high resolution , 2002, Developmental dynamics : an official publication of the American Association of Anatomists.

[26]  Vasilis Ntziachristos,et al.  Real-time imaging of cardiovascular dynamics and circulating gold nanorods with multispectral optoacoustic tomography. , 2010, Optics express.

[27]  W. Weninger,et al.  Phenotyping transgenic embryos: a rapid 3-D screening method based on episcopic fluorescence image capturing , 2002, Nature Genetics.

[28]  Vasilis Ntziachristos,et al.  Planar fluorescence imaging using normalized data. , 2005, Journal of biomedical optics.

[29]  Vasilis Ntziachristos,et al.  Imaging of mesoscopic-scale organisms using selective-plane optoacoustic tomography , 2009, Physics in medicine and biology.

[30]  M S Patterson,et al.  Imaging of fluorescent yield and lifetime from multiply scattered light reemitted from random media. , 1997, Applied optics.

[31]  V. Ntziachristos,et al.  Video rate optoacoustic tomography of mouse kidney perfusion. , 2010, Optics letters.

[32]  Lihong V. Wang.  Photoacoustic imaging and spectroscopy , 2009 .

[33]  Konstantin Sokolov,et al.  Plasmonic intravascular photoacoustic imaging for detection of macrophages in atherosclerotic plaques. , 2009, Nano letters.

[34]  Wei Wang,et al.  Simultaneous Molecular and Hypoxia Imaging of Brain Tumors In Vivo Using Spectroscopic Photoacoustic Tomography , 2008, Proceedings of the IEEE.

[35]  Vasilis Ntziachristos,et al.  Inflammation in Atherosclerosis: Visualizing Matrix Metalloproteinase Action in Macrophages In Vivo , 2006, Circulation.

[36]  J. Laufer,et al.  In vivo high-resolution 3D photoacoustic imaging of superficial vascular anatomy , 2009, Physics in medicine and biology.

[37]  Martin Frenz,et al.  Combined ultrasound and optoacoustic system for real-time high-contrast vascular imaging in vivo , 2005, IEEE Transactions on Medical Imaging.

[38]  T. Wurdinger,et al.  In-vivo imaging of murine tumors using complete-angle projection fluorescence molecular tomography. , 2009, Journal of biomedical optics.

[39]  J. Willmann,et al.  Molecular imaging in drug development , 2008, Nature Reviews Drug Discovery.

[40]  Soren D. Konecky,et al.  Diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: a case study with comparison to MRI. , 2005, Medical physics.

[41]  Vasilis Ntziachristos,et al.  Looking and listening to light: the evolution of whole-body photonic imaging , 2005, Nature Biotechnology.

[42]  James Sharpe,et al.  Tomographic molecular imaging and 3D quantification within adult mouse organs , 2007, Nature Methods.

[43]  W. Denk,et al.  Deep tissue two-photon microscopy , 2005, Nature Methods.

[44]  M. Jiang,et al.  Uniqueness theorems in bioluminescence tomography. , 2004, Medical physics.

[45]  David A Boas,et al.  Simulation study of magnetic resonance imaging-guided cortically constrained diffuse optical tomography of human brain function. , 2005, Applied optics.

[46]  Younan Xia,et al.  Near-infrared gold nanocages as a new class of tracers for photoacoustic sentinel lymph node mapping on a rat model. , 2009, Nano letters.

[47]  Ozlem Birgul,et al.  Combined Diffuse Optical Tomography (DOT) and MRI System for Cancer Imaging in Small Animals , 2006, Technology in cancer research & treatment.

[48]  H. Jiang,et al.  Frequency-domain fluorescent diffusion tomography: a finite-element-based algorithm and simulations. , 1998, Applied optics.

[49]  Ralph Weissleder,et al.  Upconverting luminescent nanomaterials: application to in vivo bioimaging. , 2009, Chemical communications.

[50]  Vasilis Ntziachristos,et al.  Performance of iterative optoacoustic tomography with experimental data , 2009 .

[51]  N. Iftimia,et al.  Imaging of in vitro and in vivo bones and joints with continuous-wave diffuse optical tomography. , 2001, Optics express.

[52]  Tymish Y. Ohulchanskyy,et al.  High contrast in vitro and in vivo photoluminescence bioimaging using near infrared to near infrared up-conversion in Tm3+ and Yb3+ doped fluoride nanophosphors. , 2008, Nano letters.

[53]  Vasilis Ntziachristos,et al.  Multispectral opto-acoustic tomography of deep-seated fluorescent proteins in vivo , 2009 .

[54]  Britton Chance,et al.  Diffuse optical tomography with physiological and spatial a priori constraints , 2004, Physics in medicine and biology.

[55]  B. Pogue,et al.  Spectrally resolved bioluminescence optical tomography. , 2006, Optics letters.

[56]  Vasilis Ntziachristos,et al.  A submillimeter resolution fluorescence molecular imaging system for small animal imaging. , 2003, Medical physics.

[57]  Massoud Motamedi,et al.  High sensitivity of in vivo detection of gold nanorods using a laser optoacoustic imaging system. , 2007, Nano letters.

[58]  Rinaldo Cubeddu,et al.  Comparison of noncontact and fiber-based fluorescence-mediated tomography. , 2006, Optics letters.

[59]  Akira Ishimaru,et al.  Wave propagation and scattering in random media , 1997 .

[60]  R. Weissleder,et al.  Imaging of molecular probe activity with Born-normalized fluorescence optical projection tomography. , 2010, Optics letters.

[61]  M. Schweiger,et al.  Diffuse optical tomography with spectral constraints and wavelength optimization. , 2005, Applied optics.

[62]  Lihong V. Wang,et al.  Photoacoustic imaging of lacZ gene expression in vivo. , 2007, Journal of biomedical optics.

[63]  R Weissleder,et al.  Near-infrared optical imaging of protease activity for tumor detection. , 1999, Radiology.

[64]  Eric L. Miller,et al.  Hybrid FMT–CT imaging of amyloid-β plaques in a murine Alzheimer's disease model , 2009, NeuroImage.

[65]  Brian W. Pogue,et al.  Magnetic resonance-guided near-infrared tomography of the breast , 2004 .

[66]  Vasilis Ntziachristos,et al.  Free-space fluorescence molecular tomography utilizing 360° geometry projections , 2007 .

[67]  Ralph Weissleder,et al.  High throughput transmission optical projection tomography using low cost graphics processing unit. , 2009, Optics express.

[68]  A. Schierloh,et al.  Ultramicroscopy: three-dimensional visualization of neuronal networks in the whole mouse brain , 2007, Nature Methods.

[69]  Lihong V. Wang,et al.  Noninvasive label-free imaging of microhemodynamics by optical-resolution photoacoustic microscopy. , 2009, Optics express.

[70]  R. Weissleder,et al.  Fluorescence molecular tomography resolves protease activity in vivo , 2002, Nature Medicine.

[71]  D. Boas,et al.  Fluorescence lifetime imaging in turbid media. , 1996, Optics letters.

[72]  Stanislav Emelianov,et al.  Molecular specific optoacoustic imaging with plasmonic nanoparticles. , 2007, Optics express.

[73]  Vasilis Ntziachristos,et al.  Multispectral photoacoustic imaging of fluorochromes in small animals. , 2007, Optics letters.

[74]  Avinash C. Kak,et al.  Principles of computerized tomographic imaging , 2001, Classics in applied mathematics.

[75]  Vasilis Ntziachristos,et al.  Fluorescence Tomography and Magnetic Resonance Imaging of Myocardial Macrophage Infiltration in Infarcted Myocardium In Vivo , 2007, Circulation.

[76]  Hua-bei Jiang,et al.  Three-dimensional bioluminescence tomography with model-based reconstruction. , 2004, Optics express.

[77]  H. Weber,et al.  Temporal backward projection of optoacoustic pressure transients using fourier transform methods. , 2001, Physics in medicine and biology.

[78]  Lihong V. Wang,et al.  Intravital imaging of amyloid plaques in a transgenic mouse model using optical-resolution photoacoustic microscopy. , 2009, Optics letters.

[79]  Vasilis Ntziachristos,et al.  Quantitative Optoacoustic Signal Extraction Using Sparse Signal Representation , 2009, IEEE Transactions on Medical Imaging.

[80]  A. Y. Bluestone,et al.  Near-Infrared Diffuse Optical Tomography , 2003, Disease markers.

[81]  Vasilis Ntziachristos,et al.  Fast Semi-Analytical Model-Based Acoustic Inversion for Quantitative Optoacoustic Tomography , 2010, IEEE Transactions on Medical Imaging.

[82]  E. Miller,et al.  Tomographic optical breast imaging guided by three-dimensional mammography. , 2003, Applied optics.

[83]  R. Kruger,et al.  Photoacoustic ultrasound (PAUS)--reconstruction tomography. , 1995, Medical physics.

[84]  Srirang Manohar,et al.  Synthesis and Bioconjugation of Gold Nanoparticles as Potential Molecular Probes for Light-Based Imaging Techniques , 2007, Int. J. Biomed. Imaging.

[85]  R. Weissleder,et al.  Experimental three-dimensional fluorescence reconstruction of diffuse media by use of a normalized Born approximation. , 2001, Optics letters.

[86]  Vasilis Ntziachristos,et al.  Normalized Transillumination of Fluorescent Proteins in Small Animals , 2006, Molecular imaging.

[87]  B. Pogue,et al.  Combining near-infrared tomography and magnetic resonance imaging to study in vivo breast tissue: implementation of a Laplacian-type regularization to incorporate magnetic resonance structure. , 2005, Journal of biomedical optics.

[88]  Xueding Wang,et al.  Picomolar sensitivity MRI and photoacoustic imaging of cobalt nanoparticles , 2009, Proceedings of the National Academy of Sciences.

[89]  Vasilis Ntziachristos,et al.  Multispectral optoacoustic tomography (MSOT) scanner for whole-body small animal imaging. , 2009, Optics express.