Whole-body optical molecular imaging of small animals is widely used to investigate fundamental biological processes in vivo and accelerate drug development. However, the actual technical implementations do not allow for robust quantitative rendering of 3D bio- distribution of the luminescent markers and require lengthy acquisition times incompatible with multiplexed studies. Our hypothesis is that by employing structured light illumination strategies and by using reconstruction algorithms based on the Monte Carlo method, the inverse optical molecular imaging problem can be solved accurately to provide quantitative spatial maps of molecular fluorescence markers distribution in the internal organs of small animals and simultaneously for multiply markers. The objective of this proposal is to develop, characterize and validate a novel pre-clinical imaging platform that will allow tracking in vivo multiple fluorophores in small animals. First, we intend to develop a fluorescence molecular small animal imager that will be able to provide quantitative fluorescent tomographic data for in vivo multiplexed study. Second, we propose to develop new reconstruction algorithm to perform multispectral time-resolved optical reconstructions. The algorithm will be based on the Monte Carlo method for accurate light propagation model in complex geometry and for complex illumination strategies. Third, we will characterize the performances of this new enabling platform to perform Fluorescence Resonance Energy Transfer (FRET) imaging in vivo. We will integrate a non-contact optical imager based on high-power NIR laser, Digital Micromirror Device (DMD) and time-resolved spectrophotometer. Reconstruction algorithms based on an adjoint Monte Carlo formulation will be developed concurrently to model light propagation in small animal and to perform fluorescent yield and lifetime reconstructions. After validating the imaging platform in vitro, whole-body in vivo small animal imaging of NIR-ligand labeled FRET pair will be performed. This new system will fill an important unmet need in pre-clinical studies. This research proposal is expected to revolutionize the investigation of fundamental biological processes in vivo and considerably accelerate drug development by providing a new imaging tool with high-sensitivity and high-throughput capability for molecular imaging studies in whole animals.

Public Health Relevance

We propose to develop a new molecular optical imaging platform for whole body fluorescence small animal imaging of multiple fluorophores. The imaging platform developed under this funding will allow imaging a large number of sites and organs in live animals with high-sensitivity, quantitative accuracy and at multiple wavelengths for multiplexed studies. It will greatly impact the development of small animal optical imaging, and will benefit different biomedical research areas, including cancer, immunologic/inflammatory and neurodegenerative diseases.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1-BMIT-J (01))
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Conroy, Richard
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Rensselaer Polytechnic Institute
Biomedical Engineering
Schools of Engineering
United States
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Yao, Ruoyang; Intes, Xavier; Fang, Qianqian (2016) Generalized mesh-based Monte Carlo for wide-field illumination and detection via mesh retessellation. Biomed Opt Express 7:171-84
Yao, Ruoyang; Pian, Qi; Intes, Xavier (2015) Wide-field fluorescence molecular tomography with compressive sensing based preconditioning. Biomed Opt Express 6:4887-98
Pian, Qi; Yao, Ruoyang; Zhao, Lingling et al. (2015) Hyperspectral time-resolved wide-field fluorescence molecular tomography based on structured light and single-pixel detection. Opt Lett 40:431-4
Zhao, Lingling; Yang, He; Cong, Wenxiang et al. (2014) L(p) regularization for early gate fluorescence molecular tomography. Opt Lett 39:4156-9
Omer, Travis; Zhao, Lingling; Intes, Xavier et al. (2014) Reduced temporal sampling effect on accuracy of time-domain fluorescence lifetime Förster resonance energy transfer. J Biomed Opt 19:086023
Abe, Ken; Zhao, Lingling; Periasamy, Ammasi et al. (2013) Non-invasive in vivo imaging of near infrared-labeled transferrin in breast cancer cells and tumors using fluorescence lifetime FRET. PLoS One 8:e80269
Venugopal, Vivek; Intes, Xavier (2013) Adaptive wide-field optical tomography. J Biomed Opt 18:036006
Venugopal, Vivek; Intes, Xavier (2013) Adaptive wide-field optical tomography. J Biomed Opt 18:036006
Chen, Jin; Fang, Qianqian; Intes, Xavier (2012) Mesh-based Monte Carlo method in time-domain widefield fluorescence molecular tomography. J Biomed Opt 17:106009
Pimpalkhare, Monish; Chen, Jin; Venugopal, Vivek et al. (2012) Ex vivo fluorescence molecular tomography of the spine. Int J Biomed Imaging 2012:942326

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