Accurate localization of diseases in humans, especially at advanced stages, is widely accomplished by modern imaging methods such as magnetic resonance imaging (MRI) and x-ray computed tomography (CT). Additional functional information is provided by radionuclear imaging such as positron emission tomography (PET). As medical practice moves into the molecular era, optical imaging (OI) promises to complement established imaging methods by reporting molecular events without using ionizing radiation. Uniquely, OI provides high throughput screening of molecular targets from analytical assays in solution and gels through cells and small animals, and eventual translation to humans. A powerful feature of OI is a set of photophysical mechanisms for actively reporting local molecular and physiological processes within living cells and animals. OI reporting strategies provide not only functional information but specific molecular events can be quantified and diagnostic and prognostic information can be multiplexed into a single imaging procedure. In particular, the fluorescence lifetime (FLT) of an optical probe is exquisitely sensitive to the local probe environment through perturbation of excited state properties. However concerted efforts to translate the FLT method from cells and phantom studies to imaging molecular processes in whole-body animals and humans are lacking. This is particularly true for near infrared (NIR) optical imaging that allows for assessment of tissue beyond the superficial layer. To realize fully the potential of FLT approach, there is a compelling need to develop NIR molecular probes with diverse and biologically sensitive FLTs. Equally important is the development of a NIR fluorescence lifetime diffuse optical tomography (FLT-DOT) platform to combine quantitative optical property maps with simultane- ous reconstructions of yield and lifetime. To address these problems, we will (1) design, synthesize and characterize new NIR fluorescent molecular probes with FLT range between 0.2 and 10 ns;(2) optimize methods of NIR FLT molecular probes for confocal fluorescence lifetime imaging of molecular and physiological processes in cells;(3) develop high performance FLT-DOT platform;and (4) optimize and validate quantitative in vivo imaging of FLT-NIR molecular probes in mice.

Public Health Relevance

The goals of this project are to (1) design and prepare biocompatible near infrared (NIR) fluorophores and bioconjugates with diverse fluorescence lifetime (FLT) range of 0.2 ns to 10 ns, (2) develop in vitro model for pre- dicting in vivo FLT of the molecular probes, (3) assess imaging of molecular processes by NIR confocal fluo- rescence lifetime microscopy using the NIR fluorophores, (4) and construct a highly sensitive NIR FLT diffuse optical tomography system for quantitative whole body FLT imaging.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-MEDI-A (09))
Program Officer
Conroy, Richard
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Washington University
Schools of Medicine
Saint Louis
United States
Zip Code
Miller, Jessica; Wang, Steven T; Orukari, Inema et al. (2017) Perfusion-based fluorescence imaging method delineates diverse organs and identifies multifocal tumors using generic near-infrared molecular probes. J Biophotonics :
Miller, Jessica P; Habimana-Griffin, LeMoyne; Edwards, Tracy S et al. (2017) Multimodal fluorescence molecular imaging for in vivo characterization of skin cancer using endogenous and exogenous fluorophores. J Biomed Opt 22:66007
Miller, Jessica P; Maji, Dolonchampa; Lam, Jesse et al. (2017) Noninvasive depth estimation using tissue optical properties and a dual-wavelength fluorescent molecular probe in vivo. Biomed Opt Express 8:3095-3109
Mondal, Suman B; Gao, Shengkui; Zhu, Nan et al. (2017) Optical See-Through Cancer Vision Goggles Enable Direct Patient Visualization and Real-Time Fluorescence-Guided Oncologic Surgery. Ann Surg Oncol 24:1897-1903
Som, Avik; Bloch, Sharon; Ippolito, Joseph E et al. (2016) Acidic extracellular pH of tumors induces octamer-binding transcription factor 4 expression in murine fibroblasts in vitro and in vivo. Sci Rep 6:27803
Miller, Jessica P; Egbulefu, Christopher; Prior, Julie L et al. (2016) Gradient-Based Algorithm for Determining Tumor Volumes in Small Animals Using Planar Fluorescence Imaging Platform. Tomography 2:17-25
Tsen, Shaw-Wei David; Donthi, Nisha; La, Victor et al. (2015) Chemical-free inactivated whole influenza virus vaccine prepared by ultrashort pulsed laser treatment. J Biomed Opt 20:051008
Kotagiri, Nalinikanth; Sudlow, Gail P; Akers, Walter J et al. (2015) Breaking the depth dependency of phototherapy with Cerenkov radiation and low-radiance-responsive nanophotosensitizers. Nat Nanotechnol 10:370-9
Sarder, Pinaki; Maji, Dolonchampa; Achilefu, Samuel (2015) Molecular probes for fluorescence lifetime imaging. Bioconjug Chem 26:963-74
Gilson, Rebecca C; Tang, Rui; Som, Avik et al. (2015) Protonation and Trapping of a Small pH-Sensitive Near-Infrared Fluorescent Molecule in the Acidic Tumor Environment Delineate Diverse Tumors in Vivo. Mol Pharm 12:4237-46

Showing the most recent 10 out of 48 publications