The recent emergence of novel molecular fluorescent probes and proteins has enabled the in-vivo interrogation of molecular function and significantly enhanced our ability to study pathogenesis in vivo. While advances in fluorochrome probe development have been rapid, the corresponding technologies for in-vivo imaging have been largely limited to qualitative photographic approaches of close to the surface events (reflectance imaging). In order to image molecular events deeper in tissue, we have recently developed a prototype scanner for fluorescence-mediated molecular tomography (FMT) of small animals and imaging of molecular targets. Major challenges that remain in vivo are a) to improve resolution, b) to quantitatively image the full-body distribution of specific molecular markers and c) to merge molecular reconstructions with high-resolution surface features for high positional accuracy rendering. In this proposal we seek to develop a highly optimized imaging system with unprecedented three-dimensional detection capacity. In particular we propose the use of a time-gated intensified CCD camera for high spatial and temporal sampling of fluorescent signals and combine it with non-contact detection geometries, concurrent reflectance imaging and high-resolution three-dimensional boundary extraction. Furthermore, we aim at developing fast reconstruction schemes, appropriate for the large data-sets acquired and for non-contact geometries, in order to resolve and quantify fluorochrome concentration, activation and fluorescence lifetime. FMT is one of the few truly enabling technologies for molecular imaging since it capitalizes on signal amplification and fluorescence activation (molecular switches or beacons), high detection sensitivity and chemical specificity. Furthermore, it uses stable reporters, non-ionizing radiation and can simultaneously image multiple targets by spectral differentiation. Recent studies have also shown the potential of using this technology to interrogate human tissues. FMT is expected to enhance our ability to study molecular pathways, perform early detection of disease, real time molecular medicine and ultimately patient-tailored treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
1R01EB000750-01
Application #
6588933
Study Section
Special Emphasis Panel (ZRG1-SSS-X (30))
Program Officer
Korte, Brenda
Project Start
2002-09-15
Project End
2006-08-31
Budget Start
2002-09-15
Budget End
2003-08-31
Support Year
1
Fiscal Year
2002
Total Cost
$370,160
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Niedre, Mark; Ntziachristos, Vasilis (2010) Comparison of fluorescence tomographic imaging in mice with early-arriving and quasi-continuous-wave photons. Opt Lett 35:369-71
Deliolanis, Nikolaos C; Dunham, Joshua; Wurdinger, Thomas et al. (2009) In-vivo imaging of murine tumors using complete-angle projection fluorescence molecular tomography. J Biomed Opt 14:030509
Niedre, Mark; Ntziachristos, Vasilis (2009) Complete angle small animal fluorescence imaging with early-arriving photons. Conf Proc IEEE Eng Med Biol Soc 2009:6331-4
Niedre, Mark J; de Kleine, Ruben H; Aikawa, Elena et al. (2008) Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo. Proc Natl Acad Sci U S A 105:19126-31
Haller, Jodi; Hyde, Damon; Deliolanis, Nikolaos et al. (2008) Visualization of pulmonary inflammation using noninvasive fluorescence molecular imaging. J Appl Physiol 104:795-802
Garofalakis, Anikitos; Zacharakis, Giannis; Meyer, Heiko et al. (2007) Three-dimensional in vivo imaging of green fluorescent protein-expressing T cells in mice with noncontact fluorescence molecular tomography. Mol Imaging 6:96-107
Meyer, Heiko; Garofalakis, Anikitos; Zacharakis, Giannis et al. (2007) Noncontact optical imaging in mice with full angular coverage and automatic surface extraction. Appl Opt 46:3617-27
Deliolanis, Nikolaos; Lasser, Tobias; Hyde, Damon et al. (2007) Free-space fluorescence molecular tomography utilizing 360 degrees geometry projections. Opt Lett 32:382-4
Sosnovik, David E; Nahrendorf, Matthias; Deliolanis, Nikolaos et al. (2007) Fluorescence tomography and magnetic resonance imaging of myocardial macrophage infiltration in infarcted myocardium in vivo. Circulation 115:1384-91
Niedre, Mark J; Turner, Gordon M; Ntziachristos, Vasilis (2006) Time-resolved imaging of optical coefficients through murine chest cavities. J Biomed Opt 11:064017

Showing the most recent 10 out of 31 publications