Initial results from a novel dual modality preclinical imager which combines non-contact fluorescence tomography (FT) and x-ray computed tomography (CT) for preclinical functional and anatomical in vivo imaging are presented. The anatomical data from CT provides a priori information to the FT reconstruction to create overlaid functional and anatomical images with accurate localization and quantification of fluorophore distribution. Phantoms with inclusions containing Indocyanine-Green (ICG), and with heterogeneous backgrounds including iodine in compartments at different concentrations for CT contrast, have been imaged with the dual modality FT/CT system. Anatomical information from attenuation maps and optical morphological information from absorption and scattering maps are used as a priori information in the FT reconstruction. Although ICG inclusions can be located without the a priori information, the recovered ICG concentration shows 75% error. When the a priori information is utilized, the ICG concentration can be recovered with only 15% error. Developing the ability to accurately quantify fluorophore concentration in anatomical regions of interest may provide a powerful tool for in vivo small animal imaging.

Structural changes in water molecules are related to physiological, anatomical and pathological properties of tissues. Near infrared (NIR) optical absorption methods are sensitive to water, however detailed characterization of water in thick tissues is difficult to achieve because subtle spectral shifts can be obscured by multiple light scattering. In the NIR, a water absorption peak is observed around 975nm. The precise NIR peak shape and position is highly sensitive to water molecular disposition. We introduce a Bound Water Index (BWI) that quantifies shifts observed in tissue water absorption spectra measured by broadband Diffuse Optical Spectroscopy (DOS). DOS quantitatively measures light absorption and scattering spectra and therefore reveals bound-water spectral shifts. BWI as a water state index was validated by comparing broadband DOS to Magnetic Resonance Spectroscopy, diffusion-weighted MRI and conductivity in bound water tissue phantoms. Non-invasive DOS measurements of malignant and normal breast tissues performed in 18 subjects showed a significantly higher fraction of free water in malignant tissues (p<0.0001) compared to normal tissues. BWI of breast cancer tissues inversely correlated with Nottingham-Bloom-Richardson histopathology scores. These results highlight broadband DOS sensitivity to molecular disposition of water, and demonstrate the potential of BWI as a non-invasive in-vivo index that correlates with tissue pathology.