Fluorescence tomography (FT) is a promising molecular imaging technique that can spatially resolve both fluorophore concentration and lifetime parameters. However, recovered fluorophore parameters highly depend on the size and depth of the object due to the ill-posedness of the FT inverse problem. Structural a priori information from another high spatial resolution imaging modality has been demonstrated to significantly improve FT reconstruction accuracy. In this study, we have constructed a combined magnetic resonance imaging (MRI) and FT system for small animal imaging. A photo-multiplier tube (PMT) is used as the detector to acquire frequency domain FT measurements. This is the first MR-compatible time-resolved FT system that can reconstruct both fluorescence concentration and lifetime maps simultaneously. The performance of the hybrid system is evaluated with phantom studies. Two different fluorophores, Indocyanine Green (ICG) and 3-3′ Diethylthiatricarbocyanine Iodide (DTTCI), which have similar excitation and emission spectra but different lifetimes, are utilized. The fluorescence concentration and lifetime maps are both reconstructed with and without the structural a priori information obtained from MRI for comparison. We show that the hybrid system can accurately recover both fluorescence intensity and lifetime within 10% error for two 4.2 mm-diameter cylindrical objects embedded in a 38 mm-diameter cylindrical phantom when MRI structural a priori information is utilized.
This study was to investigate the association between tCho and the clinical characteristics and biomarker status of breast cancer. Sixty-two patients with breast cancer which was 1.5 cm or larger in size on MR images were studied. The tCho concentration was correlated with the MR imaging features, the contrast enhancement kinetics, clinical variables, and biomarkers. Pair-wise two-tailed Spearman’s non-parametric test was used for the statistical analysis. The tCho was higher in high grade than moderate/low grade tumor (p=0.04) and in tumors with higher Ktrans and kep (p<0.001 for both). The association of tCho with age (p=0.05) and triple negative biomarker (p=0.09) approached significance. tCho was not detected in 17 patients, including 15 invasive ductal cancer and 2 infiltrating lobular cancer. Fifteen of the 17 patients had moderate to low grade cancers, and 11 had HER-2 negative cancer, suggesting these two factors might lead to false negative choline. Higher tCho in high grade tumors and tumors with higher Ktrans and kep indicates choline is associated with cell proliferation and tumor angiogenesis. Higher choline level in younger women may be due to their more aggressive tumor type. The results presented here may aid in better interpretation of 1H MRS for diagnosis of breast lesions.
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.
Fluorescence Tomography; Diffuse Optical Tomography; X-Ray Computed Tomography