A photo-multiplier tube-based hybrid MRI and frequency domain fluorescence tomography system for small animal imaging

Abstract

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.

Dynamic dual-tracer MRI-guided fluorescence tomography to quantify receptor density in vivo

“…Applying these principles, imaging fluorescence activity in relatively large tissue volumes (over 5 cm) is feasible. Substantial evidence exists suggesting that volumetric images of fluorescence activity are more accurate if additional information, such as the anatomical features of the tissue, is incorporated in the optical image reconstruction algorithm (29)(30)(31)(32)(33)(34).…”

Computed Tomography-guided Time-domain Diffuse Fluorescence Tomography in Small Animals for Localization of Cancer Biomarkers

“…However, CCD cameras have a limited dynamic range and read-out noise limits their ultimate sensitivity. The second design avoids the potential limitations of CCD camera detection by employing highly sensitive single-photon counting technology based on the use of such detectors as photomultiplier tubes or avalanche photodiodes [10][11][12][13] . The drawback of these more sensitive detection methods is that each detector can only collect light at a single point; therefore, to achieve dense tissue sampling, either many detectors have to be used (which is very expensive), or many projections have to be imaged with the same detector (which can be time consuming).…”

“…The majority of research groups have invested in charge-coupled device (CCD)-based systems that provide abundant tissue-sampling but suboptimal sensitivity [4][5][6][7][8][9] , while our group and a few others [10][11][12][13] have pursued systems based on very high sensitivity detectors, that at this time allow dense tissue sampling to be achieved only at the cost of low imaging throughput. Here we demonstrate the methodology for applying single-photon detection technology in a fluorescence tomography system to localize a cancerous brain lesion in a mouse model.…”

Temperature-modulated fluorescence tomography based on both concentration and lifetime contrast

“…Recently, there has been a great interest in developing fluorescence imaging systems based on lifetime contrast. [9][10][11] Despite the exciting development of highly sensitive and versatile fluorescence probes, the main barrier in widespread use of fluorescence imaging in vivo, including in tomographic mode, is the low spatial resolution caused by strong tissue scattering. The recovered fluorescence parameters highly depend on the size and depth of the fluorescence source.…”