Time-resolved Fluorescence Tomography Research Articles

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

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 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 and 3-3′ diethylthiatricarbocyanine iodide, 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.

Full-field time-resolved fluorescence tomography of small animals

In this experimental investigation, we explore the feasibility of using wide-field illumination for time-resolved fluorescence molecular tomography. The performance of wide-field patterns with a time-resolved imaging platform is investigated in vitro and in a small animal model. A Monte Carlo-based forward model is employed to reconstruct fluorescence yield based on time-gated datasets. An improvement in resolution and quantification when using the time-gate data type compared to the commonly used cw data type is demonstrated in vitro. Furthermore, the feasibility of wide-field strategies for fluorescence preclinical applications is established by an accurate localization of a fluorescent inclusion implanted in the chest cavity of a murine model.

Time resolved fluorescence tomography of turbid media based on lifetime contrast

A general linear model for time domain (TD) fluorescence tomography is presented that allows a lifetime-based analysis of the entire temporal fluorescence response from a turbid medium. Simulations are used to show that TD fluorescence tomography is optimally performed using two complementary approaches: A direct TD analysis of a few time points near the peak of the temporal response, which provides superior resolution; and an asymptotic multi-exponential analysis based tomography of the decay portion of the temporal response, which provides accurate localization of yield distributions for various lifetime components present in the imaging medium. These results indicate the potential of TD technology for biomedical imaging with lifetime sensitive targeted probes, and provide useful guidelines for an optimal approach to fluorescence tomography with TD data.