UC Irvine

Fluorescence diffuse optical tomography (FDOT) is one of the most sensitive imaging modalities used in whole-body preclinical research. It offers 3D distribution of endogenous tissue contrast, fluorescent proteins, and exogenous fluorescent contrast agents. The main obstacle to its clinical application has been its low spatial resolution, despite its higher sensitivity. This limitation is mostly caused by the high optical photon scattering in biological tissue and the insufficient surface measurements, which result in an ill-posed and underdetermined inverse problem. An innovative technique known as Temperature Modulated Fluorescence Tomography (TMFT) is earlier introduced by our research group to address these shortcomings of FDOT. Thermo-sensitive fluorescent agents (ThermoDots) are one of the key components of TMF in addition to high-intensity focused ultrasound (HIFU), which is employed to locate these ThermoDots. The distribution of the ThermoDots can be determined with great spatial accuracy by scanning the tissue with a focused HIFU beam (Ø =1.3 mm), while measuring the fluctuation in the detected fluorescence signals. A prototype TMFT system that makes use of optical fibers for detection has already been constructed previously by our group. Unfortunately, this fiber-based system necessitates submerging the animal in optical matching fluid. In this study, we propose an improved version that enables non-contact imaging using a ICCD camera-based detection and removes the requirement of submerging the animal by placing it on an ultrasonic transparent membrane. Performance validation studies using tissue simulating phantoms show that high spatial-resolution (~ 1.3 mm) and superior quantitative accuracy in recovered fluorophore concentration (<3% error) can be obtained using this new version. This ICCD-based TM-FT system will pave the way for the practical and widespread application of TM-FT in preclinical research.