Local molecular and physiological processes can be imaged in vivo through perturbations in the fluorescence lifetime (FLT) of optical imaging agents. In addition to providing functional information, FLT methods can quantify specific molecular events and multiplex diagnostic and prognostic information. We have developed a fluorescence lifetime diffuse optical tomography (DOT) system for in vivo preclinical imaging. Data is captured using a time-resolved intensified charge coupled device (ICCD) system to measure fluorescence excitation and emission in the time domain. Data is then converted to the frequency domain, and we simultaneously reconstruct images of yield and lifetime using an extension to the normalized Born approach. By using differential phase measurements, we demonstrate DOT imaging of short lifetimes (from 350 ps) with high precision (+/-5 ps). Furthermore, this system retains the efficiency, speed, and flexibility of transmission geometry DOT. We demonstrate feasibility of FLT-DOT through a progressive series of experiments. Lifetime range and repeatability are first measured in phantoms. Imaging of subcutaneous implants then verifies the FLT-DOT approach in vivo in the presence of inhomogeneous optical properties. Use in a common research scenario is ultimately demonstrated by imaging accumulation of a targeted near-infrared (NIR) fluorescent-labeled peptide probe (cypate-RGD) in a mouse with a subcutaneous tumor.
Three-dimensional, voxel-based, and wavelength-dependent skin lesion models are developed and simulated using Monte Carlo techniques. The optical geometry of the Nevoscope with trans-illumination is used in the simulations for characterizing the lesion thickness. Based on the correlation analysis between the lesion thickness and the diffuse reflectance, optical wavelengths are selected for multispectral imaging of skin lesions using the Nevoscope. Tissue optical properties reported by various researchers are compiled together to form a voxel library. Tissue models used in the simulations are developed using the voxel library which offers flexibility in updating the optical properties and adding new media types into the models independent of the Monte Carlo simulation code.
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