Self-normalized scanning fluorescence optical tomography

We propose a self-normalized scanning fluorescence diffuse optical tomography technique. The method requires a single modulated light source for excitation and multiple detector pairs symmetrically located at positions beside the source. The amplitude ratio and phase difference between the two detectors of each pair are measured as the source and detectors are scanned through the region of interest. It has been observed that the phase difference profile along a scanning line depends on target depth rather than fluorophore concentration enabling estimation of the target depth from the phase difference before reconstruction of the fluorophore concentration. The depth of a cylindrical target with a target-to-background contrast of 0.2:0.01 (Cy5.5) was varied from 0.7cm to 1.8cm, and the estimated depths were very close to their expected values with 15% maximum error. Based on the estimated target depth, the imaging volume can be segmented into a smaller region surrounding the target and a larger background region enabling the use of a dual-zone-mesh based image reconstruction. Fluorophore concentration was reconstructed by using both amplitude ratio and phase difference between the detector pairs. The reconstructed fluorophore concentration has achieved 90% accuracy. Because the amplitude ratio is dimensionless and the phase difference is a relative value, this technique is self-normalized and sensitive to low-contrast heterogeneity of fluorophore concentration in a turbid medium. In addition, based on the estimated target position and depth, the dual-zone mesh reconstruction scheme has significantly improved the reconstruction accuracy of fluorophore concentration.