Multiplexed fluorescence diffuse optical tomography
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Fluorescence tomography (FT) is an emerging non-invasive in vivo molecular imaging modality that aims at quantification and three-dimensional (3D) localization of fluorescent tagged inclusions, such as cancer lesions and drug molecules, buried deep in human and animal subjects. Depth-resolved 3D reconstruction of fluorescent inclusions distributed over the volume of optically turbid biological tissue using the diffuse fluorescent photons detected on the skin poses a highly ill-conditioned problem, as depth information must be extracted from boundary data. Due to this ill-posed nature of FT reconstructions, noise and errors in the data can severely impair the accuracy of the 3D reconstructions. Consequently, improvements in the signal-to-noise ratio (SNR) of the data significantly enhance the quality of the FT reconstructions. Furthermore, enhancing the SNR of the FT data can greatly contribute to the speed of FT scans. The pivotal factor in the SNR of the FT data is the power of the radiation illuminating the subject and exciting the administered fluorescent agents. In existing single-point illumination FT systems, the illumination power level is limited by the skin maximum radiation exposure levels. In this research, a multiplexed architecture governed by the Hadamard transform was conceptualized, developed, and experimentally implemented for orders-of-magnitude enhancement of the SNR and the robustness of FT reconstructions. The multiplexed FT system allows for Hadamard-coded multi-point illumination of the subject while maintaining the maximal information content of the FT data. The significant improvements offered by the multiplexed FT system were validated by numerical and experimental studies carried out using a custom-built multiplexed FT system developed exclusively in this work. The studies indicate that Hadamard multiplexing offers significantly enhanced robustness in reconstructing deep fluorescent inclusions from low-SNR FT data.