Subsurface fluorescence molecular tomography (FMT) is an emerging technique determining fluorescence distribution by tomographic means in reflectance geometry. However, due to the highly diffusive nature of the photon propagation in biological tissues and the influence of nearer source–detector separations, stand-alone subsurface FMT could not accurately reflect the fluorophore distributions. To overcome this drawback, we propose a method to improve the performance of fluorescence imaging by coupling x-ray computed tomography (XCT) and subsurface FMT modalities. A Laplacian-type regularization matrix generated with tissue prior information obtained from XCT images is used to guide the reconstruction of fluorophore distribution. Reconstruction results of both simulation and phantom studies showed that significant improvements in localization and demarcation of fluorescent targets can be obtained with the proposed method compared to the reconstruction method without structural prior information.
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