Differentiation and Localization of Adjacent Murine Tumors Using X-ray and Bioluminescence Tomography.

Abstract

IntroductionPreviously, a multimodal imaging system including x-ray computed tomography (CT) and bioluminescence tomography (BLT) has been developed on iSMAART and is capable of accurately localizing small tumors on the millimeter scale in three dimensions (3D). Here, a "2D decomposition + 3D reconstruction" strategy is proposed to recover multiple tumors that are closely spaced and may have drastically different bioluminescence intensities.MethodsIn the iSMAART system, CT provides the animal anatomy and surface contours required for BLT reconstruction. The BLT and CT are physically registered, rendering superimposed images. For BLT reconstruction, the surface bioluminescence signal is first decomposed using a Gaussian mathematical model into multiple independent signal distributions, before separate reconstruction of individual targets. The final tumor distribution is the summation of the individual reconstruction results. BLT/CT imaging was performed on two types of metastatic tumor models, PC3 prostate tumors and HCT116 colorectal tumors, with 2 mice in each model. A double-blind histopathological analysis was conducted to verify the imaging results.Results and ConclusionBy incorporating the proposed strategy, the iSMAART system accurately differentiated and localized multiple tightly clustered tumors of varying sizes and optical intensities in all mice, and four tumors in a single mouse were simultaneously diagnosed. The tumor sizes measured by BLT closely matched the histopathological results (mean value 2.76 vs 2.41 mm). In this study, we proposed a "2D decomposition + 3D reconstruction" strategy, which enables the iSMAART system to accurately localize and quantify multiple tumors in live animals despite significant signal overlap and intensity variations, providing a powerful tool to fulfill and even open up more high-demand research fields.