Abstract

Bioluminescence tomography (BLT) is a promising in vivo molecular imaging tool that allows non-invasive monitoring of physiological and pathological processes at the cellular and molecular levels. However, the accuracy of the BLT reconstruction is significantly affected by the forward modeling errors in the simplified photon propagation model, the measurement noise in data acquisition, and the inherent ill-posedness of the inverse problem. In this paper, we present a new multispectral differential strategy (MDS) on the basis of analyzing the errors generated from the simplification from radiative transfer equation (RTE) to diffusion approximation and data acquisition of the imaging system. Through rigorous theoretical analysis, we learn that spectral differential not only can eliminate the errors caused by the approximation of RTE and imaging system measurement noise but also can further increase the constraint condition and decrease the condition number of system matrix for reconstruction compared with traditional multispectral (TM) reconstruction strategy. In forward simulations, energy differences and cosine similarity of the measured surface light energy calculated by Monte Carlo (MC) and diffusion equation (DE) showed that MDS can reduce the systematic errors in the process of light transmission. In addition, in inverse simulations and in vivo experiments, the results demonstrated that MDS was able to alleviate the ill-posedness of the inverse problem of BLT. Thus, the MDS method had superior location accuracy, morphology recovery capability, and image contrast capability in the source reconstruction as compared with the TM method and spectral derivative (SD) method. In vivo experiments verified the practicability and effectiveness of the proposed method.

Highlights

  • Bioluminescence imaging (BLI), applied in preclinical molecular imaging of small animals, has attracted widespread attention in biological and medical research [1]

  • The digital mouse simulations and in vivo experiments were designed to evaluate the performance of multispectral differential strategy (MDS) in Bioluminescence tomography (BLT) reconstruction

  • By comparing the surface light distributions of Monte Carlo (MC) and diffusion equation (DE) at the same wavelength in Figures 2A, B, we find that the differences are obvious at 610- and 630-nm wavelengths, while they are relatively small at 650- and 670-nm wavelengths

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Summary

Introduction

Bioluminescence imaging (BLI), applied in preclinical molecular imaging of small animals, has attracted widespread attention in biological and medical research [1]. The non-radiation imaging method has the advantages of fast feedback, high sensitivity, high temporal resolution, and high specificity, which is often used in molecular, cellular, and gene expression imaging studies to Multispectral Differential in BLT facilitate drug development disease research and therapeutic interventions [2,3,4]. Bioluminescence tomography (BLT) employs threedimensional (3D) reconstruction of bioluminescent sources to more accurately locate and quantify tumors compared with BLI [5]. The basic idea of BLT is to utilize a “forward” model of light propagation through the tissue to the skin surface, along with an “inversion” algorithm to reconstruct the underlying bioluminescence source distribution [6, 7]. The accuracy of the BLT reconstruction is significantly affected by the forward modeling errors in the simplified photon propagation model, the measurement noise in data acquisition, and the inherent ill-posedness of the inverse problem

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