Generation of an accurate Cerenkov luminescence imaging model is a current issue of nuclear tomography with optical techniques. The article takes a pro-active approach toward whole-body Cerenkov luminescence tomography. The finite element framework employs the equation of radiative transfer via the third-order simplified spherical harmonics approximation to model Cerenkov photon propagation in a small animal. After this forward model is performed on a digital mouse with optical property heterogeneity and compared with the Monte Carlo method, we investigated the whole body reconstruction algorithm along a regularization path via coordinate descent. The endpoint of the follow-up study is the in vivo application, which provides three-dimensional biodistribution of the radiotracer uptake in the mouse from measured partial boundary currents. The combination of the forward and inverse model with elastic-net penalties is not only validated by numerical simulation, but it also effectively demonstrates in vivo imaging in small animals. Our exact reconstruction method enables optical molecular imaging to best utilize Cerenkov radiation emission from the decay of medical isotopes in tissues.
As a novel molecular imaging technology, bioluminescence tomography (BLT) has become an important tool for biomedical research in recent years, which can perform a quantitative reconstruction of an internal light source distribution with the scattered and transmitted bioluminescent signals measured on the external surface of a small animal. However, BLT is severely ill-posed because of complex photon propagation in the biological tissue and limited boundary measured data with noise. Therefore, sufficient a priori knowledge should be fused for the uniqueness and stability of BLT solution. Permissible source region strategy and spectrally resolved measurements are two kinds of a priori knowledge commonly used in BLT reconstruction. This paper compares their performance with simulation and in vivo heterogeneous mouse experiments. In order to improve the efficiency of large-scale source restoration, this paper introduces an efficient iterative shrinkage thresholding method that not only has faster convergence rate but also has better reconstruction accuracy than the modified Newton-type optimization approach. Finally, a discussion of these two kinds of a priori knowledge is given based on the comparison results.
Optical molecular imaging has been rapidly developed to noninvasively visualize in vivo physiological and pathological processes involved in normal and suffering organisms at the cellular and molecular levels, in which advanced optical imaging technology and modern molecular biology are being combined to provide a state‐of‐the‐art tool for preclinical biomedical research. Among optical molecular imaging modalities, bioluminescence tomography (BLT) has experienced considerable growth and attracted much attention in recent years for its excellent performance, unique advantages, and high cost‐effectiveness. This article focuses on the genesis and development of BLT, especially for its computational methodology, imaging system, and biomedical application. An overview of the advantages and challenges of the conventional planar bioluminescence imaging technique is first described in comparison with currently available molecular imaging modalities. The imaging algorithms for inverse source reconstruction are classified and summarized according to different a priori knowledge, followed by a simple depiction of the uniqueness theorems of BLT solution. Diverse imaging systems for obtaining three‐dimensional quantitative information of internal bioluminescent sources are then reviewed. The latest application examples of BLT in tumor study and drug discovery are introduced and compared with other mature imaging technologies. Finally, the paper is concluded and an attractive prospect for BLT is predicted.
Cerenkov luminescence imaging (CLI) is a cost-effective molecular imaging tool for biomedical applications of radiotracers. The introduction of Cerenkov luminescence tomography (CLT) relative to planar CLI can be compared to the development of X-ray CT based on radiography. With CLT, quantitative and localized analysis of a radiopharmaceutical distribution becomes feasible. In this contribution, a feasibility study of in vivo radiopharmaceutical imaging in heterogeneous medium is presented. Coupled with a multimodal in vivo imaging system, this CLT reconstruction method allows precise anatomical registration of the positron probe in heterogeneous tissues and facilitates the more widespread application of radiotracers. Source distribution inside the small animal is obtained from CLT reconstruction. The experimental results demonstrated that CLT can be employed as an available in vivo tomographic imaging of charged particle emitters in a heterogeneous medium.
A single-nucleotide polymorphism of neutrophil cytosolic factor 1 (Ncf1), leading to an impaired generation of reactive oxygen species (ROS), is a causative genetic factor for autoimmune disease. To study a possible tumor protection effect by the Ncf1 mutation in a manner dependent on cell types, we used experimental mouse models of lung colonization assay by B16F10 melanoma cells. We observed fewer tumor foci in Ncf1 mutant mice, irrespective of αβT, γδT, B-cell deficiencies, or of a functional Ncf1 expression in CD68-positive monocytes/macrophages. The susceptibility to tumor colonization was restored by the human S100A8 (MRP8) promoter directing a functional Ncf1 expression to granulocytes. This effect was associated with an increase of both ROS and interleukin 1 beta (IL-1β) production from lung neutrophils. Moreover, neutrophil depletion by anti-Ly6G antibodies increased tumor colonization in wild type but failed in the Ncf1 mutant mice. In conclusion, tumor colonization is counteracted by ROS-activated and IL-1β-secreting tissue neutrophils.
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