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To develop an automated pulmonary fibrosis (PF) segmentation methodology using a 3D multi-scale convolutional encoder-decoder approach following the robust atlas-based active volume model in thoracic CT for Rhesus Macaques with radiation-induced lung damage. 152 thoracic computed tomography scans of Rhesus Macaques with radiation-induced lung damage were collected. The 3D input data are randomly augmented with the Gaussian blurring when applying the 3D multi-scale convolutional encoder-decoder (3D MSCED) segmentation method.PF in each scan was manually segmented in which 70% scans were used as training data, 20% scans were used as validation data, and 10% scans were used as testing data. The performance of the method is assessed based on a10-fold cross validation method. The workflow of the proposed method has two parts. First, the compromised lung volume with acute radiation-induced PF was segmented using a robust atlas-based active volume model. Next, a 3D multi-scale convolutional encoder-decoder segmentation method was developed which merged the higher spatial information from low-level features with the high-level object knowledge encoded in upper network layers. It included a bottom-up feed-forward convolutional neural network and a top-down learning mask refinement process. The quantitative results of our segmentation method achieved mean Dice score of (0.769, 0.853), mean accuracy of (0.996, 0.999), and mean relative error of (0.302, 0.512) with 95% confidence interval. The qualitative and quantitative comparisons show that our proposed method can achieve better segmentation accuracy with less variance in testing data. This method was extensively validated in NHP datasets. The results demonstrated that the approach is more robust relative to PF than other methods. It is a general framework which can easily be applied to segmentation other lung lesions. [ABSTRACT FROM AUTHOR]

Radiation-induced lung injury is a highly complex combination of pathological alterations that develop over time and severity of disease development is dose-dependent. Following exposures to lethal doses of irradiation, morbidity and mortality can occur due to a combination of edema, pneumonitis and fibrosis. Protein glycosylation has essential roles in a plethora of biological and immunological processes. Alterations in glycosylation profiles have been detected in diseases ranging from infection, inflammation and cancer. We utilized mass spectrometry imaging to spatially map N-glycans to distinct pathological alterations during the clinically latent period and at 180 days post-exposure to irradiation. Results identified alterations in a number of high mannose, hybrid and complex N-glycans that were localized to regions of mucus and alveolar-bronchiolar hyperplasia, proliferations of type 2 epithelial cells, accumulations of macrophages, edema and fibrosis. The glycosylation profiles indicate most alterations occur prior to the onset of clinical symptoms as a result of pathological manifestations. Alterations in five N-glycans were identified as a function of time post-exposure. Understanding the functional roles N-glycans play in the development of these pathologies, particularly in the accumulation of macrophages and their phenotype, may lead to new therapeutic avenues for the treatment of radiation-induced lung injury. [ABSTRACT FROM AUTHOR]

The potential risk of a radiological catastrophe highlights the need for identifying and validating potential biomarkers that accurately predict radiation-induced organ damage. A key target organ that is acutely sensitive to the effects of irradiation is the gastrointestinal (GI) tract, referred to as the GI acute radiation syndrome (GI-ARS). Recently, citrulline has been identified as a potential circulating biomarker for radiation-induced GI damage. Prior to biologically validating citrulline as a biomarker for radiation-induced GI injury, there is the important task of developing and validating a quantitation assay for citrulline detection within the radiation animal models used for biomarker validation. Herein, we describe the analytical development and validation of citrulline detection using a liquid chromatography tandem mass spectrometry assay that incorporates stable-label isotope internal standards. Analytical validation for specificity, linearity, lower limit of quantitation, accuracy, intra- and interday precision, extraction recovery, matrix effects, and stability was performed under sample collection and storage conditions according to the Guidance for Industry, Bioanalytical Methods Validation issued by the US Food and Drug Administration. In addition, the method was biologically validated using plasma from well-characterized mouse, minipig, and nonhuman primate GI-ARS models. The results demonstrated that circulating citrulline can be confidently quantified from plasma. Additionally, circulating citrulline displayed a time-dependent response for radiological doses covering GI-ARS across multiple species. [ABSTRACT FROM AUTHOR]

A severe and debilitating diarrhea is a dose-limiting toxic result for patients receiving abdominal radiation or chemotherapy. To correlate changes in intestinal structure and function, nonhuman primates were exposed to 9.5 Gy total abdominal x-irradiation. Diarrhea and weight loss were correlated with intestinal crypt and villus histology, in vivo assessed intestinal permeability, and ex vivo functional studies performed in Ussing chamber assays before and at 7, 14, and 35 days after irradiation. Peak gut structural damage occurred early and paralleled functional changes of the intestinal mucosa, including increased epithelial permeability (both in vivo and ex vivo), activation of secretory pathways, decreased nutrient absorption, diarrhea, and weight loss. Recovery of gut integrity and epithelial resistance began thereafter, in spite of incomplete histological recovery. Our integrated approach allowed a comprehensive study of the relationship between postirradiation tissue injury and changes in function over time in the gastrointestinal tract of the nonhuman primate. [ABSTRACT FROM AUTHOR]