Dataset Information

New Approaches for Quantitative Reconstruction of Radiation Dose in Human Blood Cells.

ABSTRACT: In the event of a nuclear attack or large-scale radiation event, there would be an urgent need for assessing the dose to which hundreds or thousands of individuals were exposed. Biodosimetry approaches are being developed to address this need, including transcriptomics. Studies have identified many genes with potential for biodosimetry, but, to date most have focused on classification of samples by exposure levels, rather than dose reconstruction. We report here a proof-of-principle study applying new methods to select radiation-responsive genes to generate quantitative, rather than categorical, radiation dose reconstructions based on a blood sample. We used a new normalization method to reduce effects of variability of signal intensity in unirradiated samples across studies; developed a quantitative dose-reconstruction method that is generally under-utilized compared to categorical methods; and combined these to determine a gene set as a reconstructor. Our dose-reconstruction biomarker was trained using two data sets and tested on two independent ones. It was able to reconstruct dose up to 4.5?Gy with root mean squared error (RMSE) of?±?0.35?Gy on a test dataset using the same platform, and up to 6.0?Gy with RMSE of?±?1.74?Gy on a test set using a different platform.

SUBMITTER: Ghandhi SA

PROVIDER: S-EPMC6895166 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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New Approaches for Quantitative Reconstruction of Radiation Dose in Human Blood Cells.

Ghandhi Shanaz A SA Shuryak Igor I Morton Shad R SR Amundson Sally A SA Brenner David J DJ

Scientific reports 20191205 1

In the event of a nuclear attack or large-scale radiation event, there would be an urgent need for assessing the dose to which hundreds or thousands of individuals were exposed. Biodosimetry approaches are being developed to address this need, including transcriptomics. Studies have identified many genes with potential for biodosimetry, but, to date most have focused on classification of samples by exposure levels, rather than dose reconstruction. We report here a proof-of-principle study applyi ...[more]

PMID: 31804590

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Project description:BACKGROUND: High dose ionizing radiation (IR) induces potent toxic cell effects mediated by either direct DNA damage or the production of reactive oxygen species (ROS). IR-induced modulations in multiple biological processes have been proposed to be partly regulated by radiosensitive microRNA (miRNA). In order to gain new insights into the role of miRNAs in the regulation of biological processes after IR, we have investigated changes in mRNA and miRNA expression after high dose IR. RESULTS: IR induced changes in the mRNA and miRNA profiles of human peripheral blood mononuclear cells (PBMCs). When comparing non-irradiated and irradiated samples, we detected a time-dependent increase in differentially expressed mRNAs and miRNAs, with the highest differences detectable 20 hours after exposure. Gene ontology analysis revealed that very early events (up to 4 hours) after irradiation were specifically associated with p53 signaling and apoptotic pathways, whereas a large number of diverse cellular processes were deregulated after 20 hours. Transcription factor analysis of all up-regulated genes confirmed the importance of p53 in the early post-irradiation phase. When analyzing miRNA expression, we found 177 miRNAs that were significantly regulated in the late post-irradiation phase. Integrating miRNA and target gene expression data, we found a significant negative correlation between miRNA-mRNA and identified hepatic leukemia factor (HLF) as a transcription factor down-regulated in the response to IR. These regulated miRNAs and the HLF target genes were involved in modulating radio-responsive pathways, such as apoptosis, the MAKP signaling pathway, endocytosis, and cytokine-cytokine interactions. CONCLUSION: Using a large dataset of mRNA and miRNA expression profiles, we describe the interplay of mRNAs and miRNAs in the regulation of gene expression in response to IR at a posttranscriptional level and their involvement in the modulation of radiation-induced biological pathways.

Project description:ObjectiveFew studies have explored the clinical feasibility of using deep-learning reconstruction to reduce the radiation dose of CT. We aimed to compare the image quality and lung nodule detectability between chest CT using a quarter of the low dose (QLD) reconstructed with vendor-agnostic deep-learning image reconstruction (DLIR) and conventional low-dose (LD) CT reconstructed with iterative reconstruction (IR).Materials and methodsWe retrospectively collected 100 patients (median age, 61 years [IQR, 53-70 years]) who received LDCT using a dual-source scanner, where total radiation was split into a 1:3 ratio. QLD CT was generated using a quarter dose and reconstructed with DLIR (QLD-DLIR), while LDCT images were generated using a full dose and reconstructed with IR (LD-IR). Three thoracic radiologists reviewed subjective noise, spatial resolution, and overall image quality, and image noise was measured in five areas. The radiologists were also asked to detect all Lung-RADS category 3 or 4 nodules, and their performance was evaluated using area under the jackknife free-response receiver operating characteristic curve (AUFROC).ResultsThe median effective dose was 0.16 (IQR, 0.14-0.18) mSv for QLD CT and 0.65 (IQR, 0.57-0.71) mSv for LDCT. The radiologists' evaluations showed no significant differences in subjective noise (QLD-DLIR vs. LD-IR, lung-window setting; 3.23 ± 0.19 vs. 3.27 ± 0.22; P = .11), spatial resolution (3.14 ± 0.28 vs. 3.16 ± 0.27; P = .12), and overall image quality (3.14 ± 0.21 vs. 3.17 ± 0.17; P = .15). QLD-DLIR demonstrated lower measured noise than LD-IR in most areas (P < .001 for all). No significant difference was found between QLD-DLIR and LD-IR for the sensitivity (76.4% vs. 72.2%; P = .35) or the AUFROCs (0.77 vs. 0.78; P = .68) in detecting Lung-RADS category 3 or 4 nodules. Under a noninferiority limit of -0.1, QLD-DLIR showed noninferior detection performance (95% CI for AUFROC difference, -0.04 to 0.06).ConclusionQLD-DLIR images showed comparable image quality and noninferior nodule detectability relative to LD-IR images.

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New Approaches for Quantitative Reconstruction of Radiation Dose in Human Blood Cells.

Publications

New Approaches for Quantitative Reconstruction of Radiation Dose in Human Blood Cells.

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