Echocardiography Differentiates Lethally Irradiated Whole-Body From Partial-Body Exposed Rats

Background: Acute radiation syndrome (ARS) affects morbidity and mortality dependent on the amount of body exposed. We propose the use of echocardiography (EC) to differentiate between survivors and non-survivors by measuring changes in cardiac function (CF) and pulmonary arterial function (PAF). We also investigate the role of rheology in our observed changes.Methods and Results: Rats were irradiated to the whole body (WB) or partial body with two-legs shielded (2LS) at a lethal dose of 7.5Gy. EC and magnetic resonance imaging were performed, and rheological measurements conducted. Only 2LS survived past 12-days post-exposure and their CF and PAR were not significantly different from baseline. WB was significantly different from both baseline and 2LS in stroke volume (P < 0.05), velocity time integral (VTI; P < 0.05) and pulmonary artery acceleration time (PAAT; P < 0.05). Differences were identified as early as six-days post-exposure, where VTI and PAAT were significantly (P < 0.05) decreased in WB versus baseline but only PAAT was different from 2LS. Blood viscosity was significantly lower in the WB versus baseline and 2LS (P < 0.0001). WB exhibited a significant rise in dense red blood cells versus baseline (P < 0.01) and 2LS (P < 0.01). Cell-free hemoglobin, a contributor to pulmonary artery hypertension and vasculopathy, was significantly elevated in WB vs. sham.Conclusions: Non-invasive and readily available imaging can be used to identify critically affected victims. Our findings point to heart failure as one possible cause of death in WB exposed animals, potentially exacerbated by rheological, hemolytic, and pulmonary factors, and the importance of developing radiomitigators against cardiac ARS mortality

Replication Data for: PLoS One article entitled "Heterogeneous uptake of nanoparticles in mouse models of pediatric high-risk neuroblastoma"

This dataset contains computed tomography images (DICOM file format) related to the article published in PLoS One (2016), entitled "Heterogeneous uptake of nanoparticles in mouse models of pediatric high-risk neuroblastoma"

Imaging Radiation-Induced Gastrointestinal, Bone Marrow Injury and Recovery Kinetics Using ¹⁸F-FDG PET

<div><p>Positron emission tomography using ¹⁸F-Fluro-deoxy-glucose (¹⁸F-FDG) is a useful tool to detect regions of inflammation in patients. We utilized this imaging technique to investigate the kinetics of gastrointestinal recovery after radiation exposure and the role of bone marrow in the recovery process. Male Sprague-Dawley rats were either sham irradiated, irradiated with their upper half body shielded (UHBS) at a dose of 7.5 Gy, or whole body irradiated (WBI) with 4 or 7.5 Gy. Animals were imaged using ¹⁸F-FDG PET/CT at 5, 10 and 35 days post-radiation exposure. The gastrointestinal tract and bone marrow were analyzed for ¹⁸F-FDG uptake. Tissue was collected at all-time points for histological analysis. Following 7.5 Gy irradiation, there was a significant increase in inflammation in the gastrointestinal tract as indicated by the significantly higher ¹⁸F-FDG uptake compared to sham. UHBS animals had a significantly higher activity compared to 7.5 Gy WBI at 5 days post-exposure. Animals that received 4 Gy WBI did not show any significant increase in uptake compared to sham. Analysis of the bone marrow showed a significant decrease of uptake in the 7.5 Gy animals 5 days post-irradiation, albeit not observed in the 4 Gy group. Interestingly, as the metabolic activity of the gastrointestinal tract returned to sham levels in UHBS animals it was accompanied by an increase in metabolic activity in the bone marrow. At 35 days post-exposure both gastrointestinal tract and bone marrow ¹⁸F-FDG uptake returned to sham levels. ¹⁸F-FDG imaging is a tool that can be used to study the inflammatory response of the gastrointestinal tract and changes in bone marrow metabolism caused by radiation exposure. The recovery of the gastrointestinal tract coincides with an increase in bone marrow metabolism in partially shielded animals. These findings further demonstrate the relationship between the gastrointestinal syndrome and bone marrow recovery, and that this interaction can be studied using non-invasive imaging modalities.</p></div

Direct radiation exposure to gastrointestinal tract can be detected with PET/CT imaging.

<p>Graph of mean standard uptake value of ¹⁸F-FDG in the gastrointestinal tract 5 days post irradiation. A significant increase is observed in 7.5 whole body irradiated and upper half shielded groups compared to sham group. Data shown mean ± standard deviation; *P<0.05, †P<0.01, ‡P<0.001.</p

Metabolic activity in bone marrow is lower at the higher radiation dose.

<p>Reconstructed PET/CT images showing ¹⁸F-FDG uptake of (A) sham, (B) 4 Gy and (C) 7.5 Gy whole body irradiated animals 5 days post radiation exposure.</p

Villus Length at 5 Days Post irradiation.

<p>Villus Length at 5 Days Post irradiation.</p

Heterogeneous Uptake of Nanoparticles in Mouse Models of Pediatric High-Risk Neuroblastoma - Fig 5

<p>(a) Normalized cumulative leak volume as a function of normalized radial position for 15 individual NGP tumors ranging in age from 2 to 4 weeks post inoculation, and ranging in volume from 150 to 8500 mm3. (b) Normalized cumulative iodine uptake as a function of normalized radial position for 15 individual NGP tumors ranging in age from 2 to 4 weeks post inoculation, and ranging in volume from 150 to 8500mm3.</p

Recovery in the metabolic activity of the gastrointestinal tract coincides with that of the bone marrow activity.

<p>Graph of mean standard uptake value of ¹⁸F-FDG in the gastrointestinal tract and bone marrow of upper half body shielded at 5, 10 and 35 days post radiation exposure, showing full recovery of both tissues by day 35. Data shown as mean ± SD; *P<0.05, ‡P<0.001 compared to sham animals.</p