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A radiological dispersion device is a weapon that combines radioactive material with conventional explosives for spreading radioactive material across an inhabited area. This study is focused on evaluating key parameters in an radiological dispersion device scenario. The calculations were performed to include two different situations: by using explosives and by simple mechanical release. Simulations were conducted with the use of the HotSpot Health Physics Codes. The results suggest the existence of significant correlations between stability classes in scenarios where they evolve with time, producing alternations between them. As long as the stability class remains constant, this latter finding offers the possibility of creating a suitable response, based on temporal evolutions. Therefore, the purpose of this study is to: estimate the size of the potentially affected population, estimate absorbed doses, and estimate the cost-effectiveness in order to help initial responses by providing time-sensitive information about the event. A methodology capable of providing useful information allows prompt decisions and initial assessments of future risks to be made efficiently. This approach can also provide a training environment for the personnel responsible for the decision-making at an early stage of the response.

A release of radioactive material into the environment can lead to hazardous exposure of the population and serious future concerns about health issues such as an increased incidence of cancer. In this context, a practical methodology capable of providing useful basic information from the scenario can be valuable for immediate decisions and future risk assessment. For this work, the simulation of a radiological dispersal device (RDD) filled with americium-241 was considered. The radiation dose simulated by the HotSpot code was used as an input to the epidemiological equations from BEIR V producing the data used to assess the risk of lung cancer development. The methodology could be useful in providing training for responders aimed to the initial support addressed to decision-making for emergency response at the early phase of an RDD scenario. The results from the simulation allow estimating (a) the size of the potentially affected population, (b) the type of protection action considering gender and location of the individuals, (c) the absorbed doses, (d) the matrix of lung cancer incidence predictions over a period of 5 years, and (e) the cost-effectiveness in the initial decision environment.

Introduction: 1.5 Tesla (1.5T) remain a significant field strength for brain imaging worldwide. Recent computer simulations and clinical studies at 3T MRI have suggested that dynamic susceptibility contrast (DSC) MRI using a 30° flip angle ("low-FA") with model-based leakage correction and no gadolinium-based contrast agent (GBCA) preload provides equivalent relative cerebral blood volume (rCBV) measurements to the reference-standard acquisition using a single-dose GBCA preload with a 60° flip angle ("intermediate-FA") and model-based leakage correction. However, it remains unclear whether this holds true at 1.5T. The purpose of this study was to test this at 1.5T in human high-grade glioma (HGG) patients., Methods: This was a single-institution cross-sectional study of patients who had undergone 1.5T MRI for HGG. DSC-MRI consisted of gradient-echo echo-planar imaging (GRE-EPI) with a low-FA without preload (30°/P-); this then subsequently served as a preload for the standard intermediate-FA acquisition (60°/P+). Both normalized (nrCBV) and standardized relative cerebral blood volumes (srCBV) were calculated using model-based leakage correction (C+) with IBNeuro™ software. Whole-enhancing lesion mean and median nrCBV and srCBV from the low- and intermediate-FA methods were compared using the Pearson's, Spearman's and intraclass correlation coefficients (ICC)., Results: Twenty-three HGG patients composing a total of 31 scans were analyzed. The Pearson and Spearman correlations and ICCs between the 30°/P-/C+ and 60°/P+/C+ acquisitions demonstrated high correlations for both mean and median nrCBV and srCBV., Conclusion: Our study provides preliminary evidence that for HGG patients at 1.5T MRI, a low FA, no preload DSC-MRI acquisition can be an appealing alternative to the reference standard higher FA acquisition that utilizes a preload., Competing Interests: Author KS was employed IQ-AI Ltd and Imaging Biometrics LLC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shiroishi, Weinert, Cen, Varghese, Dondlinger, Prah, Mendoza, Nazemi, Ameli, Amini, Shohas, Chen, Bigjahan, Zada, Chen, Neman-Ebrahim, Chang, Chow, Fan, Yang, Attenello, Ye, Kim, Patel, Lerner, Acharya, Hu, Quarles, Boxerman, Wu and Schmainda.)

Tularemia, or rabbit fever, is a zoonotic infection caused by Francisella tularensis, a Gram-negative coccobacillus. F. tularensis subsp. holarctica (type B) is the predominant form in Slovenia. Humans become infected through arthropod bites, direct contact with an infected animal, ingestion of contaminated water or food, and inhalation of contaminated aerosol. The most common form is ulceroglandular tularemia (> 80%), which is characterized by a skin ulcer and regional lymphadenopathy. Below we present two cases of tularemia with skin involvement.

In a radiological event, the lack of preliminary information about the site of explosion and the difficulty in predicting the accurate path and distribution of radioactive plumes makes it difficult to predict expected health effects of exposed individuals. So far, in such a health evaluation, radiation-induced stochastic health effects such as cancer are not included. The Pasquill-Gifford atmospheric classes generally allow connecting atmospheric stability with dispersion of radioactive contaminants to the environment. In this work, an environmental release of radioactive Cs-137 was simulated and the resulting relative risk for solid cancer incidence among the affected population calculated. The HotSpot health physics code was used to simulate the radioactive atmospheric dispersion and calculate the Total Effective Dose Equivalent (TEDE), which was then used to estimate the relative risk of cancer incidence. The main results from this work suggest that the relative cancer risk and atmospheric stability classes are linked by differences in the TEDE. Such a finding may support triage, because it adds additional information on the potentially affected population at the early stages of an emergency response.

Background and Purpose: Brain tumor clinical trials requiring solid tumor assessment typically rely on the 2D manual delineation of enhancing tumors by ≥2 expert readers, a time-consuming step with poor interreader agreement. As a solution, we developed quantitative dT1 maps for the delineation of enhancing lesions. This retrospective analysis compares dT1 with 2D manual delineation of enhancing tumors acquired at 2 time points during the post therapeutic surveillance period of the American College of Radiology Imaging Network 6677/Radiation Therapy Oncology Group 0625 (ACRIN 6677/RTOG 0625) clinical trial., Materials and Methods: Patients enrolled in ACRIN 6677/RTOG 0625, a multicenter, randomized Phase II trial of bevacizumab in recurrent glioblastoma, underwent standard MR imaging before and after treatment initiation. For 123 patients from 23 institutions, both 2D manual delineation of enhancing tumors and dT1 datasets were evaluable at weeks 8 ( n = 74) and 16 ( n = 57). Using dT1, we assessed the radiologic response and progression at each time point. Percentage agreement with adjudicated 2D manual delineation of enhancing tumor reads and association between progression status and overall survival were determined., Results: For identification of progression, dT1 and adjudicated 2D manual delineation of enhancing tumor reads were in perfect agreement at week 8, with 73.7% agreement at week 16. Both methods showed significant differences in overall survival at each time point. When nonprogressors were further divided into responders versus nonresponders/nonprogressors, the agreement decreased to 70.3% and 52.6%, yet dT1 showed a significant difference in overall survival at week 8 ( P = .01), suggesting that dT1 may provide greater sensitivity for stratifying subpopulations., Conclusions: This study shows that dT1 can predict early progression comparable with the standard method but offers the potential for substantial time and cost savings for clinical trials., (© 2019 by American Journal of Neuroradiology.)

Background and Purpose: DSC-MR imaging using preload, intermediate (60°) flip angle and postprocessing leakage correction has gained traction as a standard methodology. Simulations suggest that DSC-MR imaging with flip angle = 30° and no preload yields relative CBV practically equivalent to the reference standard. This study tested this hypothesis in vivo., Materials and Methods: Eighty-four patients with brain lesions were enrolled in this 3-institution study. Forty-three patients satisfied the inclusion criteria. DSC-MR imaging (3T, single-dose gadobutrol, gradient recalled-echo-EPI, TE = 20-35 ms, TR = 1.2-1.63 seconds) was performed twice for each patient, with flip angle = 30°-35° and no preload (P-), which provided preload (P+) for the subsequent intermediate flip angle = 60°. Normalized relative CBV and standardized relative CBV maps were generated, including postprocessing with contrast agent leakage correction (C+) and without (C-) contrast agent leakage correction. Contrast-enhancing lesion volume, mean relative CBV, and contrast-to-noise ratio obtained with 30°/P-/C-, 30°/P-/C+, and 60°/P+/C- were compared with 60°/P+/C+ using the Lin concordance correlation coefficient and Bland-Altman analysis. Equivalence between the 30°/P-/C+ and 60°/P+/C+ protocols and the temporal SNR for the 30°/P- and 60°/P+ DSC-MR imaging data was also determined., Results: Compared with 60°/P+/C+, 30°/P-/C+ had closest mean standardized relative CBV ( P = .61), highest Lin concordance correlation coefficient (0.96), and lowest Bland-Altman bias (μ = 1.89), compared with 30°/P-/C- ( P = .02, Lin concordance correlation coefficient = 0.59, μ = 14.6) and 60°/P+/C- ( P = .03, Lin concordance correlation coefficient = 0.88, μ = -10.1) with no statistical difference in contrast-to-noise ratios across protocols. The normalized relative CBV and standardized relative CBV were statistically equivalent at the 10% level using either the 30°/P-/C+ or 60°/P+/C+ protocols. Temporal SNR was not significantly different for 30°/P- and 60°/P+ ( P = .06)., Conclusions: Tumor relative CBV derived from low-flip angle, no-preload DSC-MR imaging with leakage correction is an attractive single-dose alternative to the higher dose reference standard., (© 2019 by American Journal of Neuroradiology.)

A multi-center imaging trial by the American College of Radiology Imaging Network (ACRIN) "A Multicenter, phase II assessment of tumor hypoxia in glioblastoma using 18F Fluoromisonidazole (FMISO) with PET and MRI (ACRIN 6684)", was conducted to assess hypoxia in patients with glioblastoma (GBM). The aims of this study were to support the role of proton magnetic resonance spectroscopic imaging (1H MRSI) as a prognostic marker for brain tumor patients in multi-center clinical trials. Seventeen participants from four sites had analyzable 3D MRSI datasets acquired on Philips, GE or Siemens scanners at either 1.5T or 3T. MRSI data were analyzed using LCModel to quantify metabolites N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and lactate (Lac). Receiver operating characteristic curves for NAA/Cho, Cho/Cr, lactate/Cr, and lactate/NAA were constructed for overall survival at 1-year (OS-1) and 6-month progression free survival (PFS-6). The OS-1 for the 17 evaluable patients was 59% (10/17). Receiver operating characteristic analyses found the NAA/Cho in tumor (AUC = 0.83, 95% CI: 0.61 to 1.00) and in peritumoral regions (AUC = 0.95, 95% CI 0.85 to 1.00) were predictive for survival at 1 year. PFS-6 was 65% (11/17). Neither NAA/Cho nor Cho/Cr was effective in predicting 6-month progression free survival. Lac/Cr in tumor was a significant negative predictor of PFS-6, indicating that higher lactate/Cr levels are associated with poorer outcome. (AUC = 0.79, 95% CI: 0.54 to 1.00). In conclusion, despite the small sample size in the setting of a multi-center trial comprising different vendors, field strengths, and varying levels of expertise at data acquisition, MRS markers NAA/Cho, Lac/Cr and Lac/NAA predicted overall survival at 1 year and 6-month progression free survival. This study validates that MRSI may be useful in evaluating the prognosis in glioblastoma and should be considered for incorporating into multi-center clinical trials., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Dr. Sorensen has been an employee of Siemens Medical Solutions from 2011-2016, and is currently a board member of IMRIS (includes equity stake). He also has two patents assigned to MGH (US patent # 8,698,496 and US patent # 7,512,435). Dr. Andronesi has one patent (US patent #8,698,496). Dr. Schmainda has an ownership interest in Imaging Biometrics LLC. Dr. Barboriak is a member of the GE Medical systems Neuro MRI Advisory Committee. Dr. Mankoff is an advisory for GE Healthcare. Dr. Ratai is a member on the advisory board for BrainSpec, Inc. Erin Greco is currently employed at Novartis Institutes for BioMedical Research, Cambridge, MA, United States. All other authors declare no conflicts of interest. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Background and Purpose: Standard assessment criteria for brain tumors that only include anatomic imaging continue to be insufficient. While numerous studies have demonstrated the value of DSC-MR imaging perfusion metrics for this purpose, they have not been incorporated due to a lack of confidence in the consistency of DSC-MR imaging metrics across sites and platforms. This study addresses this limitation with a comparison of multisite/multiplatform analyses of shared DSC-MR imaging datasets of patients with brain tumors., Materials and Methods: DSC-MR imaging data were collected after a preload and during a bolus injection of gadolinium contrast agent using a gradient recalled-echo-EPI sequence (TE/TR = 30/1200 ms; flip angle = 72°). Forty-nine low-grade ( n = 13) and high-grade ( n = 36) glioma datasets were uploaded to The Cancer Imaging Archive. Datasets included a predetermined arterial input function, enhancing tumor ROIs, and ROIs necessary to create normalized relative CBV and CBF maps. Seven sites computed 20 different perfusion metrics. Pair-wise agreement among sites was assessed with the Lin concordance correlation coefficient. Distinction of low- from high-grade tumors was evaluated with the Wilcoxon rank sum test followed by receiver operating characteristic analysis to identify the optimal thresholds based on sensitivity and specificity., Results: For normalized relative CBV and normalized CBF, 93% and 94% of entries showed good or excellent cross-site agreement (0.8 ≤ Lin concordance correlation coefficient ≤ 1.0). All metrics could distinguish low- from high-grade tumors. Optimum thresholds were determined for pooled data (normalized relative CBV = 1.4, sensitivity/specificity = 90%:77%; normalized CBF = 1.58, sensitivity/specificity = 86%:77%)., Conclusions: By means of DSC-MR imaging data obtained after a preload of contrast agent, substantial consistency resulted across sites for brain tumor perfusion metrics with a common threshold discoverable for distinguishing low- from high-grade tumors., (© 2018 by American Journal of Neuroradiology.)

This paper reports on results of a multisite collaborative project launched by the MRI subgroup of Quantitative Imaging Network to assess current capability and provide future guidelines for generating a standard parametric diffusion map Digital Imaging and Communication in Medicine (DICOM) in clinical trials that utilize quantitative diffusion-weighted imaging (DWI). Participating sites used a multivendor DWI DICOM dataset of a single phantom to generate parametric maps (PMs) of the apparent diffusion coefficient (ADC) based on two models. The results were evaluated for numerical consistency among models and true phantom ADC values, as well as for consistency of metadata with attributes required by the DICOM standards. This analysis identified missing metadata descriptive of the sources for detected numerical discrepancies among ADC models. Instead of the DICOM PM object, all sites stored ADC maps as DICOM MR objects, generally lacking designated attributes and coded terms for quantitative DWI modeling. Source-image reference, model parameters, ADC units and scale, deemed important for numerical consistency, were either missing or stored using nonstandard conventions. Guided by the identified limitations, the DICOM PM standard has been amended to include coded terms for the relevant diffusion models. Open-source software has been developed to support conversion of site-specific formats into the standard representation.

Purpose: Structural and functional alterations in tumor vasculature are thought to contribute to tumor hypoxia which is a primary driver of malignancy through its negative impact on the efficacy of radiation, immune surveillance, apoptosis, genomic stability, and accelerated angiogenesis. We performed a prospective, multicenter study to test the hypothesis that abnormal tumor vasculature and hypoxia, as measured with MRI and PET, will negatively impact survival in patients with newly diagnosed glioblastoma., Experimental Design: Prior to the start of chemoradiation, patients with glioblastoma underwent MRI scans that included dynamic contrast enhanced and dynamic susceptibility contrast perfusion sequences to quantitate tumor cerebral blood volume/flow (CBV/CBF) and vascular permeability (k trans ) as well as 18 F-Fluoromisonidazole ( 18 F-FMISO) PET to quantitate tumor hypoxia. ROC analysis and Cox regression models were used to determine the association of imaging variables with progression-free and overall survival., Results: Fifty patients were enrolled of which 42 had evaluable imaging data. Higher pretreatment 18 F-FMISO SUV peak (P = 0.048), mean k trans (P = 0.024), and median k trans (P = 0.045) were significantly associated with shorter overall survival. Higher pretreatment median k trans (P = 0.021), normalized RCBV (P = 0.0096), and nCBF (P = 0.038) were significantly associated with shorter progression-free survival. SUV peak [AUC = 0.75; 95% confidence interval (CI), 0.59-0.91], nRCBV (AUC = 0.72; 95% CI, 0.56-0.89), and nCBF (AUC = 0.72; 95% CI, 0.56-0.89) were predictive of survival at 1 year., Conclusions: Increased tumor perfusion, vascular volume, vascular permeability, and hypoxia are negative prognostic markers in newly diagnosed patients with gioblastoma, and these important physiologic markers can be measured safely and reliably using MRI and 18 F-FMISO PET. Clin Cancer Res; 22(20); 5079-86. ©2016 AACR., Competing Interests: Dr. Sorensen reports stock ownership and employment with Siemens and patents/royalties/intellectual property with General Electric. Dr Schmainda reports ownership interest in Imaging Biometrics LLC. All other authors report no conflict of interest., (©2016 American Association for Cancer Research.)

Background and Purpose: For more widespread clinical use advanced imaging methods such as relative cerebral blood volume must be both accurate and repeatable. The aim of this study was to determine the repeatability of relative CBV measurements in newly diagnosed glioblastoma multiforme by using several of the most commonly published estimation techniques., Materials and Methods: The relative CBV estimates were calculated from dynamic susceptibility contrast MR imaging in double-baseline examinations for 33 patients with treatment-naïve and pathologically proved glioblastoma multiforme (men = 20; mean age = 55 years). Normalized and standardized relative CBV were calculated by using 6 common postprocessing methods. The repeatability of both normalized and standardized relative CBV, in both tumor and contralateral brain, was examined for each method with metrics of repeatability, including the repeatability coefficient and within-subject coefficient of variation. The minimum sample size required to detect a parameter change of 10% or 20% was also determined for both normalized relative CBV and standardized relative CBV for each estimation method., Results: When ordered by the repeatability coefficient, methods using postprocessing leakage correction and ΔR2*(t) techniques offered superior repeatability. Across processing techniques, the standardized relative CBV repeatability in normal-appearing brain was comparable with that in tumor (P = .31), yet inferior in tumor for normalized relative CBV (P = .03). On the basis of the within-subject coefficient of variation, tumor standardized relative CBV estimates were less variable (13%-20%) than normalized relative CBV estimates (24%-67%). The minimum number of participants needed to detect a change of 10% or 20% is 118-643 or 30-161 for normalized relative CBV and 109-215 or 28-54 for standardized relative CBV., Conclusions: The ΔR2* estimation methods that incorporate leakage correction offer the best repeatability for relative CBV, with standardized relative CBV being less variable and requiring fewer participants to detect a change compared with normalized relative CBV., (© 2015 by American Journal of Neuroradiology.)

Background: The study goal was to determine whether changes in relative cerebral blood volume (rCBV) derived from dynamic susceptibility contrast (DSC) MRI are predictive of overall survival (OS) in patients with recurrent glioblastoma multiforme (GBM) when measured 2, 8, and 16 weeks after treatment initiation., Methods: Patients with recurrent GBM (37/123) enrolled in ACRIN 6677/RTOG 0625, a multicenter, randomized, phase II trial of bevacizumab with irinotecan or temozolomide, consented to DSC-MRI plus conventional MRI, 21 with DSC-MRI at baseline and at least 1 postbaseline scan. Contrast-enhancing regions of interest were determined semi-automatically using pre- and postcontrast T1-weighted images. Mean tumor rCBV normalized to white matter (nRCBV) and standardized rCBV (sRCBV) were determined for these regions of interest. The OS rates for patients with positive versus negative changes from baseline in nRCBV and sRCBV were compared using Wilcoxon rank-sum and Kaplan-Meier survival estimates with log-rank tests., Results: Patients surviving at least 1 year (OS-1) had significantly larger decreases in nRCBV at week 2 (P = .0451) and sRCBV at week 16 (P = .014). Receiver operating characteristic analysis found the percent changes of nRCBV and sRCBV at week 2 and sRCBV at week 16, but not rCBV data at week 8, to be good prognostic markers for OS-1. Patients with positive change from baseline rCBV had significantly shorter OS than those with negative change at both week 2 and week 16 (P = .0015 and P = .0067 for nRCBV and P = .0251 and P = .0004 for sRCBV, respectively)., Conclusions: Early decreases in rCBV are predictive of improved survival in patients with recurrent GBM treated with bevacizumab., (© The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To characterize the influence of perfusion on the measurement of diffusion changes over time when ADC is computed using standard two-point methods., Materials and Methods: Functional diffusion maps (FDMs), which depict changes in diffusion over time, were compared with rCBV changes in patients with brain tumors. The FDMs were created by coregistering and subtracting ADC maps from two time points and categorizing voxels where ADC significantly increased (iADC), decreased (dADC), or did not change (ncADC). Traditional FDMs (tFDMs) were computed using b = 0,1000 s/mm(2). Flow-compensated FDMs (fcFDMs) were calculated using b = 500,1000 s/mm(2). Perfusion's influence on FDMs was determined by evaluating changes in rCBV in areas where the ADC change significantly differed between the two FDMs., Results: The mean ΔrCBV in voxels that changed from iADC (dADC) on the tFDM to ncADC on the fcFDM was significantly greater (less) than zero. In addition, mean ΔrCBV in iADC (dADC) voxels on the tFDM was significantly higher (lower) than in iADC (dADC) voxels on the fcFDM., Conclusion: The ability to accurately identify changes in diffusion on traditional FDMs is confounded in areas where perfusion and diffusion changes are colocalized. Flow-compensated FDMs, which use only non-zero b-values, should therefore be the standard approach., (Copyright © 2013 Wiley Periodicals, Inc.)

Background and Purpose: Both technical and pathophysiologic factors affect PSR in DSC-MR imaging. We aimed to determine how TE, flip angle (α), and contrast dose impact PSR in high-grade gliomas., Materials and Methods: We retrospectively computed PSR maps for 22 patients with high-grade gliomas, comparing 3 DSC-MR imaging methods by using single-dose gadodiamide without preload administration: A (n = 7), α = 35°, TE = 54 ms; B (n = 5), α = 72°, TE = 30 ms; C (n = 10), α = 90°, TE = 30 ms. Methods A-C served as preload for subsequent dynamic imaging using method D (method C parameters but with double-dose contrast). We compared first- and second-injection tumor PSR for methods C and D (paired t test) and tumor PSR for both injections grouped by the first-injection acquisition method (3-group nonparametric 1-way ANOVA). We compared PSR in tumor and normal brain for each first- and second-injection method group (paired t test)., Results: First-injection PSR in tumor and normal brain differed significantly for methods B (P = .01) and C (P = .05), but not A (P = .71). First-injection tumor PSR increased with T1 weighting with a significant main effect of method groupings (P = .0012), but there was no significant main effect for first-injection normal brain (P = .93), or second-injection tumor (P = .95) or normal brain (P = .13). In patients scanned with methods C and D, first-injection PSR significantly exceeded second-injection PSR for tumor (P = .037) and normal brain (P < .001)., Conclusions: PSR strongly depends on the T1 weighting of DSC-MR imaging, including pulse sequence (TE, α) and contrast agent (dose, preload) parameters, with implications for protocol design and the interpretation and comparison of PSR values across tumor types and imaging centers.

Hydrogen sulfide is an environmental toxicant and gaseous neurotransmitter. It is produced enterically by sulfur-reducing bacteria and invasive pathogens including Streptococcus anginosus group, Salmonella and Citrobacter. We describe putative focal hydrogen sulfide neurotoxicity after Streptococcus constellatus meningitis, treated with adjunctive sodium nitrite and hyperbaric oxygen therapy.