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Background: Cellular therapy seems to be an innovative therapeutic alternative for which mesenchymal stem cells (MSCs) have been shown to be effective for interstitial and hemorrhagic cystitis. However, the action of MSCs on chronic radiation cystitis (CRC) remains to be demonstrated. The aim of this study was to set up a rat model of CRC and to evaluate the efficacy of MSCs and their mode of action., Methods: CRC was induced by single-dose localized irradiation of the whole bladder using two beams guided by tomography in female Sprague-Dawley rat. A dose range of 20-80 Gy with follow-up 3-12 months after irradiation was used to characterize the dose effect and the kinetics of radiation cystitis in rats. For the treatment, the dose of 40 Gy was retained, and in order to potentiate the effect of the MSCs, MSCs were isolated from adipose tissue. After expansion, they were injected intravenously during the pre-chronic phase. Three injections of 5 million MSCs were administered every fortnight. Follow-up was performed for 12 months after irradiation., Results: We observed that the intensity and frequency of hematuria are proportional to the irradiation dose, with a threshold at 40 Gy and the appearance of bleeding from 100 days post-irradiation. The MSCs reduced vascular damage as well as damage to the bladder epithelium., Conclusions: These results are in favor of MSCs acting to limit progression of the chronic phase of radiation cystitis. MSC treatment may afford real hope for all patients suffering from chronic radiation cystitis resistant to conventional treatments., (© 2023. The Author(s).)

Purpose: In case of a mass-casualty radiological event, there would be a need for networking to overcome surge limitations and to quickly obtain homogeneous results (reported aberration frequencies or estimated doses) among biodosimetry laboratories. These results must be consistent within such network. Inter-laboratory comparisons (ILCs) are widely accepted to achieve this homogeneity. At the European level, a great effort has been made to harmonize biological dosimetry laboratories, notably during the MULTIBIODOSE and RENEB projects. In order to continue the harmonization efforts, the RENEB consortium launched this intercomparison which is larger than the RENEB network, as it involves 38 laboratories from 21 countries. In this ILC all steps of the process were monitored, from blood shipment to dose estimation. This exercise also aimed to evaluate the statistical tools used to compare laboratory performance., Materials and Methods: Blood samples were irradiated at three different doses, 1.8, 0.4 and 0 Gy (samples A, C and B) with 4-MV X-rays at 0.5 Gy min -1 , and sent to the participant laboratories. Each laboratory was requested to blindly analyze 500 cells per sample and to report the observed frequency of dicentric chromosomes per metaphase and the corresponding estimated dose., Results: This ILC demonstrates that blood samples can be successfully distributed among laboratories worldwide to perform biological dosimetry in case of a mass casualty event. Having achieved a substantial harmonization in multiple areas among the RENEB laboratories issues were identified with the available statistical tools, which are not capable to advantageously exploit the richness of results of a large ILCs. Even though Z - and U -tests are accepted methods for biodosimetry ILCs, setting the number of analyzed metaphases to 500 and establishing a tests' common threshold for all studied doses is inappropriate for evaluating laboratory performance. Another problem highlighted by this ILC is the issue of the dose-effect curve diversity. It clearly appears that, despite the initial advantage of including the scoring specificities of each laboratory, the lack of defined criteria for assessing the robustness of each laboratory's curve is a disadvantage for the 'one curve per laboratory' model., Conclusions: Based on our study, it seems relevant to develop tools better adapted to the collection and processing of results produced by the participant laboratories. We are confident that, after an initial harmonization phase reached by the RENEB laboratories, a new step toward a better optimization of the laboratory networks in biological dosimetry and associated ILC is on the way.

Every year, millions of people around the world benefit from radiation therapy to treat cancers localized in the pelvic area. Damage to healthy tissue in the radiation field can cause undesirable toxic effects leading to gastrointestinal complications called pelvic radiation disease. A change in the composition and/or function of the microbiota could contribute to radiation-induced gastrointestinal toxicity. In this study, we tested the prophylactic effect of a new generation of probiotic like Faecalibacterium prausnitzii ( F. prausnitzii ) on acute radiation-induced colonic lesions. Experiments were carried out in a preclinical model of pelvic radiation disease. Rats were locally irradiated at 29 Gray in the colon resulting in colonic epithelial barrier rupture. Three days before the irradiation and up to 3 d after the irradiation, the F. prausnitzii A2-165 strain was administered daily (intragastrically) to test its putative protective effects. Results showed that prophylactic F. prausnitzii treatment limits radiation-induced para-cellular hyperpermeability, as well as the infiltration of neutrophils (MPO+ cells) in the colonic mucosa. Moreover, F. prausnitzii treatment reduced the severity of the morphological change of crypts, but also preserved the pool of Sox-9+ stem/progenitor cells, the proliferating epithelial PCNA+ crypt cells and the Dclk1+/IL-25+ differentiated epithelial tuft cells. The benefit of F. prausnitzii was associated with increased production of IL-18 by colonic crypt epithelial cells. Thus, F. prausnitzii treatment protected the epithelial colonic barrier from colorectal irradiation. New-generation probiotics may be promising prophylactic treatments to reduce acute side effects in patients treated with radiation therapy and may improve their quality of life.

Background: To date, paediatric thyroid cancer has been the most severe health consequence of the Chernobyl accident, caused by radioactive iodine ( 131 I) aerosol's dispersion. WHO recommends a single dose of potassium iodide (KI) to reduce this risk. Following the Fukushima accident, it became obvious that repetitive doses of KI may be necessary due to multiple exposures to 131 I. Knowledge about the effects of repeated ITB (Iodine Thyroid Blocking) is scarce and controversial. KI may affect the thyroid hormones synthesis; which is crucial for the cardiovascular function. Furthermore, myocardial and vascular endothelial tissues are sensitizes to subtle changes at the concentration of circulating pituitary and/or thyroid hormones., Objective: In this preclinical study, we aimed to assess the effects of repeated ITB in elderly male rats., Methods: Twelve months old male Wistar rats were subjected to either KI or saline solution for eight days. Analyses were performed 24 h and 30 days after the treatment discontinuation., Findings: We reported a significant increase (18%) in some urinary parameters related to renal function, a subtle decrease of plasma TSH level, a significant increase (379%) in renin and a significant decrease (50%) in aldosterone upon KI administration. At the molecular level, the expression of thyroid and cardiovascular genes was significantly affected by the treatment. However, in our experimental settlement, animal heart rate was not significantly affected thirty days after KI discontinuation. ECG patterns did not change after administration of KI, and arrhythmia was not observed in these conditions despite the PR-intervals decreased significantly. Cardiovascular physiology was preserved., Conclusion: Our results indicate that repeated ITB in elderly rats is characterized by molecular modifications of cardiovascular key actors, particularly the Renin-angiotensin-aldosterone axis with a preserved physiological homeostasis. This new scientific evidence may be useful for the maturation of ITB guidelines especially for elderly sub-population., Competing Interests: The authors do not report any conflict of interests regarding the publication of this paper., (© 2020 The Authors. Published by Elsevier B.V.)

Purpose: The purpose of this prospective dosimetric study was to assess the dose distribution regarding the brain areas implied in cognitive functions using two approaches: volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT)., Patients and Methods: Thirty-seven patients were treated using a dual-arc VMAT approach for supratentorial glioblastoma between 2016 and 2018. The total dose of 60Gy in 30 daily fractions was administered to the planning target volume (PTV). The brain structures that play an important role in cognitive physiology, such as the hippocampi, corpus callosum, cerebellum, subventricular zones (SVZ), were delineated. For each patient, a new treatment plan in HT was determined by a second medical physicist in a blindly fashion according to the same dose constraints and priorities. Statistical analyses were performed using the Wilcoxon-signed rank test., Results: Conformity indexes remained similar with both techniques. The mean values were 0.96 (0.19-1.00) for VMAT and 0.98 (range, 0.84-1.00) for HT, respectively (P=0.73). Significant D 50% reductions were observed with VMAT compared to HT: 14.6Gy (3.8-28.0) versus 17.4Gy (12.1-25.0) for the normal brain (P=0.014); 32.5Gy (10.3-60.0) versus 35.6Gy (17.1-58.0) for the corpus callosum (P=0.038); 8.1Gy (0.4-34.0) versus 12.8Gy (0.8-27.0) for the cerebellum (P<0.001), respectively., Conclusion: The VMAT approach seemed to improve the sparing of the key brain areas implied in cognitive functions without jeopardizing PTV coverage., (Copyright © 2020 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Purpose: Stereotactic body radiation therapy offers good lung local tumor control by the administration of a high dose per fraction in small volumes. Stereotactic body radiation therapy preclinical modeling is now possible, and our aim was to develop a model of focal irradiation of the mouse lung and to investigate the impact of conditional hypoxia-inducible factor 1α (HIF-1α) deletion in the endothelium on radiation-induced tissue damage., Methods and Materials: The Small Animal Radiation Research Platform was used to create a mouse model of focal irradiation of the lung using arc therapy. HIF-1α conditional deletion was obtained by crossing mice expressing Cre recombinase under the endothelial promoter VE-cadherin (VECad-Cre +/+ mice) with HIF-1α floxed mice., Results: Lung stereotactic arc therapy allows thoracic wall sparing and long-term studies. However, isodose curves showed that neighboring organs received significant doses of radiation, as revealed by ipsilateral lung acute red hepatization and major gene expression level modifications. Conditional HIF-1α deletion reduced acute lung edema and tended to diminish neutrophil infiltrate, but it had no impact on long-term global tissue damage., Conclusions: Arc therapy for focal high-dose irradiation of mouse lung is an efficient model for long-term studies. However, irradiation may have a strong impact on the structure and function of neighboring organs, which must be considered. HIF-1α conditional deletion has no beneficial impact on lung damage in this irradiation schedule., (Copyright © 2019. Published by Elsevier Inc.)

The aim of this study was to carry out a comprehensive examination of potential genotoxic effects of low doses of tritium delivered chronically to mice and to compare these effects to the ones resulting from equivalent doses of gamma-irradiation. Mice were chronically exposed for one or eight months to either tritiated water (HTO) or organically bound tritium (OBT) in drinking water at concentrations of 10 kBq/L, 1 MBq/L or 20 MBq/L. Dose rates of internal β-particle resulting from such tritium treatments were calculated and matching external gamma-exposures were carried out. We measured cytogenetic damage in bone marrow and in peripheral blood lymphocytes (PBLs) and the cumulative tritium doses (0.009 - 181 mGy) were used to evaluate the dose-response of OBT in PBLs, as well as its relative biological effectiveness (RBE). Neither tritium, nor gamma exposures produced genotoxic effects in bone marrow. However, significant increases in chromosome damage rates in PBLs were found as a result of chronic OBT exposures at 1 and 20 M Bq/L, but not at 10 kBq/L. When compared to an external acute gamma-exposure ex vivo , the RBE of OBT for chromosome aberrations induction was evaluated to be significantly higher than 1 at cumulative tritium doses below 10 mGy. Although found non-existent at 10 kBq/L (the WHO limit), the genotoxic potential of low doses of tritium (>10 kBq/L), mainly OBT, may be higher than currently assumed., Competing Interests: CONFLICTS OF INTEREST None declared.

Background and Purpose: Arterial spin-labeling and susceptibility-weighted imaging are 2 MR imaging techniques that do not require gadolinium. The study aimed to assess the accuracy of arterial spin-labeling and SWI combined for detecting intracranial arteriovenous shunting in comparison with conventional MR imaging., Materials and Methods: Ninety-two consecutive patients with a known (n = 24) or suspected arteriovenous shunting (n = 68) underwent digital subtraction angiography and brain MR imaging, including arterial spin-labeling/SWI and conventional angiographic MR imaging (3D TOF, 4D time-resolved, and 3D contrast-enhanced MRA). Arterial spin-labeling/SWI and conventional MR imaging were reviewed separately in a randomized order by 2 blinded radiologists who judged the presence or absence of arteriovenous shunting. The accuracy of arterial spin-labeling/SWI for the detection of arteriovenous shunting was calculated by using the area under receiver operating curve with DSA as reference standard. κ coefficients were computed to determine interobserver and intermodality agreement., Results: Of the 92 patients, DSA showed arteriovenous shunting in 63 (arteriovenous malformation in 53 and dural arteriovenous fistula in 10). Interobserver agreement was excellent (κ =0.83-0.95). In 5 patients, arterial spin-labeling/SWI correctly detected arteriovenous shunting, while the conventional angiographic MR imaging did not. Compared with conventional MR imaging, arterial spin-labeling/SWI was significantly more sensitive (0.98 versus 0.90, P = .04) and equally specific (0.97) and showed significantly higher agreement with DSA (κ = 0.95 versus 0.84, P = .01) and higher area under the receiver operating curve (0.97 versus 0.93, P = .02)., Conclusions: Our study showed that the combined use of arterial spin-labeling and SWI may be an alternative to contrast-enhanced MRA for the detection of intracranial arteriovenous shunting., (© 2017 by American Journal of Neuroradiology.)

Context: Thyroid carcinoma is a frequent complication of childhood cancer radiotherapy. The dose response to thyroid radiation dose is now well established, but the potential modifier effect of other factors requires additional investigation., Objective: This study aimed to investigate the role of potential modifiers of the dose response., Design: We followed a cohort of 4338 5-year survivors of solid childhood cancer treated before 1986 over an average of 27 years. The dose received by the thyroid gland and some other anatomical sites during radiotherapy was estimated after reconstruction of the actual conditions in which irradiation was delivered., Results: Fifty-five patients developed thyroid carcinoma. The risk of thyroid carcinoma increased with a radiation dose to the thyroid of up to two tenths of Gy, then leveled off for higher doses. When taking into account the thyroid radiation dose, a surgical or radiological splenectomy (>20 Gy to the spleen) increased thyroid cancer risk (relative risk [RR] = 2.3; 95% confidence interval [CI], 1.3-4.0), high radiation doses (>5 Gy) to pituitary gland lowered this risk (RR = 0.2; 95% CI, 0.1-0.6). Patients who received nitrosourea chemotherapy had a 6.6-fold (95% CI, 2.5-15.7) higher risk than those who did not. The excess RR per Gy of radiation to the thyroid was 4.7 (95% CI, 1.7-22.6). It was 7.6 (95% CI, 1.6-33.3) if body mass index at time of interview was equal or higher than 25 kg/m(2), and 4.1 (95% CI, 0.9-17.7) if not (P for interaction = .1)., Conclusion: Predicting thyroid cancer risk following childhood cancer radiation therapy probably requires the assessment of more than just the radiation dose to the thyroid. Chemotherapy, splenectomy, radiation dose to pituitary gland, and obesity also play a role.

Background and Purpose: The diagnosis of subacute subarachnoid hemorrhage is important because rebleeding may occur with subsequent life-threatening hemorrhage. Our aim was to determine the sensitivity of the 3D double inversion recovery sequence compared with CT, 2D and 3D FLAIR, 2D T2*, and 3D SWI sequences for the detection of subacute SAH., Materials and Methods: This prospective study included 25 patients with a CT-proved acute SAH. Brain imaging was repeated between days 14 and 16 (mean, 14.75 days) after clinical onset and included MR imaging (2D and 3D FLAIR, 2D T2*, SWI, and 3D double inversion recovery) after CT (median delay, 3 hours; range, 2-5 hours). A control group of 20 healthy volunteers was used for comparison. MR images and CT scans were analyzed independently in a randomized order by 3 blinded readers. For each subject, the presence or absence of hemorrhage was assessed in 4 subarachnoid areas (basal cisterns, Sylvian fissures, interhemispheric fissure, and convexity) and in brain ventricles. The diagnosis of subacute SAH was defined by the presence of at least 1 subarachnoid area with hemorrhage., Results: For the diagnosis of subacute SAH, the double inversion recovery sequence had a higher sensitivity compared with CT (P < .001), 2D FLAIR (P = .005), T2* (P = .02), SWI, and 3D FLAIR (P = .03) sequences. Hemorrhage was present for all patients in the interhemispheric fissure on double inversion recovery images, while no signal abnormality was noted in healthy volunteers. Interobserver agreement was excellent with double inversion recovery., Conclusions: Our study showed that the double inversion recovery sequence has a higher sensitivity for the detection of subacute SAH than CT, 2D or 3D FLAIR, 2D T2*, and SWI., (© 2015 by American Journal of Neuroradiology.)

Objectives: We compared a multi-echo gradient-echo magnetic resonance sequence (susceptibility-weighted angiography [SWAN]) with the T2* sequence for the detection of an arterial thrombus in acute ischaemic stroke., Methods: Seventy-four consecutive patients with acute ischaemic stroke were included. Proximal arterial occlusions were diagnosed using time-of-flight (TOF) magnetic resonance angiography (MRA). Two-dimensional (2D) axial reformats from 3D SWAN were generated to match with 2D T2* images. For arterial thrombus detection, each set of MR images (T2*, 2D SWAN reformats and 3D multiplanar SWAN images) was examined independently and separately by three observers who assigned the images to one of three categories: (0) absence of thrombus, (1) uncertain thrombus, (2) certain thrombus. Agreement and diagnostic accuracy were calculated., Results: Twenty-four proximal arterial occlusions involving the anterior (n = 20) or posterior (n = 4) circulation were found. Inter-observer agreement was moderate using T2* images (κ = 0.58), good using 2D SWAN reformats (κ = 0.83) and excellent using multiplanar SWAN images (κ = 0.90). For the diagnosis of thrombus, T2* images were 54% sensitive and 86% specific, 2D SWAN reformats were 83% sensitive and 94% specific and SWAN multiplanar analysis was 96% sensitive and 100% specific., Conclusions: Three-dimensional SWAN sequence improves the detection of arterial thrombus in patients with acute ischaemic stroke in comparison with the 2D T2* sequence., Key Points: • Multi-echo gradient-echo MR (e.g. susceptibility-weighted angiograph, [SWAN]) is increasingly used in neuroradiology. • Compared with conventional T2* sequences, SWAN improves detection of arterial thrombus. • Multiplanar SWAN analysis had the best diagnostic performance for arterial thrombus detection. • Sensitivity was 96% and specificity 100%. • Findings support combination of time-of-flight and susceptibility effects in suspected acute stroke.