Dose Evaluation Research Articles

Investigating the suitability of newly developed epoxy-based equivalent tissues for newborn and 5-year-old in paediatric radiology

The varied radiological applications of tissue equivalent (TE) materials encompass quality checks, diagnostic imaging, and dose evaluations. However, the availability of compounds representing paediatric patient tissues for scientific use in lower diagnostic photon energy spectra is limited. In this study, several TE substitutes were developed to replicate the radiographic characteristics of neonatal soft tissue (ESST-NB), neonatal skeletal tissue (ESTB-NB), and equivalent tissues of a 5-year-old child (ESST and ESBT, respectively) within these energy ranges. The ORNL stylized computational model series was utilised as the primary reference for obtaining the desired elemental ratios. The density, effective atomic number, CT numbers, and electron densities obtained for the developed tissue substitutes exhibited a close resemblance to those of the reference phantom system, demonstrating a high level of accuracy and agreement. Furthermore, in order to accommodate constraints related to material selection and production, significant correlations were established between the obtained data and the reference values for mass densities, mass attenuation coefficients, and mass energy-absorption coefficients. In comparison to the ORNL reference samples, the neonates TE substitutions showed maximum discrepancies μ/ρ ranging from +1.6% to −3.01% and μen/ρ from +1.15% to −1.4% throughout an energy range from 47 keV to 66 keV. For the TE materials representing a 5-year-old, the corresponding comparable data ranges were +1.09% to −3.02% and +1.92% to −2.53%. These tissues may then be utilised to produce physical phantoms for neonates and 5-year-old as a result of the great concordance established between the newly built TE materials and the reference data.

Region of interest focused MRI to synthetic CT translation using regression and segmentation multi-task network

Objective. In MR-only clinical workflow, replacing CT with MR image is of advantage for workflow efficiency and reduces radiation to the patient. An important step required to eliminate CT scan from the workflow is to generate the information provided by CT via an MR image. In this work, we aim to demonstrate a method to generate accurate synthetic CT (sCT) from an MR image to suit the radiation therapy (RT) treatment planning workflow. We show the feasibility of the method and make way for a broader clinical evaluation. Approach. We present a machine learning method for sCT generation from zero-echo-time (ZTE) MRI aimed at structural and quantitative accuracies of the image, with a particular focus on the accurate bone density value prediction. The misestimation of bone density in the radiation path could lead to unintended dose delivery to the target volume and results in suboptimal treatment outcome. We propose a loss function that favors a spatially sparse bone region in the image. We harness the ability of the multi-task network to produce correlated outputs as a framework to enable localization of region of interest (RoI) via segmentation, emphasize regression of values within RoI and still retain the overall accuracy via global regression. The network is optimized by a composite loss function that combines a dedicated loss from each task. Main results. We have included 54 brain patient images in this study and tested the sCT images against reference CT on a subset of 20 cases. A pilot dose evaluation was performed on 9 of the 20 test cases to demonstrate the viability of the generated sCT in RT planning. The average quantitative metrics produced by the proposed method over the test set were—(a) mean absolute error (MAE) of 70 ± 8.6 HU; (b) peak signal-to-noise ratio (PSNR) of 29.4 ± 2.8 dB; structural similarity metric (SSIM) of 0.95 ± 0.02; and (d) Dice coefficient of the body region of 0.984 ± 0. Significance. We demonstrate that the proposed method generates sCT images that resemble visual characteristics of a real CT image and has a quantitative accuracy that suits RT dose planning application. We compare the dose calculation from the proposed sCT and the real CT in a radiation therapy treatment planning setup and show that sCT based planning falls within 0.5% target dose error. The method presented here with an initial dose evaluation makes an encouraging precursor to a broader clinical evaluation of sCT based RT planning on different anatomical regions.

Evaluation of Operator and Patient Doses after Irradiation with Handheld X-ray Devices

Evaluation of Operator and Patient Doses after Irradiation with Handheld X-ray Devices

Analysis of dual-energy mammography subtraction technique for the dose and image quality evaluation using 3D-printed breast phantom.

This study aimed to quantitatively assess the radiation dose using XR-QA2 and the image quality of the dual-energy subtraction mammography technique on an in-house phantom. The analysis was carried out to investigate the effect of targets/filters on dose value and image quality using an in-house phantom made of PLA + as an object representing compressed breasts. All irradiation parameters were performed in the craniocaudal position with manual mode. Mean glandular dose (MGD) was recorded, followed by the calculation of the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and modulation transfer function (MTF) for image quality assessment parameters. The results showed that the image quality was accepted at dose levels within the IAEA and BAPETEN tolerance limit for 60mm equivalent compressed breast using dual-energy mammography. Furthermore, the target/filter (W/Rh) reduced the dose by 1.03mGy compared to the Mo/Mo and Mo/Rh with an enhancement in image quality. This indicated that the target/filter (W/Rh) combination was optimal due to the image quality improvement obtained with lower MGD.

Radiation dose evaluation to organs in neonatal patients by field size during potable X-ray examination in incubators: A Monte Carlo simulation study.

Neonatal patients located in incubators are exposed to as many as 159 radiographs until discharge. To reduce the dose exposed to the patient, factors that may cause unnecessary exposure to the patient were judged. When conducting portable X-rays of neonatal patients located in an incubator, it is not easy to determine the exact field size because collimation light is exposed on the acrylic plate, an incubator canopy, and the resulting shadow is reflected on the patient's body. This study aims to measure the organ dose exposed to the patient according to the field size when a portable radiograph is given to a neonatal patient in a neonatal intensive care unit (NICU) incubator. To identify the absorbed organ dose depending on the radiation field size during portable X-ray examination of neonatal patient, a Monte Carlo N-Particle (MCNP) simulation, a SpeckCalc program, and a neonatal phantom from the ICRP 89 are applied for the calculation. According to the minimal field size (MinFS) standards of the European Commission (EC), the smaller field size is intended to measure tightly from the top of the lung apices to the bottom of the genitals; a larger field size is also calculated by adding 6 cm in width and length. Compared to the hospital C condition from the previous study, the larger and smaller field sizes are decreased by an average of 45% and 67%, respectively. Study results also show a 42% reduction in smaller field size compared to the larger field size. When taking chest and abdomen radiographic images of neonatal patients in incubators, appropriate field sizes are required to prevent inappropriate dose absorption for non-thoracic organs.

Size Specific Dose Estimate in Abdominal Computed Tomography by AAPM TG Report-204 and AAPM TG Report-220

Purpose: The AAPM Task Group (TG) reports 204 and 220 presented methods for evaluation of patient dose by announcing the SSDE. The TG reports provide the Size Specific Conversion factors that can be multiplied to CTDIvol to calculate the patient dose in terms of SSDE constructed from Deff (AAPM TG-204) and Dw (AAPM TG-220). Our study presents a comparison of the two TG reports on SSDE for the routine Abdominal Computed Tomography. Materials and Methods: The scan lengths of abdomen were measured from computed tomography (CT) topographic images and cross-section at the mid-slice of the abdomen were measured from tomographic images of 61 adults who had undergone abdominal CT using the GE Advance Workstation (AWS) software. The Deff and Dw was computed according to TG- 204 and TG-220 reports, respectively. Further, we performed the correlation analysis between Deff and BMI, Dw and BMI and SSDE and BMI for both the TG- reports. The Student’s paired t-test was performed to compare the two of SSDE calculation methods. Results: The results confirm that the mean value of SSDE is 13.04 (𝑚𝐺𝑦) and 13.60 (𝑚𝐺𝑦) for AAPM TG-220 and AAPM TG-204, respectively. And a good positive correlation was observed between Deff and BMI, Dw and BMI with r = 0.67 and r = 0.68 respectively. Also, the weak correlation was observed between SSDE and BMI for both the TG - reports. The Student’s paired t-test shows that the two means of SSDE calculation methods are significantly different (𝑝< 0.01) in abdominal computed tomography. Conclusion: We confirm the AAPM TG reports 204/220 using clinical data for SSDE calculation that the mean SSDE values computed from Deff and Dw in abdomenal computed tomography are significantly different and we conclude that the SSDE calculated by Dw method gives a more accurate evaluation of SSDE for the patients undergoing abdominal computed tomography scan then the SSDE calculated by Deff method.

Feasibility study of optical imaging of the boron-dose distribution by a liquid scintillator in a clinical boron neutron capture therapy field.

Evaluation of the boron dose is essential for boron neutron capture therapy (BNCT). Nevertheless, a direct evaluation method for the boron-dose distribution has not yet been established in the clinical BNCT field. To date, even in quality assurance (QA) measurements, the boron dose has been indirectly evaluated from the thermal neutron flux measured using the activation method with gold foil or wire and an assumed boron concentration in the QA procedure. Recently, we successfully conducted optical imaging of the boron-dose distribution using a cooled charge-coupled device (CCD) camera and a boron-added liquid scintillator at the E-3 port facility of the Kyoto University Research Reactor (KUR), which supplies an almost pure thermal neutron beam with very low gamma-ray contamination. However, in a clinical accelerator-based BNCT facility, there is a concern that the boron-dose distribution may not be accurately extracted because the unwanted luminescence intensity, which is irrelevant to the boron dose is expected to increase owing to the contamination of fast neutrons and gamma rays. The purpose of this research was to study the validity of a newly proposed method using a boron-added liquid scintillator and a cooled CCD camera to directly observe the boron-dose distribution in a clinical accelerator-based BNCT field. A liquid scintillator phantom with 10 B was prepared by filling a small quartz glass container with a commercial liquid scintillator and boron-containing material (trimethyl borate); its natural boron concentration was 1wt%. Luminescence images of the boron-neutron capture reaction were obtained in a water tank at several different depths using a CCD camera. The contribution of background luminescence, mainly due to gamma rays, was removed by subtracting the luminescence images obtained using another sole liquid scintillator phantom (natural boron concentration of 0wt%) at each corresponding depth, and a depth profile of the boron dose with several discrete points was obtained. The obtained depth profile was compared with that of calculated boron dose, and those of thermal neutron flux which were experimentally measured or calculated using a Monte Carlo code. The depth profile evaluated from the subtracted images indicated reasonable agreement with the calculated boron-dose profile and thermal neutron flux profiles, except for the shallow region. This discrepancy is thought to be due to the contribution of light reflected from the tank wall. The simulation results also demonstrated that the thermal neutron flux would be severely perturbed by the 10 B-containing phantom if a relatively larger container was used to evaluate a wide range of boron-dose distributions in a single shot. This indicates a trade-off between the luminescence intensity of the 10 B-added phantom and its perturbation effect on the thermal neutron flux. Although a partial discrepancy was observed, the validity of the newly proposed boron-dose evaluation method using liquid-scintillator phantoms with and without 10 B was experimentally confirmed in the neutron field of an accelerator-based clinical BNCT facility. However, this study has some limitations, including the trade-off problem stated above. Therefore, further studies are required to address these limitations.

Comparison of four synthetic CT generators for brain and prostate MR-only workflow in radiotherapy

BackgroundThe interest in MR-only workflows is growing with the introduction of artificial intelligence in the synthetic CT generators converting MR images into CT images. The aim of this study was to evaluate several commercially available sCT generators for two anatomical localizations.MethodsFour sCT generators were evaluated: one based on the bulk density method and three based on deep learning methods. The comparison was performed on large patient cohorts (brain: 42 patients and pelvis: 52 patients). It included geometric accuracy with the evaluation of Hounsfield Units (HU) mean error (ME) for several structures like the body, bones and soft tissues. Dose evaluation included metrics like the Dmean ME for bone structures (skull or femoral heads), PTV and soft tissues (brain or bladder or rectum). A 1%/1 mm gamma analysis was also performed.ResultsHU ME in the body were similar to those reported in the literature. Dmean ME were smaller than 2% for all structures. Mean gamma pass rate down to 78% were observed for the bulk density method in the brain. Performances of the bulk density generator were generally worse than the artificial intelligence generators for the brain but similar for the pelvis. None of the generators performed best in all the metrics studied.ConclusionsAll four generators can be used in clinical practice to implement a MR-only workflow but the bulk density method clearly performed worst in the brain.

PO26: Evaluation of Radiation Dose to the Bulboclitoris in Patients Receiving Interstitial Brachytherapy for Gynecologic Cancers Involving the Lower Vagina

PO26: Evaluation of Radiation Dose to the Bulboclitoris in Patients Receiving Interstitial Brachytherapy for Gynecologic Cancers Involving the Lower Vagina

Evaluation of radiation dose and image quality for dental cone-beam computed tomography in pediatric patients

Children are sensitive to radiation; therefore, it is necessary to reduce radiation dose as much as possible in pediatric patients. In addition, it is crucial to investigate the optimal imaging conditions as they considerably affect the radiation dose. In this study, we investigated the effect of different imaging conditions on image quality and optimized the imaging conditions for dental cone-beam computed tomography (CBCT) examinations to diagnose ectopic eruptions and impacted teeth in children. To achieve our aims, we evaluated radiation doses and subjective and objective image quality. The CBCT scans were performed using 3D Accuitomo F17. All combinations of a tube voltage (90 kV), tube currents (1, 2, 3 mA), fields of view (FOVs) (4 × 4, 6 × 6 cm), and rotation angles (360°, 180°) were used. Dose-area product values were measured. SedentexCT IQ cylindrical phantom was used to physically evaluate the image quality. We used the modulation transfer function as an index of resolution, the noise power spectrum as an index of noise characteristics, and the system performance function as an overall evaluation index of the image. Five dentists visually evaluated the images from the head-neck phantom. The results showed that the image quality tended to worsen, and scores for visual evaluation decreased as tube currents, FOVs and rotation angles decreased. In particular, image noise negatively affected the delineation of the periodontal ligament space. The optimal imaging conditions were 90 kV, 2 mA, 4 × 4 cm FOV and 180° rotation. These results suggest that CBCT radiation doses can be significantly reduced by optimizing the imaging conditions.

Study of Effective Atomic Number, Mass Energy Absorption Coefficient and Absorbed Dose Rate in Human Organ and Tissue Substitutes

Abstract: The effective atomic number and mass energy absorption coefficient are two essential parameters used to investigate the radiation response of composite materials of dosimetric interest in many medical applications. The effective atomic number of nine selected human tissues and eleven samples of tissue substitute materials were computed using two methods, the interpolation method and the direct method in the energy range used in brachytherapy applications (0.1-2.0) MeV. The applicability of using the effective atomic number values to investigate scatter and absorption properties of some tissue substitutes, against that of the corresponding human tissues, to validate their tissue-equivalency, is examined. The effect of partial interaction cross sections is also explicitly discussed. Further, the absorbed dose rate, for an isotropic point source, in the selected tissue samples was computed using their estimated mass energy absorption coefficient values. The obtained data are analyzed and differences in sample dose rate relative to water, for photon energies of interest, are evaluated. The results indicate that numbers of tissue substitute samples yield estimates of dose rate to within 5% of dose rate of their corresponding human tissues. The obtained results are expected to be useful in improving dose calculation accuracy in brachytherapy treatment planning or dose evaluation after treatment. Keywords: Dosimetry, Human organs and tissues, Tissue equivalent materials, Equivalent atomic number, Attenuation and absorption coefficients.

Usefulness of Ag Additional Filter on Image Quality and Radiation Dose for Low-Dose Chest Computed Tomography.

This study aimed to evaluate the effect of a silver (Ag) additional filter on dose characteristics and image quality in low-dose chest computed tomography (CT). A dose evaluation phantom, physical evaluation phantom, and chest phantom were scanned with and without an Ag additional filter. The doses were adjusted so that the displayed the volume CT dose indexes (CTDI vol ) were from 0.3 to 1.6 mGy. For dose characteristics, the spectrum of photon energies and the measured CTDI vol were calculated for each scanning condition. For task-based image quality analysis, task transfer function, noise power spectrum, and system performance were evaluated. Streak artifacts, image noise, and contrast-to-noise ratio were quantified using a chest phantom. With the Ag additional filter, mean energy was 22% higher and the CTDI vol was approximately 30% lower than those without the Ag additional filter. The task transfer function and noise power spectrum with the Ag additional filter were lower than those without the Ag additional filter. The system performance with the Ag additional filter was similar to that without the Ag additional filter. The Ag additional filter reduced streak artifact near the lung apex and image noise in the lung fields. The contrast-to-noise ratio was slightly higher with the Ag additional filter than that without the Ag additional filter. The output dose and spatial resolution with the Ag additional filter were lower than those without the Ag additional filter. However, this filter helped reduce the radiation dose, image noise, and streak artifacts, particularly when scanning at ultralow doses.

Evaluation of institutional whole-body and extremity occupational radiation doses in nuclear medicine.

This study evaluated nuclear medicine occupational radiation doses at Sultan Qaboos University Hospital, a 700-bed tertiary care teaching hospital in Oman. Personal effective whole-body doses, Hp(10), and extremity doses, Hp(0.07), were collected for 19 medical radiation workers over a 7-year period (2015-2021). Personal doses for four professional groups were measured using calibrated thermo-luminescence dosemeters ((LiF:Mg,Ti) TLD-100). The average, median and maximum cumulative doses were compared against the annual whole-body and extremity dose limits (20mSv and 500mSv y-1, respectively) and local dose investigation level (DIL; 6mSv y-1). Personal whole-body doses (average:median:maximum) for technologists, medical physicists, nuclear medicine physicians and nurses were 1.8:1.1:7.8, 0.3:0.3:0.4, 0.1:0.1:0.2 and 0.1:0.1:0.2mSv, respectively. Personal extremity doses for left and right hand (average and maximum doses) follow similar trends. Average annual effective whole-body and extremity doses were well below the recommended annual dose limits. The findings suggest lowering local DIL for all staff except for technologists.

Robustness analysis of CTV and OAR dose in clinical PBS-PT of neuro-oncological tumors: prescription-dose calibration and inter-patient variation with the Dutch proton robustness evaluation protocol.

Objective. The Dutch proton robustness evaluation protocol prescribes the dose of the clinical target volume (CTV) to the voxel-wise minimum (VWmin) dose of 28 scenarios. This results in a consistent but conservative near-minimum CTV dose (D98%,CTV). In this study, we analyzed (i) the correlation between VWmin/voxel-wise maximum (VWmax) metrics and actually delivered dose to the CTV and organs at risk (OARs) under the impact of treatment errors, and (ii) the performance of the protocol before and after its calibration with adequate prescription-dose levels.Approach. Twenty-one neuro-oncological patients were included. Polynomial chaos expansion was applied to perform a probabilistic robustness evaluation using 100,000 complete fractionated treatments per patient. Patient-specific scenario distributions of clinically relevant dosimetric parameters for the CTV and OARs were determined and compared to clinical VWmin and VWmax dose metrics for different scenario subsets used in the robustness evaluation protocol.Main results. The inclusion of more geometrical scenarios leads to a significant increase of the conservativism of the protocol in terms of clinical VWmin and VWmax values for the CTV and OARs. The protocol could be calibrated using VWmin dose evaluation levels of 93.0%-92.3%, depending on the scenario subset selected. Despite this calibration of the protocol, robustness recipes for proton therapy showed remaining differences and an increased sensitivity to geometrical random errors compared to photon-based margin recipes.Significance. The Dutch proton robustness evaluation protocol, combined with the photon-based margin recipe, could be calibrated with a VWmin evaluation dose level of 92.5%. However, it shows limitations in predicting robustness in dose, especially for the near-maximum dose metrics to OARs. Consistent robustness recipes could improve proton treatment planning to calibrate residual differences from photon-based assumptions.

Calculation of the DNA damage yield and relative biological effectiveness in boron neutron capture therapy via the Monte Carlo track structure simulation.

Objective.Boron neutron capture therapy (BNCT) is an advanced cellular-level hadron therapy that has exhibited remarkable therapeutic efficacy in the treatment of locally invasive malignancies. Despite its clinical success, the intricate nature of relative biological effectiveness (RBE) and mechanisms responsible for DNA damage remains elusive. This work aims to quantify the RBE of compound particles (i.e. alpha and lithium) in BNCT based on the calculation of DNA damage yields via the Monte Carlo track structure (MCTS) simulation.Approach. The TOPAS-nBio toolkit was employed to conduct MCTS simulations. The calculations encompassed four steps: determination of the angle and energy spectra on the nuclear membrane, quantification of the database containing DNA damage yields for ions with specific angle and energy, accumulation of the database and spectra to obtain the DNA damage yields of compound particles, and calculation of the RBE by comparison yields of double-strand break (DSB) with the reference gamma-ray. Furthermore, the impact of cell size and microscopic boron distribution was thoroughly discussed.Main results. The DSB yields induced by compound particles in three types of spherical cells (radius equal to 10, 8, and 6μm) were found to be 13.28, 17.34, 22.15 Gy Gbp-1for boronophenylalanine (BPA), and 1.07, 3.45, 8.32 Gy Gbp-1for sodium borocaptate (BSH). The corresponding DSB-based RBE values were determined to be 1.90, 2.48, 3.16 for BPA and 0.15, 0.49, 1.19 for BSH. The calculated DSB-based RBE showed agreement with experimentally values of compound biological effectiveness for melanoma and gliosarcoma. Besides, the DNA damage yield and DSB-based RBE value exhibited an increasing trend as the cell radius decreased. The impact of the boron concentration ratio on RBE diminished once the drug enrichment surpasses a certain threshold.Significance. This work is potential to provide valuable guidance for accurate biological-weighted dose evaluation in BNCT.

Gamma spectroscopy study of soil-plant transfer factor characteristics of 40K, 232Th and 226Ra in some crops cultivated in southwestern region of Nigeria

Soil-plant transfer factor (TF) is one of the vital variables employed in assessing plants uptake of radionuclides and their transfer to food chain for predictive ingestion dose and risk evaluation. To further this goal, the TF characteristics of natural 40K, 232Th and 226Ra were thus investigated in some crops (yam, cassava, rice, maize, groundnut, cowpea, okra, pumpkin leaf, banana and pawpaw) cultivated in southwestern part of Nigeria using HPGe gamma spectroscopy. The obtained results of activity concentration (AC) of the radionuclides across all the cultivated soil samples indicated average values that are less than the global average, whereas in the crops, average values of 226Ra and 232Th, were higher than reference values for different crops group. The overall range of the calculated TF of 40K, 232Th and 226Ra across all the crops was 0.05 (in maize and cowpea) to 15.01 (in banana), 0.01 (in pumpkin leaf and groundnut) to 19.80 (in pawpaw), and 0.04 (in cassava) to 21.30 (in cowpea), respectively. Overall arithmetic mean and geometric mean were estimated as 2.66 and 1.60, 1.11 and 0.43, and 1.10 and 0.54 for 40K, 232Th and 226Ra, respectively. TFs mostly correlated negatively with soil radionuclides, while positive correlation was mostly noticeable in the case of crop. Log normal transform of the TFs data indicated a near normal distribution as against the calculated data. The derived results of this study is here presented as a baseline data suggested for possible radiological risk assessment of food chain of the local population.

Evaluation of uranium content and annual ingestion dose in the surface and ground water bodies of Chittorgarh, Rajasthan, India.

Uranium, naturally occurring radionuclide is chemotoxic and nephrotoxic beyond acceptable limit. The presence of uranium beyond acceptable limit in surface and ground water, adversely affecting people's health. In the present investigation, the uranium concentration in surface and ground water of Chittorgarh, Rajasthan was studied along with the physico-chemical parameters of water (n = 87). The ground water was further sub-categorised into well water, handpump water, and borewell water. The mean uranium concentration was observed at 2.5 ± 1.9 µgL-1 and 16.5 ± 1.4 µgL-1 in the surface and ground water samples, respectively. In sub-categories of ground water, the highest uranium concentration was found in borewell water (23.3 ± 17.0 µgL-1), followed by handpump water (13.5 ± 9.1 µgL-1) and well water (6.0 ± 5.5 µgL-1). The uranium concentration was correlated significantly with the depth of the ground water table. It also correlated significantly with electrical conductivity, total dissolved solids and nitrate concentration. 100% of surface water and 88.9% of ground water samples carried uranium concentration within the acceptable limit of WHO (30 µgL-1). The annual ingestion dose was found at 3.8 µSvy-1 (for males) and 2.8 µSvy-1 (for females) in surface water and 25.4 µSvy-1 (for males) and 18.5 µSvy-1 (for females) in ground water. In the sub-categories of the ground water sample, the annual ingestion dose followed the trend in males 35.8 µSvy-1 (borewell water) > 20.7 µSvy-1 (hand pump water) > 9.2 µSvy-1 (well water) and in females 26.1 µSvy-1 (borewell water) > 15.1 µSvy-1 (hand pump water) > 6.7 µSvy-1 (well water).

A phase II dose evaluation pilot feasibility randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study)

BackgroundVitamin D deficiency (VDD) is highly prevalent in the pediatric intensive care unit (ICU) and associated with worse clinical course. Trials in adult ICU demonstrate rapid restoration of vitamin D status using an enteral loading dose is safe and may improve outcomes. There have been no published trials of rapid normalization of VDD in the pediatric ICU.MethodsWe conducted a multicenter placebo-controlled phase II pilot feasibility randomized clinical trial from 2016 to 2017. We randomized 67 critically ill children with VDD from ICUs in Canada, Chile and Austria using a 2:1 randomization ratio to receive a loading dose of enteral cholecalciferol (10,000 IU/kg, maximum of 400,000 IU) or placebo. Participants, care givers, and outcomes assessors were blinded. The primary objective was to determine whether the loading dose normalized vitamin D status (25(OH)D > 75 nmol/L). Secondary objectives were to evaluate for adverse events and assess the feasibility of a phase III trial.ResultsOf 67 randomized participants, one was withdrawn and seven received more than one dose of cholecalciferol before the protocol was amended to a single loading dose, leaving 59 participants in the primary analyses (40 treatment, 19 placebo). Thirty-one/38 (81.6%) participants in the treatment arm achieved a plasma 25(OH)D concentration > 75 nmol/L versus 1/18 (5.6%) the placebo arm. The mean 25(OH)D concentration in the treatment arm was 125.9 nmol/L (SD 63.4). There was no evidence of vitamin D toxicity and no major drug or safety protocol violations. The accrual rate was 3.4 patients/month, supporting feasibility of a larger trial. A day 7 blood sample was collected for 84% of patients. A survey administered to 40 participating families showed that health-related quality of life (HRQL) was the most important outcome for families for the main trial (30, 75%).ConclusionsA single 10,000 IU/kg dose can rapidly and safely normalize plasma 25(OH)D concentrations in critically ill children with VDD, but with significant variability in 25(OH)D concentrations. We established that a phase III multicentre trial is feasible. Using an outcome collected after hospital discharge (HRQL) will require strategies to minimize loss-to-follow-up.Trial Registration.Clinicaltrials.gov NCT02452762 Registered 25/05/2015.

Absorbed dose evaluation of a blood irradiator with alanine, TLD-100 and ionization chamber

Irradiation of blood bags using X-ray irradiators and dosimetry services are required to ensure uniform dose levels in the range 25–50 Gy to prevent Transfusion Associated Graft versus Host Disease (TA-GvHD). An absorbed dose characterization of a Raycell MK2 X-Irradiator was performed using three different dosimetric systems. Results showed a dosimetric accuracy of the ionization chamber together with the Alanine dosimeter. TLDs measurements exhibited a small overestimation by 4% of the absorbed dose. The Dose Uniformity Ratio (DUR), between maximum and minimum dose levels in the canister, was in good agreement with the manufacturer specifications (≤1.5).

Effects of cyclophosphamide and mitomycin C on radiation-induced transcriptional biomarkers in human lymphoblastoid cells

Purpose Ionizing radiation (IR)-induced transcriptional changes are considered a potential biodosimetry for dose evaluation and health risk monitoring of acute or chronic radiation exposure. It is crucial to understand the impact of confounding factors on the radiation-responsive gene expressions for accurate and reproducible dose assessment. This study aims to explore the potential influence of exposures to chemotherapeutic agents such as cyclophosphamide (CP) and mitomycin C (MMC) on IR-induced transcriptional biomarkers. Methods The human B lymphoblastoid cells (AHH-1) were exposed to 0, 20, 50, 100, 200 and 500 μg/ml CP or 0, 0.025, 0.05, 0.1 and 1 μg/ml MMC, respectively. The appropriate concentrations of CP and MMC were added for 1 h before irradiation with 0, 2, 4 and 6 Gy of 60Co γ-rays at a dose rate of 1 Gy/min. Cell viability was evaluated by CCK-8 assay. The gene expression responses of 18 radiation-induced transcriptional biomarkers were examined at 24 h after exposures to CP and MMC, respectively. The expression levels of five crucial DNA interstrand crosslinks (ICLs) repair genes were also evaluated. The biodosimetry models were established based on the specific radiation-responsive gene combinations. Results The baseline transcriptional levels of the 18 selected genes were slightly affected by CP treatment in the absence of IR, while the transcript responses to IR could be inhibited as the concentration of CP up to 50 μg/ml. MMC treatment up-regulated the background levels in most radiation-responsive gene expressions. Of 18 genes, only the relative mRNA expression levels of CDKN1A and BBC3 were repressed after treatment with IR and MMC in combination. The relative mRNA level of RAD51 was significantly up-regulated after exposure to CP, while the expression of FANCD2, RAD51 and BLM showed an overall increase in response to MMC treatment. After irradiation, the relative mRNA expression levels of FANCD2, BRCA2 and RAD51 exhibited dose-dependent increases in IR alone and MMC treatment groups. In addition, the biodosimetry models were established using 2-4 radiation-responsive genes based on different radiation exposure scenarios. Conclusion Our findings suggested that IR-induced gene expression changes were slightly affected after exposure to a relatively low concentration of CP and MMC. Gene expression combinations might improve the broad applicability of transcriptional biodosimetry across diverse radiation exposures.