A Review of Numerical Models of Radiation Injury and Repair Considering Subcellular Targets and the Extracellular Microenvironment.

Astronauts in space are subject to continuous exposure to ionizing radiation. There is concern about the acute and late-occurring adverse health effects that astronauts could incur following a protracted exposure to the space radiation environment. Therefore, it is vital to consider the current tools and models used to describe and study the organic consequences of ionizing radiation exposure. It is equally important to see where these models could be improved. Historically, radiobiological models focused on how radiation damages nuclear deoxyribonucleic acid (DNA) and the role DNA repair mechanisms play in resulting biological effects, building on the hypotheses of Crowther and Lea from the 1940s and 1960s, and they neglected other subcellular targets outside of nuclear DNA. The development of these models and the current state of knowledge about radiation effects impacting astronauts in orbit, as well as how the radiation environment and cellular microenvironment are incorporated into these radiobiological models, aid our understanding of the influence space travel may have on astronaut health. It is vital to consider the current tools and models used to describe the organic consequences of ionizing radiation exposure and identify where they can be further improved.

Medical workforce in the United States.

This section focuses on the professional workforce comprised of the primary medical specialties that utilize ionizing radiation in their practices. Those discussed include the specialties of radiology and radiation oncology, as well as the subspecialties of radiology, namely diagnostic radiology, interventional radiology, nuclear radiology, and nuclear medicine. These professionals provide essential health care services, for example, the interpretation of imaging studies, the provision of interventional procedures, radionuclide therapeutic treatments, and radiation therapy. In addition, they may be called on to function as part of a radiologic emergency response team to care for potentially exposed persons following radiation events, for example, detonation of a nuclear weapon, nuclear power plant accidents, and transportation incidents. For these reasons, maintenance of an adequate workforce in each of these professions is essential to meeting the nation's future needs. Currently, there is a shortage for all physicians in the medical radiology workforce.

Applications of a patient-specific whole-body CT-mesh hybrid computational phantom in second cancer risk prediction.

Objective.CT-mesh hybrid phantoms (or 'hybrid(s)') made from integrated patient CT data and mesh-type reference computational phantoms (MRCPs) can be beneficial for patient-specific whole-body dose evaluation, but this benefit has yet to be evaluated for second cancer risk prediction. The purpose of this study is to compare the hybrid's ability to predict risk throughout the body with a patient-scaled MRCP against ground truth whole-body CTs (WBCTs).Approach.Head and neck active scanning proton treatment plans were created for and simulated on seven hybrids and the corresponding scaled MRCPs and WBCTs. Equivalent dose throughout the body was calculated and input into five second cancer risk models for both excess absolute and excess relative risk (EAR and ERR). The hybrid phantom was evaluated by comparing equivalent dose and risk predictions against the WBCT.Main results.The hybrid most frequently provides whole-body second cancer risk predictions which are closer to the ground truth when compared to a scaled MRCP alone. The performance of the hybrid relative to the scaled MRCP was consistent across ERR, EAR, and all risk models. For all in-field organs, where the hybrid shares the WBCT anatomy, the hybrid was better than or equal to the scaled MRCP for both equivalent dose and risk prediction. For out-of-field organs across all patients, the hybrid's equivalent dose prediction was superior than the scaled MRCP in 48% of all comparisons, equivalent for 34%, and inferior for 18%. For risk assessment in the same organs, the hybrid's prediction was superior than the scaled MRCP in 51.8% of all comparisons, equivalent in 28.6%, and inferior in 19.6%.Significance.Whole-body risk predictions from the CT-mesh hybrid have shown to be more accurate than those from a reference phantom alone. These hybrids could aid in risk-optimized treatment planning and individual risk assessment to minimize second cancer incidence.

Stray neutron radiation exposures from proton therapy: physics-based analytical models of neutron spectral fluence, kerma and absorbed dose.

Objective. Patients who receive proton beam therapy are exposed to unwanted stray neutrons. Stray radiations increase the risk of late effects in normal tissues, such as second cancers and cataracts, and may cause implanted devices such as pacemakers to malfunction. Compared to therapeutic beams, little attention has been paid to modeling stray neutron exposures. In the past decade, substantial progress was made to develop semiempirical models of stray neutron dose equivalent, but models to routinely calculate neutron absorbed dose and kerma are still lacking. The objective of this work was to develop a new physics based analytical model to calculate neutron spectral fluence, kerma, and absorbed dose in a water phantom.Approach. We developed the model using dosimetric data from Monte Carlo simulations and neutron kerma coefficients from the literature. The model explicitly considers the production, divergence, scattering, and attenuation of neutrons. Neutron production was modeled for 120-250 MeV proton beams impinging on a variety of materials. Fluence, kerma and dose calculations were performed in a 30 × 180 × 44 cm3phantom at points up to 43 cm in depth and 80 cm laterally.Main Results. Predictions of the analytical model agreed reasonably with corresponding values from Monte Carlo simulations, with a mean difference in average energy deposited of 20%, average kerma coefficient of 21%, and absorbed dose to water of 49%.Significance. The analytical model is simple to implement and use, requires less configuration data that previously reported models, and is computationally fast. This model appears potentially suitable for integration in treatment planning system, which would enable risk calculations in prospective and retrospective cases, providing a powerful tool for epidemiological studies and clinical trials.

Personalized 3D-printed anthropomorphic whole-body phantom irradiated by protons, photons, and neutrons.

The objective of this study was to confirm the feasibility of three-dimensionally-printed (3D-printed), personalized whole-body anthropomorphic phantoms for radiation dose measurements in a variety of charged and uncharged particle radiation fields. We 3D-printed a personalized whole-body phantom of an adult female with a height of 154.8 cm, mass of 90.7 kg, and body mass index of 37.8 kg/m2. The phantom comprised of a hollow plastic shell filled with water and included a watertight access conduit for positioning dosimeters. It is compatible with a wide variety of radiation dosimeters, including ionization chambers that are suitable for uncharged and charged particles. Its mass was 6.8 kg empty and 98 kg when filled with water. Watertightness and mechanical robustness were confirmed after multiple experiments and transportations between institutions. The phantom was irradiated to the cranium with therapeutic beams of 170-MeV protons, 6-MV photons, and fast neutrons. Radiation absorbed dose was measured from the cranium to the pelvis along the longitudinal central axis of the phantom. The dose measurements were made using established dosimetry protocols and well-characterized instruments. For the therapeutic environments considered in this study, stray radiation from intracranial treatment beams was the lowest for proton therapy, intermediate for photon therapy, and highest for neutron therapy. An illustrative example set of measurements at the location of the thyroid for a square field of 5.3 cm per side resulted in 0.09, 0.59, and 1.93 cGy/Gy from proton, photon, and neutron beams, respectively. In this study, we found that 3D-printed personalized phantoms are feasible, inherently reproducible, and well-suited for therapeutic radiation measurements. The measurement methodologies we developed enabled the direct comparison of radiation exposures from neutron, proton, and photon beam irradiations.

A patient-specific hybrid phantom for calculating radiation dose and equivalent dose to the whole body.

Objective. As cancer survivorship increases, there is growing interest in minimizing the late effects of radiation therapy such as radiogenic second cancer, which may occur anywhere in the body. Assessing the risk of late effects requires knowledge of the dose distribution throughout the whole body, including regions far from the treatment field, beyond the typical anatomical extent of clinical computed tomography (CT) scans.Approach. A hybrid phantom was developed which consists of in-field patient CT images extracted from ground truth whole-body CT scans, out-of-field mesh phantoms scaled to basic patient measurements, and a blended transition region. Four of these hybrid phantoms were created, representing male and female patients receiving proton therapy treatment in pelvic and cranial sites. To assess the performance of the hybrid approach, we simulated treatments using the hybrid phantoms, the scaled and unscaled mesh phantoms, and the ground truth whole-body CTs. We calculated absorbed dose and equivalent dose in and outside of the treatment field, with a focus on neutrons induced in the patient by proton therapy. Proton and neutron dose was calculated using a general purpose Monte Carlo code.Main results. The hybrid phantom provided equal or superior accuracy in calculated organ dose and equivalent dose values relative to those obtained using the mesh phantoms in 78% in all selected organs and calculated dose quantities. Comparatively the default mesh and scaled mesh were equal or superior to the other phantoms in 21% and 28% of cases respectively.Significance. The proposed methodology for hybrid synthesis provides a tool for whole-body organ dose estimation for individual patients without requiring CT scans of their entire body. Such a capability would be useful for personalized assessment of late effects and risk-optimization of treatment plans.

Preliminary tests of dosimetric quality and projected therapeutic outcomes of multi-phase 4D radiotherapy with proton and carbon ion beams.

Objective. The purpose of this study was to perform preliminary pre-clinical tests to compare the dosimetric quality of two approaches to treating moving tumors with ion beams: synchronously delivering the beam with the motion of a moving planning target volume (PTV) using the recently developed multi-phase 4D dose delivery (MP4D) approach, and asynchronously delivering the ion beam to a motion-encompassing internal tumor volume (ITV) combined with rescanning.Approach. We created 4D optimized treatment plans with proton and carbon ion beams for two patients who had previously received treatment for non-small cell lung cancer. For each patient, we created several treatment plans, using approaches with and without motion mitigation: MP4D, ITV with rescanning, static deliveries to a stationary PTV, and deliveries to a moving tumor without motion compensation. Two sets of plans were optimized with margins or robust uncertainty scenarios. Each treatment plan was delivered using a recently-developed motion-synchronized dose delivery system (M-DDS); dose distributions in water were compared to measurements using gamma index analysis to confirm the accuracy of the calculations. Reconstructed dose distributions on the patient CT were analyzed to assess the dosimetric quality of the deliveries (conformity, uniformity, tumor coverage, and extent of hotspots).Main results. Gamma index analysis pass rates confirmed the accuracy of dose calculations. Dose coverage was >95% for all static and MP4D treatments. The best conformity and the lowest lung doses were achieved with MP4D deliveries. Robust optimization led to higher lung doses compared to conventional optimization for ITV deliveries, but not for MP4D deliveries.Significance. We compared dosimetric quality for two approaches to treating moving tumors with ion beams. Our findings suggest that the MP4D approach, using an M-DDS, provides conformal motion mitigation, with full target coverage and lower OAR doses.

Personalized 3D-printed anthropomorphic phantoms for dosimetry in charged particle fields.

Anthropomorphic phantoms used for radiation dose measurements are designed to mimic human tissue in shape, size, and tissue composition. Reference phantoms are widely available and are sufficiently similar to many, but not all, human subjects. 3D printing has the potential to overcome some of these shortcomings by enabling rapid fabrication of personalized phantoms for individual human subjects based on radiographic imaging data.Objective. The objective of this study was to test the efficacy of personalized 3D printed phantoms for charged particle therapy. To accomplish this, we measured dose distributions from 6 to 20 MeV electron beams, incident on printed and molded slices of phantoms.Approach. Specifically, we determined the radiological properties of 3D printed phantoms, including beam penetration range. Additionally, we designed and printed a personalized head phantom to compare results obtained with a commercial, reference head phantom for quality assurance of therapeutic electron beam dose calculations.Main Results. For regions of soft tissue, gamma index analyses revealed a 3D printed slice was able to adequately model the same electron beam penetration ranges as the molded reference slice. The printed, personalized phantom provided superior dosimetric accuracy compared to the molded reference phantom for electron beam dose calculations at all electron beam energies. However, current limitations in the ability to print high-density structures, such as bone, limited pass rates of 60% or better at 16 and 20 MeV electron beam energies.Significance. This study showed that creating personalized phantoms using 3D printing techniques is a feasible way to substantially improve the accuracy of dose measurements of therapeutic electron beams, but further improvements in printing techniques are necessary in order to increase the printable density in phantoms.

Dosimetric Validation of a System to Treat Moving Tumors Using Scanned Ion Beams That Are Synchronized With Anatomical Motion.

PURPOSE: The purpose of this study was to validate the dosimetric performance of scanned ion beam deliveries with motion-synchronization to heterogenous targets. METHODS: A 4D library of treatment plans, comprised of up to 10 3D sub-plans, was created with robust and conventional 4D optimization methods. Each sub-plan corresponded to one phase of periodic target motion. The plan libraries were delivered to a test phantom, comprising plastic slabs, dosimeters, and heterogenous phantoms. This phantom emulated range changes that occur when treating moving tumors. Similar treatment plans, but without motion synchronization, were also delivered to a test phantom with a stationary target and to a moving target; these were used to assess how the target motion degrades the quality of dose distributions and the extent to which motion synchronization can improve dosimetric quality. The accuracy of calculated dose distributions was verified by comparison with corresponding measurements. Comparisons utilized the gamma index analysis method. Plan quality was assessed based on conformity, dose coverage, overdose, and homogeneity values, each extracted from calculated dose distributions. RESULTS: High pass rates for the gamma index analysis confirmed that the methods used to calculate and reconstruct dose distributions were sufficiently accurate for the purposes of this study. Calculated and reconstructed dose distributions revealed that the motion-synchronized and static deliveries exhibited similar quality in terms of dose coverage, overdose, and homogeneity for all deliveries considered. Motion-synchronization substantially improved conformity in deliveries with moving targets. Importantly, measurements at multiple locations within the target also confirmed that the motion-synchronized delivery system satisfactorily compensated for changes in beam range caused by the phantom motion. Specifically, the overall planning and delivery approach achieved the desired dose distribution by avoiding range undershoots and overshoots caused by tumor motion. CONCLUSIONS: We validated a dose delivery system that synchronizes the movement of the ion beam to that of a moving target in a test phantom. Measured and calculated dose distributions revealed that this system satisfactorily compensated for target motion in the presence of beam range changes due to target motion. The implication of this finding is that the prototype system is suitable for additional preclinical research studies, such as irregular anatomic motion.

A Modular System for Treating Moving Anatomical Targets With Scanned Ion Beams at Multiple Facilities: Pre-Clinical Testing for Quality and Safety of Beam Delivery.

BACKGROUND: Quality management and safety are integral to modern radiotherapy. New radiotherapy technologies require new consensus guidelines on quality and safety. Established analysis strategies, such as the failure modes and effects analysis (FMEA) and incident learning systems have been developed as tools to assess the safety of several types of radiation therapies. An extensive literature documents the widespread application of risk analysis methods to photon radiation therapy. Relatively little attention has been paid to performing risk analyses of nascent radiation therapy systems to treat moving tumors with scanned heavy ion beams. The purpose of this study was to apply a comprehensive safety analysis strategy to a motion-synchronized dose delivery system (M-DDS) for ion therapy. METHODS: We applied a risk analysis method to new treatment planning and treatment delivery processes with scanned heavy ion beams. The processes utilize a prototype, modular dose delivery system, currently undergoing preclinical testing, that provides new capabilities for treating moving anatomy. Each step in the treatment process was listed in a process map, potential errors for each step were identified and scored using the risk probability number in an FMEA, and the possible causes of each error were described in a fault tree analysis. Solutions were identified to mitigate the risk of these errors, including permanent corrective actions, periodic quality assurance (QA) tests, and patient specific QA (PSQA) tests. Each solution was tested experimentally. RESULTS: The analysis revealed 58 potential errors that could compromise beam delivery quality or safety. Each of the 14 binary (pass-or-fail) tests passed. Each of the nine QA and four PSQA tests were within anticipated clinical specifications. The modular M-DDS was modified accordingly, and was found to function at two centers. CONCLUSION: We have applied a comprehensive risk analysis strategy to the M-DDS and shown that it is a clinically viable motion mitigation strategy. The described strategy can be utilized at any ion therapy center that operates with the modular M-DDS. The approach can also be adapted for use at other facilities and can be combined with existing safety analysis systems.

Everything you wanted to know about space radiation but were afraid to ask.

The space radiation environment is a complex combination of fast-moving ions derived from all atomic species found in the periodic table. The energy spectrum of each ion species varies widely but is prominently in the range of 400-600 MeV/n. The large dynamic range in ion energy is difficult to simulate in ground-based radiobiology experiments. Most ground-based irradiations with mono-energetic beams of a single one ion species are delivered at comparatively high dose rates. In some cases, sequences of such beams are delivered with various ion species and energies to crudely approximate the complex space radiation environment. This approximation may cause profound experimental bias in processes such as biologic repair of radiation damage, which are known to have strong temporal dependencies. It is possible that this experimental bias leads to an over-prediction of risks of radiation effects that have not been observed in the astronaut cohort. None of the primary health risks presumably attributed to space radiation exposure, such as radiation carcinogenesis, cardiovascular disease, cognitive deficits, etc., have been observed in astronaut or cosmonaut crews. This fundamentally and profoundly limits our understanding of the effects of GCR on humans and limits the development of effective radiation countermeasures.