Monte Carlo modeling of converging small-field contrast-enhanced radiotherapy of prostate

Radiation therapy using a kilovoltage X-ray source to irradiate a target previously loaded with a radiological contrast agent, contrast-enhanced radiotherapy (CERT), has been shown both theoretically and in a preliminary experimental study to represent a potential alternative to high-energy treatments. It has also been shown, however, to produce an integral dose that can be up to twice that resulting from a conventional megavoltage treatment. In this work, using a realistic patient model and Monte Carlo simulation, a CERT prostate treatment plan is designed that makes use of a plurality of small circular beams aimed at the target in such a way as to minimize the radiological trajectory to the target volume. Gold nanoparticles are assumed to be the contrast agent. Two cases are examined, one with a concentration level in the target of 10 mg-Au per gram of tissue and the second with a concentration of 3 mg-Au per gram of tissue in the target. A background concentration of 1 mg of contrast agent per gram of tissue was assumed everywhere else in both cases. The Cimmino feasibility algorithm was then used to find each beam weight in order to obtain the prescribed target dose, set at 72 Gy to 100% of the tumor volume. It is shown that the approach using the small circular fields, a radiosurgery treatment, produces treatment plans with excellent absorbed dose distributions while at the same time it reduces by up to 60% the non-tumor integral dose imparted to the irradiated subject. A brief discussion on the technology necessary to clinically implement this treatment modality is also presented.     

A GATE/Geant4 beam model for the MedAustron non-isocentric proton treatment plans quality assurance

PurposeTo present a reference Monte Carlo (MC) beam model developed in GATE/Geant4 for the MedAustron fixed beam line. The proposed model includes an absolute dose calibration in Dose-Area-Product (DAP) and it has been validated within clinical tolerances for non-isocentric treatments as routinely performed at MedAustron.Material and MethodsThe proton beam model was parametrized at the nozzle entrance considering optic and energy properties of the pencil beam. The calibration in terms of absorbed dose to water was performed exploiting the relationship between number of particles and DAP by mean of a recent formalism. Typical longitudinal dose distribution parameters (range, distal penumbra and modulation) and transverse dose distribution parameters (spot sizes, field sizes and lateral penumbra) were evaluated. The model was validated in water, considering regular-shaped dose distribution as well as clinical plans delivered in non-isocentric conditions.ResultsSimulated parameters agree with measurements within the clinical requirements at different air gaps. The agreement of distal and longitudinal dose distribution parameters is mostly better than 1 mm. The dose difference in reference conditions and for 3D dose delivery in water is within 0.5% and 1.2%, respectively. Clinical plans were reproduced within 3%.ConclusionA full nozzle beam model for active scanning proton pencil beam is described using GATE/Geant4. Absolute dose calibration based on DAP formalism was implemented. The beam model is fully validated in water over a wide range of clinical scenarios and will be inserted as a reference tool for research and for independent dose calculation in the clinical routine.     

Objective function based ranking method for selection of optimal beam angles in IMRT

We propose a novel method for the selection of optimal beam angles in Intensity Modulated Radiation Therapy (IMRT). The proposed approach uses an objective function based metric called “target-to-critical organ objective function ratio” to find out the optimal gantry angles. The beams are ranked based on this metric and are accordingly chosen for IMRT optimization. We have used the Pinnacle TPS (Philips Medical System V 16.2) for performing the IMRT optimization. In order to validate our approach, we have applied it in four clinical cases: Head and Neck, Lung, Abdomen and Prostate. Basically, for all clinical cases, two set of plans were created with same clinical objectives, namely Equal angle plan (EA Plan) and Suitable angle Plan (SA Plan). In the EA plans, the beam angles were placed in an equiangular manner starting from the gantry angle of 0°. In the corresponding SA plans, the beam angles were decided using the guidance provided by the algorithm. The reduction in OAR mean dose and max dose obtained in SA plans is about 3 to 16% and 3 to 15% respectively depending upon the treatment site while obtaining equal target coverage as compared to their EA counterparts. It takes approximately 15–25 min to find the optimal beam angles. The results obtained from the clinical cases indicate that the plan quality is considerably improved when the beam angles are optimized using the proposed method.     

Optimization of treatment planning for hypoxic tumours and re-modulation of radiation intensity in heavy-ion radiotherapy

AimThe purpose of this study is to optimize treatment planning in carbon ion radiotherapy, taking into account the effect of tumour hypoxia.BackgroundIn conventional hadron therapy, the goal is to create a homogenous dose in the tumour area and, thus, achieve a uniform cell survival level. Since the induction of a specific damage to cells is directly influenced by the level of hypoxia in the tissue, the varying oxygen pressure in the different regions of hypoxic tumours would disrupt the uniformity of the cell survival level.Materials and methodsUsing the Geant4 Monte Carlo Code, the physical dose profile and dose-averaged linear energy transfer were calculated in the tumour. Then, the oxygen enhancement ratio in different areas of the tumour were compared with different pressures.ResultsModulations of radiation intensities as well as energies of ion beams were calculated, both considering and disregarding the effect of hypoxia, and the required dose profiles were compared with each other. Cell survival levels were also compared between the two methods. An equation was obtained for re-modulating the beams in the presence of hypoxia, and radiation weighting factors were extracted for the beam intensities.ConclusionThe results show that taking the effect of hypoxia into account would cause the reduction of average doses delivered to the tumour tissues up to 1.54 times. In this regard, the required dose is reduced by 1.63 times in the healthy tissues before the tumour. This will result in an effective protection of healthy tissues around the tumour.     

An MCNP-based model for the evaluation of the photoneutron dose in high energy medical electron accelerators

The development of a computational model for the treatment head of a medical electron accelerator (Elekta/Philips SL-18) by the Monte Carlo code mcnp-4C2 is discussed. The model includes the major components of the accelerator head and a pmma phantom representing the patient body. Calculations were performed for a 14 MeV electron beam impinging on the accelerator target and a 10 cm×10 cm beam area at the isocentre. The model was used in order to predict the neutron ambient dose equivalent at the isocentre level and moreover the neutron absorbed dose distribution within the phantom. Calculations were validated against experimental measurements performed by gold foil activation detectors. The results of this study indicated that the equivalent dose at tissues or organs adjacent to the treatment field due to photoneutrons could be up to 10% of the total peripheral dose, for the specific accelerator characteristics examined. Therefore, photoneutrons should be taken into account when accurate dose calculations are required to sensitive tissues that are adjacent to the therapeutic X-ray beam. The method described can be extended to other accelerators and collimation configurations as well, upon specification of treatment head component dimensions, composition and nominal accelerating potential.     

Individually selected teletherapy technique for accelerated partial breast irradiation

BackgroundThe aim of the study was to individualize accelerated partial breast irradiation based on optimal dose distribution, protect risk organ and predict most advantageous technique.Materials and methods138 breast cancer patients receiving postoperative APBI were enrolled. APBI plans were generated using 3D-conformal (3D-CRT), sliding window intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT). In the case of superficial tumours, additional plans were developed by adding electron beam. To planning target volume (PTV) 37.5 Gy/10 fractions, 1 fraction/day was prescribed. A novel plan quality index (PQI) served as the basis for comparisons.ResultsIMRT was the most advantageous technique regarding homogeneity. VMAT provided best conformity, 3D-CR T — the lowest lung and heart exposure. PQI was the best in 45 (32.61%) VMAT, 13 (9.42%) IMRT, 9 (6.52%) 3D-CRT plans. In 71 cases (51.45%) no difference was detected. In patients with large PTV, 3D-CRT was the most favourable. Additional electron beam improved PQI of 3D-CRT plans but had no meaningful effect on IMRT or VMAT. IMRT was superior to VMAT if the tumour was superficial (p < 0.001), situated in the medial (p = 0.032) or upper quadrant (p = 0.046).ConclusionsIn half of all cases, individually selected teletherapy techniques provide superior results over others; relevance of a certain technique may be predicted by volume and PTV localization.     

A modular dose delivery system for treating moving targets with scanned ion beams: Performance and safety characteristics,and preliminary tests

PurposeThe purpose of this study was to develop a modular dose-delivery system (DDS) for scanned-ion radiotherapy that mitigates against organ motion artifacts by synchronizing the motion of the beam with that of the moving anatomy.MethodsWe integrated a new motion synchronization system and an existing DDS into two centers. The modular approach to integration utilized an adaptive layer of software and hardware interfaces. The method of synchronization comprised three major tasks, namely, the creation of 3D treatment plans (each representing one phase of respiratory motion and together comprising a 4D plan), monitoring anatomic motion during treatment, and synchronization of the beam to anatomic motion. The synchronization was accomplished in real time by repeatedly selecting and delivering a 3D plan, i.e., the one that most closely corresponded to the current anatomic state, until all plans were delivered. The performance characteristics of the motion mitigation system were tested by delivering 4D treatment plans to a moving phantom and comparing planned and measured dose distributions. Dosimetric performance was considered acceptable when the gamma-index pass rate was >90%, homogeneity-index value was >95%, and conformity-index value was >60%. Selected safety characteristics were tested by introducing errors during treatment and testing DDS response.ResultsAcceptable dosimetric performance and safety characteristics were observed for all treatment plans.ConclusionsWe demonstrated, for the first time, that a modular prototype system, synchronizing scanned ion beams with moving targets can deliver conformal, motion-compensated dose distributions. The prototype system was implemented and characterized at GSI and CNAO.     

The effect of beam interruption during VMAT delivery on the delivered dose distribution

PurposeThe aim of this study is to investigate the effect of beam interruptions during delivery of volumetric modulated arc therapy (VMAT) on delivered dose distributions.MethodsTen prostate and ten head and neck (H&N) VMAT plans were retrospectively selected. Each VMAT plan was delivered using Trilogy™ without beam interruption, and with 4 and 8 intentional beam interruptions per a single arc. Two-dimensional global and local gamma evaluations with a diode array were performed with gamma criteria of 3%/3 mm, 2%/2 mm, 1%/2 mm and 2%/1 mm for each VMAT plan with and without beam interruptions. The VMAT plans were reconstructed with log files recorded during delivery and the dose-volumetric parameters were calculated for each reconstructed plan. The differences among dose-volumetric parameters due to the beam interruptions were calculated.ResultsThe changes in global gamma passing rates with various gamma criteria were less than 1.6% on average, while the changes in local gamma passing rates were less than 5.3% on average. The dose-volumetric parameter changes for the target volumes of prostate and H&N VMAT plans due to beam interruptions were less than 0.72% and 1.5% on average, respectively.ConclusionThe delivered dose distributions with up to 8 beam interruptions per an arc were clinically acceptable, showing minimal changes in both gamma passing rates and dose-volumetric parameters.     

In situ biological dose mapping estimates the radiation burden delivered to 'spared' tissue between synchrotron X-ray microbeam radiotherapy tracks

Microbeam radiation therapy (MRT) using high doses of synchrotron X-rays can destroy tumours in animal models whilst causing little damage to normal tissues. Determining the spatial distribution of radiation doses delivered during MRT at a microscopic scale is a major challenge. Film and semiconductor dosimetry as well as Monte Carlo methods struggle to provide accurate estimates of dose profiles and peak-to-valley dose ratios at the position of the targeted and traversed tissues whose biological responses determine treatment outcome. The purpose of this study was to utilise γ-H2AX immunostaining as a biodosimetric tool that enables in situ biological dose mapping within an irradiated tissue to provide direct biological evidence for the scale of the radiation burden to 'spared' tissue regions between MRT tracks. Γ-H2AX analysis allowed microbeams to be traced and DNA damage foci to be quantified in valleys between beams following MRT treatment of fibroblast cultures and murine skin where foci yields per unit dose were approximately five-fold lower than in fibroblast cultures. Foci levels in cells located in valleys were compared with calibration curves using known broadbeam synchrotron X-ray doses to generate spatial dose profiles and calculate peak-to-valley dose ratios of 30-40 for cell cultures and approximately 60 for murine skin, consistent with the range obtained with conventional dosimetry methods. This biological dose mapping approach could find several applications both in optimising MRT or other radiotherapeutic treatments and in estimating localised doses following accidental radiation exposure using skin punch biopsies.     

Measuring dose from radiotherapy treatments in the vicinity of a cardiac pacemaker

This study investigated the dose absorbed by tissues surrounding artificial cardiac pacemakers during external beam radiotherapy procedures. The usefulness of out-of-field reference data, treatment planning systems, and skin dose measurements to estimate the dose in the vicinity of a pacemaker was also examined. Measurements were performed by installing a pacemaker onto an anthropomorphic phantom, and using radiochromic film and optically stimulated luminescence dosimeters to measure the dose in the vicinity of the device during the delivery of square fields and clinical treatment plans. It was found that the dose delivered in the vicinity of the cardiac device was unevenly distributed both laterally and anteroposteriorly. As the device was moved distally from the square field, the dose dropped exponentially, in line with out-of-field reference data in the literature. Treatment planning systems were found to substantially underestimate the dose for volumetric modulated arc therapy, helical tomotherapy, and 3D conformal treatments. The skin dose was observed to be either greater or lesser than the dose received at the depth of the device, depending on the treatment site, and so care should be if skin dose measurements are to be used to estimate the dose to a pacemaker. Square field reference data may be used as an upper estimate of absorbed dose per monitor unit in the vicinity of a cardiac device for complex treatments involving multiple gantry angles.     

A dosimetric comparison of IMRT versus helical tomotherapy for brain tumors

Background and purposeHelical tomotherapy (HT) can deliver highly conformal, uniform doses to the target volume. However, HT can only be delivered in a coplanar mode.The purpose of this study was to perform a dosimetric comparison of HT versus coplanar (cIMRT) and non-coplanar (n-cIMRT) beam arrangements on a conventional linear accelerator in a diverse group of brain tumors.Materials and methodsA total of 45 treatment plans were calculated retrospectively for 15 cases. For each case, 3 different delivery techniques (n-cIMRT, cIMRT and HT) were used. The treatment plans were compared using the parameters of the target coverage (conformity index; CI) and homogeneity (HI) for the planning target volume (PTV) and the maximum and mean doses for organs at risk (OARs).ResultsMedian HI and CI were the best for HT plans and the worst for cIMRT. The largest reduction of maximum dose for lenses and mean dose for both eyes was achieved for n-cIMRT plans. Mean dose for chiasm and the ipsilateral optic nerve were the lowest for HT. The contralateral optic nerve was most spared with n-cIMRT. For D_1% in the brain stem, there was no significant difference between HT and the IMRT plans.ConclusionsBoth HT and n-cIMRT are capable of producing conformal and homogeneous treatment plans with a good sparing of OARs. However, due to the non-coplanar capabilities of IMRT, n-cIMRT led to a superior dose reduction to the lenses.     

Dose distribution comparison in volumetric-modulated arc therapy plans for head and neck cancers with and without an external body contour extended technique

AimThis study compared volumetric-modulated arc therapy (VMAT) plans for head and neck cancers with and without an external body contour extended technique (EBCT).BackgroundDose calculation algorisms for VMAT have limitations in the buildup region.Materials and methodsThree VMAT plans were enrolled, with one case having a metal artifact from an artificial tooth. The proper dose was calculated using Eclipse version 11.0. The body contours were extended 2 cm outward from the skin surface in three-dimensional space, and the dose was recalculated with an anisotropic analytical algorithm (AAA) and Acuros XB (AXB). Monitor units (MUs) were set, and the dose distributions in the planning target volume (PTV), clinical target volume, and organ at risk (OAR) and conformity index (CI) with and without an EBCT were compared. The influence of a metal artifact outside of the thermoplastic head mask was also compared.ResultsThe coverage of PTV by the 95% dose line near the patient’s skin was increased drastically by using an EBCT. Plan renormalization had a negligible impact on MUs and doses delivered to OARs. CI of PTV with a 6-MV photon beam was closer to 1 than that with a 10-MV photon beam when both AAA and AXB were used in all cases. Metal artifacts outside the head mask had no effect on dose distribution.ConclusionsAn EBCT is needed to estimate the proper dose at object volumes near the patient’s skin and can improve the accuracy of the calculated dose at target volumes.     

Feasibility of intensity-modulated radiotherapy to treat gastric cancer

AimTo present a proposed gastric cancer intensity-modulated radiotherapy (IMRT) treatment planning protocol for an institution that have not introduced volumetric modulated arc therapy in clinical practice. A secondary aim was to determine the impact of 2DkV set-up corrections on target coverage and organ at risk (OAR).Methods and MaterialsTwenty consecutive patients were treated with a specially-designed non-coplanar 7-field IMRT technique. The isocenter-shift method was used to estimate the impact of 2DkV-based set-up corrections on the original base plan (BP) coverage. An alternative plan was simulated (SP) by taking into account isocenter shifts. The SP and BP were compared using dose-volume histogram (DVH) plots calculated for the internal target volume (ITV) and OARs.ResultsBoth plans delivered a similar mean dose to the ITV (100.32 vs. 100.40%), with no significant differences between the plans in internal target coverage (5.37 vs. 4.96%). Similarly, no significant differences were observed between the maximal dose to the spinal cord (67.70 and 67.09%, respectively) and volume received 50% of the prescribed dose of: the liver (62.11 vs. 59.84%), the right (17.62 vs. 18.58%) and left kidney (29.40 vs. 30.48%). Set-up margins (SM) were computed as 7.80 mm, 10.17 mm and 6.71 mm in the left-right, cranio-caudal and anterior-posterior directions, respectively.ConclusionPresented IMRT protocol (OAR dose constraints with selected SM verified by 2DkV verification) for stomach treatment provided optimal dose distribution for the target and the critical organs. Comparison of DVH for the base and the modified plan (which considered set-up uncertainties) showed no significant differences.     

Development of a four-dimensional Monte Carlo dose calculation system for real-time tumor-tracking irradiation with a gimbaled X-ray head

PurposeTo develop a four-dimensional (4D) dose calculation system for real-time tumor tracking (RTTT) irradiation by the Vero4DRT.MethodsFirst, a 6-MV photon beam delivered by the Vero4DRT was simulated using EGSnrc. A moving phantom position was directly measured by a laser displacement gauge. The pan and tilt angles, monitor units, and the indexing time indicating the phantom position were also extracted from a log file. Next, phase space data at any angle were created from both the log file and particle data under the dynamic multileaf collimator. Irradiation both with and without RTTT, with the phantom moving, were simulated using several treatment field sizes. Each was compared with the corresponding measurement using films. Finally, dose calculation for each computed tomography dataset of 10 respiratory phases with the X-ray head rotated was performed to simulate the RTTT irradiation (4D plan) for lung, liver, and pancreatic cancer patients. Dose-volume histograms of the 4D plan were compared with those calculated on the single reference respiratory phase without the gimbal rotation [three-dimensional (3D) plan].ResultsDifferences between the simulated and measured doses were less than 3% for RTTT irradiation in most areas, except the high-dose gradient. For clinical cases, the target coverage in 4D plans was almost identical to that of the 3D plans. However, the doses to organs at risk in the 4D plans varied at intermediate- and low-dose levels.ConclusionsOur proposed system has acceptable accuracy for RTTT irradiation in the Vero4DRT and is capable of simulating clinical RTTT plans.     

Integral dose: Comparison between four techniques for prostate radiotherapy

Aim

Comparisons of integral dose delivered to the treatment planning volume and to the whole patient body during stereotactic, helical and intensity modulated radiotherapy of prostate.

Background

Multifield techniques produce large volumes of low dose inside the patient body. Delivered dose could be the result of the cytotoxic injuries of the cells even away from the treatment field. We calculated the total dose absorbed in the patient body for four radiotherapy techniques to investigate whether some methods have a potential to reduce the exposure to the patient.

Materials and methods

We analyzed CyberKnife plans for 10 patients with localized prostate cancer. Five alternative plans for each patient were calculated with the VMAT, IMRT and TomoTherapy techniques. Alternative dose distributions were calculated to achieve the same coverage for PTV. Integral Dose formula was used to calculate the total dose delivered to the PTV and whole patient body.

Results

Analysis showed that the same amount of dose was deposited to the treated volume despite different methods of treatment delivery. The mean values of total dose delivered to the whole patient body differed significantly for each treatment technique. The highest integral dose in the patient''s body was at the TomoTherapy and CyberKnife treatment session. VMAT was characterized by the lowest integral dose deposited in the patient body.

Conclusions

The highest total dose absorbed in normal tissue was observed with the use of a robotic radiosurgery system and TomoTherapy. These results demonstrate that the exposure of healthy tissue is a dosimetric factor which differentiates the dose delivery methods.     

On the interplay effect for moving targets treated with the CyberKnife static tracking system

PurposeTo assess the interplay effect amplitude between different planned MU distributions and respiratory patterns in the CyberKnife system when treating moving targets with static tracking technique.MethodsSmall- and Large-Respiratory Motions (SRM and LRM) differing in amplitude and frequency were simulated in a semi-anthropomorphic dynamic thorax phantom. The interplay effect was evaluated for both respiration motions in terms of GTV coverage and conformity for three plans designed with an increasing range of MU per beam (small, medium and large). Each plan was delivered three times changing the initial beam-on phase to assess the inter-fraction variation. Dose distributions were measured using radiochromic films placed in the GTV axial and sagittal planes.ResultsGenerally, SRM plans gave higher GTV coverage and were less dependent on beam-on phases than LRM plans. For SRM (LRM) plans, the GTV coverage ranged from 95.2% to 99.7% (85.9% to 99.8%). Maximum GTV coverage was found for large MU plans in SRM and for small MU plans in LRM. Minimum GTV coverage was found for medium MU plans for both SRM and LRM. For SRM plans, dose conformity decreased with increasing MU range while the variation was reduced for LRM plans. Large MU plans reduced the inter-fraction variation for SRM and LRM.ConclusionsWe confirmed the interplay effect between target motion and beam irradiation time for CyberKnife static tracking. Plans with large MU per beam improved the GTV coverage for small motion amplitude and the inter-fraction dose variation for large motion amplitude.     

Cardiac Exposure in the Dynamic Conformal Arc Therapy,Intensity-Modulated Radiotherapy and Volumetric Modulated Arc Therapy of Lung Cancer

Purpose

To retrospectively evaluate the cardiac exposure in three cohorts of lung cancer patients treated with dynamic conformal arc therapy (DCAT), intensity-modulated radiotherapy (IMRT), or volumetric modulated arc therapy (VMAT) at our institution in the past seven years.

Methods and Materials

A total of 140 lung cancer patients were included in this institutional review board approved study: 25 treated with DCAT, 70 with IMRT and 45 with VMAT. All plans were generated in a same commercial treatment planning system and have been clinically accepted and delivered. The dose distribution to the heart and the effects of tumor laterality, the irradiated heart volume and the beam-to-heart distance on the cardiac exposure were investigated.

Results

The mean dose to the heart among all 140 plans was 4.5 Gy. Specifically, the heart received on average 2.3, 5.2 and 4.6 Gy in the DCAT, IMRT and VMAT plans, respectively. The mean heart doses for the left and right lung tumors were 4.1 and 4.8 Gy, respectively. No patients died with evidence of cardiac disease. Three patients (2%) with preexisting cardiac condition developed cardiac disease after treatment. Furthermore, the cardiac exposure was found to increase linearly with the irradiated heart volume while decreasing exponentially with the beam-to-heart distance.

Conclusions

Compared to old technologies for lung cancer treatment, modern radiotherapy treatment modalities demonstrated better heart sparing. But the heart dose in lung cancer radiotherapy is still higher than that in the radiotherapy of breast cancer and Hodgkin’s disease where cardiac complications have been extensively studied. With strong correlations of mean heart dose with beam-to-heart distance and irradiated heart volume, cautions should be exercised to avoid long-term cardiac toxicity in the lung cancer patients undergoing radiotherapy.     

Using electron beam radiation to simulate the dose distribution for whole body solar particle event proton exposure

As a part of the near solar system exploration program, astronauts may receive significant total body proton radiation exposures during a solar particle event (SPE). In the Center for Acute Radiation Research (CARR), symptoms of the acute radiation sickness syndrome induced by conventional radiation are being compared to those induced by SPE-like proton radiation, to determine the relative biological effectiveness (RBE) of SPE protons. In an SPE, the astronaut’s whole body will be exposed to radiation consisting mainly of protons with energies below 50 MeV. In addition to providing for a potentially higher RBE than conventional radiation, the energy distribution for an SPE will produce a relatively inhomogeneous total body dose distribution, with a significantly higher dose delivered to the skin and subcutaneous tissues than to the internal organs. These factors make it difficult to use a ⁶⁰Co standard for RBE comparisons in our experiments. Here, the novel concept of using megavoltage electron beam radiation to more accurately reproduce both the total dose and the dose distribution of SPE protons and make meaningful RBE comparisons between protons and conventional radiation is described. In these studies, Monte Carlo simulation was used to determine the dose distribution of electron beam radiation in small mammals such as mice and ferrets as well as large mammals such as pigs. These studies will help to better define the topography of the time-dose-fractionation versus biological response landscape for astronaut exposure to an SPE.