Proton Radiation Fields Research Articles

Therapeutic Efficacy of Variable Biological Effectiveness of Proton Therapy in U-CH2 and MUG-Chor1 Human Chordoma Cell Death.

Simple SummaryChordoma is a rare, slow-growing cancer of the spinal cord. Photon radiation therapy and surgery are the standard of care for chordoma. Proton radiation therapy has become an increasingly common treatment in comparison to photon radiation therapy due to the ability to reduce off-target radiation dose. However, there is still an increased risk of toxicity to the surrounding critical structures that lead to poor treatment outcomes. Moreover, the biologic effectiveness of protons to sterilize chordoma cells remains uncertain and likely varies according to the proton energy spectrum throughout the proton field. We aim to investigate the tumoricidal properties of proton radiation therapy at the middle and end of the proton radiation field and elucidate variations in the relative biological effectiveness for chordoma cells. Our study helps quantify the therapeutic value of treating chordoma near the end of the proton field, where linear energy transfer is relatively high.Background: Chordoma is a cancer of spinal cord, skull base, and sacral area. Currently, the standard of care to treat chordoma is resection followed by radiation therapy. Since, chordoma is present in the spinal cord and these are very sensitive structures and often complete removal by surgery is not possible. As a result, chordoma has a high chance of recurrence and developing resistance to radiation therapy. In addition, treatment of chordoma by conventional radiation therapy can also damage normal tissues surrounding chordoma. Thus, current therapeutic options to treat chordoma are insufficient and novel therapies are desperately needed to treat locally advanced and metastatic chordoma. (2) Methods: In the present investigation, human chordoma cell lines of sacral origin MUG-Chor1 and U-CH2 were cultured and irradiated with Proton Beam Radiation using the clinical superconducting cyclotron and pencil-beam (active) scanning at Middle and End of the Spread-Out Bragg Peak (SOBP). Proton radiation was given at the following doses: Mug-Chor1 at 0, 1, 2, 4, and 8 Gy and U-CH2 at 0, 4, 8, 12, and 16 Gy. These doses were selected based on a pilot study in our lab and attempted to produce approximate survival fractions in the range of 1, 0.9, 0.5, 0.1, and 0.01, respectively, chosen for linear quadratic model fitting of the dose response. (3) Results: In this study, we investigated relative biological effectiveness (RBE) of proton radiation at the end of Spread Out Bragg Peak assuming that the reference radiation is a proton radiation in the middle of the SOBP. We observed differences in the survival of both Human chordoma cell lines, U-CH2 and MUG-Chor1. The data showed that there was a significantly higher cell death at the end of the Bragg peak as compared to middle of the Bragg peak. Based on the linear quadratic (LQ) fit for cell survival we calculated the RBE between M-SOBP and E-SOBP at 95% CI level and it was observed that RBE was higher than 1 at E-SOBP and caused significantly higher cell killing. Proton field at E-SOBP caused complex DNA damage in comparison to M-EOBP and the genes such as DNA topoisomerase 1, GTSE1, RAD51B were downregulated in E-SOBP treated cells. Thus, we conclude that there seems to be substantial variation in RBE (1.3–1.7) at the E-SOBP compared with the M-SOBP.

Modelling of protons spectra encountered in space using medical accelerator and its microdosimetric characterization

Radiation environments in space are mainly composed of protons coming from the Galactic Cosmic Rays (GCRs) pervading the universe, the Solar Particle Events (SPEs) resulting from solar flares and coronal mass ejections, and the two Van Allen Belts surrounding the Earth due to the presence of the geomagnetic field trapping charged particles. Their wide spectra of energies up to hundreds of GeV imply diverse radiobiological effects to astronauts and radiation damage to electronics in the spacecraft. Even if lower in abundance, heavy ions such as He, C, O, Si, Fe are present in space and constitute an even bigger hazard due to their high penetrability and high linear energy transfer (LET). Most irradiation facilities available for research and testing worldwide provide usually only monoenergetic beams of high-energy protons or other heavier particles limiting studies of radiobiological effects and effects on electronics to a set of discrete energies.This paper introduces a procedure where a proton fluence spectra of interest for space radiation protection, previously generated by Monte Carlo simulations was delivered using a clinical proton therapy accelerator.Particularly, it reports the first results of modelling a proton radiation field in space in the energy range from 70 to 230 MeV during a single experimental session by programming a treatment planning system (TPS) to deliver required proton irradiation energies. Moreover, the angular distribution of the proton irradiation field has been varied to reproduce the isotropic exposure experienced by humans in space. The obtained proton radiation field was characterized using a 3D sensitive volume SOI microdosimeter developed by the Centre for Medical Radiation Physics (CMRP), University of Wollongong, Australia.

Orbit-Like Proton Radiation Sensitivity of CdTe Detectors: Evaluation of Mobility-Lifetime Products and Spectroscopic Properties

This article reports the proton radiation sensitivity of two 1.0-mm-thick EURORAD ohmic CdTe detectors, irradiated with a low energy proton beam generated in a positron emission tomography (PET) cyclotron facility. The CdTe crystals were exposed to a proton radiation field composed of energies of $\approx 13.8$ , $\approx 9.7$ , $\approx 5.7$ , and $\approx 3.3$ MeV, at an average flux of ~ $10^{8}$ protons cm−2s−1, a total fluence from $\approx 2.1 \times 10^{9}$ up to $\approx 4.5 \times 10^{10}$ protons cm−2, and an average dose from $\approx 5.9$ up to $\approx 130$ Gy, equivalent to the proton fluence accumulated in ~1 up to ~20 years in a low earth orbit (LEO). The impact of the proton radiation field was analyzed through its charge transport properties—the mobility-lifetime product for electrons, ( $\mu \tau $ ) e , and holes, ( $\mu \tau $ ) h ,—and spectroscopic properties—the energy resolution and the peak-to-valley ratio, for $\gamma $ -ray lines within 60–662 keV. The tested CdTe detectors, with ( $\mu \tau $ ) $_{e} \sim 5 \times 10^{-4}$ cm2V−1 and ( $\mu \tau $ ) $_{h} \sim 3\times \,\,10^{-5}$ cm2 V−1, showed good radiation hardness, with the measured upper-limit of ( $\mu \tau $ ) e and ( $\mu \tau $ ) h proton fluence (average dose) sensitivity of $\sim 2\times 10^{-15}$ cm2V−1/protons cm−2 ( $\sim 7 \times 10^{-7}$ cm2 V−1/Gy) and $\sim 3 \times 10^{-16}$ cm2 V−1/protons cm−2 ( $\sim 1 \times 10^{-7}$ cm2 V−1/Gy), respectively. Up to $\approx 130$ Gy, no significant degradation of the energy resolution and the peak-to-valley ratio was observed.

Characterization of proton pencil beam scanning and passive beam using a high spatial resolution solid-state microdosimeter.

This work aims to characterize a proton pencil beam scanning (PBS) and passive double scattering (DS) systems as well as to measure parameters relevant to the relative biological effectiveness (RBE) of the beam using a silicon on insulator (SOI) microdosimeter with well-defined 3D sensitive volumes (SV). The dose equivalent downstream and laterally outside of a clinical PBS treatment field was assessed and compared to that of a DS beam. A novel silicon microdosimeter with well-defined 3D SVs was used in this study. It was connected to low noise electronics, allowing for detection of lineal energies as low as 0.15keV/μm. The microdosimeter was placed at various depths in a water phantom along the central axis of the proton beam, and at the distal part of the spread-out Bragg peak (SOBP) in 0.5mm increments. The RBE values of the pristine Bragg peak (BP) and SOBP were derived using the measured microdosimetric lineal energy spectra as inputs to the modified microdosimetric kinetic model (MKM). Geant4 simulations were performed in order to verify the calculated depth-dose distribution from the treatment planning system (TPS) and to compare the simulated dose-mean lineal energy to the experimental results. For a 131MeV PBS spot (124.6mm R90 range in water), the measured dose-mean lineal energy yD¯ increased from 2keV/μm at the entrance to 8keV/μm in the BP, with a maximum value of 10keV/μm at the distal edge. The derived RBE distribution for the PBS beam slowly increased from 0.97±0.14 at the entrance to 1.04±0.09 proximal to the BP, then to 1.1±0.08 in the BP, and steeply rose to 1.57±0.19 at the distal part of the BP. The RBE distribution for the DS SOBP beam was approximately 0.96±0.16 to 1.01±0.16 at shallow depths, and 1.01±0.16 to 1.28±0.17 within the SOBP. The RBE significantly increased from 1.29±0.17 to 1.43±0.18 at the distal edge of the SOBP. The SOI microdosimeter with its well-defined 3D SV has applicability in characterizing proton radiation fields and can measure relevant physical parameters to model the RBE with submillimeter spatial resolution. It has been shown that for a physical dose of 1.82Gy at the BP, the derived RBE based on the MKM model increased from 1.14 to 1.6 in the BP and its distal part. Good agreement was observed between the experimental and simulation results, confirming the potential application of SOI microdosimeter with 3D SV for quality assurance in proton therapy.

Abstract ID: 108 Study on conformal proton therapy using multileaf collimated beams without tumour-specific range compensators via flat dose-layer stacking

Purpose In traditional conformal proton therapy (CPT), proximal dose conformity of tumours is sacrificed for achieving distal dose conformity due to tumour-specific range compensators. This study investigated whether CPT can be realized without tumour-specific range compensators using multileaf-collimated proton beams, and whether range-compensator-free CPT (RCF-CPT) can improve the proximal dose conformity without sacrificing distal conformity. Methods First, geometric configurations of a virtual multileaf-collimator (MLC) and three tumour cases (brain, liver, and prostate) were adopted during Geant4 geometry setup. Second, conformal proton radiation fields were generated for tumour CT slices based on the predesigned MLC using Geant4. Third, flat dose-layers corresponding to these tumour slices were produced using dose patching method in which MLC-collimated subbeams can be utilized to modulate the dose uniformity of these flat dose-layers. Forth, these flat dose-layers were stacked and integrated throughout the tumours for obtaining sufficient tumour dose coverages. Furthermore, dosimetric comparisons between the RCF-CPT and traditional CPT were performed to detail the dosimetric advantages of RCF-CPT. Results For the three tumour cases, the tumours can be sufficiently covered by 95% relative doses through RCF-CPT, and the maximum tumour doses were smaller than 110% relative doses. Approximately, the proximal doses of RCF-CPT were controlled to 60% relative doses, and 95% dose lines fit with the tumour profiles at proximal tumour regions. Conclusions Compared with traditional CPT, RCF-CPT can highly enhance the proximal dose conformity of tumours without sacrificing distal conformity. Moreover, the workflows of CPT can be largely simplified based on the range-compensator-free characteristic of RCF-CPT.

A phenomenological relative biological effectiveness approach for proton therapy based on an improved description of the mixed radiation field

Proton therapy treatment planning systems (TPSs) are based on the assumption of a constant relative biological effectiveness (RBE) of 1.1 without taking into account the found in vitro experimental variations of the RBE as a function of tissue type, linear energy transfer (LET) and dose. The phenomenological RBE models available in literature are based on the dose-averaged LET (LETD) as an indicator of the physical properties of the proton radiation field. The LETD values are typically calculated taking into account primary and secondary protons, neglecting the biological effect of heavier secondaries. In this work, we have introduced a phenomenological RBE approach which considers the biological effect of primary protons, and of secondary protons, deuterons, tritons (Z = 1) and He fragments (3He and 4He, Z = 2). The calculation framework, coupled with a Monte Carlo (MC) code, has been successfully benchmarked against clonogenic in vitro data measured in this work for two cell lines and then applied to determine biological quantities for spread-out Bragg peaks and a prostate and a head case. The introduced RBE formalism, which depends on the mixed radiation field, the dose and the ratio of the linear–quadratic model parameters for the reference radiation , predicts, when integrated in an MC code, higher RBE values in comparison to LETD-based parameterizations. This effect is particular enhanced in the entrance channel of the proton field and for low tissues. For the prostate and the head case, we found higher RBE-weighted dose values up to about 5% in the entrance channel when including or neglecting the Z = 2 secondaries in the RBE calculation. TPSs able to proper account for the mixed radiation field in proton therapy are thus recommended for an accurate determination of the RBE in the whole treatment field.

Characterizing a proton beam scanning system for Monte Carlo dose calculation in patients

The presented work has two goals. First, to demonstrate the feasibility of accurately characterizing a proton radiation field at treatment head exit for Monte Carlo dose calculation of active scanning patient treatments. Second, to show that this characterization can be done based on measured depth dose curves and spot size alone, without consideration of the exact treatment head delivery system. This is demonstrated through calibration of a Monte Carlo code to the specific beam lines of two institutions, Massachusetts General Hospital (MGH) and Paul Scherrer Institute (PSI).Comparison of simulations modeling the full treatment head at MGH to ones employing a parameterized phase space of protons at treatment head exit reveals the adequacy of the method for patient simulations. The secondary particle production in the treatment head is typically below 0.2% of primary fluence, except for low-energy electrons (<0.6 MeV for 230 MeV protons), whose contribution to skin dose is negligible. However, there is significant difference between the two methods in the low-dose penumbra, making full treatment head simulations necessary to study out-of-field effects such as secondary cancer induction.To calibrate the Monte Carlo code to measurements in a water phantom, we use an analytical Bragg peak model to extract the range-dependent energy spread at the two institutions, as this quantity is usually not available through measurements. Comparison of the measured with the simulated depth dose curves demonstrates agreement within 0.5 mm over the entire energy range. Subsequently, we simulate three patient treatments with varying anatomical complexity (liver, head and neck and lung) to give an example how this approach can be employed to investigate site-specific discrepancies between treatment planning system and Monte Carlo simulations.

Space Radiation Research Unit, International Open Laboratory in NIRS

The radiation environment encountered by astronauts during spaceflight is far more complex than any radiation field existed on Earth. Space crew living and working in the International Space Station (ISS) are exposed to a mixed radiation field comprises primary high-energy cosmic rays, including energetic protons and heavy ions, and to secondary radiations, including energetic neutrons, produced when the primary radiation interacts with the mass of the space station and its contents. The doses of ionizing radiation received by astronauts and cosmonauts aboard the ISS are many times greater than those received by radiation workers on the ground. Exposure to ionizing radiation in space includes high LET events than can produce significant biological damage in human cells and tissues, and thus represents an important risk to space crew health and safety.The Space Radiation Research Unit at the National Institute of Radiological Sciences (NIRS) includes both physicists and radiation biologists and there is extensive collaboration between these two groups. This provides us with the expertise needed to investigate the effects of space crew exposure to the highly complex, mixed radiation environment encountered in space. In addition, NIRS is home to a heavy ion accelerator, HIMAC and the Medical Cyclotron that can be used to simulate various components of the space radiation environment. Recently, we have developed a medium energy proton radiation field using the NIRS Medical Cyclotron. [How about a sentence or two on the significance of this proton facilities.] In addition, NIRS has also developed a high precision tool, the Single Particle Irradiation System to Cell (SPICE) microbeam facility, for use in investigating various radiobiological endpoints, including the bystander effect and the adaptive response of various cell types, Caenorhabditis elegans and in Medaka fish. Some of these research activities are described in these proceedings [1, 2].The Space Radiation Research Unit at NIRS has extensive international collaborations with researchers in China, Germany, Russia, USA, Sweden, Austria and other countries. In particular, collaborations with our Russian colleagues has led to opportunities to expose our dosimeters aboard the ISS and to numerous other experiments in the frame of the IOL, as described more fully elsewhere in these proceedings. We believe that the framework of the IOL is very powerful and productive and we plan to continue our collaborative research with our international colleagues.

SU‐FF‐T‐332: The Effect of Metal Implants On Proton Transport

Purpose: Proton therapy treatment planning in the presence of high‐density metal implants has considerable uncertainty. This uncertainty arises from artifacts produced through the imaging process, uncertainty in the CT density of the implant itself and the effect which both of these have on the range of protons. Because of this uncertainty, beam directions which pass through such implants are avoided if possible. However, in some cases such beams are unavoidable in order to preserve normal tissue and treat the tumor volume effectively. The goal of this ongoing project is to investigate proton transport through high‐density implants and to determine the accuracy of treatment planning software in reproducing isodose distributions when such materials are present. Methods and Materials: We have constructed a phantom with titanium and medical grade stainless steel plates of 1–4 mm thickness embedded within polystyrene. The phantom has been CT‐scanned and then planned using the Odyssey treatment planning system (PerMedics Medical Systems), which is used in routine treatment planning at Loma Linda University Medical Center. The plan generated will be compared to physical dose measurements using ion chambers inserted into the polystyrene phantom. In addition, GEANT4 Monte Carlo simulations of the experimental setup will be completed using CT data as the basis for geometry and material definitions. Additional simulations will be performed with geometry defined based on manufacturers' specifications. Results: Treatment plans of the experimental setup provide an indication of the perturbation of the proton radiation field caused by the metallic implants and indicate areas where measurements and comparisons with GEANT4 should be completed. Conclusions: This study will provide useful data on the accuracy in treatment planning in the presence of metallic implants in proton therapy, and may indicate areas in which improvements to current treatment planning methods can be made.

SU‐FF‐T‐312: Dosimetry for Radiobiological Evaluation of the Active Beam Scanning System at Loma Linda University Medical Center

Purpose: Active beam scanning is a new and important innovation in proton therapy, potentially allowing for a more conformal proton treatment through dynamic manipulation of proton pencil beams. Active beam scanning thus requires accurate online dosimetry to track the proton pencil beam both in space and time, whilst at the same time monitoring dose delivered to a given point within the patient. Radiobiological validation of this new technology is equally important. Currently, with passive proton beam delivery a uniform RBE of 1.1 is assumed, and this has lead to satisfactory clinical results both in terms of tumor control and side effects. However, it is unclear whether this RBE value is also appropriate for active beam scanning treatments. Methods and Materials: To investigate this, researchers at Loma Linda University Medical Center are utilizing a multilayered system to evaluate radiobiological parameters at multiple positions within a water tank along the depth dose profile. The results obtained are being compared with identical experiments completed with Co‐60 photons and passively delivered protons. As a prerequisite for accurate and meaningful comparisons, precise dosimetry ensuring compatibility of dose rate, depth dose profile, dose uniformity and absolute dose have to be performed for all three radiation modalities. This presentation describes in detail the dosimetry methodology associated with the project, including film and ion chamber evaluation of the three radiation modalities. Results: Initial results indicate that the active beam scanning system provides proton radiation fields comparable to that utilizing passive beam delivery with a flatness and symmetry within 3% (TG45) at all positions along the Bragg peak. Further, dose rates experienced with this system are also comparable to that for passive beam delivery. Conclusions: This preclinical work will provide a unique opportunity to discuss both dosimetry‐ and radiobiology‐associated issues of automatic beam scanning in proton therapy.

Tissue Equivalence Correction in Silicon Microdosimetry for Protons Characteristic of the LEO Space Environment

The tissue equivalence of solid state silicon detectors in proton radiation fields was determined to improve the radiation protection applications of silicon detectors in aviation and space missions. The study was performed by means of Geant4 simulations. Results are presented showing that a simple c( ~ 0.56) of linear dimensions is adequate to convert experimentally obtained microdosimetric energy deposition spectra in silicon to equivalent microdosimetric energy deposition spectra in water.

TU‐D‐AUD C‐06: Direct RBE Determination of Therapeutic Protons Using a DE‐E Telescope

Purpose: A new monolithic silicon ΔE‐E telescope was evaluated for hadron therapy applications by converting the physical data provided by the detector to relative biological effect (RBE) for both modulated and un‐modulated therapeutic proton beams. Method and Materials: The ΔE‐E telescope provides information on lineal energy and particle identification that is based on energy depositions within the ΔE and E stages of the detector, collected in coincidence. Thus, this detector provides additional information on the quality of radiation fields over existing microdosimetry systems. Since different particles with the same LET or lineal energy are known to have different RBE values, the combined lineal‐energy particle identification data provided by the ΔE‐E telescope is likely to be of radiobiological value. To investigate this, an RBE matrix based on established in‐vitro V79 radiobiology data was developed linking the output of the device directly to radiobiological effect for two biological endpoints, RBE (10%) and low‐dose‐limit RBE(α). Experimental data was collected and analyzed for 100MeV modulated and un‐modulated therapeutic proton beams within a homogeneous polystyrene phantom. Results: Proximal to the spread‐out Bragg peak (SOBP), RBE(10%) and RBE(α) values of 1.2 and 3.2 respectively were determined from the measured response of the device. The high spatial resolution of the ΔE‐E telescope allows for data collection in rapidly changing radiation fields, which is demonstrated with derived RBE(10%) and RBE(α) values of 1.82 and 4.85 obtained from the measured response of the device at the SOBP distal edge. Conclusion: This work has demonstrated the ability of the ΔE‐E telescope to provide RBE data for proton radiation fields that is based on experimental in‐vitro data for V79 cells. This system could have an application to both hadron therapy and radiation protection as it provides a means for estimation of RBE in “real‐time” and verification of Monte Carlo simulations.

Nanodosimetric cluster size distributions of therapeutic proton beams

As we move into the new millennium, it is important that we improve our understanding of radiation effects on humans and nanoelectronic systems. This understanding is essential in a number of areas including radiation therapy for cancer treatment and extended human presence in outer space. Nanodosimetry in low-pressure gases enables measurement of the energy deposition of ionizing radiation on a scale equivalent to the dimensions of the DNA molecule. This is extremely important for not only biological applications but also electronic applications, as the effect of radiation on nanoelectronics needs to be determined before they are installed and deployed in complex radiation fields. However, before nanodosimetry can be widely applied, further investigation is required to link the output of gas-based nanodosimeters to the actual effect of the radiation on a biological or electronic system. The purpose of this research is to conduct nanodosimetric measurements of proton radiation fields at the proton accelerator of Loma Linda University Medical Center (LLUMC) and to develop a Monte Carlo simulation system to validate and support further developments of experimental nanodosimetry. To achieve this, measured ion cluster size distributions are compared to the output from the Monte Carlo simulation system that simulates the characteristics of the LLUMC beam line and the performance of the nanodosimeter installed on one of LLUMC's proton research beam lines.

Is the risk for secondary cancers after proton therapy enhanced distal to the Planning Target Volume? A two-case report with possible explanations

It is often assumed that radiation-induced secondary cancer after proton therapy forms preferentially close to the distal fall-off of the spread-out Bragg peak because of an increased relative biological effectiveness (RBE) with regard to cancer induction of low-energy protons. In this study we analyze to what extent dose gradients distal to the Planning Target Volume (PTV) may, independently from the RBE, contribute to enhanced radiation carcinogenesis. The study is based on two dogs which, out of 30 dogs treated with proton therapy at the Paul Scherrer Institute (PSI), developed a secondary cancer. Both dogs were originally diagnosed and treated for a fibrosarcoma and developed an osteosarcoma 48 and almost 60 months, respectively, after radiotherapy. From the dose distributions of the initial radiotherapy for both dogs three-dimensional maps of secondary cancer complication probability (SCCP) were computed. The SCCP maps were analyzed in the regions where the dogs developed a secondary cancer. The SCCP maps showed an enhanced risk in the regions of the femur where the secondary cancers were detected, as compared to the SCCP of the total femur. Excess risk of radiation-induced cancer at the distal part of proton radiation fields can thus be explained using SCCP calculations on the basis of the physical dose distributions. Therefore, the occurrence of secondary cancer close to the distal dose gradients of proton therapy is not necessarily due to an increased RBE of low-energy protons. More extensive studies based on more patients will be necessary to further elucidate the factors influencing the development of secondary tumors.

Microdosimetry simulations of solar protons within a spacecraft

The microdosimetric spectra derived by silicon microdosimeter in a proton radiation field traversing heterogeneous structures were simulated using the GEANT4 toolkit.

Measurement of neutron dose equivalent to proton therapy patients outside of the proton radiation field

Measurements of neutron dose equivalent values and neutron spectral fluences close to but outside of the therapeutic proton radiation field are presented. The neutron spectral fluences were determined at five locations with Bonner sphere measurements and established by unfolding techniques. More than 50 additional neutron dose equivalent values were measured with LiI and BF 3 thermal neutron detectors surrounded by a 25 cm polyethylene moderating sphere. For a large-field treatment, typical values of neutron dose equivalent per therapeutic proton absorbed dose, H/ D, at 50 cm distance from isocenter, range from 1 mSv/Gy (at 0° with respect to the proton beam axis) to 5 mSv/Gy (at 90°). Experiments reveal that H/ D varies significantly with the treatment technique, e.g., patient orientation, proton beam energy, and range-modulation. The relative uncertainty in H/ D values is approximately 40% (one standard deviation).

Dosimetry of proton radiation fields in space with nuclear emulsions.

The bulk of the astronauts' radiation exposure in space is due to trapped protons in the South Atlantic Anomaly or, on a deep space mission, in the radiation belt itself. The energy spectrum of the proton flux in both cases is a broad continuum from zero to several hundred MeV, with low energy protons and protons ending in tissue carrying a substantial fraction of the total dose. As demonstrated with the emulsion data of the Earth-orbital mission Apollo VII, a method using grain counting of tracks traversing the emulsion combined with a count of those ending in it (zero energy) provides sustained accuracy over the entire energy range. Within certain limits, the counts of ending protons at various locations in the space vehicle are proportional to the corresponding total doses. Highly structured directional patterns that are generally characteristic for the low energy particles have been analyzed in detail from the unmanned Apollo VI mission during which a total proton dose of 1.56 rad was observed within the vehicle. The fact that low energy protons with their comparatively high LET contribute substantially to the total dose is reflected in large microdosimetric fluctuations of the absorbed energy in tissue, with Bragg peaks of ending tracks occurring only in a few per cent of the total cell population even at dose levels of 50–100 rad.