3D Printing of Composite Radiation Shielding for Broad Spectrum Protection of Electronic Systems.

The miniaturization of satellite systems has compounded the need to protect microelectronic components from damaging radiation. Current approaches to mitigate this damage, such as indiscriminate mass shielding, built-in redundancies, and radiation hardened electronics, introduce high size, weight, power, and cost penalties that impact the overall performance of the satellite or launch opportunities. Additive manufacturing provides an appealing strategy to deposit radiation shielding only on susceptible components within an electronic assembly. Here, we describe a versatile material platform and process to conformally print customized composite inks at room temperatures directly and selectively onto commercial-off-the-shelf electronics. The suite of inks uses a flexible styrene-isoprene-styrene block copolymer binder that can be filled with particles of varying atomic densities for varying radiation shielding capabilities. Additionally, the system readily allows blended composites that contain multiple particle species with varying atomic composition within the same structure. The method can produce graded shielding that offers improved radiation attenuation via exquisite control over both shield geometry and composition. We anticipate this alternative to traditional shielding methods will enable the rapid proliferation of the next generation of compact satellite designs. This article is protected by copyright. All rights reserved.

Voxel-wise dose rate calculation in clinical pencil beam scanning proton therapy.

OBJECTIVE: Clinical outcomes after proton therapy have shown some variability that is not fully understood. Different approaches have been suggested to explain the biological outcome, but none has yet provided a comprehensive and satisfactory rationale for observed toxicities. The relatively recent transition from passive scattering (PS) to pencil beam scanning (PBS) treatments has significantly increased the voxel-wise dose rate in proton therapy. In addition, the dose rate distribution is no longer uniform along the cross section of the target but rather highly heterogeneous, following the spot placement. We suggest investigating dose rate as potential contributor to a more complex proton RBE model. Approach. Due to the time structure of the PBS beam delivery the instantaneous dose rate is highly variable voxel by voxel. Several possible parameters to represent voxel-wise dose rate for a given clinical PBS treatment plan are detailed. These quantities were implemented in the scripting environment of our treatment planning system, and computations experimentally verified. Sample applications to treated patient plans are shown. Main Results. Computed dose rates we experimentally confirmed. Dose rate maps vary depending on which method is used to represent them. Mainly, the underlying time and dose intervals chosen determine the topography of the resultant distributions. The maximum dose rates experienced by any target voxel in a given PBS treatment plan in our system range from ~100 to ~450 Gy(RBE)/min, a factor of 10 - 100 increase compared to PS. These dose rate distributions are very heterogeneous, with distinct hot spots. Significance. Voxel-wise dose rates for current clinical PBS treatment plans vary greatly from clinically established practice with PS. The exploration of different dose rate measures to evaluate potential correlations with observed clinical outcomes is suggested, potentially adding a missing component in the understanding of proton RBE.

Absence of Tissue-Sparing Effects in Partial Proton FLASH Irradiation in Murine Intestine.

Ultra-high dose rate irradiation has been reported to protect normal tissues more than conventional dose rate irradiation. This tissue sparing has been termed the FLASH effect. We investigated the FLASH effect of proton irradiation on the intestine as well as the hypothesis that lymphocyte depletion is a cause of the FLASH effect. A 16 × 12 mm2 elliptical field with a dose rate of ~120 Gy/s was provided by a 228 MeV proton pencil beam. Partial abdominal irradiation was delivered to C57BL/6j and immunodeficient Rag1-/-/C57 mice. Proliferating crypt cells were counted at 2 days post exposure, and the thickness of the muscularis externa was measured at 280 days following irradiation. FLASH irradiation did not reduce the morbidity or mortality of conventional irradiation in either strain of mice; in fact, a tendency for worse survival in FLASH-irradiated mice was observed. There were no significant differences in lymphocyte numbers between FLASH and conventional-dose-rate mice. A similar number of proliferating crypt cells and a similar thickness of the muscularis externa following FLASH and conventional dose rate irradiation were observed. Partial abdominal FLASH proton irradiation at 120 Gy/s did not spare normal intestinal tissue, and no difference in lymphocyte depletion was observed. This study suggests that the effect of FLASH irradiation may depend on multiple factors, and in some cases dose rates of over 100 Gy/s do not induce a FLASH effect and can even result in worse outcomes.

Proton FLASH effects on mouse skin at different oxygen tensions.

Objective. Irradiation at FLASH dose rates (>40 Gy s-1) has received great attention due to its reported normal tissue sparing effect. The FLASH effect was originally observed in electron irradiations but has since been shown to also occur with both photon and proton beams. Several mechanisms have been proposed to explain the tissue sparing at high dose rates, including effects involving oxygen, such as depletion of oxygen within the irradiated cells. In this study, we investigated the protective role of FLASH proton irradiation on the skin when varying the oxygen concentration.Approach. Our double scattering proton system provided a 1.2 × 1.6 cm2elliptical field at a dose rate of ∼130 Gy s-1. The conventional dose rate was ∼0.4 Gy s-1. The legs of the FVB/N mice were marked with two tattooed dots and fixed in a holder for exposure. To alter the skin oxygen concentration, the mice were breathing pure oxygen or had their legs tied to restrict blood flow. The distance between the two dots was measured to analyze skin contraction over time.Main results. FLASH irradiation mitigated skin contraction by 15% compared to conventional dose rate irradiation. The epidermis thickness and collagen deposition at 75 d following 25 to 30 Gy exposure suggested a long-term protective function in the skin from FLASH irradiation. Providing the mice with oxygen or reducing the skin oxygen concentration removed the dose-rate-dependent difference in response.Significance. FLASH proton irradiation decreased skin contraction, epidermis thickness and collagen deposition compared to standard dose rate irradiations. The observed oxygen-dependence of the FLASH effect is consistent with, but not conclusive of, fast oxygen depletion during the exposure.

FLASH Investigations Using Protons: Design of Delivery System, Preclinical Setup and Confirmation of FLASH Effect with Protons in Animal Systems.

Extremely high-dose-rate irradiation, referred to as FLASH, has been shown to be less damaging to normal tissues than the same dose administrated at conventional dose rates. These results, typically seen at dose rates exceeding 40 Gy/s (or 2,400 Gy/min), have been widely reported in studies utilizing photon or electron radiation as well as in some proton radiation studies. Here, we report the development of a proton irradiation platform in a clinical proton facility and the dosimetry methods developed. The target is placed in the entry plateau region of a proton beam with a specifically designed double-scattering system. The energy after the double-scattering system is 227.5 MeV for protons that pass through only the first scatterer, and 225.5 MeV for those that also pass through the second scatterer. The double-scattering system was optimized to deliver a homogeneous dose distribution to a field size as large as possible while keeping the dose rate >100 Gy/s and not exceeding a cyclotron current of 300 nA. We were able to obtain a collimated pencil beam (1.6 × 1.2 cm2 ellipse) at a dose rate of ∼120 Gy/s. This beam was used for dose-response studies of partial abdominal irradiation of mice. First results indicate a potential tissue-sparing effect of FLASH.

Iterative optimization of relative stopping power by single detector based multi-projection proton radiography.

In proton therapy, range uncertainties induced by the conversion from x-ray CT (xCT) Hounsfield units (HU) to relative stopping power (RSP) compromise the precision of dose delivery. To reduce range uncertainties induced by HU-converted RSPs, this study investigates optimizing the RSP of individual voxels in xCT iteratively based on multi-projection proton radiography (pRG) acquired using a single amorphous silicon flat panel imager. Time-resolved dose rate functions (DRF) were measured by the imager placed downstream of a test phantom consisting of tissue substitute materials. Water equivalent path lengths (WEPL) in the pRG were derived. By rotating the phantom, multiple pRG projections were acquired at angles from 0 to 358° with an increment of 2°. X-ray CT of the phantom was acquired and co-registered with the pRG acquisition coordinates. RSPs of individual xCT voxels were optimized iteratively by minimizing the difference between the measured WEPLs and the calculated WEPLs by ray tracing with HU-converted RSPs. Pixels in pRGs that exhibited severe proton range mixing were rejected for the optimization. Tikhonov regularization was applied under the assumption that HU-converted RSPs are inaccurate, but the inaccuracy is within a few percent. While ~50% of WEPL pixels were rejected due to severe range mixing in pRG, RSPs of >90% CT voxels could still be optimized if multiple pRG projections, e.g. ⩾12, around the phantom are utilized. For tissue substitute materials in a cylindrical phantom, percentage errors of RSPs were reduced from a range of -8% to +4% to be within ±2%. Further optimization, achieved by implementing a material-specific regularization parameter, reduced percent errors to be within ±0.5%. This study demonstrates the concept of optimizing RSPs of individual CT voxels with multi-projection pRGs acquired by a single flat panel imager, which could be further explored and implemented in proton therapy to reduce range uncertainties.

Improvement of single detector proton radiography by incorporating intensity of time-resolved dose rate functions.

Proton radiography, which images patients with the same type of particles as those with which they are to be treated, is a promising approach to image guidance and water equivalent path length (WEPL) verification in proton radiation therapy. We have shown recently that proton radiographs could be obtained by measuring time-resolved dose rate functions (DRFs) using an x-ray amorphous silicon flat panel. The WEPL values were derived solely from the root-mean-square (RMS) of DRFs, while the intensity information in the DRFs was filtered out. In this work, we explored the use of such intensity information for potential improvement in WEPL accuracy and imaging quality. Three WEPL derivation methods based on, respectively, the RMS only, the intensity only, and the intensity-weighted RMS were tested and compared in terms of the quality of obtained radiograph images and the accuracy of WEPL values. A Gammex CT calibration phantom containing inserts made of various tissue substitute materials with independently measured relative stopping powers (RSP) was used to assess the imaging performances. Improved image quality with enhanced interfaces was achieved while preserving the accuracy by using intensity information in the calibration. Other objects, including an anthropomorphic head phantom, a proton therapy range compensator, a frozen lamb's head and an 'image quality phantom' were also imaged. Both the RMS only and the intensity-weighted RMS methods derived RSPs within ± 1% for most of the Gammex phantom inserts, with a mean absolute percentage error of 0.66% for all inserts. In the case of the insert with a titanium rod, the method based on RMS completely failed, whereas that based on the intensity-weighted RMS was qualitatively valid. The use of intensity greatly enhanced the interfaces between different materials in the obtained WEPL images, suggesting the potential for image guidance in areas such as patient positioning and tumor tracking by proton radiography.

On the nuclear halo of a proton pencil beam stopping in water.

The dose distribution of a proton beam stopping in water has components due to basic physics and may have others from beam contamination. We propose the concise terms core for the primary beam, halo (see Pedroni et al 2005 Phys. Med. Biol. 50 541-61) for the low dose region from charged secondaries, aura for the low dose region from neutrals, and spray for beam contamination. We have measured the dose distribution in a water tank at 177 MeV under conditions where spray, therefore radial asymmetry, is negligible. We used an ADCL calibrated thimble chamber and a Faraday cup calibrated integral beam monitor so as to obtain immediately the absolute dose per proton. We took depth scans at fixed distances from the beam centroid rather than radial scans at fixed depths. That minimizes the signal range for each scan and better reveals the structure of the core and halo. Transitions from core to halo to aura are already discernible in the raw data. The halo has components attributable to coherent and incoherent nuclear reactions. Due to elastic and inelastic scattering by the nuclear force, the Bragg peak persists to radii larger than can be accounted for by Molière single scattering. The radius of the incoherent component, a dose bump around midrange, agrees with the kinematics of knockout reactions. We have fitted the data in two ways. The first is algebraic or model dependent (MD) as far as possible, and has 25 parameters. The second, using 2D cubic spline regression, is model independent. Optimal parameterization for treatment planning will probably be a hybrid of the two, and will of course require measurements at several incident energies. The MD fit to the core term resembles that of the PSI group (Pedroni et al 2005), which has been widely emulated. However, we replace their T(w), a mass stopping power which mixes electromagnetic (EM) and nuclear effects, with one that is purely EM, arguing that protons that do not undergo hard single scatters continue to lose energy according to the Beth-Bloch formula. If that is correct, it is no longer necessary to measure T(w), and the dominant role played by the 'Bragg peak chamber' vanishes. For mathematical and other details we will refer to Gottschalk et al (2014, arXiv: 1409.1938v1), a long technical report of this project.

Validation of an in-vivo proton beam range check method in an anthropomorphic pelvic phantom using dose measurements.

PURPOSE: In-vivo dosimetry and beam range verification in proton therapy could play significant role in proton treatment validation and improvements. In-vivo beam range verification, in particular, could enable new treatment techniques one of which could be the use of anterior fields for prostate treatment instead of opposed lateral fields as in current practice. This paper reports validation study of an in-vivo range verification method which can reduce the range uncertainty to submillimeter levels and potentially allow for in-vivo dosimetry. METHODS: An anthropomorphic pelvic phantom is used to validate the clinical potential of the time-resolved dose method for range verification in the case of prostrate treatment using range modulated anterior proton beams. The method uses a 3 × 4 matrix of 1 mm diodes mounted in water balloon which are read by an ADC system at 100 kHz. The method is first validated against beam range measurements by dose extinction measurements. The validation is first completed in water phantom and then in pelvic phantom for both open field and treatment field configurations. Later, the beam range results are compared with the water equivalent path length (WEPL) values computed from the treatment planning system XIO. RESULTS: Beam range measurements from both time-resolved dose method and the dose extinction method agree with submillimeter precision in water phantom. For the pelvic phantom, when discarding two of the diodes that show sign of significant range mixing, the two methods agree with ±1 mm. Only a dose of 7 mGy is sufficient to achieve this result. The comparison to the computed WEPL by the treatment planning system (XIO) shows that XIO underestimates the protons beam range. Quantifying the exact XIO range underestimation depends on the strategy used to evaluate the WEPL results. To our best evaluation, XIO underestimates the treatment beam range between a minimum of 1.7% and maximum of 4.1%. CONCLUSIONS: Time-resolved dose measurement method satisfies the two basic requirements, WEPL accuracy and minimum dose, necessary for clinical use, thus, its potential for in-vivo protons range verification. Further development is needed, namely, devising a workflow that takes into account the limits imposed by proton range mixing and the susceptibility of the comparison of measured and expected WEPLs to errors on the detector positions. The methods may also be used for in-vivo dosimetry and could benefit various proton therapy treatments.

Radiation resistance of biological reagents for in situ life detection.

Life on Mars, if it exists, may share a common ancestry with life on Earth derived from meteoritic transfer of microbes between the planets. One means to test this hypothesis is to isolate, detect, and sequence nucleic acids in situ on Mars, then search for similarities to known common features of life on Earth. Such an instrument would require biological and chemical components, such as polymerase and fluorescent dye molecules. We show that reagents necessary for detection and sequencing of DNA survive several analogues of the radiation expected during a 2-year mission to Mars, including proton (H-1), heavy ion (Fe-56, O-18), and neutron bombardment. Some reagents have reduced performance or fail at higher doses. Overall, our findings suggest it is feasible to utilize space instruments with biological components, particularly for mission durations of up to several years in environments without large accumulations of charged particles, such as the surface of Mars, and have implications for the meteoritic transfer of microbes between planets.

Investigation of an implantable dosimeter for single-point water equivalent path length verification in proton therapy.

PURPOSE: In vivo range verification in proton therapy is highly desirable. A recent study suggested that it was feasible to use point dose measurement for in vivo beam range verification in proton therapy, provided that the spread-out Bragg peak dose distribution is delivered in a different and rather unconventional manner. In this work, the authors investigate the possibility of using a commercial implantable dosimeter with wireless reading for this particular application. METHODS: The traditional proton treatment technique delivers all the Bragg peaks required for a SOBP field in a single sequence, producing a constant dose plateau across the target volume. As a result, a point dose measurement anywhere in the target volume will produce the same value, thus providing no information regarding the water equivalent path length to the point of measurement. However, the same constant dose distribution can be achieved by splitting the field into a complementary pair of subfields, producing two oppositely "sloped" depth-dose distributions, respectively. The ratio between the two distributions can be a sensitive function of depth and measuring this ratio at a point inside the target volume can provide the water equivalent path length to the dosimeter location. Two types of field splits were used in the experiment, one achieved by the technique of beam current modulation and the other by manipulating the location and width of the beam pulse relative to the range modulator track. Eight MOSFET-based implantable dosimeters at four different depths in a water tank were used to measure the dose ratios for these field pairs. A method was developed to correct the effect of the well-known LET dependence of the MOSFET detectors on the depth-dose distributions using the columnar recombination model. The LET-corrected dose ratios were used to derive the water equivalent path lengths to the dosimeter locations to be compared to physical measurements. RESULTS: The implantable dosimeters measured the dose ratios with a reasonable relative uncertainty of 1%-3% at all depths, except when the ratio itself becomes very small. In total, 55% of the individual measurements reproduced the water equivalent path lengths to the dosimeters within 1 mm. For three dosimeters, the difference was consistently less than 1 mm. Half of the standard deviations over the repeated measurements were equal or less than 1 mm. CONCLUSIONS: With a single fitting parameter, the LET-correction method worked remarkably well for the MOSFET detectors. The overall results were very encouraging for a potential method of in vivo beam range verification with millimeter accuracy. This is sufficient accuracy to expand range of clinical applications in which the authors could use the distal fall off of the proton depth dose for tight margins.

PET/CT imaging for treatment verification after proton therapy: a study with plastic phantoms and metallic implants.

The feasibility of off-line positron emission tomography/computed tomography (PET/CT) for routine three dimensional in-vivo treatment verification of proton radiation therapy is currently under investigation at Massachusetts General Hospital in Boston. In preparation for clinical trials, phantom experiments were carried out to investigate the sensitivity and accuracy of the method depending on irradiation and imaging parameters. Furthermore, they addressed the feasibility of PET/CT as a robust verification tool in the presence of metallic implants. These produce x-ray CT artifacts and fluence perturbations which may compromise the accuracy of treatment planning algorithms. Spread-out Bragg peak proton fields were delivered to different phantoms consisting of polymethylmethacrylate (PMMA), PMMA stacked with lung and bone equivalent materials, and PMMA with titanium rods to mimic implants in patients. PET data were acquired in list mode starting within 20 min after irradiation at a commercial luthetium-oxyorthosilicate (LSO)-based PET/CT scanner. The amount and spatial distribution of the measured activity could be well reproduced by calculations based on the GEANT4 and FLUKA Monte Carlo codes. This phantom study supports the potential of millimeter accuracy for range monitoring and lateral field position verification even after low therapeutic dose exposures of 2 Gy, despite the delay between irradiation and imaging. It also indicates the value of PET for treatment verification in the presence of metallic implants, demonstrating a higher sensitivity to fluence perturbations in comparison to a commercial analytical treatment planning system. Finally, it addresses the suitability of LSO-based PET detectors for hadron therapy monitoring. This unconventional application of PET involves countrates which are orders of magnitude lower than in diagnostic tracer imaging, i.e., the signal of interest is comparable to the noise originating from the intrinsic radioactivity of the detector itself. In addition to PET alone, PET/CT imaging provides accurate information on the position of the imaged object and may assess possible anatomical changes during fractionated radiotherapy in clinical applications.

Dose-volume prediction of radiation-related complications after proton beam radiosurgery for cerebral arteriovenous malformations.

OBJECT: The use of radiosurgery for the treatment of cerebral arteriovenous malformations (AVMs) and other lesions demands an accurate understanding of the risk of radiation-related complications. Some commonly used formulas for predicting risk are based on extrapolation from small numbers of animal experiments, pilot human treatment series, and theoretical radiobiological considerations. The authors studied the incidence of complications after AVM radiosurgery in relation to dose, volume, and other factors in a large patient series. METHODS: A retrospective review was conducted in 1329 patients with AVM treated by Dr. Raymond Kjellberg at the Harvard Cyclotron Laboratory (HCL) between 1965 and 1993. Dose and volume were obtained from HCL records, and information about patient follow up was derived from concurrent clinical records, questionnaires, and contact with referring physicians. Multivariate logistic regression with bootstrapped confidence intervals was used. Follow up was available in 1250 patients (94%); the median follow-up duration was 6.5 years. The median radiation dose was 10.5 Gy and the median treatment volume was 33.7 cm(3). Twenty-three percent of treated lesions were smaller than 10 cm(3). Fifty-one permanent radiation-related deficits occurred (4.1%). Of 1043 patients treated with a dose predicted by the Kjellberg isoeffective centile curve to have a less than 1% complication risk, 1.8% suffered radiation-related complications. Actual complication rates were 4.7% for 128 patients treated at Kjellberg risk centile doses of 1 to 1.8%, and 34% for 61 patients treated at risk centile doses of 2 to 2.5%. The fitted logistic model showed that complication risk was related to treatment dose and volume, thalamic or brainstem location, and patient age. CONCLUSIONS: The Kjellberg isoeffective risk centile curve significantly underpredicted actual risks of permanent complications after proton beam radiosurgery for AVMs. Actual risks were best predicted using a model that accounted for treatment dose and volume, lesion location, and patient age.