Comparing radiolytic production of H2O2 and development of Zebrafish embryos after ultra high dose rate exposure with electron and transmission proton beams.

The physico-chemical and biological response to conventional and UHDR electron and proton beams was investigated, along with conventional photons. The temporal structure and nature of the beam affected both, with electron beam at ≥1400 Gy/s and proton beam at 0.1 and 1260 Gy/s found to be isoefficient at sparing zebrafish embryos.

A quantitative FLASH effectiveness model to reveal potentials and pitfalls of high dose rate proton therapy.

PURPOSE: In ultrahigh dose rate radiotherapy, the FLASH effect can lead to substantially reduced healthy tissue damage without affecting tumor control. Although many studies show promising results, the underlying biological mechanisms and the relevant delivery parameters are still largely unknown. It is unclear, particularly for scanned proton therapy, how treatment plans could be optimized to maximally exploit this protective FLASH effect. MATERIALS AND METHODS: To investigate the potential of pencil beam scanned proton therapy for FLASH treatments, we present a phenomenological model, which is purely based on experimentally observed phenomena such as potential dose rate and dose thresholds, and which estimates the biologically effective dose during FLASH radiotherapy based on several parameters. We applied this model to a wide variety of patient geometries and proton treatment planning scenarios, including transmission and Bragg peak plans as well as single- and multifield plans. Moreover, we performed a sensitivity analysis to estimate the importance of each model parameter. RESULTS: Our results showed an increased plan-specific FLASH effect for transmission compared with Bragg peak plans (19.7% vs. 4.0%) and for single-field compared with multifield plans (14.7% vs. 3.7%), typically at the cost of increased integral dose compared to the clinical reference plan. Similar FLASH magnitudes were found across the different treatment sites, whereas the clinical benefits with respect to the clinical reference plan varied strongly. The sensitivity analysis revealed that the threshold dose as well as the dose per fraction strongly impacted the FLASH effect, whereas the persistence time only marginally affected FLASH. An intermediate dependence of the FLASH effect on the dose rate threshold was found. CONCLUSIONS: Our model provided a quantitative measure of the FLASH effect for various delivery and patient scenarios, supporting previous assumptions about potentially promising planning approaches for FLASH proton therapy. Positive clinical benefits compared to clinical plans were achieved using hypofractionated, single-field transmission plans. The dose threshold was found to be an important factor, which may require more investigation.

Rodent Estrous Cycle Monitoring Utilizing Vaginal Lavage: No Such Thing As a Normal Cycle.

The current methodology establishes a reproducible, standardized, and cost-effective approach to monitoring the estrous cycle of female Sprague Dawley (SD) adolescent rats. This study demonstrates the complexity of hormonal cycles and the broad spectrum of understanding required to construct a reliable and valid monitoring technique. Through an in-depth examination of principal experimental design and procedural elements, this description of the cycle and its fundamental principles provides a framework for further understanding and deconstructs misconceptions for future replication. Along with an outline of the sample collection process employing vaginal lavage, the procedure describes the mechanism of data categorization into the four-stage model of proestrus, estrus, metestrus, and diestrus. These stages are characterized by a new proposed approach, utilizing the 4 categorizing determinants of vaginal fluid condition, cell type(s) present, cell arrangement, and cell quantity at the time of collection. Variations of each stage, favorable and unfavorable samples, the distinction between cyclicity and acyclicity, and graphic depictions of the collected categorizing components are presented alongside effective interpretive and organizational practices of the data. Overall, these tools allow for the publication of quantifiable data ranges for the first time, leading to the standardization of categorization factors upon replication.

Sex Differences in Neurophysiological Changes Following Voluntary Exercise in Adolescent Rats.

Background: Adolescence is a period of time characterized by the onset of puberty and is marked by cognitive and social developments and gross physical changes that can play a role in athletic performance. Sex differences are present with differences in body size, height, physiology and behavior which contribute to differences in athletic performance as well. Pre-clinical studies representing this active group are lacking. Methods: Acute and chronic effects of exercise were evaluated. Male and female adolescent rats were given voluntary access to a running wheel for 10 consecutive days. Running behavior (males and females) and estrous cycling (females only) were analyzed daily. A second group was given 10 days of voluntary access to a running wheel, then rested for 10 days to determine the long-term effects of exercise on the adolescent brain. Brain and muscle tissue were harvested at 10 and 20 day time points to understand exercise-dependent changes in mitochondrial activity and neuroplasticity. Animal cohorts were carried out at two different sites: University of California Los Angeles and Pepperdine University. Results: On average, running distance, intensity of run, and length of running bout increased for both male and female rats across the 10 days measured. Females ran significantly further and for longer intervals compared to males. Cortical and muscle expression of PGC1α showed similar levels at 10 days regardless of sex and exercise. There was a significant increase in expression at 20 days in all groups correlating with body size (p's < 0.05). Cortical and hippocampal levels of BDNF were similar across all groups, however, BDNF was significantly higher in exercised females at the acute compared to long-term time point. Discussion: Adolescent rats allowed 10 days of exercise show changes in physiologic function. There are sex differences in running behavior not impacted by sex hormones. These results are important to further our understanding of how exercise impacts the adolescent brain.

A feasibility study on deep learning-based individualized 3D dose distribution prediction.

PURPOSE: Radiation therapy treatment planning is a trial-and-error, often time-consuming process. An approximately optimal dose distribution corresponding to a specific patient's anatomy can be predicted by using pre-trained deep learning (DL) models. However, dose distributions are often optimized based not only on patient-specific anatomy but also on physicians' preferred trade-offs between planning target volume (PTV) coverage and organ at risk (OAR) sparing or among different OARs. Therefore, it is desirable to allow physicians to fine-tune the dose distribution predicted based on patient anatomy. In this work, we developed a DL model to predict the individualized 3D dose distributions by using not only the patient's anatomy but also the desired PTV/OAR trade-offs, as represented by a dose volume histogram (DVH), as inputs. METHODS: In this work, we developed a modified U-Net network to predict the 3D dose distribution by using patient PTV/OAR masks and the desired DVH as inputs. The desired DVH, fine-tuned by physicians from the initially predicted DVH, is first projected onto the Pareto surface, then converted into a vector, and then concatenated with feature maps encoded from the PTV/OAR masks. The network output for training is the dose distribution corresponding to the Pareto optimal DVH. The training/validation datasets contain 77 prostate cancer patients, and the testing dataset has 20 patients. RESULTS: The trained model can predict a 3D dose distribution that is approximately Pareto optimal while having the DVH closest to the input desired DVH. We calculated the difference between the predicted dose distribution and the optimized dose distribution that has a DVH closest to the desired one for the PTV and for all OARs as a quantitative evaluation. The largest absolute error in mean dose was about 3.6% of the prescription dose, and the largest absolute error in the maximum dose was about 2.0% of the prescription dose. CONCLUSIONS: In this feasibility study, we have developed a 3D U-Net model with the patient's anatomy and the desired DVH curves as inputs to predict an individualized 3D dose distribution that is approximately Pareto optimal while having the DVH closest to the desired one. The predicted dose distributions can be used as references for dosimetrists and physicians to rapidly develop a clinically acceptable treatment plan.

SDDRO-joint: simultaneous dose and dose rate optimization with the joint use of transmission beams and Bragg peaks for FLASH proton therapy.

Cancer radiotherapy (RT) with the irradiation at ultra-high dose rates, namely FLASH-RT, can substantially reduce radiation-induced normal tissue toxicities while maintaining tumor response. Currently, clinical FLASH-RT on deep-seated tumors can only be performed with proton beams. One way to achieve ultra-high dose rates at depth is through the use of high-energy transmission beams (TB), where the Bragg peaks (BP) fall outside the body. However, planning with TB alone does not fully leverage the degrees of freedom for dose shaping as traditional intensity modulated proton therapy (IMPT) which uses the BP of multi-energy proton beams at the tumor target. This work will develop a simultaneous dose and dose rate optimization (SDDRO) method with the joint use of TB and BP, namely SDDRO-Joint. Specifically, BP are placed inside tumor targets to improve the target dose conformality and sparse the normal-tissue dose, while TB primarily cover the tumor boundary to achieve ultra-high dose rate coverage of organs-at-risk (OAR) close to tumor targets. The sparing of OAR and other normal tissues via SDDRO-Joint is jointly by TB and BP, i.e. the FLASH sparing by TB and the dose sparing by BP. The results suggest that the addition of BP substantially increased the target dose conformality for SDDRO. Noticeably SDDRO-Joint also provided slightly higher conformal index values than the conventional IMPT method with BP alone.

Ultra-High Dose Rate Transmission Beam Proton Therapy for Conventionally Fractionated Head and Neck Cancer: Treatment Planning and Dose Rate Distributions.

Transmission beam (TB) proton therapy (PT) uses single, high energy beams with Bragg-peak behind the target, sharp penumbras and simplified planning/delivery. TB facilitates ultra-high dose-rates (UHDRs, e.g., ≥40 Gy/s), which is a requirement for the FLASH-effect. We investigated (1) plan quality for conventionally-fractionated head-and-neck cancer treatment using spot-scanning proton TBs, intensity-modulated PT (IMPT) and photon volumetric-modulated arc therapy (VMAT); (2) UHDR-metrics. VMAT, 3-field IMPT and 10-field TB-plans, delivering 70/54.25 Gy in 35 fractions to boost/elective volumes, were compared (n = 10 patients). To increase spot peak dose-rates (SPDRs), TB-plans were split into three subplans, with varying spot monitor units and different gantry currents. Average TB-plan organs-at-risk (OAR) sparing was comparable to IMPT: mean oral cavity/body dose were 4.1/2.5 Gy higher (9.3/2.0 Gy lower than VMAT); most other OAR mean doses differed by <2 Gy. Average percentage of dose delivered at UHDRs was 46%/12% for split/non-split TB-plans and mean dose-averaged dose-rate 46/21 Gy/s. Average total beam-on irradiation time was 1.9/3.8 s for split/non-split plans and overall time including scanning 8.9/7.6 s. Conventionally-fractionated proton TB-plans achieved comparable OAR-sparing to IMPT and better than VMAT, with total beam-on irradiation times <10s. If a FLASH-effect can be demonstrated at conventional dose/fraction, this would further improve plan quality and TB-protons would be a suitable delivery system.

A framework for defining FLASH dose rate for pencil beam scanning.

PURPOSE: To develop a method of (a) calculating the dose rate of voxels within a proton field delivered using pencil beam scanning (PBS), and (b) reporting a representative dose rate for the PBS treatment field that enables correspondence between multiple treatment modalities. This method takes into account the unique spatiotemporal delivery patterns of PBS FLASH radiotherapy. METHODS: The dose rate at each voxel of a PBS radiation field is approximately the quotient of the voxel's dose and "effective" irradiation time. Each voxel's "effective" irradiation time starts when the cumulative dose rises above a chosen threshold value, and stops when its cumulative dose reaches its total dose minus the same threshold value. The above calculation yields a distribution of dose rates for the voxels within a PBS treatment field. To report a representative dose rate for the PBS field, we propose a user-selectable parameter of pth percentile of the dose rate distribution, such that (100 - p) % of the field is above the corresponding dose rate. To demonstrate the method described above, we design FLASH transmission fields using 250 MeV protons and calculate the PBS dose rate distributions in both two-dimensional (2D) and three-dimensional (3D) models. To further evaluate the formalism, we provide an example of a clinical PBS treatment field. RESULTS: With the 2D PBS transmission field, it is demonstrated that the time to accumulate the total dose at a voxel is limited to a fraction of the delivery time of the entire field. In addition, the spatial distributions of dose and dose rate are quite different within the field. For the 10 × 10 cm2 PBS field irradiating a 3D water phantom, the prescribed dose of 10 Gy at 10 cm depth is delivered in 1.0 s. The dose rate decreases in the irradiated volume with increasing depth (until the Bragg peak) due to increase of beam spot size by Coulomb scattering. For example, 95% of the irradiated volume between 0 and 10 cm depth receive >40 Gy/s, whereas between 0-20 cm and 0-30 cm depth, 95% of the irradiated volume received >36 Gy/s and >24 Gy/s, respectively. For the clinical PBS treatment field, the scanning pattern conforms to the PTV. PBS dose rate data are presented for the PTV and adjacent normal organs. CONCLUSION: We have developed a method of calculating the dose rate distribution of a PBS proton field and have recommended nomenclature for reporting PBS treatment dose rate. We believe that standardizing the method for calculating and reporting PBS treatment dose rates, in a manner that corresponds with other treatment modalities, will advance the research and potential application of PBS FLASH radiotherapy.

Recovery From Repeat Mild Traumatic Brain Injury in Adolescent Rats Is Dependent on Pre-injury Activity State.

Adolescents and young adults have the highest incidence of mild traumatic brain injury (mTBI); sport-related activities are a major contributor. Roughly a third of these patients diagnosed with mTBI are estimated to have received a subsequent repeat mTBI (rTBI). Previously, animal studies have only modeled mTBI in sedentary animals. This study utilizes physical activity as a dependent variable prior to rTBI in adolescent rats by allowing voluntary exercise in males, establishing the rat athlete (rathlete). Rats were given access to locked or functional running wheels for 10 d prior to sham or rTBI injury. Following rTBI, rathletes were allowed voluntary access to running wheels beginning on different days post-injury: no run (rTBI+no run), immediate run (rTBI+Immed), or 3 day delay (rTBI+3dd). Rats were tested for motor and cognitive-behavioral (anxiety, social, memory) and mechanosensory (allodynia) dysfunction using a novel rat standardized concussion assessment tool on post-injury days 1,3,5,7, and 10. Protein expression of brain derived neurotrophic factor (BDNF) and proliferator-activated gamma coactivator 1-alpha (PGC1α) was measured in the parietal cortex, hippocampus, and gastrocnemius muscle. Sedentary shams displayed lower anxiety-like behaviors compared to rathlete shams on all testing days. BDNF and PGC1α levels increased in the parietal cortex and hippocampus with voluntary exercise. In rTBI rathletes, the rTBI+Immed group showed impaired social behavior, memory impairment in novel object recognition, and increased immobility compared to rathlete shams. All rats showed greater neuropathic mechanosensory sensitivity than previously published uninjured adults, with rTBI+3dd showing greatest sensitivity. These results demonstrate that voluntary exercise changes baseline functioning of the brain, and that among rTBI rathletes, delayed return to activity improved cognitive recovery.

Bringing FLASH to the Clinic: Treatment Planning Considerations for Ultrahigh Dose-Rate Proton Beams.

PURPOSE: Preclinical research into ultrahigh dose rate (eg, ≥40 Gy/s) "FLASH"-radiation therapy suggests a decrease in side effects compared with conventional irradiation while maintaining tumor control. When FLASH is delivered using a scanning proton beam, tissue becomes subject to a spatially dependent range of dose rates. This study systematically investigates dose rate distributions and delivery times for proton FLASH plans using stereotactic lung irradiation as the paradigm. METHODS AND MATERIALS: Stereotactic lung radiation therapy FLASH-plans, using 244 MeV scanning proton transmission beams, with the Bragg peak behind the body, were made for 7 patients. Evaluated parameters were dose rate distribution within a beam, overall irradiation time, number of times tissue is irradiated, and quality of the FLASH-plans compared with the clinical volumetric-modulated arc therapy (VMAT) plans. RESULTS: Sparing of lungs, thoracic wall, and heart in the FLASH-plans was equal to or better than that in the VMAT-plans. For a spot peak dose rate (SPDR, the dose rate in the middle of the spot) of 100 Gy/s, ∼40% of dose is delivered at FLASH dose rates, and for SPDR = 360 Gy/s this increased to ∼75%. One-hundred percent FLASH dose rate cannot be achieved owing to small contributions from distant spots with lower dose rates. The total irradiation time varied between 300 to 730 ms, and around 85% of the dose-receiving body volume was irradiated by either 1 or 2 beams. CONCLUSIONS: Clinical implementation of FLASH using scanning proton beams requires multiple treatment planning considerations: dosimetric, temporal, and spatial parameters all seem important. The FLASH efficiency of a scanning proton beam increases with SPDR. The methodology proposed in this proof-of-principle study provides a framework for evaluating the FLASH characteristics of scanning proton beam plans and can be adapted as FLASH parameters are better defined. It currently seems logical to optimize plans for the shortest delivery time, maximum amount of high dose rate coverage, and maximum amount of single beam and continuous irradiation.

Automated Text Message Reminders Improve Radiation Therapy Compliance.

PURPOSE: Protraction of radiation therapy courses can lead to lower cancer control and cancer-specific survival rates. The requirement for daily, consecutive radiation treatments coupled with the complexities of multimodality cancer care and quality assurance can occasionally lead to missed patient appointments or clinical inefficiency. To determine whether an automated text messaging (short message service [SMs]) platform could improve patient compliance with scheduled radiation therapy delivery, we created an automated SMS platform to send daily reminders of radiation therapy appointments. METHODS AND MATERIALS: An automated SMS text messaging program was used from July 2016 to January 2017 to deliver daily appointment time reminders to patients on an elective basis. Automated text messages were sent 2 hours before treatment appointments with appointment-specific information. We analyzed for compliance with radiation therapy appointments for patients who elected to receive SMS reminders versus those who did not. RESULTS: Multivariate analysis of >37,000 encounters involving ∼3400 patients demonstrated that of the factors considered, nonreceipt of SMS appointment reminders had a strong association with 15- to 60-minute tardiness (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.13-1.38; P < .0001), >60-minute tardiness (OR, 1.56; 95% CI, 1.34-1.82; P < .0001) and no-shows (OR, 6.77; 95% CI, 5.45-8.41; P < .0001). Other demographic factors associated with decreased compliance included being early in a radiation therapy course, having an appointment earlier in the day, younger age, and male sex. Receipt of an SMS message did not correlate with overall treatment package time. CONCLUSIONS: Receipt of text messages correlates with compliance for radiation therapy appointments. Prospective randomized trials would be required to determine conclusively whether SMS is an effective intervention for improving compliance in populations at risk for being late to or missing radiation therapy appointments.

Multi-GPU configuration of 4D intensity modulated radiation therapy inverse planning using global optimization.

We report on the design, implementation and characterization of a multi-graphic processing unit (GPU) computational platform for higher-order optimization in radiotherapy treatment planning. In collaboration with a commercial vendor (Varian Medical Systems, Palo Alto, CA), a research prototype GPU-enabled Eclipse (V13.6) workstation was configured. The hardware consisted of dual 8-core Xeon processors, 256 GB RAM and four NVIDIA Tesla K80 general purpose GPUs. We demonstrate the utility of this platform for large radiotherapy optimization problems through the development and characterization of a parallelized particle swarm optimization (PSO) four dimensional (4D) intensity modulated radiation therapy (IMRT) technique. The PSO engine was coupled to the Eclipse treatment planning system via a vendor-provided scripting interface. Specific challenges addressed in this implementation were (i) data management and (ii) non-uniform memory access (NUMA). For the former, we alternated between parameters over which the computation process was parallelized. For the latter, we reduced the amount of data required to be transferred over the NUMA bridge. The datasets examined in this study were approximately 300 GB in size, including 4D computed tomography images, anatomical structure contours and dose deposition matrices. For evaluation, we created a 4D-IMRT treatment plan for one lung cancer patient and analyzed computation speed while varying several parameters (number of respiratory phases, GPUs, PSO particles, and data matrix sizes). The optimized 4D-IMRT plan enhanced sparing of organs at risk by an average reduction of [Formula: see text] in maximum dose, compared to the clinical optimized IMRT plan, where the internal target volume was used. We validated our computation time analyses in two additional cases. The computation speed in our implementation did not monotonically increase with the number of GPUs. The optimal number of GPUs (five, in our study) is directly related to the hardware specifications. The optimization process took 35 min using 50 PSO particles, 25 iterations and 5 GPUs.

A GPU OpenCL based cross-platform Monte Carlo dose calculation engine (goMC).

Monte Carlo (MC) simulation has been recognized as the most accurate dose calculation method for radiotherapy. However, the extremely long computation time impedes its clinical application. Recently, a lot of effort has been made to realize fast MC dose calculation on graphic processing units (GPUs). However, most of the GPU-based MC dose engines have been developed under NVidia's CUDA environment. This limits the code portability to other platforms, hindering the introduction of GPU-based MC simulations to clinical practice. The objective of this paper is to develop a GPU OpenCL based cross-platform MC dose engine named goMC with coupled photon-electron simulation for external photon and electron radiotherapy in the MeV energy range. Compared to our previously developed GPU-based MC code named gDPM (Jia et al 2012 Phys. Med. Biol. 57 7783-97), goMC has two major differences. First, it was developed under the OpenCL environment for high code portability and hence could be run not only on different GPU cards but also on CPU platforms. Second, we adopted the electron transport model used in EGSnrc MC package and PENELOPE's random hinge method in our new dose engine, instead of the dose planning method employed in gDPM. Dose distributions were calculated for a 15 MeV electron beam and a 6 MV photon beam in a homogenous water phantom, a water-bone-lung-water slab phantom and a half-slab phantom. Satisfactory agreement between the two MC dose engines goMC and gDPM was observed in all cases. The average dose differences in the regions that received a dose higher than 10% of the maximum dose were 0.48-0.53% for the electron beam cases and 0.15-0.17% for the photon beam cases. In terms of efficiency, goMC was ~4-16% slower than gDPM when running on the same NVidia TITAN card for all the cases we tested, due to both the different electron transport models and the different development environments. The code portability of our new dose engine goMC was validated by successfully running it on a variety of different computing devices including an NVidia GPU card, two AMD GPU cards and an Intel CPU processor. Computational efficiency among these platforms was compared.

An analytic linear accelerator source model for GPU-based Monte Carlo dose calculations.

Recently, there has been a lot of research interest in developing fast Monte Carlo (MC) dose calculation methods on graphics processing unit (GPU) platforms. A good linear accelerator (linac) source model is critical for both accuracy and efficiency considerations. In principle, an analytical source model should be more preferred for GPU-based MC dose engines than a phase-space file-based model, in that data loading and CPU-GPU data transfer can be avoided. In this paper, we presented an analytical field-independent source model specifically developed for GPU-based MC dose calculations, associated with a GPU-friendly sampling scheme. A key concept called phase-space-ring (PSR) was proposed. Each PSR contained a group of particles that were of the same type, close in energy and reside in a narrow ring on the phase-space plane located just above the upper jaws. The model parameterized the probability densities of particle location, direction and energy for each primary photon PSR, scattered photon PSR and electron PSR. Models of one 2D Gaussian distribution or multiple Gaussian components were employed to represent the particle direction distributions of these PSRs. A method was developed to analyze a reference phase-space file and derive corresponding model parameters. To efficiently use our model in MC dose calculations on GPU, we proposed a GPU-friendly sampling strategy, which ensured that the particles sampled and transported simultaneously are of the same type and close in energy to alleviate GPU thread divergences. To test the accuracy of our model, dose distributions of a set of open fields in a water phantom were calculated using our source model and compared to those calculated using the reference phase-space files. For the high dose gradient regions, the average distance-to-agreement (DTA) was within 1 mm and the maximum DTA within 2 mm. For relatively low dose gradient regions, the root-mean-square (RMS) dose difference was within 1.1% and the maximum dose difference within 1.7%. The maximum relative difference of output factors was within 0.5%. Over 98.5% passing rate was achieved in 3D gamma-index tests with 2%/2 mm criteria in both an IMRT prostate patient case and a head-and-neck case. These results demonstrated the efficacy of our model in terms of accurately representing a reference phase-space file. We have also tested the efficiency gain of our source model over our previously developed phase-space-let file source model. The overall efficiency of dose calculation was found to be improved by ~1.3-2.2 times in water and patient cases using our analytical model.

Multi-GPU implementation of a VMAT treatment plan optimization algorithm.

PURPOSE: Volumetric modulated arc therapy (VMAT) optimization is a computationally challenging problem due to its large data size, high degrees of freedom, and many hardware constraints. High-performance graphics processing units (GPUs) have been used to speed up the computations. However, GPU's relatively small memory size cannot handle cases with a large dose-deposition coefficient (DDC) matrix in cases of, e.g., those with a large target size, multiple targets, multiple arcs, and/or small beamlet size. The main purpose of this paper is to report an implementation of a column-generation-based VMAT algorithm, previously developed in the authors' group, on a multi-GPU platform to solve the memory limitation problem. While the column-generation-based VMAT algorithm has been previously developed, the GPU implementation details have not been reported. Hence, another purpose is to present detailed techniques employed for GPU implementation. The authors also would like to utilize this particular problem as an example problem to study the feasibility of using a multi-GPU platform to solve large-scale problems in medical physics. METHODS: The column-generation approach generates VMAT apertures sequentially by solving a pricing problem (PP) and a master problem (MP) iteratively. In the authors' method, the sparse DDC matrix is first stored on a CPU in coordinate list format (COO). On the GPU side, this matrix is split into four submatrices according to beam angles, which are stored on four GPUs in compressed sparse row format. Computation of beamlet price, the first step in PP, is accomplished using multi-GPUs. A fast inter-GPU data transfer scheme is accomplished using peer-to-peer access. The remaining steps of PP and MP problems are implemented on CPU or a single GPU due to their modest problem scale and computational loads. Barzilai and Borwein algorithm with a subspace step scheme is adopted here to solve the MP problem. A head and neck (H&N) cancer case is then used to validate the authors' method. The authors also compare their multi-GPU implementation with three different single GPU implementation strategies, i.e., truncating DDC matrix (S1), repeatedly transferring DDC matrix between CPU and GPU (S2), and porting computations involving DDC matrix to CPU (S3), in terms of both plan quality and computational efficiency. Two more H&N patient cases and three prostate cases are used to demonstrate the advantages of the authors' method. RESULTS: The authors' multi-GPU implementation can finish the optimization process within ∼ 1 min for the H&N patient case. S1 leads to an inferior plan quality although its total time was 10 s shorter than the multi-GPU implementation due to the reduced matrix size. S2 and S3 yield the same plan quality as the multi-GPU implementation but take ∼4 and ∼6 min, respectively. High computational efficiency was consistently achieved for the other five patient cases tested, with VMAT plans of clinically acceptable quality obtained within 23-46 s. Conversely, to obtain clinically comparable or acceptable plans for all six of these VMAT cases that the authors have tested in this paper, the optimization time needed in a commercial TPS system on CPU was found to be in an order of several minutes. CONCLUSIONS: The results demonstrate that the multi-GPU implementation of the authors' column-generation-based VMAT optimization can handle the large-scale VMAT optimization problem efficiently without sacrificing plan quality. The authors' study may serve as an example to shed some light on other large-scale medical physics problems that require multi-GPU techniques.

Towards the clinical implementation of iterative low-dose cone-beam CT reconstruction in image-guided radiation therapy: cone/ring artifact correction and multiple GPU implementation.

PURPOSE: Compressed sensing (CS)-based iterative reconstruction (IR) techniques are able to reconstruct cone-beam CT (CBCT) images from undersampled noisy data, allowing for imaging dose reduction. However, there are a few practical concerns preventing the clinical implementation of these techniques. On the image quality side, data truncation along the superior-inferior direction under the cone-beam geometry produces severe cone artifacts in the reconstructed images. Ring artifacts are also seen in the half-fan scan mode. On the reconstruction efficiency side, the long computation time hinders clinical use in image-guided radiation therapy (IGRT). METHODS: Image quality improvement methods are proposed to mitigate the cone and ring image artifacts in IR. The basic idea is to use weighting factors in the IR data fidelity term to improve projection data consistency with the reconstructed volume. In order to improve the computational efficiency, a multiple graphics processing units (GPUs)-based CS-IR system was developed. The parallelization scheme, detailed analyses of computation time at each step, their relationship with image resolution, and the acceleration factors were studied. The whole system was evaluated in various phantom and patient cases. RESULTS: Ring artifacts can be mitigated by properly designing a weighting factor as a function of the spatial location on the detector. As for the cone artifact, without applying a correction method, it contaminated 13 out of 80 slices in a head-neck case (full-fan). Contamination was even more severe in a pelvis case under half-fan mode, where 36 out of 80 slices were affected, leading to poorer soft tissue delineation and reduced superior-inferior coverage. The proposed method effectively corrects those contaminated slices with mean intensity differences compared to FDK results decreasing from ∼497 and ∼293 HU to ∼39 and ∼27 HU for the full-fan and half-fan cases, respectively. In terms of efficiency boost, an overall 3.1 × speedup factor has been achieved with four GPU cards compared to a single GPU-based reconstruction. The total computation time is ∼30 s for typical clinical cases. CONCLUSIONS: The authors have developed a low-dose CBCT IR system for IGRT. By incorporating data consistency-based weighting factors in the IR model, cone/ring artifacts can be mitigated. A boost in computational efficiency is achieved by multi-GPU implementation.

A hybrid reconstruction algorithm for fast and accurate 4D cone-beam CT imaging.

PURPOSE: 4D cone beam CT (4D-CBCT) has been utilized in radiation therapy to provide 4D image guidance in lung and upper abdomen area. However, clinical application of 4D-CBCT is currently limited due to the long scan time and low image quality. The purpose of this paper is to develop a new 4D-CBCT reconstruction method that restores volumetric images based on the 1-min scan data acquired with a standard 3D-CBCT protocol. METHODS: The model optimizes a deformation vector field that deforms a patient-specific planning CT (p-CT), so that the calculated 4D-CBCT projections match measurements. A forward-backward splitting (FBS) method is invented to solve the optimization problem. It splits the original problem into two well-studied subproblems, i.e., image reconstruction and deformable image registration. By iteratively solving the two subproblems, FBS gradually yields correct deformation information, while maintaining high image quality. The whole workflow is implemented on a graphic-processing-unit to improve efficiency. Comprehensive evaluations have been conducted on a moving phantom and three real patient cases regarding the accuracy and quality of the reconstructed images, as well as the algorithm robustness and efficiency. RESULTS: The proposed algorithm reconstructs 4D-CBCT images from highly under-sampled projection data acquired with 1-min scans. Regarding the anatomical structure location accuracy, 0.204 mm average differences and 0.484 mm maximum difference are found for the phantom case, and the maximum differences of 0.3-0.5 mm for patients 1-3 are observed. As for the image quality, intensity errors below 5 and 20 HU compared to the planning CT are achieved for the phantom and the patient cases, respectively. Signal-noise-ratio values are improved by 12.74 and 5.12 times compared to results from FDK algorithm using the 1-min data and 4-min data, respectively. The computation time of the algorithm on a NVIDIA GTX590 card is 1-1.5 min per phase. CONCLUSIONS: High-quality 4D-CBCT imaging based on the clinically standard 1-min 3D CBCT scanning protocol is feasible via the proposed hybrid reconstruction algorithm.

Evaluation of metric, topological, and temporal ordering memory tasks after lateral fluid percussion injury.

Impairments in learning and memory occur in as many as 50% of patients following traumatic brain injury (TBI). Similar impairments occur in rodent models of TBI, and the development of new memory testing procedures provides an opportunity to examine how TBI affects memory processing in specific neural memory systems. Specifically, metric, topological, and temporal ordering tasks are object-based tests for memory of spatial orientation and temporal sequencing working memory developed for use in rodents. Previous studies demonstrated that specific lesions of the dentate gyrus/CA3 of the hippocampus and the parietal cortex resulted in deficits in the metric and topological spatial orientation tasks, respectively. Lesions of the CA1 impaired a rat's ability to recall the temporal order of odors. The purpose of the following study was to determine whether moderate lateral fluid percussion TBI would generate deficits in these working memory tasks, and whether observed deficits were associated with cell loss in the CA2/3 and/or CA1 of the hippocampus. Two weeks following a moderate lateral fluid percussion TBI, adult rats demonstrated significant deficits in both the metric and temporal ordering tasks (p<0.05) but not in the topological task. Stereological analysis identified a significant reduction in neurons in the CA2/3 (p<0.05) but not the CA1 of the hippocampus. These data demonstrate the utility of three object-based tasks to expand our understanding of how different neural memory systems are affected by TBI.

A GPU tool for efficient, accurate, and realistic simulation of cone beam CT projections.

PURPOSE: Simulation of x-ray projection images plays an important role in cone beam CT (CBCT) related research projects, such as the design of reconstruction algorithms or scanners. A projection image contains primary signal, scatter signal, and noise. It is computationally demanding to perform accurate and realistic computations for all of these components. In this work, the authors develop a package on graphics processing unit (GPU), called gDRR, for the accurate and efficient computations of x-ray projection images in CBCT under clinically realistic conditions. METHODS: The primary signal is computed by a trilinear ray-tracing algorithm. A Monte Carlo (MC) simulation is then performed, yielding the primary signal and the scatter signal, both with noise. A denoising process specifically designed for Poisson noise removal is applied to obtain a smooth scatter signal. The noise component is then obtained by combining the difference between the MC primary and the ray-tracing primary signals, and the difference between the MC simulated scatter and the denoised scatter signals. Finally, a calibration step converts the calculated noise signal into a realistic one by scaling its amplitude according to a specified mAs level. The computations of gDRR include a number of realistic features, e.g., a bowtie filter, a polyenergetic spectrum, and detector response. The implementation is fine-tuned for a GPU platform to yield high computational efficiency. RESULTS: For a typical CBCT projection with a polyenergetic spectrum, the calculation time for the primary signal using the ray-tracing algorithms is 1.2-2.3 s, while the MC simulations take 28.1-95.3 s, depending on the voxel size. Computation time for all other steps is negligible. The ray-tracing primary signal matches well with the primary part of the MC simulation result. The MC simulated scatter signal using gDRR is in agreement with EGSnrc results with a relative difference of 3.8%. A noise calibration process is conducted to calibrate gDRR against a real CBCT scanner. The calculated projections are accurate and realistic, such that beam-hardening artifacts and scatter artifacts can be reproduced using the simulated projections. The noise amplitudes in the CBCT images reconstructed from the simulated projections also agree with those in the measured images at corresponding mAs levels. CONCLUSIONS: A GPU computational tool, gDRR, has been developed for the accurate and efficient simulations of x-ray projections of CBCT with realistic configurations.