Fluence-modulated proton CT optimized with patient-specific dose and variance objectives for proton dose calculation

Particle therapy treatment planning requires accurate volumetric maps of the relative stopping power, which can directly be acquired using proton computed tomography (pCT). With fluence-modulated pCT (FMpCT) imaging fluence is concentrated in a region-of-interest (ROI), which can be the vicinity of the treatment beam path, and imaging dose is reduced elsewhere. In this work we present a novel optimization algorithm for FMpCT which, for the first time, calculates modulated imaging fluences for joint imaging dose and image variance objectives. Thereby, image quality is maintained in the ROI to ensure accurate calculations of the treatment dose, and imaging dose is minimized outside the ROI with stronger minimization penalties given to imaging organs-at-risk. The optimization requires an initial scan at uniform fluence or a previous x-ray CT scan. We simulated and optimized FMpCT images for three pediatric patients with tumors in the head region. We verified that the target image variance inside the ROI was achieved and demonstrated imaging dose reductions outside of the ROI of 74% on average, reducing the imaging dose from 1.2 to 0.3 mGy. Such dose savings are expected to be relevant compared to the therapeutic dose outside of the treatment field. Treatment doses were re-calculated on the FMpCT images and compared to treatment doses re-recalculated on uniform fluence pCT scans using a 1% criterion. Passing rates were above 98.3% for all patients. Passing rates comparing FMpCT treatment doses to the ground truth treatment dose were above 88.5% for all patients. Evaluation of the proton range with a 1 mm criterion resulted in passing rates above 97.5% (FMpCT/pCT) and 95.3% (FMpCT/ground truth). Jointly optimized fluence-modulated pCT images can be used for proton dose calculation maintaining the full dosimetric accuracy of pCT but reducing the required imaging dose considerably by three quarters. This may allow for daily imaging during particle therapy ensuring a safe and accurate delivery of the therapeutic dose and avoiding excess dose from imaging

A Scintillator Beam Monitor for Real-Time FLASH Radiotherapy

FLASH Radiotherapy (RT) is a potentially new cancer radiotherapy technique where an entire therapeutic dose is delivered in about 0.1 s and at ~1000 times higher dose rate than in conventional RT. For clinical trials to be conducted safely, precise and fast beam monitoring that can generate an out-of-tolerance beam interrupt is required. A FLASH Beam Scintillator Monitor (FBSM) is being developed based in part on two novel proprietary scintillator materials: an organic polymeric material (PM) and inorganic hybrid (HM). The FBSM provides large area coverage, low mass profile, linear response over a broad dynamic range, radiation tolerance, and real-time analysis IEC-compliant fast beam-interrupt signal. This paper includes the design concept and test results from prototype devices in radiation beams that include heavy ions, low energy protons at nA currents, FLASH level dose per pulse electron beams, and in a hospital radiotherapy clinic with electron beams. Results include image quality, response linearity, radiation hardness, spatial resolution, and real-time data processing. PM and HM scintillator exhibited no measurable drop in signal after a cumulative dose of 9 kGy and 20 kGy respectively. HM showed a small -0.02%/kGy signal decrease after a 212 kGy cumulative dose resulting from continuous exposure for 15 minutes at a high FLASH dose rate of 234 Gy/s. These tests established the linear response of the FBSM with respect to beam currents, dose per pulse, and material thickness. Comparison with commercial Gafchromic film indicates that the FBSM produces a high resolution 2D beam image and can reproduce a nearly identical beam profile, including primary beam tails. At 20 kfps or 50 microsec/frame, the real-time FPGA based computation and analysis of beam position, beam shape, and beam dose takes < 1 microsec.Comment: 15 pages, 9 figure

A Highly Accelerated Parallel Multi-GPU based Reconstruction Algorithm for Generating Accurate Relative Stopping Powers

Low-dose Proton Computed Tomography (pCT) is an evolving imaging modality that is used in proton therapy planning which addresses the range uncertainty problem. The goal of pCT is generating a 3D map of Relative Stopping Power (RSP) measurements with high accuracy within clinically required time frames. Generating accurate RSP values within the shortest amount of time is considered a key goal when developing a pCT software. The existing pCT softwares have successfully met this time frame and even succeeded this time goal, but requiring clusters with hundreds of processors. This paper describes a novel reconstruction technique using two Graphics Processing Unit (GPU) cores, such as is available on a single Nvidia P100. The proposed reconstruction technique is tested on both simulated and experimental datasets and on two different systems namely Nvidia K40 and P100 GPUs from IBM and Cray. The experimental results demonstrate that our proposed reconstruction method meets both the timing and accuracy with the benefit of having reasonable cost, and efficient use of power.Comment: IEEE NSS/MIC 201

The Particle Tracking Silicon Microscope PTSM

Abstract-A novel position-and energy-sensitive particle detector for radiobiological application is described. The aim is to support research in radiation response of biological systems, for example in the induction of mutations in C. elegans, where precise knowledge of location and intensity of the radiation is crucial to understand radiation sensitivity of individual cells. The &quot;Particle Tracking Silicon Microscope&quot; (PTSM) consists of a silicon strip detector in direct contact with radiobiological samples (e.g., C. elegans), such that the location and intensity of particle radiation can be controlled at the 10µm scale. The readout is performed with low-noise readout electronics, which allows the determination of the particle&apos;s position from the hit strip address and its energy from the specific energy loss. In our implementation, the energy loss is measured through the timeover-threshold (TOT). The noise rate at acceptable thresholds is so low that the single particles can be detected with 100% efficiency. The performance of the front-end ASIC is described, and the results of initial environmental tests are reported. These include placing biological samples and saline solutions in direct contact with the silicon detectors

Effects of common haplotypes of the ileal sodium dependent bile acid transporter gene on the development of sporadic and familial colorectal cancer: A case control study

<p>Abstract</p> <p>Background</p> <p>The genetics of sporadic and non-syndromic familial colorectal cancer (CRC) is not well defined. However, genetic factors that promote the development of precursor lesions, i.e. adenomas, might also predispose to CRC. Recently, an association of colorectal adenoma with two variants (c.507C>T;p.L169L and c.511G>T;p.A171S) of the ileal sodium dependent bile acid transporter gene (<it>SLC10A2</it>) has been reported. Here, we reconstructed haplotypes of the <it>SLC10A2 </it>gene locus and tested for association with non-syndromic familial and sporadic CRC compared to 'hyper-normal' controls who displayed no colorectal polyps on screening colonoscopy.</p> <p>Methods</p> <p>We included 150 patients with sporadic CRC, 93 patients with familial CRC but exclusion of familial adenomatous polyposis and Lynch's syndrome, and 204 'hyper-normal' controls. Haplotype-tagging <it>SLC10A2 </it>gene variants were identified in the Hapmap database and genotyped using PCR-based 5' exonuclease assays with fluorescent dye-labelled probes. Haplotypes were reconstructed using the PHASE algorithm. Association testing was performed with both SNPs and reconstructed haplotypes.</p> <p>Results</p> <p>Minor allele frequencies of all <it>SLC10A2 </it>polymorphisms are within previously reported ranges, and no deviations from Hardy-Weinberg equilibrium are observed. However, we found no association with any of the <it>SLC10A2 </it>haplotypes with sporadic or familial CRC in our samples (all P values > 0.05).</p> <p>Conclusion</p> <p>Common variants of the <it>SLC10A2 </it>gene are not associated with sporadic or familial CRC. Hence, albeit this gene might be associated with early stages of colorectal neoplasia, it appears not to represent a major risk factor for progression to CRC.</p