M.Ramish Ashraf

All Publications

• Rapid Sterilization of Clinical Apheresis Blood Products Using Ultra-High Dose Rate Radiation. International journal of molecular sciences Melemenidis, S., Nguyen, K. D., Baraceros-Pineda, R., Barclay, C. K., Bautista, J., Lau, H. D., Ashraf, M. R., Manjappa, R., Dutt, S., Soto, L. A., Katila, N., Lau, B., Viswanathan, V., Yu, A. S., Surucu, M., Skinner, L. B., Engleman, E. G., Loo, B. W., Pham, T. D. 2025; 26 (6)

  Abstract

  Blood products, including apheresis platelets and plasma, are essential for medical use but pose risks of bacterial contamination and viral transmission. Platelets are prone to bacterial growth due to their storage conditions, while plasma requires extensive screening. This study explores rapid irradiation as an innovative pathogen reduction method. A clinical linear accelerator was configured to deliver ultra-high dose rate (6 kGy/min) irradiation to platelet and plasma components. Platelets spiked with Escherichia coli (E. coli; 10⁵ colony-forming units) were irradiated at 0.1-20 kGy, followed by bacterial growth and platelet count analysis. COVID-19 convalescent plasma (CCP) was irradiated at 25 kGy, and receptor-binding domain (RBD)-specific immunoglobulins (Ig) were assessed. Irradiation at 1 kGy reduced E. coli growth by 2.7-log without significant platelet loss, while 5 kGy achieved complete suppression. The estimated 6-log bacterial reduction dose (2.3 kGy) led to a 31% platelet count drop. Administering a 25 kGy virus-sterilizing dose to CCP resulted in a 9.2% decrease in RBD-specific IgG binding. This study demonstrates the proof-of-concept for rapid blood sterilization using a clinical linear accelerator. The method maintains platelet counts and CCP antibody binding at sterilizing doses, highlighting its potential as a point-of-care blood product sterilization solution.

  View details for DOI 10.3390/ijms26062424

  View details for PubMedID 40141066

• Dosimetric calibration of anatomy-specific ultra-high dose rate electron irradiation platform for preclinical FLASH radiobiology experiments. Medical physics Wang, J., Melemenidis, S., Manjappa, R., Viswanathan, V., Ashraf, R. M., Levy, K., Skinner, L. B., Soto, L. A., Chow, S., Lau, B., Ko, R. B., Graves, E. E., Yu, A. S., Bush, K. K., Surucu, M., Rankin, E. B., Loo, B. W., Schüler, E., Maxim, P. G. 2024

  Abstract

  FLASH radiation therapy (RT) offers a promising avenue for the broadening of the therapeutic index. However, to leverage the full potential of FLASH in the clinical setting, an improved understanding of the biological principles involved is critical. This requires the availability of specialized equipment optimized for the delivery of conventional (CONV) and ultra-high dose rate (UHDR) irradiation for preclinical studies. One method to conduct such preclinical radiobiological research involves adapting a clinical linear accelerator configured to deliver both CONV and UHDR irradiation.We characterized the dosimetric properties of a clinical linear accelerator configured to deliver ultra-high dose rate irradiation to two anatomic sites in mice and for cell-culture FLASH radiobiology experiments.Delivered doses of UHDR electron beams were controlled by a microcontroller and relay interfaced with the respiratory gating system. We also produced beam collimators with indexed stereotactic mouse positioning devices to provide anatomically specific preclinical treatments. Treatment delivery was monitored directly with an ionization chamber, and charge measurements were correlated with radiochromic film measurements at the entry surface of the mice. The setup for conventional dose rate irradiation utilized the same collimation system but at increased source-to-surface distance. Monte Carlo simulations and film dosimetry were used to characterize beam properties and dose distributions.The mean electron beam energies before the flattening filter were 18.8 MeV (UHDR) and 17.7 MeV (CONV), with corresponding values at the mouse surface of 17.2 and 16.2 MeV. The charges measured with an external ion chamber were linearly correlated with the mouse entrance dose. The use of relay gating for pulse control initially led to a delivery failure rate of 20% (± 1 pulse); adjustments to account for the linac latency improved this rate to < 1/20. Beam field sizes for two anatomically specific mouse collimators (4 × 4 cm2 for whole-abdomen and 1.5 × 1.5 cm2 for unilateral lung irradiation) were accurate within < 5% and had low radiation leakage (< 4%). Normalizing the dose at the center of the mouse (∼0.75 cm depth) produced UHDR and CONV doses to the irradiated volumes with > 95% agreement.We successfully configured a clinical linear accelerator for increased output and developed a robust preclinical platform for anatomically specific irradiation, with highly accurate and precise temporal and spatial dose delivery, for both CONV and UHDR irradiation applications.

  View details for DOI 10.1002/mp.17432

  View details for PubMedID 39331834

• Improving access in medical physics residency programs for physicists with disabilities. Journal of applied clinical medical physics Fagerstrom, J. M., Eliason, G., Al-Hallaq, H., Taylor, B. A., Ashraf, M. R., Viscariello, N. 2024: e14518

  Abstract

  Within the landscape of medical physics education, residency programs are instrumental in imparting hands-on training and experiential knowledge to early-career physicists. Ensuring access to educational opportunities for physicists with disabilities is a legal, ethical, and pragmatic requirement for programs, considering that a significant proportion of the United States population has a disability. Grounded in conceptual frameworks of competency-based medical education and the social model of disability, this work provides an introduction to some practical recommendations for medical physics residency programs. Strategies include embracing universal design principles, fostering partnerships with disability service offices, using inclusive language, developing and publicizing clear procedures for disclosing disabilities and requesting accommodations, and maintaining an overall commitment to equitable access to education. This work urges medical physics residency leadership to proactively move towards training environments that support the needs of residents across the spectrum of disability, highlighting why disability inclusion fundamentally enriches diversity.

  View details for DOI 10.1002/acm2.14518

  View details for PubMedID 39284579

• Commissioning an ultra-high-dose-rate electron linac with end-to-end tests. Physics in medicine and biology Dai, T., Sloop, A., Ashraf, M. R., Sunnerberg, J. P., Clark, M. A., Bruza, P., Pogue, B. W., Jarvis, L. A., Gladstone, D., Zhang, R. 2024

  Abstract

  The FLASH effect can potentially be used to improve the therapeutic ratio of radiotherapy (RT) through delivery of Ultra-high-dose-rate (UHDR) irradiation. Research is actively being conducted to translate UHDR-RT and for this purpose the Mobetron is capable of producing electron beams at both UHDR and conventional dose rates for FLASH research and translation. This work presents commissioning of an UHDR Mobetron with end-to-end tests developed for preclinical research. Approach. UHDR electron beams were commissioned with an efficient approach utilizing a 3D-printed water tank and film to fully characterize beam characteristics and dependences on field size, pulse width (PW) and pulse repetition frequency (PRF). This commissioning data was used to implement a beam model using the GAMOS Monte Carlo toolkit for the preclinical research. Then, the workflow for preclinical FLASH irradiation was validated with end-to-end tests delivered to a 3D-printed mouse phantom with internal inhomogeneities. Main results. PDDs, profiles and output factors acquired with radiochromic films were precisely measured, with a PRF that showed little effect on the UHDR beam energy and spatial characteristics. Increasing PW reduced the Dmax and R50 by 2.08 mm/µs and 1.28 mm/µs respectively. An end-to-end test of the preclinical research workflow showed that both profiles in head-foot and lateral directions were in good agreement with the MC calculations for the heterogeneous 3D printed mouse phantom with Gamma index above 93% for 2mm/2% criteria, and 99% for 3mm/3%. Significance. The UHDR Mobetron is a versatile tool for FLASH preclinical research and this comprehensive beam model and workflow was validated to meet the requirements for conducting translational FLASH research.

  View details for DOI 10.1088/1361-6560/ad69fc

  View details for PubMedID 39084661

• Commissioning of a novel PET-Linac for biology-guided radiotherapy (BgRT). Medical physics Surucu, M., Ashraf, M. R., Romero, I. O., Zalavari, L. T., Pham, D., Vitzthum, L. K., Gensheimer, M. F., Yang, Y., Xing, L., Kovalchuk, N., Han, B. 2024

  Abstract

  Biology-guided radiotherapy (BgRT) is a novel radiotherapy delivery technique that utilizes the tumor itself to guide dynamic delivery of treatment dose to the tumor. The RefleXion X1 system is the first radiotherapy system developed to deliver SCINTIX® BgRT. The X1 is characterized by its split arc design, employing two 90-degree positron emission tomography (PET) arcs to guide therapeutic radiation beams in real time, currently cleared by FDA to treat bone and lung tumors.This study aims to comprehensively evaluate the capabilities of the SCINTIX radiotherapy delivery system by evaluating its sensitivity to changes in PET contrast, its adaptability in the context of patient motion, and its performance across a spectrum of prescription doses.A series of experimental scenarios, both static and dynamic, were designed to assess the SCINTIX BgRT system's performance, including an end-to-end test. These experiments involved a range of factors, including changes in PET contrast, motion, and prescription doses. Measurements were performed using a custom-made ArcCHECK insert which included a 2.2 cm spherical target and a c-shape structure that can be filled with a PET tracer with varying concentrations. Sinusoidal and cosine4 motion patterns, simulating patient breathing, was used to test the SCINTIX system's ability to deliver BgRT during motion-induced challenges. Each experiment was evaluated against specific metrics, including Activity Concentration (AC), Normalized Target Signal (NTS), and Biology Tracking Zone (BTZ) bounded dose-volume histogram (bDVH) pass rates. The accuracy of the delivered BgRT doses on ArcCHECK and EBT-XD film were evaluated using gamma 3%/2 mm and 3%/3 mm analysis.In static scenarios, the X1 system consistently demonstrated precision and robustness in SCINTIX dose delivery. The end-to-end delivery to the spherical target yielded good results, with AC and NTS values surpassing the critical thresholds of 5 kBq/mL and 2, respectively. Furthermore, bDVH analysis consistently confirmed 100% pass rates. These results were reaffirmed in scenarios involving changes in PET contrast, emphasizing the system's ability to adapt to varying PET avidities. Gamma analysis with 3%/2 mm (10% dose threshold) criteria consistently achieved pass rates > 91.5% for the static tests. In dynamic SCINTIX delivery scenarios, the X1 system exhibited adaptability under conditions of motion. Sinusoidal and cosine4 motion patterns resulted in 3%/3 mm gamma pass rates > 87%. Moreover, the comparison with gated stereotactic body radiotherapy (SBRT) delivery on a conventional c-arm Linac resulted in 93.9% gamma pass rates and used as comparison to evaluate the interplay effect. The 1 cm step shift tests showed low overall gamma pass rates of 60.3% in ArcCHECK measurements, while the doses in the PTV agreed with the plan with 99.9% for 3%/3 mm measured with film.The comprehensive evaluation of the X1 radiotherapy delivery system for SCINTIX BgRT demonstrated good agreement for the static tests. The system consistently achieved critical metrics and delivered the BgRT doses per plan. The motion tests demonstrated its ability to co-localize the dose where the PET signal is and deliver acceptable BgRT dose distributions.

  View details for DOI 10.1002/mp.17114

  View details for PubMedID 38703397

• Multi-Institutional Audit of FLASH and Conventional Dosimetry with a 3D-Printed Anatomically Realistic Mouse Phantom. International journal of radiation oncology, biology, physics Ashraf, M. R., Melemenidis, S., Liu, K., Grilj, V., Jansen, J., Velasquez, B., Connell, L., Schulz, J. B., Bailat, C., Libed, A., Manjappa, R., Dutt, S., Soto, L., Lau, B., Garza, A., Larsen, W., Skinner, L., Yu, A. S., Surucu, M., Graves, E. E., Maxim, P. G., Kry, S. F., Vozenin, M. C., Schüler, E., Loo, B. W. 2024

  Abstract

  We conducted a multi-institutional dosimetric audit between FLASH and conventional dose rate (CONV) electron irradiations by using an anatomically realistic 3D-printed mouse phantom.A CT scan of a live mouse was used to create a 3D model of bony anatomy, lungs, and soft tissue. A dual-nozzle 3D printer was used to print the mouse phantom using acrylonitrile butadiene styrene (∼1.02 g/cm3) and polylactic acid (∼1.24 g/cm3) simultaneously to simulate soft tissue and bone densities, respectively. The lungs were printed separately using lightweight polylactic acid (∼0.64 g/cm3). Hounsfield units (HU), densities and print-to-print stability of the phantoms were assessed. Three institutions were each provided a phantom, and each institution performed two replicates of irradiations at selected anatomic regions. The average dose difference between FLASH and CONV dose distributions and deviation from the prescribed dose were measured with radiochromic film.Compared to the reference CT scan, CT scans of the phantom demonstrated mass density differences of 0.10 g/cm3 for bone, 0.12 g/cm3 for lung, and 0.03 g/cm3 for soft tissue regions. Differences in HU between phantoms were <10 HU for soft tissue and bone, with lung showing the most variation (54 HU), but with minimal impact on dose distribution (<0.5%). Mean differences between FLASH and CONV decreased from the first to the second replicate (4.3% to 1.2%), while differences from the prescribed dose decreased for both CONV (3.6% to 2.5%) and FLASH (6.4% to 2.7%). Total dose accuracy suggests consistent pulse dose and pulse number, though these were not specifically assessed. Positioning variability was observed, likely due to the absence of robust positioning aids or image guidance.This study marks the first dosimetric audit for FLASH using a non-homogeneous phantom, challenging conventional calibration practices reliant on homogeneous phantoms. The comparison protocol offers a framework for credentialing multi-institutional studies in FLASH preclinical research to enhance reproducibility of biological findings.

  View details for DOI 10.1016/j.ijrobp.2024.03.017

  View details for PubMedID 38493902

• Exploring deep learning for estimating the isoeffective dose of FLASH irradiation from mouse intestinal histology images. International journal of radiation oncology, biology, physics Fu, J., Yang, Z., Melemenidis, S., Viswanathan, V., Dutt, S., Manjappa, R., Lau, B., Soto, L. A., Ashraf, R., Skinner, L., Yu, S. J., Surucu, M., Casey, K. M., Rankin, E. B., Graves, E., Lu, W., Loo, B. W., Gu, X. 2024

  Abstract

  Ultra-high dose rate (FLASH) irradiation has been reported to reduce normal tissue damage compared with conventional dose rate (CONV) irradiation without compromising tumor control. This proof-of-concept study aims to develop a deep learning (DL) approach to quantify the FLASH isoeffective dose (dose of CONV that would be required to produce the same effect as the given physical FLASH dose) with post-irradiation mouse intestinal histological images.84 healthy C57BL/6J female mice underwent 16 MeV electron CONV (0.12Gy/s; n=41) or FLASH (200Gy/s; n=43) single fraction whole abdominal irradiation. Physical dose ranged from 12 to 16Gy for FLASH and 11 to 15Gy for CONV in 1Gy increments. 4 days after irradiation, 9 jejunum cross-sections from each mouse were H&E stained and digitized for histological analysis. CONV dataset was randomly split into training (n=33) and testing (n=8) datasets. ResNet101-based DL models were retrained using the CONV training dataset to estimate the dose based on histological features. The classical manual crypt counting (CC) approach was implemented for model comparison. Cross-section-wise mean squared error (CS-MSE) was computed to evaluate the dose estimation accuracy of both approaches. The validated DL model was applied to the FLASH dataset to map the physical FLASH dose into the isoeffective dose.The DL model achieved a CS-MSE of 0.20Gy2 on the CONV testing dataset compared with 0.40Gy2 of the CC approach. Isoeffective doses estimated by the DL model for FLASH doses of 12, 13, 14, 15, and 16 Gy were 12.19±0.46, 12.54±0.37, 12.69±0.26, 12.84±0.26, and 13.03±0.28 Gy, respectively.Our proposed DL model achieved accurate CONV dose estimation. The DL model results indicate that in the physical dose range of 13 to 16 Gy, the biological dose response of small intestinal tissue to FLASH irradiation is represented by a lower isoeffective dose compared to the physical dose. Our DL approach can be a tool for studying isoeffective doses of other radiation dose modifying interventions.

  View details for DOI 10.1016/j.ijrobp.2023.12.032

  View details for PubMedID 38171387

• Deep learning-based fluorescence image correction for high spatial resolution precise dosimetry. Physics in medicine and biology Nomura, Y., Ashraf, M. R., Shi, M., Xing, L. 2023

  Abstract

  While radiation-excited fluorescence imaging has great potential to measure absolute 2D dose distributions with high spatial resolution, the fluorescence images are contaminated by noise or artifacts due to Cherenkov light, scattered light or background noise. This study developed a novel deep learning-based model to correct the fluorescence images for accurate dosimetric application.181 single-aperture static photon beams were delivered to an acrylic tank containing quinine hemisulfate water solution. The emitted radiation-exited optical signals were detected by a complementary metal-oxide semiconductor camera to acquire fluorescence images with 0.3×0.3 mm2 pixel size. 2D labels of projected dose distributions were obtained by applying forward projection calculation of the 3D dose distributions calculated by a clinical treatment planning system. To calibrate the projected dose distributions for Cherenkov angular dependency, a novel empirical Cherenkov emission calibration method was performed. Total 400-epoch supervised learning was applied to a convolutional neural network (CNN) model to predict the projected dose distributions from fluorescence images, gantry, and collimator angles. Accuracy of the calculated projected dose distributions was evaluated with that of uncorrected or conventional methods by using a few quantitative evaluation metrics.The projected dose distributions corrected by the empirical Cherenkov emission calibration represented more accurate noise-free images than the uncalibrated distributions. The proposed CNN model provided accurate projected dose distributions. The mean absolute error of the projected dose distributions was improved from 2.02 to 0.766 mm∙Gy by the CNN model correction. Moreover, the CNN correction provided higher gamma index passing rates for three different threshold criteria than the conventional methods.The deep learning-based method improves the accuracy of dose distribution measurements. This technique will also be applied to optical signal denoising or Cherenkov light discrimination in other imaging modalities. This method will provide an accurate dose verification tool with high spatial resolution.

  View details for DOI 10.1088/1361-6560/acf182

  View details for PubMedID 37591253

• Angular correction methodology and characterization of a high-resolution CMOS array for patient specific quality assurance on a robotic arm linac. Journal of applied clinical medical physics Ashraf, M. R., Krimmer, J., Zalavri, L., Gu, X., Wang, L., Chuang, C. F. 2023: e14110

  Abstract

  PURPOSE: To develop an angular correction methodology and characterize a high-resolution complementary metal-oxide-semiconductor (CMOS) array for patient specific quality assurance on a robotic arm linear accelerator.METHODS: Beam path files from the treatment planning software (TPS) were used to calculate the angle of radiation beam with respect to the detector plane. Beams from multiple discrete angles were delivered to the CMOS detector array and an angular dependency look up table (LUT) was created. The LUT was then used to correct for the angular dependency of the detector. An iso-centric 5mm fixed cone, non iso-centric multi-target fixed cone, 10mm Iris and a multi-leaf collimator (MLC) based collimated plan were delivered to the phantom and compared to the TPS with and without angular correction applied. Additionally, the CMOS array was compared to gafchromic film and a diode array.RESULTS: Large errors of up to 30% were observed for oblique angles. When angular correction was applied, the gamma passing rate increased from 99.2% to 100% (average gamma value decreased from 0.29 to 0.14) for the 5-mm iso-centric cone plan. Similarly, the passing rate increased from 84.0% to 100% for the Iris plan and from 49.98% to 98.4% for the MLC plan when angular correction was applied. For the multi-target plan, applying angular correction improved the gamma passing rate from 94% to 99.6%. The 5mm iso-centric fixed cone plan was also delivered to film, and the gamma passing rate was 91.3% when using gafchromic film as the reference dataset, whereas the diode array provided insufficient sampling for this plan.CONCLUSION: A methodology of calculating the beam angle based on the beam path files was developed and validated. The array was demonstrated to be superior to other quality assurance tools because of its sub-millimeter spatial resolution and immediate read out of the results.

  View details for DOI 10.1002/acm2.14110

  View details for PubMedID 37528747

• Characterization of a diode dosimeter for UHDR FLASH radiotherapy. Medical physics Rahman, M., Kozelka, J., Hildreth, J., Schönfeld, A., Sloop, A. M., Ashraf, M. R., Bruza, P., Gladstone, D. J., Pogue, B. W., Simon, W. E., Zhang, R. 2023

  Abstract

  Ultra-high dose rate (UHDR) FLASH beams typically deliver dose at rates of  >40 Gy/sec. Characterization of these beams with respect to dose, mean dose rate, and dose per pulse requires dosimeters which exhibit high temporal resolution and fast readout capabilities.A diode EDGE Detector with a newly designed electrometer has been characterized for use in an UHDR electron beam and demonstrated appropriateness for UHDR FLASH radiotherapy dosimetry.Dose linearity, mean dose rate, and dose per pulse dependencies of the EDGE Detector were quantified and compared with dosimeters including a W1 scintillator detector, radiochromic film, and ionization chamber that were irradiated with a 10 MeV UHDR beam. The dose, dose rate, and dose per pulse were controlled via an in-house developed scintillation-based feedback mechanism, repetition rate of the linear accelerator, and source-to-surface distance, respectively. Depth-dose profiles and temporal profiles at individual pulse resolution were compared to the film and scintillation measurements, respectively. The radiation-induced change in response sensitivity was quantified via irradiation of ∼5kGy.The EDGE Detector agreed with film measurements in the measured range with varying dose (up to 70 Gy), dose rate (nearly 200 Gy/s), and dose per pulse (up to 0.63 Gy/pulse) on average to within 2%, 5%, and 1%, respectively. The detector also agreed with W1 scintillation detector on average to within 2% for dose per pulse (up to 0.78 Gy/pulse). The EDGE Detector signal was proportional to ion chamber (IC) measured dose, and mean dose rate in the bremsstrahlung tail to within 0.4% and 0.2% respectively. The EDGE Detector measured percent depth dose (PDD) agreed with film to within 3% and per pulse output agreed with W1 scintillator to within -6% to +5%. The radiation-induced response decrease was 0.4% per kGy.The EDGE Detector demonstrated dose linearity, mean dose rate independence, and dose per pulse independence for UHDR electron beams. It can quantify the beam spatially, and temporally at sub millisecond resolution. It's robustness and individual pulse detectability of treatment deliveries can potentially lead to its implementation for in vivo FLASH dosimetry, and dose monitoring.

  View details for DOI 10.1002/mp.16474

  View details for PubMedID 37249058

• An Integrated 3D Printed Enclosure for a Radioluminescent-Based Phantom for Quality Assurance on a Robotic-Arm Linac. Physics in medicine and biology Ashraf, M. R., Gibson, C., Skinner, L. B., Gu, X., Xing, L., Wang, L. 2023

  Abstract

  To develop, characterize and improve upon a high-resolution 3D printed radioluminescence-based imaging phantom for quality assurance (QA) of a robotic arm linear accelerator. Approach: A phantom was constructed which consisted of a scintillating sheet, fiducial markers, a low-cost CMOS camera and a 3D printed light-tight enclosure. The camera, equipped with a 12 mm lens, was angled 45 degrees from the horizontal axis with a direct line of sight of the scintillating sheet. A perspective image transformation with optical distortion correction was employed to obtain beam's eye view images for different collimators. Beam profiles, Iris™ field size, MLC leaf positioning and central laser-radiation field coincidence QA tests were performed and compared against data obtained with gafchromic film. The phantom's short-term stability, sensitivity to changes in output, field size and leaf positioning were also assessed. Main Results: The limiting resolution of the optical system was measured to be ~ 0.26 mm. Field size, as measured by the radioluminescence system for Iris apertures, agreed to within 0.2 mm of the values measured using film. The imaging system was sensitive to field size changes well below 0.2 mm and output changes as small as 1 Monitor Unit (MU). For the optical setup, the mean leaf deviation error for banks X1 and X2 was 0.21 and 0.17 mm at 800 mm SAD, whereas the mean difference for the film dataset was 0.16 mm and 0.22 mm for banks X1 and X2, respectively. The optical system was able to detect leaf positioning errors as small as 0.2 mm. Compared with film data, excellent agreement was seen for relative central axis beam profiles for 10 mm and 5 mm beams. Significance: The phantom presented here is an alternative to film and electronic portal imager devices, due to its low-cost, portability, and high spatial and temporal resolution. .

  View details for DOI 10.1088/1361-6560/acd162

  View details for PubMedID 37116515

• Clinical LINAC-based electron FLASH: Pathway for practical translation to FLASH clinical trials: LINAC electron FLASH. International journal of radiation oncology, biology, physics No, H. J., Wu, Y. F., Dworkin, M. L., Manjappa, R., Skinner, L., Ashraf, M. R., Lau, B., Melemenidis, S., Viswanathan, V., Yu, A. S., Surucu, M., Schüler, E., Graves, E. E., Maxim, P. G., Loo, B. W. 2023

  Abstract

  Ultra-high dose rate (UHDR) radiotherapy (RT) has produced the FLASH effect in preclinical models: reduced toxicity with comparable tumor control compared to conventional dose rate RT. Early clinical trials focused on UHDR RT feasibility using specialized devices. We explore the technical feasibility of practical electron UHDR RT on a standard clinical linear accelerator (LINAC).We tuned the program board of a decommissioned electron energy for UHDR electron delivery on a clinical LINAC, without hardware modification. Pulse delivery was controlled using the respiratory gating interface. A short SSD electron set-up with a standard scattering foil was configured and tested on an anthropomorphic phantom using circular blocks with 3-20 cm field sizes. Dosimetry was evaluated using radiochromic film and an ion chamber profiler.UHDR open field mean dose rates at 100, 80, 70, and 59 cm SSD were 36.82, 59.52, 82.01, and 112.83 Gy/s, respectively. At 80 cm SSD, mean dose rate was ∼60 Gy/s for all collimated field sizes, with an R80 depth of 6.1 cm corresponding to an energy of 17.5 MeV. Heterogeneity was <5.0% with asymmetry of 2.2 to 6.2%. The short SSD set-up was feasible under realistic treatment conditions simulating broad clinical indications on an anthropomorphic phantom.Short SSD and tuning for high electron beam current on a standard clinical LINAC can deliver flat, homogenous UHDR electrons over a broad, clinically relevant range of field sizes and depths with practical working distances, in a configuration easily reversible to standard clinical use.

  View details for DOI 10.1016/j.ijrobp.2023.04.011

  View details for PubMedID 37105403

• Human enteroids as a tool to study conventional and ultra-high dose rate radiation. Integrative biology : quantitative biosciences from nano to macro Klett, K. C., Martin-Villa, B. C., Villarreal, V. S., Melemenidis, S., Viswanathan, V., Manjappa, R., Ashraf, M. R., Soto, L., Lau, B., Dutt, S., Rankin, E. B., Loo, B. W., Heilshorn, S. C. 2023; 15

  Abstract

  Radiation therapy, one of the most effective therapies to treat cancer, is highly toxic to healthy tissue. The delivery of radiation at ultra-high dose rates, FLASH radiation therapy (FLASH), has been shown to maintain therapeutic anti-tumor efficacy while sparing normal tissues compared to conventional dose rate irradiation (CONV). Though promising, these studies have been limited mainly to murine models. Here, we leveraged enteroids, three-dimensional cell clusters that mimic the intestine, to study human-specific tissue response to radiation. We observed enteroids have a greater colony growth potential following FLASH compared with CONV. In addition, the enteroids that reformed following FLASH more frequently exhibited proper intestinal polarity. While we did not observe differences in enteroid damage across groups, we did see distinct transcriptomic changes. Specifically, the FLASH enteroids upregulated the expression of genes associated with the WNT-family, cell-cell adhesion, and hypoxia response. These studies validate human enteroids as a model to investigate FLASH and provide further evidence supporting clinical study of this therapy. Insight Box Promising work has been done to demonstrate the potential of ultra-high dose rate radiation (FLASH) to ablate cancerous tissue, while preserving healthy tissue. While encouraging, these findings have been primarily observed using pre-clinical murine and traditional two-dimensional cell culture. This study validates the use of human enteroids as a tool to investigate human-specific tissue response to FLASH. Specifically, the work described demonstrates the ability of enteroids to recapitulate previous in vivo findings, while also providing a lens through which to probe cellular and molecular-level responses to FLASH. The human enteroids described herein offer a powerful model that can be used to probe the underlying mechanisms of FLASH in future studies.

  View details for DOI 10.1093/intbio/zyad013

  View details for PubMedID 37874173

• Radio-luminescent imaging for rapid, high resolution eye plaque loading verification. Medical physics Yan, H., De Jean, P., Grafil, E., Ashraf, R., Niedermayr, T., Astrahan, M., Mruthyunjaya, P., Beadle, B., Xing, L., Liu, W. 2022

  Abstract

  BACKGROUND: Eye plaque brachytherapy (EPB) is currently an optimal therapy for intraocular cancers. Due to the lack of an effective and practical technique to measure the seed radioactivity distribution, current quality assurance (QA) practice according to the AAPM TG129 only stipulates that the plaque assembly be visually inspected. Consequently, uniform seed activity is routinely adopted to avoid possible loading mistakes of differential seed loading. However, modulated dose delivery, which represents a general trend in radiotherapy to provide more personalized treatment for a given tumor and patient, requires differential activities in the loaded seeds.PURPOSE: In this study, a fast and low-cost radio-luminescent imaging and dose calculating system to verify the seed activity distribution for differential loading was developed.METHODS: A proof-of-concept system consisting of a thin scintillator sheet coupled to a camera/lens system was constructed. A seed-loaded plaque can be placed directly on the scintillator surface with the radioactive seeds facing the scintillator. The camera system collects the radioluminescent signal generated by the scintillator at its opposite side. The predicted dose distribution in the scintillator's sensitive layer was calculated using a Monte Carlo simulation with the planned plaque loading pattern of I-125 seeds. Quantitative comparisons of the distribution of relative measured signal intensity and that of the relative predicted dose in the sensitive layer were performed by gamma analysis, similar to IMRT QA.RESULTS: Data analyses showed high gamma (3%/0.3mm, global, 20% threshold) passing rates for correct seed loadings and low passing rates with distinguished high gamma value area for incorrect loadings, indicating that possible errors may be detected. The measurement and analysis only required a few extra minutes, significantly shorter than the time to assay the extra verification seeds the physicist already must perform as recommended by TG129.CONCLUSIONS: Radio-luminescent QA can be used to facilitate and assure the implementation of intensity modulated, customized plaque loading. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/mp.16003

  View details for PubMedID 36183146

• Real-time optical oximetry during FLASH radiotherapy using a phosphorescent nanoprobe. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology Ha, B., Liang, K., Liu, C., Melemenidis, S., Manjappa, R., Viswanathan, V., Das, N., Ashraf, R., Lau, B., Soto, L., Graves, E. E., Rao, J., Loo, B. W., Pratx, G. 2022

  Abstract

  The rapid depletion of oxygen during irradiation at ultra-high dose rate calls for tissue oximeters capable of high temporal resolution. This study demonstrates a water-soluble phosphorescent nanoprobe and fiber-coupled instrument, which together are used to measure the kinetics of oxygen depletion at 200 Hz during irradiation of in vitro solutions.

  View details for DOI 10.1016/j.radonc.2022.08.011

  View details for PubMedID 35964762

• Individual pulse monitoring and dose control system for pre-clinical implementation of FLASH-RT PHYSICS IN MEDICINE AND BIOLOGY Ashraf, M., Rahman, M., Cao, X., Duval, K., Williams, B. B., Hoopes, P., Gladstone, D. J., Pogue, B. W., Zhang, R., Bruza, P. 2022; 67 (9)

  Abstract

  Objective.Existing ultra-high dose rate (UHDR) electron sources lack dose rate independent dosimeters and a calibrated dose control system for accurate delivery. In this study, we aim to develop a custom single-pulse dose monitoring and a real-time dose-based control system for a FLASH enabled clinical linear accelerator (Linac).Approach.A commercially available point scintillator detector was coupled to a gated integrating amplifier and a real-time controller for dose monitoring and feedback control loop. The controller was programmed to integrate dose for each radiation pulse and stop the radiation beam when the prescribed dose was delivered. Additionally, the scintillator was mounted in a solid water phantom and placed underneath mice skin forin vivodose monitoring. The scintillator was characterized in terms of its radiation stability, mean dose-rate (Ḋm), and dose per pulse (Dp) dependence.Main results.TheDpexhibited a consistent ramp-up period across ∼4-5 pulse. The plastic scintillator was shown to be linear withḊm(40-380 Gy s-1) andDp(0.3-1.3 Gy Pulse-1) to within +/- 3%. However, the plastic scintillator was subject to significant radiation damage (16%/kGy) for the initial 1 kGy and would need to be calibrated frequently. Pulse-counting control was accurately implemented with one-to-one correspondence between the intended and the actual delivered pulses. The dose-based control was sufficient to gate on any pulse of the Linac.In vivodosimetry monitoring with a 1 cm circular cut-out revealed that during the ramp-up period, the averageDpwas ∼0.045 ± 0.004 Gy Pulse-1, whereas after the ramp-up it stabilized at 0.65 ± 0.01 Gy Pulse-1.Significance.The tools presented in this study can be used to determine the beam parameter space pertinent to the FLASH effect. Additionally, this study is the first instance of real-time dose-based control for a modified Linac at ultra-high dose rates, which provides insight into the tool required for future clinical translation of FLASH-RT.

  View details for DOI 10.1088/1361-6560/ac5f6f

  View details for Web of Science ID 000784127400001

  View details for PubMedID 35313290

• Quantification of Oxygen Depletion During FLASH Irradiation In Vitro and In Vivo INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Cao, X., Zhang, R., Esipova, T. V., Allu, S., Ashraf, R., Rahman, M., Gunn, J. R., Bruza, P., Gladstone, D. J., Williams, B. B., Swartz, H. M., Hoopes, P., Vinogradov, S. A., Pogue, B. W. 2021; 111 (1): 240-248

  Abstract

  Delivery of radiation at ultrahigh dose rates (UHDRs), known as FLASH, has recently been shown to preferentially spare normal tissues from radiation damage compared with tumor tissues. However, the underlying mechanism of this phenomenon remains unknown, with one of the most widely considered hypotheses being that the effect is related to substantial oxygen depletion upon FLASH, thereby altering the radiochemical damage during irradiation, leading to different radiation responses of normal and tumor cells. Testing of this hypothesis would be advanced by direct measurement of tissue oxygen in vivo during and after FLASH irradiation.Oxygen measurements were performed in vitro and in vivo using the phosphorescence quenching method and a water-soluble molecular probe Oxyphor 2P. The changes in oxygen per unit dose (G-values) were quantified in response to irradiation by 10 MeV electron beam at either UHDR reaching 300 Gy/s or conventional radiation therapy dose rates of 0.1 Gy/s.In vitro experiments with 5% bovine serum albumin solutions at 23°C resulted in G-values for oxygen consumption of 0.19 to 0.21 mm Hg/Gy (0.34-0.37 μM/Gy) for conventional irradiation and 0.16 to 0.17 mm Hg/Gy (0.28-0.30 μM/Gy) for UHDR irradiation. In vivo, the total decrease in oxygen after a single fraction of 20 Gy FLASH irradiation was 2.3 ± 0.3 mm Hg in normal tissue and 1.0 ± 0.2 mm Hg in tumor tissue (P < .00001), whereas no decrease in oxygen was observed from a single fraction of 20 Gy applied in conventional mode.Our observations suggest that oxygen depletion to radiologically relevant levels of hypoxia is unlikely to occur in bulk tissue under FLASH irradiation. For the same dose, FLASH irradiation induces less oxygen consumption than conventional irradiation in vitro, which may be related to the FLASH sparing effect. However, the difference in oxygen depletion between FLASH and conventional irradiation could not be quantified in vivo because measurements of oxygen depletion under conventional irradiation are hampered by resupply of oxygen from the blood.

  View details for DOI 10.1016/j.ijrobp.2021.03.056

  View details for Web of Science ID 000709361500032

  View details for PubMedID 33845146

  View details for PubMedCentralID PMC8338745

• Spatial and temporal dosimetry of individual electron FLASH beam pulses using radioluminescence imaging PHYSICS IN MEDICINE AND BIOLOGY Rahman, M., Ashraf, M., Zhang, R., Gladstone, D. J., Cao, X., Williams, B. B., Jack Hoopes, P., Pogue, B. W., Bruza, P. 2021; 66 (13)

  Abstract

  Purpose.In this study, spatio-temporal beam profiling for electron ultra-high dose rate (UHDR; >40 Gy s-1) radiation via Cherenkov emission and radioluminescence imaging was investigated using intensified complementary metal-oxide-semiconductor cameras.Methods.The cameras, gated to FLASH optimized linear accelerator pulses, imaged radioluminescence and Cherenkov emission incited by single pulses of a UHDR (>40 Gy s-1) 10 MeV electron beam delivered to the isocenter. Surface dosimetry was investigated via imaging Cherenkov emission or scintillation from a solid water phantom or Gd2O2S:Tb screen positioned on top of the phantom, respectively. Projected depth-dose profiles were imaged from a tank filled with water (Cherenkov emission) and a 1 g l-1quinine sulfate solution (scintillation). These optical results were compared with projected lateral dose profiles measured by Gafchromic film at different depths, including the surface.Results.The per-pulse beam output from Cherenkov imaging agreed with the photomultiplier tube Cherenkov output to within 3% after about the first five to seven ramp-up pulses. Cherenkov emission and scintillation were linear with dose (R2 = 0.987 and 0.995, respectively) and independent of dose rate from ∼50 to 300 Gy s-1(0.18-0.91 Gy/pulse). The surface dose distribution from film agreed better with scintillation than with Cherenkov emission imaging (3%/3 mm gamma pass rates of 98.9% and 88.8%, respectively). Using a 450 nm bandpass filter, the quinine sulfate-based water imaging of the projected depth optical profiles agreed with the projected film dose to within 5%.Conclusion.The agreement of surface dosimetry using scintillation screen imaging and Gafchromic film suggests it can verify the consistency of daily beam quality assurance parameters with an accuracy of around 2% or 2 mm. Cherenkov-based surface dosimetry was affected by the target's optical properties, prompting additional calibration. In projected depth-dose profiling, scintillation imaging via spectral suppression of Cherenkov emission provided the best match to film. Both camera-based imaging modalities resolved dose from single UHDR beam pulses of up to 60 Hz repetition rate and 1 mm spatial resolution.

  View details for DOI 10.1088/1361-6560/ac0390

  View details for Web of Science ID 000668326600001

  View details for PubMedID 34015774

• Electron FLASH Delivery at Treatment Room Isocenter for Efficient Reversible Conversion of a Clinical LINAC INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Rahman, M., Ashraf, R., Zhang, R., Bruza, P., Dexter, C. A., Thompson, L., Cao, X., Williams, B. B., Hoopes, P., Pogue, B. W., Gladstone, D. J. 2021; 110 (3): 872-882

  Abstract

  In this study, procedures were developed to achieve efficient reversible conversion of a clinical linear accelerator (LINAC) and deliver ultrahigh-dose-rate (UHDR) electron or conventional beams to the treatment room isocenter for FLASH radiation therapy.The LINAC was converted to deliver UHDR beam within 20 minutes by retracting the x-ray target from the beam's path, positioning the carousel on an empty port, and selecting 10 MV photon beam energy in the treatment console. Dose rate surface and depth dose profiles were measured in solid water phantom at different field sizes with Gafchromic film and an optically stimulated luminescent dosimeter (OSLD). A pulse controller counted the pulses via scattered radiation signal and gated the delivery for a preset pulse count. A fast photomultiplier tube-based Cherenkov detector measured the per pulse beam output at a 2-ns sampling rate. After conversion back to clinical mode, conventional beam output, flatness, symmetry, field size, and energy were measured for all clinically commissioned energies.The surface average dose rates at the isocenter for 1-cm diameter and 1.5-in diameter circular fields and for a jaws-wide-open field were 238 ± 5 Gy/s, 262 ± 5 Gy/s, and 290 ± 5 Gy/s, respectively. The radial symmetry of the beams was within 2.4%, 0.5%, and 0.2%, respectively. The doses from simultaneous irradiation of film and OSLD were within 1%. The photomultiplier tube showed the LINAC required ramp up time in the first 4 to 6 pulses before the output stabilized, after which its stability was within 3%.At the isocenter of the treatment room, 10 MeV UHDR beams were achieved. The beam output was reproducible but requires further investigation of the ramp up time, equivalent to ∼1 Gy, requiring dose monitoring. The UHDR beam can irradiate both small and large subjects to investigate potential FLASH radiobiological effects in minimally modified clinical settings, and the dose rate can be further increased by reducing the source-to-surface distance.

  View details for DOI 10.1016/j.ijrobp.2021.01.011

  View details for Web of Science ID 000657308400036

  View details for PubMedID 33444695

• The Conversion of Clinical Linear Accelerators for FLASH Radiation Delivery Reply INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Rahman, M., Ashraf, M., Zhang, R., Bruza, P., Dexter, C. A., Thompson, L., Cao, X., Williams, B. B., Hoopes, P., Pogue, B. W., Gladstone, D. J. 2021; 110 (3): 909-910

  View details for DOI 10.1016/j.ijrobp.2021.03.045

  View details for Web of Science ID 000657308400042

  View details for PubMedID 33811977

• Spatiotemporal Dose Characterization of An Electron FLASH Beam from a LINAC Using Radioluminescence and Cherenkov Imaging Rahman, M., Ashraf, M., Zhang, R., Gladstone, D., Cao, X., Williams, B., Hoopes, J., Pogue, B., Bruza, P. WILEY. 2021

  View details for Web of Science ID 000673145401212

• Pulse Resolved Beam Characterization and Feedback for FLASH-RT Using Radioluminescent Dosimeters Ashraf, M., Rahman, M., Zhang, R., Williams, B., Hoopes, J., Gladstone, D., Pogue, B., Bruza, P. WILEY. 2021

  View details for Web of Science ID 000673145401243

• Electron FLASH in Clinical Setting: LINAC Conversion, Commissioning and Treatment Planning Rahman, M., Ashraf, M., Gladstone, D., Bruza, P., Jarvis, L., Schaner, P., Cao, X., Pogue, B., Hoopes, J., Zhang, R. WILEY. 2021

  View details for Web of Science ID 000673145400306

• Technical Note: Single-pulse beam characterization for FLASH-RT using optical imaging in a water tank MEDICAL PHYSICS Ashraf, M., Rahman, M., Zhang, R., Cao, X., Williams, B. B., Hoopes, P., Gladstone, D. J., Pogue, B. W., Bruza, P. 2021; 48 (5): 2673-2681

  Abstract

  High dose rate conditions, coupled with problems related to small field dosimetry, make dose characterization for FLASH-RT challenging. Most conventional dosimeters show significant dependence on dose rate at ultra-high dose rate conditions or fail to provide sufficiently fast temporal data for pulse to pulse dosimetry. Here fast 2D imaging of radioluminescence from a water and quinine phantom was tested for dosimetry of individual 4 μs linac pulses.A modified clinical linac delivered an electron FLASH beam of >50 Gy/s to clinical isocenter. This modification removed the x-ray target and flattening filter, leading to a beam that was symmetric and gaussian, as verified with GafChromic EBT-XD film. Lateral projected 2D dose distributions for each linac pulse were imaged in a quinine-doped water tank using a gated intensified camera, and an inverse Abel transform reconstruction provided 3D images for on-axis depth dose values. A total of 20 pulses were delivered with a 10 MeV, 1.5 cm circular beam, and beam with jaws wide open (40 × 40 cm2 ), and a 3D dose distribution was recovered for each pulse. Beam output was analyzed on a pulse by pulse basis.The Rp , Dmax , and the R50 measured with film and optical methods agreed to within 1 mm for the 1.5 cm circular beam and the beam with jaws wide open. Cross beam profiles for both beams agreed with film data with >95% passing rate (2%/2 mm gamma criteria). The optical central axis depth dose agreed with film data, except for near the surface. A temporal pulse analysis revealed a ramp-up period where the dose per pulse increased for the first few pulses and then stabilized.Optical imaging of radioluminescence was presented as a valuable tool for establishing a baseline for the recently initiated electron FLASH beam at our institution.

  View details for DOI 10.1002/mp.14843

  View details for Web of Science ID 000635432500001

  View details for PubMedID 33730367

• Treatment Planning System for Electron FLASH Radiotherapy: Open-source for Clinical Implementation. International journal of radiation oncology, biology, physics Rahman, M., Ashraf, M. R., Gladstone, D. J., Bruza, P., Jarvis, L. A., Schaner, P. E., Cao, X., Pogue, B. W., Hoopes, P. J., Zhang, R. 2021

  Abstract

  A Monte Carlo (MC) beam model and its implementation in a clinical treatment planning system (TPS, Varian Eclipse) are presented for a modified ultra-high dose-rate electron FLASH radiotherapy LINAC (eFLASH-RT) utilizing clinical accessories and geometry.The gantry head without scattering foils or targets, representative of the LINAC modifications, was modelled in Geant4-based GAMOS MC toolkit. The energy spectrum (σE) and beam source emittance cone angle (θcone) were varied to match the calculated open field central-axis percent depth dose (PDD) and lateral profiles with Gafchromic film measurements. The beam model and its Eclipse configuration were validated with measured profiles of the open field and nominal fields for clinical applicators. A MC forward dose calculation was conducted for a mouse whole brain treatment and an eFLASH-RT plan was compared to a conventional (Conv-RT) electron plan in Eclipse for a human patient with metastatic renal cell carcinoma.The eFLASH beam model agreed best with measurements at σE=0.5 MeV and θcone=3.9±0.2 degrees. The model and its Eclipse configuration were validated to clinically acceptable accuracy (the absolute average error was within 1.5% for in-water lateral, 3% for in-air lateral, and 2% for PDD's). The forward calculation showed adequate dose delivery to the entire mouse brain, while sparing the organ-at-risk (lung). The human patient case demonstrated the planning capability with routine accessories to achieve an acceptable plan (90% of the tumor volume receiving 95% and 90% of the prescribed dose for eFLASH and conventional, respectively).To the best of our knowledge, this is the first functional beam model commissioned in a clinical TPS for eFLASH-RT, enabling planning and evaluation with minimal deviation from Conv-RT workflow. It facilitates the clinical translation as eFLASH-RT and Conv-RT plan quality were comparable for a human patient involving complex geometries and tissue heterogeneity. The methods can be expanded to model other eFLASH irradiators with different beam characteristics.

  View details for DOI 10.1016/j.ijrobp.2021.10.148

  View details for PubMedID 34762969

• Dosimetry for FLASH Radiotherapy: A Review of Tools and the Role of Radioluminescence and Cherenkov Emission FRONTIERS IN PHYSICS Ashraf, M., Rahman, M., Zhang, R., Williams, B. B., Gladstone, D. J., Pogue, B. W., Bruza, P. 2020; 8

  View details for DOI 10.3389/fphy.2020.00328

  View details for Web of Science ID 000569685300001

• Real Time Plan Verification of Radiotherapy Treatment Plans Using Couch and Gantry Mounted Cameras Ashraf, M., Bruza, P., Pogue, B., Gladstone, D., Williams, B. WILEY. 2020: E474-E475

  View details for Web of Science ID 000699863600081

• High Resolution Optical Imaging of 4 & 5 Millimeter Beams: A Small Field Dosimetry Technique Ashraf, M., Bruza, P., Zhang, R., Rahman, M., Williams, B., Pogue, B., Gladstone, D. WILEY. 2020: E463

  View details for Web of Science ID 000699863600037

• Optical imaging provides rapid verification of static small beams, radiosurgery, and VMAT plans with millimeter resolution MEDICAL PHYSICS Ashraf, M., Bruza, P., Pogue, B. W., Nelson, N., Williams, B. B., Jarvis, L. A., Gladstone, D. J. 2019; 46 (11): 5227-5237

  Abstract

  We demonstrate the feasibility of optical imaging as a quality assurance tool for static small beamlets, and pretreatment verification tool for radiosurgery and volumetric-modulated arc therapy (VMAT) plans.Small static beams and clinical VMAT plans were simulated in a treatment planning system (TPS) and delivered to a cylindrical tank filled with water-based liquid scintillator. Emission was imaged using a blue-sensitive, intensified CMOS camera time-gated to the linac pulses. For static beams, percentage depth and cross beam profiles of projected intensity distribution were compared to TPS data. Two-dimensional (2D) gamma analysis was performed on all clinical plans, and the technique was tested for sensitivity against common errors (multileaf collimator position, gantry angle) by inducing deliberate errors in the VMAT plans control points. The technique's detection limits for spatial resolution and the smallest number of control points that could be imaged reliably were also tested. The sensitivity to common delivery errors was also compared against a commercial 2.5D diode array dosimeter.A spatial resolution of 1 mm was achieved with our imaging setup. The optical projected percentage depth intensity profiles agreed to within 2% relative to the TPS data for small static square beams (5, 10, and 50 mm2 ). For projected cross beam profiles, a gamma pass rate >99% was achieved for a 3%/1 mm criteria. All clinical plans passed the 3%/3 mm criteria with >95% passing rate. A static 5 mm beam with 20 Monitor Units could be measured with an average percent difference of 5.5 ± 3% relative to the TPS. The technique was sensitive to multileaf collimator errors down to 1 mm and gantry angle errors of 1°.Optical imaging provides ample spatial resolution for imaging small beams. The ability to faithfully image down to 20 MU of 5 mm, 6 MV beamlets prove the ability to perform quality assurance for each control point within dynamic plans. The technique is sensitive to small offset errors in gantry angles and multileaf collimator (MLC) leaf positions, and at certain scenario, it exhibits higher sensitivity than a commercial 2.5D diode array.

  View details for DOI 10.1002/mp.13797

  View details for Web of Science ID 000494894600049

  View details for PubMedID 31472093

  View details for PubMedCentralID PMC7082501

• Real-Time 3D Scintillation Imaging Enables Rapid End-To-End Verification of Online Adaptive Replanning On MR-Linac Bruza, P., Ashraf, M., Cammin, J., Maraghechi, B., Pogue, B., Green, O. WILEY. 2019: E500

  View details for Web of Science ID 000471277704009

• Remote, Real-Time Optical Imaging of Small Beamlets in Radiotherapy Ashraf, M., Bruza, P., Nelson, N., Gladstone, D., Williams, B., Jarvis, L., Pogue, B. WILEY. 2019: E366

  View details for Web of Science ID 000471277702287

• Technical Note: Time-gating to medical linear accelerator pulses: Stray radiation detector MEDICAL PHYSICS Ashraf, M., Bruza, P., Krishnaswamy, V., Gladstone, D. J., Pogue, B. W. 2019; 46 (2): 1044-1048

  Abstract

  CCD cameras are employed to image scintillation and Cherenkov radiation in external beam radiotherapy. This is achieved by gating the camera to the linear accelerator (Linac) output. A direct output signal line from the linac is not always accessible and even in cases where such a signal is accessible, a physical wire connected to the output port can potentially alter Linac performance through electrical feedback. A scintillating detector for stray radiation inside the Linac room was developed to remotely time-gate to linac pulses for camera-based dosimetry.A scintillator coupled silicon photomultiplier detector was optimized and systematically tested for location sensitivity and for use with both x rays and electron beams, at different energies and field sizes. Cherenkov radiation emitted due to static photon beams was captured using the remote trigger and compared to the images captured using a wired trigger. The issue of false-positive event detection, due to additional neutron activated products with high energy beams, was addressed.The designed circuit provided voltage >2.5 V even for distances up to 3 m from the isocenter with a 6 MV, 5 × 5 cm beam, using a Ø3 × 20 mm3 Bi4 Ge3 O12 (BGO) crystal. With a larger scintillator size, the detector could be placed even beyond 3 m distance. False-positive triggering was reduced by a coincidence detection scheme. Negligible fluctuations were observed in time-gated imaging of Cherenkov intensity emitted from a water phantom, when comparing directly connected vs this remote triggering approach.The remote detector provides untethered synchronization to linac pulses. It is especially useful for remote Cherenkov imaging or remote scintillator dosimetry imaging during radiotherapeutic procedures when a direct line signal is not accessible.

  View details for DOI 10.1002/mp.13311

  View details for Web of Science ID 000459616200060

  View details for PubMedID 30488442

  View details for PubMedCentralID PMC7122787

• Stray Radiation Triggered Imaging of Clinical Radiotherapeutic Beams Ashraf, M., Bruza, P., Pogue, B. WILEY. 2018: E477

  View details for Web of Science ID 000434978003223