Muhammad Ramish Ashraf

All Publications

• 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