Lawrie Skinner

All Publications

• Integrating Audiovisual Immersion Into Pediatric Radiation Therapy Across Multiple Centers: Methodology, Timeliness, and Cost of the Audiovisual-Assisted Therapeutic Ambience in Radiation Therapy Prospective Multi-Institutional Trial ADVANCES IN RADIATION ONCOLOGY Oh, J., Skinner, L., Gutkin, P. M., Jiang, A., Donaldson, S. S., Loo Jr, B. W., Wang, Y., Ewongwo, A., Bredfeldt, J. S., Breneman, J. C., Constine, L. S., Faught, A. M., Haas-Kogan, D., Holmes, J. A., Krasin, M., Larkin, C., Marcus, K. J., Maxim, P. G., McClelland III, S., Murphy, B., Palmer, J. D., Perkins, S. M., Shen, C. J., Terezakis, S., Bush, K., Hiniker, S. M. 2024; 9 (10)

  View details for DOI 10.1016/j.adro.2024.101589

  View details for Web of Science ID 001313488600001

• Integrating Audiovisual Immersion Into Pediatric Radiation Therapy Across Multiple Centers: Methodology, Timeliness, and Cost of the Audiovisual-Assisted Therapeutic Ambience in Radiation Therapy Prospective Multi-Institutional Trial. Advances in radiation oncology Oh, J., Skinner, L., Gutkin, P. M., Jiang, A., Donaldson, S. S., Loo, B. W., Wang, Y. P., Ewongwo, A., Bredfeldt, J. S., Breneman, J. C., Constine, L. S., Faught, A. M., Haas-Kogan, D., Holmes, J. A., Krasin, M., Larkin, C., Marcus, K. J., Maxim, P. G., McClelland, S., Murphy, B., Palmer, J. D., Perkins, S. M., Shen, C. J., Terezakis, S., Bush, K., Hiniker, S. M. 2024; 9 (10): 101589

  Abstract

  The Audiovisual-Assisted Therapeutic Ambience in Radiotherapy (AVATAR) trial was a prospective multicenter study (NCT03991156) examining the combination of video immersion with radiation therapy and was successfully conducted through the collaboration of pediatric radiation oncology teams at 10 institutions independent of any pre-existing consortium. We sought to analyze and report the methodology of trial conception and development, process map, and cost.The study enrolled patients aged 3 to 10 years preparing to undergo radiation therapy, integrated the combination of AVATAR-based video immersion with radiation therapy at each institution, and offered AVATAR use as an alternative to anesthesia, with rates of anesthesia use and outcomes of serial standardized anxiety and quality-of-life assessments assessed among the 81 children enrolled. A process map was created based on the trial timeline with the following components: study development time (time from conception of the trial to the accrual of the first patient, including design phase, agreement and approval phase, and site preparation phase), and accrual duration time (time from the first to last accrual). Costs and institutional success rates were calculated.Time from inception of study to last accrual was 3.6 years (1313 days). The study development time was 417 days (31.7%), and accrual duration time was 896 days (68.3%), with the final 50% of accrual occurring in <6 months. Equipment cost was approximately $550 per institution and was covered by funding from the lead study institution. All 10 centers were successful with AVATAR implementation, defined as ≥50% of patients able to avoid anesthesia with the use of AVATAR, including centers with both photon and proton therapy.This report elaborates on the methodology and timeline of trial conception and development using data from a previously published supportive care study combining video immersion with radiation therapy among 10 cooperating pediatric oncology institutions. It highlights the potential for multicenter collaborations on prospective trials integrating supportive care therapies with radiation therapy.

  View details for DOI 10.1016/j.adro.2024.101589

  View details for PubMedID 39309703

  View details for PubMedCentralID PMC11415686

• 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

• A multi-institutional study to investigate the sparing effect after whole brain electron FLASH in mice: Reproducibility and temporal evolution of functional, electrophysiological, and neurogenic endpoints. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology Drayson, O. G., Melemenidis, S., Katila, N., Viswanathan, V., Kramár, E. A., Zhang, R., Kim, R., Ru, N., Petit, B., Dutt, S., Manjappa, R., Ramish Ashraf, M., Lau, B., Soto, L., Skinner, L., Yu, A. S., Surucu, M., Maxim, P. G., Zebadua-Ballasteros, P., Wood, M. A., Gruel, P. M., Baulch, J. E., Vozenin, M. C., Loo, B. W., Limoli, C. L. 2024: 110534

  Abstract

  Ultra-high dose-rate radiotherapy (FLASH) has been shown to mitigate normal tissue toxicities associated with conventional dose rate radiotherapy (CONV) without compromising tumor killing in preclinical models. A prominent challenge in preclinical radiation research, including FLASH, is validating both the physical dosimetry and the biological effects across multiple institutions.We previously demonstrated dosimetric reproducibility of two different electron FLASH devices at separate institutions using standardized phantoms and dosimeters. In this study, tumor-free adult female mice were given 10 Gy whole brain FLASH and CONV irradiation at both institutions and evaluated for the reproducibility and temporal evolution of multiple neurobiological endpoints.FLASH sparing of behavioral performance on novel object recognition (4 months post-irradiation) and of electrophysiologic long-term potentiation (LTP, 5 months post-irradiation) was reproduced between institutions. Differences between FLASH and CONV on the endpoints of hippocampal neurogenesis (Sox2, doublecortin), neuroinflammation (microglial activation), and electrophysiology (LTP) were not observed at early times (48 h to 2 weeks), but recovery of immature neurons by 3 weeks was greater with FLASH.In summary, we demonstrated reproducible FLASH sparing effects on the brain between two different beams at two different institutions with validated dosimetry. FLASH sparing effects on the endpoints evaluated manifested at later but not the earliest time points.

  View details for DOI 10.1016/j.radonc.2024.110534

  View details for PubMedID 39293721

• Volumetric modulated arc therapy total body irradiation improves toxicity outcomes compared to 2D total body irradiation. Frontiers in oncology Hui, C., Simiele, E., Lozko, Y., Romero, I., Skinner, L., Binkley, M. S., Hoppe, R., Kovalchuk, N., Hiniker, S. M. 2024; 14: 1459287

  Abstract

  Volumetric modulated arc therapy (VMAT) total body irradiation (TBI) allows for greater organ sparing with improved target coverage compared to 2D-TBI. However, there is limited evidence of whether improved organ sparing translates to decreases in toxicities and how its toxicities compare to those of the 2D technique. We aimed to compare differences in toxicities among patients treated with TBI utilizing VMAT and 2D techniques.A matched-pair single-institution retrospective analysis of 200 patients treated with TBI from 2014 to 2023 was performed. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method and compared using log-rank tests. Differences in characteristics and toxicities between the VMAT and 2D cohorts were compared using Fisher's exact test.Of the 200 patients analyzed, 100 underwent VMAT-TBI, and 100 underwent 2D-TBI. The median age for VMAT-TBI and 2D-TBI patients was 13.7 years and 16.2 years, respectively (p = 0.25). In each cohort, 53 patients were treated with myeloablative regimens (8-13.76 Gy), and 47 were treated with non-myeloablative regimens (2-4 Gy). For the entire VMAT-TBI cohort, lung Dmean, kidney Dmean, and lens Dmax were spared to 60.6% ± 5.0%, 71.0% ± 8.5%, and 90.1% ± 3.5% of prescription, respectively. For the non-myeloablative VMAT-TBI cohort, testis/ovary Dmax, brain, and thyroid Dmean were spared to 33.4% ± 7.3%, 75.4% ± 7.0%, and 76.1% ± 10.5%, respectively. For 2D-TBI, lungs were spared using partial-transmission lung blocks for myeloablative regimens. The VMAT-TBI cohort experienced significantly lower rates of any grade of pneumonitis (2% vs. 12%), nephrotoxicity (7% vs. 34%), nausea (68% vs. 81%), skin (16% vs. 35%), and graft versus host disease (GVHD) (42% vs. 62%) compared to 2D-TBI patients. For myeloablative regimen patients, rates of pneumonitis (0% vs. 17%) and nephrotoxicity (9% vs. 36%) were significantly lower with VMAT-TBI versus 2D-TBI (p < 0.01). Median follow-up was 14.3 months, and neither median OS nor PFS for the entire cohort was reached. In the VMAT versus 2D-TBI cohort, the 1-year OS was 86.0% versus 83.0% (p = 0.26), and the 1-year PFS was 86.6% and 80.0% (p = 0.36), respectively.Normal tissue sparing with VMAT-TBI compared to the 2D-TBI translated to significantly lower rates of pneumonitis, renal toxicity, nausea, skin toxicity, and GVHD in patients, while maintaining excellent disease control.

  View details for DOI 10.3389/fonc.2024.1459287

  View details for PubMedID 39351359

  View details for PubMedCentralID PMC11439880

• Chest wall pain after single-fraction thoracic stereotactic ablative Radiotherapy: Dosimetric analysis from the iSABR trial. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology Lau, B., Wu, Y. F., Cui, S., Fu, J., Jackson, S., Pham, D., Dubrowski, P., Eswarappa, S., Skinner, L., Shirato, H., Taguchi, H., Gensheimer, M. F., Gee, H., Chin, A. L., Diehn, M., Loo, B. W., Moiseenko, V., Vitzthum, L. K. 2024: 110317

  Abstract

  Concerns over chest wall toxicity has led to debates on treating tumors adjacent to the chest wall with single-fraction stereotactic ablative radiotherapy (SABR). We performed a secondary analysis of patients treated on the prospective iSABR trial to determine the incidence and grade of chest wall pain and modeled dose-response to guide radiation planning and estimate risk.This analysis included 99 tumors in 92 patients that were treated with 25 Gy in one fraction on the iSABR trial which individualized dose by tumor size and location. Toxicity events were prospectively collected and graded based on the CTCAE version 4. Dose-response modeling was performed using a logistic model with maximum likelihood method utilized for parameter fitting.There were 22 grade 1 or higher chest wall pain events, including five grade 2 events and zero grade 3 or higher events. The volume receiving at least 11 Gy (V11Gy) and the minimum dose to the hottest 2 cc (D2cc) were most highly correlated with toxicity. When dichotomized by an estimated incidence of ≥ 20 % toxicity, the D2cc > 17 Gy (36.6 % vs. 3.7 %, p < 0.01) and V11Gy > 28 cc (40.0 % vs. 8.1 %, p < 0.01) constraints were predictive of chest wall pain, including among a subset of patients with tumors abutting or adjacent to the chest wall.For small, peripheral tumors, single-fraction SABR is associated with modest rates of low-grade chest wall pain. Proximity to the chest wall may not contraindicate single fractionation when using highly conformal, image-guided techniques with sharp dose gradients.

  View details for DOI 10.1016/j.radonc.2024.110317

  View details for PubMedID 38679202

• Automated contouring, treatment planning, and quality assurance for VMAT craniospinal irradiation (VMAT-CSI). Frontiers in oncology Simiele, E., Romero, I. O., Wang, J. Y., Chen, Y., Lozko, Y., Severyn, Y., Skinner, L., Yang, Y., Xing, L., Gibbs, I., Hiniker, S. M., Kovalchuk, N. 2024; 14: 1378449

  Abstract

  Create a comprehensive automated solution for pediatric and adult VMAT-CSI including contouring, planning, and plan check to reduce planning time and improve plan quality.Seventy-seven previously treated CSI patients (age, 2-67 years) were used for creation of an auto-contouring model to segment 25 organs at risk (OARs). The auto-contoured OARs were evaluated using the Dice Similarity Coefficient (DSC), 95% Hausdorff Distance (HD95), and a qualitative ranking by one physician and one physicist (scale: 1-acceptable, 2-minor edits, 3-major edits). The auto-planning script was developed using the Varian Eclipse Scripting API and tested with 20 patients previously treated with either low-dose VMAT-CSI (12 Gy) or high-dose VMAT-CSI (36 Gy + 18 Gy boost). Clinically relevant metrics, planning time, and blinded physician review were used to evaluate significance of differences between the auto and manual plans. Finally, the plan preparation for treatment and plan check processes were automated to improve efficiency and safety of VMAT-CSI.The auto-contours achieved an average DSC of 0.71 ± 0.15, HD95 of 4.81 ± 4.68, and reviewers' ranking of 1.22 ± 0.39, indicating close to "acceptable-as-is" contours. Compared to the manual CSI plans, the auto-plans for both dose regimens achieved statistically significant reductions in body V50% and Dmean for parotids, submandibular, and thyroid glands. The variance in the dosimetric parameters decreased for the auto-plans as compared to the manual plans indicating better plan consistency. From the blinded review, the auto-plans were marked as equivalent or superior to the manual-plans 88.3% of the time. The required time for the auto-contouring and planning was consistently between 1-2 hours compared to an estimated 5-6 hours for manual contouring and planning.Reductions in contouring and planning time without sacrificing plan quality were obtained using the developed auto-planning process. The auto-planning scripts and documentation will be made freely available to other institutions and clinics.

  View details for DOI 10.3389/fonc.2024.1378449

  View details for PubMedID 38660134

  View details for PubMedCentralID PMC11039907

• 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

• A clinical solution for non-toxic 3D-printed photon blocks in external beam radiation therapy. Journal of applied clinical medical physics Schulz, J. B., Dubrowski, P., Gibson, C., Yu, A. S., Skinner, L. B. 2024: e14225

  Abstract

  A well-known limitation of multi-leaf collimators is that they cannot easily form island blocks. This can be important in mantle region therapy. Cerrobend photon blocks, currently used for supplementary shielding, are labor-intensive and error-prone. To address this, an innovative, non-toxic, automatically manufactured photon block using 3D-printing technology is proposed, offering a patient-specific and accurate alternative.The study investigates the development of patient-specific photon shielding blocks using 3D-printing for three different patient cases. A 3D-printed photon block shell filled with tungsten ball bearings (BBs) was designed to have similar dosimetric properties to Cerrobend standards. The generation of the blocks was automated using the Eclipse Scripting API and Python. Quality assurance was performed by comparing the expected and actual weight of the tungsten BBs used for shielding. Dosimetric and field geometry comparisons were conducted between 3D-printed and Cerrobend blocks, utilizing ionization chambers, imaging, and field geometry analysis.The quality assurance assessment revealed a -1.3% average difference in the mass of tungsten ball bearings for different patients. Relative dose output measurements for three patient-specific blocks in the blocked region agreed within 2% of each other. Against the Treatment Planning System (TPS), both 3D-printed and Cerrobend blocks agreed within 2%. For each patient, 6 MV image profiles taken through the 3D-printed and Cerrobend blocks agreed within 1% outside high gradient regions. Jaccard distance analysis of the MV images against the TPS planned images, found Cerrobend blocks to have 15.7% dissimilarity to the TPS, while that of the 3D-printed blocks was 6.7%.This study validates a novel, efficient 3D-printing method for photon block creation in clinical settings. Despite potential limitations, the benefits include reduced manual labor, automated processes, and greater precision. It holds potential for widespread adoption in radiation therapy, furthering non-toxic radiation shielding.

  View details for DOI 10.1002/acm2.14225

  View details for PubMedID 38213084

• 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

• A multi-institutional trial evaluating the use of an integrated quality assurance phantom for frameless single-isocenter multitarget stereotactic radiosurgery. Frontiers in oncology Capaldi, D. P., Skinner, L. B., Pinkham, D. W., Zavgorodni, S., Stafford, O., Shirmohammad, M., Matney, J. E., Dubrowski, P., De Jean, P., Grafil, E. M., Yu, A. S. 2024; 14: 1445166

  Abstract

  Background: Brain radiosurgery treatments require multiple quality-assurance (QA) procedures to ensure accurate and precise treatment delivery of ablative doses. As single-isocenter multitarget radiosurgery treatments become more popular for treating patients with multiple brain metastases, quantifying off-axis accuracy of linear accelerators is crucial. In this study, we developed a novel brain radiosurgery integrated phantom and validated this phantom at multiple institutions to enable radiosurgery QA with a single phantom to facilitate implementation of a frameless single-isocenter, multitarget radiosurgery program. The phantom combines multiple independent verification system tests including the Winston-Lutz test, off-axis accuracy evaluation (i.e., off-axis Winston-Lutz), as well as dosimetric measurements utilizing both point dose and film measurement.Methods and materials: A novel 3D-printed phantom, coined OneIso, was designed with a movable insert which can switch between Winston-Lutz test targets and dose measurement without moving the phantom itself. In total, four phantoms were printed, and eight institutions participated in this study, which included both Varian TrueBeam (n=6) and Elekta Versa (n=2) linear accelerators. For off-axis Winston-Lutz measurements, a row of off-axis ball-bearings (BBs) was integrated into the OneIso. To quantify the spatial accuracy versus distance from isocenter, two-dimensional displacements were calculated between the planned and delivered BB locations relative to their respective MLC-defined field borders. For dose verification, brain radiosurgery clinical treatment plans previously treated were delivered at multiple cancer centers (six of eight centers). Radiochromic film and pinpoint ion chamber comparison measurements were obtained with OneIso.Results: Dose verification performed using the OneIso phantom across the different centers were all within on average 3% agreement, for both film and point-dose measurements. OneIso identified a reduction in spatial accuracy further away from isocenter for all eight radiosurgery machines. Differences increased as distance from isocenter increased, exceeding recommended radiosurgery accuracy tolerances (<1mm) at different distances for each machine (2-7cm), indicating that the tolerance is machine-dependent.Conclusion: OneIso provides a streamlined, single-setup workflow for single-isocenter multitarget frameless linac-based radiosurgery QA that can be easily translated to multiple institutions. Additionally, quantifying off-axis spatial discrepancies allows for determination of the maximum distance between targets and iso that meet single-isocenter multitarget radiosurgery program recommendations.

  View details for DOI 10.3389/fonc.2024.1445166

  View details for PubMedID 39544300

• AVATAR 2.0: next level communication systems for radiotherapy through face-to-face video, biofeedback, translation, and audiovisual immersion. Frontiers in oncology Schulz, J. B., Zalavari, L., Gutkin, P., Jiang, A., Wang, Y., Gibson, C., Garza, A., Bush, K. K., Wang, L., Donaldson, S. S., Loo, B. W., Hiniker, S. M., Skinner, L. 2024; 14: 1405433

  Abstract

  Purpose: This paper discusses an advanced version of our audiovisual-assisted therapeutic ambience in radiotherapy (AVATAR) radiolucent display systems designed for pediatric radiotherapy, enabling anesthesia-free treatments, video communication, and biofeedback. The scope of the AVATAR system is expanded here in two major ways: (i) through alternative mounting systems to accommodate a broader range of radiotherapy machines (specifically to fit robotic-arm and toroidal geometry photon radiotherapy and proton radiotherapy systems) and (ii) through additional hardware to provide video-calling, optimized audio for clear communication, and combined video inputs for biofeedback, translation, and other advanced functionalities.Methods and materials: Because robustness requires strong parts and radio-transparency requires thin, light parts, three-dimensional printing was used to rapidly prototype hollow structures and to iteratively improve robustness. Two system designs were made: one that mounts superior and another that mounts inferior to the patient's head. Radiation dose measurements and calculations were conducted to assess dose perturbations at surface and depth due to the screen.Results: For 6-MV volumetric modulated arc therapy (VMAT) plans, with and without the screen, the mean and maximum dose differences inside the planning target volume were 0.2% and 2.6% of the 200 cGy prescription, respectively. For a single static beam through the screen, the maximum measured excess surface dose was 13.4 ± 0.5%, and the largest measured dose attenuation at 5-cm water-equivalent depth was 2.1 ± 0.2%. These percentages are relative to the dose without the screen at those locations.Conclusions: The radiolucent screen systems provided here are shown to give minimal dosimetric effects on megavoltage VMAT photon treatments. For static beams, however, surface dose effects should be considered when these beams pass through the thickest components of the screen. Design files are also provided.

  View details for DOI 10.3389/fonc.2024.1405433

  View details for PubMedID 39439954

• Automating the Treatment Planning Process for Volumetric Modulated Arc Therapy Craniospinal Irradiation (VMAT-CSI). Practical radiation oncology Romero, I. O., Simiele, E. A., Lozko, Y., Severyn, Y., Skinner, L. B., Yang, Y., Wang, J. Y., Xing, L., Gibbs, I., Hiniker, S. M., Kovalchuk, N. 2023

  Abstract

  The purpose of this work is to develop a method to automate the treatment planning process of craniospinal irradiation (CSI) using volumetric modulated arc therapy (VMAT).Two scripts were developed using the Eclipse Scripting Application Programming Interface (ESAPI) to perform auto-plan preparation and optimization. Ten patients (age, 5-44 years) previously treated at our institution with low dose VMAT-CSI (prescription of 12 Gy) prior to total body irradiation were selected to evaluate the efficacy of the proposed auto-planning process. Paired t-tests compared the dosimetric indices of the auto-plans to the manually generated clinical plans. All plans were normalized to 95% of PTV coverage with the prescription dose. Two physicians and one physicist were asked to evaluate the manual plans and auto-plans of each patient in a blinded retrospective review and to indicate clinical acceptability and which plans were preferred for treatment.Compared to the manual CSI plans, the auto plans obtained significant reductions in Dmean to the parotids, submandibular glands, larynx, thyroid, and significant reduction in the plan PTV Dmax and D0.03cc. The standard deviation range of the dosimetric parameters was greatly reduced for auto plans (range, 0.1-1.3 Gy) relative to manual plans (range, 0.4-5.9 Gy) indicating better plan consistency. Among the ten patients, the auto-plans were preferred over the manual plans 90% of the time by the reviewing experts. The required time for auto-planning was approximately 1 hour compared to estimated 4 or more hours for manual planning.Reductions in planning time without sacrifices in plan quality were obtained using the auto-planning process compared with manual planning. Variation in plan quality was also reduced. The auto-planning scripts will be made freely available to other institutions and clinics.

  View details for DOI 10.1016/j.prro.2023.11.014

  View details for PubMedID 38048988

• Tungsten filled 3D printed lung blocks for total body irradiation. Practical radiation oncology Capaldi, D. P., Gibson, C., Villa, A., Schulz, J. B., Ziemer, B. P., Fu, J., Dubrowski, P., Yu, A. S., Fogh, S., Chew, J., Boreta, L., Braunstein, S. E., Witztum, A., Hirata, E., Morin, O., Skinner, L. B., Nano, T. F. 2023

  Abstract

  Lung blocks for total-body-irradiation (TBI) are commonly used to reduce lung dose and prevent radiation pneumonitis. Currently, molten Cerrobend containing toxic materials, specifically lead and cadmium, is poured into molds to construct blocks. Here, we propose a streamlined method to create 3D-printed lung block shells and fill them with tungsten ball-bearings (BBs) to remove lead and improve overall accuracy in the block manufacturing workflow.3D-printed lung block shells were automatically generated using an inhouse software, printed, and filled with 2-3mm diameter tungsten BBs. Clinical Cerrobend blocks were compared to the physician drawn blocks as well as our proposed tungsten filled 3D-printed blocks. Physical and dosimetric comparisons were performed on a linac. Dose transmission through the Cerrobend and 3D-printed blocks were measured using point dosimetry (ion-chamber) and the on-board Electronic-Portal-Imaging-Device (EPID). Dose profiles from the EPID images were used to compute the full-width-half-maximum (FWHM) and to compare with the treatment-planning-system (TPS). Additionally, the coefficient-of-variation (CoV) in the central 80% of FWHM was computed and compared between Cerrobend and 3D-printed blocks.The geometric difference between TPS and 3D-printed blocks was significantly lower than Cerrobend blocks (3D: -0.88±2.21mm, Cerrobend: -2.28±2.40mm, p=0.0002). Dosimetrically, transmission measurements through the 3D-printed and Cerrobend blocks for both ion-chamber and EPID dosimetry were between 42-48%, as compared to the open field. Additionally, CoV was significantly higher in 3D-printed blocks versus Cerrobend blocks (3D: 4.2±0.6%, Cerrobend: 2.6±0.7%, p<0.0001).We designed and implemented a tungsten filled 3D-printed workflow for constructing TBI lung blocks, which serves as an alternative to the traditional Cerrobend based workflow currently used in clinics. This workflow has the capacity of producing clinically useful lung blocks with minimal effort in an attempt to facilitate the removal of toxic materials from the clinic.

  View details for DOI 10.1016/j.prro.2023.11.003

  View details for PubMedID 37981253

• FLASH-RT does not affect chromosome translocations and junction structures beyond that of CONV-RT dose-rates. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology Barghouth, P. G., Melemenidis, S., Montay-Gruel, P., Ollivier, J., Viswanathan, V., Jorge, P. G., Soto, L. A., Lau, B. C., Sadeghi, C., Edlabadkar, A., Zhang, R., Ru, N., Baulch, J. E., Manjappa, R., Wang, J., Le Bouteiller, M., Surucu, M., Yu, A., Bush, K., Skinner, L., Maxim, P. G., Loo, B. W., Limoli, C. L., Vozenin, M. C., Frock, R. L. 2023: 109906

  Abstract

  The impact of radiotherapy (RT) at ultra high vs conventional dose rate (FLASH vs CONV) on the generation and repair of DNA double strand breaks (DSBs) is an important question that remains to be investigated. Here, we tested the hypothesis as to whether FLASH-RT generates decreased chromosomal translocations compared to CONV-RT.We used two FLASH validated electron beams and high-throughput rejoin and genome-wide translocation sequencing (HTGTS-JoinT-seq), employing S. aureus and S. pyogenes Cas9 "bait" DNA double strand breaks (DSBs) in HEK239T cells, to measure differences in bait-proximal repair and their genome-wide translocations to "prey" DSBs generated after various irradiation doses, dose rates and oxygen tensions (normoxic, 21% O2; physiological, 4% O2; hypoxic, 2% and 0.5% O2). Electron irradiation was delivered using a FLASH capable Varian Trilogy and the eRT6/Oriatron at CONV (0.08-0.13Gy/s) and FLASH (1x102-5x106 Gy/s) dose rates. Related experiments using clonogenic survival and γH2AX foci in the 293T and the U87 glioblastoma lines were also performed to discern FLASH-RT vs CONV-RT DSB effects.Normoxic and physioxic irradiation of HEK293T cells increased translocations at the cost of decreasing bait-proximal repair but were indistinguishable between CONV-RT and FLASH-RT. Although no apparent increase in chromosome translocations was observed with hypoxia-induced apoptosis, the combined decrease in oxygen tension with IR dose-rate modulation did not reveal significant differences in the level of translocations nor in their junction structures. Furthermore, RT dose rate modality on U87 cells did not change γH2AX foci numbers at 1- and 24-hours post-irradiation nor did this affect 293T clonogenic survival.Irrespective of oxygen tension, FLASH-RT produces translocations and junction structures at levels and proportions that are indistinguishable from CONV-RT.

  View details for DOI 10.1016/j.radonc.2023.109906

  View details for PubMedID 37690668

• Shaping success: clinical implementation of a 3D-printed electron cutout program in external beam radiation therapy. Frontiers in oncology Schulz, J. B., Gibson, C., Dubrowski, P., Marquez, C. M., Million, L., Qian, Y., Skinner, L., Yu, A. S. 2023; 13: 1237037

  Abstract

  The integration of 3D-printing technology into radiation therapy (RT) has allowed for a novel method to develop personalized electron field-shaping blocks with improved accuracy. By obviating the need for handling highly toxic Cerrobend molds, the clinical workflow is significantly streamlined. This study aims to expound upon the clinical workflow of 3D-printed electron cutouts in RT and furnish one year of in-vivo dosimetry data.3D-printed electron cutouts for 6x6 cm, 10x10 cm, and 15x15 cm electron applicators were designed and implemented into the clinical workflow after dosimetric commissioning to ensure congruence with the Cerrobend cutouts. The clinical workflow consisted of four parts: i) the cutout aperture was extracted from the treatment planning system (TPS). A 3D printable cutout was then generated automatically through custom scripts; ii) the cutout was 3D-printed with PLA filament, filled with tungsten ball bearings, and underwent quality assurance (QA) to verify density and dosimetry; iii) in-vivo dosimetry was performed with optically stimulated luminescence dosimeters (OSLDs) for a patient's first treatment and compared to the calculated dose in the TPS; iv) after treatment completion, the 3D-printed cutout was recycled.QA and in-vivo OSLD measurements were conducted (n=40). The electron cutouts produced were 6x6 cm (n=3), 10x10 cm (n=30), and 15x15 cm (n=7). The expected weight of the cutouts differed from the measured weight by 0.4 + 1.1%. The skin dose measured with the OSLDs was compared to the skin dose in the TPS on the central axis. The difference between the measured and TPS doses was 4.0 + 5.2%.The successful clinical implementation of 3D-printed cutouts reduced labor, costs, and removed the use of toxic materials in the workplace while meeting clinical dosimetric standards.

  View details for DOI 10.3389/fonc.2023.1237037

  View details for PubMedID 37621682

  View details for PubMedCentralID PMC10445153

• 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

• 3D printing in brachytherapy: A systematic review of gynecological applications. Brachytherapy Fahimian, B. P., Liu, W., Skinner, L., Yu, A. S., Phillips, T., Steers, J. M., DeMarco, J., Fraass, B. A., Kamrava, M. 2023

  Abstract

  PURPOSE: To provide a systematic review of the applications of 3D printing in gynecological brachytherapy.METHODS: Peer-reviewed articles relating to additive manufacturing (3D printing) from the 34 million plus biomedical citations in National Center for Biotechnology Information (NCBI/PubMed), and 53 million records in Web of Science (Clarivate) were queried for 3D printing applications. The results were narrowed sequentially to, (1) all literature in 3D printing with final publications prior to July 2022 (in English, and excluding books, proceedings, and reviews), and then to applications in, (2) radiotherapy, (3) brachytherapy, (4) gynecological brachytherapy. Brachytherapy applications were reviewed and grouped by disease site, with gynecological applications additionally grouped by study type, methodology, delivery modality, and device type.RESULTS: From 47,541 3D printing citations, 96 publications met the inclusion criteria for brachytherapy, with gynecological clinical applications compromising the highest percentage (32%), followed by skin and surface (19%), and head and neck (9%). The distribution of delivery modalities was 58% for HDR (Ir-192), 35% for LDR (I-125), and 7% for other modalities. In gynecological brachytherapy, studies included design of patient specific applicators and templates, novel applicator designs, applicator additions, quality assurance and dosimetry devices, anthropomorphic gynecological applicators, and in-human clinical trials. Plots of year-to-year growth demonstrate a rapid nonlinear trend since 2014 due to the improving accessibility of low-cost 3D printers. Based on these publications, considerations for clinical use are provided.CONCLUSIONS: 3D printing has emerged as an important clinical technology enabling customized applicator and template designs, representing a major advancement in the methodology for implantation and delivery in gynecological brachytherapy.

  View details for DOI 10.1016/j.brachy.2023.02.002

  View details for PubMedID 37024350

• Feasibility of the Audio-Visual Assisted Therapeutic Ambience in Radiotherapy (AVATAR) system for anesthesia avoidance in pediatric patients: A multicenter trial. International journal of radiation oncology, biology, physics Gutkin, P. M., Skinner, L., Jiang, A., Donaldson, S. S., Loo, B. W., Oh, J., Wang, Y. P., von Eyben, R., Snyder, J., Bredfeldt, J. S., Breneman, J. C., Constine, L. S., Faught, A. M., Haas-Kogan, D., Holmes, J. A., Krasin, M., Ccls, C. L., Marcus, K. J., Maxim, P. G., Iii, S. M., Murphy, B., Palmer, J. D., Perkins, S. M., Shen, C. J., Terezakis, S., Bush, K., Hiniker, S. M. 2023

  Abstract

  The AVATAR system was the first published radiotherapy (RT) compatible system to reduce the need for pediatric anesthesia through video-based distraction. We evaluate the feasibility of AVATAR implementation and effects on anesthesia use, quality of life (QoL), and anxiety in a multicenter pediatric trial.Pediatric patients 3-10 years of age preparing to undergo RT at 10 institutions were prospectively enrolled. Children able to undergo at least one fraction of RT using AVATAR without anesthesia were considered successful (S). Patients requiring anesthesia for their entire treatment course were non-successful (NS). PedsQL3.0 Cancer Module survey (PedsQL) assessed QoL and was administered to the patient and guardian at RT simulation, midway through RT, and final treatment. The modified Yale Preoperative Assessment Survey Short Form (mYPAS) assessed anxiety and was performed at the same three timepoints. Success was evaluated using Chi-square test. PedsQL and mYPAS scores were assessed using mixed effects models with time points evaluated as fixed effects and a random intercept on the subject.Eighty-one children were included; median age was 7 years. AVATAR was successful at all 10 institutions and with photon and proton RT. There were 63 (78%) S patients; anesthesia was avoided for a median of 20 fractions per patient. Success differed by age (p=0.04) and private versus public insurance (p<0.001). Both patient (p=0.008) and parent (p=0.006) PedsQL scores significantly improved over the course of RT for patients ages 5-7. Anxiety in the treatment room decreased for both S and NS patients over RT course (p<0.001), by age (p<0.001) and by S versus NS patients (p<0.001).In this 10-center prospective trial, anesthesia avoidance with AVATAR was 78% in children age 3-10 years, higher than among age-matched historical controls (49%, p<0.001). AVATAR implementation is feasible across multiple institutions and should be further studied and made available to patients who may benefit from video-based distraction.

  View details for DOI 10.1016/j.ijrobp.2023.03.063

  View details for PubMedID 37001762

• FLASH-RT does not affect chromosome translocations and junction structures beyond that of CONV-RT dose-rates. bioRxiv : the preprint server for biology Barghouth, P. G., Melemenidis, S., Montay-Gruel, P., Ollivier, J., Viswanathan, V., Jorge, P. G., Soto, L. A., Lau, B. C., Sadeghi, C., Edlabadkar, A., Manjappa, R., Wang, J., Bouteiller, M. L., Surucu, M., Yu, A., Bush, K., Skinner, L., Maxim, P. G., Loo, B. W., Limoli, C. L., Vozenin, M., Frock, R. L. 2023

  Abstract

  The molecular and cellular mechanisms driving the enhanced therapeutic ratio of ultra-high dose-rate radiotherapy (FLASH-RT) over slower conventional (CONV-RT) radiotherapy dose-rate remain to be elucidated. However, attenuated DNA damage and transient oxygen depletion are among several proposed models. Here, we tested whether FLASH-RT under physioxic (4% O 2 ) and hypoxic conditions (≤2% O 2 ) reduces genome-wide translocations relative to CONV-RT and whether any differences identified revert under normoxic (21% O 2 ) conditions. We employed high-throughput rejoin and genome-wide translocation sequencing ( HTGTS-JoinT-seq ), using S. aureus and S. pyogenes Cas9 "bait" DNA double strand breaks (DSBs), to measure differences in bait-proximal repair and their genome-wide translocations to "prey" DSBs generated by electron beam CONV-RT (0.08-0.13Gy/s) and FLASH-RT (1*10 2 -5*10 6 Gy/s), under varying ionizing radiation (IR) doses and oxygen tensions. Normoxic and physioxic irradiation of HEK293T cells increased translocations at the cost of decreasing bait-proximal repair but were indistinguishable between CONV-RT and FLASH-RT. Although no apparent increase in chromosome translocations was observed with hypoxia-induced apoptosis, the combined decrease in oxygen tension with IR dose-rate modulation did not reveal significant differences in the level of translocations nor in their junction structures. Thus, Irrespective of oxygen tension, FLASH-RT produces translocations and junction structures at levels and proportions that are indistinguishable from CONV-RT.

  View details for DOI 10.1101/2023.03.27.534408

  View details for PubMedID 37034651

• Mitigation of IMRT/SBRT treatment planning errors on the RefleXion X1 system using FMEA within Six Sigma framework Advances in Radiation Oncology Simiele, E., Han, B., Skinner, L., Pham, D., Lewis, J., Gensheimer, M., Vitzthum, L., Chang, D., Surucu, M., Kovalchuk, N. 2023

  View details for DOI 10.1016/j.adro.2023.101186

• Dosimetric Predictors of Local Control after Stereotactic Ablative Radiotherapy (SABR) for Lung Tumors: A Secondary Analysis of a Phase II Prospective Trial of Individualized SABR (iSABR) Wu, Y., Lau, B., Fu, J., Skinner, L., Gensheimer, M., Gee, H., Diehn, M., Loo, B., Chin, A., Vitzthum, L. LIPPINCOTT WILLIAMS & WILKINS. 2022: S16

  View details for Web of Science ID 000847787800034

• Design and validation of a dosimetric comparison scheme tailored for ultra-high dose-rate electron beams to support multicenter FLASH preclinical studies. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology Gonçalves Jorge, P., Melemenidis, S., Grilj, V., Buchillier, T., Manjappa, R., Viswanathan, V., Gondré, M., Vozenin, M. C., Germond, J. F., Bochud, F., Moeckli, R., Limoli, C., Skinner, L., Joshua No, H., Fred Wu, Y., Surucu, M., Yu, A. S., Lau, B., Wang, J., Schüler, E., Bush, K., Graves, E. E., Maxim, P. G., Loo, B. W., Bailat, C. 2022

  Abstract

  We describe a multicenter cross validation of ultra-high dose rate (UHDR) (>= 40 Gy/s) irradiation in order to bring a dosimetric consensus in absorbed dose to water. UHDR refers to dose rates over 100-1000 times those of conventional clinical beams. UHDR irradiations have been a topic of intense investigation as they have been reported to induce the FLASH effect in which normal tissues exhibit reduced toxicity relative to conventional dose rates. The need to establish optimal beam parameters capable of achieving the in vivo FLASH effect has become paramount. It is therefore necessary to validate and replicate dosimetry across multiple sites conducting UHDR studies with distinct beam configurations and experimental set-ups.Using a custom cuboid phantom with a cylindrical cavity (5 mm diameter by 10.4 mm length) designed to contain three type of dosimeters (thermoluminescent dosimeters (TLDs), alanine pellets, and Gafchromic films), irradiations were conducted at expected doses of 7.5 to 16 Gy delivered at UHDR or conventional dose rates using various electron beams at the Radiation Oncology Departments of the CHUV in Lausanne, Switzerland and Stanford University, CA.Data obtained between replicate experiments for all dosimeters were in excellent agreement (+/- 3 %). In general, films and TLDs were in closer agreement with each other, while alanine provided the closest match between the expected and measured dose, with certain caveats related to absolute reference dose.In conclusion, successful cross-validation of different electron beams operating under different energies and configurations lays the foundation for establishing dosimetric consensus for UHDR irradiation studies, and, if widely implemented, decrease uncertainty between different sites investigating the mechanistic basis of the FLASH effect.

  View details for DOI 10.1016/j.radonc.2022.08.023

  View details for PubMedID 36030934

• The Stanford VMAT TBI Technique. Practical radiation oncology Kovalchuk, N., Simiele, E., Skinner, L., Yang, Y., Howell, N., Lewis, J., Hui, C., Blomain, E. S., Hoppe, R. T., Hiniker, S. M. 2022

  Abstract

  In this work, we describe the technical aspects of the XXX VMAT TBI technique, compare it to other VMAT TBI techniques, and share our initial experience.From September 2019 to August 2021, 35 patients were treated with VMAT TBI at our institution. Treatment planning was performed using in-house developed automated planning scripts. Organ sparing depended on the regimen: myeloablative (lungs, kidneys, and lenses); non-myeloablative with benign disease (lungs, kidneys, lenses, gonads, brain, and thyroid). Quality assurance was performed using EPID portal dosimetry and Mobius3D. Robustness was evaluated for the first ten patients by performing local and global isocenter shifts of 5 mm. Treatment was delivered using IGRT for every isocenter and every fraction. In-vivo measurements were performed on the matchline between the VMAT and AP/PA fields and on the testes for the first fraction.The lungs, lungs-1cm, and kidneys Dmean were consistently spared to 57.6±4.4%, 40.7±5.5%, and 70.0±9.9% of the prescription dose, respectively. Gonadal sparing (Dmean=0.69±0.13 Gy) was performed for all patients with benign disease. The average PTV D1cc was 120.7±6.4% for all patients. The average Gamma passing rate for the VMAT plans was 98.1±1.6% (criteria of 3%/2mm). Minimal differences were observed between Mobius3D- and EclipseAAA-calculated PTV Dmean (0.0±0.3%) and lungs Dmean (-2.5±1.2%). Robustness evaluation showed that the PTV Dmax and lungs Dmean are insensitive to small positioning deviations between the VMAT isocenters (1.1±2.4% and 1.2±1.0%, respectively). The average matchline dose measurement indicated patient setup was reproducible (96.1±4.5% relative to prescription dose). Treatment time, including patient setup and beam-on, was 47.5±9.5 min.The XXX VMAT TBI technique, from simulation to treatment delivery, was presented and compared to other VMAT TBI techniques. Together with publicly shared autoplanning scripts, our technique may provide the gateway for wider adaptation of this technology and the possibility of multi-institutional studies in the cooperative group setting.

  View details for DOI 10.1016/j.prro.2021.12.007

  View details for PubMedID 35182803

• Radiation Therapy without Anesthesia for a 2-Year Old Child using Audio-Visual Assisted Therapeutic Ambience in Radiotherapy (AVATAR). Practical radiation oncology Prasad, R. N., Baliga, S., Banner, J., Cadieux, C., Centnar, A., Degnan, M., Depinet, M., Ewing, A., Hobbs, N., Jiang, A. L., Manring, I., Perlow, H. K., Rock, A., Skinner, L. B., Tenney, L., Walls, V., Hiniker, S. M., Palmer, J. D. 1800

  Abstract

  Radiation therapy (RT) is essential to managing many pediatric malignancies, but can be anxiety, fear, and discomfort provoking for children due to prolonged treatment time, extended course, and restrictive immobilization. Patients under 10 years frequently require daily general anesthesia (GA), which is resource intensive, expensive, potentially toxic, and anxiety/fear provoking. The Audio-Visual Assisted Therapeutic Ambience in Radiotherapy (AVATAR), a video streaming device, has been proposed as an alternative to anesthesia in patients aged 3-10. A pilot study evaluating the efficacy of this novel innovation is accruing, but patients under 3 are ineligible. We simulated a 2-year-old with Stage IV Wilms tumor for bilateral whole lung and left flank irradiation without GA. Using the AVATAR, we attempted to deliver RT to this patient without sedation. Patient anxiety at the time of simulation and at the beginning, middle, and end of the treatment course was characterized using the validated Modified Yale Preoperative Anxiety Score (mYPAS) measurement tool. Although the patient tolerated CT simulation without GA or AVATAR use, his mYPAS of 14/18 indicated significant anxiety. Using the AVATAR, all treatments were delivered without GA; mYPAS scores were 5, 4 (lowest possible), and 4 at the first, mid-course and final treatments, indicating no significant anxiety and a decrease from pre-AVATAR baseline. Without GA, the package time to deliver RT decreased by 66% from 90 to 30 minutes. In summary, we describe an expanded, previously unreported indication for the AVATAR by demonstrating the feasibility of this anesthesia-reducing/omitting approach in appropriate younger patients currently excluded from ongoing trials. The financial and quality of life benefits (including decreased stress, anxiety, toxicity, cost, and appointment time) of AVATAR utilization may be extendable to a younger patient population than previously thought. In older children, prospective validation is ongoing, but additional study in patients under 3 is needed.

  View details for DOI 10.1016/j.prro.2021.12.009

  View details for PubMedID 34971793

• Technical report: 3D-printed patient-specific scalp shield for hair preservation in total skin electron beam therapy. Technical innovations & patient support in radiation oncology Rahimy, E., Skinner, L., Kim, Y. H., Hoppe, R. T. 2021; 18: 12-15

  Abstract

  Techniques for non-lead scalp-shielding in total skin therapy are lacking.3D-printing is a promising technique for patient-specific conformal shielding.We present a case of effective scalp shielding with 3D-printing.

  View details for DOI 10.1016/j.tipsro.2021.03.002

  View details for PubMedID 33997322

• CT-less electron radiotherapy simulation and planning with a consumer 3D camera. Journal of applied clinical medical physics Skinner, L., Knopp, R., Wang, Y., Dubrowski, P., Bush, K. K., Limmer, A., Trakul, N., Million, L., Marquez, C. M., Yu, A. S. 2021

  Abstract

  PURPOSE: Electron radiation therapy dose distributions are affected by irregular body surface contours. This study investigates the feasibility of three-dimensional (3D) cameras to substitute for the treatment planning computerized tomography (CT) scan by capturing the body surfaces to be treated for accurate electron beam dosimetry.METHODS: Dosimetry was compared for six electron beam treatments to the nose, toe, eye, and scalp using full CT scan, CT scan with Hounsfield Unit (HU) overridden to water (mimic 3D camera cases), and flat-phantom techniques. Radiation dose was prescribed to a depth on the central axis per physician's order, and the monitor units (MUs) were calculated. The 3D camera spatial accuracy was evaluated by comparing the 3D surface of a head phantom captured by a 3D camera and that generated with the CT scan in the treatment planning system. A clinical case is presented, and MUs were calculated using the 3D camera body contour with HU overridden to water.RESULTS: Across six cases the average change in MUs between the full CT and the 3Dwater (CT scan with HU overridden to water) calculations was 1.3% with a standard deviation of 1.0%. The corresponding hotspots had a mean difference of 0.4% and a standard deviation of 1.9%. The 3D camera captured surface of a head phantom was found to have a 0.59mm standard deviation from the surface derived from the CT scan. In-vivo dose measurements (213±8cGy) agreed with the 3D-camera planned dose of 209±6cGy, compared to 192±6cGy for the flat-phantom calculation (same MUs).CONCLUSIONS: Electron beam dosimetry is affected by irregular body surfaces. 3D cameras can capture irregular body contours which allow accurate dosimetry of electron beam treatment as an alternative to costly CT scans with no extra exposure to radiation. Tools and workflow for clinical implementation are provided.

  View details for DOI 10.1002/acm2.13283

  View details for PubMedID 34042253

• Radiation Therapy for Primary Cutaneous Gamma Delta Lymphoma Prior to Stem Cell Transplantation. Cancer investigation Wu, Y. F., Skinner, L., Lewis, J., Khodadoust, M. S., Kim, Y. H., Kwong, B. Y., Weng, W., Hoppe, R. T., Sodji, Q., Hui, C., Kastelowitz, N., Fernandez-Pol, S., Hiniker, S. M. 2021: 1–11

  Abstract

  We present a patient with widespread PCGD-TCL of the bilateral arms and legs, who underwent radiotherapy with 34Gy in 17 fractions using circumferential VMAT and 3-D printed bolus to the 4 extremities prior to planned stem cell transplant, who was then found to have progression in the liver, lung, and skin, followed by drastic regression of all in and out-of-field lesions on imaging 1.5months later. The cause of regression may be related to a radiation-induced abscopal effect from the immunomodulatory effects of radiation, or related to immune reactivation in the setting of cessation of systemic immunosuppressive agents.

  View details for DOI 10.1080/07357907.2021.1919696

  View details for PubMedID 33899635

• Use of Audiovisual Assisted Therapeutic Ambience in Radiotherapy (AVATAR) for Anesthesia Avoidance in a Pediatric Patient With Down Syndrome. Advances in radiation oncology Gutkin, P. M., Donaldson, S. S., Skinner, L., Callejas, M., Cimino, J., Lore, J., Bush, K., Hiniker, S. M. 2021; 6 (2): 100637

  View details for DOI 10.1016/j.adro.2020.100637

  View details for PubMedID 33732961

• A robotically assisted 3D printed quality assurance lung phantom for Calypso. Physics in medicine and biology Capaldi, D. P., Skinner, L. B., Dubrowski, P. n., Zhang, H. n., Xing, L. n., Chuang, C. F., Loo, B. W., Bush, K. K., Fahimian, B. P., Yu, A. S. 2021

  Abstract

  Purpose:Radiation dose delivered to targets located near the upper-abdomen or in the thorax are significantly affected by respiratory-motion. Relatively large-margins are commonly added to compensate for this motion, limiting radiation-dose-escalation. Internal-surrogates of target motion, such as a radiofrequency (RF) tracking system, i.e. Calypso® System, are used to overcome this challenge and improve normal-tissue sparing. RF tracking systems consist of implanting transponders in the vicinity of the tumor to be tracked using radiofrequency-waves. Unfortunately, although the manufacture provides a universal quality-assurance (QA) phantom, QA-phantoms specifically for lung-applications are limited, warranting the development of alternative solutions to fulfil the tests mandated by AAPM's TG142. Accordingly, our objective was to design and develop a motion-phantom to evaluate Calypso for lung-applications that allows the Calypso® Beacons to move in different directions to better simulate true lung-motion.Methods and Materials:A Calypso lung QA-phantom was designed, and 3D-printed. The design consists of three independent arms where the transponders were attached. A pinpoint-chamber with a buildup-cap was also incorporated. A 4-axis robotic arm was programmed to drive the motion-phantom to mimic breathing. After acquiring a four-dimensional-computed-tomography (4DCT) scan of the motion-phantom, treatment-plans were generated and delivered on a Varian TrueBeam® with Calypso capabilities. Stationary and gated-treatment plans were generated and delivered to determine the dosimetric difference between gated and non-gated treatments. Portal cine-images were acquired to determine the temporal-accuracy of delivery by calculating the difference between the observed versus expected transponders locations with the known speed of the transponders' motion.Results:Dosimetric accuracy is better than TG142 tolerance of 2%. Temporal accuracy is greater than, TG142 tolerance of 100ms for beam-on, but less than 100ms for beam-hold.Conclusions:The robotic QA-phantom designed and developed in this study provides an independent phantom for performing Calypso lung-QA for commissioning and acceptance testing of Calypso for lung treatments.

  View details for DOI 10.1088/1361-6560/abebaa

  View details for PubMedID 33657537

• Nontoxic electron collimators. Journal of applied clinical medical physics Breitkreutz, D. Y., Skinner, L., Lo, S., Yu, A. 2021

  Abstract

  The goal of this work was to develop and test nontoxic electron collimation technologies for clinical use.Two novel technologies were investigated: tungsten-silicone composite and 3D printed electron cutouts. Transmission, dose uniformity, and profiles were measured for the tungsten-silicone. Surface dose, relative dose output, and field size were measured for the 3D printed cutouts and compared with the standard cerrobend cutouts in current clinical use. Quality assurance tests including mass measurements, Megavoltage (MV) imaging, and drop testing were developed for the 3D printed cutouts as a guide to safe clinical implementation.Dose profiles of the flexible tungsten-silicone skin shields had an 80-20 penumbra values of 2-3 mm compared to 7-8 mm for cerrobend. In MV transmission image measurements of the tungsten-silicone, 80% of the pixels had a transmission value within 2% of the mean. An ∼90% reduction in electron intensity was measured for 6 MeV and a 6.4 mm thickness of tungsten-silicone and 12.7 mm thickness for 16 MeV. The maximum difference in 3D printed cutout versus cerrobend output, surface dose, and full width at half-maximum (FWHM) was 1.7%, 1.2%, and 1.5%, respectively, for the 10 cm × 10 cm cutouts.Both flexible tungsten-silicone and 3D printed cutouts were found to be feasible for clinical use. The flexible tungsten-silicone was of adequate density, flexibility, and uniformity to serve as skin shields for electron therapy. The 3D printed cutouts were dosimetrically equivalent to standard cerrobend cutouts and were robust enough for handling in the clinical environment.

  View details for DOI 10.1002/acm2.13398

  View details for PubMedID 34480841

• Deep learning-augmented radiotherapy visualization with a cylindrical radioluminescence system. Physics in medicine and biology Jia, M., Li, X., Wu, Y., Yang, Y., Kasimbeg, P., Skinner, L. B., Wang, L., Xing, L. 2020

  Abstract

  This study aims to demonstrate a low-cost camera-based radioluminescence imaging system (CRIS) for high-quality beam visualization that encourages accurate pre-treatment verifications on radiation delivery in external beam radiotherapy. To ameliorate the optical image that suffers from mirror glare and edge blurring caused by photon scattering, a deep learning model is proposed and trained to learn from an on-board electronic portal imaging device (EPID). Beyond the typical purposes of an on-board EPID, the developed system maintains independent measurement with co-planar detection ability by involving a cylindrical receptor. Three task-aware modules are integrated into the network design to enhance its robustness against the artifacts that exist in an EPID running at the cine mode for efficient image acquisition. The training data consists of various designed beam fields that were modulated via the multi-leaf collimator (MLC). Validation experiments are performed for five regular fields ranging from 2 * 2 cm2 to 10 * 10 cm2 and three clinical IMRT cases. The captured CRIS images are compared to the high-quality images collected from an EPID running at the integration-mode, in terms of gamma index and other typical similarity metrics. The mean 2% / 2mm gamma pass rate is 99.14% (range between 98.6% and 100%) and 97.1% (ranging between 96.3% and 97.9%), for the regular fields and IMRT cases, respectively. The CRIS is further applied as a tool for MLC leaf-end position verification. A rectangular field with introduced leaf displacement is designed, and the measurements using CRIS and EPID agree within 0.100 mm ± 0.072 mm with maximum of 0.292 mm. Coupled with its simple system design and low-cost nature, the technique promises to provide viable choice for routine quality assurance in radiation oncology practice.

  View details for DOI 10.1088/1361-6560/abd673

  View details for PubMedID 33361563

• Precision radiotherapy using monochromatic inverse Compton x-ray sources. Medical physics Simiele, E. A., Breitkreutz, D. Y., Capaldi, D. P., Liu, W., Bush, K. K., Skinner, L. B. 2020

  Abstract

  PURPOSE: The dosimetric properties of Inverse Compton (IC) x-ray sources were investigated to determine their utility for stereotactic radiation therapy.METHODS: Monte Carlo simulations were performed using the egs brachy user code of EGSnrc. Nominal IC source x-ray energies of 80 keV and 150 keV were considered in this work. Depth-dose and lateral dose-profiles in water were calculated, as was dose enhancement in bone. Further simulations were performed for brain and spine treatment sites. The impact of gold nanoparticle doping was also investigated for the brain treatment site. Analogous dose calculations were performed in a clinical treatment planning system using a clinical 6 MV photon beam model and were compared to the Monte Carlo simulations.RESULTS: Both 80 keV and 150 keV IC beams were observed to have sharp 80-20 penumbra (i.e., < 0.1 mm) with broad low-dose tails in water. For reference, the calculated penumbra for the 6 MV clinical beam was 3 mm. Maximum dose enhancement factors in bone of 3.1, 1.4, and 1.1 were observed for the 80 keV, 150keV, and clinical 6 MV beams, respectively. The plan quality for the single brain metastasis case was similar between the IC beams and the 6 MV beam without gold nanoparticles. As the concentration of gold within the target increased, the V12 Gy to the normal brain tissue and Dmax within the target volume significantly decreased and the conformity significantly improved, which resulted in superior plan quality over the clinical 6 MV beam plan. In the spine cases, the sharp penumbra and enhanced dose to bone of the IC beams produced superior plan quality (i.e., better conformity, normal tissue sparing, and spinal cord sparing) as compared to the clinical 6 MV beam plans.CONCLUSIONS: The findings from this work indicate that inverse Compton x-ray sources are well-suited for stereotactic radiotherapy treatments due to their sharp penumbra and dose enhancement around high atomic-number materials. Future work includes investigating the properties of intensity-modulated inverse Compton x-ray sources to improve the homogeneity within the target tissue.

  View details for DOI 10.1002/mp.14552

  View details for PubMedID 33107049

• Second window near-infrared dosimeter (NIR2D) system for radiation dosimetry. Physics in medicine and biology Kim, T. J., Cheng, K., Zhang, H., Liu, S., Skinner, L., Xing, L. 2020; 65 (17): 175013

  Abstract

  Fiber-coupled scintillation dosimeters are a cost-effective alternative to the conventional ion chambers in radiation dosimetry. However, stem effects from optical fibers such as Cerenkov radiation incur significant errors in the readout signal. Here we introduce a second near-infrared window dosimeter, dubbed as NIR2D, that can potentially be used as real-time radiation detector for clinical megavoltage beams. Lanthanide-based rare-earth NaYF4 nano-phosphors doped with both erbium and cerium elements were synthesized, and a compact 3D printed reader device integrated with a photodetector and data acquisition system was designed. The performance of the NIR2D was tested using a pre-clinical orthovoltage radiation source and a clinical megavoltage radiation source. The system was tested for dose linearity (100, 200, 600 MU), dose rate dependency (100, 200, 400, 600 MU min-1), and energy dependency (6, 10, 15 MV). Test results with the clinical linear accelerator demonstrated excellent dose linearity and dose rate independency when exposed to 6 MV linac beams-both data follows a linear trendline with R2 > 0.99. On the other hand, the NIR2D was energy dependent, where the readout dropped by 9% between 6 and 15 MV. For stem effects, we observed a finite Cerenkov contribution of 1%-3% when exposed between 100-600 MU min-1 (6 MV) and 3%-6% when exposed between 5-15 MV (600 MU min-1). While the stem effects were still observable, we expect that enhancing the current optical setup will simultaneously improve the scintillation signal and reduce the stem effects.

  View details for DOI 10.1088/1361-6560/ab9b56

  View details for PubMedID 32869751

• FLASH irradiation enhances the therapeutic index of abdominal radiotherapy in mice Natarajan, S., Levy, K., Wang, J., Chow, S., Eggold, J., Loo, P., Manjappa, R., Lartey, F. M., Schuler, E., Skinner, L., Rafat, M., Ko, R., Kim, A., Al Rawi, D., von Eyben, R., Dorigo, O., Casey, K. M., Graves, E. E., Bush, K., Yu, A. S., Koong, A. C., Maxim, P. G., Loo, B. W., Rankin, E. B. AMER ASSOC CANCER RESEARCH. 2020

  View details for DOI 10.1158/1538-7445.AM2020-5351

  View details for Web of Science ID 000590059306341

• Intensity modulated Ir-192 brachytherapy using high-Z 3D printed applicators. Physics in medicine and biology Skinner, L. B., Niedermayr, T., Prionas, N., Perl, J., Fahimian, B. P., Kidd, E. 2020

  Abstract

  Gynecologic cancers are often asymmetric, yet current Ir-192 brachytherapy techniques provide only limited radial modulation of the dose. The shielded solutions investigated here solve this by providing the ability to modulate between highly asymmetric and radially symmetric dose distributions at a given location. To find applicator designs that can modulate between full dose and less than 50% dose, at the dimensions of the urethra, a 2D calculation algorithm was developed to narrow down the search space. Two shielding design types were then further investigated using Monte Carlo and Boltzmann-solver dose calculation algorithms. 3D printing techniques using ISO10993 certified biocompatible plastics and 3D printable tungsten-loaded plastics were tested. It was also found that shadowing effects set by the shape of the shielding cannot be easily modulated out, hence careful design is required. The shielded applicator designs investigated here, allow for reduction of the dose by over 50% at 5 mm from the applicator surface in desired regions, while also allowing radially symmetric dose with isodose line (IDL) deviations less than 0.5 mm from circular. The shielding designs were also chosen with treatment delivery time in mind. Treatment times for these shielded designs were found to be less than 1.4 times longer than a six-channel unshielded cylinder for the equivalent fully symmetric dose distribution. The 2D calculation methods developed here provide a simple way to rapidly evaluate shielding designs, while the 3D printing techniques also allow for devices with novel shapes to be rapidly prototyped. Both TOPAS Monte Carlo and Acuros BV calculations show that significant dose shaping, and organ at risk (OAR) sparing can be achieved without significantly compromising the plan in regions that require the full dose.

  View details for DOI 10.1088/1361-6560/ab9b54

  View details for PubMedID 32521512

• Impact of Audio-Visual Assisted Therapeutic Ambience in Radiotherapy (AVATAR) on Anesthesia Use, Payer Charges, and Treatment Time in Pediatric Patients. Practical radiation oncology Balazy, K. E., Gutkin, P. M., Skinner, L., von Eyben, R., Fowler, T., Pinkham, D. W., Rodriguez, S., Maxim, P. G., Donaldson, S. S., Loo, B. W., Bush, K., Hiniker, S. M. 2020

  Abstract

  PURPOSE: Pediatric radiotherapy requires optimal immobilization that often necessitates daily anesthesia. To decrease anesthesia use, we implemented a novel XXX system which projects video onto a radiolucent screen within the child's line of vision to provide attentional diversion. We investigated its reduction on anesthesia use, payer charges, and treatment time, as well as its impact on radiation delivery.METHODS AND MATERIALS: A 6-year retrospective analysis was performed among children undergoing radiotherapy (n=224), 3 years before and 3 after introduction of XXX. The frequency of anesthesia use before and after XXX implementation, as well as radiotherapy treatment times were compared. The number of spared anesthesia treatments allowed for a charge to payer analysis. To document lack of surface dose perturbation by XXX, a phantom craniospinal treatment course was delivered both with and without XXX. Additionally, an ion chamber course was delivered to document changes to dose at depth.RESULTS: More children were able to avoid anesthesia use entirely in the post-XXX cohort, compared to the pre-XXX cohort (73.2% vs 63.4%, p=0.03) and fewer required anesthesia for each treatment (18.8% vs 33%; p = 0.03). XXX introduction reduced anesthesia use for all ages studied. Treatment time per session was reduced by 38% using XXX compared to anesthesia. There were 326 fewer anesthesia sessions delivered over three years after XXX was introduced, with an estimated savings of > $500,000. OSLDs revealed a small increase in dose of 0.8%-9.5% with XXX, while the use of a thermomolded face mask increased skin dose as much as 58%.CONCLUSIONS: XXX introduction decreased anesthesia use in children undergoing radiotherapy; more avoided anesthesia entirely, and fewer needed it for every treatment. This resulted in a reduction in treatment time, and savings of nearly $550,000 in approximately 3 years, with minimal perturbation of radiotherapy dose delivery.

  View details for DOI 10.1016/j.prro.2019.12.009

  View details for PubMedID 31935524

• Technical Note: Evaluation of Audiovisual Biofeedback Smartphone Application for Respiratory Monitoring in Radiation Oncology. Medical physics Capaldi, D. P., Nano, T. F., Zhang, H. n., Skinner, L. B., Xing, L. n. 2020

  Abstract

  Radiation dose delivered to targets located near the upper abdomen or thorax are significantly affected by respiratory motion, necessitating large margins, limiting dose escalation. Surrogate motion management devices, such as the Real-time Position Management (RPM™) system (Varian Medical Systems, Palo Alto, CA), are commonly used to improve normal tissue sparing. Alternative to current solutions, we have developed and evaluated the feasibility of a real-time position management system that leverages the motion data from the onboard hardware of Apple iOS devices to provide patients with visual coaching with the potential to improve the reproducibility of breathing as well as improve patient compliance and reduce treatment delivery time.The iOS application, coined the Instant Respiratory Feedback (IRF) system, was developed in Swift (Apple Inc., Cupertino, CA) using the Core-Motion library and implemented on an Apple iPhone® devices. Operation requires an iPhone®, a 3D printed arm, and a radiolucent projector screen system for feedback. Direct comparison between IRF, which leverages sensor fusion data from the iPhone®, and RPM™, an optical based system, was performed on multiple respiratory motion phantoms and volunteers. The IRF system and RPM™ camera tracking marker were placed on the same location allowing for simultaneous data acquisition. The IRF surrogate measurement of displacement was compared to the signal trace acquired using RPM™ with univariate linear regressions and Bland-Altman analysis.Periodic motion shows excellent agreement between both systems, and subject motion shows good agreement during regular and irregular breathing motion. Comparison of IRF and RPM™ show very similar signal traces that were significantly related across all phantoms, including those motion with different amplitude and frequency, and subjects' waveforms (all r>0.9, p<0.0001). We demonstrate the feasibility of four-dimensional cone beam computed tomography reconstruction using IRF can acquire dynamic phantom images with similar image quality as RPM™.Feasibility of an iOS application to provide real-time respiratory motion is demonstrated. This system generated comparable signal traces to a commercially available system and offers an alternative method to monitor respiratory motion.

  View details for DOI 10.1002/mp.14484

  View details for PubMedID 32969075

• FLASH Irradiation Results in Reduced Severe Skin Toxicity Compared to Conventional-Dose-Rate Irradiation. Radiation research Soto, L. A., Casey, K. M., Wang, J. n., Blaney, A. n., Manjappa, R. n., Breitkreutz, D. n., Skinner, L. n., Dutt, S. n., Ko, R. B., Bush, K. n., Yu, A. S., Melemenidis, S. n., Strober, S. n., Englemann, E. n., Maxim, P. G., Graves, E. E., Loo, B. W. 2020

  Abstract

  Radiation therapy, along with surgery and chemotherapy, is one of the main treatments for cancer. While radiotherapy is highly effective in the treatment of localized tumors, its main limitation is its toxicity to normal tissue. Previous preclinical studies have reported that ultra-high dose-rate (FLASH) irradiation results in reduced toxicity to normal tissues while controlling tumor growth to a similar extent relative to conventional-dose-rate (CONV) irradiation. To our knowledge this is the first report of a dose-response study in mice comparing the effect of FLASH irradiation vs. CONV irradiation on skin toxicity. We found that FLASH irradiation results in both a lower incidence and lower severity of skin ulceration than CONV irradiation 8 weeks after single-fraction hemithoracic irradiation at high doses (30 and 40 Gy). Survival was also higher after FLASH hemithoracic irradiation (median survival >180 days at doses of 30 and 40 Gy) compared to CONV irradiation (median survival 100 and 52 days at 30 and 40 Gy, respectively). No ulceration was observed at doses 20 Gy or below in either FLASH or CONV. These results suggest a shifting of the dose-response curve for radiation-induced skin ulceration to the right for FLASH, compared to CONV irradiation, suggesting the potential for an enhanced therapeutic index for radiation therapy of cancer.

  View details for DOI 10.1667/RADE-20-00090

  View details for PubMedID 32853385

• A preliminary report of gonadal-sparing TBI using a VMAT technique. Practical radiation oncology Blomain, E. S., Kovalchuk, N. n., Neilsen, E. n., Skinner, L. n., Hoppe, R. T., Hiniker, S. M. 2020

  Abstract

  Reproductive toxicity is common following total body irradiation and has major quality of life implications for patients. In that context, this is the first report of gonadal-sparing VMAT TBI, successfully delivered in a boy and a girl with aplastic anemia. Both patients' VMAT TBI plans demonstrated improved gonadal sparing versus simulated conventional 2D approach (mean testes dose 0.45 Gy VMAT versus 0.72 Gy 2D; mean ovary dose 0.64 Gy VMAT versus 1.47 Gy 2D). PTV coverage was also improved for both cases with the VMAT plan versus conventional 2D plan (2 Gy D90% versus 1.9 Gy D90%, respectively). Given these dosimetric advantages, the present study can serve as a proof-of-concept for further prospective studies evaluating this technique for wider applications in populations receiving TBI.

  View details for DOI 10.1016/j.prro.2020.07.006

  View details for PubMedID 32795616

• Patient motion tracking for non-isocentric and non-coplanar treatments via fixed frame-of-reference 3D camera. Journal of applied clinical medical physics Gasparyan, S. n., Ko, K. n., Skinner, L. B., Ko, R. B., Loo, B. W., Fahimian, B. P., Yu, A. S. 2020

  Abstract

  As C-arm linac radiation therapy evolves toward faster, more efficient delivery, and more conformal dosimetry, treatments with increasingly complex couch motions are emerging. Monitoring the patient motion independently of the couch motion during non-coplanar, non-isocentric, or dynamic couch treatments is a key bottleneck to their clinical implementation. The goal of this study is to develop a prototype real-time monitoring system for unconventional beam trajectories to ensure a safe and accurate treatment delivery.An in-house algorithm was developed for tracking using a couch-mounted three-dimensional (3D) depth camera. The accuracy of patient motion detection on the couch was tested on a 3D printed phantom created from the body surface contour exported from the treatment planning system. The technique was evaluated against a commercial optical surface monitoring system with known phantom displacements of 3, 5, and 7 mm in lateral, longitudinal, and vertical directions by placing a head phantom on a dynamic platform on the treatment couch. The stability of the monitoring system was evaluated during dynamic couch trajectories, at speeds between 10.6 and 65 cm/min.The proposed monitoring system agreed with the ceiling mounted optical surface monitoring system in longitudinal, lateral, and vertical directions within 0.5 mm. The uncertainty caused by couch vibration increased with couch speed but remained sub-millimeter for speeds up to 32 cm/min. For couch speeds of 10.6, 32.2, and 65 cm/min, the uncertainty ranges were 0.27- 0.73 mm, 0.15-0.87 mm, and 0.28-1.29 mm, respectively.By mounting a 3D camera in the same frame-of-reference as the patient and eliminating dead spots, this proof of concept demonstrates real-time patient monitoring during couch motion. For treatments with non-coplanar beams, multiple isocenters, or dynamic couch motion, this provides additional safety without additional radiation dose and avoids some of the complexity and limitations of room mounted systems.

  View details for DOI 10.1002/acm2.12842

  View details for PubMedID 32107845

• An integrated quality assurance phantom for frameless single-isocenter multitarget stereotactic radiosurgery. Physics in medicine and biology Capaldi, D. P., Skinner, L. B., Dubrowski, P. n., Yu, A. S. 2020

  Abstract

  Purpose:Brain stereotactic-radiosurgery (SRS) treatments require multiple quality-assurance (QA) procedures to ensure accurate and precise treatment delivery. As single-isocenter multitarget SRS treatments become more popular, the quantification of off-axis accuracy of the linear-accelerator is crucial. In this study, a novel brain SRS integrated phantom was developed and validated to enable SRS QA with a single phantom to facilitate implementation of a frameless single-isocenter, multitarget SRS program. This phantom combines the independent verification of each positioning system, the Winston-Lutz, off-axis accuracy evaluation (i.e. off-axis Winston-Lutz), and the dosimetric accuracy utilizing both point-dose-measurements as well as film-measurement, without moving the phantom.Methods and Materials:A novel 3D-printed phantom, coinedOneIso, was designed with a movable insert which can switch between the Winston-Lutz test target and dose measurement without moving the phantom itself. For dose verification, eight brain SRS clinical-treatment-plans with 10MV Flattening-Filter-Free (FFF) beams were delivered on a Varian TrueBeam with a high-definition-multi-leaf-collimator (HD-MLC). Radiochromic film and pinpoint ion chamber comparison measurements were made between the OneIso and solid water (SW) phantom setups. For the off-axis Winston-Lutz measurements, a row of off-axis ball-bearings (BBs) was integrated into the OneIso. To quantify the spatial accuracy versus distance from isocenter, two-dimensional displacements were calculated between the planned and delivered BB locations relative to their respective MLC defined field border.Results:OneIso and the SW phantoms agree within 1%, for both film and point-dose measurements. OneIso identified a reduction in spatial accuracy further away from isocenter. Differences increased as distance from isocenter increased exceeding recommended SRS accuracy tolerances at 3-4cm away from isocenter.Conclusions:OneIso provides a streamlined, single-setup workflow for single-isocenter multitarget frameless linac-based SRS QA. Additionally, with the ability to quantify off-axis spatial-discrepancies, we can determine limitations on the maximum distance between targets to ensure a single-isocenter multitarget SRS program meets recommended guidelines.

  View details for DOI 10.1088/1361-6560/ab8534

  View details for PubMedID 32235050

• Abdominal FLASH irradiation reduces radiation-induced gastrointestinal toxicity for the treatment of ovarian cancer in mice. Scientific reports Levy, K. n., Natarajan, S. n., Wang, J. n., Chow, S. n., Eggold, J. T., Loo, P. E., Manjappa, R. n., Melemenidis, S. n., Lartey, F. M., Schüler, E. n., Skinner, L. n., Rafat, M. n., Ko, R. n., Kim, A. n., H Al-Rawi, D. n., von Eyben, R. n., Dorigo, O. n., Casey, K. M., Graves, E. E., Bush, K. n., Yu, A. S., Koong, A. C., Maxim, P. G., Loo, B. W., Rankin, E. B. 2020; 10 (1): 21600

  Abstract

  Radiation therapy is the most effective cytotoxic therapy for localized tumors. However, normal tissue toxicity limits the radiation dose and the curative potential of radiation therapy when treating larger target volumes. In particular, the highly radiosensitive intestine limits the use of radiation for patients with intra-abdominal tumors. In metastatic ovarian cancer, total abdominal irradiation (TAI) was used as an effective postsurgical adjuvant therapy in the management of abdominal metastases. However, TAI fell out of favor due to high toxicity of the intestine. Here we utilized an innovative preclinical irradiation platform to compare the safety and efficacy of TAI ultra-high dose rate FLASH irradiation to conventional dose rate (CONV) irradiation in mice. We demonstrate that single high dose TAI-FLASH produced less mortality from gastrointestinal syndrome, spared gut function and epithelial integrity, and spared cell death in crypt base columnar cells compared to TAI-CONV irradiation. Importantly, TAI-FLASH and TAI-CONV irradiation had similar efficacy in reducing tumor burden while improving intestinal function in a preclinical model of ovarian cancer metastasis. These findings suggest that FLASH irradiation may be an effective strategy to enhance the therapeutic index of abdominal radiotherapy, with potential application to metastatic ovarian cancer.

  View details for DOI 10.1038/s41598-020-78017-7

  View details for PubMedID 33303827

• Volumetric Modulated Arc Therapy and 3-Dimensional Printed Bolus in the Treatment of Refractory Primary Cutaneous Gamma Delta Lymphoma of the Bilateral Legs PRACTICAL RADIATION ONCOLOGY Obeid, J., Gutkin, P. M., Lewis, J., Skinner, L., Wang, E. B., Khodadoust, M. S., Kim, Y. H., Weng, W., Hoppe, R. T., Hiniker, S. M. 2019; 9 (4): 220–25

  View details for DOI 10.1016/j.prro.2019.02.016

  View details for Web of Science ID 000472574100020

• Tungsten filled 3D printed field shaping devices for electron beam radiation therapy. PloS one Skinner, L., Fahimian, B. P., Yu, A. S. 2019; 14 (6): e0217757

  Abstract

  PURPOSE: Electron radiotherapy is a labor-intensive treatment option that is complicated by the need for field shaping blocks. These blocks are typically made from casting Cerrobend alloys containing lead and cadmium. This is a highly toxic process with limited precision. This work aims to provide streamlined and more precise electron radiotherapy by 3D using printing techniques.METHODS: The 3D printed electron cutout consists of plastic shells filled with 2 mm diameter tungsten ball bearings. Five clinical Cerrobend defined field were compared to the planned fields by measuring the light field edge when mounted in the electron applicator on a linear accelerator. The dose transmitted through the 3D printed and Cerrobend cutouts was measured using an IC profiler ion chamber array with 6 MeV and 16 MeV beams. Dose profiles from the treatment planning system were also compared to the measured dose profiles. Centering and full width half maximum (FWHM) metrics were taken directly from the profiler software.RESULTS: The transmission of a 16MeV beam through a 12 mm thick layer of tungsten ball bearings agreed within 1% of a 15 mm thick Cerrobend block (measured with an ion chamber array). The radiation fields shaped by ball bearing filled 3D printed cutout were centered within 0.4 mm of the planned outline, whereas the Cerrobend cutout fields had shift errors of 1-3 mm, and shape errors of 0.5-2 mm. The average shift of Cerrobend cutouts was 2.3 mm compared to the planned fields (n = 5). Beam penumbra of the 3D printed cutouts was found to be equivalent to the 15 mm thick Cerrobend cutout. The beam profiles agreed within 1.2% across the whole 30 cm profile widths.CONCLUSIONS: This study demonstrates that with a proper quality assurance procedure, 3D-printed cutouts can provide more accurate electron radiotherapy with reduced toxicity compared to traditional Cerrobend methods.

  View details for DOI 10.1371/journal.pone.0217757

  View details for PubMedID 31216296

• Optimizing efficiency and safety in external beam radiotherapy using automated plan check (APC) tool and six sigma methodology. Journal of applied clinical medical physics Liu, S. n., Bush, K. K., Bertini, J. n., Fu, Y. n., Lewis, J. M., Pham, D. J., Yang, Y. n., Niedermayr, T. R., Skinner, L. n., Xing, L. n., Beadle, B. M., Hsu, A. n., Kovalchuk, N. n. 2019; 20 (8): 56–64

  Abstract

  To develop and implement an automated plan check (APC) tool using a Six Sigma methodology with the aim of improving safety and efficiency in external beam radiotherapy.The Six Sigma define-measure-analyze-improve-control (DMAIC) framework was used by measuring defects stemming from treatment planning that were reported to the departmental incidence learning system (ILS). The common error pathways observed in the reported data were combined with our departmental physics plan check list, and AAPM TG-275 identified items. Prioritized by risk priority number (RPN) and severity values, the check items were added to the APC tool developed using Varian Eclipse Scripting Application Programming Interface (ESAPI). At 9 months post-APC implementation, the tool encompassed 89 check items, and its effectiveness was evaluated by comparing RPN values and rates of reported errors. To test the efficiency gains, physics plan check time and reported error rate were prospectively compared for 20 treatment plans.The APC tool was successfully implemented for external beam plan checking. FMEA RPN ranking re-evaluation at 9 months post-APC demonstrated a statistically significant average decrease in RPN values from 129.2 to 83.7 (P < .05). After the introduction of APC, the average frequency of reported treatment-planning errors was reduced from 16.1% to 4.1%. For high-severity errors, the reduction was 82.7% for prescription/plan mismatches and 84.4% for incorrect shift note. The process shifted from 4σ to 5σ quality for isocenter-shift errors. The efficiency study showed a statistically significant decrease in plan check time (10.1 ± 7.3 min, P = .005) and decrease in errors propagating to physics plan check (80%).Incorporation of APC tool has significantly reduced the error rate. The DMAIC framework can provide an iterative and robust workflow to improve the efficiency and quality of treatment planning procedure enabling a safer radiotherapy process.

  View details for DOI 10.1002/acm2.12678

  View details for PubMedID 31423729

• Factor 10 Expedience of Monthly Linac Quality Assurance via an Ion Chamber Array and Automation Scripts. Technology in cancer research & treatment Skinner, L. B., Yang, Y., Hsu, A., Xing, L., Yu, A. S., Niedermayr, T. 2019; 18: 1533033819876897

  Abstract

  PURPOSE: While critical for safe and accurate radiotherapy, monthly quality assurance of medical linear accelerators is time-consuming and takes physics resources away from other valuable tasks. The previous methods at our institution required 5 hours to perform the mechanical and dosimetric monthly linear accelerator quality assurance tests. An improved workflow was developed to perform these tests with higher accuracy, with fewer error pathways, in significantly less time.METHODS: A commercial ion chamber array (IC profiler, Sun Nuclear, Melbourne, Florida) is combined with automation scripts to consolidate monthly linear accelerator QA. The array was used to measure output, flatness, symmetry, jaw positions, gated dose constancy, energy constancy, collimator walkout, crosshair centering, and dosimetric leaf gap constancy. Treatment plans were combined with automation scripts that interface with Sun Nuclear's graphical user interface. This workflow was implemented on a standard Varian clinac, with no special adaptations, and can be easily applied to other C-arm linear accelerators.RESULTS: These methods enable, in 30 minutes, measurement and analysis of 20 of the 26 dosimetric and mechanical monthly tests recommended by TG-142. This method also reduces uncertainties in the measured beam profile constancy, beam energy constancy, field size, and jaw position tests, compared to our previous methods. One drawback is the increased uncertainty associated with output constancy. Output differences between IC profiler and farmer chamber in plastic water measurements over a 6-month period, across 4 machines, were found to have a 0.3% standard deviation for photons and a 0.5% standard deviation for electrons, which is sufficient for verifying output accuracy according to TG-142 guidelines. To minimize error pathways, automation scripts which apply the required settings, as well as check the exported data file integrity were employed.CONCLUSIONS: The equipment, procedure, and scripts used here reduce the time burden of routine quality assurance tests and in most instances improve precision over our previous methods.

  View details for DOI 10.1177/1533033819876897

  View details for PubMedID 31707931

• Cost Analysis of Audiovisual-Assisted Therapeutic Ambiance in Radiation Therapy (AVATAR) Aided Omission of Anesthesia in Radiation for Pediatric Malignancies. Practical radiation oncology McClelland, S. n., Overton, K. W., Overshiner, B. n., Bush, K. n., Loo, B. W., Skinner, L. B., Watson, G. A., Holmes, J. A., Hiniker, S. M., Maxim, P. G. 2019

  View details for DOI 10.1016/j.prro.2019.09.011

  View details for PubMedID 31574319

• Beyond sixfold coordinated Si in SiO2 glass at ultrahigh pressures PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Prescher, C., Prakapenka, V. B., Stefanski, J., Jahn, S., Skinner, L. B., Wang, Y. 2017; 114 (38): 10041–46

  Abstract

  We investigated the structure of SiO2 glass up to 172 GPa using high-energy X-ray diffraction. The combination of a multichannel collimator with diamond anvil cells enabled the measurement of structural changes in silica glass with total X-ray diffraction to previously unachievable pressures. We show that SiO2 first undergoes a change in Si-O coordination number from fourfold to sixfold between 15 and 50 GPa, in agreement with previous investigations. Above 50 GPa, the estimated coordination number continuously increases from 6 to 6.8 at 172 GPa. Si-O bond length shows first an increase due to the fourfold to sixfold coordination change and then a smaller linear decrease up to 172 GPa. We reconcile the changes in relation to the oxygen-packing fraction, showing that oxygen packing decreases at ultrahigh pressures to accommodate the higher than sixfold Si-O coordination. These results give experimental insight into the structural changes of silicate glasses as analogue materials for silicate melts at ultrahigh pressures.

  View details for DOI 10.1073/pnas.1708882114

  View details for Web of Science ID 000411157100045

  View details for PubMedID 28874582

  View details for PubMedCentralID PMC5617297

• The temperature dependence of intermediate range oxygen-oxygen correlations in liquid water JOURNAL OF CHEMICAL PHYSICS Schlesinger, D., Wikfeldt, K. T., Skinner, L. B., Benmore, C. J., Nilsson, A., Pettersson, L. G. 2016; 145 (8)

  Abstract

  We analyze the recent temperature dependent oxygen-oxygen pair-distribution functions from experimental high-precision x-ray diffraction data of bulk water by Skinner et al. [J. Chem. Phys. 141, 214507 (2014)] with particular focus on the intermediate range where small, but significant, correlations are found out to 17 Å. The second peak in the pair-distribution function at 4.5 Å is connected to tetrahedral coordination and was shown by Skinner et al. to change behavior with temperature below the temperature of minimum isothermal compressibility. Here we show that this is associated also with a peak growing at 11 Å which strongly indicates a collective character of fluctuations leading to the enhanced compressibility at lower temperatures. We note that the peak at ∼13.2 Å exhibits a temperature dependence similar to that of the density with a maximum close to 277 K or 4 °C. We analyze simulations of the TIP4P/2005 water model in the same manner and find excellent agreement between simulations and experiment albeit with a temperature shift of ∼20 K.

  View details for DOI 10.1063/1.4961404

  View details for Web of Science ID 000383875500037

  View details for PubMedID 27586931

• X-ray and Neutron Scattering of Water CHEMICAL REVIEWS Amann-Winkel, K., Bellissent-Funel, M., Bove, L. E., Loerting, T., Nilsson, A., Paciaroni, A., Schlesinger, D., Skinner, L. 2016; 116 (13): 7570-7589

  Abstract

  This review article focuses on the most recent advances in X-ray and neutron scattering studies of water structure, from ambient temperature to the deeply supercooled and amorphous states, and of water diffusive and collective dynamics, in disparate thermodynamic conditions and environments. In particular, the ability to measure X-ray and neutron diffraction of water with unprecedented high accuracy in an extended range of momentum transfers has allowed the derivation of detailed O-O pair correlation functions. A panorama of the diffusive dynamics of water in a wide range of temperatures (from 400 K down to supercooled water) and pressures (from ambient up to multiple gigapascals) is presented. The recent results obtained by quasi-elastic neutron scattering under high pressure are compared with the existing data from nuclear magnetic resonance, dielectric and infrared measurements, and modeling. A detailed description of the vibrational dynamics of water as measured by inelastic neutron scattering is presented. The dependence of the water vibrational density of states on temperature and pressure, and in the presence of biological molecules, is discussed. Results about the collective dynamics of water and its dispersion curves as measured by coherent inelastic neutron scattering and inelastic X-ray scattering in different thermodynamic conditions are reported.

  View details for DOI 10.1021/acs.chemrev.5b00663

  View details for Web of Science ID 000379794000006

  View details for PubMedID 27195477

• Low-Dimensional Network Formation in Molten Sodium Carbonate SCIENTIFIC REPORTS Wilding, M. C., Wilson, M., Alderman, O. G., Benmore, C., Weber, J. R., Parise, J. B., Tamalonis, A., Skinner, L. 2016; 6: 24415

  Abstract

  Molten carbonates are highly inviscid liquids characterized by low melting points and high solubility of rare earth elements and volatile molecules. An understanding of the structure and related properties of these intriguing liquids has been limited to date. We report the results of a study of molten sodium carbonate (Na2CO3) which combines high energy X-ray diffraction, containerless techniques and computer simulation to provide insight into the liquid structure. Total structure factors (F(x)(Q)) are collected on the laser-heated carbonate spheres suspended in flowing gases of varying composition in an aerodynamic levitation furnace. The respective partial structure factor contributions to F(x)(Q) are obtained by performing molecular dynamics simulations treating the carbonate anions as flexible entities. The carbonate liquid structure is found to be heavily temperature-dependent. At low temperatures a low-dimensional carbonate chain network forms, at T = 1100 K for example ~55% of the C atoms form part of a chain. The mean chain lengths decrease as temperature is increased and as the chains become shorter the rotation of the carbonate anions becomes more rapid enhancing the diffusion of Na(+) ions.

  View details for DOI 10.1038/srep24415

  View details for Web of Science ID 000374166300001

  View details for PubMedID 27080401

  View details for PubMedCentralID PMC4832186

• Exploring the structure of high temperature, iron-bearing liquids Wilding, M., Benmore, C., Weber, R., Parise, J., Lazareva, L., Skinner, L., Alderman, O., Tamalonis, A. ELSEVIER SCIENCE BV. 2015: 358–63

  View details for DOI 10.1016/j.matpr.2015.05.050

  View details for Web of Science ID 000358000300017

• The structure of water around the compressibility minimum JOURNAL OF CHEMICAL PHYSICS Skinner, L. B., Benmore, C. J., Neuefeind, J. C., Parise, J. B. 2014; 141 (21): 214507

  Abstract

  Here we present diffraction data that yield the oxygen-oxygen pair distribution function, g(OO)(r) over the range 254.2-365.9 K. The running O-O coordination number, which represents the integral of the pair distribution function as a function of radial distance, is found to exhibit an isosbestic point at 3.30(5) Å. The probability of finding an oxygen atom surrounding another oxygen at this distance is therefore shown to be independent of temperature and corresponds to an O-O coordination number of 4.3(2). Moreover, the experimental data also show a continuous transition associated with the second peak position in g(OO)(r) concomitant with the compressibility minimum at 319 K.

  View details for DOI 10.1063/1.4902412

  View details for Web of Science ID 000346014200032

  View details for PubMedID 25481152

• Molten uranium dioxide structure and dynamics SCIENCE Skinner, L. B., Benmore, C. J., Weber, J. R., Williamson, M. A., Tamalonis, A., Hebden, A., Wiencek, T., Alderman, O. G., Guthrie, M., Leibowitz, L., Parise, J. B. 2014; 346 (6212): 984–87

  Abstract

  Uranium dioxide (UO2) is the major nuclear fuel component of fission power reactors. A key concern during severe accidents is the melting and leakage of radioactive UO2 as it corrodes through its zirconium cladding and steel containment. Yet, the very high temperatures (>3140 kelvin) and chemical reactivity of molten UO2 have prevented structural studies. In this work, we combine laser heating, sample levitation, and synchrotron x-rays to obtain pair distribution function measurements of hot solid and molten UO2. The hot solid shows a substantial increase in oxygen disorder around the lambda transition (2670 K) but negligible U-O coordination change. On melting, the average U-O coordination drops from 8 to 6.7 ± 0.5. Molecular dynamics models refined to this structure predict higher U-U mobility than 8-coordinated melts.

  View details for DOI 10.1126/science.1259709

  View details for Web of Science ID 000345696000041

  View details for PubMedID 25414311

• Structure of Ba-Ti-Al-O glasses produced by aerodynamic levitation and laser heating PHYSICAL REVIEW B Kidkhunthod, P., Skinner, L. B., Barnes, A. C., Klysubun, W., Fischer, H. E. 2014; 90 (9)

  View details for DOI 10.1103/PhysRevB.90.094206

  View details for Web of Science ID 000342137700002

• Packing and the structural transformations in liquid and amorphous oxides from ambient to extreme conditions PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Zeidler, A., Salmon, P., Skinner, L. 2014; 111 (28): 10045–48

  Abstract

  Liquid and glassy oxide materials play a vital role in multiple scientific and technological disciplines, but little is known about the part played by oxygen-oxygen interactions in the structural transformations that change their physical properties. Here we show that the coordination number of network-forming structural motifs, which play a key role in defining the topological ordering, can be rationalized in terms of the oxygen-packing fraction over an extensive pressure and temperature range. The result is a structural map for predicting the likely regimes of topological change for a range of oxide materials. This information can be used to forecast when changes may occur to the transport properties and compressibility of, e.g., fluids in planetary interiors, and is a prerequisite for the preparation of new materials following the principles of rational design.

  View details for DOI 10.1073/pnas.1405660111

  View details for Web of Science ID 000338985700020

  View details for PubMedID 24982151

  View details for PubMedCentralID PMC4104877

• Ultrafast X-ray probing of water structure below the homogeneous ice nucleation temperature NATURE Sellberg, J. A., Huang, C., McQueen, T. A., Loh, N. D., Laksmono, H., Schlesinger, D., Sierra, R. G., Nordlund, D., Hampton, C. Y., Starodub, D., DePonte, D. P., Beye, M., Chen, C., Martin, A. V., Barty, A., Wikfeldt, K. T., Weiss, T. M., Caronna, C., Feldkamp, J., Skinner, L. B., Seibert, M. M., Messerschmidt, M., Williams, G. J., Boutet, S., Pettersson, L. G., Bogan, M. J., Nilsson, A. 2014; 510 (7505): 381-?

  Abstract

  Water has a number of anomalous physical properties, and some of these become drastically enhanced on supercooling below the freezing point. Particular interest has focused on thermodynamic response functions that can be described using a normal component and an anomalous component that seems to diverge at about 228 kelvin (refs 1-3). This has prompted debate about conflicting theories that aim to explain many of the anomalous thermodynamic properties of water. One popular theory attributes the divergence to a phase transition between two forms of liquid water occurring in the 'no man's land' that lies below the homogeneous ice nucleation temperature (TH) at approximately 232 kelvin and above about 160 kelvin, and where rapid ice crystallization has prevented any measurements of the bulk liquid phase. In fact, the reliable determination of the structure of liquid water typically requires temperatures above about 250 kelvin. Water crystallization has been inhibited by using nanoconfinement, nanodroplets and association with biomolecules to give liquid samples at temperatures below TH, but such measurements rely on nanoscopic volumes of water where the interaction with the confining surfaces makes the relevance to bulk water unclear. Here we demonstrate that femtosecond X-ray laser pulses can be used to probe the structure of liquid water in micrometre-sized droplets that have been evaporatively cooled below TH. We find experimental evidence for the existence of metastable bulk liquid water down to temperatures of 227(-1)(+2) kelvin in the previously largely unexplored no man's land. We observe a continuous and accelerating increase in structural ordering on supercooling to approximately 229 kelvin, where the number of droplets containing ice crystals increases rapidly. But a few droplets remain liquid for about a millisecond even at this temperature. The hope now is that these observations and our detailed structural data will help identify those theories that best describe and explain the behaviour of water.

  View details for DOI 10.1038/nature13266

  View details for Web of Science ID 000337350200031

• Low Cation Coordination in Oxide Melts PHYSICAL REVIEW LETTERS Skinner, L. B., Benmore, C. J., Weber, J. R., Du, J., Neuefeind, J., Tumber, S. K., Parise, J. B. 2014; 112 (15): 157801

  Abstract

  The complete set of partial pair distribution functions for a rare earth oxide liquid are measured by combining aerodynamic levitation, neutron and x-ray diffraction on Y2O3, and Ho2O3 melts at 2870 K. The average Y-O (or Ho-O) coordination of these isomorphic melts is measured to be 5.5(2), which is significantly less than the octahedral coordination of crystalline Y2O3 (or Ho2O3). Investigation of La2O3, ZrO2, and Al2O3 melts by x-ray diffraction and molecular dynamics simulations also show lower-than-crystal cation-oxygen coordination. These measurements suggest a general trend towards lower coordination compared to their crystalline counterparts. It is found that the coordination drop is larger for lower field strength, larger radius cations and is negligible for high field strength (network forming) cations, such as SiO2. These findings have broad implications for predicting the local structure and related physical properties of metal-oxide melts and oxide glasses.

  View details for DOI 10.1103/PhysRevLett.112.157801

  View details for Web of Science ID 000334597300014

  View details for PubMedID 24785072

• Atomistic insight into viscosity and density of silicate melts under pressure NATURE COMMUNICATIONS Wang, Y., Sakamaki, T., Skinner, L. B., Jing, Z., Yu, T., Kono, Y., Park, C., Shen, G., Rivers, M. L., Sutton, S. R. 2014; 5: 3241

  Abstract

  A defining characteristic of silicate melts is the degree of polymerization (tetrahedral connectivity), which dictates viscosity and affects compressibility. While viscosity of depolymerized silicate melts increases with pressure consistent with the free-volume theory, isothermal viscosity of polymerized melts decreases with pressure up to ~3-5 GPa, above which it turns over to normal (positive) pressure dependence. Here we show that the viscosity turnover in polymerized liquids corresponds to the tetrahedral packing limit, below which the structure is compressed through tightening of the inter-tetrahedral bond angle, resulting in high compressibility, continual breakup of tetrahedral connectivity and viscosity decrease with increasing pressure. Above the turnover pressure, silicon and aluminium coordination increases to allow further packing, with increasing viscosity and density. These structural responses prescribe the distribution of melt viscosity and density with depth and play an important role in magma transport in terrestrial planetary interiors.

  View details for DOI 10.1038/ncomms4241

  View details for Web of Science ID 000331143500001

  View details for PubMedID 24476847

• Benchmark oxygen-oxygen pair-distribution function of ambient water from x-ray diffraction measurements with a wide Q-range JOURNAL OF CHEMICAL PHYSICS Skinner, L. B., Huang, C., Schlesinger, D., Pettersson, L. G., Nilsson, A., Benmore, C. J. 2013; 138 (7)

  Abstract

  Four recent x-ray diffraction measurements of ambient liquid water are reviewed here. Each of these measurements represents a significant development of the x-ray diffraction technique applied to the study of liquid water. Sources of uncertainty from statistical noise, Q-range, Compton scattering, and self-scattering are discussed. The oxygen-hydrogen contribution to the measured x-ray scattering pattern was subtracted using literature data to yield an experimental determination, with error bars, of the oxygen-oxygen pair-distribution function, g(OO)(r), which essentially describes the distribution of molecular centers. The extended Q-range and low statistical noise of these measurements has significantly reduced truncation effects and related errors in the g(OO)(r) functions obtained. From these measurements and error analysis, the position and height of the nearest neighbor maximum in g(OO)(r) were found to be 2.80(1) Å and 2.57(5) respectively. Numerical data for the coherent differential x-ray scattering cross-section I(X)(Q), the oxygen-oxygen structure factor S(OO)(Q), and the derived g(OO)(r) are provided as benchmarks for calibrating force-fields for water.

  View details for DOI 10.1063/1.4790861

  View details for Web of Science ID 000315263500038

  View details for PubMedID 23445023

• Joint diffraction and modeling approach to the structure of liquid alumina PHYSICAL REVIEW B Skinner, L. B., Barnes, A. C., Salmon, P. S., Hennet, L., Fischer, H. E., Benmore, C. J., Kohara, S., Weber, J., Bytchkov, A., Wilding, M. C., Parise, J. B., Farmer, T. O., Pozdnyakova, I., Tumber, S. K., Ohara, K. 2013; 87 (2)

  View details for DOI 10.1103/PhysRevB.87.024201

  View details for Web of Science ID 000313029800002

• Structure and diffusion of ZnO-SrO-CaO-Na2O-SiO2 bioactive glasses: a combined high energy X-ray diffraction and molecular dynamics simulations study RSC ADVANCES Xiang, Y., Du, J., Skinner, L. B., Benmore, C. J., Wren, A. W., Boydd, D. J., Towler, M. R. 2013; 3 (17): 5966–78

  View details for DOI 10.1039/c3ra23231j

  View details for Web of Science ID 000316965800034

• Structure of the floating water bridge and water in an electric field PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Skinner, L. B., Benmore, C. J., Shyam, B., Weber, J. R., Parise, J. B. 2012; 109 (41): 16463–68

  Abstract

  The floating water bridge phenomenon is a freestanding rope-shaped connection of pure liquid water, formed under the influence of a high potential difference (approximately 15 kV). Several recent spectroscopic, optical, and neutron scattering studies have suggested that the origin of the bridge is associated with the formation of anisotropic chains of water molecules in the liquid. In this work, high energy X-ray diffraction experiments have been performed on a series of floating water bridges as a function of applied voltage, bridge length, and position within the bridge. The two-dimensional X-ray scattering data showed no direction-dependence, indicating that the bulk water molecules do not exhibit any significant preferred orientation along the electric field. The only structural changes observed were those due to heating, and these effects were found to be the same as for bulk water. These X-ray scattering measurements are supported by molecular dynamics (MD) simulations which were performed under electric fields of 10(6) V/m and 10(9) V/m. Directional structure factor calculations were made from these simulations parallel and perpendicular to the E-field. The 10(6) V/m model showed no significant directional-dependence (anisotropy) in the structure factors. The 10(9) V/m model however, contained molecules aligned by the E-field, and had significant structural anisotropy.

  View details for DOI 10.1073/pnas.1210732109

  View details for Web of Science ID 000310280300025

  View details for PubMedID 23010930

  View details for PubMedCentralID PMC3478597

• Comment on 'Molecular arrangement in water: random but not quite' JOURNAL OF PHYSICS-CONDENSED MATTER Skinner, L. B., Benmore, C. J., Parise, J. B. 2012; 24 (33): 338001; discussion 338002

  Abstract

  Accurate high energy x-ray diffraction data are presented on liquid water measured at room temperature. Sources of both systematic and statistical errors within the experiment are considered and data consistency checks are discussed. It is found that the resulting x-ray pair distribution function is smoothly varying in real space and shows no evidence of small peaks in the 3-5 Å region. Our results are in contrast to the recent findings reported in Petkov et al 2012 J. Phys.: Condens. Matter 24 155102.

  View details for DOI 10.1088/0953-8984/24/33/338001

  View details for Web of Science ID 000306997300024

  View details for PubMedID 22824868

• Structure and triclustering in Ba-Al-O glass PHYSICAL REVIEW B Skinner, L. B., Barnes, A. C., Salmon, P. S., Fischer, H. E., Drewitt, J. E., Honkimaeki, V. 2012; 85 (6)

  View details for DOI 10.1103/PhysRevB.85.064201

  View details for Web of Science ID 000300565700003

• Area detector corrections for high quality synchrotron X-ray structure factor measurements NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT Skinner, L. B., Benmore, C. J., Parise, J. B. 2012; 662 (1): 61–70

  View details for DOI 10.1016/j.nima.2011.09.031

  View details for Web of Science ID 000298571400009

• Nanostructure of Calcium Silicate Hydrates in Cements PHYSICAL REVIEW LETTERS Skinner, L. B., Chae, S. R., Benmore, C. J., Wenk, H. R., Monteiro, P. M. 2010; 104 (19): 195502

  Abstract

  Calcium silicate hydrate (CSH) is the major volume phase in the matrix of Portland cement concrete. Total x-ray scattering measurements with synchrotron x rays on synthetic CSH(I) shows nanocrystalline ordering with a particle diameter of 3.5(5) nm, similar to a size-broadened 1.1 nm tobermorite crystal structure. The CSH component in hydrated tricalcium silicate is found to be similar to CSH(I). Only a slight bend and additional disorder within the CaO sheets is required to explain its nanocrystalline structure.

  View details for DOI 10.1103/PhysRevLett.104.195502

  View details for Web of Science ID 000277699600029

  View details for PubMedID 20866975

• Liquid-Liquid Phase Transition in Supercooled Yttria-Alumina PHYSICAL REVIEW LETTERS Barnes, A. C., Skinner, L. B., Salmon, P. S., Bytchkov, A., Pozdnyakova, I., Farmer, T. O., Fischer, H. E. 2009; 103 (22): 225702

  Abstract

  The structure and thermal characteristics of aerodynamically levitated samples of yttria-alumina in the liquid, supercooled liquid and solid phases were explored in an extensive series of high energy x-ray diffraction, small angle neutron scattering, and pyrometric cooling measurements. Particular focus was placed on the compound (Y2O3)(x)(Al2O3)(1-x) with x = 0.2 for which a liquid-liquid phase transition at a temperature of 1788 K has recently been reported. No structural or thermal signature in support of this metastable phase transition could be found.

  View details for DOI 10.1103/PhysRevLett.103.225702

  View details for Web of Science ID 000272182000034

  View details for PubMedID 20366109

• Phase separation, crystallization and polyamorphism in the Y2O3-Al2O3 system Skinner, L. B., Barnes, A. C., Salmon, P. S., Crichton, W. A. IOP PUBLISHING LTD. 2008: 205103

  Abstract

  A detailed study of glass formation from aerodynamically levitated liquids in the (Y(2)O(3))(x)(Al(2)O(3))(1-x) system for the composition range 0.21≤x≤0.41 was undertaken by using pyrometric, optical imaging and x-ray diffraction methods. Homogeneous and clear single-phase glasses were produced over the composition range [Formula: see text]. For Y(2)O(3)-rich compositions ([Formula: see text]), cloudy materials were produced which contain inclusions of crystalline yttrium aluminium garnet (YAG) of diameter up to 40 µm in a glassy matrix. For Y(2)O(3)-poor compositions around x = 0.24, cloudy materials were also produced, but it was not possible to deduce whether this resulted from (i) sub-micron inclusions of a nano-crystalline or glassy material in a glassy matrix or (ii) a glass formed by spinodal decomposition. For x = 0.21, however, the sample cloudiness results from crystallization into at least two phases comprising yttrium aluminium perovskite and alumina. The associated pyrometric cooling curve shows slow recalescence events with a continuous and slow evolution of excess heat which contrasts with the sharp recalescence events observed for the crystallization of YAG at compositions near x = 0.375. The materials that are the most likely candidates for demonstrating homogeneous nucleation of a second liquid phase occur around x = 0.25, which corresponds to the limit for formation of a continuous random network of corner-shared AlO(4) tetrahedra.

  View details for DOI 10.1088/0953-8984/20/20/205103

  View details for Web of Science ID 000255661500058

  View details for PubMedID 21694284

• An oscillating coil system for contactless electrical conductivity measurements of aerodynamically levitated melts REVIEW OF SCIENTIFIC INSTRUMENTS Skinner, L., Barnes, A. C. 2006; 77 (12)

  View details for DOI 10.1063/1.2403939

  View details for Web of Science ID 000243159100021