Multi-Institutional Audit of FLASH and Conventional Dosimetry With a 3D Printed Anatomically Realistic Mouse Phantom.

PURPOSE: We conducted a multi-institutional dosimetric audit between FLASH and conventional dose rate (CONV) electron irradiations by using an anatomically realistic 3-dimensional (3D) printed mouse phantom. METHODS AND MATERIALS: A computed tomography (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 2 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. RESULTS: Compared with 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 effect on dose distribution (<0.5%). Mean differences between FLASH and CONV decreased from the first to the second replicate (4.3%-1.2%), and differences from the prescribed dose decreased for both CONV (3.6%-2.5%) and FLASH (6.4%-2.7%). Total dose accuracy suggests consistent pulse dose and pulse number, although these were not specifically assessed. Positioning variability was observed, likely due to the absence of robust positioning aids or image guidance. CONCLUSIONS: This study marks the first dosimetric audit for FLASH using a nonhomogeneous 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 biologic findings.

A clinical solution for non-toxic 3D-printed photon blocks in external beam radiation therapy.

PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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%. CONCLUSIONS: 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.

A Couch Mounted Smartphone-based Motion Monitoring System for Radiation Therapy.

PURPOSE: Surface-guided radiation-therapy (SGRT) systems are being adopted into clinical practice for patient setup and motion monitoring. However, commercial systems remain cost prohibitive to resource-limited clinics around the world. Our aim is to develop and validate a smartphone-based application using LiDAR cameras (such as on recent Apple iOS devices) for facilitating SGRT in low-resource centers. The proposed SGRT application was tested at multiple institutions and validated using phantoms and volunteers against various commercial systems to demonstrate feasibility. METHODS AND MATERIALS: An iOS application was developed in Xcode and written in Swift using the Augmented-Reality (AR) Kit and implemented on an Apple iPhone 13 Pro with a built-in LiDAR camera. The application contains multiple features: 1) visualization of both the camera and depth video feeds (at a ∼60Hz sample-frequency), 2) region-of-interest (ROI) selection over the patient's anatomy where motion is measured, 3) chart displaying the average motion over time in the ROI, and 4) saving/exporting the motion traces and surface map over the ROI for further analysis. The iOS application was tested to evaluate depth measurement accuracy for: 1) different angled surfaces, 2) different field-of-views over different distances, and 3) similarity to a commercially available SGRT systems (Vision RT AlignRT and Varian IDENTIFY) with motion phantoms and healthy volunteers across 3 institutions. Measurements were analyzed using linear-regressions and Bland-Altman analysis. RESULTS: Compared with the clinical system measurements (reference), the iOS application showed excellent agreement for depth (r = 1.000, P < .0001; bias = -0.07±0.24 cm) and angle (r = 1.000, P < .0001; bias = 0.02±0.69°) measurements. For free-breathing traces, the iOS application was significantly correlated to phantom motion (institute 1: r = 0.99, P < .0001; bias =-0.003±0.03 cm; institute 2: r = 0.98, P < .0001; bias = -0.001±0.10 cm; institute 3: r = 0.97, P < .0001; bias = 0.04±0.06 cm) and healthy volunteer motion (institute 1: r = 0.98, P < .0001; bias = -0.008±0.06 cm; institute 2: r = 0.99, P < .0001; bias = -0.007±0.12 cm; institute 3: r = 0.99, P < .0001; bias = -0.001±0.04 cm). CONCLUSIONS: The proposed approach using a smartphone-based application provides a low-cost platform that could improve access to surface-guided radiation therapy accounting for motion.

Tungsten Filled 3-Dimensional Printed Lung Blocks for Total Body Irradiation.

PURPOSE: Lung blocks for total-body irradiation 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. We propose a streamlined method to create 3-dimensional (3D)-printed lung block shells and fill them with tungsten ball bearings to remove lead and improve overall accuracy in the block manufacturing workflow. METHODS AND MATERIALS: 3D-printed lung block shells were automatically generated using an inhouse software, printed, and filled with 2 to 3 mm diameter tungsten ball bearings. Clinical Cerrobend blocks were compared with 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 and to compare with the treatment-planning-system. Additionally, the coefficient-of-variation in the central 80% of full-width-half-maximum was computed and compared between Cerrobend and 3D-printed blocks. RESULTS: The geometric difference between treatment-planning-system and 3D-printed blocks was significantly lower than Cerrobend blocks (3D: -0.88 ± 2.21 mm, Cerrobend: -2.28 ± 2.40 mm, P = .0002). Dosimetrically, transmission measurements through the 3D-printed and Cerrobend blocks for both ion-chamber and EPID dosimetry were between 42% to 48%, compared with the open field. Additionally, coefficient-of-variation was significantly higher in 3D-printed blocks versus Cerrobend blocks (3D: 4.2% ± 0.6%, Cerrobend: 2.6% ± 0.7%, P < .0001). CONCLUSIONS: We designed and implemented a tungsten filled 3D-printed workflow for constructing total-body-irradiation 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 to facilitate the removal of toxic materials from the clinic.

Multi-Institutional Audit of FLASH and Conventional Dosimetry with a 3D-Printed Anatomically Realistic Mouse Phantom.

We conducted a multi-institutional audit of dosimetric variability 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 ($~1.02 g/cm^3$) and polylactic acid ($~1.24 g/cm^3$) simultaneously to simulate soft tissue and bone densities, respectively. The lungs were printed separately using lightweight polylactic acid ($~0.64 g/cm^3$). Hounsfield units (HU) and densities were compared with the reference CT scan of the live mouse. Print-to-print reproducibility of the phantom was assessed. Three institutions were each provided a phantom, and each institution performed two replicates of irradiations at selected mouse 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 $0.10 g/cm^3$ for bone, $0.12 g/cm^3$ for lung, and $0.03 g/cm^3$ for soft tissue regions. Between phantoms, the difference in HU for soft tissue and bone was <10 HU from print to print. Lung exhibited the most variation (54 HU) but minimally affected dose distribution (<0.5% dose differences between phantoms). The mean difference between FLASH and CONV from the first replicate to the second decreased from 4.3% to 1.2%, and the mean difference from the prescribed dose decreased from 3.6% to 2.5% for CONV and 6.4% to 2.7% for FLASH. The framework presented here is promising for credentialing of multi-institutional studies of FLASH preclinical research to maximize the reproducibility of biological findings.

Shaping success: clinical implementation of a 3D-printed electron cutout program in external beam radiation therapy.

Purpose: 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. Methods and materials: 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. Results: 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%. Conclusion: 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.

Introduction to concept inventories for medical physics education.

Concept inventories are multiple choice exams designed with the intention to test core concepts on specific subjects and evaluate common misconceptions. These tests serve as a useful tool in the classroom to assess value added by the instructor's educational methods and to better understand how students learn. They can provide educators with a method to evaluate their current teaching strategies and to make modifications that enhance student learning and ultimately elevate the quality of medical physics education. The use of concept inventories in introductory college physics courses revealed important gaps in conceptual understanding of physics by undergraduate students and motivated a shift of physics teaching towards more effective methods, such as active learning techniques. The goal of this review is to introduce medical physicists to concept inventories as educational evaluation tools and discuss potential applications to medical physics education by development through multi-institutional collaboration.

An Affordable Platform for Virtual Reality-Based Patient Education in Radiation Therapy.

PURPOSE: The goal of this study was to develop and assess the effectiveness of an affordable smartphone-based virtual reality (VR) patient education platform with 360-degree videos produced depicting a first-person patient perspective during the radiation therapy (RT) care path to reduce patient anxiety. METHODS AND MATERIALS: Three disease site-specific (breast, pelvis, head and neck) VR videos were filmed using a 360-degree camera to portray the first-person perspective of a patient's standard RT appointments, including a computed tomography simulation and the first RT treatment session. Instruction is given for possible clinical implementation. Patient participation was divided into 2 groups: (1) Group A (n = 28) included patients participating before simulation and later after the first treatment, and (2) Group B (n = 33) included patients participating only while undergoing treatment. Patients viewed their disease site-specific video using an inexpensive cardboard VR viewer and their smartphone, emulating an expensive VR-headset. Surveys were administered assessing patient anxiety, comfort, satisfaction, and knowledge of RT on a 5-point Likert-type scale. RESULTS: Patients in Group A and Group B while undergoing treatment both indicated that their anxiety "decreased a little" in the survey, after watching the VR video (Group A, median on a 5-point Likert-type scale, 4 [IQR, 4-5]; Group B, 4 [IQR, 4-4]). The VR aspect of the videos was especially liked by patients while undergoing treatment, with 96.4% in Group A and 90.9% in Group B reporting that the VR aspect of the videos was helpful. All Group A participants believed that the VR videos would be beneficial to new patients. CONCLUSIONS: Our affordable VR patient education platform effectively immerses a patient in their care path from simulation through initial treatment delivery, reducing anxiety and increasing familiarity with the treatment process.

3D printing in brachytherapy: A systematic review of gynecological applications.

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.

Design and validation of a dosimetric comparison scheme tailored for ultra-high dose-rate electron beams to support multicenter FLASH preclinical studies.

BACKGROUND AND PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Radiation therapy practice changes in the COVID-19 pandemic era: A pilot study in California.

PURPOSE: This study aims to investigate practice changes among Southern and Northern California's radiation oncology centers during the COVID-19 pandemic. METHODS: On the online survey platform SurveyMonkey, we designed 10 survey questions to measure changes in various aspects of medical physics practice. The questions covered patient load and travel rules; scopes to work from home; new protocols to reduce corona virus disease-2019 (COVID-19) infection risk; availability of telemedicine; and changes in fractionation schedules and/or type of treatment plans. We emailed the survey to radiation oncology centers throughout Northern and Southern California, requesting one completed survey per center. All responses were anonymized, and data were analyzed using both qualitative and quantitative research methods. RESULTS: At the end of a 4-month collection period (July 2, 2021 to October 11, 2021), we received a total of 61 responses throughout Southern and Northern California. On average, 4111 patients were treated per day across the 61 centers. New COVID-19-related department and hospital policies, along with hybrid workflow changes, infectious control policies, and changes in patient load have been reported. Results also showed changes in treatment methods during the pandemic, such as increased use of telemedicine, hypofractionation for palliative, breast cancer, and prostate cancer cases; and simultaneous boosts, compared to sequential boosts. CONCLUSION: Our California radiation oncology center population study shows changes in various aspects of radiation oncology practices during the COVID-19 pandemic. This study serves as a pilot study to identify possible correlations and new strategies that allow radiation oncology centers to continue providing quality patient care while ensuring the safety of both staff and patients.

CT-less electron radiotherapy simulation and planning with a consumer 3D camera.

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 0.59 mm standard deviation from the surface derived from the CT scan. In-vivo dose measurements (213 ± 8 cGy) agreed with the 3D-camera planned dose of 209 ± 6 cGy, compared to 192 ± 6 cGy 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.

A robotically assisted 3D printed quality assurance lung phantom for Calypso.

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 truelung-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 the TG142 tolerance of 2%. Temporal accuracy is greater than, TG142 tolerance of 100 ms for beam-on, but less than 100 ms 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.

Abdominal FLASH irradiation reduces radiation-induced gastrointestinal toxicity for the treatment of ovarian cancer in mice.

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.

FLASH Irradiation Results in Reduced Severe Skin Toxicity Compared to Conventional-Dose-Rate Irradiation.

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.

An integrated quality assurance phantom for frameless single-isocenter multitarget stereotactic radiosurgery.

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. A novel 3D printed phantom, coined OneIso, 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, ten brain SRS clinical treatment plans with 10 MV flattening-filter-free beams were delivered on a Varian TrueBeam with a high-definition multileaf 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 the isocenter, two-dimensional displacements were calculated between the planned and delivered BB locations relative to their respective MLC defined field border. 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 the isocenter. Differences increased as distance from the isocenter increased, exceeding recommended SRS accuracy tolerances at 7 cm away from the isocenter. 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.

Patient motion tracking for non-isocentric and non-coplanar treatments via fixed frame-of-reference 3D camera.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Probing Estrogen Sulfotransferase-Mediated Inflammation with [11C]-PiB in the Living Human Brain.

BACKGROUND: 2-(4'- [11C]Methylaminophenyl)-6-hydroxybenzothiazole ([11C]-PiB), purportedly a specific imaging agent for cerebral amyloid-ß plaques, is a specific, high affinity substrate for estrogen sulfotransferase (SULT1E1), an enzyme that regulates estrogen homeostasis. OBJECTIVE: In this work, we use positron emission tomography (PET) imaging with [11C]-PiB to assess the functional activity of SULT1E1 in the brain of moyamoya disease patients. METHODS: Ten moyamoya subjects and five control patients were evaluated with [11C]-PiB PET and structural MRI scans. Additionally, a patient with relapsing-remitting multiple sclerosis (RRMS) received [11C]-PiB PET scans before and after steroidal and immunomodulatory therapy. Parametric PET images were established to assess SULT1E1 distribution in the inflamed brain tissue. RESULTS: Increased [11C]-PiB SRTM DVR in the thalamus, pons, corona radiata, and internal capsule of moyamoya cohort subjects was observed in comparison with controls (p ≤ 0.01). This was observed in patients without treatment, with collateralization, and also after radiation. The post-treatment [11C]-PiB PET scan in one RRMS patient also revealed substantially reduced subcortical brain inflammation. In validation studies, [11C]-PiB autoradiography signal in the peri-infarct area of the rat middle cerebral arterial occlusion stroke model was shown to correlate with SULT1E1 immunohistochemistry. CONCLUSION: Strong [11C]-PiB PET signal associated with intracranial inflammation in the moyamoya syndrome cohort and a single RRMS patient appears consistent with functional imaging of SULT1E1 activity in the human brain. This preliminary work offers substantial and direct evidence that significant [11C]-PiB PET focal signals can be obtained from the living human brain with intracranial inflammation, signals not attributable to amyloid-ß plaques.

Does 2-FDG PET Accurately Reflect Quantitative In Vivo Glucose Utilization?

2-Deoxy-2-18F-fluoro-d-glucose (2-FDG) with PET is undeniably useful in the clinic, being able, among other uses, to monitor change over time using the 2-FDG SUV metric. This report suggests some potentially serious caveats for this and related roles for 2-FDG PET. Most critical is the assumption that there is an exact proportionality between glucose metabolism and 2-FDG metabolism, called the lumped constant, or LC. This report describes that LC is not constant for a specific tissue and may be variable before and after disease treatment. The purpose of this work is not to deny the clinical value of 2-FDG PET; it is a reminder that when one extends the use of an appropriately qualified imaging method, new observations may arise and further validation would be necessary. The current understanding of glucose-based energetics in vivo is based on the quantification of glucose metabolic rates with 2-FDG PET, a method that permits the noninvasive assessment of various human disorders. However, 2-FDG is a good substrate only for facilitated-glucose transporters (GLUTs), not for sodium-dependent glucose cotransporters (SGLTs), which have recently been shown to be distributed in multiple human tissues. Thus, the GLUT-mediated in vivo glucose utilization measured by 2-FDG PET would be masked to the potentially substantial role of functional SGLTs in glucose transport and use. Therefore, under these circumstances, the 2-FDG LC used to quantify in vivo glucose utilization should not be expected to remain constant. 2-FDG LC variations have been especially significant in tumors, particularly at different stages of cancer development, affecting the accuracy of quantitative glucose measures and potentially limiting the prognostic value of 2-FDG, as well as its accuracy in monitoring treatments. SGLT-mediated glucose transport can be estimated using α-methyl-4-deoxy-4-18F-fluoro-d-glucopyranoside (Me-4FDG). Using both 2-FDG and Me-4FDG should provide a more complete picture of glucose utilization via both GLUT and SGLT transporters in health and disease states. Given the widespread use of 2-FDG PET to infer glucose metabolism, it is relevant to appreciate the potential limitations of 2-FDG as a surrogate for glucose metabolic rate and the potential reasons for variability in LC. Even when the readout for the 2-FDG PET study is only an SUV parameter, variability in LC is important, particularly if it changes over the course of disease progression (e.g., an evolving tumor).