Spatially fractionated radiotherapy has shown potential to improve therapeutic outcomes possibly with an immunogenic mechanistic component. Here we report on in vivo mouse studies investigating mini-GRID pencil-beam radiotherapy combined with anti-PD-1 immune checkpoint blockade. Methods: GRID therapy was delivered at 225kV using the XStrahl Small Animal Radiation Research Platform with two custom lead mini-GRIDs, each consisting of an array of equally spaced holes: 1 mm diameter with 1mm spacing and 254 µm diameter with 508 µm spacing. GRID dosimetry was characterized using EBT3 film to determine peak-to-valley dose ratios and output. Two studies were performed with C57BL/6J mice bearing subcutaneous LLC1 flank tumors. In the first, mice (n=5/group) were treated in 3 groups with a single fraction: 15 Gy open field, 15 Gy 1 mm GRID, or 24 Gy 1 mm GRID. In the second, mice (n=6-7/group) were treated with fractionated GRID radiotherapy in 5 groups: 15 Gy open field x 3 fractions, 15 Gy hemi-irradiation x 3 fractions, (15 Gy 1 mm GRID x 3 fractions, or 15 Gy 254 µm GRID x 3 fractions. All mice were treated with 200 μg anti-PD-1 antibody on days 0, 3, and 6, then weekly until humane endpoint (tumor >15 mm in any dimension or ulceration). Results: Peak to valley ratios were 24.5 ± 0.6 and 19.8 ± 0.7 for the 1 mm and 254 µm GRIDs, respectively. Tumor growth and mean survival times in both studies were significantly shorter for all non-open field arms (p < 0.05; Log Rank for survival; 2-way ANOVA for tumor growth). Conclusions: Two novel mini-GRIDs were characterized and tested in combination with anti-PD-1 therapy. In this study, neither single dose nor fractionated GRID therapy with anti-PD-1 improved tumor growth delay or survival. Similarly, hemi-irradiation resulted in worse tumor control compared to conventional open field radiotherapy. ### Competing Interest Statement The authors have declared no competing interest.

Purpose Ultrahigh dose rate (FLASH) radiation therapy is reported to reduce normal tissue toxicity while maintaining tumor control; however, mechanism(s) remain obscure. To study FLASH mechanisms in brain tissue, we developed a novel experimental platform featuring a specialized high-energy electron linear accelerator, High Intensity Gamma Ray Source (HIGS), paired with an organotypic ex vivo brain metastasis model. Methods and Materials We varied interpulse spacing to modulate the mean dose rate (MDR) of our unique 35 MeV electron beam, while maintaining extremely high instantaneous dose rate (IDR). We characterized dosimetry and targeting accuracy of the FLASH beam with film dosimetry. We combined this FLASH beam with an organotypic rat brain slice/breast carcinoma coculture model of brain metastasis to assess effects on normal and neoplastic tissues. Live-cell and bioluminescence imaging demonstrated cancer cell growth effects, whereas normal tissue responses and immune activation were assessed using live-cell imaging, cytokine profiles, and confocal microscopy. We performed comparison experiments with 20 MeV electrons from a Varian clinical linear accelerator (VCLA) using conventional dose rates. Results The highest IDR of the FLASH beam to date was 20.7 ± 0.6 MGy/s, with maximum MDR of 20.7 MGy/s delivered in 1 pulse of 1 µs duration. Beam targeting was accurate to <1 mm and reproducible. HIGS-FLASH and VCLA dose rates equivalently decreased cancer cell growth. HIGS-FLASH irradiation significantly increased tumor necrosis factor α and fractalkine levels and confocal microscopy revealed distinct changes in microglial morphology slices suggesting microglia activation. Conclusions Our novel experimental platform produces extremely high dose rates and rapid normal/neoplastic tissue readouts for mechanistic research into the effects of FLASH radiation in the brain. HIGS-FLASH irradiation induces comparable cancer cell growth inhibition but differential effects on cytokines and microglial morphology, suggesting that acute innate immune responses may be involved in FLASH normal tissue effects in the brain.

Purpose:Ultra-high dose rate (FLASH) irradiation is reported to reduce normal tissue toxicity while maintaining tumor control, however mechanism(s) remain obscure. To study FLASH mechanisms in brain tissue, we developed a novel experimental platform featuring a unique high-energy electron linear accelerator (High Intensity Gamma Source, HIGS) paired with an organotypic ex vivo brain metastasis model. Methods:We varied inter-pulse spacing to modulate the mean dose rate (MDR) of our unique 35 MeV electron beam, while maintaining extremely high instantaneous dose rate (IDR), and used film dosimetry to characterize dosimetry and targeting accuracy. We combined this HIGS-FLASH beam with an organotypic rat brain slice/breast carcinoma co-culture model of brain metastasis to assess effects on normal and neoplastic tissues. Live cell and bioluminescence imaging demonstrated cancer cell growth effects, while normal tissue responses and immune activation were assessed with live cell imaging, cytokine profiles, and confocal microscopy. We performed comparison experiments with 20 MeV electrons from a Varian clinical linear accelerator (VCLA) operating at conventional dose rate. Results:The highest IDR of the HIGS-FLASH beam to-date was 20.7 ± 0.6 MGy/s, with maximum MDR of 20.7 MGy/s (1 μs pulse of 20.7 Gy). Beam targeting was accurate to < 1 mm and reproducible. HIGS-FLASH and VCLA dose rates equivalently decreased cancer cell growth. HIGS-FLASH irradiation significantly increased TNFα and fractalkine levels and confocal microscopy revealed distinct changes in microglial morphology in normal brain slices, suggesting microglia activation following HIGS-FLASH irradiation. Conclusions:Our novel experimental platform produces extremely high dose rates and rapid normal/neoplastic tissue readouts for mechanistic research into the effects of FLASH radiation on the brain. HIGS-FLASH irradiation induces comparable cancer cell growth inhibition but differential effects on cytokines and microglial morphology, suggesting that acute innate immune responses may be involved in FLASH normal tissue effects in the brain.

BACKGROUND:Advanced radiation therapy techniques, including intensity-modulated radiation therapy (IMRT), stereotactic radiosurgery (SRS), adaptive therapy, and proton therapy, offer high precision in delivering radiation doses to tumors while minimizing exposure to surrounding healthy tissues. These sophisticated methods necessitate stringent quality assurance (QA) measures to ensure their accuracy and safety. Three-dimensional (3D) dosimetry systems have the potential to play an important role in this context for verifying dose distributions in a comprehensive manner but have not been widely implemented partially due to a lack of streamlined systems that include dosimeter, readout, and analysis. PURPOSE:The ClearView radiochromic dosimeter, the Vista 16 Optical CT scanner, and the VistaAce analysis software have the potential as a fully integrated 3D dosimetry tool for commissioning and verifying complex radiotherapy treatment plans. We aim to benchmark this integrated 3D dosimetry system and investigate its clinical utility. METHODS:The performance of this system was benchmarked against an independent Monte Carlo dose calculation software, the Duke Large Field of View Optical CT Scanner (DLOS), and an open-source analysis software (3D Slicer v4.13). We measured two simple radiotherapy plans and a selection from the AAPM (American Association of Physicists in Medicine) Task Group 119 IMRT commissioning tests. Treatment plans were prepared within the Eclipse planning system (AAA v15.6.03) after which a Varian Truebeam linac was used to deliver the treatment plans. Vista 16 was used to reconstruct the measured 3D dose distribution which was compared to the dose distribution obtained from an independent Monte Carlo-based dose calculation algorithm, as well as the 3D dose distribution reconstructed using the well-established DLOS. Image registration, conversion from optical density to dose, and comparative analysis were done using the VistaAce software and validated against results obtained using 3D Slicer for a subset of tests. RESULTS:ClearView dosimeters exhibited a linear dose-response up to 60 Gy. For the 3-field benchmarking irradiation, the agreement (2%/2 mm 3D global gamma Index, 10% threshold) between ClearView/VistaAce versus the TPS and Monte Carlo was 97.8% and 98.8%, respectively. For the AAPM TG119 mock head and neck plan, the agreement (2%/2 mm) with the treatment planning system and Monte Carlo was 99.1% and 95.1%, respectively. For the TG119 mock prostate, the agreement was 99.7% and 98.9%, respectively. Agreement for the ClearView/ Vista 16 dose reconstruction was equivalent or superior to that of the ClearView/DLOS reconstruction for the benchmarking irradiations. CONCLUSION:The ClearView/Vista 3D dosimetry system demonstrated robust performance in measuring and verifying realistic clinical dose distributions, with good agreement with an independent Monte Carlo algorithm and equivalent or better agreement than DLOS. The system's integrated approach, combining dosimetry, scanning, and analysis, streamlines QA processes in advanced radiation therapy, potentially enhancing clinical practice by providing consistent and accurate dosimetric verification.

A comprehensive 3D dosimetry system consisting of the ClearView (TM) 3D dosimeter, VistaScan (TM) optical CT scanner, and VistaAce (TM) analysis software is commercially available and has the potential to be a strong verification tool with widespread applications. The clinical utility of this system (termed ClearView/Vista) has yet to be determined, and this work presents our first investigation. Clinical utility was evaluated using real patients' treatment plans: spine, head and neck, Single Isocenter Multi-Targets SRS (SIMT-SRS), and prostate cases. Independent validation was performed with a Monte Carlo-based dose calculation algorithm that was previously commissioned for clinical independent dose calculation. The analysis included line profile comparison (1D), isodose line comparison (2D), and global gamma analysis (3D). Results indicated a remarkable agreement between ClearView/Vista, the treatment planning system, and Monte Carlo, where gamma pass rates for all cases exceeded 94% even while using 2%2mm and a dose threshold of 10%. The ClearView/Vista 3D dosimetry system showed clinically acceptable accuracy and robust measurement and analysis in clinical settings.

Modern radiotherapy delivers highly conformal dose distributions to irregularly shaped target volumes while sparing the surrounding normal tissue. Due to the complex planning and delivery techniques, dose verification and validation of the whole treatment workflow by end-to-end tests became much more important and polymer gel dosimeters are one of the few possibilities to capture the delivered dose distribution in 3D. The basic principles and formulations of gel dosimetry and its evaluation methods are described and the available studies validating device-specific geometrical parameters as well as the dose delivery by advanced radiotherapy techniques, such as 3D-CRT/IMRT and stereotactic radiosurgery treatments, the treatment of moving targets, online-adaptive magnetic resonance-guided radiotherapy as well as proton and ion beam treatments, are reviewed. The present status and limitations as well as future challenges of polymer gel dosimetry for the validation of complex radiotherapy techniques are discussed.

Objective. To develop and benchmark a novel 3D dose verification technique consisting of polymer gel dosimetry (PGD) with cone-beam-CT (CBCT) readout through a two-institution study. The technique has potential for wide and robust applicability through reliance on CBCT readout. Approach. Three treatment plans (3-field, TG119-C-shape spine, 4-target SRS) were created by two independent institutions (Institutions A and B). A Varian Truebeam linear accelerator was used to deliver the plans to NIPAM polymer gel dosimeters produced at both institutions using an identical approach. For readout, a slow CBCT scan mode was used to acquire pre- and post-irradiation images of the gel (1 mm slice thickness). Independent gel analysis tools were used to process the PGD images (A: VistaAce software, B: in-house MATLAB code). Comparing planned and measured doses, the analysis involved a combination of 1D line profiles, 2D contour plots, and 3D global gamma maps (criteria ranging between 2%1 mm and 5%2 mm, with a 10% dose threshold). Main results. For all gamma criteria tested, the 3D gamma pass rates were all above 90% for 3-field and 88% for the SRS plan. For the C-shape spine plan, we benchmarked our 2% 2 mm result against previously published work using film analysis (93.4%). For 2%2 mm, 99.4% (Institution A data), and 89.7% (Institution B data) were obtained based on VistaAce software analysis, 83.7% (Institution A data), and 82.9% (Institution B data) based on MATLAB. Significance. The benchmark data demonstrate that when two institutions follow the same rigorous procedures gamma passing rates up to 99%, for 2%2 mm criteria can be achieved for substantively different treatment plans. The use of different software and calibration techniques may have contributed to the variation in the 3D gamma results. By sharing the data across institutions, we observe the gamma passing rate is more consistent within each pipeline, indicating the need for standardized analysis methods.

BACKGROUND:Sophisticated modern radiation therapy treatments require comprehensive validation in 3D.PURPOSE:Investigation and characterization of a novel 3D dosimetry system consisting of ClearView radiochromic gel dosimeters (commercially available from Modus Inc) and an in-house telecentric optical CT scanner DLOS (the Duke Large Field of View Optical-CT Scanner).METHODS:Spectrophotometry measurements were made on small volumes of ClearView gel irradiated with 6X photon doses up to 40 Gy to determine linearity and temporal stability of dose response. Clinical evaluation of Clearview/DLOS system was conducted in two phases. Phase one involved simple photon and electron benchmark irradiations, delivered to 15 and 10 cm diameter dosimeters, at various energies and doses. Phase 2 investigated application to the verification of two single isocenter multi-target (SIMT) stereotactic radiosurgery (SRS) deliveries. These were patient treatments for two and five brain lesions, respectively, and delivered to 15 cm diameter dosimeters. SIMT treatments were delivered by Varian TrueBeam 6X with doses of 40 Gy. For dose read-out, dosimeters were optically scanned in the DLOS both pre- and post- irradiation (within 24 h). 3D reconstructions (1 mm3 resolution) of the change in linear-optical- attenuation (proportional to dose) was obtained using in-house software and 3D Slicer. Measured and predicted (Eclipse TPS) doses were compared through percent depth-dose (PDD), cross plane and in-plane profiles, and relative 3D gamma analysis (performed at a range of 7%/4 mm down to 2%/2 mm). Regions of known artifacts were excluded from analysis (jar base, neck, and wall). The SIMT SRS deliveries were additionally compared to SciMoca, an independent Monte Carlo second check software.RESULTS:Linearity of dose response was confirmed with R2 ≥ 0.9986 at both 520 and 630 nm wavelengths and at three post-irradiation time points: 21 h, 6 and 10 days. Dose profiles of all benchmark irradiations, in both 15 and 10 cm dosimeters, show good agreement in useable areas of the gel compared to Eclipse dose calculations, with root mean square errors (RMSE) ≤ 0.0054, and R2 ≥ 0.9808. Gamma pass rates for the 15 cm dosimeter benchmark irradiations were ≥ 94% at 2%/2 mm (central axis), ≥ 90% at 3%/3 mm (left lateral), ≥ 90% at 2%/2 mm (electron), and ≥ 94% at 3%/2 mm (stacking field). Similar high passing rates were observed for benchmark irradiations to the smaller 10 cm diameter dosimeters. Very high Gamma pass rates were found for SIMT SRS deliveries, with 99.82% and 97.80% at 3%/2 mm, for the two and five target plans, respectively.CONCLUSION:This work presents the first investigation of ClearView dosimeters in combination with a telecentric optical-CT scanner (DLOS). Simple benchmark irradiations demonstrate ClearView/DLOS can accurately recreate and measure relative 3D dose within non-artifact regions (i.e., > 1 cm away from walls). Application to SIMT SRS deliveries demonstrated the viability of the system as a means for comprehensive 3D verification of complex treatment deliveries as well as confirming the treatment planning system dose distribution. The results indicate that DLOS/ClearView system is a highly effective 3D verification tool for SIMT irradiations and can be applied with 3%/2 mm gamma criteria where passing rates of > 95% are to be expected.

Medulloblastoma is the most common malignant brain tumor of children. Although standard of care radiotherapy for pediatric medulloblastoma (PM) can lead to long-term remission or cure in many patients, it can also cause life-long cognitive impairment and other adverse effects. The pathophysiological mechanisms involved in radiation-induced cerebral damage are incompletely understood, and their elucidation may lead to interventions that mitigate radiation toxicity. To explore the mechanisms of radiation-induced cerebral damage, transgenic mouse models of PM and non-tumor-bearing controls were exposed to radiation doses that ranged from 0 to 30 Gy. Between 0–20 Gy, a significant dose-dependent reduction in tumor-associated hydrocephalus and increase in overall survival were observed. However, at 30 Gy, hydrocephalus incidence increased and median overall survival fell to near-untreated levels. Immunohistochemistry revealed that both tumor-bearing and non-tumor-bearing mice treated with 30 Gy of radiation had significantly more reactive astrocytes and microvascular damage compared to untreated controls. This effect was persistent across mice that were given 1 and 2 weeks of recovery time after irradiation. Our data suggest that radiation therapy promotes neural death by inducing long-term neuroinflammation in PM, suggesting radiation delivery methods that limit inflammation may be effective at widening the therapeutic window of radiation therapy in PM patients.

Linac Synchronized NIPAM (LS-NIPAM) 3D dosimetry utilizes on-board CBCT to read 3D dosimeters, while the measured dose is inherently synchronized with the on-board imaging coordinate system. The main issues are the limited signal strength and the lack of reliable and widely available analysis tools. Our goal is to develop a practical LS-NIPAM 3D dosimetry system that is applicable on a wide scale for accurate 3D dosimetry. An initial irradiation consisted of a simple 3-field plan (6 MV-FFF, 25 Gy), then an AAPM TG119 C-Shape plan was used as a clinical verification. We compared iterative and standard reconstruction algorithms as well as the impact of a variety of imaging metrics on NIPAM image quality. VistaAce (v 0.7) was used for data analysis. The Contrast to Noise Ratio (CNR) increased considerably when the iterative reconstruction algorithm was used (4.7 to 11.8). The measured dose agreed with the dose from the treatment planning system for the 3-field plan, with a pass rate of 95.6% for 3%3mm and 94.5% for 5%2mm. The results from VistaAce were verified via a second analysis using MATLAB and 3D Slicer with both analyses methods in agreement. The initial analysis of the TG119 C-Shape plan shows promising agreement. The developed CBCT technique demonstrated high CNR and high agreement with TPS dose which uses averaged pre-irradiation CBCTs subtracted from averaged post-irradiation CBCTs and using an iterative reconstruction technique. The VistaAce software shows promise as a robust and widely applicable 3D dosimetry analysis tool, including for LS-NIPAM 3D dosimetry.

Delayed radiation myelopathy is a rare, but significant late side effect from radiation therapy that can lead to paralysis. The cellular and molecular mechanisms leading to delayed radiation myelopathy are not completely understood but may be a consequence of damage to oligodendrocyte progenitor cells and vascular endothelial cells. Here, we aimed to determine the contribution of endothelial cell damage to the development of radiation-induced spinal cord injury using a genetically defined mouse model in which endothelial cells are sensitized to radiation due to loss of the tumor suppressor p53. Tie2Cre; p53FL/+ and Tie2Cre; p53FL/– mice, which lack one and both alleles of p53 in endothelial cells, respectively, were treated with focal irradiation that specifically targeted the lumbosacral region of the spinal cord. The development of hindlimb paralysis was followed for up to 18 weeks after either a 26.7 Gy or 28.4 Gy dose of radiation. During 18 weeks of follow-up, 83% and 100% of Tie2Cre; p53FL/– mice developed hindlimb paralysis after 26.7 and 28.4 Gy, respectively. In contrast, during this period only 8% of Tie2Cre; p53FL/+ mice exhibited paralysis after 28.4 Gy. In addition, 8 weeks after 28.4 Gy the irradiated spinal cord from Tie2Cre; p53FL/– mice showed a significantly higher fractional area positive for the neurological injury marker glial fibrillary acidic protein (GFAP) compared with the irradiated spinal cord from Tie2Cre; p53FL/+ mice. Together, our findings show that deletion of p53 in endothelial cells sensitizes mice to the development of delayed radiation myelopathy indicating that endothelial cells are a critical cellular target of radiation that regulates myelopathy.

Diffuse midline gliomas arise in the brainstem and other midline brain structures and cause a large proportion of childhood brain tumor deaths. Radiation therapy is the most effective treatment option, but these tumors ultimately progress. Inhibition of the phosphoinositide-3-kinase (PI3K)-like kinase, ataxia–telangiectasia mutated (ATM), which orchestrates the cellular response to radiation-induced DNA damage, may enhance the efficacy of radiation therapy. Diffuse midline gliomas in the brainstem contain loss-of-function mutations in the tumor suppressor PTEN, or functionally similar alterations in the phosphoinositide-3-kinase (PI3K) pathway, at moderate frequency. Here, we sought to determine if ATM inactivation could radiosensitize a primary mouse model of brainstem glioma driven by Pten loss. Using Cre/loxP recombinase technology and the RCAS/TVA retroviral gene delivery system, we established a mouse model of brainstem glioma driven by Pten deletion. We find that Pten-null brainstem gliomas are relatively radiosensitive at baseline. In addition, we show that deletion of Atm in the tumor cells does not extend survival of mice bearing Pten-null brainstem gliomas after focal brain irradiation. These results characterize a novel primary mouse model of PTEN-mutated brainstem glioma and provide insights into the mechanism of radiosensitization by ATM deletion, which may guide the design of future clinical trials.

Diffuse midline gliomas arise in the brainstem and other midline brain structures and cause a large proportion of childhood brain tumor deaths. Radiation therapy is the most effective treatment option, but these tumors ultimately progress. Inhibition of the phosphoinositide-3-kinase (PI3K)-like kinase ataxia telangiectasia mutated (ATM), which orchestrates the cellular response to radiation-induced DNA damage, may enhance the efficacy of radiation therapy. Diffuse midline gliomas in the brainstem contain loss-of-function mutations in the tumor suppressor PTEN , or functionally similar alterations in the phosphoinositide-3-kinase (PI3K) pathway, at moderate frequency. Here, we sought to determine if Atm inactivation could radiosensitize a primary mouse model of brainstem glioma driven by Pten loss. Using Cre/loxP recombinase technology and the RCAS/TVA retroviral gene delivery system, we established a mouse model of brainstem glioma driven by Pten deletion. We find that Pten -null brainstem gliomas are relatively radiosensitive at baseline. In addition, we show that deletion of Atm in the tumor cells does not extend survival of mice bearing Pten -null brainstem gliomas after focal brain irradiation. These results characterize a novel primary mouse model of PTEN -mutated brainstem glioma and provide insights into the mechanism of radiosensitization by Atm deletion, which may guide the design of future clinical trials. Brief Summary We develop a mouse model of PTEN -mutated brainstem glioma and find that perturbation of the ATM does not enhance radiation efficacy in this model.

Purpose. This work introduces and evaluates a method for accurate in-vitro measurement of fluorescent cell burden in complex 3D-culture conditions.Methods.The Fluorescent Cell Burden (FCB) method was developed to analyze the burden of 4T1 mCherry-expressing cells grown in an organotypic co-culture model of brain metastasis using 400μm rat brain slices. As a first step, representative simulated image-data accurately reflecting the 4T1 experimental data, but with known ground truth burden, were created. The FCB method was then developed in the CellProfiler software to measure the integrated intensity and area of the colonies in the simulated image data. Parameters in the pipeline were varied to span the experimentally observed range (e.g. of cell colony size) and the result compared with simulation ground truth to evaluate and optimize FCB performance. The optimized CellProfiler pipeline was then applied to the original 4T1 tumor cell images to determine colony growth with time, and re-applied with upper and lower bound parameters to determine uncertainty estimates.Results.The FCB method measured integrated intensity across 10 simulated images with an accuracy of 99.23% ± 0.75%. When colony density was increased by increasing colony number to 450, 600, and 750, the FCB measurement was 98.68%, 100.9%, 97.6% and 113.5% of the true value respectively. For the increasing number of cells plated on the rat brain slices, the integrated intensity increased nearly linearly with cell count except for at high cell counts, where it is hypothesized that shadowing from clumped cells causes a sub-linear relationship.Conclusion. The FCB method accurately measured an integrated fluorescent light intensity to within 5% of ground truth for a wide range of simulated image data spanning the range of observed variability in experimental data. The method is readily customizable to in-vitro studies requiring estimation of fluorescent tumor cell burden.

We report our progress towards developing a clinical application of NIPAM kV-CBCT dosimetry. The goal is to develop a practical kV-MV isocenter verification test for which the measurement and analysis can be carried out quickly (within an hour), and that eliminates the need for separate readout (other than on board kV-CBCT) or extra analysis steps such as image registration. Isocenter verification is performed using a NIPAM 3D gel dosimeter which is irradiated with a small field to ~16Gy at eight unique couch/gantry angles. Pre- and post-irradiation kV-CBCT images are acquired and dose is manifest as the intensity difference between pre- and post-CBCTs due to radiation induced changes in density. Code was developed to detect the geometry of each beam in the kV-CBCT and quantify relevant parameters. We applied this technique to verify the isocenter for MLCs as well as for SRS cones. The measured radius to encompass all beams for 4mm, 6mm, 7.5mm, 12.5mm, and 15mm cones was 0.55±0.11mm. The efficiency, robustness to setup errors, and unique ability to visualize spatial uncertainties in the kV-CBCT coordinate system make the NIPAM kV-CBCT test a practical and unique tool for kV-MV isocenter verification.

Purpose/Objective(s) Verification of Single Isocenter Multitarget SRS treatments (SIM-SRS) is uniquely challenging due to the combination of high dose, steep dose gradients and the requirement for very high spatial accuracy. Here we demonstrate the feasibility of a novel 3D dosimetry system for uniquely comprehensive dosimetry validation and commissioning of this exceptionally challenging technique. Materials/Methods The 3D dosimetry system utilizes a new commercially available radiochromic gel dosimeter and a state-of-art in-house telecentric optical-CT readout system DLOS (Duke Large Field of View telecentric Optical CT Scanner). The system was used to quantify the accuracy in 3D and in high resolution (isotropic 1mm) of two SIM-SRS treatments: a simpler two target treatment, and a more complex 5 target treatment. The SIM-SRS plans were created on patient anatomy and then recalculated on a CT of a 15cm diameter dosimeter, with isocenter placed such that each target was located within the dosimeter. Both treatments were delivered to the dosimeters which are gellan gum based radiochromic dosimeters containing a water-soluble tetrazolium salt which reduces into an insoluble formazan dye (with associated color change) under ionizing radiation. Optical-CT readout of the dosimeters pre and post irradiation enabled a high-resolution comprehensive evaluation of the accuracy of delivery. The DLOS is a bi-telecentric system which enables highest accuracy optical-CT readout through strong scatter and stray light rejection. The measured optical density distribution was spatially registered to the dose from the planning system and converted to dose via a calibration curve. Independent verification of treatment accuracy was also performed with a commercial Monte Carlo dose calculation algorithm. Results For the 2-target plan, the measured dose agreed with the planning system with a Gamma-Index passing rate of 99.88%, 99.27%, and 92.75%, using a 3%/3mm, 3%/2mm, 5%/1mm criteria, respectively. For the 5-target plan, the Gamma-Index passing rate was 99.59%, 97.35%, and 93.82%, using a 3%/3mm, 3%/2mm, 5%/1mm criteria, respectively. In comparison, the dose calculated using Monte Carlo agreed with the planning system with a Gamma-Index passing rate of 100.0% using 3%/1mm for both the 2 target and 5 target plans. Mean dose for the PTVs of the 2-target plan was within –0.71% and –1.53%. Mean dose for the PTVs of the 5-target plan was within (1.08±0.97)%. Conclusion This study demonstrates the feasibility of a new 3D dosimetry tool for verification of advanced radiation treatments. Application to SIM-SRS treatments has demonstrated excellent agreement between measured and predicted dose in the phantom. The combination of DLOS optical-CT with Clearview dosimeters was found to be important in obtaining accurate 3D dosimetry. The method introduced here is anticipated to be applicable to a wide range of clinically challenging treatment techniques.