Abstract Objective . Phase gating is a critical technique to mitigate tumor motion during radiotherapy, particularly in spot-scanned particle therapy where internal motion can interfere with dynamic spot scanning patterns and, simultaneously, introducing substantial range uncertainties. However, the current commercial state of the art in real-time phase prediction is challenged by patient-specific breathing variability as well as detection and delivery system latencies. This leads to suboptimal efficiency, mis-timed radiation delivery and requires frequent manual intervention. This study aims to improve phase prediction accuracy using deep learning (DL)-based time series forecasting to enable more accurate dose delivery. Approach . Retrospective breathing waveforms from 69 proton therapy patients, sampled at 30 Hz, were labeled with inspiratory peaks and assigned subjective regularity scores (four levels). DL models with various architectures were trained using waveform amplitude to predict current or future breathing phases. Model performance was evaluated using mean squared error, phase binning accuracy, and timing deviation for radiation on/off events. Bayesian optimization was used for hyperparameter tuning. Results were compared between models and against a commercial algorithm currently in clinical use. Main Results . The curated waveform dataset included 165 242 s for training, 24 057 s for validation, and 30 322 s for testing, with an additional 40 604 s from separate patients for extended validation. The long short-term memory and temporal fusion transformer models significantly outperformed the commercial algorithm, improving phase prediction accuracy by nearly 20% and reducing timing deviations across all regularity levels. Significance . DL-based time series forecasting may substantially improve breathing phase prediction accuracy over current clinically available methods, offering a more precise and reliable approach to phase-gated radiation delivery.
The impact of neck tilt on the accuracy of deep learning generated contours for CT images of the head and neck
Abstract Background Deep learning auto segmentation (DLAS) tools are widely used for radiation therapy planning, yet limited information exists on how patient positioning impacts their performance, particularly in head and neck (HN) computed tomography (CT) imaging. Purpose This study investigates the impact of abnormal neck tilt on the accuracy of DLAS‐generated contours in HN CT scans. We hypothesize that abnormal positioning degrades auto segmentation performance, particularly for organs at risk (OARs) influenced by cervical spine orientation. Methods A total of 35 HN CT scans were retrospectively analyzed. Neck tilt was quantified using principal component analysis of the spinal cord contours from C1 to C4, with patients stratified into normal and abnormal tilt groups based on percentile thresholds. Seven FDA‐cleared DLAS tools were evaluated for OAR segmentation accuracy across brainstem, parotid glands, submandibular glands, brachial plexus, and optic nerves. Gold‐standard contours were curated from manually created clinical contours and compared to DLAS output using Sorenson's volumetric dice similarity coefficient (DSC), surface Dice similarity coefficient with a 2 mm threshold (sDSC), mean distance to agreement (MDA) and difference in mean dose. Statistical differences were assessed using Wilcoxon rank‐sum tests ( p < 0.05). Results Among the evaluated OARs, the parotid glands showed consistent and statistically significant degradation in contouring accuracy for patients with abnormal neck tilt across all metrics (DSC, sDSC, MDA) and across all seven DLAS tools. Changes in contouring accuracy resulted in significant differences in both absolute and signed difference in mean dose. No consistent differences were observed for other structures across multiple DLAS tools. Conclusions Abnormal neck tilt is associated with reduced DLAS accuracy and greater dose variability for parotid gland segmentation in HN radiotherapy planning. These findings underscore the need for enhanced patient quality assurance strategies for patients with abnormal positioning when using clinical DLAS workflows. Future work should explore automated detection of anatomical outliers and site‐specific model retraining to ensure accurate contouring delineation for patients with atypical positioning or anatomy.
Digital twin creation of a proton therapy treatment environment with hybrid LiDAR and RGB 3D camera
AbstractIntroductionThis study evaluates the feasibility of utilizing a commercial‐grade 3D LiDAR/RGB camera, combined with 3D reconstruction software, to create an accurate and hyper‐realistic digital model of a proton therapy treatment room. This reconstructed model aims to enhance collision avoidance strategies and improve 3D machine model accessibility. Utilization of a 3D LiDAR/RGB camera as a radiotherapy environment modeling has not been reported prior.MethodsTo create a comprehensive 3D model of a half‐gantry proton therapy system, colored point cloud data was captured using the Matterport Pro 3 camera, a hybrid LiDAR and RGB imaging system with high‐resolution capabilities (134.2 MP), a 360° horizontal field of view, and 20 mm accuracy at 10 m. A total of 117 acquisition points, distributed across the treatment room with three camera heights, ensured complete coverage and minimal occlusions. Scanning, completed in under 3 hours, was monitored in real time using the Matterport App. Post‐scan processing involved denoising and converting the point cloud into 3D mesh structures using MeshLab, followed by refined pair‐wise iterative closest point (ICP) alignments. Textures and materials were assigned to reflect real‐world objects, and a ray‐tracing engine simulated realistic lighting in Blender. Animations illustrating the kinematics of the treatment couch and gantry were simulated in Blender for enhanced visualization.ResultsThe scanning process achieved complete data capture without missing information, attributed to strategic oversampling during data acquisition. The mean root mean square error (RMSE) of the ICP registration was 0.008 m. The validation process confirmed that the dimensions of the treatment couch within the digital model closely matched the actual measurements with less than 2 cm deviation, indicating high accuracy. The resulting digital twin provided a photorealistic and immersive representation of the proton therapy treatment room, serving as a valuable digital asset for various applications.ConclusionIt is possible to generate vendor‐independent and highly accurate 3D models of the proton treatment room environment with a commercial grade LiDAR/RGB camera to expand future research opportunities and education endeavors.
Enhancing proton therapy quality assurance with custom‐designed Octopoint phantom and Gafchromic film
Abstract Background Proton therapy offers precise tumor targeting while minimizing damage to surrounding healthy tissue, making it especially valuable for treating tumors near critical organs and in pediatric patients. However, its success depends on accurate beam delivery, requiring rigorous quality assurance (QA) to maintain treatment precision and effectiveness. Purpose This study aims to standardize the measurement of key aspects of proton therapy delivery, such as gantry and couch isocentricity, spot position accuracy, and spot size consistency. The goal is to enhance the delivery accuracy of proton therapy across various clinical settings, improving patient outcomes. Methods The QA framework uses the Octopoint phantom, Gafchromic film, and spot position monitor (SPM) log data to evaluate proton beam isocentricity, spot position, and spot size. The Octopoint phantom, made from acrylic, was used with Gafchromic films at various gantry and couch angles to measure isocentricity. MATLAB tools were used to analyze spot positions, and SPM logs provided verification. Sensitivity tests were conducted to assess the system's response to intentional shifts and errors, ensuring alignment with clinical QA standards. Results The Octopoint phantom's stepwise two‐dimensional (2D) fitting process, validated against film‐measured dose profiles, accurately identified beam and ball bearing (BB) centroid locations. Isocentricity tests conducted over 8 months across four gantries demonstrated consistent beam‐to‐BB radial offsets. The phantom showed excellent repeatability, with a maximum standard deviation of 0.1 mm across various couch‐gantry combinations. Sensitivity testing across all axes revealed a strong alignment between intended shifts and measured values. Over the course of a year, film measurements tracked spot position and size consistency, with deviations remaining within acceptable clinical limits. Comparisons with SPM data further confirmed the system's reliability in maintaining beam accuracy across different gantry angles and energy levels. Conclusions This study presents a reliable QA framework for ensuring precision in proton therapy delivery. By combining the Octopoint phantom, Gafchromic film analysis, and SPM log file evaluation, we effectively measured isocentricity, spot position accuracy, and spot size stability. The framework demonstrated adaptability across various clinical QA tasks, enhancing the accuracy and safety of proton therapy treatments.
The impact of therapeutic radiation on drug distribution across the blood-brain barrier in normal mouse brain and orthotopic glioblastoma tumors
Abstract Background Most oncology therapeutics have limited distribution into the brain, and developing strategies to overcome this limitation would be clinically impactful. While therapeutic radiation is often cited as a strategy to accomplish this, there are no published studies demonstrating the effect of radiation on drug distribution into the brain or brain tumors. Methods Mice were treated with brain radiation (6 Gy × 5, 4 Gy × 10; 40 Gy × 1) and dosed with drugs (levetiracetam, cefazolin, nedisertib, brigimadlin, apitolisib, or GNE-317) at times ranging from just prior to months after radiation. Plasma and tissue drug concentrations were measured by LC-MS/MS. Results Radiation did not significantly enhance drug delivery into brain tissue for levetiracetam, cefazolin, GNE-317, apitolisib, or nedisertib at any time post-radiation. Even a single, supra-therapeutic dose of radiation (40 Gy) did not significantly affect brain distribution of GNE-317 or apitolisib (P ≥ .07) from 16 to 160 hours post-radiation. For brigimadlin, radiation (6 Gy × 5) was associated with a modest but significant increase in drug accumulation only at 72 hours post-radiation (brain-to-plasma ratio 0.014 ± 0.006 vs. 0.025 ± 0.010, respectively; P = .04), but not at any other timepoint (24 hours, 15, 28, 94, 133, 183 days; P > .05). Similarly, radiation (6 Gy × 5) of orthotopic tumors did not increase levels of brigimadlin in GBM10 or GBM108 or nedisertib in GBM108 (P > .05). Conclusions Radiation had no meaningful impact on drug delivery into brain or brain tumors for the drugs tested.
Purpose: To evaluate the performance of a new, highly flexible radiofrequency (RF) coil system for imaging patients undergoing MR simulation. Methods: Volumetric phantom and in vivo images were acquired with a commercially available and prototype RF coil set. Phantom evaluation was performed using a silicone-filled humanoid phantom of the head and shoulders. In vivo assessment was performed in five healthy and six patient subjects. Phantom data included T1-weighted volumetric imaging, while in vivo acquisitions included both T1- and T2-weighted volumetric imaging. Signal to noise ratio (SNR) and uniformity metrics were calculated in the phantom data, while SNR values were calculated in vivo. Statistical significance was tested by means of a non-parametric analysis of variance test. Results: At a threshold of p = 0.05, differences in measured SNR distributions within the entire phantom volume were statistically different in two of the three paired coil set comparisons. Differences in per slice average SNR between the two coil sets were all statistically significant, as well as differences in per slice image uniformity. For patients, SNRs within the entire imaging volume were statistically significantly different in four of the nine comparisons and seven of the nine comparisons performed on the per slice average SNR values. For healthy subjects, SNRs within the entire imaging volume were statistically significantly different in seven of the nine comparisons and eight of the nine comparisons when per slice average SNR was tested. Conclusions: Phantom and in vivo results demonstrate that image quality obtained from the novel flexible RF coil set was similar or improved over the conventional coil system. The results also demonstrate that image quality is impacted by the specific coil configurations used for imaging and should be matched appropriately to the anatomic site imaged to ensure optimal and reproducible image quality.
Characterization of Transgenic NSG-SGM3 Mouse Model of Precision Radiation-Induced Chronic Hyposalivation
Abstract Dose uncertainty induced by respiratory motion remains a major concern for treating thoracic and abdominal lesions using particle beams. This Task Group report reviews the impact of tumor motion and dosimetric considerations in particle radiotherapy, current motion‐management techniques, and limitations for different particle‐beam delivery modes (i.e., passive scattering, uniform scanning, and pencil‐beam scanning). Furthermore, the report provides guidance and risk analysis for quality assurance of the motion‐management procedures to ensure consistency and accuracy, and discusses future development and emerging motion‐management strategies. This report supplements previously published AAPM report TG76, and considers aspects of motion management that are crucial to the accurate and safe delivery of particle‐beam therapy. To that end, this report produces general recommendations for commissioning and facility‐specific dosimetric characterization, motion assessment, treatment planning, active and passive motion‐management techniques, image guidance and related decision‐making, monitoring throughout therapy, and recommendations for vendors. Key among these recommendations are that: (1) facilities should perform thorough planning studies (using retrospective data) and develop standard operating procedures that address all aspects of therapy for any treatment site involving respiratory motion; (2) a risk‐based methodology should be adopted for quality management and ongoing process improvement.
Characterization and commissioning of a Leksell Gamma Knife ICON system for framed and frameless stereotactic radiosurgery
AbstractPurposeThe Leksell Gamma Knife Icon unit (IU) was introduced recently as an upgrade to the Perfexion unit (PU) at our Gamma Knife practice. In the current study, we sought mainly to characterize dosimetry and targeting accuracy of the IU treatment deliveries using both invasive frame and frameless treatment workflows.MethodsRelative output factors were measured by delivering single‐shot 4, 8 and 16 mm radiation profiles in the manufacturer's acrylonitrile butadiene styrene spherical phantom in coronal and sagittal planes using EBT3 film. Resultant dosimetry was compared with the manufacturer's dose calculation and derived output factors were compared with the manufacturer's published value. Geometric consistency of stereotactic coordinates based on cone‐beam computed tomography (CBCT) versus the traditional conventional CT‐based method was characterized using a rigid phantom containing nine fiducial indicators over four separate trials. End‐to‐end (E2E) testing using EBT3 film was designed to evaluate both dosimetric and geometric accuracy for hypothetical framed and frameless workflows.ResultsRelative output factors as measured by the manufacturer were independently confirmed using EBT3 film measurements to within 2%. The mean 3D radial discrepancy in stereotactic space between CBCT and CT‐based definition over the sampled locations in our rigid geometry phantom was demonstrated to be between 0.40 mm and 0.56 mm over the set of trials, larger than prior reported values. E2E performed in 2D demonstrates sub‐mm (and typically < 0.5 mm) accuracy for framed and frameless workflows; geometric accuracy of framed treatments using CBCT‐defined stereotactic coordinates was shown to be slightly improved in comparison with those defined using conventional CT. Furthermore, in phantom, frameless workflows exhibited better accuracy than framed workflows for fractionated treatments, despite large magnitudes of introduced interfraction setup error. Accuracy of dosimetric delivery was confirmed in terms of qualitative comparisons of dose profiles and in terms of 2D gamma pass rates based on 1%/1 mm criteria.ConclusionThe IU was commissioned for clinical use of frameless and framed treatment protocols. The present study outlines an extensive E2E methodology for confirmation of dosimetric and geometric treatment accuracy.