Development and first implementation of a novel multi-modality cardiac motion and dosimetry phantom for radiotherapy applications.

BACKGROUND: Cardiac applications in radiation therapy are rapidly expanding including magnetic resonance guided radiation therapy (MRgRT) for real-time gating for targeting and avoidance near the heart or treating ventricular tachycardia (VT). PURPOSE: This work describes the development and implementation of a novel multi-modality and magnetic resonance (MR)-compatible cardiac phantom. METHODS: The patient-informed 3D model was derived from manual contouring of a contrast-enhanced Coronary Computed Tomography Angiography scan, exported as a Stereolithography model, then post-processed to simulate female heart with an average volume. The model was 3D-printed using Elastic50A to provide MR contrast to water background. Two rigid acrylic modules containing cardiac structures were designed and assembled, retrofitting to an MR-safe programmable motor to supply cardiac and respiratory motion in superior-inferior directions. One module contained a cavity for an ion chamber (IC), and the other was equipped with multiple interchangeable cavities for plastic scintillation detectors (PSDs). Images were acquired on a 0.35 T MR-linac for validation of phantom geometry, motion, and simulated online treatment planning and delivery. Three motion profiles were prescribed: patient-derived cardiac (sine waveform, 4.3 mm peak-to-peak, 60 beats/min), respiratory (cos4 waveform, 30 mm peak-to-peak, 12 breaths/min), and a superposition of cardiac (sine waveform, 4 mm peak-to-peak, 70 beats/min) and respiratory (cos4 waveform, 24 mm peak-to-peak, 12 breaths/min). The amplitude of the motion profiles was evaluated from sagittal cine images at eight frames/s with a resolution of 2.4 mm × 2.4 mm. Gated dosimetry experiments were performed using the two module configurations for calculating dose relative to stationary. A CT-based VT treatment plan was delivered twice under cone-beam CT guidance and cumulative stationary doses to multi-point PSDs were evaluated. RESULTS: No artifacts were observed on any images acquired during phantom operation. Phantom excursions measured 49.3 ± 25.8%/66.9 ± 14.0%, 97.0 ± 2.2%/96.4 ± 1.7%, and 90.4 ± 4.8%/89.3 ± 3.5% of prescription for cardiac, respiratory, and cardio-respiratory motion profiles for the 2-chamber (PSD) and 12-substructure (IC) phantom modules respectively. In the gated experiments, the cumulative dose was <2% from expected using the IC module. Real-time dose measured for the PSDs at 10 Hz acquisition rate demonstrated the ability to detect the dosimetric consequences of cardiac, respiratory, and cardio-respiratory motion when sampling of different locations during a single delivery, and the stability of our phantom dosimetric results over repeated cycles for the high dose and high gradient regions. For the VT delivery, high dose PSD was <1% from expected (5-6 cGy deviation of 5.9 Gy/fraction) and high gradient/low dose regions had deviations <3.6% (6.3 cGy less than expected 1.73 Gy/fraction). CONCLUSIONS: A novel multi-modality modular heart phantom was designed, constructed, and used for gated radiotherapy experiments on a 0.35 T MR-linac. Our phantom was capable of mimicking cardiac, cardio-respiratory, and respiratory motion while performing dosimetric evaluations of gated procedures using IC and PSD configurations. Time-resolved PSDs with small sensitive volumes appear promising for low-amplitude/high-frequency motion and multi-point data acquisition for advanced dosimetric capabilities. Illustrating VT planning and delivery further expands our phantom to address the unmet needs of cardiac applications in radiotherapy.

Technical note: Characterization of a multi-point scintillation dosimetry research platform for a low-field MR-Linac.

BACKGROUND: MRI-guided radiation therapy (MRgRT) requires unique quality assurance equipment to address MR-compatibility needs, minimize electron return effect, handle complex dose distributions, and evaluate real-time dosimetry for gating. Plastic scintillation detectors (PSDs) are an attractive option to address these needs. PURPOSE: To perform a comprehensive characterization of a multi-probe PSD system in a low-field 0.35 T MR-linac, including detector response assessment and gating performance. METHODS: A four-channel PSD system (HYPERSCINT RP-200) was assembled. A single channel was used to evaluate repeatability, percent depth dose (PDD), detector response as a function of orientation with respect to the magnetic field, and intersession variability. All four channels were used to evaluate repeatability, linearity, and output factors. The four PSDs were integrated into an MR-compatible motion phantom at isocenter and in gradient regions. Experiments were conducted to evaluate gating performance and tracking efficacy. RESULTS: For repeatability, the maximum standard deviation of repeated measurements was 0.13% (single PSD). Comparing the PSD to reference data, PDD had a maximum difference of 1.12% (10 cm depth, 6.64 × 6.64 cm2). Percent differences for rotated detector setups were negligible (< 0.3%). All four PSDs demonstrated linear response over 10-1000 MU delivered and the maximum percent difference between the baseline and measured output factors was 0.78% (2.49 × 2.49 cm2). Gating experiments had 400 cGy delivered to isocenter with < 0.8 cGy variation for central axis measures and < 0.7 cGy for the gradient sampled region. Real-time dosimetry measurements captured spurious beam-on incidents that correlated to tracking algorithm inaccuracies and highlighted gating parameter impact on delivery efficiency. CONCLUSIONS: Characterization of the multi-point PSD dosimetry system in a 0.35 T MR-linac demonstrated reliability in a low-field MR-Linac setting, with high repeatability, linearity, small intersession variability, and similarity to baseline data for PDD and output factors. Time-resolved, multi-point dosimetry also showed considerable promise for gated MR-Linac applications.

Enhancing Precision in Cardiac Segmentation for Magnetic Resonance-Guided Radiation Therapy Through Deep Learning.

PURPOSE: Cardiac substructure dose metrics are more strongly linked to late cardiac morbidities than to whole-heart metrics. Magnetic resonance (MR)-guided radiation therapy (MRgRT) enables substructure visualization during daily localization, allowing potential for enhanced cardiac sparing. We extend a publicly available state-of-the-art deep learning framework, "No New" U-Net, to incorporate self-distillation (nnU-Net.wSD) for substructure segmentation for MRgRT. METHODS AND MATERIALS: Eighteen (institute A) patients who underwent thoracic or abdominal radiation therapy on a 0.35 T MR-guided linear accelerator were retrospectively evaluated. On each image, 1 of 2 radiation oncologists delineated reference contours of 12 cardiac substructures (chambers, great vessels, and coronary arteries) used to train (n = 10), validate (n = 3), and test (n = 5) nnU-Net.wSD by leveraging a teacher-student network and comparing it to standard 3-dimensional U-Net. The impact of using simulation data or including 3 to 4 daily images for augmentation during training was evaluated for nnU-Net.wSD. Geometric metrics (Dice similarity coefficient, mean distance to agreement, and 95% Hausdorff distance), visual inspection, and clinical dose-volume histograms were evaluated. To determine generalizability, institute A's model was tested on an unlabeled data set from institute B (n = 22) and evaluated via consensus scoring and volume comparisons. RESULTS: nnU-Net.wSD yielded a Dice similarity coefficient (reported mean ± SD) of 0.65 ± 0.25 across the 12 substructures (chambers, 0.85 ± 0.05; great vessels, 0.67 ± 0.19; and coronary arteries, 0.33 ± 0.16; mean distance to agreement, <3 mm; mean 95% Hausdorff distance, <9 mm) while outperforming the 3-dimensional U-Net (0.583 ± 0.28; P <.01). Leveraging fractionated data for augmentation improved over a single MR simulation time point (0.579 ± 0.29; P <.01). Predicted contours yielded dose-volume histograms that closely matched those of the clinical treatment plans where mean and maximum (ie, dose to 0.03 cc) doses deviated by 0.32 ± 0.5 Gy and 1.42 ± 2.6 Gy, respectively. There were no statistically significant differences between institute A and B volumes (P >.05) for 11 of 12 substructures, with larger volumes requiring minor changes and coronary arteries exhibiting more variability. CONCLUSIONS: This work is a critical step toward rapid and reliable cardiac substructure segmentation to improve cardiac sparing in low-field MRgRT.

Repeat it without me: Crowdsourcing the T1 mapping common ground via the ISMRM reproducibility challenge.

PURPOSE: T1 mapping is a widely used quantitative MRI technique, but its tissue-specific values remain inconsistent across protocols, sites, and vendors. The ISMRM Reproducible Research and Quantitative MR study groups jointly launched a challenge to assess the reproducibility of a well-established inversion-recovery T1 mapping technique, using acquisition details from a seminal T1 mapping paper on a standardized phantom and in human brains. METHODS: The challenge used the acquisition protocol from Barral et al. (2010). Researchers collected T1 mapping data on the ISMRM/NIST phantom and/or in human brains. Data submission, pipeline development, and analysis were conducted using open-source platforms. Intersubmission and intrasubmission comparisons were performed. RESULTS: Eighteen submissions (39 phantom and 56 human datasets) on scanners by three MRI vendors were collected at 3 T (except one, at 0.35 T). The mean coefficient of variation was 6.1% for intersubmission phantom measurements, and 2.9% for intrasubmission measurements. For humans, the intersubmission/intrasubmission coefficient of variation was 5.9/3.2% in the genu and 16/6.9% in the cortex. An interactive dashboard for data visualization was also developed: https://rrsg2020.dashboards.neurolibre.org. CONCLUSION: The T1 intersubmission variability was twice as high as the intrasubmission variability in both phantoms and human brains, indicating that the acquisition details in the original paper were insufficient to reproduce a quantitative MRI protocol. This study reports the inherent uncertainty in T1 measures across independent research groups, bringing us one step closer to a practical clinical baseline of T1 variations in vivo.

AAPM Task Group 334: A guidance document to using radiotherapy immobilization devices and accessories in an MR environment.

Use of magnetic resonance (MR) imaging in radiation therapy has increased substantially in recent years as more radiotherapy centers are having MR simulators installed, requesting more time on clinical diagnostic MR systems, or even treating with combination MR linear accelerator (MR-linac) systems. With this increased use, to ensure the most accurate integration of images into radiotherapy (RT), RT immobilization devices and accessories must be able to be used safely in the MR environment and produce minimal perturbations. The determination of the safety profile and considerations often falls to the medical physicist or other support staff members who at a minimum should be a Level 2 personnel as per the ACR. The purpose of this guidance document will be to help guide the user in making determinations on MR Safety labeling (i.e., MR Safe, Conditional, or Unsafe) including standard testing, and verification of image quality, when using RT immobilization devices and accessories in an MR environment.

Advancing the care of individuals with cancer through innovation & technology: Proceedings from the cardiology oncology innovation summit 2020 and 2021.

As cancer therapies increase in effectiveness and patients' life expectancies improve, balancing oncologic efficacy while reducing acute and long-term cardiovascular toxicities has become of paramount importance. To address this pressing need, the Cardiology Oncology Innovation Network (COIN) was formed to bring together domain experts with the overarching goal of collaboratively investigating, applying, and educating widely on various forms of innovation to improve the quality of life and cardiovascular healthcare of patients undergoing and surviving cancer therapies. The COIN mission pillars of innovation, collaboration, and education have been implemented with cross-collaboration among academic institutions, private and public establishments, and industry and technology companies. In this report, we summarize proceedings from the first two annual COIN summits (inaugural in 2020 and subsequent in 2021) including educational sessions on technological innovations for establishing best practices and aligning resources. Herein, we highlight emerging areas for innovation and defining unmet needs to further improve the outcome for cancer patients and survivors of all ages. Additionally, we provide actionable suggestions for advancing innovation, collaboration, and education in cardio-oncology in the digital era.

Experimental determination of magnetic field quality conversion factors for eleven ionization chambers in 1.5 T and 0.35 T MR-linac systems.

BACKGROUND: The static magnetic field present in magnetic resonance (MR)-guided radiotherapy systems can influence dose deposition and charged particle collection in air-filled ionization chambers. Thus, accurately quantifying the effect of the magnetic field on ionization chamber response is critical for output calibration. Formalisms for reference dosimetry in a magnetic field have been proposed, whereby a magnetic field quality conversion factor kB,Q is defined to account for the combined effects of the magnetic field on the radiation detector. Determination of kB,Q in the literature has focused on Monte Carlo simulation studies, with experimental validation limited to only a few ionization chamber models. PURPOSE: The purpose of this study is to experimentally measure kB,Q for 11 ionization chamber models in two commercially available MR-guided radiotherapy systems: Elekta Unity and ViewRay MRIdian. METHODS: Eleven ionization chamber models were characterized in this study: Exradin A12, A12S, A28, and A26, PTW T31010, T31021, and T31022, and IBA FC23-C, CC25, CC13, and CC08. The experimental method to measure kB,Q utilized cross-calibration against a reference Exradin A1SL chamber. Absorbed dose to water was measured for the reference A1SL chamber positioned parallel to the magnetic field with its centroid placed at the machine isocenter at a depth of 10 cm in water for a 10 × 10 cm2 field size at that depth. Output was subsequently measured with the test chamber at the same point of measurement. kB,Q for the test chamber was computed as the ratio of reference dose to test chamber output, with this procedure repeated for each chamber in each MR-guided radiotherapy system. For the high-field 1.5 T Elekta Unity system, the dependence of kB,Q on the chamber orientation relative to the magnetic field was quantified by rotating the chamber about the machine isocenter. RESULTS: Measured kB,Q values for our test dataset of ionization chamber models ranged from 0.991 to 1.002, and 0.995 to 1.004 for the Elekta Unity and ViewRay MRIdian, respectively, with kB,Q tending to increase as the chamber sensitive volume increased. Measured kB,Q values largely agreed within uncertainty to published Monte Carlo simulation data and available experimental data. kB,Q deviation from unity was minimized for ionization chamber orientation parallel or antiparallel to the magnetic field, with increased deviations observed at perpendicular orientations. Overall (k = 1) uncertainty in the experimental determination of the magnetic field quality conversion factor, kB,Q was 0.71% and 0.72% for the Elekta Unity and ViewRay MRIdian systems, respectively. CONCLUSIONS: For a high-field MR-linac, the characterization of ionization chamber performance as angular orientation varied relative to the magnetic field confirmed that the ideal orientation for output calibration is parallel. For most of these chamber models, this study represents the first experimental characterization of chamber performance in clinical MR-linac beams. This is a critical step toward accurate output calibration for MR-guided radiotherapy systems and the measured kB,Q values will be an important reference data source for forthcoming MR-linac reference dosimetry protocols.

Dose-rate dependence and IMRT QA suitability of EBT3 radiochromic films for pulse reduced dose-rate radiotherapy (PRDR) dosimetry.

BACKGROUND: Pulsed reduced dose rate (PRDR) is an emerging radiotherapy technique for recurrent diseases. It is pertinent that the linac beam characteristics are evaluated for PRDR dose rates and a suitable dosimeter is employed for IMRT QA. PURPOSE: This study sought to investigate the pulse characteristics of a 6 MV photon beam during PRDR irradiations on a commercial linac. The feasibility of using EBT3 radiochromic film for use in IMRT QA was also investigated by comparing its response to a commercial diode array phantom. METHODS: A plastic scintillator detector was employed to measure the photon pulse characteristics across nominal repetition rates (NRRs) in the 5-600 MU/min range. Film was irradiated with dose rates in the 0.033-4 Gy/min range to study the dose rate dependence. Five clinical PRDR treatment plans were selected for IMRT QA with the Delta4 phantom and EBT3 film sheets. The planned and measured dose were compared using gamma analysis with a criterion of 3%/3 mm. EBT3 film QA was performed using a cumulative technique and a weighting factor technique. RESULTS: Negligible differences were observed in the pulse width and height data between the investigated NRRs. The pulse width was measured to be 3.15 ± 0.01 µ s $\mu s$ and the PRF was calculated to be 3-357 Hz for the 5-600 MU/min NRRs. The EBT3 film was found to be dose rate independent within 3%. The gamma pass rates (GPRs) were above 99% and 90% for the Delta4 phantom and the EBT3 film using the cumulative QA method, respectively. GPRs as low as 80% were noted for the weighting factor EBT3 QA method. CONCLUSIONS: Altering the NRRs changes the mean dose rate while the instantaneous dose rate remains constant. The EBT3 film was found to be suitable for PRDR dosimetry and IMRT QA with minimal dose rate dependence.

Stereotactic MR-guided on-table adaptive radiation therapy (SMART) for borderline resectable and locally advanced pancreatic cancer: A multi-center, open-label phase 2 study.

BACKGROUND AND PURPOSE: Radiation dose escalation may improve local control (LC) and overall survival (OS) in select pancreatic ductal adenocarcinoma (PDAC) patients. We prospectively evaluated the safety and efficacy of ablative stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) for borderline resectable (BRPC) and locally advanced pancreas cancer (LAPC). The primary endpoint of acute grade ≥ 3 gastrointestinal (GI) toxicity definitely related to SMART was previously published with median follow-up (FU) 8.8 months from SMART. We now present more mature outcomes including OS and late toxicity. MATERIALS AND METHODS: This prospective, multi-center, single-arm open-label phase 2 trial (NCT03621644) enrolled 136 patients (LAPC 56.6 %; BRPC 43.4 %) after ≥ 3 months of any chemotherapy without distant progression and CA19-9 ≤ 500 U/mL. SMART was delivered on a 0.35 T MR-guided system prescribed to 50 Gy in 5 fractions (biologically effective dose10 [BED10] = 100 Gy). Elective coverage was optional. Surgery and chemotherapy were permitted after SMART. RESULTS: Mean age was 65.7 years (range, 36-85), induction FOLFIRINOX was common (81.7 %), most received elective coverage (57.4 %), and 34.6 % had surgery after SMART. Median FU was 22.9 months from diagnosis and 14.2 months from SMART, respectively. 2-year OS from diagnosis and SMART were 53.6 % and 40.5 %, respectively. Late grade ≥ 3 toxicity definitely, probably, or possibly attributed to SMART were observed in 0 %, 4.6 %, and 11.5 % patients, respectively. CONCLUSIONS: Long-term outcomes from the phase 2 SMART trial demonstrate encouraging OS and limited severe toxicity. Additional prospective evaluation of this novel strategy is warranted.

A Multi-Institutional Phase 2 Trial of Ablative 5-Fraction Stereotactic Magnetic Resonance-Guided On-Table Adaptive Radiation Therapy for Borderline Resectable and Locally Advanced Pancreatic Cancer.

PURPOSE: Magnetic resonance (MR) image guidance may facilitate safe ultrahypofractionated radiation dose escalation for inoperable pancreatic ductal adenocarcinoma. We conducted a prospective study evaluating the safety of 5-fraction Stereotactic MR-guided on-table Adaptive Radiation Therapy (SMART) for locally advanced (LAPC) and borderline resectable pancreatic cancer (BRPC). METHODS AND MATERIALS: Patients with LAPC or BRPC were eligible for this multi-institutional, single-arm, phase 2 trial after ≥3 months of systemic therapy without evidence of distant progression. Fifty gray in 5 fractions was prescribed on a 0.35T MR-guided radiation delivery system. The primary endpoint was acute grade ≥3 gastrointestinal (GI) toxicity definitely attributed to SMART. RESULTS: One hundred thirty-six patients (LAPC 56.6%, BRPC 43.4%) were enrolled between January 2019 and January 2022. Mean age was 65.7 (36-85) years. Head of pancreas lesions were most common (66.9%). Induction chemotherapy mostly consisted of (modified)FOLFIRINOX (65.4%) or gemcitabine/nab-paclitaxel (16.9%). Mean CA19-9 after induction chemotherapy and before SMART was 71.7 U/mL (0-468). On-table adaptive replanning was performed for 93.1% of all delivered fractions. Median follow-up from diagnosis and SMART was 16.4 and 8.8 months, respectively. The incidence of acute grade ≥3 GI toxicity possibly or probably attributed to SMART was 8.8%, including 2 postoperative deaths that were possibly related to SMART in patients who had surgery. There was no acute grade ≥3 GI toxicity definitely related to SMART. One-year overall survival from SMART was 65.0%. CONCLUSIONS: The primary endpoint of this study was met with no acute grade ≥3 GI toxicity definitely attributed to ablative 5-fraction SMART. Although it is unclear whether SMART contributed to postoperative toxicity, we recommend caution when pursuing surgery, especially with vascular resection after SMART. Additional follow-up is ongoing to evaluate late toxicity, quality of life, and long-term efficacy.

Multi-parametric MRI for radiotherapy simulation.

Magnetic resonance imaging (MRI) has become an important imaging modality in the field of radiotherapy (RT) in the past decade, especially with the development of various novel MRI and image-guidance techniques. In this review article, we will describe recent developments and discuss the applications of multi-parametric MRI (mpMRI) in RT simulation. In this review, mpMRI refers to a general and loose definition which includes various multi-contrast MRI techniques. Specifically, we will focus on the implementation, challenges, and future directions of mpMRI techniques for RT simulation.

Transcatheter Arterial Chemoembolization Imaging Features in MR-Linac Radiation Therapy Planning for the Liver.

For MR-guided radiation therapy treatment planning, an MRI and CT of the intended treatment site are typically acquired. Patients' prior treatments or procedures can cause image artifacts in one or both scans, which may impact treatment planning or the radiation dose calculation. In this case report, a patient with several previous transcatheter arterial chemoembolization (TACE) procedures was planned for radiation therapy on a low-field MR-linac, and the impact of residual iodinated oil on the radiation dose calculation and MR-guided adaptive workflow was evaluated.

MAGNET: A MODALITY-AGNOSTIC NETWORK FOR 3D MEDICAL IMAGE SEGMENTATION.

In this paper, we proposed MAGNET, a novel modality-agnostic network for 3D medical image segmentation. Different from existing learning methods, MAGNET is specifically designed to handle real medical situations where multiple modalities/sequences are available during model training, but fewer ones are available or used at time of clinical practice. Our results on multiple datasets show that MAGNET trained on multi-modality data has the unique ability to perform predictions using any subset of training imaging modalities. It outperforms individually trained uni-modality models while can further boost performance when more modalities are available at testing.

Artificial Intelligence in Radiation Therapy.

Artificial intelligence (AI) has great potential to transform the clinical workflow of radiotherapy. Since the introduction of deep neural networks, many AI-based methods have been proposed to address challenges in different aspects of radiotherapy. Commercial vendors have started to release AI-based tools that can be readily integrated to the established clinical workflow. To show the recent progress in AI-aided radiotherapy, we have reviewed AI-based studies in five major aspects of radiotherapy including image reconstruction, image registration, image segmentation, image synthesis, and automatic treatment planning. In each section, we summarized and categorized the recently published methods, followed by a discussion of the challenges, concerns, and future development. Given the rapid development of AI-aided radiotherapy, the efficiency and effectiveness of radiotherapy in the future could be substantially improved through intelligent automation of various aspects of radiotherapy.

Integrated MRI-guided radiotherapy - opportunities and challenges.

MRI can help to categorize tissues as malignant or non-malignant both anatomically and functionally, with a high level of spatial and temporal resolution. This non-invasive imaging modality has been integrated with radiotherapy in devices that can differentially target the most aggressive and resistant regions of tumours. The past decade has seen the clinical deployment of treatment devices that combine imaging with targeted irradiation, making the aspiration of integrated MRI-guided radiotherapy (MRIgRT) a reality. The two main clinical drivers for the adoption of MRIgRT are the ability to image anatomical changes that occur before and during treatment in order to adapt the treatment approach, and to image and target the biological features of each tumour. Using motion management and biological targeting, the radiation dose delivered to the tumour can be adjusted during treatment to improve the probability of tumour control, while simultaneously reducing the radiation delivered to non-malignant tissues, thereby reducing the risk of treatment-related toxicities. The benefits of this approach are expected to increase survival and quality of life. In this Review, we describe the current state of MRIgRT, and the opportunities and challenges of this new radiotherapy approach.

Low-rank inversion reconstruction for through-plane accelerated radial MR fingerprinting applied to relaxometry at 0.35 T.

PURPOSE: To reduce scan time, methods to accelerate phase-encoded/non-Cartesian MR fingerprinting (MRF) acquisitions for variable density spiral acquisitions have recently been developed. These methods are not applicable to MRF acquisitions, wherein a single k-space spoke is acquired per frame. Therefore, we propose a low-rank inversion method to resolve MRF contrast dynamics from through-plane accelerated Cartesian/radial measurements applied to quantitative relaxation-time mapping on a 0.35T system. METHODS: An algorithm was implemented to reconstruct through-plane aliased low-rank images describing the contrast dynamics occurring because of the transient-state MRF acquisition. T1 and T2 times from accelerated acquisitions were compared with those from unaccelerated linear reconstructions in a standardized system phantom and within in vivo brain and prostate experiments on a hybrid 0.35T MRI/linear accelerator. RESULTS: No significant differences between T1 and T2 times for the accelerated reconstructions were observed compared to fully sampled acquisitions (p = 0.41 and p = 0.36, respectively). The mean absolute errors in T1 and T2 were 5.6% and 2.9%, respectively, between the full and accelerated acquisitions. The SDs in T1 and T2 decreased with the advanced accelerated reconstruction compared with the unaccelerated reconstruction (p = 0.02 and p = 0.03, respectively). The quality of the T1 and T2 maps generated with the proposed approach are comparable to those obtained using the unaccelerated data sets. CONCLUSIONS: Through-plane accelerated MRF with radial k-space coverage was demonstrated at a low field strength of 0.35 T. This method enabled 3D T1 and T2 mapping at 0.35 T with a 3-min scan.

Characterizing Sensitive Cardiac Substructure Excursion Due to Respiration.

PURPOSE: Whole-heart dose metrics are not as strongly linked to late cardiac morbidities as radiation doses to individual cardiac substructures. Our aim was to characterize the excursion and dosimetric variation throughout respiration of sensitive cardiac substructures for future robust safety margin design. METHODS AND MATERIALS: Eleven patients with cancer treatments in the thorax underwent 4-phase noncontrast 4-dimensional computed tomography (4DCT) with T2-weighted magnetic resonance imaging in end-exhale. The end-exhale phase of the 4DCT was rigidly registered with the magnetic resonance imaging and refined with an assisted alignment surrounding the heart from which 13 substructures (chambers, great vessels, coronary arteries, etc) were contoured by a radiation oncologist on the 4DCT. Contours were deformed to the other respiratory phases via an intensity-based deformable registration for radiation oncologist verification. Measurements of centroid and volume were evaluated between phases. Mean and maximum dose to substructures were evaluated across respiratory phases for the breast (n = 8) and thoracic cancer (n = 3) cohorts. RESULTS: Paired t tests revealed reasonable maintenance of geometric and anatomic properties (P < .05 for 4/39 volume comparisons). Maximum displacements >5 mm were found for 24.8%, 8.5%, and 64.5% of the cases in the left-right, anterior-posterior, and superior-inferior axes, respectively. Vector displacements were largest for the inferior vena cava and the right coronary artery, with displacements up to 17.9 mm. In breast, the left anterior descending artery Dmean varied 3.03 ± 1.75 Gy (range, 0.53-5.18 Gy) throughout respiration whereas lung showed patient-specific results. Across all patients, whole heart metrics were insensitive to breathing phase (mean and maximum dose variations <0.5 Gy). CONCLUSIONS: This study characterized the intrafraction displacement of the cardiac substructures through the respiratory cycle and highlighted their increased dosimetric sensitivity to local dose changes not captured by whole heart metrics. Results suggest value of cardiac substructure margin generation to enable more robust cardiac sparing and to reduce the effect of respiration on overall treatment plan quality.

Application of Continuous Positive Airway Pressure for Thoracic Respiratory Motion Management: An Assessment in a Magnetic Resonance Imaging-Guided Radiation Therapy Environment.

PURPOSE: Patient tolerability of magnetic resonance (MR)-guided radiation treatment delivery is limited by the need for repeated deep inspiratory breath holds (DIBHs). This volunteer study assessed the feasibility of continuous positive airway pressure (CPAP) with and without DIBH for respiratory motion management during radiation treatment with an MR-linear accelerator (MR-linac). METHODS AND MATERIALS: MR imaging safety was first addressed by placing the CPAP device in an MR-safe closet and configuring a tube circuit via waveguide to the magnet bore. Reproducibility and linearity of the final configuration were assessed. Six healthy volunteers underwent thoracic imaging in a 0.35T MR-linac, with one free breathing (FB) and 2 DIBH acquisitions being obtained at 5 pressures from 0 to 15 cm-H2O. Lung and heart volumes and positions were recorded; repeatability was assessed by comparing 2 consecutive DIBH scans. Blinded reviewers graded images for motion artifact using a 3-point grading scale. Participants completed comfort and perception surveys before and after imaging sessions. RESULTS: Compared with FB alone, FB-10, FB-12, and FB-15 cm H2O significantly increased lung volumes (+23%, +34%, +44%; all P <.05) and inferiorly displaced the heart (0.86 cm, 0.96 cm, 1.18 cm; all P < . 05). Lung volumes were significantly greater with DIBH-0 cm H2O compared with FB-15 cm H2O (+105% vs +44%, P = .01), and DIBH-15 cm H2O yielded additional volume increase (+131% vs +105%, P = .01). Adding CPAP to DIBH decreased lung volume differences between consecutive breath holds (correlation coefficient 0.97 at 15 cm H2O vs 0.00 at 0 cm H2O). The addition of 15 cm H2O CPAP reduced artifact scores (P = .03) compared with FB; all DIBH images (0-15 cm H2O) had less artifact (P < .01). CONCLUSIONS: This work demonstrates the feasibility of integrating CPAP in an MR-linac environment in healthy volunteers. Extending this work to a larger patient cohort is warranted to further establish the role of CPAP as an alternative and concurrent approach to DIBH in MR-guided radiation therapy.

Cardiac Magnetic Resonance Imaging and Blood Biomarkers for Evaluation of Radiation-Induced Cardiotoxicity in Patients With Breast Cancer: Results of a Phase 2 Clinical Trial.

PURPOSE: Radiation therapy (RT) can increase the risk of cardiac events in patients with breast cancer (BC), but biomarkers predicting risk for developing RT-induced cardiac disease are currently lacking. We report results from a prospective clinical trial evaluating early magnetic resonance imaging (MRI) and serum biomarker changes as predictors of cardiac injury and risk of subsequent cardiac events after RT for left-sided disease. METHODS: Women with node-negative and node-positive (N-/+) left-sided BC were enrolled on 2 institutional review board (IRB)-approved protocols at 2 institutions. MRI was conducted pretreatment (within 1 week of starting radiation), at the end of treatment (last day of treatment ±1 week), and 3 months after the last day of treatment (±2 weeks) to quantify left and right ventricular volumes and function, myocardial fibrosis, and edema. Perfusion changes during regadenoson stress perfusion were also assessed on a subset of patients (n = 28). Serum was collected at the same time points. Whole heart and cardiac substructures were contoured using CT and MRI. Models were constructed using baseline cardiac and clinical risk factors. Associations between MRI-measured changes and dose were evaluated. RESULTS: Among 51 women enrolled, mean heart dose ranged from 0.80 to 4.7 Gy and mean left ventricular (LV) dose from 1.1 to 8.2 Gy, with mean heart dose 2.0 Gy. T1 time, a marker of fibrosis, and right ventricular (RV) ejection fraction (EF) significantly changed with treatment; these were not dose dependent. T2 (marker of edema) and LV EF did not significantly change. No risk factors were associated with baseline global perfusion. Prior receipt of doxorubicin was marginally associated with decreased myocardial perfusion after RT (P = .059), and mean MHD was not associated with perfusion changes. A significant correlation between baseline IL-6 and mean heart dose (MHD) at the end of RT (ρ 0.44, P = .007) and a strong trend between troponin I and MHD at 3 months post-treatment (ρ 0.33, P = .07) were observed. No other significant correlations were identified. CONCLUSIONS: In this prospective study of women with left-sided breast cancer treated with contemporary treatment planning, cardiac radiation doses were very low relative to historical doses reported by Darby et al. Although we observed significant changes in T1 and RV EF shortly after RT, these changes were not correlated with whole heart or substructure doses. Serum biomarker analysis of cardiac injury demonstrates an interesting trend between markers and MHD that warrants further investigation.