Magnetic resonance linear accelerator technology and adaptive radiation therapy: An overview for clinicians.

Radiation therapy (RT) continues to play an important role in the treatment of cancer. Adaptive RT (ART) is a novel method through which RT treatments are evolving. With the ART approach, computed tomography or magnetic resonance (MR) images are obtained as part of the treatment delivery process. This enables the adaptation of the irradiated volume to account for changes in organ and/or tumor position, movement, size, or shape that may occur over the course of treatment. The advantages and challenges of ART maybe somewhat abstract to oncologists and clinicians outside of the specialty of radiation oncology. ART is positioned to affect many different types of cancer. There is a wide spectrum of hypothesized benefits, from small toxicity improvements to meaningful gains in overall survival. The use and application of this novel technology should be understood by the oncologic community at large, such that it can be appropriately contextualized within the landscape of cancer therapies. Likewise, the need to test these advances is pressing. MR-guided ART (MRgART) is an emerging, extended modality of ART that expands upon and further advances the capabilities of ART. MRgART presents unique opportunities to iteratively improve adaptive image guidance. However, although the MRgART adaptive process advances ART to previously unattained levels, it can be more expensive, time-consuming, and complex. In this review, the authors present an overview for clinicians describing the process of ART and specifically MRgART.

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.

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.

Incorporating sensitive cardiac substructure sparing into radiation therapy planning.

PURPOSE: Rising evidence suggests that cardiac substructures are highly radiosensitive. However, they are not routinely considered in treatment planning as they are not readily visualized on treatment planning CTs (TPCTs). This work integrated the soft tissue contrast provided by low-field MRIs acquired on an MR-linac via image registration to further enable cardiac substructure sparing on TPCTs. METHODS: Sixteen upper thoracic patients treated at various breathing states (7 end-exhalation, 7 end-inhalation, 2 free-breathing) on a 0.35T MR-linac were retrospectively evaluated. A hybrid MR/CT atlas and a deep learning three-dimensional (3D) U-Net propagated 13 substructures to TPCTs. Radiation oncologists revised contours using registered MRIs. Clinical treatment plans were re-optimized and evaluated for beam arrangement modifications to reduce substructure doses. Dosimetric assessment included mean and maximum (0.03cc) dose, left ventricular volume receiving 5Gy (LV-V5), and other clinical endpoints. As metrics of plan complexity, total MU and treatment time were evaluated between approaches. RESULTS: Cardiac sparing plans reduced the mean heart dose (mean reduction 0.7 ± 0.6, range 0.1 to 2.5 Gy). Re-optimized plans reduced left anterior descending artery (LADA) mean and LADA0.03cc (0.0-63.9% and 0.0 to 17.3 Gy, respectively). LV0.03cc was reduced by >1.5 Gy for 10 patients while 6 cases had large reductions (>7%) in LV-V5. Left atrial mean dose was equivalent/reduced in all sparing plans (mean reduction 0.9 ± 1.2 Gy). The left main coronary artery was better spared in all cases for mean dose and D0.03cc . One patient exhibited >10 Gy reduction in D0.03cc to four substructures. There was no statistical difference in treatment time and MU, or clinical endpoints to the planning target volume, lung, esophagus, or spinal cord after re-optimization. Four patients benefited from new beam arrangements, leading to further dose reductions. CONCLUSIONS: By introducing 0.35T MRIs acquired on an MR-linac to verify cardiac substructure segmentations for CT-based treatment planning, an opportunity was presented for more effective sparing with limited increase in plan complexity. Validation in a larger cohort with appropriate margins offers potential to reduce radiation-related cardiotoxicities.

Development and evaluation of a novel MR-compatible pelvic end-to-end phantom.

MR-only treatment planning and MR-IGRT leverage MRI's powerful soft tissue contrast for high-precision radiation therapy. However, anthropomorphic MR-compatible phantoms are currently limited. This work describes the development and evaluation of a custom-designed, modular, pelvic end-to-end (PETE) MR-compatible phantom to benchmark MR-only and MR-IGRT workflows. For construction considerations, subject data were assessed for phantom/skeletal geometry and internal organ kinematics to simulate average male pelvis anatomy. Various materials for the bone, bladder, and rectum were evaluated for utility within the phantom. Once constructed, PETE underwent CT-SIM, MR-Linac, and MR-SIM imaging to qualitatively assess organ visibility. Scans were acquired with various bladder and rectal volumes to assess component interactions, filling capabilities, and filling reproducibility via volume and centroid differences. PETE simulates average male pelvis anatomy and comprises an acrylic body oval (height/width = 23.0/38.1 cm) and a cast-mold urethane skeleton, with silicone balloons simulating bladder and rectum, a silicone sponge prostate, and hydrophilic poly(vinyl alcohol) foam to simulate fat/tissue separation between organs. Access ports enable retrofitting the phantom with other inserts including point/film-based dosimetry options. Acceptable contrast was achievable in CT-SIM and MR-Linac images. However, the bladder was challenging to distinguish from background in CT-SIM. The desired contrast for T1-weighted and T2-weighted MR-SIM (dark and bright bladders, respectively) was achieved. Rectum and bone exhibited no MR signal. Inputted volumes differed by <5 and <10 mL from delineated rectum (CT-SIM) and bladder (MR-SIM) volumes. Increasing bladder and rectal volumes induced organ displacements and shape variations. Reproduced volumes differed by <4.5 mL, with centroid displacements <1.4 mm. A point dose measurement with an MR-compatible ion chamber in an MR-Linac was within 1.5% of expected. A novel, modular phantom was developed with suitable materials and properties that accurately and reproducibly simulate status changes with multiple dosimetry options. Future work includes integrating more realistic organ models to further expand phantom options.

Impact of a novel exponential weighted 4DCT reconstruction algorithm.

PURPOSE: This work characterizes a novel exponential 4DCT reconstruction algorithm (EXPO), in phantom and patient, to determine its impact on image quality as compared to the standard cosine-squared weighted 4DCT reconstruction. METHODS: A motion platform translated objects in the superior-inferior (S-I) direction at varied breathing rates (8-20 bpm) and couch pitches (0.06-0.1) to evaluate interplay between parameters. Ten-phase 4DCTs were acquired and data were reconstructed with cosine squared and EXPO weighting. To quantify the magnitude of image blur, objects were translated in the anterior-posterior (A-P) and S-I directions for full-width half maximum (FWHM) analysis between both 4DCT algorithms and a static case. 4DCT sinogram data for 10 patients were retrospectively reconstructed using both weighting factors. Image subtractions elucidated intensity and boundary differences. Subjective image quality grading (presence of image artifacts, noise, spatial resolution (i.e., lung/liver boundary sharpness), and overall image quality) was conducted yielding 200 evaluations. RESULTS: After taking static object size into account, the FWHM of EXPO reconstructions in the A-P direction was 3.3 ± 1.7 mm (range: 0-4.9) as compared to cosine squared 9.8 ± 4.0 mm (range: 2.6-14.4). The FWHM of objects translated in the S-I direction reconstructed with EXPO agreed better with the static FWHM than the cosine-squared reconstructions. Slower breathing periods, faster couch pitches, and intermediate 4DCT phases had the largest reductions of blurring with EXPO. 18 of 60 comparisons of artifacts were improved with EXPO reconstruction, whereas no appreciable changes were observed in image quality scores. In 18 of 20 cases, EXPO provided sharper images although the reduced projections also increased baseline noise. CONCLUSION: Exponential weighted 4DCT offers potential for reducing image blur (i.e., improving image sharpness) in 4DCT with a tendency to reduce artifacts. Future work will involve evaluating the impact on treatment planning including delineation ability and dose calculation.

Optimization of a novel large field of view distortion phantom for MR-only treatment planning.

PURPOSE: MR-only treatment planning requires images of high geometric fidelity, particularly for large fields of view (FOV). However, the availability of large FOV distortion phantoms with analysis software is currently limited. This work sought to optimize a modular distortion phantom to accommodate multiple bore configurations and implement distortion characterization in a widely implementable solution. METHOD AND MATERIALS: To determine candidate materials, 1.0 T MR and CT images were acquired of twelve urethane foam samples of various densities and strengths. Samples were precision-machined to accommodate 6 mm diameter paintballs used as landmarks. Final material candidates were selected by balancing strength, machinability, weight, and cost. Bore sizes and minimum aperture width resulting from couch position were tabulated from the literature (14 systems, 5 vendors). Bore geometry and couch position were simulated using MATLAB to generate machine-specific models to optimize the phantom build. Previously developed software for distortion characterization was modified for several magnet geometries (1.0 T, 1.5 T, 3.0 T), compared against previously published 1.0 T results, and integrated into the 3D Slicer application platform. RESULTS: All foam samples provided sufficient MR image contrast with paintball landmarks. Urethane foam (compressive strength ∼1000 psi, density ~20 lb/ft3 ) was selected for its accurate machinability and weight characteristics. For smaller bores, a phantom version with the following parameters was used: 15 foam plates, 55 × 55 × 37.5 cm3 (L×W×H), 5,082 landmarks, and weight ~30 kg. To accommodate > 70 cm wide bores, an extended build used 20 plates spanning 55 × 55 × 50 cm3 with 7,497 landmarks and weight ~44 kg. Distortion characterization software was implemented as an external module into 3D Slicer's plugin framework and results agreed with the literature. CONCLUSION: The design and implementation of a modular, extendable distortion phantom was optimized for several bore configurations. The phantom and analysis software will be available for multi-institutional collaborations and cross-validation trials to support MR-only planning.

Impact of incorporating visual biofeedback in 4D MRI.

Precise radiation therapy (RT) for abdominal lesions is complicated by respiratory motion and suboptimal soft tissue contrast in 4D CT. 4D MRI offers improved con-trast although long scan times and irregular breathing patterns can be limiting. To address this, visual biofeedback (VBF) was introduced into 4D MRI. Ten volunteers were consented to an IRB-approved protocol. Prospective respiratory-triggered, T2-weighted, coronal 4D MRIs were acquired on an open 1.0T MR-SIM. VBF was integrated using an MR-compatible interactive breath-hold control system. Subjects visually monitored their breathing patterns to stay within predetermined tolerances. 4D MRIs were acquired with and without VBF for 2- and 8-phase acquisitions. Normalized respiratory waveforms were evaluated for scan time, duty cycle (programmed/acquisition time), breathing period, and breathing regularity (end-inhale coefficient of variation, EI-COV). Three reviewers performed image quality assessment to compare artifacts with and without VBF. Respiration-induced liver motion was calculated via centroid difference analysis of end-exhale (EE) and EI liver contours. Incorporating VBF reduced 2-phase acquisition time (4.7 ± 1.0 and 5.4 ± 1.5 min with and without VBF, respectively) while reducing EI-COV by 43.8% ± 16.6%. For 8-phase acquisitions, VBF reduced acquisition time by 1.9 ± 1.6 min and EI-COVs by 38.8% ± 25.7% despite breathing rate remaining similar (11.1 ± 3.8 breaths/min with vs. 10.5 ± 2.9 without). Using VBF yielded higher duty cycles than unguided free breathing (34.4% ± 5.8% vs. 28.1% ± 6.6%, respectively). Image grading showed that out of 40 paired evaluations, 20 cases had equivalent and 17 had improved image quality scores with VBF, particularly for mid-exhale and EI. Increased liver excursion was observed with VBF, where superior-inferior, anterior-posterior, and left-right EE-EI displacements were 14.1± 5.8, 4.9 ± 2.1, and 1.5 ± 1.0 mm, respectively, with VBF compared to 11.9 ± 4.5, 3.7 ± 2.1, and 1.2 ± 1.4 mm without. Incorporating VBF into 4D MRI substantially reduced acquisition time, breathing irregularity, and image artifacts. However, differences in excursion were observed, thus implementation will be required throughout the RT workflow.

Initial clinical experience with a radiation oncology dedicated open 1.0T MR-simulation.

The purpose of this study was to describe our experience with 1.0T MR-SIM including characterization, quality assurance (QA) program, and features necessary for treatment planning. Staffing, safety, and patient screening procedures were developed. Utilization of an external laser positioning system (ELPS) and MR-compatible couchtop were illustrated. Spatial and volumetric analyses were conducted between CT-SIM and MR-SIM using a stereotactic QA phantom with known landmarks and volumes. Magnetic field inhomogeneity was determined using phase difference analysis. System-related, in-plane distortion was evaluated and temporal changes were assessed. 3D distortion was characterized for regions of interest (ROIs) 5-20 cm away from isocenter. American College of Radiology (ACR) recommended tests and impact of ELPS on image quality were analyzed. Combined ultrashort echotime Dixon (UTE/Dixon) sequence was evaluated. Amplitude-triggered 4D MRI was implemented using a motion phantom (2-10 phases, ~ 2 cm excursion, 3-5 s periods) and a liver cancer patient. Duty cycle, acquisition time, and excursion were evaluated between maximum intensity projection (MIP) datasets. Less than 2% difference from expected was obtained between CT-SIM and MR-SIM volumes, with a mean distance of < 0.2 mm between landmarks. Magnetic field inhomogeneity was < 2 ppm. 2D distortion was < 2 mm over 28.6-33.6 mm of isocenter. Within 5 cm radius of isocenter, mean 3D geometric distortion was 0.59 ± 0.32 mm (maximum = 1.65 mm) and increased 10-15 cm from isocenter (mean = 1.57 ± 1.06 mm, maximum = 6.26 mm). ELPS interference was within the operating frequency of the scanner and was characterized by line patterns and a reduction in signal-to-noise ratio (4.6-12.6% for TE = 50-150 ms). Image quality checks were within ACR recommendations. UTE/Dixon sequences yielded detectability between bone and air. For 4D MRI, faster breathing periods had higher duty cycles than slow (50.4% (3 s) and 39.4% (5 s), p < 0.001) and ~fourfold acquisition time increase was measured for ten-phase versus two-phase. Superior-inferior object extent was underestimated 8% (6 mm) for two-phase as compared to ten-phase MIPs, although < 2% difference was obtained for ≥ 4 phases. 4D MRI for a patient demonstrated acceptable image quality in ~ 7 min. MR-SIM was integrated into our workflow and QA procedures were developed. Clinical applicability was demonstrated for 4D MRI and UTE imaging to support MR-SIM for single modality treatment planning.

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.

Evaluation of two synchronized external surrogates for 4D CT sorting.

The purpose of this study was to quantify the performance and agreement between two different external surrogate acquisition systems: Varian's Real-Time Position Management (RPM) and Philips Medical Systems' pneumatic bellows, in the context of waveform and 4D CT image analysis. Eight patient displacement curves derived from RPM data were inputted into a motion platform with varying amplitudes (0.5 to 3 cm) and patterns. Simultaneous 4D CT acquisition, with synchronized X-ray on detection, was performed with the bellows and RPM block placed on the platform. Bellows data were used for online retrospective phase-based sorting, while RPM data were used for off-line reconstruction of raw 4D CT data. RPM and bellows breathing curves were resampled, normalized, and analyzed to determine associations between different external surrogates, relative amplitude differences, and system latency. Maximum intensity projection (MIP) images were generated, phantom targets were delineated, and volume differences, overlap index, and Dice similarity coefficient differences were evaluated. A prospective patient study of ten patients was performed and waveforms were evaluated for latency (i.e., absolute time differences) and overall agreement. 4D CT sorting quality and subtraction images were assessed. Near perfect associations between the RPM and bellows-acquired breathing traces were found (Pearson's r = 0.987-0.999). Target volumes were 200.4 ± 12 cc and 199.8 ± 12.6 cc for RPM and bellows targets, respectively, which was not significantly different (U = 33, p > 0.05). Negligible centroid variations were observed between bellows and RPM-contoured MIP targets (largest discrepancy = -0.24 ± 0.31 mm in superior-inferior direction). The maximum volume difference was observed for an RPM target 2.5 cc (1%) less than bellows, yielding the largest difference in centroid displacement (0.9 mm). Strong correlations in bellows and RPM waveforms were observed for all patients (0.947 ± 0.037). Latency between external surrogates was < 100 ms for phantom and patient data. Negligible differences were observed between MIP, end-exhale, and end-inhale phase images for all cases, with delineated RPM and bellows lung volumes demonstrating a mean difference of -0.3 ± 0.51%. Dice similarity coefficients and overlap indices were near unity for phantom target volumes and patient lung volumes. Slight differences were observed in waveform and latency analysis between Philips bellows and Varian's RPM, although these did not translate to differences in image quality or impact delineations. Therefore, the two systems were found to be equivalent external surrogates in the context of 4D CT for treatment planning purposes.

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.

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.

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.

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.

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.

Coupling surface cameras with on-board fluoroscopy: a feasibility study.

PURPOSE: To investigate the feasibility of using three-dimensional surface imaging cameras as an external surrogate of tumor motion through a temporal synchronization with kV imaging. METHODS: To obtain an "x-ray on" signal from the on-board kV fluoroscopy system (XVI, Elekta), a hardware controller (Gate Controller) was interfaced between the kV fluoroscopy and Gate CT (VisionRT Ltd., London) computers. First, phantom experiments were performed using a programmable respiratory motion platform (sinusoidal motion, period = 3-5 s). The platform included a chest-wall component (A-P amplitude = 1 cm) tracked with the surface camera, while tumorlike objects translated in the superior-inferior direction were tracked using kV fluoroscopy (300 frames, frequency 5.5 fps). Accuracy of tracking the chest-wall platform was assessed, and the latency of the system was characterized by performing linear regression between the peak times obtained from Gate CT and fluoroscopy. Increasing the complexity of experiments, tumor displacement curves from three patients were simulated using synchronous tumor-abdomen data (RTRT). Our approach was further validated by imaging four free-breathing lung cancer patients with simultaneous Gate CT and kV fluoroscopy for approximately 55 s. Consideration was also given to varied sizes and locations of the tracked region of interest on the patient surface. RESULTS: For simple sinusoidal curves, measured amplitude (peak-to-peak) was 1.005 +/- 0.003 cm, 1.013 +/- 0.003 cm, and 1.003 +/- 0.005 cm for periods of 5, 4, and 3.3 s, respectively, demonstrating an excellent agreement with the actual chest platform amplitude of 1.0 cm. Period measurements were within 0.2% of actual using the surface cameras and within 0.9% of actual value using fluoroscopy. For the sinusoidal motion, the system latency was 0.64 +/- 0.02 s. This was further validated for the simulated tumor motion from three patients (latency = 0.65 +/- 0.03 s). Five of the nine patient fractions studied showed the associations between the abdomen and tumor were equivalent or better (Pearson r = 0.93-0.98) than those observed between the diaphragm and tumor (Pearson r = 0.89-0.95). A repeat analysis of five different tracked surfaces on the same patient further demonstrated strong agreement with the diaphragm and tumor, although no improvement in association strength was observed with increased size of region of interest. CONCLUSIONS: The feasibility of using surface imaging cameras to track the patient's abdomen as an external surrogate, while using kV imaging to track internal anatomy in synchrony, has been demonstrated. With further validation through additional patient studies to confirm these findings, gated radiation therapy treatments using surface imaging cameras as the external surrogate can be facilitated.

Task group 284 report: magnetic resonance imaging simulation in radiotherapy: considerations for clinical implementation, optimization, and quality assurance.

The use of dedicated magnetic resonance simulation (MR-SIM) platforms in Radiation Oncology has expanded rapidly, introducing new equipment and functionality with the overall goal of improving the accuracy of radiation treatment planning. However, this emerging technology presents a new set of challenges that need to be addressed for safe and effective MR-SIM implementation. The major objectives of this report are to provide recommendations for commercially available MR simulators, including initial equipment selection, siting, acceptance testing, quality assurance, optimization of dedicated radiation therapy specific MR-SIM workflows, patient-specific considerations, safety, and staffing. Major contributions include guidance on motion and distortion management as well as MRI coil configurations to accommodate patients immobilized in the treatment position. Examples of optimized protocols and checklists for QA programs are provided. While the recommendations provided here are minimum requirements, emerging areas and unmet needs are also highlighted for future development.