Inter-scanner super-resolution of 3D cine MRI using a transfer-learning network for MRgRT.

OBJECTIVE: Deep-learning networks for super-resolution (SR) reconstruction enhance the spatial-resolution of 3D magnetic resonance imaging (MRI) for MR-guided radiotherapy (MRgRT). However, variations between MRI scanners and patients impact the quality of SR for real-time 3D low-resolution (LR) cine MRI. In this study, we present a personalized super-resolution (psSR) network that incorporates transfer-learning to overcome the challenges in inter-scanner SR of 3D cine MRI. Approach: Development of the proposed psSR network comprises two-stages: 1) a cohort-specific SR (csSR) network using clinical patient datasets, and 2) a psSR network using transfer-learning to target datasets. The csSR network was developed by training on breath-hold and respiratory-gated high-resolution (HR) 3D MRIs and their k-space down-sampled LR MRIs from 53 thoracoabdominal patients scanned at 1.5 T. The psSR network was developed through transfer-learning to retrain the csSR network using a single breath-hold HR MRI and a corresponding 3D cine MRI from 5 healthy volunteers scanned at 0.55 T. Image quality was evaluated using the peak-signal-noise-ratio (PSNR) and the structure-similarity-index-measure (SSIM). The clinical feasibility was assessed by liver contouring on the psSR MRI using an auto-segmentation network and quantified using the Dice-similarity-coefficient (DSC). Results. Mean PSNR and SSIM values of psSR MRIs were increased by 57.2% (13.8 to 21.7) and 94.7% (0.38 to 0.74) compared to cine MRIs, with the reference 0.55 T breath-hold HR MRI. In the contour evaluation, DSC was increased by 15% (0.79 to 0.91). Average time consumed for transfer-learning was 90 s, psSR was 4.51 ms per volume, and auto-segmentation was 210 ms, respectively. Significance. The proposed psSR reconstruction substantially increased image and segmentation quality of cine MRI in an average of 215 ms across the scanners and patients with less than 2 minutes of prerequisite transfer-learning. This approach would be effective in overcoming cohort- and scanner-dependency of deep-learning for MRgRT. .

Characterization of real-time cine MR imaging distortion on 0.35 T MRgRT with concentric cine imaging QA phantom.

Objective. Real-time MRgRT uses 2D-cine imaging for target tracking and motion evaluation. Rotation of gantry inducedB0off-resonance, resulting in image artifacts and imaging isocenter-shift precluding MR-guided arc therapy. Standard MRI phantoms designed for higher resolution images face challenges when low-resolution cine imaging is needed to achieve high frame rates. This work aimed to examine the spatial accuracy including geometric distortion and isocenter shift in real-time during gantry rotation on a 0.35 T MR-Linac using the concentric Cine imaging quality assurance (QA) phantom and its associated image analysis software.Approach. The Cine imaging QA phantom consists of two concentric shells of low-T1mineral oil and a central alignment structure. The phantom was scanned on three different MRI systems; 0.55 T Siemens Free.Max, 1.5 T Philips Ingenia, and 0.35 T ViewRay MRIdian MR-Linac using 2D balanced steady-state free precession (bSSFP) imaging sequence. In addition, bSSFP cine MRI with the banding artifact correction was tested on 0.35 T ViewRay MR-Linac. Images from the MR-Linac were acquired with the Linac gantry stationary and rotating from gantry 300°â†’ 0° and vice versa. Three orthogonal image planes were scanned excluding the 1.5 T Philips Ingenia, where only the axial plane was scanned. The image analysis software calculated the distortion values as well as the isocenter position for each cine frame.Main results. The geometric distortion of cine imaging on MRIs and MR-Linac at gantry stationary are within 1 mm while the substantial geometric distortion of 2 and 2.2 mm were observed on 0.35 T MR-Linac while rotating the gantry clockwise (300°â†’ 0°) and counterclockwise 0°â†’ 300° respectively. The average imaging isocenter shift was 0.1 mm for both MRIs and the static gantry and imaging isocenter shift of ≤1.5 mm was observed during the gantry rotation. The imaging isocenter shift decreased by 1 ± 0.2 mm clockwise and counterclockwise withB0compensation.Significance. The concentric Cine imaging QA phantom and its associated software effectively demonstrate the image distortion on real-time cine imaging on regular MRIs and 0.35 T MR-Linac. The results of significant geometric distortion with a rotating gantry in the MR-Linac system require further investigation to alleviate the extent of the image distortion.

Technical note: Minimizing CIED artifacts on a 0.35 T MRI-Linac using deep learning.

BACKGROUND: Artifacts from implantable cardioverter defibrillators (ICDs) are a challenge to magnetic resonance imaging (MRI)-guided radiotherapy (MRgRT). PURPOSE: This study tested an unsupervised generative adversarial network to mitigate ICD artifacts in balanced steady-state free precession (bSSFP) cine MRIs and improve image quality and tracking performance for MRgRT. METHODS: Fourteen healthy volunteers (Group A) were scanned on a 0.35 T MRI-Linac with and without an MR conditional ICD taped to their left pectoral to simulate an implanted ICD. bSSFP MRI data from 12 of the volunteers were used to train a CycleGAN model to reduce ICD artifacts. The data from the remaining two volunteers were used for testing. In addition, the dataset was reorganized three times using a Leave-One-Out scheme. Tracking metrics [Dice similarity coefficient (DSC), target registration error (TRE), and 95 percentile Hausdorff distance (95% HD)] were evaluated for whole-heart contours. Image quality metrics [normalized root mean square error (nRMSE), peak signal-to-noise ratio (PSNR), and multiscale structural similarity (MS-SSIM) scores] were evaluated. The technique was also tested qualitatively on three additional ICD datasets (Group B) including a patient with an implanted ICD. RESULTS: For the whole-heart contour with CycleGAN reconstruction: 1) Mean DSC rose from 0.910 to 0.935; 2) Mean TRE dropped from 4.488 to 2.877 mm; and 3) Mean 95% HD dropped from 10.236 to 7.700 mm. For the whole-body slice with CycleGAN reconstruction: 1) Mean nRMSE dropped from 0.644 to 0.420; 2) Mean MS-SSIM rose from 0.779 to 0.819; and 3) Mean PSNR rose from 18.744 to 22.368. The three Group B datasets evaluated qualitatively displayed a reduction in ICD artifacts in the heart. CONCLUSION: CycleGAN-generated reconstructions significantly improved both tracking and image quality metrics when used to mitigate artifacts from ICDs.

Comprehensive MR imaging QA of 0.35 T MR-Linac using a multi-purpose large FOV phantom: A single-institution experience.

PURPOSE: Magnetic resonance-guided radiotherapy (MRgRT) is desired for the treatment of diseases in the abdominothoracic region, which has a broad imaging area and continuous motion. To ensure accurate treatment delivery, an effective image quality assurance (QA) program, with a phantom that covers the field of view (FOV) similar to a human torso, is required. However, routine image QA for a large FOV is not readily available at many MRgRT centers. In this work, we present the clinical experience of the large FOV MRgRT Insight phantom for periodic daily and monthly comprehensive magnetic resonance imaging (MRI)-QA and its feasibility compared to the existing institutional routine MRI-QA procedures in 0.35 T MRgRT. METHODS: Three phantoms; ViewRay cylindrical water phantom, Fluke 76-907 uniformity and linearity phantom, and Modus QA large FOV MRgRT Insight phantom, were imaged on the 0.35 T MR-Linac. The measurements were made in MRI mode with the true fast imaging with steady-state free precession (TRUFI) sequence. The ViewRay cylindrical water phantom was imaged in a single-position setup whereas the Fluke phantom and Insight phantom were imaged in three different orientations: axial, sagittal, and coronal. Additionally, the phased array coil QA was performed using the horizontal base plate of the Insight phantom by placing the desired coil around the base section which was compared to an in-house built Polyurethane foam phantom for reference. RESULT: The Insight phantom captured image artifacts across the entire planar field of view, up to 400 mm, in a single image acquisition, which is beyond the FOV of the conventional phantoms. The geometric distortion test showed a similar distortion of 0.45 ± 0.01  and 0.41 ± 0.01 mm near the isocenter, that is, within 300 mm lengths for Fluke and Insight phantoms, respectively, but showed higher geometric distortion of 0.8 ± 0.4 mm in the peripheral region between 300 and 400 mm of the imaging slice for the Insight phantom. The Insight phantom with multiple image quality features and its accompanying software utilized the modulation transform function (MTF) to evaluate the image spatial resolution. The average MTF values were 0.35 ± 0.01, 0.35 ± 0.01, and 0.34 ± 0.03 for axial, coronal, and sagittal images, respectively. The plane alignment and spatial accuracy of the ViewRay water phantom were measured manually. The phased array coil test for both the Insight phantom and the Polyurethane foam phantoms ensured the proper functionality of each coil element. CONCLUSION: The multifunctional large FOV Insight phantom helps in tracking MR imaging quality of the system to a larger extent compared to the routine daily and monthly QA phantoms currently used in our institute. Also, the Insight phantom is found to be more feasible for routine QA with easy setup.

Real-time B0 compensation during gantry rotation in a 0.35-T MRI-Linac.

BACKGROUND: Rotation of the ferromagnetic gantry of a low magnetic field MRI-Linac was previously demonstrated to cause large center frequency offsets of ±400 Hz. The B0 off-resonances cause image artifacts and imaging isocenter shifts that would preclude MRI-guided arc therapy. PURPOSE: The purpose of this study was to measure and compensate for center frequency offsets in real time during gantry rotation on a 0.35-T MRI-Linac using a free induction decay (FID) navigator. METHODS: A nonselective FID navigator was added before each 2D balanced steady-state free precession cine image acquisition on a 0.35-T MRI-Linac. Images were acquired at 7.3 frames per second. Phase data from the initial FID navigator (while the gantry was stationary) was used as a reference. The phase data from each subsequent FID navigator was used to calculate the real-time B0 off-resonance. The transmitter/receiver phase and the phase accrual over the adjacent image acquisition were adjusted to correct for the center frequency offset. Measurements were performed using an MRI-Linac dynamic phantom prior to and while the gantry rotated clockwise and counterclockwise. Image quality and signal-to-noise ratio (SNR) were compared between uncorrected and B0 -corrected MRIs using a reference image acquired while the gantry was stationary. Four targets in the phantom were manually contoured on the first image frame, and an active contouring algorithm was used retrospectively on each subsequent frame to assess image variations and calculate Dice coefficients. Additionally, three healthy volunteers were imaged using the same pulse sequences with and without real-time B0 compensation during gantry rotation. Normalized root mean square errors (nRMSEs) were calculated for the phantom and in vivo to assess the efficacy of the B0 compensation on image quality. The measured center frequency offsets from the volunteer and MRI dynamic phantom navigator data were also compared. The sinusoidal behavior of the center frequency offsets was modeled based on the gantry layout and long-time constant eddy currents resulting from gantry rotation. RESULTS: The duration of the FID navigator and processing was 4.5 ms. The FID navigator resulted in a ≤11% drop in SNR in the phantom and in vivo (liver). Dice coefficients from the MRI-guided radiation therapy (MR-IGRT) phantom contour measurements remained above 0.8 with B0 compensation. Without B0 compensation, the Dice coefficients dropped below 0.8 for up to 21% of the time depending on the contour. Real-time B0 compensation resulted in mean reductions in nRMSE of 51% and 16% for the MR-IGRT phantom and in vivo, respectively. Peak-to-peak center frequency offsets ranged from 757 to 773 Hz in the phantom and 760 to 871 Hz in vivo. CONCLUSION: Dynamic real-time B0 compensation significantly improved image quality and reduced artifacts during gantry rotation in the phantom and in vivo. However, the FID navigator resulted in a small drop in the imaging duty cycle and SNR.

Phase I Trial of Stereotactic MRI-Guided Online Adaptive Radiation Therapy (SMART) for the Treatment of Oligometastatic Ovarian Cancer.

PURPOSE: Stereotactic body radiation therapy is increasingly used to treat a variety of oligometastatic histologies, but few data exist for ovarian cancer. Ablative stereotactic body radiation therapy dosing is challenging in sites like the abdomen, pelvis, and central thorax due to proximity and motion of organs at risk. A novel radiation delivery method, stereotactic magnetic-resonance-guided online-adaptive radiation therapy (SMART), may improve the therapeutic index of stereotactic body radiation therapy through enhanced soft-tissue visualization, real-time nonionizing imaging, and ability to adapt to the anatomy-of-the-day, with the goal of producing systemic-therapy-free intervals. This phase I trial assessed feasibility, safety, and dosimetric advantage of SMART to treat ovarian oligometastases. METHODS AND MATERIALS: Ten patients with recurrent oligometastatic ovarian cancer underwent SMART for oligometastasis ablation. Initial plans prescribed 35 Gy/5 fractions with goal 95% planning target volume coverage by 95% of prescription, with dose escalation permitted, subject to strict organ-at-risk dose constraints. Daily adaptive planning was used to protect organs-at-risk and/or increase target dose. Feasibility (successful delivery of >80% of fractions in the first on-table attempt) and safety of this approach was evaluated, in addition to efficacy, survival metrics, quality-of-life, prospective timing and dosimetric outcomes. RESULTS: Ten women with seventeen ovarian oligometastases were treated with SMART, and 100% of treatment fractions were successfully delivered. Online adaptive plans were selected at time of treatment for 58% of fractions, due to initial plan violation of organs-at-risk constraints (84% of adapted fractions) or observed opportunity for planning target volume dose escalation (16% of adapted fractions), with a median on-table time of 64 minutes. A single Grade ≥3 acute (within 6 months of SMART) treatment-related toxicity (duodenal ulcer) was observed. Local control at 3 months was 94%; median progression-free survival was 10.9 months. Median Kaplan-Meier estimated systemic-therapy-free survival after radiation completion was 11.5 months, with concomitant quality-of-life improvements. CONCLUSIONS: SMART is feasible and safe for high-dose radiation therapy ablation of ovarian oligometastases of the abdomen, pelvis, and central thorax with minimal toxicity, high rates of local control, and prolonged systemic-therapy-free survival translating into improved quality-of-life.

Technical Note: Effects of rotating gantry on magnetic field and eddy currents in 0.35 T MRI-guided radiotherapy (MR-IGRT) system.

PURPOSE: The purpose of this study was to identify the cause of severe image artifacts that occurred during gantry rotation in a 0.35 T MRI-Linac by comparing measurements of eddy currents, center frequency, and field inhomogeneities made with the gantry in motion and stationary. METHODS: Gradient and B0 eddy currents were calculated from the free induction decays (FIDs) resulting from selective excitation at a temporal resolution of 200 ms/measurement. B0 eddy currents were also calculated from FIDs acquired with nonselective excitation at a temporal resolution of 100 ms/measurement. Center frequencies and B0 inhomogeneities were measured by acquiring FIDs with a repetition time (TR) of 290 ms. Cartesian and radial 2D true fast imaging with steady-state precession (TrueFISP) pulse sequences used in real-time MRI-guided radiation therapy (MR-IGRT) were acquired. To assess artifact severity, the normalized root mean square error (nRMSE) was calculated between a reference MRI (static gantry) and MRIs acquired during gantry rotation for each serial acquisition. Image artifacts were qualitatively graded as nominal, minor, or severe. Measurements were conducted while the gantry was rotated through its entire range for both clockwise and counterclockwise. Measurements during gantry rotation were compared to measurements with a stationary gantry (every 30°). RESULTS: Severe image artifacts were observed 22-35% of the time while the gantry was rotating. Short time constant eddy currents were not affected by gantry rotation. The peak to peak center frequency and FWHM rose by factors of 13.2-14.5 and 1.1-1.6, respectively, for the rotating versus stationary gantry. The magnitude of the center frequency offset and field inhomogeneities depended on the direction of the gantry rotation. CONCLUSIONS: Image artifacts during gantry rotation were primarily caused by center frequency variations and field inhomogeneities. Therefore, dynamic B0 compensation techniques should be able to reduce artifacts during gantry rotation.

Effects of B0 eddy currents on imaging isocenter shifts in 0.35-T MRI-guided radiotherapy (MR-IGRT) system.

PURPOSE: The purpose of this study was to measure gantry angle-related eddy currents in a 0.35-T MRI-Linac and determine if B0 (zeroth order) eddy currents are the primary cause of gantry angle-dependent imaging isocenter shifts vs other potential causes like B0 inhomogeneities and gradient (first order) eddy currents. For conventional Cartesian acquisitions, B0 eddy currents can cause imaging isocenter shifts along both phase encode and readout directions. Gradient eddy currents can cause spatial distortion along both the phase encode and readout directions. Center frequency offsets can cause imaging isocenter shifts along the readout direction that vary with readout gradient polarity. METHODS: MRI-related eddy currents and imaging isocenter shifts were measured on a 0.35-T MRI-Linac at gantry angles from 0° to 330° in increments of 30° . All measurements were made after gradient shimming and center frequency tuning at each planned gantry angle. Eddy current and field homogeneity measurements were conducted using a 24-cm diameter spherical phantom. Gradient and B0 eddy currents were calculated from the free induction decays (FIDs) resulting from selective excitation of slices located ±5 cm from isocenter. B0 eddy currents were also calculated from FIDs acquired with nonselective excitation and compared with B0 eddy current values derived using selective excitation. B0 inhomogeneities and center frequency offsets were measured by acquiring FIDs with nonselective excitation. Imaging isocenter shifts were measured using a 33x33x10.5 cm3 uniformity linearity (grid) phantom and a 3D true fast imaging with steady-state precession (TrueFISP) sequence used in MRI-guided radiation therapy. Eddy currents were compared to vendor specifications and correlated with the imaging isocenter shifts. Measurements were conducted before and after the MRI-Linac's waveguide was replaced with an updated design to reduce eddy currents. RESULTS: B0 eddy currents were highly correlated (r = 0.986, P << 0.001) for measurements made with vs without selective excitation. Transverse (X and Y) axis B0 eddy currents before and after the waveguide upgrade were out of specification (specification: ≤0.1 µT m/mT for delays < 10 ms) for most of the measured gantry angles. Gradient eddy currents before and after the upgrade were within specifications for the measured gantry angles (≤0.1% for delays < 10 ms). B0 eddy currents and imaging isocenter shifts were highly correlated (r = 0.965, P << 0.001). After the Linac waveguide upgrade, root mean square (RMS) peak B0 and gradient eddy currents dropped 45% and 11%, respectively, for delays <10 ms, while imaging isocenter shifts dropped 53%. Isocenter shifts were observed in both phase encode and readout directions. Center frequency offsets were <26 Hz while B0 inhomogeneities were <33 Hz full width at half maximum (FWHM). CONCLUSIONS: Imaging isocenter shifts measured in a 0.35-T MRI-Linac were highly correlated with B0 eddy currents. The eddy currents and imaging isocenter shifts decreased after the MRI-Linac's waveguide was replaced.

B0 field homogeneity recommendations, specifications, and measurement units for MRI in radiation therapy.

PURPOSE: The purpose is: (a) Relate magnetic resonance imaging (MRI) quality recommendations for radiation therapy (RT) to B0 field homogeneity; (b) Evaluate manufacturer specifications of B0 homogeneity for 34 commercial whole-body MRI systems based on the MRI quality recommendations and RT application; (c) Measure field homogeneity in five commercial MRI systems and one commercial MRI-Linac used in RT and compare the results with their B0 homogeneity specifications. METHODS: Magnetic resonance imaging quality recommendations for spatial integrity, image blurring, fat saturation, and null banding in RT were developed based on the literature. Guaranteed (maximum) and typical B0 field homogeneity specifications for various diameter spherical volumes (DSVs) were provided by GE, Philips, Siemens, and Canon. For each system, the DSV that conforms to each MRI quality recommendation and anatomical RT application was estimated based on the manufacturer specifications. B0 field homogeneity was measured on six MRI systems including Philips (1.5 T), Siemens (1.5 and 3 T), and ViewRay MRI (0.35 T) systems using 24 and 35 cm DSV spherical phantoms. Two measurement techniques were used: (a) MRI using phase contrast field mapping to measure peak-to-peak (pk-pk), volume root mean square (VRMS), and standard deviation (SD); and (b) Magnetic resonance (MR) spectroscopy by acquiring a volumetric free induction decay (FID) to measure full width at half maximum (FWHM). The measurements were used to assess: (a) conformance with the manufacturer specifications; and (b) the relationship between the various field homogeneity measurement units. Measurements were made with and without gradient shimming (gradshim) or second-order active shimming. Multiple comparisons, analysis of variance (ANOVA), and Pearson correlations were performed to assess the dependence of pk-pk, VRMS, SD, and FWHM measurements of field homogeneity on shim volume, level of shim, and MRI system. RESULTS: For a 40 cm DSV, the B0 homogeneity specifications ranged from 0.35 to 5 ppm (median = 0.75 ppm) VRMS for 1.5 T systems and 0.2 to 1.4 ppm (median = 0.5 ppm) VRMS for 3 T systems. The usable DSVs ranged from 16 to 49 cm (median = 35 cm) based on the image quality recommendations and the manufacturer specifications. There was general compliance between the six measured field homogeneities and manufacturer specifications although signal dephasing was observed in two systems at < 35 cm DSV. The relationships between pk-pk, VRMS, SD, and FWHM varied based on MRI system, shim volume, and quality of shim. However, VRMS and SD measurements were highly correlated. CONCLUSIONS: The delineation of the diseased lesion from organs at risk is the main priority for RT. Therefore, field homogeneity performance for RT must minimize image blurring and image artifacts (null bands and signal dephasing) while optimizing spatial integrity and fat saturation. Based on the specifications and recommendations for field homogeneity, some MRI systems are not well suited to meet the strict demands of RT particularly for the large imaging volumes used in body MRI. VRMS and SD measurements of B0 field homogeneity tend to be more stable and sensitive to field inhomogeneities in RT applications than pk-pk and FWHM.

MRI quality control for low-field MR-IGRT systems: Lessons learned.

PURPOSE: To present lessons learned from magnetic resonance imaging (MRI) quality control (QC) tests for low-field MRI-guided radiation therapy (MR-IGRT) systems. METHODS: MRI QC programs were established for low-field MRI-60 Co and MRI-Linac systems. A retrospective analysis of MRI subsystem performance covered system commissioning, operations, maintenance, and quality control. Performance issues were classified into three groups: (a) Image noise and artifact; (b) Magnetic field homogeneity and linearity; and (c) System reliability and stability. RESULTS: Image noise and artifacts were attributed to room noise sources, unsatisfactory system cabling, and broken RF receiver coils. Gantry angle-dependent magnetic field inhomogeneities were more prominent on the MRI-Linac due to the high volume of steel shielding in the gantry. B0 inhomogeneities measured in a 24-cm spherical phantom were <5 ppm for both MR-IGRT systems after using MRI gradient offset (MRI-GO) compensation on the MRI-Linac. However, significant signal dephasing occurred on the MRI-Linac while the gantry was rotating. Spatial integrity measurements were sensitive to gradient calibration and vulnerable to shimming. The most common causes of MR-IGRT system interruptions were software disconnects between the MRI and radiation therapy delivery subsystems caused by patient table, gantry, and multi-leaf collimator (MLC) faults. The standard deviation (SD) of the receiver coil signal-to-noise ratio was 1.83 for the MRI-60 Co and 1.53 for the MRI-Linac. The SD of the deviation from the mean for the Larmor frequency was 1.41 ppm for the MRI-60 Co and 1.54 ppm for the MRI-Linac. The SD of the deviation from the mean for the transmitter reference amplitude was 0.90% for the MRI-60 Co and 1.68% for the MRI-Linac. High SDs in image stability data corresponded to reports of spike noise. CONCLUSIONS: There are significant technological challenges associated with implementing and maintaining MR-IGRT systems. Most of the performance issues were identified and resolved during commissioning.

Stereotactic MR-Guided Online Adaptive Radiation Therapy (SMART) for Ultracentral Thorax Malignancies: Results of a Phase 1 Trial.

PURPOSE: Stereotactic body radiation therapy (SBRT) is an effective treatment for oligometastatic or unresectable primary malignancies, although target proximity to organs at risk (OARs) within the ultracentral thorax (UCT) limits safe delivery of an ablative dose. Stereotactic magnetic resonance (MR)-guided online adaptive radiation therapy (SMART) may improve the therapeutic ratio using reoptimization to account for daily variation in target and OAR anatomy. This study assessed the feasibility of UCT SMART and characterized dosimetric and clinical outcomes in patients treated for UCT lesions on a prospective phase 1 trial. METHODS AND MATERIALS: Five patients with oligometastatic (n = 4) or unresectable primary (n = 1) UCT malignancies underwent SMART. Initial plans prescribed 50 Gy in 5 fractions with goal 95% planning target volume (PTV) coverage by 95% of prescription, subject to strict OAR constraints. Daily real-time online adaptive plans were created as needed to preserve hard OAR constraints, escalate PTV dose, or both, based on daily setup MR image set anatomy. Treatment times, patient outcomes, and dosimetric comparisons were prospectively recorded. RESULTS: All initial and daily adaptive plans met strict OAR constraints based on simulation and daily setup MR imaging anatomy, respectively. Four of the 5 patients received ≥1 adapted fraction. Ten of the 25 total delivered fractions were adapted. A total of 30% of plan adaptations were performed to improve PTV coverage; 70% were for reversal of ≥1 OAR violation. Local control by Response Evaluation Criteria in Solid Tumors was 100% at 3 and 6 months. No grade ≥3 acute (within 6 months of radiation completion) treatment-related toxicities were identified. CONCLUSIONS: SMART may allow PTV coverage improvement and/or OAR sparing compared with nonadaptive SBRT and may widen the therapeutic index of UCT SBRT. In this small prospective cohort, we found that SMART was clinically deliverable to 100% of patients, although treatment delivery times surpassed our predefined, timing-based feasibility endpoint. This technique is well tolerated, offering excellent local control with no identified acute grade ≥3 toxicity.

In Silico Trial of MR-Guided Midtreatment Adaptive Planning for Hypofractionated Stereotactic Radiation Therapy in Centrally Located Thoracic Tumors.

PURPOSE: Hypofractionated (>5 fraction) stereotactic radiation therapy (HSRT) may allow for ablative biologically equivalent dose to tumors with a lower risk of organ-at-risk (OAR) toxicity in central thoracic tumors. Adaptive planning may further improve OAR sparing while maintaining planning target volume (PTV) coverage. We hypothesized that midtreatment adaptive replanning would offer dosimetric advantages during HSRT for central thorax malignancies using magnetic resonance imaging (MRI)-guided radiation therapy. METHODS AND MATERIALS: Twelve patients with central thorax tumors received HSRT using MRI-guided radiation therapy. Clinically delivered regimens were 60 Gy in 12 fractions or 62.5 Gy in 10 fractions, with low-field magnetic resonance (0.35 T) volumetric setup imaging acquired at each fraction. Daily gross tumor volume (GTV) and OARs were retrospectively redefined on fraction 1, 6, and 10 MRIs, and GTV response was recorded. Simulated initial plans prescribed a dose of 60 Gy in 12 fractions based on fraction 1 MRI. Midtreatment adaptive plans were created based on fraction 6 anatomy-of-the-day. All plans were created using an isotoxicity approach with a goal of 95% PTV coverage, subject to hard OAR constraints, to represent clinically ideal OAR sparing. Plans were then compared for projected OAR sparing and PTV coverage. RESULTS: Patients demonstrated significant on-treatment MRI-defined GTV reduction (median 41.8%; range 16.7%-65.7%). At fraction 6, median reduction was 26.7%. All initial plans met OAR constraints. Initial plan application to fraction 6 and fraction 10 anatomy resulted in 8 OAR violations (5 of 13 patients) and 10 OAR violations (6 of 13 patients). All fraction 6 violations persisted at fraction 10. Midpoint adaptive planning reversed 100% of midpoint OAR violations and tended to reduce the magnitude of OAR violations incurred at fraction 10. In 40% of fractions (2 of 5) in which OAR violation resulted from initial plan application to fraction 6 anatomy, PTV coverage was increased concomitant with violation reversal. CONCLUSIONS: Midtreatment adaptive planning based on tumor response may be dosimetrically advantageous for sparing of surrounding critical structures in HSRT for central thorax malignancies and could be applied using either an online or offline paradigm.

First clinical implementation of real-time, real anatomy tracking and radiation beam control.

PURPOSE: We describe the acceptance testing, commissioning, periodic quality assurance, and workflow procedures developed for the first clinically implemented magnetic resonance imaging-guided radiation therapy (MR-IGRT) system for real-time tracking and beam control. METHODS: The system utilizes real-time cine imaging capabilities at 4 frames per second for real-time tracking and beam control. Testing of the system was performed using an in-house developed motion platform and a commercially available motion phantom. Anatomical tracking is performed by first identifying a target (a region of interest that is either tissue to be treated or a critical structure) and generating a contour around it. A boundary contour is also created to identify tracking margins. The tracking algorithm deforms the anatomical contour (target or a normal organ) on every subsequent cine frame and compares it to the static boundary contour. If the anatomy of interest moves outside the boundary, the radiation delivery is halted until the tracked anatomy returns to treatment portal. The following were performed to validate and clinically implement the system: (a) spatial integrity evaluation; (b) tracking accuracy; (c) latency; (d) relative point dose and spatial dosimetry; (e) development of clinical workflow for gating; and (f) independent verification by an outside credentialing service. RESULTS: The spatial integrity of the MR system was found to be within 2 mm over a 45-cm diameter field-of-view. The tracking accuracy for geometric targets was within 1.2 mm. The average system latency was measured to be within 394 ms. The dosimetric accuracy using ionization chambers was within 1.3% ± 1.7%, and the dosimetric spatial accuracy was within 2 mm. The phantom irradiation for the outside credentialing service had satisfactory results, as well. CONCLUSIONS: The first clinical MR-IGRT system was validated for real-time tracking and gating capabilities and shown to be reliable and accurate. Patient workflow methods were developed for efficient treatment. Periodic quality assurance tests can be efficiently performed with commercially available equipment to ensure accurate system performance.

Remote Cherenkov imaging-based quality assurance of a magnetic resonance image-guided radiotherapy system.

PURPOSE: Tools to perform regular quality assurance of magnetic resonance image-guided radiotherapy (MRIgRT) systems should ideally be independent of interference from the magnetic fields. Remotely acquired optical Cherenkov imaging-based dosimetry measurements in water were investigated for this purpose, comparing measures of dose accuracy, temporal dynamics, and overall integrated IMRT delivery. METHODS: A 40 × 30.5 × 37.5 cm3 water tank doped with 1 g/L of quinine sulfate was imaged using an intensified charge-coupled device (ICCD) to capture the Cherenkov emission while being irradiated by a commercial MRIgRT system (ViewRay™). The ICCD was placed down-bore at the end of the couch, 4 m from treatment isocenter and behind the 5-Gauss line of the 0.35-T MRI. After establishing optimal camera acquisition settings, square beams of increasing size (4.2 × 4.2 cm2 , 10.5 × 10.5 cm2 , and 14.7 × 14.7 cm2 ) were imaged at 0.93 frames per second, from an individual cobalt-60 treatment head, to develop projection measures related to percent depth dose (PDD) curves and cross beam profiles (CPB). These Cherenkov-derived measurements were compared to ionization chamber (IC) and radiographic film dosimetry data, as well as simulation data from the treatment planning system (TPS). An intensity-modulated radiotherapy (IMRT) commissioning plan from AAPM TG-119 (C4:C-Shape) was also imaged at 2.1 frames per second, and the single linear sum image from 509 s of plan delivery was compared to the dose volume prediction generated by the TPS using gamma index analysis. RESULTS: Analysis of standardized test target images (1024 × 1024 pixels) yielded a pixel resolution of 0.37 mm/pixel. The beam width measured from the Cherenkov image-generated projection CBPs was within 1 mm accuracy when compared to film measurements for all beams. The 502 point measurements (i.e., pixels) of the Cherenkov image-based projection percent depth dose curves (pPDDs) were compared to pPDDs simulated by the treatment planning system (TPS), with an overall average error of 0.60%, 0.56%, and 0.65% for the 4.2, 10.5, and 14.7 cm square beams, respectively. The relationships between pPDDs and central axis PDDs derived from the TPS were used to apply a weighting factor to the Cherenkov pPDD, so that the Cherenkov data could be directly compared to IC PDDs (average error of -0.07%, 0.10%, and -0.01% for the same sized beams, respectively). Finally, the composite image of the TG-119 C4 treatment plan achieved a 95.1% passing rate using 4%/4 mm gamma index agreement criteria between Cherenkov intensity and TPS dose volume data. CONCLUSIONS: This is the first examination of Cherenkov-generated pPDDs and pCBPs in an MR-IGRT system. Cherenkov imaging measurements were fast to acquire, and minimal error was observed overall. Cherenkov imaging also provided novel real-time data for IMRT QA. The strengths of this imaging are the rapid data capture ability providing real-time, high spatial resolution data, combined with the remote, noncontact nature of imaging. The biggest limitation of this method is the two-dimensional (2D) projection-based imaging of three-dimensional (3D) dose distributions through the transparent water tank.

Phase I trial of stereotactic MR-guided online adaptive radiation therapy (SMART) for the treatment of oligometastatic or unresectable primary malignancies of the abdomen.

PURPOSE/OBJECTIVES: SBRT is used to treat oligometastatic or unresectable primary abdominal malignancies, although ablative dose delivery is limited by proximity of organs-at-risk (OAR). Stereotactic, magnetic resonance (MR)-guided online-adaptive radiotherapy (SMART) may improve SBRT's therapeutic ratio. This prospective Phase I trial assessed feasibility and potential advantages of SMART to treat abdominal malignancies. MATERIALS/METHODS: Twenty patients with oligometastatic or unresectable primary liver (n = 10) and non-liver (n = 10) abdominal malignancies underwent SMART. Initial plans prescribed 50 Gy/5 fractions (BED 100 Gy) with goal 95% PTV coverage by 95% of prescription, subject to hard OAR constraints. Daily real-time online-adaptive plans were created as needed, based on daily setup MR-image-set tumor/OAR "anatomy-of-the-day" to preserve hard OAR constraints, escalate PTV dose, or both. Treatment times, patient outcomes, and dosimetric comparisons between initial and adaptive plans were prospectively recorded. RESULTS: Online adaptive plans were created at time of treatment for 81/97 fractions, due to initial plan violation of OAR constraints (61/97) or observed opportunity for PTV dose escalation (20/97). Plan adaptation increased PTV coverage in 64/97 fractions. Zero Grade ≥ 3 acute (<6 months) treatment-related toxicities were observed. DISCUSSION: SMART is clinically deliverable and safe, allowing PTV dose escalation and/or simultaneous OAR sparing compared to non-adaptive abdominal SBRT.

Performance of a multi leaf collimator system for MR-guided radiation therapy.

PURPOSE: The purpose of this study was to investigate and characterize the performance of a Multi Leaf Collimator (MLC) designed for Cobalt-60 based MR-guided radiation therapy system in a 0.35 T magnetic field. METHODS: The MLC design and unique assembly features in the ViewRay MRIdian system were first reviewed. The RF cage shielding of MLC motor and cables were evaluated using ACR phantoms with real-time imaging and quantified by signal-to-noise ratio. The dosimetric characterizations, including the leaf transmission, leaf penumbra, tongue-and-groove effect, were investigated using radiosensitive films. The output factor of MLC-defined fields was measured with ionization chambers for both symmetric fields from 2.1 × 2.1 cm2 to 27.3 × 27.3 cm2 and asymmetric fields from 10.5 × 10.5 cm2 to 10.5 × 2.0 cm2 . Multi leaf collimator (MLC) positional accuracy was assessed by delivering either a picket fence (PF) style pattern on radiochromic films with wire-jig phantom or double and triple-rectangular patterns on ArcCheck-MR (Sun Nuclear, Melbourne, FL, USA) with gamma analysis as the pass/fail indicator. Leaf speed tests were performed to assess the capability of full range leaf travel within manufacture's specifications. Multi leaf collimator plan delivery reproducibility was tested by repeatedly delivering both open fields and fields with irregular shaped segments over 1-month period. RESULTS: Comparable SNRs within 4% were observed for MLC moving and stationary plans on vendor-reconstructed images, and the direct k-space reconstructed images showed that the three SNRs are within 1%. The maximum leaf transmission for all three MLCs was less than 0.35% and the average leakage was 0.153 ± 0.006%, 0.151 ± 0.008%, and 0.159 ± 0.015% for head 1, 2, and 3, respectively. Both the leaf edge and leaf end penumbra showed comparable values within 0.05 cm, and the measured values are within 0.1 cm with TPS values. The leaf edge TG effect indicated 10% underdose and the leaf end TG showed a shifted dose distribution with 0.3 cm offset. The leaf positioning test showed a 0.2 cm accuracy in the PF style test, and a gamma passing rate above 96% was observed with a 3%/2 mm criteria when comparing the measured double/triple-rectangular pattern fluence with TPS calculated fluence. The average leaf speed when executing the test plan fell in a range from 1.86 to 1.95 cm/s. The measured and TPS calculated output factors were within 2% for squared fields and within 3% for rectangular fields. The reproducibility test showed the deviation of output factors were well within 2% for square fields and the gamma passing rate within 1.5% for fields with irregular segments. The Monte Carlo predicted output factors were within 2% compared to TPS values. 15 out of the 16 IMRT plans have gamma passing rate more than 98% compared to the TPS fluence with an average passing rate of 99.1 ± 0.6%. CONCLUSION: The MRIdian MLC has a good RF noise shielding design, low radiation leakage, good positioning accuracy, comparable TG effect, and can be modeled by an independent Monte Carlo calculation platform.

A method to reconstruct and apply 3D primary fluence for treatment delivery verification.

MOTIVATION: In this study, a method is reported to perform IMRT and VMAT treatment delivery verification using 3D volumetric primary beam fluences reconstructed directly from planned beam parameters and treatment delivery records. The goals of this paper are to demonstrate that 1) 3D beam fluences can be reconstructed efficiently, 2) quality assurance (QA) based on the reconstructed 3D fluences is capable of detecting additional treatment delivery errors, particularly for VMAT plans, beyond those identifiable by other existing treatment delivery verification methods, and 3) QA results based on 3D fluence calculation (3DFC) are correlated with QA results based on physical phantom measurements and radiation dose recalculations. METHODS: Using beam parameters extracted from DICOM plan files and treatment delivery log files, 3D volumetric primary fluences are reconstructed by forward-projecting the beam apertures, defined by the MLC leaf positions and modulated by beam MU values, at all gantry angles using first-order ray tracing. Treatment delivery verifications are performed by comparing 3D fluences reconstructed using beam parameters in delivery log files against those reconstructed from treatment plans. Passing rates are then determined using both voxel intensity differences and a 3D gamma analysis. QA sensitivity to various sources of errors is defined as the observed differences in passing rates. Correlations between passing rates obtained from QA derived from both 3D fluence calculations and physical measurements are investigated prospectively using 20 clinical treatment plans with artificially introduced machine delivery errors. RESULTS: Studies with artificially introduced errors show that common treatment delivery problems including gantry angle errors, MU errors, jaw position errors, collimator rotation errors, and MLC leaf position errors were detectable at less than normal machine tolerances. The reported 3DFC QA method has greater sensitivity than measurement-based QA methods. Statistical analysis-based Spearman's correlations shows that the 3DFC QA passing rates are significantly correlated with passing rates of physical phantom measurement-based QA methods. CONCLUSION: Among measurement-less treatment delivery verification methods, the reported 3DFC method is less demanding than those based on full dose re-calculations, and more comprehensive than those that solely checks beam parameters in treatment log files. With QA passing rates correlating to measurement-based passing rates, the 3DFC QA results could be useful for complementing the physical phantom measurements, or verifying treatment deliveries when physical measurements are not available. For the past 4+ years, the reported method has been implemented at authors' institution 1) as a complementary metric to physical phantom measurements for pretreatment, patient-specific QA of IMRT and VMAT plans, and 2) as an important part of the log file-based automated verification of daily patient treatment deliveries. It has been demonstrated to be useful in catching both treatment plan data transfer errors and treatment delivery problems.

Three-Dimensional Dosimetric Validation of a Magnetic Resonance Guided Intensity Modulated Radiation Therapy System.

PURPOSE: To validate the dosimetric accuracy of a commercially available magnetic resonance guided intensity modulated radiation therapy (MRgIMRT) system using a hybrid approach: 3-dimensional (3D) measurements and Monte Carlo calculations. METHODS AND MATERIALS: We used PRESAGE radiochromic plastic dosimeters with remote optical computed tomography readout to perform 3D high-resolution measurements, following a novel remote dosimetry protocol. We followed the intensity modulated radiation therapy commissioning recommendations of American Association of Physicists in Medicine Task Group 119, adapted to incorporate 3D data. Preliminary tests ("AP" and "3D-Bands") were delivered to 9.5-cm usable diameter cylindrical PRESAGE dosimeters to validate the treatment planning system (TPS) for nonmodulated deliveries; assess the sensitivity, uniformity, and rotational symmetry of the PRESAGE dosimeters; and test the robustness of the remote dosimetry protocol. Following this, 4 clinical MRgIMRT plans ("MultiTarget," "Prostate," "Head/Neck," and "C-Shape") were measured using 13-cm usable diameter PRESAGE dosimeters. For all plans, 3D-γ (3% or 3 mm global, 10% threshold) passing rates were calculated and 3D-γ maps were examined. Point doses were measured with an IBA-CC01 ionization chamber for validation of absolute dose. Finally, by use of an in-house-developed, GPU-accelerated Monte Carlo algorithm (gPENELOPE), we independently calculated dose for all 6 Task Group 119 plans and compared against the TPS. RESULTS: For PRESAGE measurements, 3D-γ analysis yielded passing rates of 98.7%, 99.2%, 98.5%, 98.0%, 99.2%, and 90.7% for AP, 3D-Bands, MultiTarget, Prostate, Head/Neck, and C-Shape, respectively. Ion chamber measurements were within an average of 0.5% (±1.1%) from the TPS dose. Monte Carlo calculations demonstrated good agreement with the TPS, with a mean 3D-γ passing rate of 98.5% ± 1.9% using a stricter 2%/2-mm criterion. CONCLUSIONS: We have validated the dosimetric accuracy of a commercial MRgIMRT system using high-resolution 3D techniques. We have demonstrated for the first time that hybrid 3D remote dosimetry is a comprehensive and feasible approach to commissioning MRgIMRT. This may provide better sensitivity in error detection compared with standard 2-dimensional measurements and could be used when implementing complex new magnetic resonance guided radiation therapy technologies.

Technical Note: Magnetic field effects on Gafchromic-film response in MR-IGRT.

PURPOSE: Magnetokinetic changes may affect crystal orientation and polymerization within the active layer of radiochromic film (RCF). This effect is investigated in a magnetic resonance image-guided radiotherapy unit within the context of film dosimetry. METHODS: Gafchromic EBT2 RCF was irradiated in a 30 × 30 × 30 cm3 solid water phantom using a Co-60 MRI guided radiotherapy system (B = 0.35 T) under normal operating conditions, and under the exact conditions and setup without a magnetic field. Fifteen 20.3 × 25.4 cm2 EBT2 film sheets were placed at three different depths (d = 0.5, 5, and 10 cm) using five different treatment plans. The plans were computed using the MRIdian (ViewRay, Inc.) treatment planning system to deliver doses between 0 and 17.6 Gy. Films were analyzed before and after irradiation to obtain the net optical density (netOD) for each color channel separately. Scanning electron microscope (SEM) images were obtained to compare the active layer of selected samples. RESULTS: The results indicated that the red channel netOD decreased between 0.013 and 0.123 (average of 0.060 ± 0.033) for doses above 2.8 Gy, with a linear increase in this effect for higher doses. Green channel netOD showed similar results with a decrease between 0.012 and 0.105 (average of 0.041 ± 0.027) for doses above 3.5 Gy. The blue channel showed the weakest effect with a netOD decrease between 0.013 and 0.029 (average of 0.020 ± 0.006) for doses above 8.0 Gy. SEM images show changes in crystal orientation within active layer in RCF exposed in a magnetic field. CONCLUSIONS: The presence of a magnetic field affects crystal orientation and polymerization during irradiation, where netOD decreased by an average of 8.7%, 8.0%, and 4.3% in the red, green, and blue channels, respectively. The under response was dependent on dose and differed by up to 15% at 17.6 Gy.