Evaluation of the impact of cardiac implantable electronic devices on cine MRI for real-time adaptive cardiac radioablation on a 1.5 T MR-linac.

BACKGROUND: Stereotactic arrhythmia radioablation (STAR) is a novel treatment approach for refractory ventricular tachycardia (VT). The risk of treatment-induced toxicity and geographic miss can be reduced with online MRI-guidance on an MR-linac. However, most VT patients carry cardiac implantable electronic devices (CIED), which compromise MR images. PURPOSE: Robust MR-linac imaging sequences are required for cardiac visualization and accurate motion monitoring in presence of a CIED during MRI-guided STAR. We optimized two clinically available cine sequences for cardiorespiratory motion estimation in presence of a CIED on a 1.5 T MR-linac. The image quality, motion estimation accuracy, and geometric fidelity using these cine sequences were evaluated. METHODS: Clinically available 2D balanced steady-state free precession (bSSFP, voxel size = 3.0 × $\times$ 3.0 × $\times$ 10 mm3, Tscan = 96 ms, bandwidth (BW) = 1884 Hz/px) and T 1 ${\rm T}_{1}$ -spoiled gradient echo ( T 1 ${\rm T}_{1}$ -GRE, voxel size = 4.0 × $ \times$ 4.0 × $ \times$ 10 mm3, Tscan = 97 ms, BW = 500 Hz/px) sequences were adjusted for real-time cardiac visualization and cardiorespiratory motion estimation on a 1.5 T Unity MR-linac (Elekta AB, Stockholm, Sweden), while complying with safety guidelines for MRI in presence of CIEDs (specific absorption rate < $ <$ 2 W/kg and d B d t < $\frac{dB}{dt}<$ 80 mT/s). Cine acquisitions were performed in five healthy volunteers, with and without an implantable cardioverter- defibrillator (ICD) placed on the clavicle, and a VT patient. Generalized divergence-curl (GDC) deformable image registration (DIR) was used for automated landmark motion estimation in the left ventricle (LV). Gaussian processes (GP), a machine-learning technique, was trained using GDC landmarks and deployed for real-time cardiorespiratory motion prediction. B 0 $B_{0}$ -mapping was performed to assess geometric image fidelity in the presence of CIEDs. RESULTS: CIEDs introduced banding artifacts partially obscuring cardiac structures in bSSFP acquisitions. In contrast, the T 1 ${\rm T}_{1}$ -GRE was more robust to CIED-induced artifacts at the expense of a lower signal-to-noise ratio. In presence of an ICD, image-based cardiorespiratory motion estimation was possible for 85% (100%) of the volunteers using the bSSFP ( T 1 ${\rm T}_{1}$ -GRE) sequence. The in-plane 2D root-mean-squared deviation (RMSD) range between GDC-derived landmarks and manual annotations using the bSSFP (T1-GRE) sequence was 3.1-3.3 (3.3-4.1) mm without ICD and 4.6-4.6 (3.2-3.3) mm with ICD. Without ICD, the RMSD between the GP-predictions and GDC-derived landmarks ranged between 0.9 and 2.2 mm (1.3-3.0 mm) for the bSSFP (T1-GRE) sequence. With ICD, the RMSD between the GP-predictions and GDC-derived landmarks ranged between 1.3 and 2.2 mm (1.2-3.2 mm) using the bSSFP (T1-GRE) sequence resulting in an RMSD-increase of 42%-143% (bSSFP) and -61%-142% (T1-GRE). Lead-induced spatial distortions ranged between -0.2 and 0.2 mm (-0.7-1.2 mm) using the bSSFP ( T 1 ${\rm T}_{1}$ -GRE) sequence. The 98th percentile range of the spatial distortions in the gross target volume of the patient was between 0.0 and 0.4 mm (0.0-1.8 mm) when using bSSFP ( T 1 ${\rm T}_{1}$ -GRE). CONCLUSIONS: Tailored bSSFP and T 1 ${\rm T}_{1}$ -GRE sequences can facilitate real-time cardiorespiratory estimation using GP trained with GDC-derived landmarks in the majority of landmark locations in the LV despite the presence of CIEDs. The need for high temporal resolution noticeably reduced achievable spatial resolution of the cine MRIs. However, the effect of the CIED-induced artifacts is device, patient and sequence dependent and requires specific assessment per case.

Automated dose evaluation on daily cone-beam computed tomography for breast cancer patients.

BACKGROUND AND PURPOSE: Our goal was to develop a workflow to automatically evaluate delivered dose on daily cone beam computed tomography (CBCT) in all breast cancer patients to assess dosimetric impact of anatomical changes and guide decision-making for offline plan adaptation. MATERIALS AND METHODS: The workflow automatically processes the daily CBCTs of all breast cancer patients receiving local and locoregional radiotherapy. The planning-CT is registered to the CBCT to create a synthetic CT and propagate contours. A forward dose calculation is performed, and DVH parameters are extracted and printed in a report. We evaluated the workflow on a group level and in a subset of 30 patients on a patient-specific level, including comparison to clinical evaluation on additional planning-CT in 10 patients. RESULTS: 7454 fractions in 647 patients were analyzed over a period of seven months. Median breast clinical target volume V95% was ≥ 95 % for 97 % of the patients. The workflow would have provided useful additional insights for decision-making for the requirement of plan adaptation, based on debatable disagreement with the clinical decision in half of the cases with an additional planning-CT. The workflow also identified cases with suboptimal coverage not identified in the clinical procedure. CONCLUSION: We developed a fully automated workflow for dose evaluation on daily CBCT for local and locoregional breast radiotherapy. We have demonstrated its potential for aiding decision-making for plan adaptation in patients with changing anatomy and its capability to highlight patients that may receive suboptimal treatment and require closer clinical evaluation of treatment quality.

Investigating the use of comprehensive motion monitoring for intrafraction 3D drift assessment of hypofractionated prostate cancer patients on a 1.5T magnetic resonance imaging radiotherapy system.

This work investigates the use of a multi-2D cine magnetic resonance imaging-based comprehensive motion monitoring (CMM) system for the assessment of prostate intrafraction 3D drifts. The data of six healthy volunteers were analyzed and the values of a clinically-relevant registration quality factor metric exported by CMM were presented. Additionally, the CMM-derived prostate motion was compared to a 3D-based reference and the 2D-3D tracking agreement was reported. Due to the low quality of SI motion tracking (often > 2 mm tracking mismatch between anatomical planes) we conclude that further improvements are desirable prior to clinical introduction of CMM for prostate drift corrections.

Generalized div-curl based regularization for physically constrained deformable image registration.

Variational image registration methods commonly employ a similarity metric and a regularization term that renders the minimization problem well-posed. However, many frequently used regularizations such as smoothness or curvature do not necessarily reflect the underlying physics that apply to anatomical deformations. This, in turn, can make the accurate estimation of complex deformations particularly challenging. Here, we present a new highly flexible regularization inspired from the physics of fluid dynamics which allows applying independent penalties on the divergence and curl of the deformations and/or their nth order derivative. The complexity of the proposed generalized div-curl regularization renders the problem particularly challenging using conventional optimization techniques. To this end, we develop a transformation model and an optimization scheme that uses the divergence and curl components of the deformation as control parameters for the registration. We demonstrate that the original unconstrained minimization problem reduces to a constrained problem for which we propose the use of the augmented Lagrangian method. Doing this, the equations of motion greatly simplify and become managable. Our experiments indicate that the proposed framework can be applied on a variety of different registration problems and produce highly accurate deformations with the desired physical properties.

On Patient Experience and Anxiety During Treatment With Magnetic Resonance-Guided Radiation Therapy.

Purpose: To assess patient experience and anxiety during magnetic resonance (MR)-guided radiation therapy (MRgRT) using a hybrid 1.5Tesla (T) MR-guided linear accelerator (MR-Linac) when offered calming video content. Methods and Materials: A single-center study was conducted within the Multi-Outcome Evaluation of Radiation Therapy Using the MR-Linac (MOMENTUM) cohort. Patients were offered to watch calming video content on a video monitor during treatment. Questionnaires were used to assess patient experience (MR-Linac patient-reported experience) and anxiety (State-Trait Anxiety Inventory, STAI) at first treatment fraction (M1) and at third, fourth, or fifth treatment fraction (M2). Paired t tests were used to test for significant differences, and effect sizes (ESs) were used to estimate the magnitude of the difference. Results: Between November 2021 and November 2022, 66 patients were included. The majority were men (n = 59, 89%). MRgRT was most frequently delivered to prostate cancer (n = 45, 68%) followed by a lesion in the pancreas (n = 8, 12%). At M1 and M2, 24 of 59 patients (41%) preferred to watch calming video content. One patient was not able to look at the video monitor comfortably at M1. Patient experience was generally favorable or neutral; tingling sensations were reported by 17% of patients. Anxiety levels were high (16%), moderate (18%), or low to none (67%) prior to M1. STAI scores were 33 (SD, 9) prior to M1 and 29 (SD, 7) after M1 (ES, 0.7; P < .001). STAI scores were 32 (SD, 9) prior to M2 and 31 (SD, 8) after M2 (ES, 0.4; P = .009). Conclusions: Patients were able to comfortably view the video monitor during MRgRT. Consequently, this setup could be used for future applications, such as biofeedback. A sizable minority of patients preferred to watch calming videos that distracted them during treatment. Although the patients' experience was overall excellent, anxiety was reported. Anxiety levels were highest prior to treatment and decreased after treatment.

Bringing online adaptive radiotherapy to a standard C-arm linac.

Current online adaptive radiotherapy (oART) workflows require dedicated equipment. Our aim was to develop and implement an oART workflow for a C-arm linac which can be performed using standard clinically available tools. A workflow was successfully developed and implemented. Three patients receiving palliative radiotherapy for bladder cancer were treated, with 33 of 35 total fractions being delivered with the cone-beam computed tomography (CBCT)-guided oART workflow. Average oART fraction duration was 24 min from start of CBCT acquisition to end of beam on. This work shows how oART could be performed without dedicated equipment, broadening oART availability for application at existing treatment machines.

Treatment planning evaluation and experimental validation of the magnetic resonance-based intrafraction drift correction.

Background and purpose: MRI-guided online adaptive treatments can account for interfractional variations, however intrafraction motion reduces treatment accuracy. Intrafraction plan adaptation methods, such as the Intrafraction Drift Correction (IDC) or sub-fractionation, are needed. IDC uses real-time automatic monitoring of the tumor position to initiate plan adaptations by repositioning segments. IDC is a fast adaptation method that occurs only when necessary and this method could enable margin reduction. This research provides a treatment planning evaluation and experimental validation of the IDC. Materials and methods: An in silico treatment planning evaluation was performed for 13 prostate patients mid-treatment without and with intrafraction plan adaptation (IDC and sub-fractionation). The adaptation methods were evaluated using dose volume histogram (DVH) metrics. To experimentally verify IDC a treatment was mimicked whereby a motion phantom containing an EBT3 film moved mid-treatment, followed by repositioning of segments. In addition, the delivered treatment was irradiated on a diode array phantom for plan quality assurance purposes. Results: The planning study showed benefits for using intrafraction adaptation methods relative to no adaptation, where the IDC and sub-fractionation showed consistently improved target coverage with median target coverages of 100.0%. The experimental results verified the IDC with high minimum gamma passing rates of 99.1% and small mean dose deviations of maximum 0.3%. Conclusion: The straightforward and fast IDC technique showed DVH metrics consistent with the sub-fractionation method using segment weight re-optimization for prostate patients. The dosimetric and geometric accuracy was shown for a full IDC workflow using film and diode array dosimetry.

Experimental demonstration of real-time cardiac physiology-based radiotherapy gating for improved cardiac radioablation on an MR-linac.

BACKGROUND: Cardiac radioablation is a noninvasive stereotactic body radiation therapy (SBRT) technique to treat patients with refractory ventricular tachycardia (VT) by delivering a single high-dose fraction to the VT isthmus. Cardiorespiratory motion induces position uncertainties resulting in decreased dose conformality. Electocardiograms (ECG) are typically used during cardiac MRI (CMR) to acquire images in a predefined cardiac phase, thus mitigating cardiac motion during image acquisition. PURPOSE: We demonstrate real-time cardiac physiology-based radiotherapy beam gating within a preset cardiac phase on an MR-linac. METHODS: MR images were acquired in healthy volunteers (n = 5, mean age = 29.6 years, mean heart-rate (HR) = 56.2 bpm) on the 1.5 T Unity MR-linac (Elekta AB, Stockholm, Sweden) after obtaining written informed consent. The images were acquired using a single-slice balance steady-state free precession (bSSFP) sequence in the coronal or sagittal plane (TR/TE = 3/1.48 ms, flip angle = 48 ∘ $^{\circ }$ , SENSE = 1.5, field-of-view = 400 × 207 $\text{field-of-view} = {400}\times {207}$ mm 2 ${\text{mm}}^{2}$ , voxel size = 3 × 3 × 15 $3\times 3\times 15$ mm 3 ${\rm mm}^{3}$ , partial Fourier factor = 0.65, frame rate = 13.3 Hz). In parallel, a 4-lead ECG-signal was acquired using MR-compatible equipment. The feasibility of ECG-based beam gating was demonstrated with a prototype gating workflow using a Quasar MRI4D motion phantom (IBA Quasar, London, ON, Canada), which was deployed in the bore of the MR-linac. Two volunteer-derived combined ECG-motion traces (n = 2, mean age = 26 years, mean HR = 57.4 bpm, peak-to-peak amplitude = 14.7 mm) were programmed into the phantom to mimic dose delivery on a cardiac target in breath-hold. Clinical ECG-equipment was connected to the phantom for ECG-voltage-streaming in real-time using research software. Treatment beam gating was performed in the quiescent phase (end-diastole). System latencies were compensated by delay time correction. A previously developed MRI-based gating workflow was used as a benchmark in this study. A 15-beam intensity-modulated radiotherapy (IMRT) plan ( 1 × 6.25 ${1}\times {6.25}$ Gy) was delivered for different motion scenarios onto radiochromic films. Next, cardiac motion was then estimated at the basal anterolateral myocardial wall via normalized cross-correlation-based template matching. The estimated motion signal was temporally aligned with the ECG-signal, which were then used for position- and ECG-based gating simulations in the cranial-caudal (CC), anterior-posterior (AP), and right-left (RL) directions. The effect of gating was investigated by analyzing the differences in residual motion at 30, 50, and 70% treatment beam duty cycles. RESULTS: ECG-based (MRI-based) beam gating was performed with effective duty cycles of 60.5% (68.8%) and 47.7% (50.4%) with residual motion reductions of 62.5% (44.7%) and 43.9% (59.3%). Local gamma analyses (1%/1 mm) returned pass rates of 97.6% (94.1%) and 90.5% (98.3%) for gated scenarios, which exceed the pass rates of 70.3% and 82.0% for nongated scenarios, respectively. In average, the gating simulations returned maximum residual motion reductions of 88%, 74%, and 81% at 30%, 50%, and 70% duty cycles, respectively, in favor of MRI-based gating. CONCLUSIONS: Real-time ECG-based beam gating is a feasible alternative to MRI-based gating, resulting in improved dose delivery in terms of high γ -pass $\gamma {\text{-pass}}$ rates, decreased dose deposition outside the PTV and residual motion reduction, while by-passing cardiac MRI challenges.

Influence of magnetic field on a novel scintillation dosimeter in a 1.5 T MR-linac.

For commissioning and quality assurance for adaptive workflows on the MR-linac, a dosimeter which can measure time-resolved dose during MR image acquisition is desired. The Blue Physics model 10 scintillation dosimeter is potentially an ideal detector for such measurements. However, some detectors can be influenced by the magnetic field of the MR-linac. To assess the calibration methods and magnetic field dependency of the Blue Physics scintillator in the 1.5 T MR-linac. Several calibration methods were assessed for robustness. Detector characteristics and the influence of the calibration methods were assessed based on dose reproducibility, dose linearity, dose rate dependency, relative output factor (ROF), percentage depth dose profile, axial rotation and the radial detector orientation with respect to the magnetic field. The potential application of time-resolved dynamic dose measurements during MRI acquisition was assessed. A variation of calibration factors was observed for different calibration methods. Dose reproducibility, dose linearity and dose rate stability were all found to be within tolerance and were not significantly affected by different calibration methods. Measurements with the detector showed good correspondence with reference chambers. The ROF and radial orientation dependence measurements were influenced by the calibration method used. Axial detector dependence was assessed and relative readout differences of up to 2.5% were observed. A maximum readout difference of 10.8% was obtained when rotating the detector with respect to the magnetic field. Importantly, measurements with and without MR image acquisition were consistent for both static and dynamic situations. The Blue Physics scintillation detector is suitable for relative dosimetry in the 1.5 T MR-linac when measurements are within or close to calibration conditions.

Performance characterization of a novel hybrid dosimetry insert for simultaneous spatial, temporal, and motion-included dosimetry for MR-linac.

BACKGROUND: Several (online) adaptive radiotherapy procedures are available to maximize healthy tissue sparing in the presence of inter/intrafractional motion during stereotactic body radiotherapy (SBRT) on an MR-linac. The increased treatment complexity and the motion-delivery interplay during these treatments require MR-compatible motion phantoms with time-resolved dosimeters to validate end-to-end workflows. This is not possible with currently available phantoms. PURPOSE: Here, we demonstrate a new commercial hybrid film-scintillator cassette, combining high spatial resolution radiochromic film with four time-resolved plastic scintillator dosimeters (PSDs) in an MRI-compatible motion phantom. METHODS: First, the PSD's performance for consistency, dose linearity, and pulse repetition frequency (PRF) dependence was evaluated using an RW3 solid water slab phantom. We then demonstrated the MRI4D scintillator cassette's suitability for time-resolved and motion-included quality assurance for adapt-to-shape (ATS), trailing, gating, and multileaf collimator (MLC) tracking adaptations on a 1.5 T MR-linac. To do this, the cassette was inserted into the Quasar MRI4D phantom, which we used statically or programmed with artificial and patient-derived motion. Simultaneously with dose measurements, the beam-gating latency was estimated from the time difference between the target entering/leaving the gating window and the beam-on/off times derived from the time-resolved dose measurements. RESULTS: Experiments revealed excellent detector consistency (standard deviation ≤ $\le$ 0.6%), dose linearity (R2 = 1), and only very low PRF dependence ( ≤ $\le$ 0.4%). The dosimetry cassette demonstrated a near-perfect agreement during an ATS workflow between the time-resolved PSD and treatment planning system (TPS) dose (0%-2%). The high spatial resolution film measurements confirmed this with a 1%/1-mm local gamma pass-rate of 90%. When trailing patient-derived prostate motion for a prostate SBRT delivery, the time-resolved cassette measurements demonstrated how trailing mitigated the motion-induced dose reductions from 1%-17% to 1%-2% compared to TPS dose. The cassette's simultaneously measured spatial dose distribution highlighted the dosimetric gain of trailing by improving the 3%/3-mm local gamma pass-rates from 80% to 97% compared to the static dose. Similarly, the cassette demonstrated the benefit of real-time adaptations when compensating patient-derived respiratory motion by showing how the TPS dose was restored from 2%-56% to 0%-12% (gating) and 1%-26% to 1%-7% (MLC tracking) differences. Larger differences are explainable by TPS-PSD coregistration uncertainty combined with a steep dose gradient outside the PTV. The cassette also demonstrated how the spatial dose distributions were drastically improved by the real-time adaptations with 1%/1-mm local gamma pass-rates that were increased from 8 to 79% (gating) and from 35 to 89% (MLC tracking). The cassette-determined beam-gating latency agreed within ≤ $\le$ 12 ms with the ground truth latency measurement. Film and PSD dose agreed well for most cases (differences relative to TPS dose < $<$ 4%), while film-PSD coregistration uncertainty caused relative differences of 5%-8%. CONCLUSIONS: This study demonstrates the excellent suitability of a new commercial hybrid film-scintillator cassette for simultaneous spatial, temporal, and motion-included dosimetry.

MRI-Guided Radiation Therapy Systems.

MR-Guided Radiation Therapy (MRIgRT) has been made possible only due to the ingenuity and commitment of commercial radiation therapy system vendors. Unlike conventional linear accelerator systems, MRIgRT systems have had to overcome significant and previously untested techniques to integrate the MRI systems with the radiation therapy delivery systems. Each of these three commercial systems has developed different approaches to integrating their MR and Linac functions. Each has also decided on a different main magnetic field strength, from 0.35T to 1.5T, as well as different design philosophies for other systems, such as the patient support assembly and treatment planning workflow. This paper is intended to provide the reader with a detailed understanding of each system's configuration so that the reader can better interpret the scientific literature concerning these commercial MRIgRT systems.

SOLID: a novel similarity metric for mono-modal and multi-modal deformable image registration.

Medical image registration is an integral part of various clinical applications including image guidance, motion tracking, therapy assessment and diagnosis. We present a robust approach for mono-modal and multi-modal medical image registration. To this end, we propose the novel shape operator based local image distance (SOLID) which estimates the similarity of images by comparing their second-order curvature information. Our similarity metric is rigorously tailored to be suitable for comparing images from different medical imaging modalities or image contrasts. A critical element of our method is the extraction of local features using higher-order shape information, enabling the accurate identification and registration of smaller structures. In order to assess the efficacy of the proposed similarity metric, we have implemented a variational image registration algorithm that relies on the principle of matching the curvature information of the given images. The performance of the proposed algorithm has been evaluated against various alternative state-of-the-art variational registration algorithms. Our experiments involve mono-modal as well as multi-modal and cross-contrast co-registration tasks in a broad variety of anatomical regions. Compared to the evaluated alternative registration methods, the results indicate a very favorable accuracy, precision and robustness of the proposed SOLID method in various highly challenging registration tasks.

Experimental validation of multi-fraction online adaptations in magnetic resonance guided radiotherapy.

Background and purpose: Radiotherapy plan verification is generally performed on the reference plan based on the pre-treatment anatomy. However, the introduction of online adaptive treatments demands a new approach, as plans are created daily on different anatomies. The aim of this study was to experimentally validate the accuracy of total doses of multi-fraction plan adaptations in magnetic resonance imaging guided radiotherapy in a phantom study, isolated from the uncertainty of deformable image registration. Materials and methods: We experimentally verified the total dose, measured on external beam therapy 3 (EBT3) film, using a treatment with five online adapted fractions. Three series of experiments were performed, each focusing on a category of inter-fractional variation; translations, rotations and body modifications. Variations were introduced during each fraction and adapted plans were generated and irradiated. Single fraction doses and total doses over five online adapted fractions were investigated. Results: The online adapted measurements and calculations showed a good agreement for single fractions and multi-fraction treatments for the dose profiles, gamma passing rates, dose deviations and distances to agreement. The gamma passing rate using a 2%/2 mm criterion ranged from 99.2% to 99.5% for a threshold dose of 10% of the maximum dose (Dmax) and from 96.2% to 100% for a threshold dose of 90% of Dmax, for the total translations, rotations and body modifications. Conclusions: The total doses of multi-fraction treatments showed similar accuracies compared to single fraction treatments, indicating an accurate dosimetric outcome of a multi-fraction treatment in adaptive magnetic resonance imaging guided radiotherapy.

Gating and intrafraction drift correction on a 1.5 T MR-Linac: Clinical dosimetric benefits for upper abdominal tumors.

This work reports on the first seven patients treated with gating and baseline drift correction on the high-field MR-Linac system. Dosimetric analysis showed that the active motion management system improved congruence to the planned dose, efficiently mitigating detrimental effects of intrafraction motion in the upper abdomen.

Integration of operator-validated contours in deformable image registration for dose accumulation in radiotherapy.

Background and Purpose: Deformable image registration (DIR) is a core element of adaptive radiotherapy workflows, integrating daily contour propagation and/or dose accumulation in their design. Propagated contours are usually manually validated and may be edited, thereby locally invalidating the registration result. This means the registration cannot be used for dose accumulation. In this study we proposed and evaluated a novel multi-modal DIR algorithm that incorporated contour information to guide the registration. This integrates operator-validated contours with the estimated deformation vector field and warped dose. Materials and Methods: The proposed algorithm consisted of both a normalized gradient field-based data-fidelity term on the images and an optical flow data-fidelity term on the contours. The Helmholtz-Hodge decomposition was incorporated to ensure anatomically plausible deformations. The algorithm was validated for same- and cross-contrast Magnetic Resonance (MR) image registrations, Computed Tomography (CT) registrations, and CT-to-MR registrations for different anatomies, all based on challenging clinical situations. The contour-correspondence, anatomical fidelity, registration error, and dose warping error were evaluated. Results: The proposed contour-guided algorithm considerably and significantly increased contour overlap, decreasing the mean distance to agreement by a factor of 1.3 to 13.7, compared to the best algorithm without contour-guidance. Importantly, the registration error and dose warping error decreased significantly, by a factor of 1.2 to 2.0. Conclusions: Our contour-guided algorithm ensured that the deformation vector field and warped quantitative information were consistent with the operator-validated contours. This provides a feasible semi-automatic strategy for spatially correct warping of quantitative information even in difficult and artefacted cases.

Feasibility of online radial magnetic resonance imaging for adaptive radiotherapy of pancreatic tumors.

Background and purpose: Online adaptive magnetic resonance (MR)-guided treatment planning for pancreatic tumors on 1.5T systems typically employs Cartesian 3D T 2w magnetic resonance imaging (MRI). The main disadvantage of this sequence is that respiratory motion results in substantial blurring in the abdomen, which can hamper delineation accuracy. This study investigated the use of two motion-robust radial MRI sequences as main delineation scan for pancreatic MR-guided radiotherapy. Materials and methods: Twelve patients with pancreatic tumors were imaged with a 3D T 2w scan, a Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction (PROPELLER) scan (partially overlapping strips), and a 3D Vane scan (stack-of-stars), on a 1.5T MR-Linac under abdominal compression. The scans were assessed by three radiation oncologists for their suitability for online adaptive delineation. A quantitative comparison was made for gradient entropy and the effect of motion on apparent target position. Results: The PROPELLER scans were selected as first preference in 56% of the cases, the 3D T 2w in 42% and the 3D Vane in 3%. PROPELLER scans sometimes contained a large interslice variation which would have compromised delineation. Gradient entropy was significantly higher in 3D T 2w patient scans. The apparent target position was more sensitive to motion amplitude in the PROPELLER scans, but substantial offsets did not occur under 10 mm peak-to-peak. Conclusion: PROPELLER MRI may be a superior imaging sequence for pancreatic MRgRT compared to standard Cartesian sequences. The large interslice variation should be mitigated through further sequence optimization before PROPELLER can be adopted for online treatment adaptation.

Technical note: Intensity-based quality assurance criteria for deformable image registration in image-guided radiotherapy.

BACKGROUND: Deformable image registration is increasingly used in radiotherapy to adapt the treatment plan and accumulate the delivered dose. Consequently, clinical workflows using deformable image registration require quick and reliable quality assurance to accept registrations. Additionally, for online adaptive radiotherapy, quality assurance without the need for an operator to delineate contours while the patient is on the treatment table is needed. Established quality assurance criteria such as the Dice similarity coefficient or Hausdorff distance lack these qualities and also display a limited sensitivity to registration errors beyond soft tissue boundaries. PURPOSE: The purpose of this study is to investigate the existing intensity-based quality assurance criteria structural similarity and normalized mutual information for their ability to quickly and reliably identify registration errors for (online) adaptive radiotherapy and compare them to contour-based quality assurance criteria. METHODS: All criteria were tested using synthetic and simulated biomechanical deformations of 3D MR images as well as manually annotated 4D CT data. The quality assurance criteria were scored for classification performance, for their ability to predict the registration error, and for their spatial information. RESULTS: We found that besides being fast and operator-independent, the intensity-based criteria have the highest area under the receiver operating characteristic curve and provide the best input for models to predict the registration error on all data sets. Structural similarity furthermore provides spatial information with a higher gamma pass rate of the predicted registration error than commonly used spatial quality assurance criteria. CONCLUSIONS: Intensity-based quality assurance criteria can provide the required confidence in decisions about using mono-modal registrations in clinical workflows. They thereby enable automated quality assurance for deformable image registration in adaptive radiotherapy treatments.

Feasibility of delivered dose reconstruction for MR-guided SBRT of pancreatic tumors with fast, real-time 3D cine MRI.

BACKGROUND AND PURPOSE: In MR-guided SBRT of pancreatic cancer, intrafraction motion is typically monitored with (interleaved) 2D cine MRI. However, tumor surroundings are often not fully captured in these images, and motion might be distorted by through-plane movement. In this study, the feasibility of highly accelerated 3D cine MRI to reconstruct the delivered dose during MR-guided SBRT was assessed. MATERIALS AND METHODS: A 3D cine MRI sequence was developed for fast, time-resolved 4D imaging, featuring a low spatial resolution that allows for rapid volumetric imaging at 430 ms. The 3D cines were acquired during the entire beam-on time of 23 fractions of online adaptive MR-guided SBRT for pancreatic tumors on a 1.5 T MR-Linac. A 3D deformation vector field (DVF) was extracted for every cine dynamic using deformable image registration. Next, these DVFs were used to warp the partial dose delivered in the time interval between consecutive cine acquisitions. The warped dose plans were summed to obtain a total delivered dose. The delivered dose was also calculated under various motion correction strategies. Key DVH parameters of the GTV, duodenum, small bowel and stomach were extracted from the delivered dose and compared to the planned dose. The uncertainty of the calculated DVFs was determined with the inverse consistency error (ICE) in the high-dose regions. RESULTS: The mean (SD) relative (ratio delivered/planned) D99% of the GTV was 0.94 (0.06), and the mean (SD) relative D0.5cc of the duodenum, small bowel, and stomach were respectively 0.98 (0.04), 1.00 (0.07), and 0.98 (0.06). In the fractions with the lowest delivered tumor coverage, it was found that significant lateral drifts had occurred. The DVFs used for dose warping had a low uncertainty with a mean (SD) ICE of 0.65 (0.07) mm. CONCLUSION: We employed a fast, real-time 3D cine MRI sequence for dose reconstruction in the upper abdomen, and demonstrated that accurate DVFs, acquired directly from these images, can be used for dose warping. The reconstructed delivered dose showed only a modest degradation of tumor coverage, mostly attainable to baseline drifts. This emphasizes the need for motion monitoring and development of intrafraction treatment adaptation solutions, such as baseline drift corrections.

Performance of the HYPERSCINT scintillation dosimetry research platform for the 1.5 T MR-linac.

Objective.Adaptive radiotherapy techniques available on the MR-linac, such as daily plan adaptation, gating, and dynamic tracking, require versatile dosimetric detectors to validate end-to-end workflows. Plastic scintillator detectors (PSDs) offer great potential with features including: water equivalency, MRI-compatibility, and time-resolved dose measurements. Here, we characterize the performance of the HYPERSCINT RP-200 PSD (MedScint, Quebec, CA) in a 1.5 T MR-linac, and we demonstrate its suitability for dosimetry, including in a moving target.Approach.Standard techniques of detector testing were performed using a Beamscan water tank (PTW, Freiburg, DE) and compared to microDiamond (PTW, Freiburg, DE) readings. Orientation dependency was tested using the same phantom. An RW3 solid water phantom was used to evaluate detector consistency, dose linearity, and dose rate dependence. To determine the sensitivity to motion and to MRI scanning, the Quasar MRI4Dphantom (Modus, London, ON) was used statically or with sinusoidal motion (A= 10 mm,T= 4 s) to compare PSD and Semiflex ionization chamber (PTW, Freiburg, DE) readings. Conformal beams from gantry 0° and 90° were used as well as a 15-beam 8 × 7.5 Gy lung IMRT plan.Main results.Measured profiles, PDD curves and field-size dependence were consistent with the microDiamond readings with differences well within our clinical tolerances. The angular dependence gave variations up to 0.8% when not irradiating directly from behind the scintillation point. Experiments revealed excellent detector consistency between repeated measurements (SD = 0.06%), near-perfect dose linearity (R2= 1) and a dose rate dependence <0.3%. Dosimetric effects of MRI scanning (≤0.3%) and motion (≤1.3%) were minimal. Measurements were consistent with the Semiflex (differences ≤1%), and with the treatment planning system with differences of 0.8% and 0.4%, with and without motion.Significance.This study demonstrates the suitability of the HYPERSCINT PSD for accurate time-resolved dosimetry measurements in the 1.5 T MR-linac, including during MR scanning and target motion.

On the feasibility of cardiac substructure sparing in magnetic resonance imaging guided stereotactic lung radiotherapy.

BACKGROUND: Lung stereotactic body radiotherapy (SBRT) has proven an effective treatment for medically inoperable lung tumors, even for (ultra-)central tumors. Recently, there has been growing interest in radiation-induced cardiac toxicity in lung radiotherapy. More specifically, dose to cardiac (sub-)structures (CS) was found to correlate with survival after radiotherapy. PURPOSE: Our goal is first, to investigate the percentage of patients who require CS sparing in an magnetic resonance imaging guided lung SBRT workflow, and second, to quantify how successful implementation of cardiac sparing would be. METHODS: The patient cohort consists of 34 patients with stage II-IV lung cancer who were treated with SBRT between 2017 and 2020. A mid-position computed tomography (CT) image was used to create treatment plans for the 1.5 T Unity MR-linac (Elekta AB, Stockholm, Sweden) following clinical templates. Under guidance of a cardio-thoracic radiologist, 11 CS were contoured manually for each patient. Dose constraints for five CS were extracted from the literature. Patients were stratified according to their need for cardiac sparing depending on the CS dose in their non-CS constrained MR-linac treatment plans. Cardiac sparing treatment plans (CSPs) were then created and dosimetrically compared with their non-CS constrained treatment plan counterparts. CSPs complied with the departmental constraints and were considered successful when fulfilling all CS constraints, and partially successful if some CS constraints could be fulfilled. Predictors for the need for and feasibility of cardiac sparing were explored, specifically planning target volume (PTV) size, cranio-caudal (CC) distance, 3D distance, and in-field overlap volume histograms (iOVH). RESULTS: 47% of the patients (16 out of 34) were in need of cardiac sparing. A successful CSP could be created for 62.5% (10 out of 16) of these patients. Partially successful CSPs still complied with two to four CS constraints. No significant difference in dose to organs at risk (OARs) or targets was identified between CSPs and the corresponding non-CS constrained MR-linac plans. The need for cardiac sparing was found to correlate with distance in the CC direction between target and all of the individual CS (Mann-Whitney U-test p-values <10-6 ). iOVHs revealed that complying with dose constraints for CS is primarily determined by in-plane distance and secondarily by PTV size. CONCLUSION: We demonstrated that CS can be successfully spared in lung SBRT on the MR-linac for most of this patient cohort, without compromising doses to the tumor or to other OARs. CC distance between the target and CS can be used to predict the need for cardiac sparing. iOVHs, in combination with PTV size, can be used to predict if cardiac sparing will be successful for all constrained CS except the left ventricle.