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.

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.

A Framework for Assessing the Effect of Cardiac and Respiratory Motion for Stereotactic Arrhythmia Radioablation Using a Digital Phantom With a 17-Segment Model: A STOPSTORM.eu Consortium Study.

PURPOSE: The optimal motion management strategy for patients receiving stereotactic arrhythmia radioablation (STAR) for the treatment of ventricular tachycardia (VT) is not fully known. We developed a framework using a digital phantom to simulate cardiorespiratory motion in combination with different motion management strategies to gain insight into the effect of cardiorespiratory motion on STAR. METHODS AND MATERIALS: The 4-dimensional (4D) extended cardiac-torso (XCAT) phantom was expanded with the 17-segment left ventricular (LV) model, which allowed placement of STAR targets in standardized ventricular regions. Cardiac- and respiratory-binned 4D computed tomography (CT) scans were simulated for free-breathing, reduced free-breathing, respiratory-gating, and breath-hold scenarios. Respiratory motion of the heart was set to population-averaged values of patients with VT: 6, 2, and 1 mm in the superior-inferior, posterior-anterior, and left-right direction, respectively. Cardiac contraction was adjusted by reducing LV ejection fraction to 35%. Target displacement was evaluated for all segments using envelopes encompassing the cardiorespiratory motion. Envelopes incorporating only the diastole plus respiratory motion were created to simulate the scenario where cardiac motion is not fully captured on 4D respiratory CT scans used for radiation therapy planning. RESULTS: The average volume of the 17 segments was 6 cm3 (1-9 cm3). Cardiac contraction-relaxation resulted in maximum segment (centroid) motion of 4, 6, and 3.5 mm in the superior-inferior, posterior-anterior, and left-right direction, respectively. Cardiac contraction-relaxation resulted in a motion envelope increase of 49% (24%-79%) compared with individual segment volumes, whereas envelopes increased by 126% (79%-167%) if respiratory motion also was considered. Envelopes incorporating only the diastole and respiration motion covered on average 68% to 75% of the motion envelope. CONCLUSIONS: The developed LV-segmental XCAT framework showed that free-wall regions display the most cardiorespiratory displacement. Our framework supports the optimization of STAR by evaluating the effect of (cardio)respiratory motion and motion management strategies for patients with VT.

Intrafraction Motion Management With MR-Guided Radiation Therapy.

High quality radiation therapy requires highly accurate and precise dose delivery. MR-guided radiotherapy (MRgRT), integrating an MRI scanner with a linear accelerator, offers excellent quality images in the treatment room without subjecting patient to ionizing radiation. MRgRT therefore provides a powerful tool for intrafraction motion management. This paper summarizes different sources of intrafraction motion for different disease sites and describes the MR imaging techniques available to visualize and quantify intrafraction motion. It provides an overview of MR guided motion management strategies and of the current technical capabilities of the commercially available MRgRT systems. It describes how these motion management capabilities are currently being used in clinical studies, protocols and provides a future outlook.

Stereotactic Arrhythmia Radioablation (STAR): Assessment of cardiac and respiratory heart motion in ventricular tachycardia patients - A STOPSTORM.eu consortium review.

AIM: To identify the optimal STereotactic Arrhythmia Radioablation (STAR) strategy for individual patients, cardiorespiratory motion of the target volume in combination with different treatment methodologies needs to be evaluated. However, an authoritative overview of the amount of cardiorespiratory motion in ventricular tachycardia (VT) patients is missing. METHODS: In this STOPSTORM consortium study, we performed a literature review to gain insight into cardiorespiratory motion of target volumes for STAR. Motion data and target volumes were extracted and summarized. RESULTS: Out of the 232 studies screened, 56 provided data on cardiorespiratory motion, of which 8 provided motion amplitudes in VT patients (n = 94) and 10 described (cardiac/cardiorespiratory) internal target volumes (ITVs) obtained in VT patients (n = 59). Average cardiac motion of target volumes was < 5 mm in all directions, with maximum values of 8.0, 5.2 and 6.5 mm in Superior-Inferior (SI), Left-Right (LR), Anterior-Posterior (AP) direction, respectively. Cardiorespiratory motion of cardiac (sub)structures showed average motion between 5-8 mm in the SI direction, whereas, LR and AP motions were comparable to the cardiac motion of the target volumes. Cardiorespiratory ITVs were on average 120-284% of the gross target volume. Healthy subjects showed average cardiorespiratory motion of 10-17 mm in SI and 2.4-7 mm in the AP direction. CONCLUSION: This review suggests that despite growing numbers of patients being treated, detailed data on cardiorespiratory motion for STAR is still limited. Moreover, data comparison between studies is difficult due to inconsistency in parameters reported. Cardiorespiratory motion is highly patient-specific even under motion-compensation techniques. Therefore, individual motion management strategies during imaging, planning, and treatment for STAR are highly recommended.

Real-time myocardial landmark tracking for MRI-guided cardiac radio-ablation using Gaussian Processes.

Objective.The high speed of cardiorespiratory motion introduces a unique challenge for cardiac stereotactic radio-ablation (STAR) treatments with the MR-linac. Such treatments require tracking myocardial landmarks with a maximum latency of 100 ms, which includes the acquisition of the required data. The aim of this study is to present a new method that allows to track myocardial landmarks from few readouts of MRI data, thereby achieving a latency sufficient for STAR treatments.Approach.We present a tracking framework that requires only few readouts of k-space data as input, which can be acquired at least an order of magnitude faster than MR-images. Combined with the real-time tracking speed of a probabilistic machine learning framework called Gaussian Processes, this allows to track myocardial landmarks with a sufficiently low latency for cardiac STAR guidance, including both the acquisition of required data, and the tracking inference.Main results.The framework is demonstrated in 2D on a motion phantom, andin vivoon volunteers and a ventricular tachycardia (arrhythmia) patient. Moreover, the feasibility of an extension to 3D was demonstrated byin silico3D experiments with a digital motion phantom. The framework was compared with template matching-a reference, image-based, method-and linear regression methods. Results indicate an order of magnitude lower total latency (<10 ms) for the proposed framework in comparison with alternative methods. The root-mean-square-distances and mean end-point-distance with the reference tracking method was less than 0.8 mm for all experiments, showing excellent (sub-voxel) agreement.Significance.The high accuracy in combination with a total latency of less than 10 ms-including data acquisition and processing-make the proposed method a suitable candidate for tracking during STAR treatments. Additionally, the probabilistic nature of the Gaussian Processes also gives access to real-time prediction uncertainties, which could prove useful for real-time quality assurance during treatments.

STereotactic Arrhythmia Radioablation (STAR): the Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary consortium (STOPSTORM.eu) and review of current patterns of STAR practice in Europe.

The EU Horizon 2020 Framework-funded Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary (STOPSTORM) consortium has been established as a large research network for investigating STereotactic Arrhythmia Radioablation (STAR) for ventricular tachycardia (VT). The aim is to provide a pooled treatment database to evaluate patterns of practice and outcomes of STAR and finally to harmonize STAR within Europe. The consortium comprises 31 clinical and research institutions. The project is divided into nine work packages (WPs): (i) observational cohort; (ii) standardization and harmonization of target delineation; (iii) harmonized prospective cohort; (iv) quality assurance (QA); (v) analysis and evaluation; (vi, ix) ethics and regulations; and (vii, viii) project coordination and dissemination. To provide a review of current clinical STAR practice in Europe, a comprehensive questionnaire was performed at project start. The STOPSTORM Institutions' experience in VT catheter ablation (83% ≥ 20 ann.) and stereotactic body radiotherapy (59% > 200 ann.) was adequate, and 84 STAR treatments were performed until project launch, while 8/22 centres already recruited VT patients in national clinical trials. The majority currently base their target definition on mapping during VT (96%) and/or pace mapping (75%), reduced voltage areas (63%), or late ventricular potentials (75%) during sinus rhythm. The majority currently apply a single-fraction dose of 25 Gy while planning techniques and dose prescription methods vary greatly. The current clinical STAR practice in the STOPSTORM consortium highlights potential areas of optimization and harmonization for substrate mapping, target delineation, motion management, dosimetry, and QA, which will be addressed in the various WPs.

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.

Towards mid-position based Stereotactic Body Radiation Therapy using online magnetic resonance imaging guidance for central lung tumours.

Background and purpose: Central lung tumours can be treated by magnetic resonance (MR)-guided radiotherapy. Complications might be reduced by decreasing the Planning Target Volume (PTV) using mid-position (midP)-based planning instead of Internal Target Volume (ITV)-based planning. In this study, we aimed to verify a method to automatically derive patient-specific PTV margins for midP-based planning, and show dosimetric robustness of midP-based planning for a 1.5T MR-linac. Materials and methods: Central(n = 12) and peripheral(n = 4) central lung tumour cases who received 8x7.5 Gy were included. A midP-image was reconstructed from ten phases of the 4D-Computed Tomography using deformable image registration. The Gross Tumor Volume (GTV) was delineated on the midP-image and the PTV margin was automatically calculated based on van Herk's margin recipe, treating the standard deviation of all Deformation Vector Fields, within the GTV, as random error component. Dosimetric robustness of midP-based planning for MR-linac using automatically derived margins was verified by 4D dose-accumulation. MidP-based plans were compared to ITV-based plans. Automatically derived margins were verified with manually derived margins. Results: The mean D95% target coverage in GTV + 2 mm was 59.9 Gy and 62.0 Gy for midP- and ITV-based central lung plans, respectively. The mean lung dose was significantly lower for midP-based treatment plans (difference:-0.3 Gy; p < 0.042 ). Automatically derived margins agreed within one millimeter with manually derived margins. Conclusions: This retrospective study indicates that mid-position-based treatment plans for central lung Stereotactic Body Radiation Therapy yield lower OAR doses compared to ITV-based treatment plans on the MR-linac. Patient-specific GTV-to-PTV margins can be derived automatically and result in clinically acceptable target coverage.

First experimental demonstration of VMAT combined with MLC tracking for single and multi fraction lung SBRT on an MR-linac.

BACKGROUND AND PURPOSE: VMAT is not currently available on MR-linacs but could maximize plan conformality. To mitigate respiration without compromising delivery efficiency, MRI-guided MLC tumour tracking was recently developed for the 1.5 T Unity MR-linac (Elekta AB, Stockholm, Sweden) in combination with IMRT. Here, we provide a first experimental demonstration of VMAT + MLC tracking for several lung SBRT indications. MATERIALS AND METHODS: We created central patient and phantom VMAT plans (8×7.5 Gy, 2 arcs) and we created peripheral phantom plans (3×18 & 1×34 Gy, 4 arcs). A motion phantom mimicked subject-recorded respiratory motion (A‾=11 mm, f‾=0.33 Hz, drift‾=0.3 mm/min). This was monitored using 2D-cine MRI at 4 Hz to continuously realign the beam with the target. VMAT + MLC tracking performance was evaluated using 2D film dosimetry and a novel motion-encoded and time-resolved pseudo-3D dosimetry approach. RESULTS: We found an MLC leaf and jaw end-to-end latency of 328.05(±3.78) ms and 317.33(±4.64) ms, which was mitigated by a predictor. The VMAT plans required maximum MLC speeds of 12.1 cm/s and MLC tracking superimposed an additional 1.48 cm/s. A local 2%/1 mm gamma analysis with a static measurement as reference, revealed pass-rates of 28-46% without MLC tracking and 88-100% with MLC tracking for the 2D film analysis. Similarly, the pseudo-3D gamma passing-rates increased from 22-77% to 92-100%. The dose area histograms showed that MLC tracking increased the GTV D98% by 5-20% and the PTV D95% by 7-24%, giving similar target coverage as their respective static reference. CONCLUSION: MRI-guided VMAT + MLC tracking is technically feasible on the MR-linac and results in highly conformal dose distribution.

A hybrid 2D/4D-MRI methodology using simultaneous multislice imaging for radiotherapy guidance.

PURPOSE: Respiratory motion management is important in abdominothoracic radiotherapy. Fast imaging of the tumor can facilitate multileaf collimator (MLC) tracking that allows for smaller treatment margins, while repeatedly imaging the full field-of-view is necessary for 4D dose accumulation. This study introduces a hybrid 2D/4D-MRI methodology that can be used for simultaneous MLC tracking and dose accumulation on a 1.5 T Unity MR-linac (Elekta AB, Stockholm, Sweden). METHODS: We developed a hybrid 2D/4D-MRI methodology that uses a simultaneous multislice (SMS) accelerated MRI sequence, which acquires two coronal slices simultaneously and repeatedly cycles through slice positions over the image volume. As a result, the fast 2D imaging can be used prospectively for MLC tracking and the SMS slices can be sorted retrospectively into respiratory-correlated 4D-MRIs for dose accumulation. Data were acquired in five healthy volunteers with an SMS-bTFE and SMS-TSE MRI sequence. For each sequence, a prebeam dataset and a beam-on dataset were acquired simulating the two phases of MR-linac treatments. Prebeam data were used to generate a 4D-based motion model and a reference mid-position volume, while beam-on data were used for real-time motion extraction and reconstruction of beam-on 4D-MRIs. In addition, an in-silico computational phantom was used for validation of the hybrid 2D/4D-MRI methodology. MLC tracking experiments were performed with the developed methodology, for which real-time SMS data reconstruction was enabled on the scanner. A 15-beam 8× 7.5 Gy intensity-modulated radiotherapy plan for lung stereotactic body radiotherapy with isotropic 3 mm GTV-to-PTV margins was created. Dosimetry experiments were performed using a 4D motion phantom. The latency between target motion and updating the radiation beam was determined and compensated. Local gamma analyses were performed to quantify dose differences compared to a static reference delivery, and dose area histograms (DAHs) were used to quantify the GTV and PTV coverage. RESULTS: In-vivo data acquisition and MLC tracking experiments were successfully performed with the developed hybrid 2D/4D-MRI methodology. Real-time liver-lung interface motion estimation had a Pearson's correlation of 0.996 (in-vivo) and 0.998 (in-silico). A median (5th-95th percentile) error of 0.0 (-0.9 to 0.7) mm and 0.0 (-0.2 to 0.2) mm was found for real-time motion estimation for in-vivo and in-silico, respectively. Target motion prediction beyond the liver-lung interface had a median root mean square error of 1.6 mm (in-vivo) and 0.5 mm (in-silico). Beam-on 4D MRI reconstruction required a median amount of data equal to an acquisition time of 2:21-3:17 min, which was 20% less data compared to the prebeam-derived 4D-MRI. System latency was reduced from 501 ± 12 ms to -1 ± 3 ms (SMS-TSE) and from 398 ± 10 ms to -10 ± 4 ms (SMS-bTFE) by a linear regression prediction filter. The local gamma analysis agreed within - 3.8 % $-3.8\%$ to 3.3% (SMS-bTFE) and - 5.3 % $-5.3\%$ to 10% (SMS-TSE) with a reference MRI sequence. The DAHs revealed a relative D 98 % $D_{98\%}$ GTV coverage between 97% and 100% (SMS-bTFE) and 100% and 101% (SMS-TSE) compared to the static reference. CONCLUSIONS: The presented 2D/4D-MRI methodology demonstrated the potential for accurately extracting real-time motion for MLC tracking in abdominothoracic radiotherapy, while simultaneously reconstructing contiguous respiratory-correlated 4D-MRIs for dose accumulation.

Feasibility of cardiac-synchronized quantitative T1 and T2 mapping on a hybrid 1.5 Tesla magnetic resonance imaging and linear accelerator system.

Background and Purpose: The heart is important in radiotherapy either as target or organ at risk. Quantitative T1 and T2 cardiac magnetic resonance imaging (qMRI) may aid in target definition for cardiac radioablation, and imaging biomarker for cardiotoxicity assessment. Hybrid MR-linac devices could facilitate daily cardiac qMRI of the heart in radiotherapy. The aim of this work was therefore to enable cardiac-synchronized T1 and T2 mapping on a 1.5 T MR-linac and test the reproducibility of these sequences on phantoms and in vivo between the MR-linac and a diagnostic 1.5 T MRI scanner. Materials and methods: Cardiac-synchronized MRI was performed on the MR-linac using a wireless peripheral pulse-oximeter unit. Diagnostically used T1 and T2 mapping sequences were acquired twice on the MR-linac and on a 1.5 T MR-simulator for a gel phantom and 5 healthy volunteers in breath-hold. Phantom T1 and T2 values were compared to gold-standard measurements and percentage errors (PE) were computed, where negative/positive PE indicate underestimations/overestimations. Manually selected regions-of-interest were used for in vivo intra/inter scanner evaluation. Results: Cardiac-synchronized T1 and T2 qMRI was enabled after successful hardware installation on the MR-linac. From the phantom experiments, the measured T1/T2 relaxation times had a maximum percentage error (PE) of -4.4%/-8.8% on the MR-simulator and a maximum PE of -3.2%/+8.6% on the MR-linac. Mean T1/T2 of the myocardium were 1012 ± 34/51 ± 2 ms on the MR-simulator and 1034 ± 42/51 ± 1 ms on the MR-linac. Conclusions: Accurate cardiac-synchronized T1 and T2 mapping is feasible on a 1.5 T MR-linac and might enable novel plan adaptation workflows and cardiotoxicity assessments.

Validation of a 4D-MRI guided liver stereotactic body radiation therapy strategy for implementation on the MR-linac.

Purpose. Accurate tumor localization for image-guided liver stereotactic body radiation therapy (SBRT) is challenging due to respiratory motion and poor tumor visibility on conventional x-ray based images. Novel integrated MRI and radiotherapy systems enable direct in-room tumor visualization, potentially increasing treatment accuracy. As these systems currently do not provide a 4D image-guided radiotherapy strategy, we developed a 4D-MRI guided liver SBRT workflow and validated all steps for implementation on the Unity MR-linac.Materials and Methods. The proposed workflow consists of five steps: (1) acquisition of a daily 4D-MRI scan, (2) 4D-MRI to mid-position planning-CT rigid tumor registration, (3) calculation of daily tumor midP misalignment, (4) plan adaptation using adapt-to-position (ATP) with segment-weights optimization and (5) adapted plan delivery. The workflow was first validated in a motion phantom, performing regular motion at different baselines (±5 to ±10 mm) and patient-derived respiratory signals with varying degrees of irregularity. 4D-MRI derived respiratory signals and 4D-MRI to planning CT registrations were compared to the phantom input, and gamma and dose-area-histogram analyses were performed on the delivered dose distributions on film. Additionally, 4D-MRI to CT registration performance was evaluated in patient images using the full-circle method (transitivity analysis). Plan adaption was further analyzedin-silicoby creating adapted treatment plans for 15 patients with oligometastatic liver disease.Results. Phantom trajectories could be reliably extracted from 4D-MRI scans and 4D-MRI to CT registration showed submillimeter accuracy. The DAH-analysis demonstrated excellent coverage of the dose evaluation structures GTV and GTVTD. The median daily rigid 4D-MRI to midP-CT registration precision in patient images was <2 mm. The ATP strategy restored the target dose without increased exposure to the OARs and plan quality was independent from 3D shift distance in the range of 1-26 mm.Conclusions. The proposed 4D-MRI guided strategy showed excellent performance in all workflow tests in preparation of the clinical introduction on the Unity MR-linac.

Dosimetric evaluation of MRI-guided multi-leaf collimator tracking and trailing for lung stereotactic body radiation therapy.

PURPOSE: The treatment margins for lung stereotactic body radiotherapy (SBRT) are often large to cover the tumor excursions resulting from respiration, such that underdosage of the tumor can be avoided. Magnetic resonance imaging (MRI)-guided multi-leaf collimator (MLC) tracking can potentially reduce the influence of respiration to allow for smaller treatment margins. However, tracking is accompanied by system latency that may induce residual tracking errors. Alternatively, a simpler mid-position delivery combined with trailing can be used. Trailing reduces influences of respiration by compensating for baseline motion, to potentially improve target coverage. In this study, we aim to show the feasibility of MRI-guided tracking and trailing to reduce influences of respiration during lung SBRT. METHODS: We implemented MRI-guided tracking on the MR-linac using an Elekta research tracking interface to track tumor motion during intensity modulated radiotherapy (IMRT). A Quasar MRI 4 D phantom was used to generate Lujan motion ( cos 4 , 4 s period, 20 mm peak-to-peak amplitude) with and without 1.0 mm/min cranial drift. Phantom tumor positions were estimated from sagittal 2D cine-MRI (4 or 8 Hz) using cross-correlation-based template matching. To compensate the anticipated system latency, a linear ridge regression predictor was optimized for online MRI by comparing two predictor training approaches: training on multiple traces and training on a single trace. We created 15-beam clinical-grade lung SBRT plans for central targets (8 × 7.5 Gy) and peripheral targets (3 × 18 Gy) with different PTV margins for mid-position based motion management (3-5 mm) and for MLC tracking (3 mm). We used a film insert with a 3 cm spherical target to measure the spatial distribution and quantity of the delivered dose. A 1%/1 mm local gamma-analysis quantified dose differences between motion management strategies and reference cases. Additionally, a dose area histogram (DAH) revealed the target coverage relative to the reference scenario. RESULTS: The prediction filter gain was on average 25% when trained on multiple traces and 44% when trained on a single trace. The filter reduced system latency from 313 ± 2 ms to 0 ± 5 ms for 4 Hz imaging and from 215 ± 3 ms to 3 ± 3 ms for 8 Hz. The local gamma analysis for the central delivery showed that tracking improved the gamma pass-rate from 23% to 96% for periodic motion and from 14% to 93% when baseline drift was applied. For the peripheral delivery during periodic motion, delivery pass-rates improved from 22% to 93%. Comparing mid-position delivery to trailing for periodic+drift motion increased the local gamma pass rate from 15% to 98% for a central delivery and from 8% to 98% for a peripheral delivery. Furthermore, the DAHs revealed a relative D 98 % GTV coverage of 101% and 97% compared to the reference scenario for, respectively, central and peripheral tracking of periodic+drift motion. For trailing, a relative D 98 % of 99% for central and 98% for peripheral trailing was found. CONCLUSIONS: We provided a first experimental demonstration of the technical feasibility of MRI-guided MLC tracking and trailing for central and peripheral lung SBRT. Tracking maximizes the sparing of healthy tissue, while trailing is highly effective in mitigating baseline motion.

A multivariable study of deformable image registration evaluation metrics in 4DCT of thoracic cancer patients.

Deformable image registration (DIR) accuracy is often validated using manually identified landmarks or known deformations generated using digital or physical phantoms. In daily practice, the application of these approaches is limited since they are time-consuming or require additional equipment. An alternative is the use of metrics automatically derived from the registrations, but their interpretation is not straightforward. In this work we aim to determine the suitability of DIR-derived metrics to validate the accuracy of 4 commonly used DIR algorithms. First, we investigated the DIR accuracy using a landmark-based metric (target registration error (TRE)) and a digital phantom-based metric (known deformation recovery error (KDE)). 4DCT scans of 16 thoracic cancer patients along with corresponding pairwise anatomical landmarks (AL) locations were collected from two public databases. Digital phantoms with known deformations were generated by each DIR algorithm to test all other algorithms and compute KDE. TRE and KDE were evaluated at AL. KDE was additionally quantified in coordinates randomly sampled (RS) inside the lungs. Second, we investigated the associations of 5 DIR-derived metrics (distance discordance metric (DDM), inverse consistency error (ICE), transitivity (TE), spatial (SS) and temporal smoothness (TS)) with DIR accuracy through uni- and multivariable linear regression models. TRE values were found higher compared to KDE values and these varied depending on the phantom used. The algorithm with the best accuracy achieved average values of TRE = 1.1 mm and KDE ranging from 0.3 to 0.8 mm. DDM was the best predictor of DIR accuracy, with moderate correlations (R 2 < 0.61). Poor correlations were obtained at AL for algorithms with better accuracy, which improved when evaluated at RS. Only slight correlation improvement was obtained with a multivariable analysis (R 2 < 0.64). DDM can be a useful metric to identify inaccuracies for different DIR algorithms without employing landmarks or digital phantoms.

AAPM Task Group 264: The safe clinical implementation of MLC tracking in radiotherapy.

The era of real-time radiotherapy is upon us. Robotic and gimbaled linac tracking are clinically established technologies with the clinical realization of couch tracking in development. Multileaf collimators (MLCs) are a standard equipment for most cancer radiotherapy systems, and therefore MLC tracking is a potentially widely available technology. MLC tracking has been the subject of theoretical and experimental research for decades and was first implemented for patient treatments in 2013. The AAPM Task Group 264 Safe Clinical Implementation of MLC Tracking in Radiotherapy Report was charged to proactively provide the broader radiation oncology community with (a) clinical implementation guidelines including hardware, software, and clinical indications for use, (b) commissioning and quality assurance recommendations based on early user experience, as well as guidelines on Failure Mode and Effects Analysis, and (c) a discussion of potential future developments. The deliverables from this report include: an explanation of MLC tracking and its historical development; terms and definitions relevant to MLC tracking; the clinical benefit of, clinical experience with and clinical implementation guidelines for MLC tracking; quality assurance guidelines, including example quality assurance worksheets; a clinical decision pathway, future outlook and overall recommendations.

Investigating the impact of patient arm position in an MR-linac on liver SBRT treatment plans.

PURPOSE: The superior soft-tissue contrast offered by the integrated magnetic resonance imaging (MRI) of the Unity MR-linac compared to the x-ray-based image guidance on conventional linacs potentially allows for liver stereotactic body radiation therapy (SBRT) without the need for implanted markers or other surrogates. On conventional linacs, liver SBRT patients are typically positioned with their arms above their heads (arms-up) to minimize exposure to healthy tissue. However, the spatial confinement of the MRI-bore and increased treatment delivery times can make the arms-up position straining. Therefore, we assessed the plan quality for MR-linac treatment plans with the patient in the arms-up and in the arms-down position. Additionally, we compared the MR-linac plans with clinically used arms-up treatment plans made for a conventional linac. METHODS: Fifteen consecutively treated patients with oligometastatic liver disease were included in this retrospective study. For each patient, a planning computed tomography (CT) with delineations, a diagnostic MRI, and a 3 × 20 Gy dual-arc volumetric modulated arc therapy (VMAT) plan, which was used to treat the patient in an arms-up position on the conventional linac, were available. For the MR-linac, 15-beam step-and-shoot intensity-modulated radiation therapy (IMRT) plans were created for four patient positioning scenarios: arms-up, mimicking current clinical practice; arms-down, with treatment beams avoiding the arms on the entrance side; arms-through, arms are down but not avoided, and right-arm-up; only the right arm is up and the left arm is avoided on the entrance side. Resulting treatment plans were compared. Bonferroni-corrected two-sided Wilcoxon signed-ranks tests were used to assess statistical significance (P < 0.05). RESULTS: No significant differences were found in gross tumour volume (GTV) coverage (D 2 % , D 50 % , and D 98 % ) or liver sparing (liver-GTV V < 15 Gy ) between the clinical plans and any of the MR-linac plans. The median target conformity [exterior V 40 % /planning target volume (PTV)] was significantly better in the clinical plans (5.8) than in the MR-linac scenarios (arms-down: 6.6, arms-up/right-arm-up: 6.2, arms-through: 6.3). No MR-linac plan violated any additional organ-at-risk (OAR) constraint that was not already violated in the clinical plans. In the arms-down scenario a significantly increased median spinal cord D 1 % (14.5 Gy) was detected compared to the clinical setup (7.2 Gy). For the arms-down (arms-through) scenario, the median left arm D 1 % was 1.5 (2.7) Gy, the median right arm D 1 % was 5.8 (22.7) Gy, and the median right arm V 20 Gy was 0.0 (14.7) cc. These differences were statistically significant. For the right-arm-up scenario, the median left arm D 1 % (2.3 Gy) and V 5 Gy (0.0) were not significantly different compared to the arms-down scenario. CONCLUSIONS: Mimicking the current clinical practice by treating patients in the arms-up/right-arm-up position on the MR-linac leads to plans which are dosimetrically very similar to the conventional linac plans. Treating in the arms-down position is expected to increase patient comfort at the cost of a small reduction in OAR sparing for individual patients. Treating through the arms is not encouraged due to substantial dose deposition in the arms.