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.

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.

Arterial spin labeling using spatio-temporal encoding readout for robust perfusion imaging in inhomogenous magnetic fields.

PURPOSE: To evaluate the feasibility of spatio-temporal encoding (SPEN) readout for pseudo-continuous ASL (pCASL) in brain, and its robustness to susceptibility artifacts as introduced by aneurysm clips. METHODS: A 2D self-refocused T2 *-compensated hybrid SPEN scheme, with super-resolution reconstruction was implemented on a 1.5T Philips system. Q (=BWchirp *Tchirp ) was varied and, the aneurysm clip-induced artifact was evaluated in phantom (label-images) as well as in vivo (perfusion-weighted signal (PWS)-maps and temporal SNR (tSNR)). In vivo results were compared to gradient-echo EPI (GE-EPI) and spin-echo EPI (SE-EPI). The dependence of tSNR on TR was evaluated separately for SPEN and SE-EPI. SPEN with Q Ëœ 75 encodes with the same off-resonance robustness as EPI. RESULTS: The clip-induced artifact with SPEN decreased with increase in Q, and was smaller compared to SE-EPI and GE-EPI in vivo. tSNR decreased with Q and the tSNR of GE-EPI and SE-EPI corresponded to SPEN with a Q-value of approximately ˜85 and ˜108, respectively. In addition, SPEN perfusion images showed a higher tSNR (p < 0.05) for TR = 4000 ms compared to TR = 2100 ms, while SE-EPI did not. tSNR remained relatively stable when the time between SPEN-excitation and start of the next labeling-module was more than ˜1000 ms. CONCLUSION: Feasibility of combining SPEN with pCASL imaging was demonstrated, enabling cerebral perfusion measurements with a higher robustness to field inhomogeneity (Q > 75) compared to SE-EPI and GE-EPI. However, the SPEN chirp-pulse saturates incoming blood, thereby reducing pCASL labeling efficiency of the next acquisition for short TRs. Future developments are needed to enable 3D scanning.

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.

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.