MR signature matching (MRSIGMA) implementation for true real-time free-breathing volumetric imaging with sub-200 ms latency on an MR-Linac.

PURPOSE: Develop a true real-time implementation of MR signature matching (MRSIGMA) for free-breathing 3D MRI with sub-200 ms latency on the Elekta Unity 1.5T MR-Linac. METHODS: MRSIGMA was implemented on an external computer with a network connection to the MR-Linac. Stack-of-stars with partial kz sampling was used to accelerate data acquisition and ReconSocket was employed for simultaneous data transmission. Movienet network computed the 4D MRI motion dictionary and correlation analysis was used for signature matching. A programmable 4D MRI phantom was utilized to evaluate MRSIGMA with respect to a ground-truth translational motion reference. In vivo validation was performed on patients with pancreatic cancer, where 15 patients were employed to train Movienet and 7 patients to test the real-time implementation of MRSIGMA. Dice coefficients between real-time MRSIGMA and a retrospectively computed 4D reference were used to evaluate motion tracking performance. RESULTS: Motion dictionary was computed in under 5 s. Signature acquisition and matching presented 173 ms latency on the phantom and 193 ms on patients. MRSIGMA presented a mean error of 1.3-1.6 mm for all phantom experiments, which was below the 2 mm acquisition resolution along the motion direction. The Dice coefficient over time between MRSIGMA and reference contours was 0.88 ± 0.02 (GTV), 0.87 ± 0.02(duodenum-stomach), and 0.78 ± 0.02(small bowel), demonstrating high motion tracking performance for both tumor and organs at risk. CONCLUSION: The real-time implementation of MRSIGMA enabled true real-time free-breathing 3D MRI with sub-200 ms imaging latency on a clinical MR-Linac system, which can be used for treatment monitoring, adaptive radiotherapy and dose accumulation mapping in tumors affected by respiratory motion.

Risk analysis of the Unity 1.5 T MR-Linac adapt-to-position workflow.

BACKGROUND AND PURPOSE: Newer technologies allow for daily treatment adaptation, providing the ability to account for setup variations and organ motion but comes at the cost of increasing the treatment workflow complexity. One such technology is the adapt-to-position (ATP) workflow on the Unity MR-Linac. Prospective risk assessment of a new workflow allows clinics to catch errors before they occur, especially for processes that include novel and unfamiliar steps. METHODS: As part of a quality management program, failure modes and effects analysis was performed on the ATP treatment workflow following the recommendations of AAPM's Task Group 100. A multidisciplinary team was formed to identify and evaluate failure modes for all the steps taken during a daily treatment workflow. Failure modes of high severity and overall score were isolated and addressed. RESULTS: Mitigations were determined for high-ranking failure modes and implemented into the clinic. High-ranking failure modes existed in all steps of the workflow. Failure modes were then rescored to evaluate the effectiveness of the mitigations. CONCLUSION: Failure modes and effects analysis on the Unity MR-Linac highlighted areas in the ATP workflow that could be prone to failures and allowed our clinic to change the process to be more robust.

Longitudinal assessment of quality assurance measurements in a 1.5 T MR-linac: Part II-Magnetic resonance imaging.

PURPOSE: To describe and report longitudinal quality assurance (QA) measurements for the magnetic resonance imaging (MRI) component of the Elekta Unity MR-linac during the first year of clinical use in our institution. MATERIALS AND METHODS: The performance of the MRI component of Unity was evaluated with daily, weekly, monthly, and annual QA testing. The measurements monitor image uniformity, signal-to-noise ratio (SNR), resolution/detectability, slice position/thickness, linearity, central frequency, and geometric accuracy. In anticipation of routine use of quantitative imaging (qMRI), we characterize B0/B1 uniformity and the bias/reproducibility of longitudinal/transverse relaxation times (T1/T2) and apparent diffusion coefficient (ADC). Tolerance levels for QA measurements of qMRI biomarkers are derived from weekly monitoring of T1, T2, and ADC. RESULTS: The 1-year assessment of QA measurements shows that daily variations in each MR quality metric are well below the threshold for failure. Routine testing procedures can reproducibly identify machine issues. The longitudinal three-dimensional (3D) geometric analysis reveals that the maximum distortion in a diameter of spherical volume (DSV) of 20, 30, 40, and 50 cm is 0.4, 0.6, 1.0, and 3.1 mm, respectively. The main source of distortion is gradient nonlinearity. Maximum peak-to-peak B0 inhomogeneity is 3.05 ppm, with gantry induced B0 inhomogeneities an order of magnitude smaller. The average deviation from the nominal B1 is within 2%, with minimal dependence on gantry angle. Mean ADC, T1, and T2 values are measured with high reproducibility. The median coefficient of variation for ADC, T1, and T2 is 1.3%, 1.1%, and 0.5%, respectively. The median bias for ADC, T1, and T2 is -0.8%, -0.1%, and 3.9%, respectively. CONCLUSION: The MRI component of Unity operates within the guidelines and recommendations for scanner performance and stability. Our findings support the recently published guidance in establishing clinically acceptable tolerance levels for image quality. Highly reproducible qMRI measurements are feasible in Unity.

Dosimetric evaluation of irradiation geometry and potential air gaps in an acrylic miniphantom used for external audit of absolute dose calibration for a hybrid 1.5 T MR-linac system.

INTRODUCTION: To investigate the impact of partial lateral scatter (LS), backscatter (BS) and presence of air gaps on optically stimulated luminescence dosimeter (OSLD) measurements in an acrylic miniphantom used for dosimetry audit on the 1.5 T magnetic resonance-linear accelerator (MR-linac) system. METHODS: The following irradiation geometries were investigated using OSLDs, A26 MR/A12 MR ion chamber (IC), and Monaco Monte Carlo system: (a) IC/OSLD in an acrylic miniphantom (partial LS, partial BS), (b) IC/OSLD in a miniphantom placed on a solid water (SW) stack at a depth of 1.5 cm (partial LS, full BS), (c) IC/OSLD placed at a depth of 1.5 cm inside a 3 cm slab of SW/buildup (full LS, partial BS), and (d) IC/OSLD centered inside a 3 cm slab of SW/buildup at a depth of 1.5 cm placed on top of a SW stack (full LS, full BS). Average of two irradiated OSLDs with and without water was used at each setup. An air gap of 1 and 2 mm, mimicking presence of potential air gap around the OSLDs in the miniphantom geometry was also simulated. The calibration condition of the machine was 1 cGy/MU at SAD = 143.5 cm, d = 5 cm, G90, and 10 × 10 cm2 . RESULTS: The Monaco calculation (0.5% uncertainty and 1.0 mm voxel size) for the four setups at the measurement point were 108.2, 108.1, 109.4, and 110.0 cGy. The corresponding IC measurements were 109.0 ± 0.03, 109.5 ± 0.06, 110.2 ± 0.02, and 109.8 ± 0.03 cGy. Without water, OSLDs measurements were ∼10% higher than the expected. With added water to minimize air gaps, the measurements were significantly improved to within 2.2%. The dosimetric impacts of 1 and 2 mm air gaps were also verified with Monaco to be 13.3% and 27.9% higher, respectively, due to the electron return effect. CONCLUSIONS: A minimal amount of air around or within the OSLDs can cause measurement discrepancies of 10% or higher when placed in a high b-field MR-linac system. Care must be taken to eliminate the air from within and around the OSLD.

Longitudinal assessment of quality assurance measurements in a 1.5T MR-linac: Part I-Linear accelerator.

PURPOSE: To describe and report longitudinal quality assurance (QA) measurements for the mechanical and dosimetric performance of an Elekta Unity MR-linac during the first year of clinical use in our institution. MATERIALS AND METHODS: The mechanical and dosimetric performance of the MR-linac was evaluated with daily, weekly, monthly, and annual QA testing. The measurements monitor the size of the radiation isocenter, the MR-to-MV isocenter concordance, MLC and jaw position, the accuracy and reproducibility of step-and-shoot delivery, radiation output and beam profile constancy, and patient-specific QA for the first 50 treatments in our institution. Results from end-to-end QA using anthropomorphic phantoms are also included as a reference for baseline comparisons. Measurements were performed in water or water-equivalent plastic using ion chambers of various sizes, an ion chamber array, MR-compatible 2D/3D diode array, portal imager, MRI, and radiochromic film. RESULTS: The diameter of the radiation isocenter and the distance between the MR/MV isocenters was (µ ± σ) 0.39 ± 0.01 mm and 0.89 ± 0.05 mm, respectively. Trend analysis shows both measurements to be well within the tolerance of 1.0 mm. MLC and jaw positional accuracy was within 1.0 mm while the dosimetric performance of step-and-shoot delivery was within 2.0%, irrespective of gantry angle. Radiation output and beam profile constancy were within 2.0% and 1.0%, respectively. End-to-end testing performed with ion-chamber and radiochromic film showed excellent agreement with treatment plan. Patient-specific QA using a 3D diode array identified gantry angles with low-pass rates allowing for improvements in plan quality after necessary adjustments. CONCLUSION: The MR-linac operates within the guidelines of current recommendations for linear accelerator performance, stability, and safety. The analysis of the data supports the recently published guidance in establishing clinically acceptable tolerance levels for relative and absolute measurements.

An investigation of using log-file analysis for automated patient-specific quality assurance in MRgRT.

OBJECTIVE: Adaptive radiation therapy (ART) is an integral part of MR-guided RT (MRgRT), requiring a new RT plan for each treatment fraction and resulting in a significant increase in patient-specific quality assurance (PSQA). This study investigates the possibility of using treatment log-file for automated PSQA. METHOD: All treatment plans were delivered in 1.5T Unity MR-Linac (Elekta). A Unity compatible version of LinacView (Standard Imaging) was commissioned to automatically monitor and analyze the log-files. A total of 220 fields were delivered and measured by ArcCheck® -MR (Sun Nuclear) and LinacView. Thirty incorrectly matched fields were also delivered to check for error detection sensitivity. The gamma analysis, γ, with 3%, 3 mm criteria was used in both ArcCheck® -MR and LinacView. Additionally, the gantry angle, jaws, and multileaf collimators (MLC) positions reported in the log-file were compared with plan positions using TG-142 criteria. RESULT: The γ (3%, 3 mm) for the 190 plans were found to be between the range of 72.5%-100.0% and 95.4%-100.0% for ArcCheck® -MR and LinacVeiw, respectively. All the delivered gantry angle and jaws were found to be within 0.2° and 2 mm. MLCs that were outside the guard leaves or under the diaphragms were found to have more than 1.0 mm discrepancy. This was attributed to the linac internal override for these MLCs and had no dosimetric impact. Excluding these discrepancies, all MLC positions were found to be within 1.0 mm. The γ (3%, 3 mm) for the 30 incorrectly matched fields were found to be 3.9%-84.8% and 0.1%-64.4% for ArcCheck® -MR and LinacVeiw, respectively. CONCLUSION: Significant ranked correlation demonstrates the automated log-file analysis can be used for PSQA and expedite the ART workflow. Ongoing PSQA will be compared with log-file analysis to investigate the longer term reproducibility and correlation.

A multi-institutional analysis of a general pelvis continuous Hounsfield unit synthetic CT software for radiotherapy.

PURPOSE: To validate a synthetic computed tomography (sCT) software with continuous HUs and large field-of-view (FOV) coverage for magnetic resonance imaging (MRI)-only workflow of general pelvis anatomy in radiotherapy (RT). METHODS: An sCT software for general pelvis anatomy (prostate, rectum, and female pelvis) has been developed by Philips Healthcare and includes continuous HUs assignment along with large FOV coverage. General pelvis sCTs were generated using a two-stack T1-weighted mDixon fast-field echo (FFE) sequence with a superior-inferior coverage of 36 cm. Seventy-seven prostate, 43 rectum, and 27 gynecological cases were scanned by three different institutions. mDixon image quality and sCTs were evaluated for soft tissue contrast by using a confidence level scale from 1 to 5 for bladder, prostate/rectum interface, mesorectum, and fiducial maker visibility. Dosimetric comparison was performed by recalculating the RT plans on the sCT after rigid registration. For 12 randomly selected cases, the mean absolute error (MAE) between sCT and CT was calculated to evaluate HU similarity, and the Pearson correlation coefficients (PCC) between the CT- and sCT-generated digitally reconstructed radiographs (DRRs) were obtained for quantitative comparison. To examine geometric accuracy of sCT as a reference for cone beam CT (CBCT), the difference between bone-based alignment of CBCT to CT and CBCT to sCT was obtained for 19 online-acquired CBCTs from three patients. RESULTS: Two-stack mDixon scans with large FOV did not show any image inhomogeneity or fat-water swap artifact. Fiducials, Foley catheter, and even rectal spacer were visible as dark signal on the sCT. Average visibility confidence level (average ± standard deviation) on the sCT was 5.0 ± 0.0, 4.6 ± 0.5, 3.8 ± 0.4, and 4.0 ± 1.1 for bladder, prostate/rectum interface, mesorectum and fiducial markers. Dosimetric accuracy showed on average < 1% difference with the CT-based plans for target and normal structures. The MAE of bone and soft tissue between the sCT and CT are 120.9 ± 15.4 HU, 33.4 ± 4.1 HU, respectively. Average PCC of all evaluated DRR pairs was 0.975. The average offset between CT and sCT as reference was (LR, AP, SI) = (0.19 ± 0.35, 0.14 ± 0.60, 0.44 ± 0.54) mm. CONCLUSIONS: The continuous HU sCT software-generated realistic sCTs and DRRs to enable MRI-only planning for general pelvis anatomy.

MRSIGMA: Magnetic Resonance SIGnature MAtching for real-time volumetric imaging.

PURPOSE: To propose a real-time 3D MRI technique called MR SIGnature MAtching (MRSIGMA) for high-resolution volumetric imaging and motion tracking with very low imaging latency. METHODS: MRSIGMA consists of two steps: (1) offline learning of a database of possible 3D motion states and corresponding motion signature ranges and (2) online matching of new motion signatures acquired in real time with prelearned motion states. Specifically, the offline learning step (non-real-time) reconstructs motion-resolved 4D images representing different motion states and assigns a unique motion range to each state. The online matching step (real-time) acquires motion signatures only and selects one of the prelearned 3D motion states for each newly acquired signature, which generates 3D images efficiently in real time. The MRSIGMA technique was evaluated on 15 golden-angle stack-of-stars liver data sets, and the performance of respiratory motion tracking with the online-generated real-time 3D MRI was compared with the corresponding 2D projections acquired in real time. RESULTS: The total latency of generating each 3D image during online matching was about 300 ms, including acquisition of the motion signature data (~138 ms) and corresponding matching process (~150 ms). Linear correlation assessment suggested excellent correlation (R2  = 0.948) between motion displacement measured from the online-generated real-time 3D images and the 2D real-time projections. CONCLUSION: This proof-of-concept study demonstrates the feasibility of MRSIGMA for high-resolution real-time volumetric imaging, which shifts the acquisition and reconstruction burden to an offline learning step and leaves fast online matching for online imaging with very low imaging latency. The MRSIGMA technique can potentially be used for real-time motion tracking in MRI-guided radiation therapy.

Impact of varying air cavity on planning dosimetry for rectum patients treated on a 1.5 T hybrid MR-linac system.

PURPOSE: To investigate the dosimetric impact of magnetic (B) field on varying air cavities in rectum patients treated on the hybrid 1.5 T MR-linac. METHODS: Artificial air cavities of varying diameters (0.0, 1.0, 1.5, 2.0, 2.5, 3.0, and 5.0 cm) were created for four rectum patients (two prone and two supine). A total of 56 plans using a 7 MV flattening filter-free beam were generated with and without B-field. Reference intensity-modulated radiation therapy treatment plans without air cavity in the presence and absence of B-field were generated to a total dose of 45/50 Gy. The reference plans were copied and recalculated for the varying air cavities. D95 (PTV45 -PTV50 ), D95 (PTV50 -aircavity), V50 (PTV50 -aircavity), Dmax (PTV50 -aircavity), and V110% (PTV50 -aircavity) were extracted for each patient. Annulus rings of 1-mm-diameter step size were generated for one of the air cavity plans (3.0 cm) for all four patients to determine Dmax (%) and V110% (cc) within each annulus. RESULTS: In the presence of B-field, hot spots at the cavity interface start to become visible at ~1 cm air cavity in both supine and prone positioning due to electron return effect (ERE). In the presence of B-field Dmax and V110% varied from 5523 ± 49 cGy and 0.09 ± 0.16 cc for 0 cm air cavity size to 6050 ± 109 cGy and 11.6 ± 6.7 cc for 5 cm air cavity size. The hot spots were located within 3 mm inside the rectal-air interface, where Dmax increased from 110.4 ± 0.5% without B-field to 119.2 ± 0.8 % with B-field. CONCLUSIONS: Air cavities inside rectum affects rectum plan dosimetry due ERE. Location and magnitude of hot spots are dependent on the size of the air cavity.

Volumetric 3D assessment of ablation zones after thermal ablation of colorectal liver metastases to improve prediction of local tumor progression.

PURPOSE: The goal of this study was to develop and evaluate a volumetric three-dimensional (3D) approach to improve the accuracy of ablation margin assessment following thermal ablation of hepatic tumors. METHODS: The 3D margin assessment technique was developed to generate the new 3D assessment metrics: volumes of insufficient coverage (VICs) measuring volume of tissue at risk post-ablation. VICs were computed for the tumor and tumor plus theoretical 5- and 10-mm margins. The diagnostic accuracy of the 3D assessment to predict 2-year local tumor progression (LTP) was compared to that of manual 2D assessment using retrospective analysis of a patient cohort that has previously been reported as a part of an outcome-centered study. Eighty-six consecutive patients with 108 colorectal cancer liver metastases treated with radiofrequency ablation (2002-2012) were used for evaluation. The 2-year LTP discrimination power was assessed using receiver operating characteristic area under the curve (AUC) analysis. RESULTS: A 3D assessment of margins was successfully completed for 93 out of 108 tumors. The minimum margin size measured using the 3D method had higher discrimination power compared with the 2D method, with an AUC value of 0.893 vs. 0.790 (p = 0.01). The new 5-mm VIC metric had the highest 2-year LTP discrimination power with an AUC value of 0.923 (p = 0.004). CONCLUSIONS: Volumetric semi-automated 3D assessment of the ablation zone in the liver is feasible and can improve accuracy of 2-year LTP prediction following thermal ablation of hepatic tumors. KEY POINTS: • More accurate prediction of local tumor progression risk using volumetric 3D ablation zone assessment can help improve the efficacy of image-guided percutaneous thermal ablation of hepatic tumors. • The accuracy of evaluation of ablation zone margins after thermal ablation of colorectal liver metastases can be improved using a volumetric 3D semi-automated assessment approach and the volume of insufficient coverage assessment metric. • The new 5-mm volume-of-insufficient-coverage metric, indicating the volume of tumor plus 5-mm margin that remained untreated, had the highest 2-year local tumor progression discrimination power.

Dosimetric evaluation of an atlas-based synthetic CT generation approach for MR-only radiotherapy of pelvis anatomy.

PURPOSE: To investigate the potential of an atlas-based approach in generation of synthetic CT for pelvis anatomy. METHODS: Twenty-three matched pairs of computed tomography (CT) and magnetic resonance imaging (MRI) scans were selected from a pool of prostate cancer patients. All MR scans were preprocessed to reduce scanner- and patient-induced intensity inhomogeneities and to standardize their intensity histograms. Ten (training dataset) of 23 pairs were then utilized to construct the coregistered CT-MR atlas. The synthetic CT for a new patient is generated by appropriately weighting the deformed atlas of CT-MR onto the new patient MRI. The training dataset was used as an atlas to generate the synthetic CT for the rest of the patients (test dataset). The mean absolute error (MAE) between the deformed planning CT and synthetic CT was computed over the entire CT image, bone, fat, and muscle tissues. The original treatment plans were also recomputed on the new synthetic CTs and dose-volume histogram metrics were compared. The results were compared with a commercially available synthetic CT Software (MRCAT) that is routinely used in our clinic. RESULTS: MAE errors (±SD) between the deformed planning CT and our proposed synthetic CTs in the test dataset were 47 ± 5, 116 ± 12, 36 ± 6, and 47 ± 5 HU for the entire image, bone, fat, and muscle tissues respectively. The MAEs were 65 ± 5, 172 ± 9, 43 ± 7, and 42 ± 4 HU for the corresponding tissues in MRCAT CT. The dosimetric comparison showed consistent results for all plans using our synthetic CT, deformed planning CT and MRCAT CT. CONCLUSION: We investigated the potential of a multiatlas approach to generate synthetic CT images for the pelvis. Our results demonstrate excellent results in terms of HU value assignment compared to the original CT and dosimetric consistency.

Dual-input tracer kinetic modeling of dynamic contrast-enhanced MRI in thoracic malignancies.

Pulmonary perfusion with dynamic contrast-enhanced (DCE-) MRI is typically assessed using a single-input tracer kinetic model. Preliminary studies based on perfusion CT are indicating that dual-input perfusion modeling of lung tumors may be clinically valuable as lung tumors have a dual blood supply from the pulmonary and aortic system. This study aimed to investigate the feasibility of fitting dual-input tracer kinetic models to DCE-MRI datasets of thoracic malignancies, including malignant pleural mesothelioma (MPM) and nonsmall cell lung cancer (NSCLC), by comparing them to single-input (pulmonary or systemic arterial input) tracer kinetic models for the voxel-level analysis within the tumor with respect to goodness-of-fit statistics. Fifteen patients (five MPM, ten NSCLC) underwent DCE-MRI prior to radiotherapy. DCE-MRI data were analyzed using five different single- or dual-input tracer kinetic models: Tofts-Kety (TK), extended TK (ETK), two compartment exchange (2CX), adiabatic approximation to the tissue homogeneity (AATH) and distributed parameter (DP) models. The pulmonary blood flow (BF), blood volume (BV), mean transit time (MTT), permeability-surface area product (PS), fractional interstitial volume (vI ), and volume transfer constant (KTrans ) were calculated for both single- and dual-input models. The pulmonary arterial flow fraction (γ), pulmonary arterial blood flow (BFPA ) and systemic arterial blood flow (BFA ) were additionally calculated for only dual-input models. The competing models were ranked and their Akaike weights were calculated for each voxel according to corrected Akaike information criterion (cAIC). The optimal model was chosen based on the lowest cAIC value. In both types of tumors, all five dual-input models yielded lower cAIC values than their corresponding single-input models. The 2CX model was the best-fitted model and most optimal in describing tracer kinetic behavior to assess microvascular properties in both MPM and NSCLC. The dual-input 2CX-model-derived BFA was the most significant parameter in differentiating adenocarcinoma from squamous cell carcinoma histology for NSCLC patients.

Diffusion-weighted MRI of the lung at 3T evaluated using echo-planar-based and single-shot turbo spin-echo-based acquisition techniques for radiotherapy applications.

PURPOSE: To compare single-shot echo-planar (SS-EPI)-based and turbo spin-echo (SS-TSE)-based diffusion-weighted imaging (DWI) in Non-Small Cell Lung Cancer (NSCLC) patients and to characterize the distributions of apparent diffusion coefficient (ADC) values generated by the two techniques. METHODS: Ten NSCLC patients were enrolled in a prospective IRB-approved study to compare and optimize DWI using EPI and TSE-based techniques for radiotherapy planning. The imaging protocol included axial T2w, EPI-based DWI and TSE-based DWI on a 3 T Philips scanner. Both EPI-based and TSE-based DWI sequences used three b values (0, 400, and 800 s/mm2 ). The acquisition times for EPI-based and TSE-based DWI were 5 and 8 min, respectively. DW-MR images were manually coregistered with axial T2w images, and tumor volume contoured on T2w images were mapped onto the DWI scans. A pixel-by-pixel fit of tumor ADC was calculated based on monoexponential signal behavior. Tumor ADC mean, standard deviation, kurtosis, and skewness were calculated and compared between EPI and TSE-based DWI. Image distortion and ADC values between the two techniques were also quantified using fieldmap analysis and a NIST traceable ice-water diffusion phantom, respectively. RESULTS: The mean ADC for EPI and TSE-based DWI were 1.282 ± 0.42 × 10-3 and 1.211 ± 0.31 × 10-3  mm2 /s. The average skewness and kurtosis were 0.14 ± 0.4 and 2.43 ± 0.40 for DWI-EPI and -0.06 ± 0.69 and 2.89 ± 0.62 for DWI-TSE. Fieldmap analysis showed a mean distortion of 13.72 ± 8.12 mm for GTV for DWI-EPI and 0.61 ± 0.4 mm for DWI-TSE. ADC values obtained using the diffusion phantom for the two techniques were within 0.03 × 10-3  mm2 /s with respect to each other as well as the established values. CONCLUSIONS: Diffusion-weighted turbo spin-echo shows better geometrical accuracy compared to DWI-EPI. Mean ADC values were similar with both acquisitions but the shape of the histograms was different based on the skewness and kurtosis values. The impact of differences in respiratory technique on ADC values requires further investigation.

Impact of daily soft-tissue image guidance to prostate on pelvic lymph node (PLN) irradiation for prostate patients receiving SBRT.

PURPOSE: To determine the impact of using fiducial match for daily image-guidance on pelvic lymph node (PLN) coverage for prostate cancer patients receiving stereotactic body radiation therapy (SBRT). METHODS: Thirty patients underwent SBRT treatment to the prostate and PLN from 2014 to 2016. Each patient received either 800cGy × 5 or 500cGy × 5 to the prostate and 500cGy × 5 to the PLN. A 5 mm clinical target volume (CTV)-to-planning target volume (PTV) margin around the PLN was used for planning. Two registrations with planning computed tomography (PCT) for each of the daily cone beam CTs (CBCTs) were performed: a rigid registration to fiducials and to the bony anatomy. The average translational difference between fiducial and bony match as well as percentage of fractions with differences > 5mm were calculated. Changes in bladder and rectal volume as well as center-of-mass (COM) position from simulation parameters, and their correlation with translational difference were also evaluated. The dosimetric impact of the translational differences was calculated by shifting the plan isocenter. RESULTS: The average translational difference between fiducial and bony match was 0.06 ± 0.82, 2.1 ± 4.1, -2.8 ± 4.3, and 5.5 ± 4.2 mm for lateral, vertical, longitudinal, and vector directions. The average change in bladder and rectal volume from simulation was -67.2 ± 163.04 cc (-12 ± 52%) and -1.6 ± 18.75 (-2 ± 30%) cc. The average change in COM of bladder from the simulation position was 0.34 ± 2.49, 4.4 ± 8.1, and -3.9 ± 7.5 mm along the LR, AP, and SI directions. The corresponding COM change for the rectum was 0.17 ± 1.9, 1.34 ± 3.5, and -0.6 ± 5.2 mm. CONCLUSIONS: The 5 mm margin covered ~75% of fractions receiving PLN irradiation with SBRT, daily CBCT and fiducial-guided setup. The dosimetric impact on PLN coverage was significant in 19% of fractions or 25% of patients. A larger translational shift was due to variation in rectal volume and changes in COM position of the bladder and rectum. A consistent bladder positioning and/or rectum filling compared with presimulation volume were essential for adequate coverage of PLN in a hypofractionated treatment regime.

Comparing measurement-derived (3DVH) and machine log file-derived dose reconstruction methods for VMAT QA in patient geometries.

The purpose of this study was to compare the measurement-derived (3DVH) dose reconstruction method with machine log file-derived dose reconstruction method in patient geometries for VMAT delivery. A total of ten patient plans were selected from a regular fractionation plan to complex SBRT plans. Treatment sites in the lung and abdomen were chosen to explore the effects of tissue heterogeneity on the respective dose reconstruction algorithms. Single- and multiple-arc VMAT plans were generated to achieve the desired target objectives. Delivered plan in the patient geometry was reconstructed by using ArcCHECK Planned Dose Perturbation (ACPDP) within 3DVH software, and by converting the machine log file to Pinnacle3 9.0 treatment plan format and recalculating dose with CVSP algorithm. In addition, delivered gantry angles between machine log file and 3DVH 4D measurement were also compared to evaluate the accuracy of the virtual inclinometer within the 3DVH. Measured ion chamber and 3DVH-derived isocenter dose agreed with planned dose within 0.4% ± 1.2% and -1.0% ± 1.6%, respectively. 3D gamma analysis showed greater than 98% between log files and 3DVH reconstructed dose. Machine log file reconstructed doses and TPS dose agreed to within 2% in PTV and OARs over the entire treatment. 3DVH reconstructed dose showed an average maximum dose difference of 3% ± 1.2% in PTV, and an average mean difference of -4.5% ± 10.5% in OAR doses. The average virtual inclinometer error (VIE) was -0.65° ± 1.6° for all patients, with a maximum error of -5.16° ± 4.54° for an SRS case. The time averaged VIE was within 1°-2°, and did not have a large impact on the overall accuracy of the estimated patient dose from ACPDP algorithm. In this study, we have compared two independent dose reconstruction methods for VMAT QA. Both methods are capable of taking into account the measurement and delivery parameter discrepancy, and display the delivered dose in CT patient geometry rather than the phantom geometry. The dose discrepancy can be evaluated in terms of DVH of the structures and provides a more intuitive understanding of the dosimetric impact of the delivery errors on the target and normal structure dose.

A Phase II Study Evaluating the Effect of Intensity Modulated Postmastectomy Radiation Therapy on Implant Failure Rates in Breast Cancer Patients With Immediate, 2-Stage Implant Reconstruction With an MRI Imaging Correlative Substudy.

PURPOSE: Postmastectomy radiation therapy is a mainstay in the adjuvant treatment of node-positive breast cancer, but it poses risks for women with breast reconstruction. Multibeam intensity-modulated radiation therapy improves dose conformality and homogeneity, potentially reducing complications in breast cancer patients with implant-based reconstruction. To investigate this hypothesis, we conducted a single-arm phase 2 clinical trial of breast cancer patients who underwent mastectomy/axillary dissection and prosthesis-based reconstruction. METHODS AND MATERIALS: The primary endpoint was the rate of implant failure (IF) within 24 months of permanent implant placement, which would be considered an improvement over historical controls if below 16%. IF was defined as removal leading to a flat chest wall or replacement with another reconstruction. Patients were analyzed in 2 cohorts. Cohort 1 (RT-PI) received radiation therapy to the permanent implant. Cohort 2 (RT-TE) received radiation therapy to the TE. IF rates, adverse events, and quality of life were analyzed. Follow-up/postradiation therapy assessments were compared with the baseline/preradiation therapy assessments at 3 to 10 weeks after exchange surgery. A subgroup underwent serial magnetic resonance imaging (MRI) sessions to explore the association between MRI-detected changes and capsular contracture, a known adverse effect of radiation therapy. RESULTS: Between June 2014 and March 2017, 119 women were enrolled. Cohort 1 included 45 patients, and cohort 2 had 74 patients. Among 100 evaluable participants, 25 experienced IF during the study period. IF occurred in 8/42 (19%) and 17/58 (29%) in cohorts 1 and 2, respectively. Among the IFs, the majority were due to capsular contracture (13), infection (7), exposure (3), and other reasons (2). Morphologic shape features observed in longitudinal MRI images were associated with the development of Baker grade 3 to 4 contractures. CONCLUSIONS: The rate of IF in reconstructed breast cancer patients treated with intensity-modulated radiation therapy was similar to, but not improved over, that observed with conventional, 3-dimensional-conformal methods. MRI features show promise for predicting capsular contracture but require validation in larger studies.

Treatment planning for MR-guided SBRT of pancreatic tumors on a 1.5 T MR-Linac: A global consensus protocol.

Background and purpose: Treatment planning for MR-guided stereotactic body radiotherapy (SBRT) for pancreatic tumors can be challenging, leading to a wide variation of protocols and practices. This study aimed to harmonize treatment planning by developing a consensus planning protocol for MR-guided pancreas SBRT on a 1.5 T MR-Linac. Materials and methods: A consortium was founded of thirteen centers that treat pancreatic tumors on a 1.5 T MR-Linac. A phased planning exercise was conducted in which centers iteratively created treatment plans for two cases of pancreatic cancer. Each phase was followed by a meeting where the instructions for the next phase were determined. After three phases, a consensus protocol was reached. Results: In the benchmarking phase (phase I), substantial variation between the SBRT protocols became apparent (for example, the gross tumor volume (GTV) D99% ranged between 36.8 - 53.7 Gy for case 1, 22.6 - 35.5 Gy for case 2). The next phase involved planning according to the same basic dosimetric objectives, constraints, and planning margins (phase II), which led to a large degree of harmonization (GTV D99% range: 47.9-53.6 Gy for case 1, 33.9-36.6 Gy for case 2). In phase III, the final consensus protocol was formulated in a treatment planning system template and again used for treatment planning. This not only resulted in further dosimetric harmonization (GTV D99% range: 48.2-50.9 Gy for case 1, 33.5-36.0 Gy for case 2) but also in less variation of estimated treatment delivery times. Conclusion: A global consensus protocol has been developed for treatment planning for MR-guided pancreatic SBRT on a 1.5 T MR-Linac. Aside from harmonizing the large variation in the current clinical practice, this protocol can provide a starting point for centers that are planning to treat pancreatic tumors on MR-Linac systems.

A model for gastrointestinal tract motility in a 4D imaging phantom of human anatomy.

BACKGROUND: Gastrointestinal (GI) tract motility is one of the main sources for intra/inter-fraction variability and uncertainty in radiation therapy for abdominal targets. Models for GI motility can improve the assessment of delivered dose and contribute to the development, testing, and validation of deformable image registration (DIR) and dose-accumulation algorithms. PURPOSE: To implement GI tract motion in the 4D extended cardiac-torso (XCAT) digital phantom of human anatomy. MATERIALS AND METHODS: Motility modes that exhibit large amplitude changes in the diameter of the GI tract and may persist over timescales comparable to online adaptive planning and radiotherapy delivery were identified based on literature research. Search criteria included amplitude changes larger than planning risk volume expansions and durations of the order of tens of minutes. The following modes were identified: peristalsis, rhythmic segmentation, high amplitude propagating contractions (HAPCs), and tonic contractions. Peristalsis and rhythmic segmentations were modeled by traveling and standing sinusoidal waves. HAPCs and tonic contractions were modeled by traveling and stationary Gaussian waves. Wave dispersion in the temporal and spatial domain was implemented by linear, exponential, and inverse power law functions. Modeling functions were applied to the control points of the nonuniform rational B-spline surfaces defined in the reference XCAT library. GI motility was combined with the cardiac and respiratory motions available in the standard 4D-XCAT phantom. Default model parameters were estimated based on the analysis of cine MRI acquisitions in 10 patients treated in a 1.5T MR-linac. RESULTS: We demonstrate the ability to generate realistic 4D multimodal images that simulate GI motility combined with respiratory and cardiac motion. All modes of motility, except tonic contractions, were observed in the analysis of our cine MRI acquisitions. Peristalsis was the most common. Default parameters estimated from cine MRI were used as initial values for simulation experiments. It is shown that in patients undergoing stereotactic body radiotherapy for abdominal targets, the effects of GI motility can be comparable or larger than the effects of respiratory motion. CONCLUSION: The digital phantom provides realistic models to aid in medical imaging and radiation therapy research. The addition of GI motility will further contribute to the development, testing, and validation of DIR and dose accumulation algorithms for MR-guided radiotherapy.

Deep learning-based dominant index lesion segmentation for MR-guided radiation therapy of prostate cancer.

BACKGROUND: Dose escalation radiotherapy enables increased control of prostate cancer (PCa) but requires segmentation of dominant index lesions (DIL). This motivates the development of automated methods for fast, accurate, and consistent segmentation of PCa DIL. PURPOSE: To construct and validate a model for deep-learning-based automatic segmentation of PCa DIL defined by Gleason score (GS) ≥3+4 from MR images applied to MR-guided radiation therapy. Validate generalizability of constructed models across scanner and acquisition differences. METHODS: Five deep-learning networks were evaluated on apparent diffusion coefficient (ADC) MRI from 500 lesions in 365 patients arising from internal training Dataset 1 (156 lesions in 125 patients, 1.5Tesla GE MR with endorectal coil), testing using Dataset 1 (35 lesions in 26 patients), external ProstateX Dataset 2 (299 lesions in 204 patients, 3Tesla Siemens MR), and internal inter-rater Dataset 3 (10 lesions in 10 patients, 3Tesla Philips MR). The five networks include: multiple resolution residually connected network (MRRN) and MRRN regularized in training with deep supervision implemented into the last convolutional block (MRRN-DS), Unet, Unet++, ResUnet, and fast panoptic segmentation (FPSnet) as well as fast panoptic segmentation with smoothed labels (FPSnet-SL). Models were evaluated by volumetric DIL segmentation accuracy using Dice similarity coefficient (DSC) and the balanced F1 measure of detection accuracy, as a function of lesion aggressiveness and size (Dataset 1 and 2), and accuracy with respect to two-raters (on Dataset 3). Upon acceptance for publication segmentation models will be made available in an open-source GitHub repository. RESULTS: In general, MRRN-DS more accurately segmented tumors than other methods on the testing datasets. MRRN-DS significantly outperformed ResUnet in Dataset2 (DSC of 0.54 vs. 0.44, p < 0.001) and the Unet++ in Dataset3 (DSC of 0.45 vs. p = 0.04). FPSnet-SL was similarly accurate as MRRN-DS in Dataset2 (p = 0.30), but MRRN-DS significantly outperformed FPSnet and FPSnet-SL in both Dataset1 (0.60 vs. 0.51 [p = 0.01] and 0.54 [p = 0.049] respectively) and Dataset3 (0.45 vs. 0.06 [p = 0.002] and 0.24 [p = 0.004] respectively). Finally, MRRN-DS produced slightly higher agreement with experienced radiologist than two radiologists in Dataset 3 (DSC of 0.45 vs. 0.41). CONCLUSIONS: MRRN-DS was generalizable to different MR testing datasets acquired using different scanners. It produced slightly higher agreement with an experienced radiologist than that between two radiologists. Finally, MRRN-DS more accurately segmented aggressive lesions, which are generally candidates for radiative dose ablation.

Real-time 4D MRI using MR signature matching (MRSIGMA) on a 1.5T MR-Linac system.

Objective. To develop real-time 4D MRI using MR signature matching (MRSIGMA) for volumetric motion imaging in patients with pancreatic cancer on a 1.5T MR-Linac system.Approach. Two consecutive MRI scans with 3D golden-angle radial stack-of-stars acquisitions were performed on ten patients with inoperable pancreatic cancer. The complete first scan (905 angles) was used to compute a 4D motion dictionary including ten pairs of 3D motion images and signatures. The second scan was used for real-time imaging, where each angle (275 ms) was processed separately to match it to one of the dictionary entries. The complete second scan was also used to compute a 4D reference to assess motion tracking performance.Dicecoefficients of the gross tumor volume (GTV) and two organs-at-risk (duodenum-stomach and small bowel) were calculated between signature matching and reference. In addition, volume changes, displacements, center of mass shifts, andDicescores over time were calculated to characterize motion.Main results. Total imaging latency of MRSIGMA (acquisition + matching) was less than 300 ms. TheDicecoefficients were 0.87 ± 0.06 (GTV), 0.86 ± 0.05 (duodenum-stomach), and 0.85 ± 0.05 (small bowel), which indicate high accuracy (high mean value) and low uncertainty (low standard deviation) of MRSIGMA for real-time motion tracking. The center of mass shift was 3.1 ± 2.0 mm (GTV), 5.3 ± 3.0 mm (duodenum-stomach), and 3.4 ± 1.5 mm (small bowel). TheDicescores over time (0.97 ± [0.01-0.03]) were similarly high for MRSIGMA and reference scans in all the three contours.Significance. This work demonstrates the feasibility of real-time 4D MRI using MRSIGMA for volumetric motion tracking on a 1.5T MR-Linac system. The high accuracy and low uncertainty of real-time MRSIGMA is an essential step towards continuous treatment adaptation of tumors affected by real-time respiratory motion and could ultimately improve treatment safety by optimizing ablative dose delivery near gastrointestinal organs.