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.

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.

Tumor location, but not H3.3K27M, significantly influences the blood-brain-barrier permeability in a genetic mouse model of pediatric high-grade glioma.

Pediatric high-grade gliomas (pHGGs) occur with strikingly different frequencies in infratentorial and supratentorial regions. Although histologically these malignancies appear similar, they represent distinct diseases. Recent genomic studies have identified histone K27M H3.3/H3.1 mutations in the majority of brainstem pHGGs; these mutations are rarely encountered in pHGGs that arise in the cerebral cortex. Previous research in brainstem pHGGs suggests a restricted permeability of the blood-brain-barrier (BBB). In this work, we use dynamic contrast-enhanced (DCE) MRI to evaluate BBB permeability in a genetic mouse model of pHGG as a function of location (cortex vs. brainstem, n = 8 mice/group) and histone mutation (mutant H3.3K27M vs. wild-type H3.3, n = 8 mice/group). The pHGG models are induced either in the brainstem or the cerebral cortex and are driven by PDGF signaling and p53 loss with either H3.3K27M or wild-type H3.3. T2-weighted MRI was used to determine tumor location/extent followed by 4D DCE-MRI for estimating the rate constant (K (trans) ) for tracer exchange across the barrier. BBB permeability was 67 % higher in cortical pHGGs relative to brainstem pHGGs (t test, p = 0.012) but was not significantly affected by the expression of mutant H3.3K27M versus wild-type H3.3 (t-test, p = 0.78). Although mice became symptomatic at approximately the same time, the mean volume of cortical tumors was 3.6 times higher than the mean volume of brainstem tumors. The difference between the mean volume of gliomas with wild-type and mutant H3.3 was insignificant. Mean K (trans) was significantly correlated to glioma volume. These results present a possible explanation for the poor response of brainstem pHGGs to systemic therapy. Our findings illustrate a potential role played by the microenvironment in shaping tumor growth and BBB permeability.

4D MRI of polycystic kidneys from rapamycin-treated Glis3-deficient mice.

Polycystic kidney disease (PKD) is a life-threatening disease that leads to a grotesque enlargement of the kidney and significant loss of function. Several imaging studies with MRI have demonstrated that cyst size in polycystic kidneys can determine disease severity and progression. In the present study, we found that, although kidney volume and cyst volume decreased with drug treatment, renal function did not improve with treatment. Here, we applied dynamic contrast-enhanced MRI to study PKD in a Glis3 (GLI-similar 3)-deficient mouse model. Cysts from this model have a wide range of sizes and develop at an early age. To capture this crucial stage and assess cysts in detail, we imaged during early development (3-17 weeks) and applied high spatiotemporal resolution MRI (125 × 125 × 125 cubic microns every 7.7 s). A drug treatment with rapamycin (also known as sirolimus) was applied to determine whether disease progression could be halted. The effect and synergy (interaction) of aging and treatment were evaluated using an analysis of variance (ANOVA). Structural measurements, including kidney volume, cyst volume and cyst-to-kidney volume ratio, changed significantly with age. Drug treatment significantly decreased these metrics. Functional measurements of time-to-peak (TTP) mean and TTP variance were determined. TTP mean did not change with age, whereas TTP variance increased with age. Treatment with rapamycin generally did not affect these functional metrics. Synergistic effects of treatment and age were not found for any measurements. Together, the size and volume ratio of cysts decreased with drug treatment, whereas renal function remained the same. The quantification of renal structure and function with MRI can comprehensively assess the pathophysiology of PKD and response to treatment.

Four-dimensional MRI of renal function in the developing mouse.

The major roles of filtration, metabolism and high blood flow make the kidney highly vulnerable to drug-induced toxicity and other renal injuries. A method to follow kidney function is essential for the early screening of toxicity and malformations. In this study, we acquired high spatiotemporal resolution (four dimensional) datasets of normal mice to follow changes in kidney structure and function during development. The data were acquired with dynamic contrast-enhanced MRI (via keyhole imaging) and a cryogenic surface coil, allowing us to obtain a full three-dimensional image (isotropic resolution, 125 microns) every 7.7 s over a 50-min scan. This time course permitted the demonstration of both contrast enhancement and clearance. Functional changes were measured over a 17-week course (at 3, 5, 7, 9, 13 and 17 weeks). The time dimension of the MRI dataset was processed to produce unique image contrasts to segment the four regions of the kidney: cortex (CO), outer stripe (OS) of the outer medulla (OM), inner stripe (IS) of the OM and inner medulla (IM). Local volumes, time-to-peak (TTP) values and decay constants (DC) were measured in each renal region. These metrics increased significantly with age, with the exception of DC values in the IS and OS. These data will serve as a foundation for studies of normal renal physiology and future studies of renal diseases that require early detection and intervention.

Technical Development and In Silico Implementation of SyntheticMR in Head and Neck Adaptive Radiation Therapy: A Prospective R-IDEAL Stage 0/1 Technology Development Report.

Objective: The purpose of this study was to investigate the technical feasibility of integrating the quantitative maps available from SyntheticMR into the head and neck adaptive radiation oncology workflow. While SyntheticMR has been investigated for diagnostic applications, no studies have investigated its feasibility and potential for MR-Simulation or MR-Linac workflow. Demonstrating the feasibility of using this technique will facilitate rapid quantitative biomarker extraction which can be leveraged to guide adaptive radiation therapy decision making. Approach: Two phantoms, two healthy volunteers, and one patient were scanned using SyntheticMR on the MR-Simulation and MR-Linac devices with scan times between four to six minutes. Images in phantoms and volunteers were conducted in a test/retest protocol. The correlation between measured and reference quantitative T1, T2, and PD values were determined across clinical ranges in the phantom. Distortion was also studied. Contours of head and neck organs-at-risk (OAR) were drawn and applied to extract T1, T2, and PD. These values were plotted against each other, clusters were computed, and their separability significance was determined to evaluate SyntheticMR for differentiating tumor and normal tissue. Main Results: The Lin's Concordance Correlation Coefficient between the measured and phantom reference values was above 0.98 for both the MR-Sim and MR-Linac. No significant levels of distortion were measured. The mean bias between the measured and phantom reference values across repeated scans was below 4% for T1, 7% for T2, and 4% for PD for both the MR-Sim and MR-Linac. For T1 vs. T2 and T1 vs. PD, the GTV contour exhibited perfect purity against neighboring OARs while being 0.7 for T2 vs. PD. All cluster significance levels between the GTV and the nearest OAR, the tongue, using the SigClust method was p < 0.001. Significance: The technical feasibility of SyntheticMR was confirmed. Application of this technique to the head and neck adaptive radiation therapy workflow can enrich the current quantitative biomarker landscape.

4D lung MRI with high-isotropic-resolution using half-spoke (UTE) and full-spoke 3D radial acquisition and temporal compressed sensing reconstruction.

Objective. To develop a respiratory motion-resolved four-dimensional (4D) magnetic resonance imaging (MRI) technique with high-isotropic-resolution (1.1 mm) using 3D radial sampling, camera-based respiratory motion sensing, and temporal compressed sensing reconstruction for lung cancer imaging.Approach. Free-breathing half- and full-spoke 3D golden-angle radial acquisitions were performed on eight healthy volunteers and eight patients with lung tumors of varying size. A back-and-forth k-space ordering between consecutive interleaves of the 3D radial acquisition was performed to minimize eddy current-related artifacts. Data were sorted into respiratory motion states using camera-based motion navigation and 4D images were reconstructed using temporal compressed sensing to reduce scan time. Normalized sharpness indices of the diaphragm, apparent signal-to-noise ratio (aSNR) and contrast-to-noise ratio (CNR) of the lung tumor (patients only), liver, and aortic arch were compared between half- and full-spoke 4D MRI images to evaluate the impact of respiratory motion and image contrast on 4D MRI image quality. Respiration-induced changes in lung volumes and center of mass shifts were compared between half- and full-spoke 4D MRI measurements. In addition, the motion measurements from 4D MRI and the same-day 4D CT were presented in one of the lung tumor patients.Main results. Half-spoke 4D MRI provides better visualization of the lung parenchyma, while full-spoke 4D MRI presents sharper diaphragm images and higher aSNR and CNR in the lung tumor, liver, and aortic arch. Lung volume changes and center of mass shifts measured by half- and full-spoke 4D MRI were not statistically different. For the patient with 4D MRI and same-day 4D CT, lung volume changes and center of mass shifts were generally comparable.Significance. This work demonstrates the feasibility of a motion-resolved 4D MRI technique with high-isotropic-resolution using 3D radial acquisition, camera-based respiratory motion sensing, and temporal compressed sensing reconstruction for treatment planning and motion monitoring in radiotherapy of lung cancer.

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.

SBRT focal dose intensification using an MR-Linac adaptive planning for intermediate-risk prostate cancer: An analysis of the dosimetric impact of intra-fractional organ changes.

INTRODUCTION: Using an magnetic resonance linear accelerator (MR-Linac) may improve the precision of visible tumor boosting with ultra-hypofractionation by accounting for daily positional changes in the target and organs at risk (OAR). PATIENTS AND METHODS: Fifteen patients with prostate cancer and an MR-detected dominant lesion were treated on the MR-Linac with stereotactic body radiation (SBRT) to 40 Gy in 5 fractions, boosting the gross tumor volume (GTV) to 45 Gy with daily adaptive planning. Imaging was acquired again after initial planning (verification scan), and immediately after treatment (post-treatment scan). Prior to beam-on, additional adjustments were made on the verification scan. Contours were retrospectively adjusted on verification and post-treatment scans, and the daily plan recalculated on these scans to estimate the true dose delivered. RESULTS: The median prostate D95% for plan 1, 2 and 3 was 40.3 Gy, 40.5 Gy and 40.3 Gy and DIL D95% was 45.7 Gy, 45.2 Gy and 44.6 Gy, respectively. Bladder filling was associated with reduced GTV coverage (p = 0.03, plan 1 vs 2) and prostate coverage (p = 0.03, plan 2 vs 3). The D0.035 cc constraint was exceeded on verification and post-treatment plans in 24 % and 33 % of fractions for the urethra, 31 % and 45 % for the bladder, and 35 % and 25 % for the rectum, respectively. CONCLUSION: MR-Linac guided, daily adaptive SBRT with focal boosting of the GTV yields acceptable planned and delivered dosimetry. Adaptive planning with a MR-Linac may reliably deliver the prescribed dose to the intended tumor target.

View-sharing for 4D magnetic resonance imaging with randomized projection-encoding enables improvements of respiratory motion imaging for treatment planning in abdominothoracic radiotherapy.

Background and Purpose: The accuracy and precision of radiation therapy are dependent on the characterization of organ-at-risk and target motion. This work aims to demonstrate a 4D magnetic resonance imaging (MRI) method for improving spatial and temporal resolution in respiratory motion imaging for treatment planning in abdominothoracic radiotherapy. Materials and Methods: The spatial and temporal resolution of phase-resolved respiratory imaging is improved by considering a novel sampling function based on quasi-random projection-encoding and peripheral k-space view-sharing. The respiratory signal is determined directly from k-space, obviating the need for an external surrogate marker. The average breathing curve is used to optimize spatial resolution and temporal blurring by limiting the extent of data sharing in the Fourier domain. Improvements in image quality are characterized by evaluating changes in signal-to-noise ratio (SNR), resolution, target detection, and level of artifact. The method is validated in simulations, in a dynamic phantom, and in-vivo imaging. Results: Sharing of high-frequency k-space data, driven by the average breathing curve, improves spatial resolution and reduces artifacts. Although equal sharing of k-space data improves resolution and SNR in stationary features, phases with large temporal changes accumulate significant artifacts due to averaging of high frequency features. In the absence of view-sharing, no averaging and detection artifacts are observed while spatial resolution is degraded. Conclusions: The use of a quasi-random sampling function, with view-sharing driven by the average breathing curve, provides a feasible method for self-navigated 4D-MRI at improved spatial resolution.

Quantitative longitudinal mapping of radiation-treated prostate cancer using MR fingerprinting with radial acquisition and subspace reconstruction.

MR fingerprinting (MRF) enables fast multiparametric quantitative imaging with a single acquisition and has been shown to improve diagnosis of prostate cancer. However, most prostate MRF studies were performed with spiral acquisitions that are sensitive to B0 inhomogeneities and consequent blurring. In this work, a radial MRF acquisition with a novel subspace reconstruction technique was developed to enable fast T1/T2 mapping in the prostate in under 4 min. The subspace reconstruction exploits the extensive temporal correlations in the MRF dictionary to pre-compute a low dimensional space for the solution and thus reduce the number of radial spokes to accelerate the acquisition. Iterative reconstruction with the subspace model and additional regularization of the signal representation in the subspace is performed to minimize the number of spokes and maintain matching quality and SNR. Reconstruction accuracy was assessed using the ISMRM NIST phantom. In-vivo validation was performed on two healthy subjects and two prostate cancer patients undergoing radiation therapy. The longitudinal repeatability was quantified using the concordance correlation coefficient (CCC) in one of the healthy subjects by repeated scans over 1 year. One prostate cancer patient was scanned at three time points, before initiating therapy and following brachytherapy and external beam radiation. Changes in the T1/T2 maps obtained with the proposed method were quantified. The prostate, peripheral and transitional zones, and visible dominant lesion were delineated for each study, and the statistics and distribution of the quantitative mapping values were analyzed. Significant image quality improvements compared with standard reconstruction methods were obtained with the proposed subspace reconstruction method. A notable decrease in the spread of the T1/T2 values without biasing the estimated mean values was observed with the subspace reconstruction and agreed with reported literature values. The subspace reconstruction enabled visualization of small differences in T1/T2 values in the tumor region within the peripheral zone. Longitudinal imaging of a volunteer subject yielded CCC of 0.89 for MRF T1, and 0.81 for MRF T2 in the prostate gland. Longitudinal imaging of the prostate patient confirmed the feasibility of capturing radiation treatment related changes. This work is a proof-of-concept for a high resolution and fast quantitative mapping using golden-angle radial MRF combined with a subspace reconstruction technique for longitudinal treatment response assessment in subjects undergoing radiation treatment.

An evaluation of the use of EBT-XD film for SRS/SBRT commissioning of a 1.5 Tesla MR-Linac system.

PURPOSE: The goal of this study was to evaluate the use of EBT-XD film for SRS/SBRT commissioning in a 1.5T hybrid MR-Linac (MRL). METHOD: The output factors (St), from 1x1, 2x2, 3x3 cm2, were measured with film in solid water. The results were compared with (1) the measurements by a PTW diamond detector (CVD) and an Exradin® A26MR ion chamber in 3D water phantom; (2) Monte Carlo calculation by Monaco TPS (MTPS) in water. The inline (IN) and crossline (CR) profiles, measured by films and the CVD, were also compared. An SRS plan with two targets was created in MTPS and was measured with EBT-XD film in a StereoPHANTM phantom serving as an end-to-end test. The 3x3 cm2 was used for film calibration with doses ranging from 0 to 28 Gy. Water was added to the phantom-film-phantom interface to reduce the electron-return-effect (ERE). Films were calibrated with One-scan-dosimetry protocol. RESULTS: The film St were within 1.2% and 2.2% compared to other detectors and MTPS respectively. At the central B-field induced asymmetric region, films were within 0.6% between the CVD and the MTPS, but 5-8% differences were observed in the 40%-5% gradient region in CR due to ERE. The differences in localization and dose were found to be 0.6 mm and 3.3%. The γ(3%/2mm), γ (5%/2mm), γ (5%/1mm) were 97.7%, 99.3%, 94.6%. CONCLUSIONS: Films can provide accurate dosimetric results under ERE and are valuable for commissioning MRL. Using the One-scan-dosimetry protocol with EBT-XD film for MRL increases accuracy and efficiency in commissioning and QA of SRS/SBRT.

Integration of an Independent Monitor Unit Check for High-Magnetic-Field MR-Guided Radiation Therapy System.

Purpose: Commercial independent monitor unit (IMU) check systems for high-magnetic-field MR-guided radiation therapy (RT) systems are lacking. We investigated the feasibility of adopting an existing treatment planning system (TPS) as an IMU check for online adaptive radiotherapy using 1.5-Tesla MR-Linac. Methods: The 7-MV flattening filter free (FFF) beam and multi-leaf collimator (MLC) models of a 1.5-T Elekta Unity MR-Linac within Monte Carlo-based Monaco TPS were used to generate an optimized beam model in Eclipse TPS. The MLC dosimetric leaf gap of the beam in Eclipse was determined by matching the dose distribution of Eclipse-generated intensity-modulated radiation therapy (IMRT) plans using the Analytical Anisotropic Algorithm (AAA) algorithm to Monaco plans. The plans were automatically adjusted for different source-to-axis distances (SADs) between the two systems. For IMU check, the treatment plans developed in Monaco were transferred to Eclipse to recalculate the dose using AAA. A plug-in within Eclipse was created to perform a 2D gamma analysis of the AAA and Monte Carlo dose distribution on a beam's eye view parallel plane. Monaco dose distribution was shifted laterally by 2 mm during gamma analysis to account for the impact of magnetic field on electron trajectories. Eclipse doses for posterior beams were corrected for both the Unity couch and the posterior MR coil attenuation. Thirteen patients, each with 4-5 fractions for a variety of tumor sites (pancreas, rectum, and prostate), were tested. Results: After thorough commissioning, the method was implemented as part of the standard clinical workflow. A total of 62 online plans, each with approximately 15 beams, were evaluated. The average per-beam gamma (3%/3 mm) pass rate for plans was 97.9% (range, 95.9% to 98.8%). The average pass rate per beam for all 932 beams used in these plans was 97.9% ± 1.9%, with the lowest per-beam gamma pass rate at 88.4%. The time for the process was within 3.2 ± 0.9 min. Conclusion: The use of a second planning system provides an efficient way to perform IMU checks with clinically acceptable accuracy for online adaptive plans on Unity MR-Linac. This is essential for meeting the safety requirements for second checks as outlined in American Association of Physicists in Medicine Task Group (AAPM TG) reports 114 and 219.

Inter- and intrafraction motion assessment and accumulated dose quantification of upper gastrointestinal organs during magnetic resonance-guided ablative radiation therapy of pancreas patients.

BACKGROUND AND PURPOSE: Stereotactic body radiation therapy (SBRT) of locally advanced pancreatic cancer (LAPC) is challenging due to significant motion of gastrointestinal (GI) organs. The goal of our study was to quantify inter and intrafraction deformations and dose accumulation of upper GI organs in LAPC patients. MATERIALS AND METHODS: Five LAPC patients undergoing five-fraction magnetic resonance-guided radiation therapy (MRgRT) using abdominal compression and daily online plan adaptation to 50 Gy were analyzed. A pre-treatment, verification, and post-treatment MR imaging (MRI) for each of the five fractions (75 total) were used to calculate intra and interfraction motion. The MRIs were registered using Large Deformation Diffeomorphic Metric Mapping (LDDMM) deformable image registration (DIR) method and total dose delivered to stomach_duodenum, small bowel (SB) and large bowel (LB) were accumulated. Deformations were quantified using gradient magnitude and Jacobian integral of the Deformation Vector Fields (DVF). Registration DVFs were geometrically assessed using Dice and 95th percentile Hausdorff distance (HD95) between the deformed and physician's contours. Accumulated doses were then calculated from the DVFs. RESULTS: Median Dice and HD95 were: Stomach_duodenum (0.9, 1.0 mm), SB (0.9, 3.6 mm), and LB (0.9, 2.0 mm). Median (max) interfraction deformation for stomach_duodenum, SB and LB was 6.4 (25.8) mm, 7.9 (40.5) mm and 7.6 (35.9) mm. Median intrafraction deformation was 5.5 (22.6) mm, 8.2 (37.8) mm and 7.2 (26.5) mm. Accumulated doses for two patients exceeded institutional constraints for stomach_duodenum, one of whom experienced Grade1 acute and late abdominal toxicity. CONCLUSION: LDDMM method indicates feasibility to measure large GI motion and accumulate dose. Further validation on larger cohort will allow quantitative dose accumulation to more reliably optimize online MRgRT.

Feasibility of ablative stereotactic body radiation therapy of pancreas cancer patients on a 1.5 Tesla magnetic resonance-linac system using abdominal compression.

BACKGROUND AND PURPOSE: Stereotactic body radiation therapy delivered using MR-guided radiotherapy (MRgRT) and automatic breathold gating has shown to improve overall survival for locally advanced pancreatic cancer (LAPC) patients. The goal of our study was to evaluate feasibility of treating LAPC patients using abdominal compression (AC) and impact of potential intrafraction motion on planned dose on a 1.5T MR-linac. METHODS & MATERIALS: Ten LAPC patients were treated with MRgRT to 50 Gy in 5 fractions with daily online plan adaptation and AC. Three orthogonal plane cine MRI were acquired to assess stability of AC pressure in minimizing tumor motion. Three sets of T2w MR scans, pre-treatment (MRIpre), verification (MRIver) and post-treatment (MRIpost) MRI, were acquired for every fraction. A total of 150 MRIs and doses were evaluated. Impact of intrafraction organ motion was evaluated by propagating pre-treatment plan and structures to MRIver and MRIpost, editing contours and recalculating doses. Gross tumor volume (GTV) coverage and organs-at-risk (OARs) doses were evaluated on MRIver and MRIpost. RESULTS: Median total treatment time was 75.5 (49-132) minutes. Median tumor motion in AC for all fractions was 1.7 (0.7-7), 2.1 (0.6-6.3) and 4.1 (1.4-10.0) mm in anterior-posterior, left-right and superior-inferior direction. Median GTV V50Gy was 78.7%. Median D5cm3 stomach_duodenum was 24.2 (18.4-29.3) Gy on MRIver and 24.2 (18.3-30.5) Gy on MRIpost. Median D5cm3 small bowel was 24.3 (18.2-32.8) Gy on MRIver and 24.4 (16.0-33.6) Gy on MRIpost. CONCLUSION: Dose-volume constraints for OARs were exceeded for some fractions on MRIver and MRIpost. Longer follow up is needed to see the dosimetric impact of intrafraction motion on gastrointestinal toxicity.

Lung perfusion imaging in small animals using 4D micro-CT at heartbeat temporal resolution.

PURPOSE: Quantitative in vivo imaging of lung perfusion in rodents can provide critical information for preclinical studies. However, the combined challenges of high temporal and spatial resolution have made routine quantitative perfusion imaging difficult in small animals. The purpose of this work is to demonstrate 4D micro-CT for perfusion imaging in rodents at heartbeat temporal resolution and isotropic spatial resolution. METHODS: We have recently developed a dual tube/detector micro-CT scanner that is well suited to capture first pass kinetics of a bolus of contrast agent used to compute perfusion information. Our approach is based on the paradigm that similar time density curves can be reproduced in a number of consecutive, small volume injections of iodinated contrast agent at a series of different angles. This reproducibility is ensured by the high-level integration of the imaging components of our system with a microinjector, a mechanical ventilator, and monitoring applications. Sampling is controlled through a biological pulse sequence implemented in LABVIEW. Image reconstruction is based on a simultaneous algebraic reconstruction technique implemented on a graphic processor unit. The capabilities of 4D micro-CT imaging are demonstrated in studies on lung perfusion in rats. RESULTS: We report 4D micro-CT imaging in the rat lung with a heartbeat temporal resolution (approximately 150 ms) and isotropic 3D reconstruction with a voxel size of 88 microm based on sampling using 16 injections of 50 microL each. The total volume of contrast agent injected during the experiments (0.8 mL) was less than 10% of the total blood volume in a rat. This volume was not injected in a single bolus, but in multiple injections separated by at least 2 min interval to allow for clearance and adaptation. We assessed the reproducibility of the time density curves with multiple injections and found that these are very similar. The average time density curves for the first eight and last eight injections are slightly different, i.e., for the last eight injections, both the maximum of the average time density curves and its area under the curve are decreased by 3.8% and 7.2%, respectively, relative to the average time density curves based on the first eight injections. The radiation dose associated with our 4D micro-CT imaging is 0.16 Gy and is therefore in the range of a typical micro-CT dose. CONCLUSIONS: 4D micro-CT-based perfusion imaging demonstrated here has immediate application in a wide range of preclinical studies such as tumor perfusion, angiogenesis, and renal function. Although our imaging system is in many ways unique, we believe that our approach based on the multiple injection paradigm can be used with the newly developed flat-panel slip-ring-based micro-CT to increase their temporal resolution in dynamic perfusion studies.