Abdominal MR Multitasking for radiotherapy treatment planning: A motion-resolved and multicontrast 3D imaging approach.

PURPOSE: Radiotherapy treatment planning (RTP) using MR has been used increasingly for the abdominal site. Multiple contrast weightings and motion-resolved imaging are desired for accurate delineation of the target and various organs-at-risk and patient-tailored planning. Current MR protocols achieve these through multiple scans with distinct contrast and variable respiratory motion management strategies and acquisition parameters, leading to a complex and inaccurate planning process. This study presents a standalone MR Multitasking (MT)-based technique to produce volumetric, motion-resolved, multicontrast images for abdominal radiotherapy treatment planning. METHODS: The MT technique resolves motion and provides a wide range of contrast weightings by repeating a magnetization-prepared (saturation recovery and T2 preparations) spoiled gradient-echo readout series and adopting the MT image reconstruction framework. The performance of the technique was assessed through digital phantom simulations and in vivo studies of both healthy volunteers and patients with liver tumors. RESULTS: In the digital phantom study, the MT technique presented structural details and motion in excellent agreement with the digital ground truth. The in vivo studies showed that the motion range was highly correlated (R2 = 0.82) between MT and 2D cine imaging. MT allowed for a flexible contrast-weighting selection for better visualization. Initial clinical testing with interobserver analysis demonstrated acceptable target delineation quality (Dice coefficient = 0.85 ± 0.05, Hausdorff distance = 3.3 ± 0.72 mm). CONCLUSION: The developed MT-based, abdomen-dedicated technique is capable of providing motion-resolved, multicontrast volumetric images in a single scan, which may facilitate abdominal radiotherapy treatment planning.

Clinical Outcomes of Prostate SBRT Using Non-adaptive MR-Guided Radiotherapy.

OBJECTIVES: Stereotactic body radiotherapy (SBRT) is widely used for localized prostate cancer and implementation of MR-guided radiotherapy has the advantage of tighter margins and improved sparing of organs at risk. Here we evaluate outcomes and time required to treat using non-adaptive MR-guided SBRT (MRgSBRT) for localized prostate cancer at our institution. METHODS: From 9/2019 to 11/2021 we conducted a retrospective review of 80 consecutive patients who were treated with MRgSBRT to the prostate. Patients included low (LR) (5%), favorable intermediate (FIR) (40%), unfavorable intermediate (UIR) (49%), and high risk (HR) (6%). Short-term androgen deprivation therapy was used in 32% of patients. Target volumes included prostate gland and proximal seminal vesicles with an isotropic 3 mm margin. Treatment was prescribed to 36.25 Gy in 5 fractions every other day with urethral sparing. Hydrogel spacer was used in 18% of patients. Time on the linac was recorded as beam on time (BOT) plus total treatment time (TTT) including gating. Analyzed outcomes included PSA response and patient reported outcomes scored by the American Urological Association (AUA) questionnaire and toxicity per CTCAE v5. General linear regression model was used to analyze factors affecting PSA and AUA in longitudinal follow up, and chi-square test was used to assess factors affecting toxicity. RESULTS: Median follow up was 19.3 months (3.8 - 36.6). Median BOT was 4.6 min (2.6 - 7.2) with a median TTT of 11 min (7.6 - 15.8). Pre-treatment vs post-RT median PSA was 6.36 (2.20 - 19.6) vs 0.85 (0.19 - 3.6), respectively (P < 0.001). PSA decrease differed significantly when patients were stratified by risk category, favoring LR/FIR vs UIF/HR group (P = 0.019). Four (5%) patients experienced a biochemical failure (BCF), with a median time to BCF of 20.4 months (7.9 - 34.5). Median biochemical failure free survival (BCFFS) was not reached, with 2-yr and 4-yr BCFFS of 97.1% and 72.1%, respectively. Patients with LR/FIR disease had 100% 2-yr and 4-yr BCFFS, whereas patients with UIF/HR had 95% and 41% 2-yr and 4-yr BCFFS (P = 0.05). Mean pre-treatment AUA was 7.3 (1 - 25) vs 11.3 (1 - 26) at first follow-up; however, AUA normalized to baseline over time. Urethral Dmax ≥35 Gy trended to lower AUA score at all follow-ups (P = 0.07). Forty-one (51%) patients reported grade 1-2 genitourinary toxicities at the 1 month follow up. Grade 3 toxicity (proctitis) was noted in 1 patient. There was no decrease in any grade rectal toxicity with use of hydrogel spacer (3 vs 6, P = 0.2). No grade ≥4 toxicities was observed. CONCLUSIONS: MRgSBRT has the potential for treatment adaptation but this comes at the cost of increased resource utilization. Our experience with non-adaptive MRgSBRT of the prostate highlights its short treatment times as well as efficacy with good PSA control and low toxicity profile.

Radiomics-enhanced early regression index for predicting treatment response in rectal cancer: a multi-institutional 0.35 T MRI-guided radiotherapy study.

PURPOSE: The accurate prediction of treatment response in locally advanced rectal cancer (LARC) patients undergoing MRI-guided radiotherapy (MRIgRT) is essential for optimising treatment strategies. This multi-institutional study aimed to investigate the potential of radiomics in enhancing the predictive power of a known radiobiological parameter (Early Regression Index, ERITCP) to evaluate treatment response in LARC patients treated with MRIgRT. METHODS: Patients from three international sites were included and divided into training and validation sets. 0.35 T T2*/T1-weighted MR images were acquired during simulation and at each treatment fraction. The biologically effective dose (BED) conversion was used to account for different radiotherapy schemes: gross tumour volume was delineated on the MR images corresponding to specific BED levels and radiomic features were then extracted. Multiple logistic regression models were calculated, combining ERITCP with other radiomic features. The predictive performance of the different models was evaluated on both training and validation sets by calculating the receiver operating characteristic (ROC) curves. RESULTS: A total of 91 patients was enrolled: 58 were used as training, 33 as validation. Overall, pCR was observed in 25 cases. The model showing the highest performance was obtained combining ERITCP at BED = 26 Gy with a radiomic feature (10th percentile of grey level histogram, 10GLH) calculated at BED = 40 Gy. The area under ROC curve (AUC) of this combined model was 0.98 for training set and 0.92 for validation set, significantly higher (p = 0.04) than the AUC value obtained using ERITCP alone (0.94 in training and 0.89 in validation set). CONCLUSION: The integration of the radiomic analysis with ERITCP improves the pCR prediction in LARC patients, offering more precise predictive models to further personalise 0.35 T MRIgRT treatments of LARC patients.

A pilot study of MRI radiomics for high-risk prostate cancer stratification in 1.5 T MR-guided radiotherapy.

PURPOSE: To investigate the potential value of MRI radiomics obtained from a 1.5 T MRI-guided linear accelerator (MR-LINAC) for D'Amico high-risk prostate cancer (PC) classification in MR-guided radiotherapy (MRgRT). METHODS: One hundred seventy-six consecutive PC patients underwent 1.5 T MRgRT treatment were retrospectively enrolled. Each patient received one or two pretreatment T2 -weighted MRI scans on a 1.5 T MR-LINAC. The endpoint was to differentiate high-risk from low/intermediate-risk PC based on D'Amico criteria using MRI-radiomics. Totally 1023 features were extracted from clinical target volume (CTV) and planning target volume (PTV). Intraclass correlation coefficient of scan-rescan repeatability, feature correlation, and recursive feature elimination were used for feature dimension reduction. Least absolute shrinkage and selection operator regression was employed for model construction. Receiver operating characteristic area under the curve (AUC) analysis was used for model performance assessment in both training and testing data. RESULTS: One hundred and eleven patients fulfilled all criteria were finally included: 76 for training and 35 for testing. The constructed MRI-radiomics models extracted from CTV and PTV achieved the AUC of 0.812 and 0.867 in the training data, without significant difference (P = 0.083). The model performances remained in the testing. The sensitivity, specificity, and accuracy were 85.71%, 64.29%, and 77.14% for the PTV-based model; and 71.43%, 71.43%, and 71.43% for the CTV-based model. The corresponding AUCs were 0.718 and 0.750 (P = 0.091) for CTV- and PTV-based models. CONCLUSION: MRI-radiomics obtained from a 1.5 T MR-LINAC showed promising results in D'Amico high-risk PC stratification, potentially helpful for the future PC MRgRT. Prospective studies with larger sample sizes and external validation are warranted for further verification.

A randomized phase II trial of MR-guided prostate stereotactic body radiotherapy administered in 5 or 2 fractions for localized prostate cancer (FORT).

BACKGROUND: Ultra-hypofractionated regimens for definitive prostate cancer (PCa) radiotherapy are increasingly utilized due in part to promising safety and efficacy data complemented by greater patient convenience from a treatment course requiring fewer sessions. As such, stereotactic body radiation therapy (SBRT) is rapidly emerging as a standard definitive treatment option for patients with localized PCa. The commercially available magnetic resonance linear accelerator (MR-LINAC) integrates MR imaging with radiation delivery, providing several theoretical advantages compared to computed tomography (CT)-guided radiotherapy. MR-LINAC technology facilitates improved visualization of the prostate, real-time intrafraction tracking of prostate and organs-at-risk (OAR), and online adaptive planning to account for target movement and anatomical changes. These features enable reduced treatment volume margins and improved sparing of surrounding OAR. The theoretical advantages of MR-guided radiotherapy (MRgRT) have recently been shown to significantly reduce rates of acute grade ≥ 2 GU toxicities as reported in the prospective randomized phase III MIRAGE trial, which compared MR-LINAC vs CT-based 5 fraction SBRT in patients with localized PCa (Kishan et al. JAMA Oncol 9:365-373, 2023). Thus, MR-LINAC SBRT-utilizing potentially fewer treatments-is warranted and clinically relevant for men with low or intermediate risk PCa electing for radiotherapy as definitive treatment. METHODS/DESIGN: A total of 136 men with treatment naïve low or intermediate risk PCa will be randomized in a 1:1 ratio to 5 or 2 fractions of MR-guided SBRT using permuted block randomization. Randomization is stratified by baseline Expanded PCa Index Composite (EPIC) bowel and urinary domain scores. Patients undergoing 5 fractions will receive 37.5 Gy to the prostate over 10-14 days and patients undergoing 2 fractions will receive 25 Gy to the prostate over 7-10 days. The co-primary endpoints are GI and GU toxicities as measured by change scores in the bowel and urinary EPIC domains, respectively. The change scores will be calculated as pre-treatment (baseline) score subtracted from the 2-year score. DISCUSSION: FORT is an international, multi-institutional prospective randomized phase II trial evaluating whether MR-guided SBRT delivered in 2 fractions versus 5 fractions is non-inferior from a gastrointestinal (GI) and genitourinary (GU) toxicity standpoint at 2 years post-treatment in men with low or intermediate risk PCa. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04984343 . Date of registration: July 30, 2021. PROTOCOL VERSION: 4.0, Nov 8, 2022.

Prediction of pathologic complete response after single-dose MR-guided partial breast irradiation in low-risk breast cancer patients: the ABLATIVE-2 trial-a study protocol.

BACKGROUND: Partial breast irradiation (PBI) is standard of care in low-risk breast cancer patients after breast-conserving surgery (BCS). Pre-operative PBI can result in tumor downstaging and more precise target definition possibly resulting in less treatment-related toxicity. This study aims to assess the pathologic complete response (pCR) rate one year after MR-guided single-dose pre-operative PBI in low-risk breast cancer patients. METHODS: The ABLATIVE-2 trial is a multicenter prospective single-arm trial using single-dose ablative PBI in low-risk breast cancer patients. Patients ≥ 50 years with non-lobular invasive breast cancer ≤ 2 cm, grade 1 or 2, estrogen receptor-positive, HER2-negative, and tumor-negative sentinel node procedure are eligible. A total of 100 patients will be enrolled. PBI treatment planning will be performed using a radiotherapy planning CT and -MRI in treatment position. The treatment delivery will take place on a conventional or MR-guided linear accelerator. The prescribed radiotherapy dose is a single dose of 20 Gy to the tumor, and 15 Gy to the 2 cm of breast tissue surrounding the tumor. Follow-up MRIs, scheduled at baseline, 2 weeks, 3, 6, 9, and 12 months after PBI, are combined with liquid biopsies to identify biomarkers for pCR prediction. BCS will be performed 12 months after radiotherapy or after 6 months, if MRI does not show a radiologic complete response. The primary endpoint is the pCR rate after PBI. Secondary endpoints are radiologic response, toxicity, quality of life, cosmetic outcome, patient distress, oncological outcomes, and the evaluation of biomarkers in liquid biopsies and tumor tissue. Patients will be followed up to 10 years after radiation therapy. DISCUSSION: This trial will investigate the pathological tumor response after pre-operative single-dose PBI after 12 months in patients with low-risk breast cancer. In comparison with previous trial outcomes, a longer interval between PBI and BCS of 12 months is expected to increase the pCR rate of 42% after 6-8 months. In addition, response monitoring using MRI and biomarkers will help to predict pCR. Accurate pCR prediction will allow omission of surgery in future patients. TRIAL REGISTRATION: The trial was registered prospectively on April 28th 2022 at clinicaltrials.gov (NCT05350722).

System-dependent image distortion related to gantry positions of a 0.35 T MRgRT: Characterization and the corresponding correction.

PURPOSE: MR-guided radiotherapy with high accuracy treatment planning requires addressing MR imaging artifacts that originate from system imperfections. This work presents the characterization and corresponding correction of gantry-related imaging distortions including geometric distortion and isocenter shift in a 0.35 T magnetic resonance imaging (MRI)-guided radiotherapy (MRgRT) system using distortion vector fields (DVFs). METHODS: Two phantoms, the magnetic resonance imaging distortion in 3D (MRID3D ) phantom and the Fluke phantom, along with a human volunteer were imaged at different gantry angles on a 0.35 T MR-Linac. The geometric distortion and isocenter shift were characterized for both phantom images. DVFs with a field of view extended beyond the physical boundary of the MRID3D phantom were extracted from images taken at 30° gantry angle increments, with vendor-provided distortion correction turned on and off (DstOff). These extended DVFs were then applied to the relevant phantom images to correct their geometric distortions and isocenter shift at the respective gantry angles. The extended DVFs produced from the MRID3D phantom were also applied to Fluke phantom and human MR images at their respective gantry angles. The resampled images were evaluated using structural similarity index measure (SSIM) comparison with the vendor corrected images from the MRgRT system. RESULTS: Geometric distortion with "mean (± SD) distortion" of 3.2 ± 0.02, 2.9 ± 0.02, and 1.8 ± 0.01 mm and isocenter shift (±SD) of 0.49 ± 0.3, 0.05 ± 0.2, and 0.01 ± 0.03 mm were present in the DstOff MRID3D phantom images in right-left (RL), anterior-posterior (AP), and superior-inferior (SI) directions, respectively. After resampling the originally acquired images by applying extended DVFs, the distortion was corrected to 0.18 ± 0.02, 0.09 ± 0.01, 0.15 ± 0.01 mm, and isocenter shift was corrected to 0.14 ± 0.05, -0.02 ± 0.04, and -0.07 ± 0.05 mm in RL, AP, and SI directions, respectively. The Fluke phantom average geometric distortion with "mean (± SD) distortion" of 2.7 ± 0.1 mm was corrected to 0.2 ± 0. 1 mm and the average isocenter shift (± SD) of 0.51 ± 0.2 mm, and 0.05 ± 0.03 was corrected to -0.08 ± 0.03 mm, and -0.05 ± 0.01 in RL and AP directions, respectively. SSIM (mean ± SD) of the original images to resampled images was increased from 0.49 ± 0.02 to 0.78 ± 0.01, 0.45 ± 0.02 to 0.75 ± 0.01, and 0.86 ± 0.25 to 0.98 ± 0.08 for MRID3D phantom, Fluke phantom, and human MR images, respectively, for all the gantry angles compared to the vendor corrected images. CONCLUSION: The gantry-related MR imaging distortion including geometric distortion and isocenter shift was characterized and a corresponding correction was demonstrated using extended DVFs on 0.35 T MRgRT system. The characterized gantry-related isocenter shift can be combined with geometric distortion correction to provide a technique for the correction of the full system-dependent distortion in an MRgRT system.

Online adaptive MR-guided stereotactic radiotherapy for unresectable malignancies in the upper abdomen using a 1.5T MR-linac.

BACKGROUND: Introduction of online adaptive MR-guided radiotherapy enables stereotactic body radiation therapy (SBRT) of upper abdominal tumors. This study aimed to evaluate the feasibility of MR-guided SBRT on a 1.5 T MR-linac in patients with unresectable upper abdominal malignancies. MATERIAL AND METHODS: Patients treated at the UMC Utrecht (April 2019 to December 2020) were identified in the prospective 'Multi-OutcoMe EvaluatioN of radiation Therapy Using the MR-linac' (MOMENTUM) study. Feasibility of treatment was arbitrarily defined as an on-table time interval of ≤60 min for >75% of delivered fractions and completion of >95% of fractions as scheduled, reflecting patient tolerability. Acute treatment-related toxicity was assessed at 3 months of follow-up and graded according to the National Cancer Institute Common Terminology Criteria of Adverse Events version 5.0. RESULTS: Twenty-five consecutive patients with a median follow-up time of 8 (range 4-23) months were treated with 35 Gray (n = 4) and 40 Gray (n = 21) in five fractions over 2 weeks. For all fractions, contours were adapted based on the daily anatomy and delivered within 47 min/fraction (range 30-74). In 98/117 fractions (84%), adapted treatment was completed within 1 h. All patients received the scheduled irradiation dose as planned. No acute grade 3 toxicity or higher was reported. Treatment resulted in pain alleviation in 11/13 patients. DISCUSSION: Online adaptive MR-guided SBRT on a 1.5 T MR-linac is feasible and well-tolerated in patients with unresectable upper abdominal malignancies. Dose escalation studies, followed by comparative studies, are needed to determine the optimal radiation dose for irradiation of upper abdominal malignancies.

MRI-GUIDED RADIOTHERAPY FOR PROSTATE CANCER: A NEW PARADIGM.

Radiotherapy is one of the key treatment modalities for primary prostate cancer. During the last decade, significant advances were made in radiotherapy technology leading to increasing both physical and biological precision. Being a loco-regional treatment approach, radiotherapy requires accurate target dose deposition while sparing surrounding healthy tissue. Conventional radiotherapy is based on computerized tomography (CT) images both for radiotherapy planning and image-guidance, however, shortcomings of CT as soft tissue imaging tool are well known. Nowadays, our ability to further escalate radiotherapy dose using hypofractionation is limited by uncertainties in CT-based image guidance and verification. Magnetic resonance imaging (MRI) is a well established imaging method for pelvic organs. In prostate cancer specifically, MRI accurately depicts prostate zonal anatomy, rectum, bladder, and pelvic floor structures with previously unseen precision owing to its sharp soft tissue contrast. The advantages of including MRI in the clinical workflow of prostate cancer radiotherapy are multifold. MRI allows for true adaptive radiotherapy to unfold based on daily MRI images taken before, during and after each radiotherapy fraction. It enables accurate dose escalation to the prostate and intraprostatic tumor lesions. Technically, MRI high-strength magnetic field and linear accelerator high energy electromagnetic beams are hardly compatible, and important efforts were made to overcome these technical challenges and integrate MRI and linear accelerator into one single treatment device, called MRI-linac. Different systems are produced by two leading vendors in the field and currently, there are around 100 MRI-linacs worldwide in clinical operations. In this narrative review paper, we discuss historical perspective of image guidance in radiotherapy, basic elements of MRI, current clinical developments in MRI-guided prostate cancer radiotherapy, and challenges associated with the use of MRI-linac in clinical practice.

Reliability of radiomics features due to image reconstruction using a standardized T2 -weighted pulse sequence for MR-guided radiotherapy: An anthropomorphic phantom study.

PURPOSE: To prospectively investigate the impact of image reconstruction on MRI radiomics features. METHODS: An anthropomorphic phantom was scanned at 1.5 T using a standardized sequence for MR-guided radiotherapy under SENSE and compressed-SENSE reconstruction settings. A total of 93 first-order and texture radiomics features in 10 volumes of interest were assessed based on (1) accuracy measured by the percentage deviation from the reference, (2) robustness on reconstruction in all volumes of interest measured by the intraclass correlation coefficient, and (3) repeatability measured by the coefficient of variance over the repetitive acquisitions. Finally, reliable and unreliable radiomics features were comprehensively determined based on their accuracy, robustness, and repeatability. RESULTS: Better accuracy and robustness of the radiomics features were achieved under SENSE than compressed-SENSE reconstruction. The feature accuracy under SENSE reconstruction was more affected by acceleration factor than direction, whereas under compressed-SENSE reconstruction, accuracy was substantially impacted by the increasing denoising levels. Feature repeatability was dependent more on feature types than on reconstruction. A total of 45 reliable features and 13 unreliable features were finally determined for SENSE, compared with 22 reliable and 26 unreliable features for compressed SENSE. First-order and gray-level co-occurrence matrix features were generally more reliable than other features. CONCLUSION: Radiomics features could be substantially affected by MRI reconstruction, so precautions need to be taken regarding their reliability for clinical use. This study helps the guidance of the preselection of reliable radiomics features and the preclusion of unreliable features in MR-guided radiotherapy.

Nonrigid 3D motion estimation at high temporal resolution from prospectively undersampled k-space data using low-rank MR-MOTUS.

PURPOSE: With the recent introduction of the MR-LINAC, an MR-scanner combined with a radiotherapy LINAC, MR-based motion estimation has become of increasing interest to (retrospectively) characterize tumor and organs-at-risk motion during radiotherapy. To this extent, we introduce low-rank MR-MOTUS, a framework to retrospectively reconstruct time-resolved nonrigid 3D+t motion fields from a single low-resolution reference image and prospectively undersampled k-space data acquired during motion. THEORY: Low-rank MR-MOTUS exploits spatiotemporal correlations in internal body motion with a low-rank motion model, and inverts a signal model that relates motion fields directly to a reference image and k-space data. The low-rank model reduces the degrees-of-freedom, memory consumption, and reconstruction times by assuming a factorization of space-time motion fields in spatial and temporal components. METHODS: Low-rank MR-MOTUS was employed to estimate motion in 2D/3D abdominothoracic scans and 3D head scans. Data were acquired using golden-ratio radial readouts. Reconstructed 2D and 3D respiratory motion fields were, respectively, validated against time-resolved and respiratory-resolved image reconstructions, and the head motion against static image reconstructions from fully sampled data acquired right before and right after the motion. RESULTS: Results show that 2D+t respiratory motion can be estimated retrospectively at 40.8 motion fields per second, 3D+t respiratory motion at 7.6 motion fields per second and 3D+t head-neck motion at 9.3 motion fields per second. The validations show good consistency with image reconstructions. CONCLUSIONS: The proposed framework can estimate time-resolved nonrigid 3D motion fields, which allows to characterize drifts and intra and inter-cycle patterns in breathing motion during radiotherapy, and could form the basis for real-time MR-guided radiotherapy.

Clinical assessment of geometric distortion for a 0.35T MR-guided radiotherapy system.

PURPOSE: To estimate the overall spatial distortion on clinical patient images for a 0.35 T MR-guided radiotherapy system. METHODS: Ten patients with head-and-neck cancer underwent CT and MR simulations with identical immobilization. The MR images underwent the standard systematic distortion correction post-processing. The images were rigidly registered and landmark-based analysis was performed by an anatomical expert. Distortion was quantified using Euclidean distance between each landmark pair and tagged by tissue interface: bone-tissue, soft tissue, or air-tissue. For baseline comparisons, an anthropomorphic phantom was imaged and analyzed. RESULTS: The average spatial discrepancy between CT and MR landmarks was 1.15 ± 1.14 mm for the phantom and 1.46 ± 1.78 mm for patients. The error histogram peaked at 0-1 mm. 66% of the discrepancies were <2 mm and 51% <1 mm. In the patient data, statistically significant differences (p-values < 0.0001) were found between the different tissue interfaces with averages of 0.88 ± 1.24 mm, 2.01 ± 2.20 mm, and 1.41 ± 1.56 mm for the air/tissue, bone/tissue, and soft tissue, respectively. The distortion generally correlated with the in-plane radial distance from the image center along the longitudinal axis of the MR. CONCLUSION: Spatial distortion remains in the MR images after systematic distortion corrections. Although the average errors were relatively small, large distortions observed at bone/tissue interfaces emphasize the need for quantitative methods for assessing and correcting patient-specific spatial distortions.

[Primary treatment of prostate cancer using 1.5 T MR-linear accelerator]. / Stellenwert des 1,5-T-MR-Linearbeschleunigers für die primäre Therapie des Prostatakarzinoms.

BACKGROUND: Hybrid devices of MR-scanners and linear accelerators (MR-Linacs) represent a new and promising extension of radiotherapeutic options for prostate cancer. The potential advantage of magnetic resonance imaging (MRI) over computed tomography (CT) for soft tissue contrast is well-known and leads to more consistent and smaller target volumes and improved normal tissue sparing. OBJECTIVES: This article presents an overview of clinical experience, indications, advantages and challenges of utilizing a 1.5 T MR-Linac in the setting of radiotherapy of prostate cancer. RESULTS: All current indications for radiotherapy of prostate cancer can be treated with an MR-Linac. The advantages include daily MR-based imaging in treatment position and daily adaption of the treatment plan on current anatomy (adaptive radiotherapy). Additionally, functional MRI sequences might be exploited to enhance treatment individualization and response assessment. Ultimately treatment on an MR-Linac might further increase the therapeutic window. The limitations of using MR-Linac include treatment complexity and the duration of each session. CONCLUSIONS: MR-Linacs expand the spectrum of radiotherapeutic options for prostate cancer. Increased precision can be reached with daily MRI-based target volume definition and plan adaption. Clinical studies are necessary to identify patient groups who would benefit most from radiotherapy on a MR-Linac.

Targeted Radiosensitizers for MR-Guided Radiation Therapy of Prostate Cancer.

Adjuvant radiotherapy is frequently prescribed to treat cancer. To minimize radiation-related damage to healthy tissue, it requires high precision in tumor localization and radiation dose delivery. This can be achieved by MR guidance and targeted amplification of radiation dose selectively to tumors by using radiosensitizers. Here, we demonstrate prostate cancer-targeted gold nanoparticles (AuNPs) for MR-guided radiotherapy to improve the targeting precision and efficacy. By conjugating Gd(III) complexes and prostate-specific membrane antigen (PSMA) targeting ligands to AuNP surfaces, we found enhanced uptake of AuNPs by PSMA-expressing cancer cells with excellent MR contrast and radiation therapy outcome in vitro and in vivo. The AuNPs binding affinity and r1 relaxivity were dramatically improved and the combination of Au and Gd(III)provided better tumor suppression after radiation. The precise tumor localization by MR and selective tumor targeting of the PSMA-1-targeted AuNPs could enable precise radiotherapy, reduction in irradiating dose, and minimization of healthy tissue damage.

Quantitative analysis of MRI-guided radiotherapy treatment process time for tumor real-time gating efficiency.

PURPOSE: Magnetic Resonance-guided radiotherapy (MRgRT) systems allow continuous monitoring of therapy volumes during treatment delivery and personalized respiratory gating approaches. Treatment length may therefore be significantly affected by patient's compliance and breathing control. We quantitatively analyzed treatment process time efficiency (TE ) using data obtained from real-world patient treatment logs to optimize MRgRT delivery settings. METHODS: Data corresponding to the first 100 patients treated with a low T hybrid MRI-Linac system, both in free breathing (FB) and in breath hold inspiration (BHI) were collected. TE has been computed as the percentage difference of the actual single fraction's total treatment time and the predicted treatment process time, as computed by the TPS during plan optimization. Differences between the scheduled and actual treatment room occupancy time were also evaluated. Finally, possible correlations with planning, delivery and clinical parameters with TE were also investigated. RESULTS: Nine hundred and nineteen treatment fractions were evaluated. TE difference between BHI and FB patients' groups was statistically significant and the mean TE were 42.4%, and -0.5% respectively. No correlation was found with TE for BHI and FB groups. Planning, delivering and clinical parameters classified BHI and FB groups, but no correlation with TE was found. CONCLUSION: The use of BHI gating technique can increase the treatment process time significantly. BHI technique could be not always an adequate delivery technique to optimize the treatment process time. Further gating techniques should be considered to improve the use of MRgRT.

Characterization of an inorganic scintillator for small-field dosimetry in MR-guided radiotherapy.

INTRODUCTION: Aim of this study is to dosimetrically characterize a new inorganic scintillator designed for magnetic resonance-guided radiotherapy (MRgRT) in the presence of 0.35 tesla magnetic field (B). METHODS: The detector was characterized in terms of signal to noise ratio (SNR), reproducibility, dose linearity, angular response, and dependence by energy, field size, and B orientation using a 6 MV magnetic resonance (MR)-Linac and a water tank. Field size dependence was investigated by measuring the output factor (OF) at 1.5 cm. The results were compared with those measured using other detectors (ion chamber and synthetic diamond) and those calculated using a Monte Carlo (MC) algorithm. Energy dependence was investigated by acquiring a percentage depth dose (PDD) curve at two field sizes (3.32 × 3.32 and 9.96 × 9.96 cm2 ) and repeating the OF measurements at 5 and 10 cm depths. RESULTS: The mean SNR was 116.3 ± 0.6. Detector repeatability was within 1%, angular dependence was <2% and its response variation based on the orientation with respect to the B lines was <1%. The detector has a temporal resolution of 10 Hz and it showed a linear response (R2  = 1) in the dose range investigated. All the OF values measured at 1.5 cm depth using the scintillator are in accordance within 1% with those measured with other detectors and are calculated using the MC algorithm. PDD values are in accordance with MC algorithm only for 3.32 × 3.32 cm2 field. Numerical models can be applied to compensate for energy dependence in case of larger fields. CONCLUSION: The inorganic scintillator in the present form can represent a valuable detector for small-field dosimetry and periodic quality controls at MR-Linacs such as dose stability, OFs, and dose linearity. In particular, the detector can be effectively used for small-field dosimetry at 1.5 cm depth and for PDD measurements if the field dimension of 3.32 × 3.32 cm2 is not exceeded.

The quantification and potential impact of dark current on treatments with an MR-guided radiotherapy (MRgRT) system.

PURPOSE: Dark current radiation produced during linac beam-hold has the potential to lead to unplanned dose delivered to the patient. With the increased usage of motion management and step-and-shoot IMRT deliveries for MR-guided systems leading to increased beam-hold time, it is necessary to consider the impact of dark current radiation on patient treatments. METHODS: The relative dose rate due to dark current for the ViewRay MRIdian linac was measured longitudinally over 15 months (June 2018-August 2019). Ion chamber measurements were acquired with the linac in the beam-hold state and the beam-on state, with the ratio representing the relative dark current dose rate. The potential contribution of the dark current dose to the overall prescription was retrospectively analyzed for 972 fractions from 83 patients over the same time period. The amount of time spent in the beam-hold state was combined with the monthly measured relative dark current dose rate to estimate the dark current dose contribution. RESULTS: The relative dark current dose rate compared to the beam-on dose rate was 0.12% ± 0.027%. In a near worst-case estimation, the dark current dose contribution accounted for 0.90% ± 0.67% of the prescription dose across all fractions (3.61% maximum). Gantry and MLC motion between segments accounted for 87% of the dark current contribution, with the remaining 13% attributable to gating during segment delivery. The largest dark current contributions were associated with plans delivering a small dose per treatment segment. CONCLUSIONS: The dark current associated with new clinical treatment units should be considered prior to treatment delivery to ensure it will not lead to dosimetric inaccuracies. For the MRIdian linac system investigated in this work, the contribution from dark current remained relatively low, though users should be cognizant of the larger potential dosimetric contribution for plans with small doses per segment.

On the accuracy of bulk synthetic CT for MR-guided online adaptive radiotherapy.

PURPOSE: MR-guided radiotherapy (MRgRT) relies on the daily assignment of a relative electron density (RED) map to allow the fraction specific dose calculation. One approach to assign the RED map consists of segmenting the daily magnetic resonance image into five different density levels and assigning a RED bulk value to each level to generate a synthetic CT (sCT). The aim of this study is to evaluate the dose calculation accuracy of this approach for applications in MRgRT. METHODS: A planning CT (pCT) was acquired for 26 patients with abdominal and pelvic lesions and segmented in five levels similar to an online approach: air, lung, fat, soft tissue and bone. For each patient, the median RED value was calculated for fat, soft tissue and bone. Two sCTs were generated assigning different bulk values to the segmented levels on pCT: The sCTICRU uses the RED values recommended by ICRU46, and the sCTtailor uses the median patient-specific RED values. The same treatment plan was calculated on two the sCTs and the pCT. The dose calculation accuracy was investigated in terms of gamma analysis and dose volume histogram parameters. RESULTS: Good agreement was found between dose calculated on sCTs and pCT (gamma passing rate 1%/1 mm equal to 91.2% ± 6.9% for sCTICRU and 93.7% ± 5.3% b or sCTtailor). The mean difference in estimating V95 (PTV) was equal to 0.2% using sCTtailor and 1.2% using sCTICRU, respect to pCT values CONCLUSIONS: The bulk sCT guarantees a high level of dose calculation accuracy also in presence of magnetic field, making this approach suitable to MRgRT. This accuracy can be improved by using patient-specific RED values.

Evaluation of a simplified optimizer for MR-guided adaptive RT in case of pancreatic cancer.

PURPOSE: Magnetic resonance-guided adaptive radiotherapy (MRgART) is considered a promising resource for pancreatic cancer, as it allows to online modify the dose distribution according to daily anatomy. This study aims to compare the dosimetric performance of a simplified optimizer implemented on a MR-Linac treatment planning system (TPS) with those obtained using an advanced optimizer implemented on a conventional Linac. METHODS: Twenty patients affected by locally advanced pancreatic cancer (LAPC) were considered. Gross tumor volume (GTV) and surrounding organ at risks (OARs) were contoured on the average 4DCT scan. Planning target volume was generated from GTV by adding an isotropic 3 mm margin and excluding overlap areas with OARs. Treatment plans were generated by using the simple optimizer for the MR-Linac in intensity-modulated radiation therapy (IMRT) and the advanced optimizer for conventional Linac in IMRT and volumetric modulated arc therapy (VMAT) technique. Prescription dose was 40 Gy in five fractions. The dosimetric comparison was performed on target coverage, dosimetric indicators, and low dose diffusion. RESULTS: The simplified optimizer of MR-Linac generated clinically acceptable plans in 80% and optimal plans in 55% of cases. The number of clinically acceptable plans obtained using the advanced optimizer of the conventional Linac with IMRT was the same of MR-Linac, but the percentage of optimal plans was higher (65%). Using the VMAT technique, it is possible to obtain clinically acceptable plan in 95% and optimal plans in 90% of cases. The advanced optimizer combined with VMAT technique ensures higher target dose homogeneity and minor diffusion of low doses, but its actual optimization time is not suitable for MRgART. CONCLUSION: Simplified optimization solutions implemented in the MR-Linac TPS allows to elaborate in most of cases treatment plans dosimetrically comparable with those obtained by using an advanced optimizer. A superior treatment plan quality is possible using the VMAT technique that could represent a breakthrough for the MRgART if the modern advancements will lead to shorter optimization times.

Characterization and longitudinal assessment of daily quality assurance for an MR-guided radiotherapy (MRgRT) linac.

PURPOSE: To describe and characterize daily machine quality assurance (QA) for an MR-guided radiotherapy (MRgRT) linac system, in addition to reporting a longitudinal assessment of the dosimetric and mechanical stability over a 7-month period of clinical operation. METHODS: Quality assurance procedures were developed to evaluate MR imaging/radiation isocenter, imaging and patient handling system, and linear accelerator stability. A longitudinal assessment was characterized for safety interlocks, laser and imaging isocenter coincidence, imaging and radiation (RT) isocentricity, radiation dose rate and output, couch motion, and MLC positioning. A cylindrical water phantom and an MR-compatible A1SL detector were utilized. MR and RT isocentricity and MLC positional accuracy was quantified through dose measured with a 0.40 cm2  x 0.83 cm2 field at each cardinal angle. The relationship between detector response to MR/RT isocentricity and MLC positioning was established through introducing known errors in phantom position. RESULTS: Correlation was found between detector response and introduced positional error (N = 27) with coefficients of determination of 0.9996 (IEC-X), 0.9967 (IEC-Y), 0.9968 (IEC-Z) in each respective shift direction. The relationship between dose (DoseMR/RT+MLC ) and the vector magnitude of MLC and MR/RT positional error (Errormag ) was calculated to be a nonlinear response and resembled a quadratic function: DoseMR/RT+MLC [%] = -0.0253 Errormag [mm]2  - 0.0195 Errormag [mm]. For the temporal assessment (N = 7 months), safety interlocks were functional. Laser coincidence to MR was within ±2.0 mm (99.6%) and ±1.0 mm (86.8%) over the 7-month assessment. IGRT position-reposition shifts were within ±2.0 mm (99.4%) and ±1.0 mm (92.4%). Output was within ±3% (99.4%). Mean MLC and MR/RT isocenter accuracy was 1.6 mm, averaged across cardinal angles for the 7-month period. CONCLUSIONS: The linac and IGRT accuracy of an MR-guided radiotherapy system has been validated and monitored over seven months for daily QA. Longitudinal assessment demonstrated a drift in dose rate, but temporal assessment of output, MLC position, and isocentricity has been stable.