MRI-guided Radiotherapy Research Articles

Automatic Contour Refinement for Deep Learning Auto-segmentation of Complex Organs in MRI-guided Adaptive Radiation Therapy

PurposeFast and accurate auto-segmentation on daily images is essential for magnetic resonance imaging (MRI)–guided adaptive radiation therapy (ART). However, the state-of-the-art auto-segmentation based on deep learning still has limited success, particularly for complex structures in the abdomen. This study aimed to develop an automatic contour refinement (ACR) process to quickly correct for unacceptable auto-segmented contours. Methods and MaterialsAn improved level set–based active contour model (ACM) was implemented for the ACR process and was tested on the deep learning–based auto-segmentation of 80 abdominal MRI sets along with their ground truth contours. The performance of the ACR process was evaluated using 4 contour accuracy metrics: the Dice similarity coefficient (DSC), mean distance to agreement (MDA), surface DSC, and added path length (APL) on the auto-segmented contours of the small bowel, large bowel, combined bowels, pancreas, duodenum, and stomach. ResultsA portion (3%-39%) of the corrected contours became practically acceptable per the American Association of Physicists in Medicine Task Group 132 (TG-132) recommendation (DSC >0.8 and MDA <3 mm). The best correction performance was seen in the combined bowels, where for the contours with major errors (initial DSC <0.5 or MDA >8 mm), the mean DSC increased from 0.34 to 0.59, the mean MDA decreased from 7.02 mm to 5.23 mm, and the APL reduced by almost 20 mm, whereas for the contours with minor errors, the mean DSC increased from 0.72 to 0.79, the mean MDA decreased from 3.35 mm to 3.29 mm, and more than one-third (39%) of the ACR contours became clinically acceptable. The execution time for the ACR process on one subregion was less than 2 seconds using an NVIDIA GTX 1060 GPU. ConclusionsThe ACR process implemented based on the ACM was able to quickly correct for some inaccurate contours produced from MRI-based deep learning auto-segmentation of complex abdominal anatomy. The ACR method may be integrated into the auto-segmentation step to accelerate the process of MRI-guided ART.

Integrated MRI-guided radiotherapy - opportunities and challenges.

MRI can help to categorize tissues as malignant or non-malignant both anatomically and functionally, with a high level of spatial and temporal resolution. This non-invasive imaging modality has been integrated with radiotherapy in devices that can differentially target the most aggressive and resistant regions of tumours. The past decade has seen the clinical deployment of treatment devices that combine imaging with targeted irradiation, making the aspiration of integrated MRI-guided radiotherapy (MRIgRT) a reality. The two main clinical drivers for the adoption of MRIgRT are the ability to image anatomical changes that occur before and during treatment in order to adapt the treatment approach, and to image and target the biological features of each tumour. Using motion management and biological targeting, the radiation dose delivered to the tumour can be adjusted during treatment to improve the probability of tumour control, while simultaneously reducing the radiation delivered to non-malignant tissues, thereby reducing the risk of treatment-related toxicities. The benefits of this approach are expected to increase survival and quality of life. In this Review, we describe the current state of MRIgRT, and the opportunities and challenges of this new radiotherapy approach.

Stereotactic MRI-guided radiation therapy for localized prostate cancer (SMILE): a prospective, multicentric phase-II-trial

BackgroundNormofractionated radiation regimes for definitive prostate cancer treatment usually extend over 7–8 weeks. Recently, moderate hypofractionation with doses per fraction between 2.2 and 4 Gy has been shown to be safe and feasible with oncologic non-inferiority compared to normofractionation. Radiobiologic considerations lead to the assumption that prostate cancer might benefit in particular from hypofractionation in terms of tumor control and toxicity. First data related to ultrahypofractionation demonstrate that the overall treatment time can be reduced to 5–7 fractions with single doses > 6 Gy safely, even with simultaneous focal boosting of macroscopic tumor(s). With MR-guided linear accelerators (MR-linacs) entering clinical routine, invasive fiducial implantations become unnecessary. The aim of the multicentric SMILE study is to evaluate the use of MRI-guided stereotactic radiotherapy for localized prostate cancer in 5 fractions regarding safety and feasibility.MethodsThe study is designed as a prospective, one-armed, two-stage, multi-center phase-II-trial with 68 patients planned. Low- and intermediate-risk localized prostate cancer patients will be eligible for the study as well as early high-risk patients (cT3a and/or Gleason Score ≤ 8 and/or PSA ≤ 20 ng/ml) according to d’Amico. All patients will receive definitive MRI-guided stereotactic radiation therapy with a total dose of 37.5 Gy in 5 fractions (single dose 7.5 Gy) on alternating days. A focal simultaneous integrated boost to MRI-defined tumor(s) up to 40 Gy can optionally be applied. The primary composite endpoint includes the assessment of urogenital or gastrointestinal toxicity ≥ grade 2 or treatment-related discontinuation of therapy. The use of MRI-guided radiotherapy enables online plan adaptation and intrafractional gating to ensure optimal target volume coverage and protection of organs at risk.DiscussionWith moderate hypofractionation being the standard in definitive radiation therapy for localized prostate cancer at many institutions, ultrahypofractionation could be the next step towards reducing treatment time without compromising oncologic outcomes and toxicities. MRI-guided radiotherapy could qualify as an advantageous tool as no invasive procedures have to precede in therapeutic workflows. Furthermore, MRI guidance combined with gating and plan adaptation might be essential in order to increase treatment effectivity and reduce toxicity at the same time.

SPIO-enhanced 0.35T MRI-guided radiotherapy for liver malignancies: usefulness in tumor visualization.

The purpose of this study was to investigate the changes of tumor-to-liver signal ratio in a 0.35T MRI-guided radiotherapy system and to evaluate the usefulness and pitfalls of superparamagnetic iron oxide (SPIO) administration for visualization of liver tumors. Forty-two patients treated with MRI-guided stereotactic ablative radiotherapy (SABR) for liver tumors were included in this study. The tumor-to-liver signal ratios before and after SPIO administration were retrospectively assessed and compared on true fast imaging with steady-state precession (FISP). Before SPIO administration, liver tumors were either invisible or barely visible in 15 cases (36%), but all tumors became visible after SPIO administration. The mean values of tumor-to-liver signal ratio before and after SPIO administration were 0.939 ± 0.201 and 1.336 ± 0.300, respectively (mean ± standard deviation, p < 0.001). In six (14%) patients, liver tumors were visible on true FISP imaging before SPIO administration, but became invisible after administration. This study showed that liver tumors that are invisible on true FISP imaging can be made visible by administration of SPIO, and that MRI-guided SABR can be performed accurately. This is the first report to examine the usefulness of liver-specific contrast agent superparamagnetic iron oxides in 0.35T MRI-guided radiation therapy. Liver tumors that are invisible on true fast imaging with steady-state precession can be made visible by administration of superparamagnetic iron oxides.

Dosimetric feasibility of hippocampal avoidance whole brain radiotherapy with an MRI-guided linear accelerator.

Purpose/Objective(s)Whole brain radiotherapy with hippocampal avoidance (HA‐WBRT) is a technique utilized to treat metastatic brain disease while preserving memory and neurocognitive function. We hypothesized that the treatment planning and delivery of HA‐WBRT plans is feasible with an MRI‐guided linear accelerator (linac) and compared plan results with clinical non‐MRI‐guided C‐Arm linac plans.Materials/MethodsTwelve HA‐WBRT patients treated on a non‐MRI‐guided C‐Arm linac were selected for retrospective analysis. Treatment plans were developed using a 0.35T MRI‐guided linac system for comparison to clinical plans. Treatment planning goals were defined as provided in the Phase II Trial NRG CC001. MRI‐guided radiotherapy (MRgRT) treatment plans were developed by a dosimetrist and compared with clinical plans. quality assurance (QA) plans were generated and delivered on the MRI‐guided linac to a cylindrical diode detector array. Planning target volume (PTV) coverage was normalized to ∼95% to provide a control point for comparison of dose to the organs at risk.ResultsMRgRT plans were deliverable and met all clinical goals. Mean values demonstrated that the clinical plans were less heterogeneous than MRgRT plans with mean PTV V37.5 Gy of 0.00% and 0.03% (p = 0.013), respectively. Average hippocampi maximum doses were 14.19 ± 1.29 Gy and 15.00 ± 1.51 Gy, respectively. The gamma analysis comparing planned and measured doses resulted in a mean of 99.9% ± 0.12% of passing points (3%/2mm criteria). MRgRT plans had an average of 38.33 beams with average total delivery time and beam‐on time of 13.7 (11.2–17.5) min and 4.1 (3.2–5.4) min, respectively. Clinical plan delivery times ranged from 3 to 7 min depending on the number of noncoplanar arcs. Planning time between the clinical and MRgRT plans was comparable.ConclusionThis study demonstrates that HA‐WBRT can be treated using an MRI‐guided linear accelerator with comparable treatment plan quality and delivery accuracy.

Gating has a negligible impact on dose delivered in MRI-guided online adaptive radiotherapy of prostate cancer

Background and purposeMR-guided radiotherapy (MRgRT) allows real-time beam-gating to compensate for intra-fractional target position variations. This study investigates the dosimetric impact of beam-gating and the impact of PTV margin on prostate coverage for prostate cancer patients treated with online-adaptive MRgRT. Materials and methods20 consecutive prostate cancer patients were treated with online-adaptive MRgRT SBRT with 36.25 Gy in 5 fractions (PTV D95% ≥ 95% (N = 5) and PTV D95% ≥ 100% (N = 15)). Sagittal 2D cine MRIs were used for gating on the prostate with a 3 mm expansion as the gating window. We computed motion-compensated dose distributions for (i) all prostate positions during treatment (simulating non-gated treatments) and (ii) for prostate positions within the gating window (gated treatments). To evaluate the impact of PTV margin on prostate coverage, we simulated coverage with smaller margins than clinically applied both for gated and non-gated treatments. Motion-compensated fraction doses were accumulated and dose metrics were compared. ResultsWe found a negligible dosimetric impact of beam-gating on prostate coverage (median of 0.00 Gy for both D95% and Dmean). For 18/20 patients, prostate coverage (D95% ≥ 100%) would have been ensured with a prostate-to-PTV margin of 3 mm, even without gating. The same was true for all but one fraction. ConclusionBeam-gating has negligible dosimetric impact in online-adaptive MRgRT of prostate cancer. Accounting for motion, the clinically used prostate-to-PTV margin could potentially be reduced from 5 mm to 3 mm for 18/20 patients.

Multi-parametric magnetic resonance imaging for radiation treatment planning.

In recent years, multi-parametric magnetic resonance imaging (MpMRI) has played a major role in radiation therapy treatment planning. The superior soft tissue contrast, functional or physiological imaging capabilities, and the flexibility of site-specific image sequence development has placed MpMRI at the forefront. In this article, the present status of MpMRI for external beam radiation therapy planning is reviewed. Common MpMRI sequences, preprocessing, and quality assurance strategies are briefly discussed, and various image registration techniques and strategies are addressed. Image segmentation methods including automatic segmentation and deep learning techniques for organs at risk and target delineation are reviewed. Due to the advancement in MRI-guided online adaptive radiotherapy, treatment planning considerations addressing MRI only planning are also discussed.

Reducing MRI-guided radiotherapy planning and delivery times via efficient leaf sequencing and segment shape optimization algorithms

Objective. Extended treatment session times are an operational limitation in magnetic resonance imaging guided adaptive radiotherapy (MRIgRT). In this study a novel leaf sequencing algorithm called optimal fluence levels (OFL) and an optimization algorithm called pseudo gradient descent (PGD) are evaluated with respect to plan quality, beam complexity, and the ability to reduce treatment session times on the Elekta Unity MRIgRT system. Approach. Ten total patients were evaluated on this Institutional Review Board approved study: three with prostate cancer, three with oligometastases, two with pancreatic cancer, and two with liver cancer. Plans were generated using the clinical Monaco Hyperion optimizer and leaf sequencer and then re-optimized using OFL and PGD (OFL + PGD) while holding all IMRT constraints and planning parameters constant. All plans were normalized to ensure 95% of the PTV received the prescription dose. A paired t-test was used to evaluate statistical significance. Main Results. Plan quality in terms of dosimetric OAR sparing was found to be equivalent between the OFL + PGD and conventional Monaco Hyperion optimizer plans. The OFL + PGD plans had a reduction in optimization time of 51.4% ± 5.0% (p = 0.002) and reduction in treatment delivery time of 10.6% ± 7.5% (p = 0.005). OFL + PGD generated plans had on average 13.2% ± 12.6% fewer multi-leaf collimator (MLC) segments (p = 0.009) and 0.1 ± 0.1 lower plan averaged beam modulation (PM) (p = 0.004) relative to the Monaco Hyperion plans. Significance. The OFL + PGD algorithms more quickly generate Unity treatment plans that are faster to deliver than with the conventional approach and without compromising dosimetric plan quality. This is likely due to a delivery complexity reduction enabled by OFL + PGD relative to the Monaco Hyperion plans.

The Role of MRI-Guided Radiotherapy for Soft Tissue Sarcomas.

Soft tissue sarcomas (STS) are a rare class of tumors that originate from mesenchymal tissues and occur most frequently in the extremities, trunk, and retroperitoneum. Surgical resection with R0 margins is the primary curative treatment for most localized STS. In this setting, radiation therapy is used either pre-operatively or post-operatively to reduce the rate of local recurrence. Modern pre- or post-operative radiation therapy rely on the use of MRI sequences to guide target delineation during treatment planning. MRI-guided radiotherapy also offers unique advantages over CT-guided approaches in differentiating STS from surrounding normal soft tissues and enabling better identification of target volumes on daily imaging. For patients with unresectable STS, radiation therapy may offer the best chance for local tumor control. However, most STS are relatively radioresistant with modest rates of local control achieved using conventionally fractionated radiation. Specialized techniques such as hypofractionated radiation may allow for dose intensification and may increase rates of local control for STS. In these settings, MRI becomes even more critical for the delineation of targets and organs at risk and management of tumor and organ at risk motion during and between radiotherapy treatment fractions.

Commissioning a secondary dose calculation software for a 0.35T MR-linac.

Secondary external dose calculations for a 0.35 T magnetic resonance image‐guided radiation therapy (MRgRT) are needed within the radiation oncology community to follow safety standards set forth within the field. We evaluate the commercially available software, RadCalc, in its ability to accurately perform monitor unit dose calculations within a magnetic field. We also evaluate the potential effects of a 0.35 T magnetic field upon point dose calculations.Monitor unit calculations were evaluated with (wMag) and without (noMag) a magnetic field considerations in RadCalc for the ViewRay MRIdian. The magnetic field is indirectly accounted for by using asymmetric profiles for calculation. The introduction of double‐stacked multi‐leaf collimator leaves was also included in the monitor unit calculations and a single transmission value was determined. A suite of simple and complex geometries with a variety field arrangements were calculated for each method to demonstrate the effect of the 0.35 T magnetic field on monitor unit calculations. Finally, 25 patient‐specific treatment plans were calculated using each method for comparison.All simple geometries calculated in RadCalc were within 2% of treatment planning system (TPS) values for both methods, except for a single noMag off‐axis comparison. All complex muilt‐leaf collimator (MLC) pattern calculations were within 5%. All complex phantom geometry calculations were within 5% except for a single field within a lung phantom at a distal point. For the patient calculations, the noMag method average percentage difference was 0.09 ± 2.5% and the wMag average percentage difference was 0.08 ± 2.5%. All results were within 5% for the wMag method.We performed monitor unit calculations for a 0.35 T MRgRT system using a commercially available secondary monitor unit dose calculation software and demonstrated minimal impact of the 0.35 T magnetic field on monitor unit dose calculations. This is the first investigation demonstrating successful calculations of dose using RadCalc in the low‐field 0.35 T ViewRay MRIdian system.

MR-guided radiotherapy for prostate cancer: state of the art and future perspectives.

Advances in radiotherapy technology have increased precision of treatment delivery and in some tumour types, improved cure rates and decreased side effects. A new generation of radiotherapy machines, hybrids of an MRI scanner and a linear accelerator, has the potential to further transform the practice of radiation therapy in some cancers. Facilitating superior image quality and the ability to change the dose distribution online on a daily basis (termed “daily adaptive replanning”), MRI-guided radiotherapy machines allow for new possibilities including increasing dose, for hard to treat cancers, and more selective sparing of healthy tissues, where toxicity reduction is the key priority.These machines have already been used to treat most types of cancer, although experience is still in its infancy. This review summarises the potential and current evidence for MRI-guided radiotherapy, with a predominant focus on prostate cancer. Current advantages and disadvantages are discussed including a realistic appraisal of the likely potential to improve patient outcomes. In addition, horizon scanning for near-term possibilities for research and development will hopefully delineate the potential role for this technology over the next decade.

Pathological outcomes of pancreatic adenocarcinoma (PA) after preoperative high biological effective dose (BED) magnetic resonance image-guided radiation therapy (MRgRT).

573 Background: Pre-operative radiotherapy (RT) for PA has the potential to reduce positive surgical margin rates and increase pathologic tumor response, which has been associated with improved survival. Increasing the BED can improve local control and overall survival for patients with unresectable PA. Use of stereotactic body radiation therapy (SBRT) to achieve a higher BED has been limited by toxicity to adjacent radiosensitive structures, but this can be mitigated by MRgRT. We describe our use of MRgRT prior to potentially curative resection of localized PA. Methods: We performed a single institution retrospective analysis of all patients with localized PA who received high BED SBRT on the MR Linac followed by surgical resection with curative intent. Toxicity was evaluated according to Common Terminology Criteria for Adverse Events, version 5.0. Tumor response was evaluated according to the College of American Pathologists tumor regression grading criteria (CAP-TRG), ranging from CAP 0 indicating pathologic complete response to CAP grade 3 indicating no response. Ordinal logistic regression model was used to assess the association between time from RT to surgery and TRG. Follow up included MRI or CT scans at least every three months. Results: We analyzed 26 patients with borderline resectable (80.8%), locally advanced (11.5%), and resectable (7.7%) tumors who received high BED MRgRT followed by surgical resection. Median age at diagnosis was 68 years (34 - 86). Most patients received chemotherapy (80.8%) prior to RT, with 81% of these receiving FOLFINIRNOX and 19% receiving gemcitabine/nab-paclitaxel. All patients received MR-guided high BED SBRT to a median dose of 50 Gy (40 - 50) in 5 fractions. On-table adaptive replanning was performed in 88% of patients, with 74% having all 5 fractions adapted. No acute grade 2+ toxicity associated with RT was observed. The median time to resection was 50 days (37 – 115), and the procedure types included: Whipple (69%), distal (23%), or total pancreatectomy (8%). The R0 resection rate was 96% and no perioperative deaths occurred within 90 days. Complete (0) or near-complete (1) pathologic response was observed in 35% of cases and the time from RT to surgery was positively associated with TRG (R2= 0.22, p = 0.0003). The median follow-up after RT was 16.5 months (3.9- 26.2) during which 9 patients recurred, and 3 patients died of disease. The derived median progression-free survival from RT was 13.2 months. Conclusions: These initial pathology outcomes following high BED MR-guided SBRT are encouraging and suggest that the time from SBRT to surgical resection is associated with response. This finding is consistent with results from other preoperative GI tumor sites and results from prospective studies using high BED SBRT with MRI guidance in combined modality therapy against PA are eagerly awaited.

MRI-Guided Online Adaptive Stereotactic Body Radiation Therapy of Liver and Pancreas Tumors on an MR-Linac System.

Simple SummaryThe hybrid magnetic resonance imaging and medical linear accelerator (MR-Linac) systems are expected to revolutionize radiation therapy, uniquely offering high quality soft-tissue contrast and fast imaging to facilitate the online re-planning and guidance of the treatment delivery. While the clinical procedures for stereotactic body radiotherapy are well-established for conventional linacs (with their strengths and weaknesses), they still require significant development and refinement for the MR-Linac systems. Adjustment of fractionation schemes including clinical goals, patient selection, organ motion management, treatment session length, staff logistics, and overall complexity of the online re-planning sessions are key factors that drive the adoption of MR-Linac technologies. In this report, we present the clinical implementation of an MRI-guided radiation therapy workflow, which was used to treat 16 upper gastro-intestinal cancer patients on a 1.5 T MR-Linac platform. The workflow was proven to be feasible for a wide range of clinical scenarios, and the overall treatment session time was significantly reduced as tasks were optimized and the clinical team gradually gained expertise.Purpose: To describe a comprehensive workflow for MRI-guided online adaptive stereotactic body radiation therapy (SBRT) specific to upper gastrointestinal cancer patients with abdominal compression on a 1.5T MR-Linac system. Additionally, we discuss the workflow’s clinical feasibility and early experience in the case of 16 liver and pancreas patients. Methods: Eleven patients with liver cancer and five patients with pancreas cancer were treated with online adaptive MRI-guidance under abdominal compression. Two liver patients received single-fraction treatments; the remainder plus all pancreas cancer patients received five fractions. A total of 65 treatment sessions were investigated to provide analytics relevant to the online adaptive processes. The quantification of target and organ motion as well as definition and validation of internal target volume (ITV) margins were performed via multi-contrast imaging provided by three different 2D cine sequences. The plan generation was driven by full re-optimization strategies and using T2-weighted 3D image series acquired by means of a respiratory-triggered exhale phase or a time-averaged imaging protocol. As a pre-requisite for the clinical development of the procedure, the image quality was thoroughly investigated via phantom measurements and numerical simulations specific to upper abdominal sites. The delivery of the online adaptive treatments was facilitated by real-time monitoring with 2D cine imaging. Results: Liver 1-fraction and 5-fraction online adaptive session time were on average 80 and 67.5 min, respectively. The total session length varied between 70–90 min for a single fraction and 55–90 min for five fractions. The pancreas sessions were 54–85 min long with an average session time of 68.2 min. Target visualization on the 2D cine image data varied per patient, with at least one of the 2D cine sequences providing sufficient contrast to confidently identify its location and confirm reproducibility of ITV margins. The mean/range of absolute and relative dose values for all treatment sessions evaluated with ArcCheck were 90.6/80.9–96.1% and 99/95.4–100%, respectively. Conclusion: MR-guidance is feasible for liver and pancreas tumors when abdominal compression is used to reduce organ motion, improve imaging quality, and achieve a robust intra- and inter-fraction patient setup. However, the treatment length is significantly longer than for the conventional linac, and patient compliance is paramount for the successful completion of the treatment. Opportunities for reducing the online adaptive session time should be explored. As the next steps, dose-of-the-day and dose accumulation analysis and tools are needed to enhance the workflow and to help further refine the online re-planning processes.

A portable magnet for radiation biology and dosimetry studies in magnetic fields.

In the current and rapidly evolving era of real-time MRI-guided radiotherapy, our radiation biology and dosimetry knowledge is being tested in a novel way. This paper presents the successful design and implementation of a portable device used to generate strong localized magnetic fields. These are ideally suited for small-scale experiments that mimic the magnetic field environment inside an MRI-linac system, or more broadly MRI-guided particle therapy aswell. A portable permanent magnet-based device employing an adjustable steel yoke and magnetic field focusing cones has been designed, constructed, and tested. The apparatus utilizes two banks of Nd Fe B permanent magnets totaling around 50 kg in mass to generate a strong magnetic field throughout a small volume between two pole tips. The yoke design allows adjustment of the pole tip gap and exchanging of the focusing cones. Further to this, beam portal holes are present in the yoke and focusing cones, allowing for radiation beams of up to 5 5 cm to pass through the region of high magnetic field between the focusing cone tips. Finite element magnetic modeling was performed to design and characterize the performance of the device. Automated physical measurements of the magnetic field components at various locations were measured to confirm the performance. The adjustable pole gap and interchangeable cones allows rapid changing of the experimental set-up to allow different styles of measurements to beperformed. A mostly uniform magnetic field of 1.2 T can be achieved over a volume of at least 3 3 3 cm . This can be reduced in strength to 0.3 T but increased in volume to 10 10 10 cm via removal of the cone tips and/or adjustment of the steel yoke. Although small, these volumes are sufficient to house radiation detectors, cell culture dishes, and various phantom arrangements targeted at examining small radiation field dosimetry inside magnetic field strengths that can be changed with ease. Most important is the ability to align the magnetic field both perpendicular to, or inline with, the radiation beam. To date, the system has been successfully used to conduct published research in the areas of radiation detector performance, lung phantom dosimetry, and how small clinical electron beams behave in these strong magneticfields. A portable, relatively inexpensive, and simple to operate device has successfully been constructed and used for performing radiation oncology studies around the theme of MRI-guided radiotherapy. This can be in either inline and perpendicular magnetic fields of up to 1.2 T with x-ray and particlebeams.

Monte Carlo investigation of electron fluence perturbation in MRI-guided radiotherapy beams using six commercial radiation detectors

With the integration of treatments with MRI-linacs to the clinical workflow, the understanding and characterization of detector response in reference dosimetry in magnetic fields are required. The external magnetic field perturbs the electron fluence. The degree of perturbation depends on the irradiation conditions and on the detector type. The purpose of this study is to evaluate the magnetic field impact on the electron fluence spectra in several detectors to provide a deeper understanding of detector response in these conditions. Monte Carlo calculations of the electron fluence are performed in six detectors (solid-state: PTW60012 and PTW60019, ionization chambers: PTW30013, PTW31010, PTW31021, and PTW31022) in water and irradiated by a 7 MV FFF photon beam with a small and a reference field, at 0 and 1.5 T. Three chamber axis orientations are investigated: parallel or perpendicular (either the Lorentz force pointing towards the stem or the tip) to the magnetic field and always perpendicular to the photon beam. One orientation for the solid-state detector is studied: parallel to the photon beam and perpendicular to the magnetic field. Additionally, electron fluence spectra are calculated in modified detector geometries to identify the underlying physical mechanisms behind the fluence perturbations. The total electron fluence in the Farmer chamber varies up to 1.24% and 5.12% at 1.5 T, in the parallel and perpendicular orientation, respectively. The interplay between the gyration radius and the Farmer chamber cavity length significantly affects the electron fluence in the perpendicular orientation. For the small-cavity chambers, the maximal variation in total electron fluence is 0.19% in the parallel orientation for the reference field. Significant small-field effects occur in these chambers; the magnetic field reduces the total electron fluence (with respect to the no field case) between 9.86% and 14.50%, depending on the orientation. The magnetic field strongly impacted the solid-state detectors in both field sizes, probably due to the high-Z components and cavity density. The maximal reductions of total electron fluence are 15.06 ± 0.09% (silicon) and 16.00 ± 0.07% (microDiamond). This work provides insights into detector response in magnetic fields by illustrating the interplay between several factors causing dosimetric perturbation effects: (1) chamber and magnetic field orientation, (2) cavity size and shape, (3) extracameral components, (4) air gaps and their asymmetry, (5) electron energy. Low-energy electron trajectories are more susceptible to change in magnetic fields, and are associated with detector response perturbation. Detectors with higher density and high-Z extracameral components exhibit more significant perturbations in the presence of a magnetic field, regardless of field size.

THUNDER 2: THeragnostic Utilities for Neoplastic DisEases of the Rectum by MRI guided radiotherapy

BackgroundNeoadjuvant chemoradiation therapy (nCRT) is the standard treatment modality in locally advanced rectal cancer (LARC). Since response to radiotherapy (RT) is dose dependent in rectal cancer, dose escalation may lead to higher complete response rates. The possibility to predict patients who will achieve complete response (CR) is fundamental. Recently, an early tumour regression index (ERI) was introduced to predict pathological CR (pCR) after nCRT in LARC patients.The primary endpoints will be the increase of CR rate and the evaluation of feasibility of delta radiomics-based predictive MRI guided Radiotherapy (MRgRT) model.MethodsPatients affected by LARC cT2-3, N0-2 or cT4 for anal sphincter involvement N0-2a, M0 without high risk features will be enrolled in the trial. Neoadjuvant CRT will be administered using MRgRT. The initial RT treatment will consist in delivering 55 Gy in 25 fractions on Gross Tumor Volume (GTV) plus the corresponding mesorectum and 45 Gy in 25 fractions on the drainage nodes. Chemotherapy with 5-fluoracil (5-FU) or oral capecitabine will be administered continuously.A 0.35 Tesla MRI will be acquired at simulation and every day during MRgRT. At fraction 10, ERI will be calculated: if ERI will be inferior than 13.1, the patient will continue the original treatment; if ERI will be higher than 13.1 the treatment plan will be reoptimized, intensifying the dose to the residual tumor at the 11th fraction to reach 60.1 Gy.At the end of nCRT instrumental examinations are to be performed in order to restage patients. In case of stable disease or progression, the patient will undergo surgery. In case of major or complete clinical response, conservative approaches may be chosen. Patients will be followed up to evaluate toxicity and quality of life.The number of cases to be enrolled will be 63: all the patients will be treated at Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome.DiscussionThis clinical trial investigates the impact of RT dose escalation in poor responder LARC patients identified using ERI, with the aim of increasing the probability of CR and consequently an organ preservation benefit in this group of patients.Trial registrationClinicalTrials.gov Identifier: NCT04815694 (25/03/2021).

Dosimetric Effects of Air Cavities for MRI-Guided Online Adaptive Radiation Therapy (MRgART) of Prostate Bed after Radical Prostatectomy.

Purpose: To evaluate dosimetric impact of air cavities and their corresponding electron density correction for 0.35 tesla (T) Magnetic Resonance-guided Online Adaptive Radiation Therapy (MRgART) of prostate bed patients. Methods: Three 0.35 T MRgRT plans (anterior–posterior (AP) beam, AP–PA beams, and clinical intensity modulated radiation therapy (IMRT)) were generated on a prostate bed patient’s (Patient A) planning computed tomography (CT) with artificial rectal air cavities of various sizes (0–3 cm, 0.5 cm increments). Furthermore, two 0.35 T MRgART plans (‘Deformed’ and ‘Override’) were generated on a prostate bed patient’s (Patient B) daily magnetic resonance image (MRI) with artificial rectal air cavities of various sizes (0–3 cm, 0.5 cm increments) and on five prostate bed patient’s (Patient 1–5) daily MRIs (2 MRIs: Fraction A and B) with real air cavities. For each MRgART plan, daily MRI electron density map was obtained by deformable registration with simulation CT. In the ‘Deformed’ plan, a clinical IMRT plan is calculated on the daily MRI with electron density map obtained from deformable registration only. In the ‘Override’ plan, daily MRI and simulation CT air cavities are manually corrected and bulk assigned air and water density on the registered electron density map, respectively. Afterwards, the clinical IMRT plan is calculated. Results: For the MRgRT plans, AP and AP–PA plans’ rectum/rectal wall max dose increased with increasing air cavity size, where the 3 cm air cavity resulted in a 20%/17% and 13%/13% increase, relative to no air cavity, respectively. Clinical IMRT plan was robust to air cavity size, where dose change remained less than 1%. For the MRgART plans, daily MRI electron density maps, obtained from deformable registration with simulation CT, was unable to accurately produce electron densities reflecting the air cavities. However, for the artificial daily MRI air cavities, dosimetric change between ‘Deformed’ and ‘Override’ plan was small (<4%). Similarly, for the real daily MRI air cavities, clinical constraint changes between ‘Deformed’ and ‘Override’ plan was negligible and did not lead to change in clinical decision for adaptive planning except for two fractions. In these fractions, the ‘Override’ plan indicated that the bladder max dose and rectum V35.7 exceeded the constraint, while the ‘Deformed’ plan showed acceptable dose, although the absolute difference was only 0.3 Gy and 0.03 cc, respectively. Conclusion: Clinical 0.35 T IMRT prostate bed plans are dosimetrically robust to air cavities. MRgART air cavity electron density correction shows clinically insignificant change and is not warranted on low-field systems.

Application of Continuous Positive Airway Pressure for Thoracic Respiratory Motion Management: An Assessment in a Magnetic Resonance Imaging–Guided Radiation Therapy Environment

PurposePatient tolerability of magnetic resonance (MR)–guided radiation treatment delivery is limited by the need for repeated deep inspiratory breath holds (DIBHs). This volunteer study assessed the feasibility of continuous positive airway pressure (CPAP) with and without DIBH for respiratory motion management during radiation treatment with an MR-linear accelerator (MR-linac). Methods and MaterialsMR imaging safety was first addressed by placing the CPAP device in an MR-safe closet and configuring a tube circuit via waveguide to the magnet bore. Reproducibility and linearity of the final configuration were assessed. Six healthy volunteers underwent thoracic imaging in a 0.35T MR-linac, with one free breathing (FB) and 2 DIBH acquisitions being obtained at 5 pressures from 0 to 15 cm-H2O. Lung and heart volumes and positions were recorded; repeatability was assessed by comparing 2 consecutive DIBH scans. Blinded reviewers graded images for motion artifact using a 3-point grading scale. Participants completed comfort and perception surveys before and after imaging sessions. ResultsCompared with FB alone, FB-10, FB-12, and FB-15 cm H2O significantly increased lung volumes (+23%, +34%, +44%; all P <.05) and inferiorly displaced the heart (0.86 cm, 0.96 cm, 1.18 cm; all P < . 05). Lung volumes were significantly greater with DIBH-0 cm H2O compared with FB-15 cm H2O (+105% vs +44%, P = .01), and DIBH-15 cm H2O yielded additional volume increase (+131% vs +105%, P = .01). Adding CPAP to DIBH decreased lung volume differences between consecutive breath holds (correlation coefficient 0.97 at 15 cm H2O vs 0.00 at 0 cm H2O). The addition of 15 cm H2O CPAP reduced artifact scores (P = .03) compared with FB; all DIBH images (0-15 cm H2O) had less artifact (P < .01). ConclusionsThis work demonstrates the feasibility of integrating CPAP in an MR-linac environment in healthy volunteers. Extending this work to a larger patient cohort is warranted to further establish the role of CPAP as an alternative and concurrent approach to DIBH in MR-guided radiation therapy.

Inter-fraction dynamics during post-operative 5 fraction cavity hypofractionated stereotactic radiotherapy with a MR LINAC: a prospective serial imaging study.

This study examined changes in the clinical target volume (CTV) and associated clinical implications on a magnetic resonance imaging linear accelerator (MR LINAC) during hypofractionated stereotactic radiotherapy (HSRT) to resected brain metastases. In addition, the suitability of using T2/FLAIR (T2f) sequence to define CTV was explored by assessing contouring variability between gadolinium-enhanced T1 (T1c) and T2f sequences. Fifteen patients treated to either 27.5 or 30Gy with five fraction HSRT were imaged with T1c and T2f sequences during treatment; T1c was acquired at planning (FxSim), and fraction 3 (Fx3), and T2f was acquired at FxSim and all five fractions. The CTV were contoured on all acquired images. Inter-fraction cavity dynamics and CTV contouring variability were quantified using absolute volume, Dice similarity coefficient (DSC), and Hausdorff distance (HD) metrics. The median CTV on T1c and T2f sequences at FxSim were 12.0cm3 (range, 1.2-30.1) and 10.2cm3 (range, 2.9-27.9), respectively. At Fx3, the median CTV decreased in both sequences to 9.3cm3 (range, 3.7-25.9) and 8.6cm3 (range, 3.3-22.5), translating to a median % relative reduction of - 11.4% on T1c (p = 0.009) and - 8.4% on T2f (p = 0.032). We observed a median % relative reduction in CTV between T1c and T2f at FxSim of - 6.0% (p = 0.040). The mean DSC was 0.85 ± 0.10, and the mean HD was 5.3 ± 2.7mm when comparing CTV on T1c and T2f at FxSim. Statistically significant reductions in cavity CTV was observed during HSRT, supporting the use of MR image guided radiation therapy and treatment adaptation to mitigate toxicity. Significant CTV contouring variability was seen between T1c and T2f sequences. Trial registration NCT04075305 - August 30, 2019.

Safety of gadolinium based contrast agents in magnetic resonance imaging-guided radiotherapy - An investigation of chelate stability using relaxometry.

With the introduction of hybrid magnetic resonance linacs (MR-linac), improved imaging has enabled daily treatment adaptation. However, the use of gadolinium based contrast agents (GBCAs) is desired to further improve MR image contrast. GBCAs are in the form of a non-toxic metalorganic gadolinium complex, but toxic un-chelated aqueous gadolinium(III), Gd3+(aq), can be released in patients if the organic ligand is degraded by the radiation. In this study, T1 relaxation measurements were performed to study the effect of radiation on three GBCAs. GBCAs, gadoteric acid, gadobutrol and gadoxectic acid were investigated in a concentration range of 10-100mM. Measurements were performed on a 500MHz nuclear MR (NMR) spectrometer with a high-resolution inversion recovery sequence to determine T1. Samples were irradiated with 7 MV photons on an MR-linac to a total dose of 100Gy. The lower detection limit of Gd3+(aq) was established by estimating the overall measurement uncertainty and comparing to corresponding changes in R1 when replacing chelated Gd3+ with gadolinium nitrate at predefined percentages. The overall measurement uncertainty was estimated to ±0.0053ms-1, corresponding to Gd3+(aq) detection levels 1%-1.5% or 1-4.5 micro molar at clinical GBCA dosage. No detectable differences in R1 were observed between irradiated and non-irradiated samples for any GBCA. This study did not find any measurable degradation of GBCAs due to irradiation with high-energy X-rays, however, in-vivo investigations are needed to provide the clinical basis for safe use of contrast agents in a radiotherapy workflow.