Single institution experience of MRI-guided radiotherapy for thoracic tumors and clinical characteristics impacting treatment duty cycle.

Introduction: MRI-guided radiotherapy (MRgRT) allows for direct motion management and real-time radiation treatment plan adaptation. We report our institutional experience using low strength 0.35T MRgRT for thoracic malignancies, and evaluate changes in treatment duty cycle between first and final MRgRT fractions. Methods: All patients with intrathoracic tumors treated with MRgRT were included. The primary reason for MRgRT (adjacent organ at risk [OAR] vs. motion management [MM] vs. other) was recorded. Tumor location was classified as central (within 2cm of tracheobronchial tree) vs. non-central, and further classified by the Expanded HILUS grouping. Gross tumor volume (GTV) motion, planning target volume expansions, dose/fractionation, treatment plan time, and total delivery time were extracted from the treatment planning system. Treatment plan time was defined as the time for beam delivery, including multileaf collimator (MLC) motion, and gantry rotation. Treatment delivery time was defined as the time from beam on to completion of treatment, including treatment plan time and patient respiratory breath holds. Duty cycle was calculated as treatment plan time/treatment delivery time. Duty cycles were compared between first and final fraction using a two-sample t-test. Results: Twenty-seven patients with thoracic tumors (16 non-small cell lung cancer and 11 thoracic metastases) were treated with MRgRT between 12/2021 and 06/2023. Fifteen patients received MRgRT due to OAR and 11 patients received MRgRT for motion management. 11 patients had central tumors and all were treated with MRgRT due to OAR risk. The median dose/fractionation was 50 Gy/5 fractions. For patients treated due to OAR (n=15), 80% had at least 1 adapted fraction during their course of radiotherapy. There was no plan adaptation for patients treated due to motion management (n=11). Mean GTV motion was significantly higher for patients treated due to motion management compared to OAR (16.1mm vs. 6.5mm, p=0.011). Mean duty cycle for fraction 1 was 54.2% compared to 62.1% with final fraction (p=0.004). Mean fraction 1 duty cycle was higher for patients treated due to OAR compared to patients treated for MM (61% vs. 45.0%, p=0.012). Discussion: Duty cycle improved from first fraction to final fraction possibly due to patient familiarity with treatment. Duty cycle was improved for patients treated due to OAR risk, likely due to more central location and thus decreased target motion.

Magnetic resonance - guided treatment of low-flow vascular malformations and the technologies to potentiate adoption.

Vascular malformations are congenital, non-neoplastic lesions that arise secondary to defects in angiogenesis. Vascular malformations are divided into high-flow (arteriovenous malformation) and low-flow (venous malformations and lymphatic malformations). Magnetic resonance imaging (MRI) is the standard for pre-and post-intervention assessments, while ultrasound (US), X-ray fluoroscopy and computed tomography (CT) are used for intra-procedural guidance. Sclerotherapy, an image-guided therapy that involves the injection of a sclerosant directly into the malformation, is typically the first-line therapy for treating low-flow vascular malformations. Sclerotherapy induces endothelial damage and necrosis/fibrosis with eventual involution of the malformation. Image-guided thermal therapies involve freezing or heating target tissue to induce cell death and necrosis. MRI is an alternative for intra-procedural guidance and monitoring during the treatment of vascular malformations. MR can provide dynamic, multiplanar imaging that delineates surrounding critical structures such as nerves and vasculature. Multiple studies have demonstrated that MR-guided treatment of vascular malformations is safe and effective. This review will detail (1) the use of MR for the classification and diagnosis of vascular malformations, (2) the current literature surrounding MR-guided treatment of vascular malformations, (3) a series of cases of MR-guided sclerotherapy and thermal ablation for the treatment of vascular malformations, and (4) a discussion of technologies that may potentiate interventional MRI adoption including high intensity focused ultrasound and guided laser ablation.

Magnetic Resonance Imaging-Aided SmartFlow Convection Delivery of DNX-2401: A Pilot, Prospective Case Series.

BACKGROUND: The Combination Adenovirus + Pembrolizumab to Trigger Immune Virus Effects (CAPTIVE) study is a phase II clinical trial testing the efficacy of a recombinant adenovirus DNX-2401 combined with the immune checkpoint inhibitor pembrolizumab. Here, we report the first patients in this study who underwent viral delivery through real-time magnetic resonance imaging (MRI) stereotaxis-guided SmartFlow convection delivery of DNX-2401. METHODS: Patients who underwent real-time MRI-guided DNX-2401 delivery through the SmartFlow convection catheter were prospectively followed. RESULTS: Precise catheter placement was achieved in all patients treated, and no adverse events were noted. Average radial error from target was 0.9 mm. Average procedural time was 3 hours 16 minutes and was comparable to other convection-enhanced delivery techniques. In 2 patients, delivery of DNX-2401 was visualized as >1 cm maximal diameter of T1 hypointensity infusate on MRI obtained immediately after completion of viral infusion. These patients exhibited partial response based on Response Assessment in Neuro-Oncology assessment. The remaining patient showed <1 cm maximal diameter of infusate on immediate postinfusion MRI and showed disease progression on subsequent MRI. CONCLUSIONS: Our pilot case series supports compatibility of the SmartFlow system with oncolytic adenovirus delivery and provides the basis for future validation studies.

Clinical outcomes of 3T magnetic resonance imaging-guided lumbar and sacral foraminal injections.

PURPOSE: This article evaluates the feasibility, safety, and efficacy of MRI-guided lumbar or sacral nerve root infiltration for chronic back pain. We compared the outcomes of our MRI-guided infiltrations with data from CT-guided infiltrations reported in the literature and explored the potential advantages of MRI guidance. METHOD: Forty-eight MRI-guided nerve root infiltrations were performed using a 3 T MRI machine. The optimal needle path was determined using breathhold T2-weighted sequences, and the needle was advanced under interleaved guidance based on breathhold PD-weighted images. Pain levels were assessed using a numeric rating scale (NRS) before the procedure and up to 5 months after, during follow-up. Procedure success was evaluated by comparing patients' pain levels before and after the infiltration. RESULTS: The MRI-guided infiltrations yielded pain reduction 1 week after the infiltration in 92% of cases, with an average NRS substantial change of 3.9 points. Pain reduction persisted after 5 months for 51% of procedures. No procedure-related complications occurred. The use of a 22G needle and reconstructed subtraction images from T2 FatSat sequences improved the workflow. CONCLUSION: Our study showed that MRI-guided nerve root infiltration is a feasible, safe, and effective treatment option for chronic back pain. Precise positioning of the needle tip and accurate distribution of the injected solution contributed to the effectiveness of MRI-guided infiltration, which appeared to be as accurate as CT-guided procedures. Further research is needed to explore the potential benefits of metal artifact reduction sequences to optimize chronic back pain management.

Automatic image-based tracking of gadolinium-filled balloon wedge catheters for MRI-guided cardiac catheterization using deep learning.

Introduction: Magnetic Resonance Imaging (MRI) is a promising alternative to standard x-ray fluoroscopy for the guidance of cardiac catheterization procedures as it enables soft tissue visualization, avoids ionizing radiation and provides improved hemodynamic data. MRI-guided cardiac catheterization procedures currently require frequent manual tracking of the imaging plane during navigation to follow the tip of a gadolinium-filled balloon wedge catheter, which unnecessarily prolongs and complicates the procedures. Therefore, real-time automatic image-based detection of the catheter balloon has the potential to improve catheter visualization and navigation through automatic slice tracking. Methods: In this study, an automatic, parameter-free, deep-learning-based post-processing pipeline was developed for real-time detection of the catheter balloon. A U-Net architecture with a ResNet-34 encoder was trained on semi-artificial images for the segmentation of the catheter balloon. Post-processing steps were implemented to guarantee a unique estimate of the catheter tip coordinates. This approach was evaluated retrospectively in 7 patients (6M and 1F, age = 7 ± 5 year) who underwent an MRI-guided right heart catheterization procedure with all images acquired in an orientation unseen during training. Results: The overall accuracy, specificity and sensitivity of the proposed catheter tracking strategy over all 7 patients were 98.4 ± 2.0%, 99.9 ± 0.2% and 95.4 ± 5.5%, respectively. The computation time of the deep-learning-based segmentation step was ∼10 ms/image, indicating its compatibility with real-time constraints. Conclusion: Deep-learning-based catheter balloon tracking is feasible, accurate, parameter-free, and compatible with real-time conditions. Online integration of the technique and its evaluation in a larger patient cohort are now warranted to determine its benefit during MRI-guided cardiac catheterization.

Deep learning based automatic segmentation of organs-at-risk for 0.35 T MRgRT of lung tumors.

BACKGROUND AND PURPOSE: Magnetic resonance imaging guided radiotherapy (MRgRT) offers treatment plan adaptation to the anatomy of the day. In the current MRgRT workflow, this requires the time consuming and repetitive task of manual delineation of organs-at-risk (OARs), which is also prone to inter- and intra-observer variability. Therefore, deep learning autosegmentation (DLAS) is becoming increasingly attractive. No investigation of its application to OARs in thoracic magnetic resonance images (MRIs) from MRgRT has been done so far. This study aimed to fill this gap. MATERIALS AND METHODS: 122 planning MRIs from patients treated at a 0.35 T MR-Linac were retrospectively collected. Using an 80/19/23 (training/validation/test) split, individual 3D U-Nets for segmentation of the left lung, right lung, heart, aorta, spinal canal and esophagus were trained. These were compared to the clinically used contours based on Dice similarity coefficient (DSC) and Hausdorff distance (HD). They were also graded on their clinical usability by a radiation oncologist. RESULTS: Median DSC was 0.96, 0.96, 0.94, 0.90, 0.88 and 0.78 for left lung, right lung, heart, aorta, spinal canal and esophagus, respectively. Median 95th percentile values of the HD were 3.9, 5.3, 5.8, 3.0, 2.6 and 3.5 mm, respectively. The physician preferred the network generated contours over the clinical contours, deeming 85 out of 129 to not require any correction, 25 immediately usable for treatment planning, 15 requiring minor and 4 requiring major corrections. CONCLUSIONS: We trained 3D U-Nets on clinical MRI planning data which produced accurate delineations in the thoracic region. DLAS contours were preferred over the clinical contours.

Automated tracking of morphologic changes in weekly magnetic resonance imaging during head and neck radiotherapy.

BACKGROUND AND PURPOSE: Anatomic changes during head and neck radiotherapy can impact dose delivery, necessitate adaptive replanning, and indicate patient-specific response to treatment. We have developed an automated system to track these changes through longitudinal MRI scans to aid identification and clinical intervention. The purpose of this article is to describe this tracking system and present results from an initial cohort of patients. MATERIALS AND METHODS: The Automated Watchdog in Adaptive Radiotherapy Environment (AWARE) was developed to process longitudinal MRI data for radiotherapy patients. AWARE automatically identifies and collects weekly scans, propagates radiotherapy planning structures, computes structure changes over time, and reports important trends to the clinical team. AWARE also incorporates manual structure review and revision from clinical experts and dynamically updates tracking statistics when necessary. AWARE was applied to patients receiving weekly T2-weighted MRI scans during head and neck radiotherapy. Changes in nodal gross tumor volume (GTV) and parotid gland delineations were tracked over time to assess changes during treatment and identify early indicators of treatment response. RESULTS: N = 91 patients were tracked and analyzed in this study. Nodal GTVs and parotids both shrunk considerably throughout treatment (-9.7 ± 7.7% and -3.7 ± 3.3% per week, respectively). Ipsilateral parotids shrunk significantly faster than contralateral (-4.3 ± 3.1% vs. -2.9 ± 3.3% per week, p = 0.005) and increased in distance from GTVs over time (+2.7 ± 7.2% per week, p < 1 × 10-5 ). Automatic structure propagations agreed well with manual revisions (Dice = 0.88 ± 0.09 for parotids and 0.80 ± 0.15 for GTVs), but for GTVs the agreement degraded 4-5 weeks after the start of treatment. Changes in GTV volume observed by AWARE as early as one week into treatment were predictive of large changes later in the course (AUC = 0.79). CONCLUSION: AWARE automatically identified longitudinal changes in GTV and parotid volumes during radiotherapy. Results suggest that this system may be useful for identifying rapidly responding patients as early as one week into treatment.

Adaptive hypofractionted and stereotactic body radiotherapy for lung tumors with real-time MRI guidance.

The treatment of central and ultracentral lung tumors with radiotherapy remains an ongoing clinical challenge. The risk of Grade 5 toxicity with ablative radiotherapy doses to these high-risk regions is significant as shown in recent prospective studies. Magnetic resonance (MR) image-guided adaptive radiotherapy (MRgART) is a new technology and may allow the delivery of ablative radiotherapy to these high-risk regions safely. MRgART is able to achieve this by utilizing small treatment margins, real-time gating/tracking and on-table plan adaptation to maintain dose to the tumor but limit dose to critical structures. The process of MRgART is complex and has nuances and challenges for the treatment of lung tumors. We outline the critical steps needed for appropriate delivery of MRgART for lung tumors safely and effectively.

Synthetic CT in Carbon Ion Radiotherapy of the Abdominal Site.

The generation of synthetic CT for carbon ion radiotherapy (CIRT) applications is challenging, since high accuracy is required in treatment planning and delivery, especially in an anatomical site as complex as the abdomen. Thirty-nine abdominal MRI-CT volume pairs were collected and a three-channel cGAN (accounting for air, bones, soft tissues) was used to generate sCTs. The network was tested on five held-out MRI volumes for two scenarios: (i) a CT-based segmentation of the MRI channels, to assess the quality of sCTs and (ii) an MRI manual segmentation, to simulate an MRI-only treatment scenario. The sCTs were evaluated by means of similarity metrics (e.g., mean absolute error, MAE) and geometrical criteria (e.g., dice coefficient). Recalculated CIRT plans were evaluated through dose volume histogram, gamma analysis and range shift analysis. The CT-based test set presented optimal MAE on bones (86.03 ± 10.76 HU), soft tissues (55.39 ± 3.41 HU) and air (54.42 ± 11.48 HU). Higher values were obtained from the MRI-only test set (MAEBONE = 154.87 ± 22.90 HU). The global gamma pass rate reached 94.88 ± 4.9% with 3%/3 mm, while the range shift reached a median (IQR) of 0.98 (3.64) mm. The three-channel cGAN can generate acceptable abdominal sCTs and allow for CIRT dose recalculations comparable to the clinical plans.

Preclinical robotic device for magnetic resonance imaging guided focussed ultrasound.

BACKGROUND: A robotic device featuring three motion axes was manufactured for preclinical research on focussed ultrasound (FUS). The device comprises a 2.75 MHz single element ultrasonic transducer and is guided by Magnetic Resonance Imaging (MRI). METHODS: The compatibility of the device with the MRI was evaluated by estimating the influence on the signal-to-noise ratio (SNR). The efficacy of the transducer in generating ablative temperatures was evaluated in phantoms and excised porcine tissue. RESULTS: System's activation in the MRI scanner reduced the SNR to an acceptable level without compromising the image quality. The transducer demonstrated efficient heating ability as proved by MR thermometry. Discrete and overlapping thermal lesions were inflicted in excised tissue. CONCLUSIONS: The FUS system was proven effective for FUS thermal applications in the MRI setting. It can thus be used for multiple preclinical applications of the emerging MRI-guided FUS technology. The device can be scaled-up for human use with minor modifications.

Concordance of MRI-Guided Fusion and Systematic 12-Core Prostate Biopsy for the Detection of Prostate Cancer.

Background: MRI-guided fusion biopsy is increasingly utilized over systematic 12-core biopsy for men with MRI-visible prostate lesions. Patients and Methods: Patients with MRI visible lesions who underwent MRI-guided fusion and systematic 12-core biopsy from 2016-2020 in the Intermountain Healthcare (IHC) system were consecutively analyzed. This was in the setting of a continuous quality assurance initiative among the reading radiologists. Primary outcome was prostate cancer (PCa) detection defined by Gleason grade group (GGG) 1 or higher. Clinically significant cancer (CSC) was defined as GGG 2 or higher. Patients were stratified by biopsy date, 2016-2017 and 2018-2021, and lesions were stratified by PI-RADS v2 category. Results: A total of 184 patients with 324 MRI-detectable lesions underwent both biopsy modalities in the IHC system from 2016 to 2021. CSC was detected in 23.5% of MRI-guided fusion biopsies. Comparing PI-RAD v2 categories 1-3 to categories 4-5, rate of CSC was 10% and 42% respectively. MRI-guided fusion and systematic 12-core biopsies were concordant for PCa in 77% of men and CSC in 83%. MRI-guided fusion biopsy detected PCa in 26/103 and CSC in 20/131 men in whom systematic 12-core biopsy was negative. Systematic 12-core biopsy detected PCa in 17/94 and CSC in 11/122 men in whom MRI-guided fusion was negative. Conclusions: Omitting MRI-guided fusion or systematic 12-core biopsy would have resulted in underdiagnosis of CSC in 11% or 6% of patients respectively. Combining biopsies increased detection rate of CSC. This was in the setting of a continuous quality assurance program at a large community-based hospital.

Series of High Magnetic Resonance-Guided Photoinduced Nanodelivery Systems for Precisely Improving the Efficiency of Cancer Therapy.

Nanochemotherapy is recognized as one of the most promising cancer treatment options, and the design of the carrier has a crucial impact on the final efficacy. To precisely improve the efficacy and reduce the toxicity, we combined the clinical contrast agent (Gd-DTPA) with a stimulus-sensitive o-nitrobenzyl ester and then prepared a series of nNBGD lipids by varying the carbon chain length of the hydrophobic group. The self-assembled nNBGD liposomes can be tracked by MRI to localize the aggregation of drug carriers in vivo, so as to prompt the application of light stimulation at the optimal time to facilitate the precise release of carriers at the lesion site. And the application potential of this strategy was verified with 88% tumor suppression effect in the 12NBGD-DOX+UV group. In addition, this paper emphasizes that small differences in structure can affect the overall performance of the carriers. By exploration of the differences in stability, drug loading, stimulus responsiveness, MRI imaging effect, and toxicity of the series of nNBGD carriers, the relationship between the length of the hydrophobic group of nNBGD lipids and the overall performance of the carriers is given, which provides experimental support and design reference for other carriers.

Offline and online LSTM networks for respiratory motion prediction in MR-guided radiotherapy.

Objective.Gated beam delivery is the current clinical practice for respiratory motion compensation in MR-guided radiotherapy, and further research is ongoing to implement tracking. To manage intra-fractional motion using multileaf collimator tracking the total system latency needs to be accounted for in real-time. In this study, long short-term memory (LSTM) networks were optimized for the prediction of superior-inferior tumor centroid positions extracted from clinically acquired 2D cine MRIs.Approach.We used 88 patients treated at the University Hospital of the LMU Munich for training and validation (70 patients, 13.1 h), and for testing (18 patients, 3.0 h). Three patients treated at Fondazione Policlinico Universitario Agostino Gemelli were used as a second testing set (1.5 h). The performance of the LSTMs in terms of root mean square error (RMSE) was compared to baseline linear regression (LR) models for forecasted time spans of 250 ms, 500 ms and 750 ms. Both the LSTM and the LR were trained with offline (offlineLSTM andofflineLR) and online schemes (offline+onlineLSTM andonlineLR), the latter to allow for continuous adaptation to recent respiratory patterns.Main results.We found theoffline+onlineLSTM to perform best for all investigated forecasts. Specifically, when predicting 500 ms ahead it achieved a mean RMSE of 1.20 mm and 1.00 mm, while the best performing LR model achieved a mean RMSE of 1.42 mm and 1.22 mm for the LMU and Gemelli testing set, respectively.Significance.This indicates that LSTM networks have potential as respiratory motion predictors and that continuous online re-optimization can enhance their performance.

Technical feasibility and clinical evaluation of 4D-MRI guided liver SBRT on the MR-linac.

PURPOSE: Image-guided stereotactic body radiation therapy (SBRT) is an important local treatment for liver metastases. MRI-guidance enables direct tumor visualization, eliminating fiducial marker implantation. The purpose of this study was to test technical feasibility of our 4D-MRI guided liver SBRT workflow. Additionally, intra-fraction target motion and consequent target-coverage were studied. MATERIALS & METHODS: Patients with liver metastases were included in this sub-study of the prospective UMBRELLA-II clinical trial. Patients received mid-position (midP) SBRT. The daily adapt-to-position workflow included localization, verification and intra-fraction tumor midP monitoring using 4D-MRI. Technical feasibility was established based on persistence of the treatment protocol, treatment time ≤1 h, no geographical miss and no unexpected acute toxicity grade >3. All 4D-MRIs were registered to the planning midP-CT and tumor midP and amplitude were calculated. Additionally, delivered target dose was accumulated incorporating the 4D-MRI intra-fraction tumor motion and evaluated with Monte-Carlo error simulations. RESULTS: 20 patients with liver metastases were included and treated with 4D-MRI guided SBRT. Feasibility criteria were met in all-but-one patient. No grade ≥3 acute toxicity was observed. Group mean (M), systematic and random midP-drifts were 2.4 mm, 2.6 mm and 3.1 mm in CC-direction. 4D-MRI tumor CC-amplitudes were reduced compared to the simulation 4D-CT (M = -1.9 mm) and decreased during treatment (M = -1.4 mm). Dose accumulation showed adequate target-coverage on a population level. CONCLUSION: We successfully demonstrated technical feasibility of 4D-MRI guided SBRT in a cohort of 20 patients with liver metastases. However, substantial midposition drifts occurred which stress the need for intra-fraction motion management strategies to further increase the precision of treatment delivery.

Magnetic resonance imaging-guided lumbar nerve root infiltrations: optimization of an in-house protocol.

BACKGROUND: For the treatment of radicular pain, nerve root infiltrations can be performed under MRI guidance in select, typically younger, patients where repeated CT exams are not desirable due to associated radiation risk, or potential allergic reactions to iodinated contrast medium. METHODS: Fifteen 3 T MRI-guided nerve root infiltrations were performed in 12 patients with a dedicated surface coil combined with the standard spine coil, using a breathhold PD sequence. The needle artifact on the MR images and the distance between the needle tip and the infiltrated nerve root were measured. RESULTS: The distance between the needle tip and the nerve root was 2.1 ± 1.4 mm. The visual artifact width, perpendicular to the needle long axis, was 2.1 ± 0.7 mm. No adverse events were reported. CONCLUSION: This technical note describes the optimization of the procedure in a 3 T magnetic field, including reported procedure time and an assessment of targeting precision.

Technical Note: Four-dimensional deformable digital phantom for MRI sequence development.

PURPOSE: MR-guided radiotherapy has different requirements for the images than diagnostic radiology, thus requiring development of novel imaging sequences. MRI simulation is an excellent tool for optimizing these new sequences; however, currently available software does not provide all the necessary features. In this paper, we present a digital framework for testing MRI sequences that incorporates anatomical structure, respiratory motion, and realistic presentation of MR physics. METHODS: The extended Cardiac-Torso (XCAT) software was used to create T1 , T2 , and proton density maps that formed the anatomical structure of the phantom. Respiratory motion model was based on the XCAT deformation vector fields, modified to create a motion model driven by a respiration signal. MRI simulation was carried out with JEMRIS, an open source Bloch simulator. We developed an extension for JEMRIS, which calculates the motion of each spin independently, allowing for deformable motion. RESULTS: The performance of the framework was demonstrated through simulating the acquisition of a two-dimensional (2D) cine and demonstrating expected motion ghosts from T2 weighted spin echo acquisitions with different respiratory patterns. All simulations were consistent with behavior previously described in literature. Simulations with deformable motion were not more time consuming than with rigid motion. CONCLUSIONS: We present a deformable four-dimensional (4D) digital phantom framework for MR sequence development. The framework incorporates anatomical structure, realistic breathing patterns, deformable motion, and Bloch simulation to achieve accurate simulation of MRI. This method is particularly relevant for testing novel imaging sequences for the purpose of MR-guided radiotherapy in lungs and abdomen.

Magnetic Resonance Guided Radiation Therapy for Pancreatic Adenocarcinoma, Advantages, Challenges, Current Approaches, and Future Directions.

INTRODUCTION: Pancreatic adenocarcinoma (PAC) has some of the worst treatment outcomes for any solid tumor. PAC creates substantial difficulty for effective treatment with traditional RT delivery strategies primarily secondary to its location and limited visualization using CT. Several of these challenges are uniquely addressed with MR-guided RT. We sought to summarize and place into context the currently available literature on MR-guided RT specifically for PAC. METHODS: A literature search was conducted to identify manuscript publications since September 2014 that specifically used MR-guided RT for the treatment of PAC. Clinical outcomes of these series are summarized, discussed, and placed into the context of the existing pancreatic literature. Multiple international experts were involved to optimally contextualize these publications. RESULTS: Over 300 manuscripts were reviewed. A total of 6 clinical outcomes publications were identified that have treated patients with PAC using MR guidance. Successes, challenges, and future directions for this technology are evident in these publications. MR-guided RT holds theoretical promise for the treatment of patients with PAC. As with any new technology, immediate or dramatic clinical improvements associated with its use will take time and experience. There remain no prospective trials, currently publications are limited to small retrospective experiences. The current level of evidence for MR guidance in PAC is low and requires significant expansion. Future directions and ongoing studies that are currently open and accruing are identified and reviewed. CONCLUSIONS: The potential promise of MR-guided RT for PAC is highlighted, the challenges associated with this novel therapeutic intervention are also reviewed. Outcomes are very early, and will require continued and long term follow up. MR-guided RT should not be viewed in the same fashion as a novel chemotherapeutic agent for which dosing, administration, and toxicity has been established in earlier phase studies. Instead, it should be viewed as a novel procedural intervention which must be robustly tested, refined and practiced before definitive conclusions on the potential benefits or detriments can be determined. The future of MR-guided RT for PAC is highly promising and the potential implications on PAC are substantial.

Deuterium oxide as a contrast medium for real-time MRI-guided endovascular neurointervention.

Rationale: Endovascular intervention plays an important role in the treatment of various diseases, in which MRI-guidance can potentially improve precision. However, the clinical applications of currently available contrast media, including Gadolinium-based contrast agents and superparamagnetic iron oxide particles (SPIO), are hindered by safety concerns. In the present study, we sought to develop D2O as a novel contrast agent for guiding endovascular neurointervention. Methods: Animal studies were approved by institutional ACUC and conducted using an 11.7 T Bruker Biospec system and a 3T Siemens Trio clinical scanner for rodent and canine imaging, respectively. The locally selective blood brain barrier opening (BBBO) in rat brains was obtained by intraarterial (IA) injection of mannitol. The dynamic T2w* EPI MRI sequence was used to study the trans-catheter perfusion territory by IA administered SPIO before mannitol administration, whereas a dynamic T1w FLASH sequence was used to acquire Gd contrast-enhanced MRI for assessing BBBO after injection of mannitol. The contrast generated by D2O assessed by either EPI or FLASH methods was compared with the corresponding results assessed by SPIO or Gd. The utility of D2O MRI was also demonstrated to guide drug delivery to glioma in a mouse model. Finally, the clinical utility of D2O-MRI was demonstrated in a canine model. Results: Our study has shown that the contrast generated by D2O can be used to precisely delineate trans-catheter perfusion territory in both small and large animals. The perfusion territories determined by D2O-MRI show moderate correlation with those by SPIO-MRI (Spearman coefficient r = 0.5234, P < 0.001). Moreover, our results show that the perfusion territory determined by D2O-MRI can successfully predict the areas with BBBO after mannitol treatment similar to that assessed by Gd-MRI (Spearman coefficient r = 0.6923, P < 0.001). Using D2O-MRI as imaging guidance, the optimal infusion rate in the mouse brain was determined to be 150 µL/min to maximize the delivery efficacy to the tumor without serious off-target delivery to the brain parenchyma. The enhanced drug delivery of antibodies to the brain tumor was confirmed by fluorescence imaging. Conclusion: Our study demonstrated that D2O can be used as a negative MRI contrast medium to guide endovascular neurointervention. The established D2O -MRI method is safe and quantitative, without the concern of contrast accumulation. These qualities make it an attempting approach for a variety of endovascular procedures.

An MRI framework for respiratory motion modelling validation.

INTRODUCTION: Respiratory motion models establish a correspondence between respiratory-correlated (RC) 4-dimensional (4D) imaging and respiratory surrogates, to estimate time-resolved (TR) 3D breathing motion. To evaluate the performance of motion models on real patient data, a validation framework based on magnetic resonance imaging (MRI) is proposed, entailing the use of RC 4DMRI to build the model, and on both (i) TR 2D cine-MRI and (ii) additional 4DMRI data for testing intra-/inter-fraction breathing motion variability. METHODS: Repeated MRI data were acquired in 7 patients with abdominal lesions. The considered model relied on deformable image registration (DIR) for building the model and compensating for inter-fraction baseline variations. Both 2D and 3D validation were performed, by comparing model estimations with the ground truth 2D cine-MRI and 4DMRI respiratory phases, respectively. RESULTS: The median DIR error was comparable to the voxel size (1.33 × 1.33 × 5 mm3 ), with higher values in the presence of large inter-fraction motion (median value: 2.97 mm). In the 2D validation, the median estimation error on anatomical landmarks' position resulted below 4 mm in every scenario, whereas in the 3D validation it was 1.33 mm and 4.21 mm when testing intra- and inter-fraction motion, respectively. The range of motion described in the cine-MRI was comparable to the motion of the building 4DMRI, being always above the estimation error. Overall, the model performance was dependent on DIR error, presenting reduced accuracy when inter-fraction baseline variations occurred. CONCLUSIONS: Results suggest the potential of the proposed framework in evaluating global motion models for organ motion management in MRI-guided radiotherapy.

HDR brachytherapy boost using MR-only workflow for intermediate- and high-risk prostate cancer: 8-year results of a pilot study.

PURPOSE: To report 8-year clinical outcome with high-dose-rate brachytherapy (HDRBT) boost using MRI-only workflow for intermediate (IR) and high-risk (HR) prostate cancer (PC) patients. METHODS AND MATERIALS: Fifty-two patients were treated with 46-60 Gy of 3D conformal radiotherapy preceded and/or followed by a single dose of 8-10 Gy MRI-guided HDRBT. Interventions were performed in a 0.35 T MRI scanner. Trajectory planning, navigation, contouring, catheter reconstruction, and dose calculation were exclusively based on MRI images. Biochemical relapse-free- (BRFS), local relapse-free- (LRFS), distant metastasis-free- (DMFS), cancer-specific-(CCS) and overall survival (OS) were analyzed. Late morbidity was scored using the Common Terminology Criteria for Adverse Events (CTCAE 4.0) combined with RTOG (Radiation Therapy Oncology Group) scale for urinary toxicity and rectal urgency (RU) determined by Yeoh. RESULTS: Median follow-up time was 107 (range: 19-143) months. The 8-year actuarial rates of BRFS, LRFS, DMFS, CSS and OS were 85.7%, 97%, 97.6%, and 77.6%, respectively. There were no Gr.3 GI side effects. The 8-year actuarial rate of Gr.2 proctitis was 4%. The 8-year cumulative incidence of Gr.3 GU side effects was 8%, including two urinary stenoses (5%) and one cystitis (3%). EPIC urinary and bowel scores did not change significantly over time. CONCLUSIONS: MRI-only HDR-BT boost with moderate dose escalation provides excellent 8-year disease control with a favorable toxicity profile for IRPC and HRPC patients. Our results support the clinical importance of MRI across the BT workflow.