Magnetic resonance linear accelerator technology and adaptive radiation therapy: An overview for clinicians.

Radiation therapy (RT) continues to play an important role in the treatment of cancer. Adaptive RT (ART) is a novel method through which RT treatments are evolving. With the ART approach, computed tomography or magnetic resonance (MR) images are obtained as part of the treatment delivery process. This enables the adaptation of the irradiated volume to account for changes in organ and/or tumor position, movement, size, or shape that may occur over the course of treatment. The advantages and challenges of ART maybe somewhat abstract to oncologists and clinicians outside of the specialty of radiation oncology. ART is positioned to affect many different types of cancer. There is a wide spectrum of hypothesized benefits, from small toxicity improvements to meaningful gains in overall survival. The use and application of this novel technology should be understood by the oncologic community at large, such that it can be appropriately contextualized within the landscape of cancer therapies. Likewise, the need to test these advances is pressing. MR-guided ART (MRgART) is an emerging, extended modality of ART that expands upon and further advances the capabilities of ART. MRgART presents unique opportunities to iteratively improve adaptive image guidance. However, although the MRgART adaptive process advances ART to previously unattained levels, it can be more expensive, time-consuming, and complex. In this review, the authors present an overview for clinicians describing the process of ART and specifically MRgART.

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.

Evaluating contouring accuracy and dosimetry impact of current MRI-guided adaptive radiation therapy for brain metastases: a retrospective study.

BACKGROUND: Magnetic resonance imaging (MRI) guided adaptive radiotherapy (MRgART) has gained increasing attention, showing clinical advantages over conventional radiotherapy. However, there are concerns regarding online target delineation and modification accuracy. In our study, we aimed to investigate the accuracy of brain metastases (BMs) contouring and its impact on dosimetry in 1.5 T MRI-guided online adaptive fractionated stereotactic radiotherapy (FSRT). METHODS: Eighteen patients with 64 BMs were retrospectively evaluated. Pre-treatment 3.0 T MRI scans (gadolinium contrast-enhanced T1w, T1c) and initial 1.5 T MR-Linac scans (non-enhanced online-T1, T2, and FLAIR) were used for gross target volume (GTV) contouring. Five radiation oncologists independently contoured GTVs on pre-treatment T1c and initial online-T1, T2, and FLAIR images. We assessed intra-observer and inter-observer variations and analysed the dosimetry impact through treatment planning based on GTVs generated by online MRI, simulating the current online adaptive radiotherapy practice. RESULTS: The average Dice Similarity Coefficient (DSC) for inter-observer comparison were 0.79, 0.54, 0.59, and 0.64 for pre-treatment T1c, online-T1, T2, and FLAIR, respectively. Inter-observer variations were significantly smaller for the 3.0 T pre-treatment T1c than for the contrast-free online 1.5 T MR scans (P < 0.001). Compared to the T1c contours, the average DSC index of intra-observer contouring was 0.52‒0.55 for online MRIs. For BMs larger than 3 cm3, visible on all image sets, the average DSC indices were 0.69, 0.71 and 0.64 for online-T1, T2, and FLAIR, respectively, compared to the pre-treatment T1c contour. For BMs < 3 cm3, the average visibility rates were 22.3%, 41.3%, and 51.8% for online-T1, T2, and FLAIR, respectively. Simulated adaptive planning showed an average prescription dose coverage of 63.4‒66.9% when evaluated by ground truth planning target volumes (PTVs) generated on pre-treatment T1c, reducing it from over 99% coverage by PTVs generated on online MRIs. CONCLUSIONS: The accuracy of online target contouring was unsatisfactory for the current MRI-guided online adaptive FSRT. Small lesions had poor visibility on 1.5 T non-contrast-enhanced MR-Linac images. Contour inaccuracies caused a one-third drop in prescription dose coverage for the target volume. Future studies should explore the feasibility of contrast agent administration during daily treatment in MRI-guided online adaptive FSRT procedures.

Volumetric hyperthermia delivery using the ExAblate Body MR-guided focused ultrasound system.

OBJECTIVES: To investigate image-guided volumetric hyperthermia strategies using the ExAblate Body MR-guided focused ultrasound ablation system, involving mechanical transducer movement and sector-vortex beamforming. MATERIALS AND METHODS: Acoustic and thermal simulations were performed to investigate volumetric hyperthermia using mechanical transducer movement combined with sector-vortex beamforming, specifically for the ExAblate Body transducer. The system control in the ExAblate Body system was modified to achieve fast transducer movement and MR thermometry-based hyperthermia control, mechanical transducer movements and electronic sector-vortex beamforming were combined to optimize hyperthermia delivery. The experimental validation was performed using a tissue-mimicking phantom. RESULTS: The developed simulation framework allowed for a parametric study with varying numbers of heating spots, sonication durations, and transducer movement times to evaluate the hyperthermia characteristics for mechanical transducer movement and sector-vortex beamforming. Hyperthermic patterns involving 2-4 sequential focal spots were analyzed. To demonstrate the feasibility of volumetric hyperthermia in the system, a tissue-mimicking phantom was sonicated with two distinct spots through mechanical transducer movement and sector-vortex beamforming. During hyperthermia, the average values of Tmax, T10, Tavg, T90, and Tmin over 200 s were measured within a circular ROI with a diameter of 10 pixels. These values were found to be 8.6, 7.9, 6.6, 5.2, and 4.5 °C, respectively, compared to the baseline temperature. CONCLUSIONS: This study demonstrated the volumetric hyperthermia capabilities of the ExAblate Body system. The simulation framework developed in this study allowed for the evaluation of hyperthermia characteristics that could be implemented with the ExAblate MRgFUS system.

Revolutionizing brain interventions: the multifaceted potential of histotripsy.

Histotripsy, a non-thermal ultrasound technique, holds significant promise in various applications within the realm of brain interventions. While its use for treating brain tumors is somewhat limited, focused ultrasound technology has been extensively investigated for a wide range of purposes within the brain, including disrupting the blood-brain barrier, supporting immunotherapy, addressing conditions like essential tremor, Parkinson's disease, Alzheimer's disease, epilepsy, and neuropathic pain. Research findings indicate that histotripsy can reduce tumor cells with fewer pulses, minimizing the risk of bleeding and cellular injury. The use of MRI sequences such as T2 and T2* enhances the evaluation of the effects of histotripsy treatment, facilitating non-invasive assessment of treated areas. Furthermore, histotripsy displays promise in creating precise brain lesions with minimal edema and inflammation, particularly in porcine models, suggesting considerable progress in the treatment of brain lesions. Moreover, studies confirm its feasibility, safety, and effectiveness in treating intracerebral hemorrhage by safely liquefying clots without causing significant harm to surrounding brain tissue., opening exciting possibilities for clinical applications. The development of transcranial MR-guided focused ultrasound systems based on histotripsy represents a significant breakthrough in overcoming the limitations associated with thermal ablation techniques. Histotripsy's ability to efficiently liquefy clots, minimize skull heating, and target shallow lesions near the skull establishes it as a promising alternative for various brain treatments. In conclusion, histotripsy offers diverse potential in the field of brain interventions, encompassing applications ranging from tumor treatment to the management of intracerebral hemorrhage. While challenges such as accurate monitoring and differentiation of treatment effects persist, ongoing research efforts and technological advancements continue to expand the role of histotripsy in both neurology and neurosurgery.

MR-guided laser interstitial thermal therapy in the treatment of brain tumors and epilepsy.

MR-guided Laser Interstitial Thermal Therapy (MRgLITT) is a minimally invasive neurosurgical technique increasingly used for the treatment of drug-resistant epilepsy and brain tumors. Utilizing near-infrared light energy delivery guided by real-time MRI thermometry, MRgLITT enables precise ablation of targeted brain tissues, resulting in limited corridor-related morbidity and expedited postoperative recovery. Since receiving CE marking in 2018, the adoption of MRgLITT has expanded to more than 40 neurosurgical centers across Europe. In epilepsy treatment, MRgLITT can be applied to various types of focal lesional epilepsy, including mesial temporal lobe epilepsy, hypothalamic hamartoma, focal cortical dysplasias, periventricular heterotopias, cavernous malformations, dysembryoplastic neuroepithelial tumors (DNET), low-grade gliomas, tuberous sclerosis, and in disconnective surgeries. In neuro-oncology, MRgLITT is used for treating newly diagnosed and recurrent primary brain tumors, brain metastases, and radiation necrosis. This comprehensive review presents an overview of the current evidence and technical considerations for the use of MRgLITT in treating various pathologies associated with drug-resistant epilepsy and brain tumors.

An Overview of MR-Guided Laser Interstitial Thermal Therapy (MRg-LITT) in Disrupting the Blood-Brain Barrier: Efficacy and Duration.

The blood-brain barrier (BBB) is a selectively semi-permeable layer, crucial in shielding the brain from external pathogens and toxic substances while maintaining ionic homeostasis and sufficient nutrient supply. However, it poses a significant challenge for drugs to penetrate the BBB in order to effectively target brain tumors. Magnetic resonance-guided laser interstitial thermal therapy (MRg-LITT) is a minimally invasive technique that employs thermal energy to cauterize intracranial lesions with the potential to temporarily disrupt the BBB. This further opens a possible therapeutic window to enhance patient outcomes. Here, we review the impact of MRg-LITT on BBB and blood tumor barrier (BTB) and the duration of the BBB disruption. Studies have shown that MRg-LITT is effective due to its minimally invasive nature, precise tumor targeting, and low complication rates. Although the disruption duration varies across studies, the average peak disruption is within the initial two weeks post-ablation period and subsequently exhibits a gradual decline. However, further research involving larger groups with extended follow-up periods is required to determine disruption duration more accurately. In addition, evaluating toxicity and glymphatic system disruption is crucial to circumvent potential risks associated with this procedure.

Double lesion MRgFUS thalamotomy for essential tremor: 4.5-year outcomes and framework for assessing loss of efficacy and tremor progression.

BACKGROUND: The essential tremor (ET) course to 54 months post-unilateral VIM/PSA magnetic resonance-guided focused ultrasound (MRgFUS) in the treated arm (TA) and non-treated arm (NTA) of 12 patients is reported. METHODS: Tremor severity was rated using Bain Findley spirography (BFS) scores in the TA and NTA. We divided follow-up into 'Early' (0-6 months) and 'Late' (6-54 months) phases, to minimise the effect of peri-lesion oedema resolution on the latter. RESULTS: The mean baseline BFS score was 6.2 in TA and 5.7 in the NTA. After unilateral VIM/PSA MRgFUS, mean BFS improved in TA at all subsequent time points (p < 0.001), with no significant differences between BFS scores at consecutive assessments or between 1 and 54 months, while the NTA BFS scores worsened between 12 and 24 months (p < 0.003). Three patients showed worsening of their TA BFS scores and an increasing NTA-TA BFS difference, indicating slower tremor worsening in TA compared to NTA, whilst one patient showed a greater rate of worsening in the TA compared to NTA BFS. CONCLUSION: After 54 months, the beneficial effect of MRgFUS is usually maintained with any worsening of BFS scores in TA slower than in NTA. Loss of treatment benefit is rare.

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.

Acute toxicity comparison of magnetic resonance-guided adaptive versus fiducial or computed tomography-guided non-adaptive prostate stereotactic body radiotherapy: A systematic review and meta-analysis.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is gaining wider adoption for prostate cancer management but there remain significant toxicity risks when delivering prostate SBRT with standard techniques. Magnetic resonance-guided daily adaptive SBRT (MRg-A-SBRT) offers technological advantages in precision of radiation dose delivery, but the toxicity profile associated with MRg-A-SBRT compared to more standardly used fiducial or computed tomography-guided non-adaptive prostate SBRT (CT-SBRT) remains unknown. METHODS: A meta-analysis to compare acute toxicity rates associated with MRg-A-SBRT and CT-SBRT for prostate cancer was performed in compliance with PRISMA guidelines. MEDLINE (PubMed) and Google Scholar were searched for prospective studies of prostate SBRT that were published between January 1, 2018 and August 31, 2022. Random effects and fixed effects models were used to estimate pooled toxicity rates, and meta-regression was performed to compare toxicity between MRg-A-SBRT and CT-SBRT study groups. RESULTS: Twenty-nine prospective studies were identified that met the inclusion criteria and included a total of 2547 patients. The pooled estimates for acute grade 2 or higher (G2+) genitourinary (GU) and gastrointestinal (GI) toxicity for MRg-A-SBRT were 16% (95% confidence interval [CI], 10%-24%) and 4% (95% CI, 2%-7%) and for CT-SBRT they were 28% (95% CI, 23%-33%) and 9% (95% CI, 6%-12%), respectively. On meta-regression, the odds ratios for acute G2+ GU and GI toxicities comparing MRg-A-SBRT and CT-SBRT were 0.56 (95% CI, 0.33-0.97, p = .04) and 0.40 (95% CI, 0.17-0.96, p = .04), respectively. CONCLUSION: MRg-A-SBRT is associated with a significantly reduced risk of acute G2+ GU or GI toxicity compared to CT-SBRT. Longer follow-up will be needed to evaluate late toxicity and disease control outcomes. PLAIN LANGUAGE SUMMARY: Magnetic resonance imaging-guided daily adaptive prostate stereotactic radiation (MRg-A-SBRT) is a treatment that may allow for delivery of prostate radiation more precisely than other radiotherapy techniques, but it is unknown whether this reduces side effects compared to standardly used computed tomography-guided SBRT (CT-SBRT). In this systematic review and meta-analysis combining data from 29 clinical trials including 2547 patients, it was found that the risk of short-term urinary side effects was reduced by 44% and the risk of short-term bowel side effects was reduced by 60% with MRg-A-SBRT compared to CT-SBRT.

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.

Simultaneous T2 -weighted real-time MRI of two orthogonal slices.

PURPOSE: MR guidance is used during therapy to detect and compensate for lesion motion. T2 -weighted MRI often has a superior lesion contrast in comparison to T1 -weighted real-time imaging. The purpose of this work was to design a fast T2 -weighted sequence capable of simultaneously acquiring two orthogonal slices, enabling real-time tracking of lesions. METHODS: To generate a T2 contrast in two orthogonal slices simultaneously, a sequence (Ortho-SFFP-Echo) was designed that samples the T2 -weighted spin echo (S- ) signal in a TR-interleaved acquisition of two slices. Slice selection and phase-encoding directions are swapped between the slices, leading to a unique set of spin-echo signal conditions. To minimize motion-related signal dephasing, additional flow-compensation strategies are implemented. In both the abdominal breathing phantom and in vivo experiments, a time series was acquired using Ortho-SSFP-Echo. The centroid of the target was tracked in postprocessing steps. RESULTS: In the phantom, the lesion could be identified and delineated in the dynamic images. In the volunteer experiments, the kidney was visualized with a T2 contrast at a temporal resolution of 0.45 s under free-breathing conditions. A respiratory belt demonstrated a strong correlation with the time course of the kidney centroid in the head-foot direction. A hypointense saturation band at the slice overlap did not inhibit lesion tracking in the semi-automatic postprocessing steps. CONCLUSION: The Ortho-SFFP-Echo sequence delivers real-time images with a T2 -weighted contrast in two orthogonal slices. The sequence allows for simultaneous acquisition, which could be beneficial for real-time motion tracking in radiotherapy or interventional MRI.

Improved MR temperature imaging at 0.5 T using view-sharing accelerated multiecho thermometry for MR-guided laser interstitial thermal therapy.

The aim of the current study was to improve temperature-monitoring precision using multiecho proton resonance frequency shift-based thermometry with view-sharing acceleration for MR-guided laser interstitial thermal therapy (MRgLITT) on a 0.5-T low-field MR system. Both precision and speed of the temperature measurement for clinical MRgLITT treatments suffer at low field, due to reduced image signal-to-noise ratio (SNR), decreased temperature-induced phase changes, and limited RF receiver channels. In this work, a bipolar multiecho gradient-recalled echo sequence with a temperature-to-noise ratio optimal weighted echo combination is applied to improve the temperature precision. A view-sharing-based approach is utilized to accelerate signal acquisitions while preserving image SNRs. The method was evaluated using ex vivo (pork and pig brain) LITT heating experiments and in vivo (human brain) nonheating experiments on a high-performance 0.5-T scanner. In terms of results, (1) after echo combination, multiecho thermometry (i.e., ~7.5-40.5 ms, 7 TEs) provides ~1.5-1.9 times higher temperature precision than the no echo combination case (i.e., TE7 = 40.5 ms) within the same readout bandwidth. Additionally, echo registration is necessary for the bipolar multiecho sequence; (2) for a threefold acceleration, the view-sharing approach with variable-density subsampling shows around 1.8 times lower temperature errors than the GRAPPA method. Particularly for view-sharing, variable-density subsampling performs better than Interleave subsampling; and (3) ex vivo heating and in vivo nonheating experiments demonstrated that the temperature accuracy was less than 0.5 ° C and that the temperature precision was less than 0.6 ° C using the proposed 0.5-T thermometry. It was concluded that view-sharing accelerated multiecho thermometry is a practical temperature measurement approach for MRgLITT at 0.5 T.

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).

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.

Motion-robust, multi-slice, real-time MR thermometry for MR-guided thermal therapy in abdominal organs.

PURPOSE: To develop an effective and practical reconstruction pipeline to achieve motion-robust, multi-slice, real-time MR thermometry for monitoring thermal therapy in abdominal organs. METHODS: The application includes a fast spiral magnetic resonance imaging (MRI) pulse sequence and a real-time reconstruction pipeline based on multi-baseline proton resonance frequency shift (PRFS) method with visualization of temperature imaging. The pipeline supports multi-slice acquisition with minimal reconstruction lag. Simulations with a virtual motion phantom were performed to investigate the influence of the number of baselines and respiratory rate on the accuracy of temperature measurement. Phantom experiments with ultrasound heating were performed using a custom-made motion phantom to evaluate the performance of the pipeline. Lastly, experiments in healthy volunteers (N = 2) without heating were performed to evaluate the accuracy and stability of MR thermometry in abdominal organs (liver and kidney). RESULTS: The multi-baseline approach with greater than 25 baselines resulted in minimal temperature errors in the simulation. Phantom experiments demonstrated a 713 ms update time for 3-slice acquisitions. Temperature maps with 30 baselines showed clear temperature distributions caused by ultrasound heating in the respiratory phantom. Finally, the pipeline was evaluated with physiologic motions in healthy volunteers without heating, which demonstrated the accuracy (root mean square error [RMSE]) of 1.23 ± 0.18 °C (liver) and 1.21 ± 0.17 °C (kidney) and precision of 1.13 ± 0.11 °C (liver) and 1.16 ± 0.15 °C (kidney) using 32 baselines. CONCLUSIONS: The proposed real-time acquisition and reconstruction pipeline allows motion-robust, multi-slice, real-time temperature monitoring within the abdomen during free breathing.

Histological findings in resected leiomyomas following MR-HIFU treatment, single-institution data from seven patients with unfavorable focal therapy.

PURPOSE: Magnetic resonance - high-intensity focused ultrasound (MR-HIFU) is a noninvasive treatment option for symptomatic uterine leiomyomas. Currently, pretreatment MRI is used to assess tissue characteristics and predict the most likely therapeutic response for individual patients. However, these predictions still entail significant uncertainties. The impact of tissue properties on therapeutic outcomes remains poorly understood and detailed knowledge of the histological effects of ultrasound ablation is lacking. Investigating these aspects could aid in optimizing patient selection, enhancing treatment effects and improving treatment outcomes. METHODS AND MATERIALS: We present seven patients who underwent MR-HIFU treatment for leiomyoma followed by second-line surgical treatment. Tissue samples obtained during the surgery were stained with hematoxylin and eosin, Masson's trichrome and Herovici to evaluate general morphology, fibrosis and collagen deposition of leiomyomas. Immunohistochemical CD31, Ki-67 and MMP-2 stainings were performed to study vascularization, proliferation and matrix metalloproteinase-2 protein expression in leiomyomas, respectively. RESULTS: The clinical characteristics and radiological findings of the leiomyomas prior to treatment as well as qualitative histological findings after the treatment are presented and discussed in the context of current literature. A tentative model for volume reduction is presented. CONCLUSION: These findings provide insights into potential factors contributing to suboptimal therapeutic outcomes and the variability in histological changes following treatment.

RF-induced heating of interventional devices at 23.66 MHz.

OBJECTIVE: Low-field MRI systems are expected to cause less RF heating in conventional interventional devices due to lower Larmor frequency. We systematically evaluate RF-induced heating of commonly used intravascular devices at the Larmor frequency of a 0.55 T system (23.66 MHz) with a focus on the effect of patient size, target organ, and device position on maximum temperature rise. MATERIALS AND METHODS: To assess RF-induced heating, high-resolution measurements of the electric field, temperature, and transfer function were combined. Realistic device trajectories were derived from vascular models to evaluate the variation of the temperature increase as a function of the device trajectory. At a low-field RF test bench, the effects of patient size and positioning, target organ (liver and heart) and body coil type were measured for six commonly used interventional devices (two guidewires, two catheters, an applicator and a biopsy needle). RESULTS: Electric field mapping shows that the hotspots are not necessarily localized at the device tip. Of all procedures, the liver catheterizations showed the lowest heating, and a modification of the transmit body coil could further reduce the temperature increase. For common commercial needles no significant heating was measured at the needle tip. Comparable local SAR values were found in the temperature measurements and the TF-based calculations. CONCLUSION: At low fields, interventions with shorter insertion lengths such as hepatic catheterizations result in less RF-induced heating than coronary interventions. The maximum temperature increase depends on body coil design.

MR-Guided Transurethral Ultrasound Ablation of Prostate Cancer: Initial Experience of Monitoring Tumor Response by Dynamic Apparent Diffusion Coefficient Measurements at 3.0 T.

INTRODUCTION: Diffusion-weighted imaging (DWI) as part of multiparametric magnetic resonance imaging (mpMRI) is an important sequence for the detection of prostate cancer (PCa). The objective of this retrospective analysis was to evaluate changes in apparent diffusion coefficient (ADC) measurements in biopsy-proven PCa undergoing TULSA-PRO (MR-guided transurethral ultrasound ablation of the prostate) at 3.0 T after 1, 3, and 6-12 months posttreatment. METHODS: Nineteen patients underwent follow-up examinations after 1, 3, and 6-12 months including mpMRI at 3.0 T and urological-clinical examinations with quantitative analysis of ADCs. RESULTS: In PCa, a significant increase of ADC values after 6-12 months was measured after TULSA-PRO treatment by 29.1% (pre-TULSA: 0.79 ± 0.16 × 10-3 mm2/s, 6-12 months: 1.02 ± 0.35 × 10-3 mm2/s), while the corresponding value in the reference tissue decreased by 48.5% (pre-TULSA: 1.20 ± 0.15 × 10-3 mm2/s, 6-12 months: 0.91 ± 0.29 × 10-3 mm2/s). The mean ADC values in the early follow-up groups at 1 and 3 months did not change significantly. CONCLUSION: DWI with ADC as part of mpMRI can serve as a biomarker to dynamically monitor the follow-up after TULSA after 6-12 months. For early posttreatment progression, it is not suitable due to too many confounding variables.

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.