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.

Fast, automated, real-time 3D passive balloon catheter tracking during MRI-guided cardiac catheterization using orthogonal projection imaging and real-time image-based catheter detection.

PURPOSE: MRI-guidance of cardiac catheterization is currently performed using one or multiple 2D imaging planes, which may be suboptimal for catheter navigation, especially in patients with complex anatomies. The purpose of the work was to develop a robust real-time 3D catheter tracking method and 3D visualization strategy for improved MRI-guidance of cardiac catheterization procedures. METHODS: A fast 3D tracking technique was developed using continuous acquisition of two orthogonal 2D-projection images. Each projection corresponds to a gradient echo stack of slices with only the central k-space lines being collected for each slice. To enhance catheter contrast, a saturation pulse is added ahead of the projection pair. An offline image processing algorithm was developed to identify the 2D coordinates of the balloon in each projection image and to estimate its corresponding 3D coordinates. Post-processing includes background signal suppression using an atlas of background 2D-projection images. 3D visualization of the catheter and anatomy is proposed using three live sagittal, coronal, and axial (MPR) views and 3D rendering. The technique was tested in a subset of a catheterization step in three patients undergoing MRI-guided cardiac catheterization using a passive balloon catheter. RESULTS: The extraction of the catheter balloon 3D coordinates was successful in all patients and for the majority of time-points (accuracy >96%). This tracking method enabled a novel 3D visualization strategy for passive balloon catheter, providing enhanced anatomical context during catheter navigation. CONCLUSION: The proposed tracking strategy shows promise for robust tracking of passive balloon catheter and may enable enhanced visualization during MRI-guided cardiac catheterization.

Real-time automatic image-based slice tracking of gadolinium-filled balloon wedge catheter during MR-guided cardiac catheterization: A proof-of-concept study.

PURPOSE: MR-guided cardiac catheterization procedures currently use passive tracking approaches to follow a gadolinium-filled catheter balloon during catheter navigation. This requires frequent manual tracking and repositioning of the imaging slice during navigation. In this study, a novel framework for automatic real-time catheter tracking during MR-guided cardiac catheterization is presented. METHODS: The proposed framework includes two imaging modes (Calibration and Runtime). The sequence starts in Calibration mode, in which the 3D catheter coordinates are determined using a stack of 10-20 contiguous saturated slices combined with real-time image processing. The sequence then automatically switches to Runtime mode, where three contiguous slices (acquired with partial saturation), initially centered on the catheter balloon using the Calibration feedback, are acquired continuously. The 3D catheter balloon coordinates are estimated in real time from each Runtime slice stack using image processing. Each Runtime stack is repositioned to maintain the catheter balloon in the central slice based on the prior Runtime feedback. The sequence switches back to Calibration mode if the catheter is not detected. This framework was evaluated in a heart phantom and 3 patients undergoing MR-guided cardiac catheterization. Catheter detection accuracy and rate of catheter visibility were evaluated. RESULTS: The automatic detection accuracy for the catheter balloon during the Calibration/Runtime mode was 100%/95% in phantom and 100%/97 ± 3% in patients. During Runtime, the catheter was visible in 82% and 98 ± 2% of the real-time measurements in the phantom and patients, respectively. CONCLUSION: The proposed framework enabled real-time continuous automatic tracking of a gadolinium-filled catheter balloon during MR-guided cardiac catheterization.

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

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

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.

Characterization of mechanical and radiation isocenter on an MR-guided radiotherapy (MRgRT) Linac.

BACKGROUND AND PURPOSE: In the emerging paradigm of stereotactic radiosurgery being proposed for MR-guided radiotherapy (MRgRT), assessment of mechanical geometric accuracy is critical for the implementation of stereotactic delivery. We benchmarked the mechanical accuracy of an MR Linac system that lacks an onboard detector/array. Our mechanical tests utilize a half beam block (HBB) geometry that takes advantage of the sensitivity of a partially occluded detector. MATERIALS AND METHODS: Mechanical tests benchmarked the couch, MLC, and gantry geometric accuracy for an MR-Linac system. An HBB technique was used to irradiate an ionization chamber profiler (ICP) array with partial occlusion of individual detectors for characterization of MLC skew, beam divergence displacement, and RT isocenter localization. The sensitivity of the partially occluded detector's ICP-X (detector width) and ICP-Y (detector length) was characterized by displacing the detector relative to radiation isocenter by 0.2 mm increments, introduced through couch motion. The accuracy of the HBB ICP technique was verified with a starshot using radiochromic film, and the reproducibility was verified on a conventional C-arm Linac and compared to Winston-Lutz. RESULTS: The sensitivity of the HBB technique as quantified through the dose difference normalized to open field as a function of displacement from RT isocenter was 6.4%/mm and 13.0%/mm for the ICP-X and ICP-Y orientation, respectively, due to the oblong detector orientation. Couch positional accuracy and sag was within ±0.1 mm. Maximum MLC positional displacement was 0.7 mm with mean MLC skew at 0.07°. The maximum beam divergence displacement was 0.03 mm. The gantry angle was within 0.1°. Independent verification of the RT isocenter localization procedure produced repeatable results. CONCLUSION: This work serves for characterizing the mechanical and geometric radiation accuracy for the foundation of an MR-guided stereotactic radiosurgery program, as demonstrated with high sensitivity and independent validation.

[Percutaneous MR-guided prostate cancer cryoablation: Predictive factors and oncologic outcomes]. / Cryothérapie totale de la prostate sous IRM par voie périnéale : résultats carcinologiques et facteurs prédictifs.

OBJECTIVE: To determine the pejorative predictive factors on oncologic outcomes of percutaneous MR-guided whole gland prostate cancer cryoablation (CA). METHODS: Medical records of patients treated from 2009 to 2012, to assess medium-term oncologic outcomes, were reviewed. Prostate biopsies were performed in local recurrence suspicion (biochemical failure, MR follow-up failure). RESULTS: Among 18 patients, mean age of 72.6 (61-78), 2 (11 %) and 7 (38.9 %) biological and reported biopsy-proven local recurrence respectively with our initial technic of CA. Mean follow-up and recurrence were 56.3 (±21.7) and 20.7 (±13.9) months respectively. A previous treatment of prostate cancer (P=0.5), pre-treatment PSA (P=0.2), pre-treatment Gleason/ISUP score (P=0.4), nadir PSA post-CA (P=0.22) were not associated with recurrence. Bilateral positive cores appears as a pejorative predictive factor (P=0.04). However mean pre-treatment positive cores percentage, 25 (±16.5) in responding patients versus 40.7 (±25.2) in case of recurrence, and maximum percentage of cancer extent in each positive core, 10.6 (±9.3) in responding patients versus 18.7 (±16.5) in case of recurrence, seemed associated with local recurrence after prostate CA but our analysis wasn't able to find a difference (P=0.09 and P=0.3 respectively) due to a lack of power. CONCLUSION: Bilateral positive cores appears as a pejorative predictive factor. In our experience, important tumor volume seem to be a pejorative predictive factor for oncologic outcomes after PCA whereas treatment, PSA, Gleason/ISUP score, nadir PSA are not. LEVEL OF EVIDENCE: 4.

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

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

Greater occipital nerve infiltration under MR guidance: Feasibility study and preliminary results.

OBJECTIVE: To assess the feasibility of greater occipital nerve (GON) intermediate site infiltration with MRI guidance. METHODS: Eleven consecutive patients suffering from chronic refractory cranio-facial pain who underwent 16 GON infiltrations were included in this prospective study. All of the procedures were performed on an outpatient basis in the research facility of our institution, with a 1.5 T scanner. The fatty space between inferior obliquus and semispinalis muscles at C1-C2 level was defined as the target. Technical success was defined as the ability to accurately inject the products at the target, assessed by post-procedure axial and sagittal proton density-weighted sequences. Clinical success was defined as a 50% pain decrease at 1 month. RESULTS: Technical success was 100%. GON was depicted in 6/11 cases on planning MRI sequences. Mean duration of procedure was 22.5 min (range 16-41). Clinical success was obtained in 7/11 included patients (63.6%) with a mean self-reported improvement of 78%. CONCLUSION: Interventional MR-guidance for GON infiltration is a feasible technique offering similar results to an already established effective procedure. It may appear as a useful tool in specific populations, such as young patients and repeat infiltrations, and should be considered in these settings. KEY POINTS: • MR guidance for GON infiltration is a feasible technique. • Preliminary results are in agreement with other guidance modalities. • MR guidance may be seen as a useful tool in specific populations. • Specific populations include young patients and repeat infiltrations. • Target patients may also include patients with potentionally previously reported complications (torticollis).

In vitro artifact assessment of an MR-compatible, microwave antenna device for percutaneous tumor ablation with fluoroscopic MRI-sequences.

OBJECTIVE: To evaluate artifact configuration and diameters of a magnetic resonance (MR) compatible microwave (MW) applicator using near-realtime MR-fluoroscopic sequences for percutaneous tumor ablation procedures. MATERIAL AND METHODS: Two MW applicators (14 G and 16 G) were tested in an ex-vivo phantom at 1.5 T with two 3 D fluoroscopic sequences: T1-weighted spoiled Gradient Echo (GRE) and T1/T2-weighted Steady State Free Precession (SSFP) sequence. Applicator orientation to main magnetic field (B0), slice orientation and phase encoding direction (PED) were systematically varied. The influence of these variables was assessed with ANOVA and post-hoc testing. RESULTS: The artifact was homogenous along the whole length of both antennas with all tested parameters. The tip artifact diameter of the 16 G antenna measured 6.9 ± 1.0 mm, the shaft artifact diameter 8.6 ± 1.2 mm and the Tip Location Error (TLE) was 1.5 ± 1.2 mm.The tip artifact diameter of the 14 G antenna measured 7.7 ± 1.2 mm, the shaft artifact diameter 9.6 ± 1.5 mm and TLE was 1.6 ± 1.2 mm. Orientation to B0 had no statistically significant influence on tip artifact diameters (16 G: p = .55; 14 G: p = .07) or TLE (16 G: p = .93; 14 G: p = .26). GRE sequences slightly overestimated the antenna length with TLE(16 G) = 2.6 ± 0.5 mm and TLE(14 G) = 2.7 ± 0.7 mm. CONCLUSIONS: The MR-compatible MW applicator's artifact seems adequate with an acceptable TLE for safe applicator positioning during near-realtime fluoroscopic MR-guidance.

Comparison of outcomes for MR-guided versus CT-guided high-dose-rate interstitial brachytherapy in women with locally advanced carcinoma of the cervix.

OBJECTIVE: The purpose was to compare local control (LC), overall survival (OS) and dose to the organs at risk (OAR) in women with locally advanced cervical cancer treated with MR-guided versus CT-guided interstitial brachytherapy (BT). METHODS: 56 patients (29 MR, 27 CT) were treated with high-dose-rate (HDR) interstitial BT between 2005-2015. The MR patients had been prospectively enrolled on a Phase II clinical trial. Data were analyzed using Kaplan-Meier (K-M) and Cox proportional hazards statistical modeling in JMP® & R®. RESULTS: Median follow-up time was 19.7months (MR group) and 18.4months (CT group). There were no statistically significant differences in patient age at diagnosis, histology, percent with tumor size >4cm, grade, FIGO stage or lymph node involvement between the groups. Patients in the MR group had more lymphovascular involvement compared to patients in the CT group (p<0.01). When evaluating plans generated, there were no statistically significant differences in median cumulative dose to the high-risk clinical target volume or the OAR. 2-year K-M LC rates for MR-based and CT-based treatments were 96% and 87%, respectively (log-rank p=0.65). At 2years, OS was significantly better in the MR-guided cohort (84% vs. 56%, p=0.036). On multivariate analysis, squamous histology was associated with longer OS (HR 0.23, 95% CI 0.07-0.72) in a model with MR BT (HR 0.35, 95% CI 0.08-1.18). There was no difference in toxicities between CT and MR BT. CONCLUSION: In this population of locally advanced cervical-cancer patients, MR-guided HDR BT resulted in estimated 96% 2-year local control and excellent survival and toxicity rates.

MR-guided microwave ablation in hepatic tumours: initial results in clinical routine.

OBJECTIVES: Evaluation of the technical success, patient safety and technical effectiveness of magnetic resonance (MR)-guided microwave ablation of hepatic malignancies. METHODS: Institutional review board approval and informed patient consent were obtained. Fifteen patients (59.8 years ± 9.5) with 18 hepatic malignancies (7 hepatocellular carcinomas, 11 metastases) underwent MR-guided microwave ablation using a 1.5-T MR system. Mean tumour size was 15.4 mm ± 7.7 (7-37 mm). Technical success and ablation zone diameters were assessed by post-ablative MR imaging. Technique effectiveness was assessed after 1 month. Complications were classified according to the Common Terminology Criteria for Adverse Events (CTCAE). Mean follow-up was 5.8 months ± 2.6 (1-10 months). RESULTS: Technical success and technique effectiveness were achieved in all lesions. Lesions were treated using 2.5 ± 1.2 applicator positions. Mean energy and ablation duration per tumour were 37.6 kJ ± 21.7 (9-87 kJ) and 24.7 min ± 11.1 (7-49 min), respectively. Coagulation zone short- and long-axis diameters were 31.5 mm ± 10.5 (16-65 mm) and 52.7 mm ± 15.4 (27-94 mm), respectively. Two CTCAE-2-complications occurred (pneumothorax, pleural effusion). Seven patients developed new tumour manifestations in the untreated liver. Local tumour progression was not observed. CONCLUSIONS: Microwave ablation is feasible under near real-time MR guidance and provides effective treatment of hepatic malignancies in one session. KEY POINTS: • Planning, applicator placement and therapy monitoring are possible without using contrast enhancement • Energy transmission from the generator to the scanner room is safely possible • MR-guided microwave ablation provides effective treatment of hepatic malignancies in one session • Therapy monitoring is possible without applicator retraction from the ablation site.

FUS-mediated BBB opening leads to transient perfusion decrease and inflammation without acute or chronic brain lesion.

Impact: The permeabilization of the BBB to deliver therapeutics with MR-guided FUS redefines therapeutic strategies as it improves patient outcomes. To ensure the best translation towards clinical treatment, the evaluation of hemodynamic modifications in the CNS is necessary to refine treatment parameters. Methods: MR-guided FUS was applied at 1.5 MHz with a 50 ms burst every 1 s to open the BBB. CBF, BVf and ADC parameters were monitored with MRI. Cavitation was monitored with a PCD during the FUS sequence and classified with the IUD index into three cavitation levels. We distinctly applied the FUS in the cortex or the striatum. After the BBB permeabilization, neuroinflammation markers were quantified longitudinally. Results: The BBB was successfully opened in all animals in this study and only one animal was classified as "hard" and excluded from the rest of the study. 30 min after FUS-induced BBB opening in the cortex, we measured a 54% drop in CBF and a 13% drop in BVf compared to the contralateral side. After permeabilization of the striatum, a 38% drop in CBF and a 15% drop in BVf were measured. CBF values rapidly returned to baseline, and 90 min after BBB opening, no significant differences were observed. We quantified the subsequent neuroinflammation, noting a significant increase in astrocytic recruitment at 2 days and microglial activation at 1 day after FUS. After 7 days, no more inflammation was visible in the brain. Conclusion: FUS-induced BBB opening transiently modifies hemodynamic parameters such as CBF and BVf, suggesting limited nutrients and oxygen supply to the CNS in the hour following the procedure.

Daily AI-Based Treatment Adaptation under Weekly Offline MR Guidance in Chemoradiotherapy for Cervical Cancer 1: The AIM-C1 Trial.

(1) Background: External beam radiotherapy (EBRT) and concurrent chemotherapy, followed by brachytherapy (BT), offer a standard of care for patients with locally advanced cervical carcinoma. Conventionally, large safety margins are required to compensate for organ movement, potentially increasing toxicity. Lately, daily high-quality cone beam CT (CBCT)-guided adaptive radiotherapy, aided by artificial intelligence (AI), became clinically available. Thus, online treatment plans can be adapted to the current position of the tumor and the adjacent organs at risk (OAR), while the patient is lying on the treatment couch. We sought to evaluate the potential of this new technology, including a weekly shuttle-based 3T-MRI scan in various treatment positions for tumor evaluation and for decreasing treatment-related side effects. (2) Methods: This is a prospective one-armed phase-II trial consisting of 40 patients with cervical carcinoma (FIGO IB-IIIC1) with an age ≥ 18 years and a Karnofsky performance score ≥ 70%. EBRT (45-50.4 Gy in 25-28 fractions with 55.0-58.8 Gy simultaneous integrated boosts to lymph node metastases) will be accompanied by weekly shuttle-based MRIs. Concurrent platinum-based chemotherapy will be given, followed by 28 Gy of BT (four fractions). The primary endpoint will be the occurrence of overall early bowel and bladder toxicity CTCAE grade 2 or higher (CTCAE v5.0). Secondary outcomes include clinical feasibility, quality of life, and imaging-based response assessment.

Sustained reduction of essential tremor with low-power non-thermal transcranial focused ultrasound stimulations in humans.

BACKGROUND: Transcranial ultrasound stimulation (TUS) is a non-invasive brain stimulation technique; when skull aberrations are compensated for, this technique allows, with millimetric accuracy, circumvention of the invasive surgical procedure associated with deep brain stimulation (DBS) and the limited spatial specificity of transcranial magnetic stimulation. OBJECTIVE: /hypothesis: We hypothesize that MR-guided low-power TUS can induce a sustained decrease of tremor power in patients suffering from medically refractive essential tremor. METHODS: The dominant hand only was targeted, and two anatomical sites were sonicated in this exploratory study: the ventral intermediate nucleus of the thalamus (VIM) and the dentato-rubro-thalamic tract (DRT). Patients (N = 9) were equipped with MR-compatible accelerometers attached to their hands to monitor their tremor in real-time during TUS. RESULTS: VIM neurostimulations followed by a low-duty cycle (5 %) DRT stimulation induced a substantial decrease in the tremor power in four patients, with a minimum of 89.9 % reduction when compared with the baseline power a few minutes after the DRT stimulation. The only patient stimulated in the VIM only and with a low duty cycle (5 %) also experienced a sustained reduction of the tremor (up to 93.4 %). Four patients (N = 4) did not respond. The temperature at target was 37.2 ± 1.4 °C compared to 36.8 ± 1.4 °C for a 3 cm away control point. CONCLUSIONS: MR-guided low power TUS can induce a substantial and sustained decrease of tremor power. Follow-up studies need to be conducted to reproduce the effect and better to understand the variability of the response amongst patients. MR thermometry during neurostimulations showed no significant thermal rise, supporting a mechanical effect.

Online MR-guided proton and ion beam radiotherapy: investigation of image quality.

OBJECTIVE: Magnetic resonance (MR) images free of artefacts are of pivotal importance for MR-guided ion radiotherapy. This study investigates MR image quality for simultaneous irradiation in an experimental setup using phantom imaging as well as in-vivo imaging. Observed artefacts are described within the study and their cause is investigated with the goal to find conclusions and solutions for potential future hybrid devices. Approach: An open magnetic resonance scanner with a field strength of 0.25 T has been installed in front of an ion beamline. Simultaneous MRI and irradiation using raster scanning were performed to analyze image quality in dedicated phantoms. Magnetic field measurements were performed to assist the explanation of observed artifacts. In addition, in-vivo images were acquired by operating the magnets for beam scanning without transporting a beam. Main Results: The additional frequency component within the isocenter caused by the fringe field of the horizontal beam scanning magnet correlates with the amplitude and frequency of the scanning magnet steering and can cause ghosting artifacts in the images. These are amplified with high currents and fast operating of the scanning magnet. Applying a real-time capable pulse sequence in-vivo revealed no ghosting artifacts despite a continuously changing current pattern and a clinical treatment plan activation scheme, suggesting that the use of fast imaging is beneficial for the aim of creating high quality in-beam MR images. This result suggests, that the influence of the scanning magnets on the MR acquisition might be of negligible importance and does not need further measures like extensive magnetic shielding of the scanning magnets. Significance: Our study delimited artefacts observed in MR images acquired during simultaneous raster scanning ion beam irradiation. The application of a fast pulse sequence showed no image artefacts and holds the potential that online MR imaging in future hybrid devices might be feasible. .

The impact of motion on onboard MRI-guided pencil beam scanned proton therapy treatments.

Objective.Online magnetic resonance imaging (MRI) guidance could be especially beneficial for pencil beam scanned (PBS) proton therapy of tumours affected by respiratory motion. For the first time to our knowledge, we investigate the dosimetric impact of respiratory motion on MRI-guided proton therapy compared to the scenario without magnetic field.Approach.A previously developed analytical proton dose calculation algorithm accounting for perpendicular magnetic fields was extended to enable 4D dose calculations. For two geometrical phantoms and three liver and two lung patient cases, static treatment plans were optimised with and without magnetic field (0, 0.5 and 1.5 T). Furthermore, plans were optimised using gantry angle corrections (0.5 T +5° and 1.5 T +15°) to reproduce similar beam trajectories compared to the 0 T reference plans. The effect of motion was then considered using 4D dose calculations without any motion mitigation and simulating 8-times volumetric rescanning, with motion for the patient cases provided by 4DCT(MRI) data sets. Each 4D dose calculation was performed for different starting phases and the CTV dose coverageV95%and homogeneityD5%-D95%were analysed.Main results.For the geometrical phantoms with rigid motion perpendicular to the beam and parallel to the magnetic field, a comparable dosimetric effect was observed independent of the magnetic field. Also for the five 4DCT(MRI) cases, the influence of motion was comparable for all magnetic field strengths with and without gantry angle correction. On average, the motion-induced decrease in CTVV95%from the static plan was 17.0% and 18.9% for 1.5 T and 0.5 T, respectively, and 19.9% without magnetic field.Significance.For the first time, this study investigates the combined impact of magnetic fields and respiratory motion on MR-guided proton therapy. The comparable dosimetric effects irrespective of magnetic field strength indicate that the effects of motion for future MR-guided proton therapy may not be worse than for conventional PBS proton therapy.

3.0-T MR-guided transgluteal in-bore-targeted prostate biopsy under local anesthesia in patients without rectal access: a single-institute experience and review of literature.

PURPOSE: To describe the technique and evaluate the performance of MRI-guided transgluteal in-bore-targeted biopsy of the prostate gland under local anesthesia in patients without rectal access. METHODS: Ten men (mean age, 69 (range 57-86) years) without rectal access underwent 13 MRI-guided transgluteal in-bore-targeted biopsy of the prostate gland under local anesthesia. All patients underwent mp-MRI at our institute prior to biopsy. Three patients had prior US-guided transperineal biopsy which was unsuccessful in one, negative in one, and yielded GG1 (GS6) PCa in one. Procedure time, complications, histopathology result, and subsequent management were recorded. RESULTS: Median interval between rectal surgery and presentation with elevated PSA was 12.5 years (interquartile range (IQR) 25-75, 8-36.5 years). Mean PSA was 11.9 (range, 4.8 -59.0) ng/ml and PSA density was 0.49 (0.05 -3.2) ng/ml/ml. Distribution of PI-RADS v2.0/2.1 scores of the targeted lesions were PI-RADS 5-3; PI-RADS 4-6; and PI-RADS 3-1. Mean lesion size was 1.5 cm (range, 1.0-3.6 cm). Median interval between MRI and biopsy was 5.5 months (IQR 25-75, 1.5-9 months). Mean procedure time was 47.4 min (range, 29-80 min) and the number of cores varied between 3 and 5. Of the 13 biopsies, 4 yielded clinically significant prostate cancer (csPca), with a Gleason score ≥ 7, 1 yielded insignificant prostate cancer (Gleason score = 6), 7 yielded benign prostatic tissue, and one was technically unsuccessful. 3/13 biopsies were repeat biopsies which detected csPCa in 2 out of the 3 patients. None of the patients had biopsy-related complication. Biopsy result changed management to radiation therapy with ADT in 2 patients with the rest on active surveillance. CONCLUSION: MRI-guided transgluteal in-bore-targeted biopsy of the prostate gland under local anesthesia is feasible in patients without rectal access.

A fast analytical dose calculation approach for MRI-guided proton therapy.

Objective.Magnetic resonance (MR) is an innovative technology for online image guidance in conventional radiotherapy and is also starting to be considered for proton therapy as well. For MR-guided therapy, particularly for online plan adaptations, fast dose calculation is essential. Monte Carlo (MC) simulations, however, which are considered the gold standard for proton dose calculations, are very time-consuming. To address the need for an efficient dose calculation approach for MRI-guided proton therapy, we have developed a fast GPU-based modification of an analytical dose calculation algorithm incorporating beam deflections caused by magnetic fields.Approach.Proton beams (70-229 MeV) in orthogonal magnetic fields (0.5/1.5 T) were simulated using TOPAS-MC and central beam trajectories were extracted to generate look-up tables (LUTs) of incremental rotation angles as a function of water-equivalent depth. Beam trajectories are then reconstructed using these LUTs for the modified ray casting dose calculation. The algorithm was validated against MC in water, different materials and for four example patient cases, whereby it has also been fully incorporated into a treatment plan optimisation regime.Main results.Excellent agreement between analytical and MC dose distributions could be observed with sub-millimetre range deviations and differences in lateral shifts <2 mm even for high densities (1000 HU). 2%/2 mm gamma pass rates were comparable to the 0 T scenario and above 94.5% apart for the lung case. Further, comparable treatment plan quality could be achieved regardless of magnetic field strength.Significance.A new method for accurate and fast proton dose calculation in magnetic fields has been developed and successfully implemented for treatment plan optimisation.

Feasibility of cardiac MR thermometry at 0.55†T.

Radiofrequency catheter ablation is an established treatment strategy for ventricular tachycardia, but remains associated with a low success rate. MR guidance of ventricular tachycardia shows promises to improve the success rate of these procedures, especially due to its potential to provide real-time information on lesion formation using cardiac MR thermometry. Modern low field MRI scanners (<1 T) are of major interest for MR-guided ablations as the potential benefits include lower costs, increased patient access and device compatibility through reduced device-induced imaging artefacts and safety constraints. However, the feasibility of cardiac MR thermometry at low field remains unknown. In this study, we demonstrate the feasibility of cardiac MR thermometry at 0.55 T and characterized its in vivo stability (i.e., precision) using state-of-the-art techniques based on the proton resonance frequency shift method. Nine healthy volunteers were scanned using a cardiac MR thermometry protocol based on single-shot EPI imaging (3 slices in the left ventricle, 150 dynamics, TE = 41 ms). The reconstruction pipeline included image registration to align all the images, multi-baseline approach (look-up-table length = 30) to correct for respiration-induced phase variations, and temporal filtering to reduce noise in temperature maps. The stability of thermometry was defined as the pixel-wise standard deviation of temperature changes over time. Cardiac MR thermometry was successfully acquired in all subjects and the stability averaged across all subjects was 1.8 ± 1.0°C. Without multi-baseline correction, the overall stability was 2.8 ± 1.6°C. In conclusion, cardiac MR thermometry is feasible at 0.55 T and further studies on MR-guided catheter ablations at low field are warranted.