Electroanatomical mapping after cardiac radioablation for treatment of incessant electrical storm: a case report from the RAVENTA trial.

BACKGROUND: Electroanatomical mapping (EAM)-guided stereotactic arrhythmia radioablation (STAR) is a novel noninvasive therapy option for patients with monomorphic ventricular tachycardia (VT) refractory to antiarrhythmic drugs and/or urgent catheter ablation (CA). Data on success rates in an emergency situation such as electrical storm (ES) are rare. We present a case of a patient with an initially very poor life expectancy after extensive myocardial infarction with therapy-resistant ES, not amendable for further antiarrhythmic drug therapy, implantable cardioverter-defibrillator implantation, or repeated CA who was introduced to the radiation oncology department for emergency STAR as a bail-out therapy. METHODS: Target volume definition and transfer from EAM to CT were validated and quality assured with a semi-automatic, dedicated visualization tool (CARDIO-RT). Emergency STAR was performed with 25 Gy in the framework of the RAVENTA study. The VT burden gradually decreased after STAR; however, a second VT morphology occurred, which was successfully treated with EAM-guided CA 12 days after STAR. RESULTS: The second EAM-guided CA showed areas of low voltage in the irradiated segments, indicating a precise targeting and early functional response to STAR. The patient remained free of any VT recurrence or any radiation-related toxicities and in good general condition during the recent follow-up of 18 months. CONCLUSION: The case highlights the possible approach, caveats, difficulties, and prognosis of a patient severely affected by therapy-resistant VT in whom CA could not lead to VT suppression. Further studies of putative mechanisms of STAR in the acute and chronic phase of this novel therapy are warranted.

Radiosurgery for ventricular tachycardia (RAVENTA): interim analysis of a multicenter multiplatform feasibility trial.

BACKGROUND: Single-session cardiac stereotactic radiation therapy (SBRT) has demonstrated promising results for patients with refractory ventricular tachycardia (VT). However, the full safety profile of this novel treatment remains unknown and very limited data from prospective clinical multicenter trials are available. METHODS: The prospective multicenter multiplatform RAVENTA (radiosurgery for ventricular tachycardia) study assesses high-precision image-guided cardiac SBRT with 25 Gy delivered to the VT substrate determined by high-definition endocardial and/or epicardial electrophysiological mapping in patients with refractory VT ineligible for catheter ablation and an implanted cardioverter defibrillator (ICD). Primary endpoint is the feasibility of full-dose application and procedural safety (defined as an incidence of serious [grade ≥ 3] treatment-related complications ≤ 5% within 30 days after therapy). Secondary endpoints comprise VT burden, ICD interventions, treatment-related toxicity, and quality of life. We present the results of a protocol-defined interim analysis. RESULTS: Between 10/2019 and 12/2021, a total of five patients were included at three university medical centers. In all cases, the treatment was carried out without complications. There were no serious potentially treatment-related adverse events and no deterioration of left ventricular ejection fraction upon echocardiography. Three patients had a decrease in VT episodes during follow-up. One patient underwent subsequent catheter ablation for a new VT with different morphology. One patient with local VT recurrence died 6 weeks after treatment in cardiogenic shock. CONCLUSION: The interim analysis of the RAVENTA trial demonstrates early initial feasibility of this new treatment without serious complications within 30 days after treatment in five patients. Recruitment will continue as planned and the study has been expanded to further university medical centers. TRIAL REGISTRATION NUMBER: NCT03867747 (clinicaltrials.gov). Registered March 8, 2019. Study start: October 1, 2019.

Tumor-dose-rate variations during robotic radiosurgery of oligo and multiple brain metastases.

PURPOSE: For step-and-shoot robotic stereotactic radiosurgery (SRS) the dose delivered over time, called local tumor-dose-rate (TDR), may strongly vary during treatment of multiple lesions. The authors sought to evaluate technical parameters influencing TDR and correlate TDR to clinical outcome. MATERIAL AND METHODS: A total of 23 patients with 162 oligo (1-3) and multiple (>3) brain metastases (OBM/MBM) treated in 33 SRS sessions were retrospectively analyzed. Median PTV were 0.11 cc (0.01-6.36 cc) and 0.50 cc (0.12-3.68 cc) for OBM and MBM, respectively. Prescription dose ranged from 16 to 20 Gy prescribed to the median 70% isodose line. The maximum dose-rate for planning target volume (PTV) percentage p in time span s during treatment (TDRs,p) was calculated for various p and s based on treatment log files and in-house software. RESULTS: TDR60min,98% was 0.30 Gy/min (0.23-0.87 Gy/min) for OBM and 0.22 Gy/min (0.12-0.63 Gy/min) for MBM, respectively, and increased by 0.03 Gy/min per prescribed Gy. TDR60min,98% strongly correlated with treatment time (ρ = -0.717, p < 0.001), monitor units (MU) (ρ = -0.767, p < 0.001), number of beams (ρ = -0.755, p < 0.001) and beam directions (ρ = -0.685, p < 0.001) as well as lesions treated per collimator (ρ = -0.708, P < 0.001). Median overall survival (OS) was 20 months and 1­ and 2­year local control (LC) was 98.8% and 90.3%, respectively. LC did not correlate with any TDR, but tumor response (partial response [PR] or complete response [CR]) correlated with all TDR in univariate analysis (e.g., TDR60min,98%: hazard ration [HR] = 0.974, confidence interval [CI] = 0.952-0.996, p = 0.019). In multivariate analysis only concomitant targeted therapy or immunotherapy and breast cancer tumor histology remained a significant factor for tumor response. Local grade ≥2 radiation-induced tissue reactions were noted in 26.3% (OBM) and 5.2% (MBM), respectively, mainly influenced by tumor volume (p < 0.001). CONCLUSIONS: Large TDR variations are noted during MBM-SRS which mainly arise from prolonged treatment times. Clinically, low TDR corresponded with decreased local tumor responses, although the main influencing factor was concomitant medication.

Treatment planning for spinal radiosurgery : A competitive multiplatform benchmark challenge.

PURPOSE: To investigate the quality of treatment plans of spinal radiosurgery derived from different planning and delivery systems. The comparisons include robotic delivery and intensity modulated arc therapy (IMAT) approaches. Multiple centers with equal systems were used to reduce a bias based on individual's planning abilities. The study used a series of three complex spine lesions to maximize the difference in plan quality among the various approaches. METHODS: Internationally recognized experts in the field of treatment planning and spinal radiosurgery from 12 centers with various treatment planning systems participated. For a complex spinal lesion, the results were compared against a previously published benchmark plan derived for CyberKnife radiosurgery (CKRS) using circular cones only. For two additional cases, one with multiple small lesions infiltrating three vertebrae and a single vertebra lesion treated with integrated boost, the results were compared against a benchmark plan generated using a best practice guideline for CKRS. All plans were rated based on a previously established ranking system. RESULTS: All 12 centers could reach equality (n = 4) or outperform (n = 8) the benchmark plan. For the multiple lesions and the single vertebra lesion plan only 5 and 3 of the 12 centers, respectively, reached equality or outperformed the best practice benchmark plan. However, the absolute differences in target and critical structure dosimetry were small and strongly planner-dependent rather than system-dependent. Overall, gantry-based IMAT with simple planning techniques (two coplanar arcs) produced faster treatments and significantly outperformed static gantry intensity modulated radiation therapy (IMRT) and multileaf collimator (MLC) or non-MLC CKRS treatment plan quality regardless of the system (mean rank out of 4 was 1.2 vs. 3.1, p = 0.002). CONCLUSIONS: High plan quality for complex spinal radiosurgery was achieved among all systems and all participating centers in this planning challenge. This study concludes that simple IMAT techniques can generate significantly better plan quality compared to previous established CKRS benchmarks.

Inverse treatment planning for spinal robotic radiosurgery: an international multi-institutional benchmark trial.

Stereotactic radiosurgery (SRS) is the accurate, conformal delivery of high-dose radiation to well-defined targets while minimizing normal structure doses via steep dose gradients. While inverse treatment planning (ITP) with computerized optimization algorithms are routine, many aspects of the planning process remain user-dependent. We performed an international, multi-institutional benchmark trial to study planning variability and to analyze preferable ITP practice for spinal robotic radiosurgery. 10 SRS treatment plans were generated for a complex-shaped spinal metastasis with 21 Gy in 3 fractions and tight constraints for spinal cord (V14Gy < 2 cc, V18Gy < 0.1 cc) and target (coverage > 95%). The resulting plans were rated on a scale from 1 to 4 (excellent-poor) in five categories (constraint compliance, optimization goals, low-dose regions, ITP complexity, and clinical acceptability) by a blinded review panel. Additionally, the plans were mathemati-cally rated based on plan indices (critical structure and target doses, conformity, monitor units, normal tissue complication probability, and treatment time) and compared to the human rankings. The treatment plans and the reviewers' rankings varied substantially among the participating centers. The average mean overall rank was 2.4 (1.2-4.0) and 8/10 plans were rated excellent in at least one category by at least one reviewer. The mathematical rankings agreed with the mean overall human rankings in 9/10 cases pointing toward the possibility for sole mathematical plan quality comparison. The final rankings revealed that a plan with a well-balanced trade-off among all planning objectives was preferred for treatment by most par-ticipants, reviewers, and the mathematical ranking system. Furthermore, this plan was generated with simple planning techniques. Our multi-institutional planning study found wide variability in ITP approaches for spinal robotic radiosurgery. The participants', reviewers', and mathematical match on preferable treatment plans and ITP techniques indicate that agreement on treatment planning and plan quality can be reached for spinal robotic radiosurgery.

Microstructure of the superior longitudinal fasciculus predicts stimulation-induced interference with on-line motor control.

A cortical visuomotor network, comprising the medial intraparietal sulcus (mIPS) and the dorsal premotor area (PMd), encodes the sensorimotor transformations required for the on-line control of reaching movements. How information is transmitted between these two regions and which pathways are involved, are less clear. Here, we use a multimodal approach combining repetitive transcranial magnetic stimulation (rTMS) and diffusion tensor imaging (DTI) to investigate whether structural connectivity in the 'reaching' circuit is associated to variations in the ability to control and update a movement. We induced a transient disruption of the neural processes underlying on-line motor adjustments by applying 1Hz rTMS over the mIPS. After the stimulation protocol, participants globally showed a reduction of the number of corrective trajectories during a reaching task that included unexpected visual perturbations. A voxel-based analysis revealed that participants exhibiting higher fractional anisotropy (FA) in the second branch of the superior longitudinal fasciculus (SLF II) suffered less rTMS-induced behavioral impact. These results indicate that the microstructural features of the white matter bundles within the parieto-frontal 'reaching' circuit play a prominent role when action reprogramming is interfered. Moreover, our study suggests that the structural alignment and cohesion of the white matter tracts might be used as a predictor to characterize the extent of motor impairments.

Micro-anatomical and functional assessment of ciliated epithelium in mouse trachea using optical coherence phase microscopy.

Motile cilia perform a range of important mechanosensory and chemosensory functions, along with expulsion of mucus and inhaled pathogens from the lungs. Here we demonstrate that spectral domain optical coherence phase microscopy (SD-OCPM), which combines the principles of optical coherence tomography (OCT) and confocal microscopy, is particularly well-suited for characterization of both morphology and the ciliary dynamics of mouse trachea. We present micro-anatomical images of mouse trachea, where different cell types can be clearly visualized. The phase contrast, which measures the sub-nanometer changes in axial optical pathlength is used to determine the frequency and direction of cilia beatings.

Ultrahigh-resolution, high-speed spectral domain optical coherence phase microscopy.

We present an ultrahigh-resolution, high-speed spectral domain optical coherence phase microscopy (SD-OCPM) system that combines submicrometer transverse spatial resolution and subnanometer optical path length sensitivity, with an acquisition speed of over 217,000 voxels/s. The proposed SD-OCPM system overcomes two significant drawbacks of traditional common-path interferometers-limited transverse spatial resolution and suboptimal detection sensitivity-while maintaining phase stability that is comparable with common-path interferometer setups. The transverse and axial spatial resolution of the setup is measured to be 0.6 and 1.9 µm, respectively, with a phase sensitivity of 0.0027 rad (corresponds to optical path length sensitivity of 110 pm). High-speed acquisition allows for phase-sensitive 4D imaging of biological samples with subcellular resolution.

Quality assurance process within the RAdiosurgery for VENtricular TAchycardia (RAVENTA) trial for the fusion of electroanatomical mapping and radiotherapy planning imaging data in cardiac radioablation.

A novel quality assurance process for electroanatomical mapping (EAM)-to-radiotherapy planning imaging (RTPI) target transport was assessed within the multi-center multi-platform framework of the RAdiosurgery for VENtricular TAchycardia (RAVENTA) trial. A stand-alone software (CARDIO-RT) was developed to enable platform independent registration of EAM and RTPI of the left ventricle (LV), based on pre-generated radiotherapy contours (RTC). LV-RTC were automatically segmented into the American-Heart-Association 17-segment-model and a manual 3D-3D method based on EAM 3D-geometry data and a semi-automated 2D-3D method based on EAM screenshot projections were developed. The quality of substrate transfer was evaluated in five clinical cases and the structural analyses showed substantial differences between manual target transfer and target transport using CARDIO-RT.

Treatment Planning for Cardiac Radioablation: Multicenter Multiplatform Benchmarking for the RAdiosurgery for VENtricular TAchycardia (RAVENTA) Trial.

PURPOSE: Cardiac radioablation is a novel treatment option for patients with refractory ventricular tachycardia unsuitable for catheter ablation. The quality of treatment planning depends on dose specifications, platform capabilities, and experience of the treating staff. To harmonize the treatment planning, benchmarking of this process is necessary for multicenter clinical studies such as the RAdiosurgery for VENtricular TAchycardia trial. METHODS AND MATERIALS: Planning computed tomography data and consensus structures from 3 patients were sent to 5 academic centers for independent plan development using a variety of platforms and techniques with the RAdiosurgery for VENtricular TAchycardia study protocol serving as guideline. Three-dimensional dose distributions and treatment plan details were collected and analyzed. In addition, an objective relative plan quality ranking system for ventricular tachycardia treatments was established. RESULTS: For each case, 3 coplanar volumetric modulated arc (VMAT) plans for C-arm linear accelerators (LINAC) and 3 noncoplanar treatment plans for robotic arm LINAC were generated. All plans were suitable for clinical applications with minor deviations from study guidelines in most centers. Eleven of 18 treatment plans showed maximal one minor deviation each for target and cardiac substructures. However, dose-volume histograms showed substantial differences: in one case, the planning target volume ≥30 Gy ranged from 0.0% to 79.9% and the ramus interventricularis anterior V14Gy ranged from 4.0% to 45.4%. Overall, the VMAT plans had steeper dose gradients in the high-dose region, while the plans for the robotic arm LINAC had smaller low-dose regions. Thereby, VMAT plans required only about half as many monitor units, resulting in shorter delivery times, possibly an important factor in treatment outcome. CONCLUSIONS: Cardiac radioablation is feasible with robotic arm and C-arm LINAC systems with comparable plan quality. Although cross-center training and best practice guidelines have been provided, further recommendations, especially for cardiac substructures, and ranking of dose guidelines will be helpful to optimize cardiac radioablation outcomes.

Predicting the outcome of respiratory motion prediction.

PURPOSE: Prediction of respiratory motion traces has become an important research topic. Especially for motion compensated radiotherapy, compensation of the latencies arising from mechanical constraints and signal processing is necessary. In recent years, many algorithms have been developed and evaluated. It is, however, still unclear how well a specific patient will be suited to motion prediction before the treatment actually starts. METHODS: In this work, we have analyzed 304 respiratory motion traces with an average duration of 71 min. A total of 21 features characterizing these signals (12 from the frequency domain and 9 from the time domain) have been determined for each motion trace. The correlation between these features and the overall prediction quality for three different algorithms (based on wavelet-based multiscale autoregression, support vector regression, and linear expansion of the prediction error) has been analyzed and six dominant features have been identified (three each from the time and frequency domains). Additionally, the optimized results of the multistep-linear method (MULIN) prediction algorithm on the first 300 s of motion data have been used as a seventh, independent feature. Assessing the prediction algorithms' quality was done by calculating the relative root mean squared (RMS(rel)) error, i.e., the ratio between the RMS error of the prediction output and the RMS error of the delayed signal (the RMS error obtained when doing no prediction). Then, for each algorithm, the signals themselves were grouped into four classes according to the quality of prediction: relative RMS less than 0.8 (C1), between 0.8 and 0.9 (C2), between 0.9 and 1.0 (C3), and over 1.0 (C4). The goal of this work is to identify, prior to treatment, those patients whose respiratory behavior indicates probable (RMS(rel) ≥ 0.9) or certain (RMS(rel) ≥ 1.0) failure of respiratory motion prediction. Consequently, all signals from C4 must be identified and rejected and no signals from C1 may be falsely rejected. The restriction on C2 and C3 is slightly weaker: C2 are those signals that should be kept and C3 are those signals that should be rejected. RESULTS: Rejecting all signals from C4 and C3, keeping as many signals from C1 and as few from C2 as possible, has been achieved for the wLMS algorithm when using six feature pairs and the result of prediction on the short signal. Here, the false rejectance rate for C1 was less than 13% and the false acceptance rate for C2 was 15%. For the SVRpred and MULIN algorithms, the results are somewhat worse: in both cases, signals from C3 were falsely accepted (25.0% and 14.3%, respectively) but all signals from C4 were rejected. The false rejectance rate for C1 was 11.4% (MULIN) and 26.3% (SVRpred). CONCLUSIONS: In general, it has been shown that pretreatment classification of the quality of respiratory motion prediction is possible and that signals with high relative RMS error can be identified with great reliability. This is especially true for the wLMS algorithm, which has also been identified as the most precise and robust of the presented methods.

Towards automated ultrasound imaging-robotic image acquisition in liver and prostate for long-term motion monitoring.

Real-time volumetric (4D) ultrasound has shown high potential for diagnostic and therapy guidance tasks. One of the main drawbacks of ultrasound imaging to date is the reliance on manual probe positioning and the resulting user dependence. Robotic assistance could help overcome this issue and facilitate the acquisition of long-term image data to observe dynamic processesin vivoover time. The aim of this study is to assess the feasibility of robotic probe manipulation and organ motion quantification during extended imaging sessions. The system consists of a collaborative robot and a 4D ultrasound system providing real-time data access. Five healthy volunteers received liver and prostate scans during free breathing over 30 min. Initial probe placement was performed with real-time remote control with a predefined contact force of 10 N. During scan acquisition, the probe position was continuously adjusted to the body surface motion using impedance control. Ultrasound volumes, the pose of the end-effector and the estimated contact forces were recorded. For motion analysis, one anatomical landmark was manually annotated in a subset of ultrasound frames for each experiment. Probe contact was uninterrupted over the entire scan duration in all ten sessions. Organ drift and imaging artefacts were successfully compensated using remote control. The median contact force along the probe's longitudinal axis was 10.0 N with maximum values of 13.2 and 21.3 N for liver and prostate, respectively. Forces exceeding 11 N only occurred in 0.3% of the time. Probe and landmark motion were more pronounced in the liver, with median interquartile ranges of 1.5 and 9.6 mm, compared to 0.6 and 2.7 mm in the prostate. The results show that robotic ultrasound imaging with dynamic force control can be used for stable, long-term imaging of anatomical regions affected by motion. The system facilitates the acquisition of 4D image datain vivoover extended scanning periods for the first time and holds the potential to be used for motion monitoring for therapy guidance as well as diagnostic tasks.

Interdisciplinary Clinical Target Volume Generation for Cardiac Radioablation: Multicenter Benchmarking for the RAdiosurgery for VENtricular TAchycardia (RAVENTA) Trial.

PURPOSE: Cardiac radioablation is a novel treatment option for therapy-refractory ventricular tachycardia (VT) ineligible for catheter ablation. Three-dimensional clinical target volume (CTV) definition is a key step, and this complex interdisciplinary procedure includes VT-substrate identification based on electroanatomical mapping (EAM) and its transfer to the planning computed tomography (PCT). Benchmarking of this process is necessary for multicenter clinical studies such as the RAVENTA trial. METHODS AND MATERIALS: For benchmarking of the RAVENTA trial, patient data (epicrisis, electrocardiogram, high-resolution EAM, contrast-enhanced cardiac computed tomography, PCT) of 3 cases were sent to 5 university centers for independent CTV generation, subsequent structure analysis, and consensus finding. VT substrates were first defined on multiple EAM screenshots/videos and manually transferred to the PCT. The generated structure characteristics were then independently analyzed (volume, localization, surface distance and conformity). After subsequent discussion, consensus structures were defined. RESULTS: VT substrate on the EAM showed visible variability in extent and localization for cases 1 and 2 and only minor variability for case 3. CTVs ranged from 6.7 to 22.9 cm3, 5.9 to 79.9 cm3, and 9.4 to 34.3 cm3; surface area varied from 1087 to 3285 mm2, 1077 to 9500 mm2, and 1620 to 4179 mm2, with a Hausdorff-distance of 15.7 to 39.5 mm, 23.1 to 43.5 mm, and 15.9 to 43.9 mm for cases 1 to 3, respectively. The absolute 3-dimensional center-of-mass difference was 5.8 to 28.0 mm, 8.4 to 26 mm, and 3.8 to 35.1 mm for cases 1 to 3, respectively. The entire process resulted in CTV structures with a conformity index of 0.2 to 0.83, 0.02 to 0.85, and 0.02 to 0.88 (ideal 1) with the consensus CTV as reference. CONCLUSIONS: Multicenter efficacy endpoint assessment of cardiac radioablation for therapy-refractory VT requires consistent CTV transfer methods from the EAM to the PCT. VT substrate definition and CTVs were comparable with current clinical practice. Remarkable differences regarding the degree of agreement of the CTV definition on the EAM and the PCT were noted, indicating a loss of agreement during the transfer process between EAM and PCT. Cardiac radioablation should be performed under well-defined protocols and in clinical trials with benchmarking and consensus forming.

Smoothing of respiratory motion traces for motion-compensated radiotherapy.

PURPOSE: The CyberKnife system has been used successfully for several years to radiosurgically treat tumors without the need for stereotactic fixation or sedation of the patient. It has been shown that tumor motion in the lung, liver, and pancreas can be tracked with acceptable accuracy and repeatability. However, highly precise targeting for tumors in the lower abdomen, especially for tumors which exhibit strong motion, remains problematic. Reasons for this are manifold, like the slow tracking system operating at 26.5 Hz, and using the signal from the tracking camera "as is." Since the motion recorded with the camera is used to compensate for system latency by prediction and the predicted signal is subsequently used to infer the tumor position from a correlation model based on x-ray imaging of gold fiducials around the tumor, camera noise directly influences the targeting accuracy. The goal of this work is to establish the suitability of a new smoothing method for respiratory motion traces used in motion-compensated radiotherapy. The authors endeavor to show that better prediction--With a lower rms error of the predicted signal--and/or smoother prediction is possible using this method. METHODS: The authors evaluated six commercially available tracking systems (NDI Aurora, PolarisClassic, Polaris Vicra, MicronTracker2 H40, FP5000, and accuTrack compact). The authors first tracked markers both stationary and while in motion to establish the systems' noise characteristics. Then the authors applied a smoothing method based on the a trous wavelet decomposition to reduce the devices' noise level. Additionally, the smoothed signal of the moving target and a motion trace from actual human respiratory motion were subjected to prediction using the MULIN and the nLMS2 algorithms. RESULTS: The authors established that the noise distribution for a static target is Gaussian and that when the probe is moved such as to mimic human respiration, it remains Gaussian with the exception of the FP5000 and the Aurora systems. The authors also showed that the proposed smoothing method can indeed be used to filter noise. The signal's jitter dropped by as much as 95% depending on the tracking system employed. Subsequently, the 3D prediction error (rms) for a prediction horizon of 150 ms on a synthetic signal dropped by up to 37% when using a normalized LMS prediction algorithm (nLMS2) and hardly changed when using a MULIN algorithm. When smoothing a real signal obtained in our laboratory, the improvement of prediction was similar: Up to 30% for both the nLMS2 and the best MULIN algorithm. The authors also found a noticeable increase in smoothness of the predicted signal, the relative jitter dropped by up to 95% on the real signal, and on the simulated signal. CONCLUSIONS: In conclusion, the authors can say that preprocessing of marker data is very useful in motion-compensated radiotherapy since the quality of prediction increases. This will result in better performance of the correlation model. As a side effect, since the prediction of a preprocessed signal is also less noisy, the authors expect less robot vibration resulting in better targeting accuracy and less strain on the robot gears.

Robot-assisted image-guided transcranial magnetic stimulation for somatotopic mapping of the motor cortex: a clinical pilot study.

PURPOSE: Shape and exact location of motor cortical areas varies among individuals. The exact knowledge of these locations is crucial for planning of neurosurgical procedures. In this study, we have used robot-assisted image-guided transcranial magnetic stimulation (Ri-TMS) to elicit MEP response recorded for individual muscles and reconstruct functional motor maps of the primary motor cortex. METHODS: One healthy volunteer and five patients with intracranial tumors neighboring the precentral gyrus were selected for this pilot study. Conventional MRI and fMRI were obtained. Transcranial magnetic stimulation was performed using a MagPro X100 stimulator and a standard figure-of-eight coil positioned by an Adept Viper s850 robot. The fMRI activation/Ri-TMS response pattern were compared. In two cases, Ri-TMS was additionally compared to intraoperative direct electrical cortical stimulation. RESULTS: Maximal MEP response of the m. abductor digiti minimi was located in an area corresponding to the "hand knob" of the precentral gyrus for both hemispheres. Repeated Ri-TMS measurements showed a high reproducibility. Simultaneous registration of the MEP response for m. brachioradialis, m. abductor pollicis brevis, and m. abductor digiti minimi demonstrated individual peak areas of maximal MEP response for the individual muscle groups. Ri-TMS mapping was compared to the corresponding fMRI studies. The areas of maximal MEP response localized within the "finger tapping" activated areas by fMRI in all six individuals. CONCLUSIONS: Ri-TMS is suitable for high resolution non-invasive preoperative somatotopic mapping of the motor cortex. Ri-TMS may help in the planning of neurosurgical procedures and may be directly used in navigation systems.

Radiosurgery for ventricular tachycardia: preclinical and clinical evidence and study design for a German multi-center multi-platform feasibility trial (RAVENTA).

BACKGROUND: Single-session high-dose stereotactic radiotherapy (radiosurgery) is a new treatment option for otherwise untreatable patients suffering from refractory ventricular tachycardia (VT). In the initial single-center case studies and feasibility trials, cardiac radiosurgery has led to significant reductions of VT burden with limited toxicities. However, the full safety profile remains largely unknown. METHODS/DESIGN: In this multi-center, multi-platform clinical feasibility trial which we plan is to assess the initial safety profile of radiosurgery for ventricular tachycardia (RAVENTA). High-precision image-guided single-session radiosurgery with 25 Gy will be delivered to the VT substrate determined by high-definition endocardial electrophysiological mapping. The primary endpoint is safety in terms of successful dose delivery without severe treatment-related side effects in the first 30 days after radiosurgery. Secondary endpoints are the assessment of VT burden, reduction of implantable cardioverter defibrillator (ICD) interventions [shock, anti-tachycardia pacing (ATP)], mid-term side effects and quality-of-life (QoL) in the first year after radiosurgery. The planned sample size is 20 patients with the goal of demonstrating safety and feasibility of cardiac radiosurgery in ≥ 70% of the patients. Quality assurance is provided by initial contouring and planning benchmark studies, joint multi-center treatment decisions, sequential patient safety evaluations, interim analyses, independent monitoring, and a dedicated data and safety monitoring board. DISCUSSION: RAVENTA will be the first study to provide the initial robust multi-center multi-platform prospective data on the therapeutic value of cardiac radiosurgery for ventricular tachycardia. TRIAL REGISTRATION NUMBER: NCT03867747 (clinicaltrials.gov). Registered March 8, 2019. The study was initiated on November 18th, 2019, and is currently recruiting patients.

Automated segmentation of tissue structures in optical coherence tomography data.

Segmentation of optical coherence tomography (OCT) images provides useful information, especially in medical imaging applications. Because OCT images are subject to speckle noise, the identification of structures is complicated. Addressing this issue, two methods for the automated segmentation of arbitrary structures in OCT images are proposed. The methods perform a seeded region growing, applying a model-based analysis of OCT A-scans for the seed's acquisition. The segmentation therefore avoids any user-intervention dependency. The first region-growing algorithm uses an adaptive neighborhood homogeneity criterion based on a model of an OCT intensity course in tissue and a model of speckle noise corruption. It can be applied to an unfiltered OCT image. The second performs region growing on a filtered OCT image applying the local median as a measure for homogeneity in the region. Performance is compared through the quantitative evaluation of artificial data, showing the capabilities of both in terms of structures detected and leakage. The proposed methods were tested on real OCT data in different scenarios and showed promising results for their application in OCT imaging.

Computer- and robot-assisted stereotaxy for high-precision small animal brain exploration.

This contribution introduces a computer- and robot-assisted framework for stereotactic neurosurgery on small animals. Two major elements of this framework are presented in detail: a robotic stereotactic assistant and the software framework for placement of probes into the brain. The latter integrates modules for registration, insertion control, and preoperative path planning. Two options for path planning are addressed: (a) atlas-based planning and (b) image-based planning based on computed tomography data. The framework is tested performing robot-assisted insertion of microelectrodes and acquisition of electrophysiological recordings in vivo. Concepts for data analysis pointing towards a mapping of position and neural structure to functional data are introduced. Results show that the presented framework allows precise small animal stereotaxy and therefore offers new options for brain research.

Efficient Registration of High-Resolution Feature Enhanced Point Clouds.

We present a novel framework for rigid point cloud registration. Our approach is based on the principles of mechanics and thermodynamics. We solve the registration problem by assuming point clouds as rigid bodies consisting of particles. Forces can be applied between both particle systems so that they attract or repel each other. These forces are used to cause rigid-body motion of one particle system toward the other, until both are aligned. The framework supports physics-based registration processes with arbitrary driving forces, depending on the desired behaviour. Additionally, the approach handles feature-enhanced point clouds, e.g., by colours or intensity values. Our framework is freely accessible for download. In contrast to already existing algorithms, our contribution is to precisely register high-resolution point clouds with nearly constant computational effort and without the need for pre-processing, sub-sampling or pre-alignment. At the same time, the quality is up to 28 percent higher than for state-of-the-art algorithms and up to 49 percent higher when considering feature-enhanced point clouds. Even in the presence of noise, our registration approach is one of the most robust, on par with state-of-the-art implementations.

A visual probe positioning tool for 4D ultrasound-guided radiotherapy.

Ultrasound (US) guidance is a rapidly growing area in image-guided radiotherapy. For motion compensation, the therapy target needs to be visualized with the US probe to continuously determine its position and adapt for shifts. While US has obvious benefits such as real-time capability and proven safety, one of the main drawbacks to date is its user dependency - high quality results require long years of clinical experience. To provide positioning assistance for the setup of US equipment by non-experts, we developed a visual guidance tool combining real-time US volume and CT visualization in a geometrically calibrated setup. By using a 4D US station with real-time data access and an optical tracking system, we achieved a calibration accuracy of 1.2 mm and a mean 2D contour distance of 1.7 mm between organ boundaries identified in US and CT. With this low calibration error as well as the good visual alignment of the structures, the developed probe positioning tool could be a valuable aid for ultrasound-guided radiotherapy and other interventions by guiding the user to a suitable acoustic window while potentially improving setup reproducibility.