Shape-constrained deformable brain segmentation: Methods and quantitative validation.

MRI-guided neuro interventions require rapid, accurate, and reproducible segmentation of anatomical brain structures for identification of targets during surgical procedures and post-surgical evaluation of intervention efficiency. Segmentation algorithms must be validated and cleared for clinical use. This work introduces a methodology for shape-constrained deformable brain segmentation, describes the quantitative validation used for its clinical clearance, and presents a comparison with manual expert segmentation and FreeSurfer, an open source software for neuroimaging data analysis. ClearPoint Maestro is software for fully-automatic brain segmentation from T1-weighted MRI that combines a shape-constrained deformable brain model with voxel-wise tissue segmentation within the cerebral hemispheres and the cerebellum. The performance of the segmentation was validated in terms of accuracy and reproducibility. Segmentation accuracy was evaluated with respect to training data and independently traced ground truth. Segmentation reproducibility was quantified and compared with manual expert segmentation and FreeSurfer. Quantitative reproducibility analysis indicates superior performance compared to both manual expert segmentation and FreeSurfer. The shape-constrained methodology results in accurate and highly reproducible segmentation. Inherent point based-correspondence provides consistent target identification ideal for MRI-guided neuro interventions.

Learning Curve Associated with ClearPoint Neuronavigation System: A Case Series.

BACKGROUND: The ClearPoint neuronavigation system affords real-time magnetic resonance imaging (MRI) guidance during stereotactic procedures. While such information confers potential clinical benefits, additional operative time may be needed. METHODS: We conducted a retrospective analysis of procedural time associated with ClearPoint Stereotaxis, with hypothesis that this procedural time is comparable with that associated with frame-based biopsy. RESULTS: Of the 52 patients evaluated, the total procedural time for ClearPoint stereotactic biopsy averaged 150.0 (±40.4) minutes, of which 111.5 (±16.5) minutes were dedicated to real-time MRI acquisition and trajectory adjustment. This procedural time is within the range of those reported for frame-based needle biopsies. Approximately 5 minutes of the procedural time is related to the mounting of the MRI-compatible stereotactic frame. Based on the procedural time, we estimate that four cases are required in the learning curve to achieve this efficiency. Efficient algorithms for distortion corrections and isocenter localization are keys to ClearPoint stereotaxis. Routine quality assurance/control after each MRI software update and institutional information technology maintenance also contribute to efficiency. Real-time MRI is essential for definitive diagnosis in select cases. CONCLUSIONS: ClearPoint stereotactic needle biopsy can be achieved in time frames comparable to frame-based stereotaxis. However, procedural efficiency requires 4 "learning curve" cases as well as vigilance in terms of MR distortion correction and information technology maintenance.

Clinical outcomes of globus pallidus deep brain stimulation for Parkinson disease: a comparison of intraoperative MRI- and MER-guided lead placement.

OBJECTIVE: Deep brain stimulation (DBS) lead placement is increasingly performed with the patient under general anesthesia by surgeons using intraoperative MRI (iMRI) guidance without microelectrode recording (MER) or macrostimulation. The authors assessed the accuracy of lead placement, safety, and motor outcomes in patients with Parkinson disease (PD) undergoing DBS lead placement into the globus pallidus internus (GPi) using iMRI or MER guidance. METHODS: The authors identified all patients with PD who underwent either MER- or iMRI-guided GPi-DBS lead placement at Emory University between July 2007 and August 2016. Lead placement accuracy and adverse events were determined for all patients. Clinical outcomes were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) part III motor scores for patients completing 12 months of follow-up. The authors also assessed the levodopa-equivalent daily dose (LEDD) and stimulation parameters. RESULTS: Seventy-seven patients were identified (MER, n = 28; iMRI, n = 49), in whom 131 leads were placed. The stereotactic accuracy of the surgical procedure with respect to the planned lead location was 1.94 ± 0.21 mm (mean ± SEM) (95% CI 1.54-2.34) with frame-based MER and 0.84 ± 0.007 mm (95% CI 0.69-0.98) with iMRI. The rate of serious complications was similar, at 6.9% for MER-guided DBS lead placement and 9.4% for iMRI-guided DBS lead placement (RR 0.71 [95% CI 0.13%-3.9%]; p = 0.695). Fifty-seven patients were included in clinical outcome analyses (MER, n = 16; iMRI, n = 41). Both groups had similar characteristics at baseline, although patients undergoing MER-guided DBS had a lower response on their baseline levodopa challenge (44.8% ± 5.4% [95% CI 33.2%-56.4%] vs 61.6% ± 2.1% [95% CI 57.4%-65.8%]; t = 3.558, p = 0.001). Greater improvement was seen following iMRI-guided lead placement (43.2% ± 3.5% [95% CI 36.2%-50.3%]) versus MER-guided lead placement (25.5% ± 6.7% [95% CI 11.1%-39.8%]; F = 5.835, p = 0.019). When UPDRS III motor scores were assessed only in the contralateral hemibody (per-lead analyses), the improvements remained significantly different (37.1% ± 7.2% [95% CI 22.2%-51.9%] and 50.0% ± 3.5% [95% CI 43.1%-56.9%] for MER- and iMRI-guided DBS lead placement, respectively). Both groups exhibited similar reductions in LEDDs (21.2% and 20.9%, respectively; F = 0.221, p = 0.640). The locations of all active contacts and the 2D radial distance from these to consensus coordinates for GPi-DBS lead placement (x, ±20; y, +2; and z, -4) did not differ statistically by type of surgery. CONCLUSIONS: iMRI-guided GPi-DBS lead placement in PD patients was associated with significant improvement in clinical outcomes, comparable to those observed following MER-guided DBS lead placement. Furthermore, iMRI-guided DBS implantation produced a similar safety profile to that of the MER-guided procedure. As such, iMRI guidance is an alternative to MER guidance for patients undergoing GPi-DBS implantation for PD.

Adapting to Space Limitations During Prone Real-Time Magnetic Resonance Imaging-Guided Stereotaxic Laser Ablation: Technical Pearls.

BACKGROUND: New techniques of intraoperative magnetic resonance imaging (MRI)-guided stereotaxy enable minimally invasive approaches to intracranial pathology. Laser interstitial thermal therapy (LITT), convection-enhanced drug delivery, and stereotactic biopsy can be performed with a real-time confirmation of location and the ability to adjust for intracranial shift during the procedure. However, these procedures are constrained by patient positioning and the need for trajectories that avoid collision between stereotactic elements and the small MRI bore. To our knowledge, this is the first report to outline the technical details of safe intraoperative MRI (iMRI)-guided stereotaxy, performed with prone positioning. OBJECTIVE: To present technical pearls to guide the safe conduction of iMRI-guided stereotaxy and LITT while in the prone position. METHODS: The details of the positioning and trajectories for a series of patients who underwent Clearpoint® (MRI Interventions Inc) frameless real-time MRI-guided stereotaxis using a posterior approach were reviewed. RESULTS: In this series, 5 patients underwent selective amygdalohippocampectomy, and 2 underwent tumor biopsy/ablation while in the prone position without any complications. CONCLUSION: Prone iMRI procedures can be performed safely even in a 60-cm MRI bore.

Biopsy and Ablation of H3K27 Glioma Using Skull-Mounted Smartframe Device: Technical Case Report.

BACKGROUND: Clearpoint Smartframe is a magnetic resonance imaging-compatible stereotactic system often used to perform magnetic resonance imaging-guided biopsies. The system is typically mounted on the scalp through screws that pierce the skin and penetrate the outer table of the cranium. However, the frame can also be configured to be mounted directly onto the skull. CASE DESCRIPTION: Here, we describe the clinical context well suited for a skull-mount Clearpoint Smartframe surgery. The patient suffered from a subcentimeter right parafourth ventricular contrast-enhancing lesion with hydrocephalus and underwent a right suboccipital needle biopsy followed by an occipital ventriculoperitoneal shunt. Although the hydrocephalus resolved with the ventriculoperitoneal shunt, the biopsy sample proved nondiagnostic. The patient underwent a second procedure during which the Clearpoint Smartframe was mounted onto the skull through space dissected free during the previous surgery. Diagnostic biopsy (H3K27 glioma) was performed followed by stereotactic laser ablation of the lesion. CONCLUSIONS: We describe a case in which the skull mount Clearpoint Smartframe was used to biopsy and ablate a midline H3K27 glioma.

Clinical outcomes of pallidal deep brain stimulation for dystonia implanted using intraoperative MRI.

OBJECTIVE: Lead placement for deep brain stimulation (DBS) using intraoperative MRI (iMRI) relies solely on real-time intraoperative neuroimaging to guide electrode placement, without microelectrode recording (MER) or electrical stimulation. There is limited information, however, on outcomes after iMRI-guided DBS for dystonia. The authors evaluated clinical outcomes and targeting accuracy in patients with dystonia who underwent lead placement using an iMRI targeting platform. METHODS: Patients with dystonia undergoing iMRI-guided lead placement in the globus pallidus pars internus (GPi) were identified. Patients with a prior ablative or MER-guided procedure were excluded from clinical outcomes analysis. Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) scores and Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) scores were assessed preoperatively and at 6 and 12 months postoperatively. Other measures analyzed include lead accuracy, complications/adverse events, and stimulation parameters. RESULTS: A total of 60 leads were implanted in 30 patients. Stereotactic lead accuracy in the axial plane was 0.93 ± 0.12 mm from the intended target. Nineteen patients (idiopathic focal, n = 7; idiopathic segmental, n = 5; DYT1, n = 1; tardive, n = 2; other secondary, n = 4) were included in clinical outcomes analysis. The mean improvement in BFMDRS score was 51.9% ± 9.7% at 6 months and 63.4% ± 8.0% at 1 year. TWSTRS scores in patients with predominant cervical dystonia (n = 13) improved by 53.3% ± 10.5% at 6 months and 67.6% ± 9.0% at 1 year. Serious complications occurred in 6 patients (20%), involving 8 of 60 implanted leads (13.3%). The rate of serious complications across all patients undergoing iMRI-guided DBS at the authors' institution was further reviewed, including an additional 53 patients undergoing GPi-DBS for Parkinson disease. In this expanded cohort, serious complications occurred in 11 patients (13.3%) involving 15 leads (10.1%). CONCLUSIONS: Intraoperative MRI-guided lead placement in patients with dystonia showed improvement in clinical outcomes comparable to previously reported results using awake MER-guided lead placement. The accuracy of lead placement was high, and the procedure was well tolerated in the majority of patients. However, a number of patients experienced serious adverse events that were attributable to the introduction of a novel technique into a busy neurosurgical practice, and which led to the revision of protocols, product inserts, and on-site training.

Improved operative efficiency using a real-time MRI-guided stereotactic platform for laser amygdalohippocampotomy.

OBJECTIVE MR-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive method for thermal destruction of benign or malignant tissue that has been used for selective amygdalohippocampal ablation for the treatment of temporal lobe epilepsy. The authors report their initial experience adopting a real-time MRI-guided stereotactic platform that allows for completion of the entire procedure in the MRI suite. METHODS Between October 2014 and May 2016, 17 patients with mesial temporal sclerosis were selected by a multidisciplinary epilepsy board to undergo a selective amygdalohippocampal ablation for temporal lobe epilepsy using MRgLITT. The first 9 patients underwent standard laser ablation in 2 phases (operating room [OR] and MRI suite), whereas the next 8 patients underwent laser ablation entirely in the MRI suite with the ClearPoint platform. A checklist specific to the real-time MRI-guided laser amydalohippocampal ablation was developed and used for each case. For both cohorts, clinical and operative information, including average case times and accuracy data, was collected and analyzed. RESULTS There was a learning curve associated with using this real-time MRI-guided system. However, operative times decreased in a linear fashion, as did total anesthesia time. In fact, the total mean patient procedure time was less in the MRI cohort (362.8 ± 86.6 minutes) than in the OR cohort (456.9 ± 80.7 minutes). The mean anesthesia time was significantly shorter in the MRI cohort (327.2 ± 79.9 minutes) than in the OR cohort (435.8 ± 78.4 minutes, p = 0.02). CONCLUSIONS The real-time MRI platform for MRgLITT can be adopted in an expedient manner. Completion of MRgLITT entirely in the MRI suite may lead to significant advantages in procedural times.

Magnetic Resonance Imaging-Guided Delivery of Neural Stem Cells into the Basal Ganglia of Nonhuman Primates Reveals a Pulsatile Mode of Cell Dispersion.

Optimal stem cell delivery procedures are critical to the success of the cell therapy approach. Variables such as flow rate, suspension solution, needle diameter, cell density, and tissue mechanics affect tissue penetration, backflow along the needle, and the dispersion and survival of injected cells during delivery. Most cell transplantation centers engaged in human clinical trials use custom-designed cannula needles, syringes, or catheters, sometimes precluding the use of magnetic resonance imaging (MRI)-guided delivery to target tissue. As a result, stem cell therapies may be hampered because more than 80% of grafted cells do not survive the delivery-for example, to the heart, liver/pancreas, and brain-which translates to poor patient outcomes. We developed a minimally invasive interventional MRI (iMRI) approach for intraoperatively imaging neural stem cell (NSC) delivery procedures. We used NSCs prelabeled with a contrast agent and real-time magnetic resonance imaging to guide the injection cannula to the target and to track the delivery of the cells into the putamen of baboons. We provide evidence that cell injection into the brain parenchyma follows a novel pulsatile mode of cellular discharge from the delivery catheter despite a constant infusion flow rate. The rate of cell infusion significantly affects the dispersion and viability of grafted cells. We report on our investigational use of a frameless navigation system for image-guided NSC transplantation using a straight cannula. Through submillimeter accuracy and real-time imaging, iMRI approaches may improve the safety and efficacy of neural cell transplantation therapies. Stem Cells Translational Medicine 2017;6:877-885.

Clinical outcomes using ClearPoint interventional MRI for deep brain stimulation lead placement in Parkinson's disease.

OBJECTIVE: The ClearPoint real-time interventional MRI-guided methodology for deep brain stimulation (DBS) lead placement may offer advantages to frame-based approaches and allow accurate implantation under general anesthesia. In this study, the authors assessed the safety and efficacy of DBS in Parkinson's disease (PD) using this surgical method. METHODS: This was a prospective single-center study of bilateral DBS therapy in patients with advanced PD and motor fluctuations. Symptom severity was evaluated at baseline and 12 months postimplantation using the change in Unified Parkinson's Disease Rating Scale (UPDRS) Part III "off" medication score as the primary outcome variable. RESULTS: Twenty-six PD patients (15 men and 11 women) were enrolled from 2010 to 2013. Twenty patients were followed for 12 months (16 with a subthalamic nucleus target and 4 with an internal globus pallidus target). The mean UPDRS Part III "off" medication score improved from 40.75 ± 10.9 to 24.35 ± 8.8 (p = 0.001). "On" medication time without troublesome dyskinesia increased 5.2 ± 2.6 hours per day (p = 0.0002). UPDRS Parts II and IV, total UPDRS score, and dyskinesia rating scale "on" medication scores also significantly improved (p < 0.01). The mean levodopa equivalent daily dose decreased from 1072.5 ± 392 mg to 828.25 ± 492 mg (p = 0.046). No significant cognitive or mood declines were observed. A single brain penetration was used for placement of all leads, and the mean targeting error was 0.6 ± 0.3 mm. There were 3 serious adverse events (1 DBS hardware-related infection, 1 lead fracture, and 1 unrelated death). CONCLUSIONS: DBS leads placed using the ClearPoint interventional real-time MRI-guided method resulted in highly accurate lead placement and outcomes comparable to those seen with frame-based approaches.