Variations in Determining Actual Orientations of Segmented Deep Brain Stimulation Leads Using the DiODe Algorithm: A Retrospective Study Across Different Lead Designs and Medical Institutions.

INTRODUCTION: Directional deep brain stimulation (DBS) leads have become widely used in the past decade. Understanding the asymmetric stimulation provided by directional leads requires precise knowledge of the exact orientation of the lead in respect to its anatomical target. Recently, the DiODe algorithm was developed to automatically determine the orientation angle of leads from the artifact on postoperative computed tomography (CT) images. However, manual DiODe results are user-dependent. This study analyzed the extent of lead rotation as well as the user agreement of DiODe calculations across the two most common DBS systems, namely, Boston Scientific's Vercise and Abbott's Infinity, and two independent medical institutions. METHODS: Data from 104 patients who underwent an anterior-facing unilateral/bilateral directional DBS implantation at either Northwestern Memorial Hospital (NMH) or Albany Medical Center (AMC) were retrospectively analyzed. Actual orientations of the implanted leads were independently calculated by three individual users using the DiODe algorithm in Lead-DBS and patients' postoperative CT images. The deviation from the intended orientation and user agreement were assessed. RESULTS: All leads significantly deviated from the intended 0° orientation (p < 0.001), regardless of DBS lead design (p < 0.05) or institution (p < 0.05). However, the Boston Scientific leads showed an implantation bias toward the left at both institutions (p = 0.014 at NMH, p = 0.029 at AMC). A difference of 10° between at least two users occurred in 28% (NMH) and 39% (AMC) of all Boston Scientific and 76% (NMH) and 53% (AMC) of all Abbott leads. CONCLUSION: Our results show that there is a significant lead rotation from the intended surgical orientation across both DBS systems and both medical institutions; however, a bias toward a single direction was only seen in the Boston Scientific leads. Additionally, these results raise questions into the user error that occurs when manually refining the orientation angles calculated with DiODe.

Effect of Device Configuration and Patient's Body Composition on the RF Heating and Nonsusceptibility Artifact of Deep Brain Stimulation Implants During MRI at 1.5T and 3T.

BACKGROUND: Patients with deep brain stimulation (DBS) implants have limited access to MRI due to safety concerns associated with RF-induced heating. Currently, MRI in these patients is allowed in 1.5T horizontal bore scanners utilizing pulse sequences with reduced power. However, the use of 3T MRI in such patients is increasingly reported based on limited safety assessments. Here we present the results of comprehensive RF heating measurements for two commercially available DBS systems during MRI at 1.5T and 3T. PURPOSE: To assess the effect of imaging landmark, DBS lead configuration, and patient's body composition on RF heating of DBS leads during MRI at 1.5T and 3T. STUDY TYPE: Phantom and ex vivo study. POPULATION/SUBJECTS/PHANTOM/SPECIMEN/ANIMAL MODEL: Gel phantoms and cadaver brain. FIELD STRENGTH/SEQUENCE: 1.5T and 3T, T1 -weighted turbo spin echo. ASSESSMENT: RF heating was measured at the tips of DBS leads implanted in brain-mimicking gel. Image artifact was assessed in a cadaver brain implanted with an isolated DBS lead. STATISTICAL TESTS: Descriptive. RESULTS: We observed substantial fluctuation in RF heating, mainly affected by phantom composition and DBS lead configuration, ranging from 0.14°C to 23.73°C at 1.5T, and from 0.10°C to 7.39°C at 3T. The presence of subcutaneous fat substantially altered RF heating at the electrode tips (3.06°C < ∆T < 19.05° C). Introducing concentric loops in the extracranial portion of the lead at the surgical burr hole reduced RF heating by up to 89% at 1.5T and up to 98% at 3T compared to worst-case heating scenarios. DATA CONCLUSION: Device configuration and patient's body composition substantially altered the RF heating of DBS leads during MRI. Interestingly, certain lead trajectories consistently reduced RF heating and image artifact. Level of Evidence 1 Technical Efficacy Stage 1 J. MAGN. RESON. IMAGING 2021;53:599-610.

Prospective Evaluation of the Time Course of White Matter Edema Associated with Implanted Deep Brain Stimulation Electrodes.

INTRODUCTION: Deep brain stimulation (DBS) is commonly used in the treatment of medically refractory movement disorders. There have been several reports in the literature of edema developing around the implanted electrode. Most of these studies have been retrospective, suggesting that the time course and incidence of this edema are underestimated. An understanding of the incidence and time course of edema related to DBS leads is important to allow clinicians to better assess the correct course of action when edema following DBS implantation is observed. METHODS: We examined both the time course and prevalence of edema following DBS implantation by obtaining a series of postoperative MRI scans from patients who underwent DBS surgery. Edema volume was quantified by a single neuroradiologist, measuring the peri-electrode T2 signal change. RESULTS: We examined postoperative MRIs in thirteen patients with fifteen DBS electrode implants. Eleven patients exhibited white matter edema on at least 1 postoperative MRI, with none being symptomatic. Edema was completely resolved in 4 of the electrode implants through postoperative day 70, with the remaining cases still exhibiting edema at the last imaged time point. DISCUSSION/CONCLUSION: In this study, we obtained a regimented series of postoperative MRIs in an effort to determine the time course and incidence of edema. Our results show that edema following DBS implant is not rare, is often asymptomatic, and may resolve over many weeks.

EphB controls NMDA receptor function and synaptic targeting in a subunit-specific manner.

Dynamic regulation of the localization and function of NMDA receptors (NMDARs) is critical for synaptic development and function. The composition and localization of NMDAR subunits at synapses are tightly regulated and can influence the ability of individual synapses to undergo long-lasting changes in response to stimuli. Here, we examine mechanisms by which EphB2, a receptor tyrosine kinase that binds and phosphorylates NMDARs, controls NMDAR subunit localization and function at synapses. We find that, in mature neurons, EphB2 expression levels regulate the amount of NMDARs at synapses, and EphB activation decreases Ca(2+)-dependent desensitization of NR2B-containing NMDARs. EphBs are required for enhanced localization of NR2B-containing NMDARs at synapses of mature neurons; triple EphB knock-out mice lacking EphB1-3 exhibit homeostatic upregulation of NMDAR surface expression and loss of proper targeting to synaptic sites. These findings demonstrate that, in the mature nervous system, EphBs are key regulators of the synaptic localization of NMDARs.

Intraoperative Computed Tomography for Registration of Stereotactic Frame in Frame-Based Deep Brain Stimulation.

BACKGROUND: Deep brain stimulation (DBS) electrode placement utilizing a frame-based technique requires registration of the stereotactic frame with computed tomography (CT) or magnetic resonance (MR) imaging. This traditionally has been accomplished with a conventional CT scanner. In recent years, intraoperative CT has become more prevalent. OBJECTIVE: To compare the coordinates obtained with intraoperative CT and conventional CT for registration of the stereotactic frame for DBS. METHODS: Patients undergoing DBS electrode placement between 2015 and 2017, who underwent both conventional and intraoperative CT for registration of the stereotactic frame, were included for analysis. The coordinates for the stereotactic target, anterior commissure, and posterior commissure for each CT method were recorded. The mean, maximum, minimum, and standard deviation of the absolute difference for each of the paired coordinates was calculated. Paired t-tests were performed to test for statistical significance of the difference. The directional difference as well as the vector error between the paired coordinates was also calculated. RESULTS: The mean absolute difference between conventional and intraoperative CT for the coordinate pairs was less than 0.279 mm or 0.211 degrees for all coordinate pairs analyzed. This was not statistically significant for any of the coordinate pairs. Moreover, the maximum absolute difference between all coordinate pairs was 1.04 mm. CONCLUSION: Intraoperative CT imaging provides stereotactic frame registration coordinates that are similar to those obtained by a standard CT scanner. This may save time and hospital resources by obviating the need for the patient to go to the radiology department for a CT scan.

Safety and image quality at 7T MRI for deep brain stimulation systems: Ex vivo study with lead-only and full-systems.

Ultra-high field MRI at 7 T can produce much better visualization of sub-cortical structures compared to lower field, which can greatly help target verification as well as overall treatment monitoring for patients with deep brain stimulation (DBS) implants. However, use of 7 T MRI for such patients is currently contra-indicated by guidelines from the device manufacturers due to the safety issues. The aim of this study was to provide an assessment of safety and image quality of ultra-high field magnetic resonance imaging at 7 T in patients with deep brain stimulation implants. We performed experiments with both lead-only and complete DBS systems implanted in anthropomorphic phantoms. RF heating was measured for 43 unique patient-derived device configurations. Magnetic force measurements were performed according to ASTM F2052 test method, and device integrity was assessed before and after experiments. Finally, we assessed electrode artifact in a cadaveric brain implanted with an isolated DBS lead. RF heating remained below 2°C, similar to a fever, with the 95% confidence interval between 0.38°C-0.52°C. Magnetic forces were well below forces imposed by gravity, and thus not a source of concern. No device malfunctioning was observed due to interference from MRI fields. Electrode artifact was most noticeable on MPRAGE and T2*GRE sequences, while it was minimized on T2-TSE images. Our work provides the safety assessment of ultra-high field MRI at 7 T in patients with DBS implants. Our results suggest that 7 T MRI may be performed safely in patients with DBS implants for specific implant models and MRI hardware.

Device Configuration and Patient's Body Composition Significantly Affect RF Heating of Deep Brain Stimulation Implants During MRI: An Experimental Study at 1.5T and 3T.

Patients with deep brain stimulation (DBS) devices have limited access to magnetic resonance imaging (MRI) due to safety concerns associated with RF heating generated around the implant. The problem of predicting RF heating of conductive leads is complex with a large parameter space and several interplaying factors. Recently however, off-label use of MRI in patients with DBS devices has been reported based on limited safety assessments, raising the concern that potentially dangerous scenarios may have been overlooked. In this work, we present results of a systematic assessment of RF heating of a commercial DBS device during MRI at 1.5T and 3T, taking into account the effect of device configuration, imaging landmark, and patient's body composition. Ninety-six (96) RF heating measurements were performed using anthropomorphic phantoms implanted with a full DBS system. We evaluated eight clinically relevant device configurations, implanted in phantoms with different material compositions, and imaged at three different landmarks (head, shoulder, and lower chest) in 1.5 T and 3T scanners. We observed a substantial fluctuation in the RF heating depending on phantom's composition and device configuration. RF heating in the brain-mimicking gel varied from 0.1°C to 12°C during 1.5 T MRI and from <0.1°C to 4.5°C during 3T MRI. We also observed that certain device configurations consistently reduced RF heating across different phantom compositions, imaging landmarks, and MRI transmit frequencies.

The effects of chronic levodopa treatments on the neuronal firing properties of the subthalamic nucleus and substantia nigra reticulata in hemiparkinsonian rhesus monkeys.

Dopamine replacement therapy with levodopa (LD) is currently the most effective pharmacological treatment for Parkinson's disease (PD), a neurodegenerative disorder characterized by dysfunction of basal ganglia electrophysiology. The effects of chronic LD treatments on the electrophysiological activity of the subthalamic nucleus (STN) and the substantia nigra reticulata (SNR) in parkinsonism are not clear. In the present study we examined the effects of chronic LD treatments on the firing rate and firing pattern of STN and SNR neurons in the stable hemiparkinsonian monkey model of PD. We also evaluated local field potentials of both nuclei before and after LD treatments. In a stable hemiparkinsonian state, STN and SNR had a mean firing rate of 42.6 ± 3.5H z (mean ± SEM) and 52.1 ± 5.7 Hz, respectively. Chronic intermittent LD exposure induced marked amelioration of parkinsonism with no apparent drug-induced motor complications. LD treatments did not significantly change the mean firing rate of STN neurons (41.3 ± 3.3 Hz) or bursting neuronal firing patterns. However, LD treatments induced a significant reduction of the mean firing rates of SNR neurons to 36.2 ± 3.3 Hz (p<0.05) and a trend toward increased burstiness. The entropy of the spike sequences from STN and SNR was unchanged by LD treatment, while there was a shift of spectral power into higher frequency bands in the LFPs. The inability of chronic LD treatments to reduce the bursty firing patterns in the STN and SNR should be further examined as a potential pathophysiological mechanism for PD symptoms that are refractory to LD treatments.

EphB receptors couple dendritic filopodia motility to synapse formation.

Motile dendritic filopodial processes are thought to be precursors of spine synapses, but how motility relates to cell-surface cues required for axon-dendrite recognition and synaptogenesis remains unclear. We demonstrate with dynamic imaging that loss of EphBs results in reduced motility of filopodia in cultured cortical neurons and brain slice. EphB knockdown and rescue experiments during different developmental time windows show that EphBs are required for synaptogenesis only when filopodia are most abundant and motile. In the context of EphB knockdown and reduced filopodia motility, independent rescue of either motility with PAK or of Eph-ephrin binding with an EphB2 kinase mutant is not sufficient to restore synapse formation. Strikingly, the combination of PAK and kinase-inactive EphB2 rescues synaptogenesis. Deletion of the ephrin-binding domain from EphB2 precludes rescue, indicating that both motility and trans-cellular interactions are required. Our findings provide a mechanistic link between dendritic filopodia motility and synapse differentiation.

Precision, reliability, and information-theoretic analysis of visual thalamocortical neurons.

High-order statistics of neural responses allow one to gain insight into neural function that may not be evident from firing rate alone. In this study, we compared the precision, reliability, and information content of spike trains from X- and Y-cells in the lateral geniculate nucleus (LGN) and layer IV simple cells of area 17 in the cat. To a stochastic, contrast-modulated Gabor patch, layer IV simple cells responded as precisely as their primary inputs, LGN X-cells, but less reliably. LGN Y-cells were more precise and reliable than LGN X-cells. Also, within each LGN cell type, 1) responses to the same stimulus were nearly identical if they shared the same center sign and 2) responses of neurons with the same center sign were nearly identical to the responses of neurons of opposite center sign if the stimulus' contrasts were inverted. These results suggest simple cells receive highly precise and synchronous LGN input, resulting in precise responses. Nonetheless, the response precision of simple cells was greater than expected. Finally, information-theoretic calculations of our cell responses revealed that 1) LGN X-cells encoded information at half the rate of LGN Y-cells but 2.5 times the rate of layer IV simple cells; 2) LGN cells encoded information in their responses using temporal patterns, whereas simple cells did not; and 3) simple cells used more of their information capacity than LGN X-cells. We propose mechanisms that simple cells might use to ensure high precision.