Publications by authors named "Volker A Coenen"

82 Publications

SPECTRE-A novel dMRI visualization technique for the display of cerebral connectivity.

Hum Brain Mapp 2021 Feb 27. Epub 2021 Feb 27.

Department of Stereotactic and Functional Neurosurgery, Freiburg University Medical Center, Freiburg, Germany.

The visualization of diffusion MRI related properties in a comprehensive way is still a challenging problem. We propose a simple visualization technique to give neuroradiologists and neurosurgeons a more direct and personalized view of relevant connectivity patterns estimated from clinically feasible diffusion MRI. The approach, named SPECTRE (Subject sPEcific brain Connectivity display in the Target REgion), is based on tract-weighted imaging, where diffusion MRI streamlines are used to aggregate information from a different MRI contrast. Instead of using native MRI contrasts, we propose to use continuous template information as the underlying contrast for aggregation. In this respect, the SPECTRE approach is complementary to normative approaches where connectivity information is warped from the group level to subject space by anatomical registration. For the purpose of demonstration, we focus the presentation of the SPECTRE approach on the visualization of connectivity patterns in the midbrain regions at the level of subthalamic nucleus due to its importance for deep brain stimulation. The proposed SPECTRE maps are investigated with respect to plausibility, robustness, and test-retest reproducibility. Clear dependencies of reliability measures with respect to the underlying tracking algorithms are observed.
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http://dx.doi.org/10.1002/hbm.25385DOI Listing
February 2021

The rostro-caudal gradient in the prefrontal cortex and its modulation by subthalamic deep brain stimulation in Parkinson's disease.

Sci Rep 2021 Jan 22;11(1):2138. Epub 2021 Jan 22.

Department of Neurology, Medical Center, University of Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) alleviates motor symptoms in Parkinson's disease (PD) but also affects the prefrontal cortex (PFC), potentially leading to cognitive side effects. The present study tested alterations within the rostro-caudal hierarchy of neural processing in the PFC induced by STN-DBS in PD. Granger-causality analyses of fast functional near-infrared spectroscopy (fNIRS) measurements were used to infer directed functional connectivity from intrinsic PFC activity in 24 PD patients treated with STN-DBS. Functional connectivity was assessed ON stimulation, in steady-state OFF stimulation and immediately after the stimulator was switched ON again. Results revealed that STN-DBS significantly enhanced the rostro-caudal hierarchical organization of the PFC in patients who had undergone implantation early in the course of the disease, whereas it attenuated the rostro-caudal hierarchy in late-implanted patients. Most crucially, this systematic network effect of STN-DBS was reproducible in the second ON stimulation measurement. Supplemental analyses demonstrated the significance of prefrontal networks for cognitive functions in patients and matched healthy controls. These findings show that the modulation of prefrontal functional networks by STN-DBS is dependent on the disease duration before DBS implantation and suggest a neurophysiological mechanism underlying the side effects on prefrontally-guided cognitive functions observed under STN-DBS.
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http://dx.doi.org/10.1038/s41598-021-81535-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822958PMC
January 2021

Robust intra-individual estimation of structural connectivity by Principal Component Analysis.

Neuroimage 2021 02 1;226:117483. Epub 2020 Dec 1.

Department of Stereotaxy and Functional Neurosurgery, Medical Center, University of Freiburg, Germany; Medical Physics, Department of Radiology, Medical Center, University of Freiburg, Germany; Faculty of Medicine, University of Freiburg, Germany.

Fiber tractography based on diffusion-weighted MRI provides a non-invasive characterization of the structural connectivity of the human brain at the macroscopic level. Quantification of structural connectivity strength is challenging and mainly reduced to "streamline counting" methods. These are however highly dependent on the topology of the connectome and the particular specifications for seeding and filtering, which limits their intra-subject reproducibility across repeated measurements and, in consequence, also confines their validity. Here we propose a novel method for increasing the intra-subject reproducibility of quantitative estimates of structural connectivity strength. To this end, the connectome is described by a large matrix in positional-orientational space and reduced by Principal Component Analysis to obtain the main connectivity "modes". It was found that the proposed method is quite robust to structural variability of the data.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117483DOI Listing
February 2021

Deep brain stimulation for refractory obsessive-compulsive disorder (OCD): emerging or established therapy?

Mol Psychiatry 2021 01 3;26(1):60-65. Epub 2020 Nov 3.

Department of Neurosurgery, University Hospitals Leuven, KU Leuven, Leuven, Belgium.

A consensus has yet to emerge whether deep brain stimulation (DBS) for treatment-refractory obsessive-compulsive disorder (OCD) can be considered an established therapy. In 2014, the World Society for Stereotactic and Functional Neurosurgery (WSSFN) published consensus guidelines stating that a therapy becomes established when "at least two blinded randomized controlled clinical trials from two different groups of researchers are published, both reporting an acceptable risk-benefit ratio, at least comparable with other existing therapies. The clinical trials should be on the same brain area for the same psychiatric indication." The authors have now compiled the available evidence to make a clear statement on whether DBS for OCD is established therapy. Two blinded randomized controlled trials have been published, one with level I evidence (Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score improved 37% during stimulation on), the other with level II evidence (25% improvement). A clinical cohort study (N = 70) showed 40% Y-BOCS score improvement during DBS, and a prospective international multi-center study 42% improvement (N = 30). The WSSFN states that electrical stimulation for otherwise treatment refractory OCD using a multipolar electrode implanted in the ventral anterior capsule region (including bed nucleus of stria terminalis and nucleus accumbens) remains investigational. It represents an emerging, but not yet established therapy. A multidisciplinary team involving psychiatrists and neurosurgeons is a prerequisite for such therapy, and the future of surgical treatment of psychiatric patients remains in the realm of the psychiatrist.
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http://dx.doi.org/10.1038/s41380-020-00933-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815503PMC
January 2021

Navigated Deep Brain Stimulation Surgery: Evaluating the Combined Use of a Frame-Based Stereotactic System and a Navigation System.

Stereotact Funct Neurosurg 2021 19;99(1):48-54. Epub 2020 Oct 19.

Department of Stereotactic and Functional Neurosurgery, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany,

Deep brain stimulation (DBS) is a complex surgical procedure that requires detailed anatomical knowledge. In many fields of neurosurgery navigation systems are used to display anatomical structures during an operation to aid performing these surgeries. In frame-based DBS, the advantage of visualization has not yet been evaluated during the procedure itself. In this study, we added live visualization to a frame-based DBS system, using a standard navigation system and investigated its accuracy and potential use in DBS surgery. As a first step, a phantom study was conducted to investigate the accuracy of the navigation system in conjunction with a frame-based approach. As a second step, 5 DBS surgeries were performed with this combined approach. Afterwards, 3 neurosurgeons and 2 neurologists with different levels of experience evaluated the potential use of the system with a questionnaire. Moreover, the additional personnel, costs and required set up time were noted and compared to 5 consecutive standard procedures. In the phantom study, the navigation system showed an inaccuracy of 2.1 mm (mean SD 0.69 mm). In the questionnaire, a mean of 9.4/10 points was awarded for the use of the combined approach as a teaching tool, a mean of 8.4/10 for its advantage in creating a 3-dimensional (3-D) map and a mean of 8/10 points for facilitating group discussions. Especially neurosurgeons and neurologists in training found it useful to better interpret clinical results and side effects (mean 9/10 points) and neurosurgeons appreciated its use to better interpret microelectrode recordings (mean 9/10 points). A mean of 6/10 points was awarded when asked if the benefits were worth the additional efforts. Initially 2 persons, then one additional person was required to set up the system with no relevant added time or costs. Using a navigation system for live visualization during frame-based DBS surgery can improve the understanding of the complex 3-D anatomy and many aspects of the procedure itself. For now, we would regard it as an excellent teaching tool rather than a necessity to perform DBS surgeries.
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http://dx.doi.org/10.1159/000510528DOI Listing
October 2020

Neuromodulation in Psychiatric disorders: Experimental and Clinical evidence for reward and motivation network Deep Brain Stimulation: Focus on the medial forebrain bundle.

Eur J Neurosci 2021 Jan 30;53(1):89-113. Epub 2020 Sep 30.

Laboratory of Stereotaxy and Interventional Neurosciences, Department of Stereotactic and Functional Neurosurgery, University Hospital Freiburg, Freiburg, Germany.

Deep brain stimulation (DBS) in psychiatric illnesses has been clinically tested over the past 20 years. The clinical application of DBS to the superolateral branch of the medial forebrain bundle in treatment-resistant depressed patients-one of several targets under investigation-has shown to be promising in a number of uncontrolled open label trials. However, there are remain numerous questions that need to be investigated to understand and optimize the clinical use of DBS in depression, including, for example, the relationship between the symptoms, the biological substrates/projections and the stimulation itself. In the context of precision and customized medicine, the current paper focuses on clinical and experimental research of medial forebrain bundle DBS in depression or in animal models of depression, demonstrating how clinical and scientific progress can work in tandem to test the therapeutic value and investigate the mechanisms of this experimental treatment. As one of the hypotheses is that depression engenders changes in the reward and motivational networks, the review looks at how stimulation of the medial forebrain bundle impacts the dopaminergic system.
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http://dx.doi.org/10.1111/ejn.14975DOI Listing
January 2021

Identifying controllable cortical neural markers with machine learning for adaptive deep brain stimulation in Parkinson's disease.

Neuroimage Clin 2020 12;28:102376. Epub 2020 Aug 12.

Brain State Decoding Lab (BrainLinks-BrainTools) and Autonomous Intelligent Systems, Dept. of Computer Science at the University of Freiburg, Germany; Artificial Cognitive Systems Lab, Artificial Intelligence Dept., Donders Institute for Brain, Cognition and Behaviour, Faculty of Social Sciences, Radboud University, Nijmegen, The Netherlands. Electronic address:

The identification of oscillatory neural markers of Parkinson's disease (PD) can contribute not only to the understanding of functional mechanisms of the disorder, but may also serve in adaptive deep brain stimulation (DBS) systems. These systems seek online adaptation of stimulation parameters in closed-loop as a function of neural markers, aiming at improving treatment's efficacy and reducing side effects. Typically, the identification of PD neural markers is based on group-level studies. Due to the heterogeneity of symptoms across patients, however, such group-level neural markers, like the beta band power of the subthalamic nucleus, are not present in every patient or not informative about every patient's motor state. Instead, individual neural markers may be preferable for providing a personalized solution for the adaptation of stimulation parameters. Fortunately, data-driven bottom-up approaches based on machine learning may be utilized. These approaches have been developed and applied successfully in the field of brain-computer interfaces with the goal of providing individuals with means of communication and control. In our contribution, we present results obtained with a novel supervised data-driven identification of neural markers of hand motor performance based on a supervised machine learning model. Data of 16 experimental sessions obtained from seven PD patients undergoing DBS therapy show that the supervised patient-specific neural markers provide improved decoding accuracy of hand motor performance, compared to group-level neural markers reported in the literature. We observed that the individual markers are sensitive to DBS therapy and thus, may represent controllable variables in an adaptive DBS system.
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http://dx.doi.org/10.1016/j.nicl.2020.102376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479445PMC
August 2020

Neuroimaging and electrophysiology meet invasive neurostimulation for causal interrogations and modulations of brain states.

Neuroimage 2020 10 4;220:117144. Epub 2020 Jul 4.

Movement Disorders and Neurostimulation, Biomedical Statistics and Multimodal Signal Processing Unit, Department of Neurology, Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Germany. Electronic address:

Deep brain stimulation (DBS) has developed over the last twenty years into a highly effective evidenced-based treatment option for neuropsychiatric disorders. Moreover, it has become a fascinating tool to provide illustrative insights into the functioning of brain networks. New anatomical and pathophysiological models of DBS action have accelerated our understanding of neurological and psychiatric disorders and brain functioning. The description of the brain networks arose through the unique ability to illustrate long-range interactions between interconnected brain regions as derived from state-of-the-art neuroimaging (structural, diffusion, and functional MRI) and the opportunity to record local and large-scale brain activity at millisecond temporal resolution (microelectrode recordings, local field potential, electroencephalography, and magnetoencephalography). In the first part of this review, we describe how neuroimaging techniques have led to current understanding of DBS effects, by identifying and refining the DBS targets and illustrate the actual view on the relationships between electrode locations and clinical effects. One step further, we discuss how neuroimaging has shifted the view of localized DBS effects to a modulation of specific brain circuits, which has been possible from the combination of electrode location reconstructions with recently introduced network imaging methods. We highlight how these findings relate to clinical effects, thus postulating neuroimaging as a key factor to understand the mechanisms of DBS action on behavior and clinical effects. In the second part, we show how invasive electrophysiology techniques have been efficiently integrated into the DBS set-up to precisely localize the neuroanatomical targets of DBS based on distinct region-specific patterns of neural activity. Next, we show how multi-site electrophysiological recordings have granted a real-time window into the aberrant brain circuits within and beyond DBS targets to quantify and map the dynamic properties of rhythmic oscillations. We also discuss how DBS alters the transient synchrony states of oscillatory networks in temporal and spatial domains during resting, task-based and motion conditions, and how this modulation of brain states ultimately shapes the functional response. Finally, we show how a successful decoding and management of electrophysiological proxies (beta bursts, phase-amplitude coupling) of aberrant brain circuits was translated into adaptive DBS stimulation paradigms for a targeted and state-dependent invasive electrical neuromodulation.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117144DOI Listing
October 2020

Johann Bernhard Aloys von Gudden: The Unrecognized Role of the Psychiatrist and Neuroanatomist in Modern Stereotactic Neurosurgery.

Stereotact Funct Neurosurg 2020 11;98(1):65-69. Epub 2020 Feb 11.

Division of Interventional Biological Psychiatry, Department of Psychiatry, Freiburg University Medical Center and Medical Faculty of Freiburg University, Freiburg, Germany.

Bernhard von Gudden was the founder of the famous school of psychiatry and neuroanatomy in Munich, Germany. Beyond his association with the mysterious death of King Ludwig II of Bavaria, not much is known about Bernhard von Gudden's work in neuroanatomy. He pioneered fiber tract mapping by studying the effects of neurodegeneration following brain lesions. His ideas and work lay the foundation for subsequent fiber tract mapping strategies including the latest method using diffusion tensor magnetic resonance. This paper describes and acknowledges his contribution to the field, now collectively known as connectomics, and describes how it has become an essential tool in modern stereotactic neurosurgery.
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http://dx.doi.org/10.1159/000505704DOI Listing
February 2020

Medial forebrain bundle DBS differentially modulates dopamine release in the nucleus accumbens in a rodent model of depression.

Exp Neurol 2020 05 5;327:113224. Epub 2020 Feb 5.

BrainLinks-BrainTools Cluster of Excellence, University of Freiburg, Georges-Kohler-Allee 80, 79110 Freiburg, Germany; Laboratory for Stereotaxy and Interventional Neurosciences (SIN), Freiburg University, Department of Stereotactic and Functional Neurosurgery, University Medical Center Freiburg, Breisacher Strasse, 64 79106 Freiburg i.Br, Germany; Center for Basics in Neuromodulation, Freiburg University, Freiburg, Germany. Electronic address:

Background: Medial forebrain bundle (MFB) deep brain stimulation (DBS) has anti-depressant effects clinically and in depression models. Currently, therapeutic mechanisms of MFB DBS or how stimulation parameters acutely impact neurotransmitter release, particularly dopamine, are unknown. Experimentally, MFB DBS has been shown to evoke dopamine response in healthy controls, but not yet in a rodent model of depression.

Objective: The study investigated the impact of clinically used stimulation parameters on the dopamine induced response in a validated rodent depression model and in healthy controls.

Method: The stimulation-induced dopamine response in Flinders Sensitive Line (FSL, n = 6) rat model of depression was compared with Sprague Dawley (SD, n = 6) rats following MFB DSB, using Fast Scan Cyclic Voltammetry to assess the induced response in the nucleus accumbens. Stimulation parameters were 130 Hz ("clinically" relevant) with pulse widths between 100 and 350 μs.

Results: Linear mixed model analysis showed significant impact in both models following MFB DBS both at 130 and 60 Hz with 100 μs pulse width in inducing dopamine response. Furthermore, at 130 Hz the evoked dopamine responses were different across the groups at the different pulse widths.

Conclusion: The differential impact of MFB DBS on the induced dopamine response, including different response patterns at given pulse widths, is suggestive of physiological and anatomical divergence in the MFB in the pathological and healthy state. Studying how varying stimulation parameters affect the physiological outcome will promote a better understanding of the biological substrate of the disease and the possible anti-depressant mechanisms at play in clinical MFB DBS.
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http://dx.doi.org/10.1016/j.expneurol.2020.113224DOI Listing
May 2020

Deep Brain Stimulation of the Medial Forebrain Bundle in a Rodent Model of Depression: Exploring Dopaminergic Mechanisms with Raclopride and Micro-PET.

Stereotact Funct Neurosurg 2020 24;98(1):8-20. Epub 2020 Jan 24.

Department of Stereotactic and Functional Neurosurgery, University of Freiburg Medical Center, Freiburg, Germany,

Background: Deep brain stimulation (DBS) of the medial forebrain bundle (MFB) can reverse depressive-like symptoms clinically and in experimental models of depression, but the mechanisms of action are unknown.

Objectives: This study investigated the role of dopaminergic mechanisms in MFB stimulation-mediated behavior changes, in conjunction with raclopride administration and micropositron emission tomography (micro-PET).

Methods: Flinders Sensitive Line (FSL) rats were allocated into 4 groups: FSL (no treatment), FSL+ (DBS), FSL.R (FSL with raclopride), and FSL.R+ (FSL with raclopride and DBS). Animals were implanted with bilateral electrodes targeting the MFB and given 11 days access to raclopride in the drinking water with or without concurrent continuous bilateral DBS over the last 10 days. Behavioral testing was conducted after stimulation. A PET scan using [18F]desmethoxyfallypride was performed to determine D2 receptor availability before and after raclopride treatment. Changes in gene expression in the nucleus accumbens and the hippocampus were assessed using quantitative polymerase chain reaction.

Results: Micro-PET imaging showed that raclopride administration blocked 36% of the D2 receptor in the striatum, but the relative level of blockade was reduced/modulated by stimulation. Raclopride treatment enhanced depressive-like symptoms in several tasks, and the MFB DBS partially reversed the depressive-like phenotype. The raclopride-treated MFB DBS animals had increased levels of mRNA coding for dopamine receptor D1 and D2 suggestive of a stimulation-mediated increase in dopamine receptors.

Conclusion: Data suggest that chronic and continuous MFB DBS could act via the modulation of the midbrain dopaminergic transmission, including impacting on the postsynaptic dopamine receptor profile.
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http://dx.doi.org/10.1159/000504860DOI Listing
January 2020

Tractographic description of major subcortical projection pathways passing the anterior limb of the internal capsule. Corticopetal organization of networks relevant for psychiatric disorders.

Neuroimage Clin 2020 11;25:102165. Epub 2020 Jan 11.

Department of Stereotactic and Functional Neurosurgery, Freiburg University Medical Center and Medical Faculty of Freiburg University, Breisacher Strasse 64, Freiburg im Breisgau 79106, Germany.

Background: Major depression (MD) and obsessive-compulsive disorder (OCD) are psychiatric diseases with a huge impact on individual well-being. Despite optimal treatment regiments a subgroup of patients remains treatment resistant and stereotactic surgery (stereotactic lesion surgery, SLS or Deep Brain Stimulation, DBS) might be an option. Recent research has described four networks related to MD and OCD (affect, reward, cognitive control, default network) but only on a cortical and the adjacent sub-cortical level. Despite the enormous impact of comparative neuroanatomy, animal science and stereotactic approaches a holistic theory of subcortical and cortical network interactions is elusive. Because of the dominant hierarchical rank of the neocortex, corticofugal approaches have been used to identify connections in subcortical anatomy without anatomical priors and in part confusing results. We here propose a different corticopetal approach by identifying subcortical networks and search for neocortical convergences thereby following the principle of phylogenetic and ontogenetic network development.

Material And Methods: This work used a diffusion tensor imaging data from a normative cohort (Human Connectome Project, HCP; n = 200) to describe eight subcortical fiber projection pathways (PPs) from subthalamic nucleus (STN), substantia nigra (SNR), red nucleus (RN), ventral tegmental area (VTA), ventrolateral thalamus (VLT) and mediodorsal thalamus (MDT) in a normative space (MNI). Subcortical and cortical convergences were described including an assignment of the specific pathways to MD/OCD-related networks. Volumes of activated tissue for different stereotactic stimulation sites and procedures were simulated to understand the role of the distinct networks, with respect to symptoms and treatment of OCD and MD.

Results: The detailed course of eight subcortical PPs (stnPP, snrPP, rnPP, vlATR, vlATRc, mdATR, mdATRc, vtaPP/slMFB) were described together with their subcortical and cortical convergences. The anterior limb of the internal capsule can be subdivided with respect to network occurrences in ventral-dorsal and medio-lateral gradients. Simulation of stereotactic procedures for OCD and MD showed dominant involvement of mdATR/mdATRc (affect network) and vtaPP/slMFB (reward network).

Discussion: Corticofugal search strategies for the evaluation of stereotactic approaches without anatomical priors often lead to confusing results which do not allow for a clear assignment of a procedure to an involved network. According to our simulation of stereotactic procedures in the treatment of OCD and MD, most of the target regions directly involve the reward (and affect) networks, while side-effects can in part be explained with a co-modulation of the control network.

Conclusion: The here proposed corticopetal approach of a hierarchical description of 8 subcortical PPs with subcortical and cortical convergences represents a new systematics of networks found in all different evolutionary and distinct parts of the human brain.
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http://dx.doi.org/10.1016/j.nicl.2020.102165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965747PMC
January 2021

Impact of Stereotactic Ventriculocisternostomy on Delayed Cerebral Infarction and Outcome After Subarachnoid Hemorrhage.

Stroke 2020 02 4;51(2):431-439. Epub 2019 Dec 4.

Department of Stereotactic and Functional Neurosurgery (B.S., V.A.C., P.C.R.), University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Germany.

Background and Purpose- Delayed cerebral infarction (DCI) is an important cause of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). Stereotactic catheter ventriculocisternostomy (STX-VCS) and fibrinolytic/spasmolytic lavage is a new method for DCI prevention. Here, we assess the effects of implementing STX-VCS in an unselected aSAH patient population of a tertiary referral center. Methods- Retrospective cohort study of all consecutive aSAH patients admitted to a neurosurgical referral center during a 7-year period (April 2012 to April 2019). Midterm STX-VCS was introduced and offered to patients at high risk for DCI. We compared the incidence and burden of DCI, neurological outcome, and the use of induced hypertension and endovascular rescue therapy in this consecutive aSAH population 3.5 years before versus 3.5 years after STX-VCS became available. Results- Four hundred thirty-six consecutive patients were included: 222 BEFORE and 214 AFTER. Fifty-seven of 214 (27%) patients received STX-VCS. Stereotactic procedures resulted in one (2%) subdural hematoma. Favorable neurological outcome at 6 months occurred in 118 (53%) patients BEFORE and 139 (65%) patients AFTER (relative risk, 0.79 [95% CI, 0.66-0.95]). DCI occurred in 40 (18.0%) patients BEFORE and 17 (7.9%) patients AFTER (relative risk, 0.68 [95% CI, 0.57-0.86]), and total DCI volumes were 8933 (100%) and 3329 mL (36%), respectively. Induced hypertension was used in 97 (44%) and 30 (15%) patients, respectively (relative risk, 0.55 [95% CI, 0.46-0.65]). Thirty (13.5%) patients BEFORE versus 5 (2.3%) patients AFTER underwent endovascular rescue therapies (relative risk, 0.17 [95% CI, 0.07-0.42]). Conclusions- Selecting high-risk patients for STX-VCS reduced the DCI incidence, burden, and related mortality in a consecutive aSAH patient population. This was associated with an improved neurological outcome.
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http://dx.doi.org/10.1161/STROKEAHA.119.027424DOI Listing
February 2020

An Easy-to-Use and Fast Assessment of Patient-Specific DBS-Induced Changes in Hand Motor Control in Parkinson's Disease.

IEEE Trans Neural Syst Rehabil Eng 2019 10 16;27(10):2155-2163. Epub 2019 Sep 16.

For Parkinson's disease (PD), efficient and fast monitoring of fine motor function is fundamental for capturing transient phenomena induced by deep brain stimulation (DBS), thus, enabling a fast and accurate tuning of stimulation parameters. Tuning of DBS parameters is important for obtaining a patient-specific optimal clinical effect and to regularly compensate for disease progress. We propose a fine motor function assessment framework for capturing transient DBS-induced changes. The main goals are to obtain a fast, repeatable, objective, robust, and DBS-sensitive motor-score, in addition to a high-dimensional characterization of motor components by means of an interpretable data-driven model. To achieve this, we combine a hand motor-task, termed the copy-draw test, with a linear model for analyzing features extracted from the proposed task. The approach was tested with four patients totaling eight sessions analyzed. Our approach delivers a motor-score that is sensitive to DBS-induced changes in motor function. It can be applied repeatedly within seconds. The interpretability of the underlying machine learning model provides a direct overview of the feature relevance. This analysis allows to detect and characterize single movement components that are sensitive to DBS. The proposed assessment framework is an useful tool to push forward the data-driven identification of PD-relevant neural markers. Consequent to this end, the source code of the paradigm is made publicly available.
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http://dx.doi.org/10.1109/TNSRE.2019.2941453DOI Listing
October 2019

Frontal white matter architecture predicts efficacy of deep brain stimulation in major depression.

Transl Psychiatry 2019 08 21;9(1):197. Epub 2019 Aug 21.

Department of Stereotactic and Functional Neurosurgery, Freiburg University Medical Center, Freiburg, Germany.

Major depression is a frequent and severe disorder, with a combination of psycho- and pharmacotherapy most patients can be treated. However, ~20% of all patients suffering from major depressive disorder remain treatment resistant; a subgroup might be treated with deep brain stimulation (DBS). We present two trials of DBS to the superolateral medial forebrain bundle (slMFB DBS; FORESEE I and II). The goal was to identify informed features that allow to predict treatment response. Data from N = 24 patients were analyzed. Preoperative imaging including anatomical sequences (T1 and T2) and diffusion tensor imaging (DTI) magnetic resonance imaging sequences were used together with postoperative helical CT scans (for DBS electrode position). Pathway activation modeling (PAM) as well as preoperative structural imaging and morphometry was used to understand the response behavior of patients (MADRS). A left fronto-polar and partly orbitofrontal region was identified that showed increased volume in preoperative anatomical scans. Further statistical analysis shows that the volume of this "HUB-region" is predictive for later MADRS response from DBS. The HUB region connects to typical fiber pathways that have been addressed before in therapeutic DBS in major depression. Left frontal volume growth might indicate intrinsic activity upon disconnection form the main emotional network. The results are significant since for the first time we found an informed feature that might allow to identify and phenotype future responders for slMFB DBS. This is a clear step into the direction of personalized treatments.
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http://dx.doi.org/10.1038/s41398-019-0540-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6704187PMC
August 2019

Enhanced mGlu5 Signaling in Excitatory Neurons Promotes Rapid Antidepressant Effects via AMPA Receptor Activation.

Neuron 2019 10 13;104(2):338-352.e7. Epub 2019 Aug 13.

Department of Stereotactic and Functional Neurosurgery, Medical Center - University Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Str. 64, 79106 Freiburg, Germany; Department for Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hauptstrasse 5, 79104 Freiburg, Germany. Electronic address:

Conventional antidepressants have limited efficacy and many side effects, highlighting the need for fast-acting and specific medications. Induction of the synaptic protein Homer1a mediates the effects of different antidepressant treatments, including the rapid action of ketamine and sleep deprivation (SD). We show here that mimicking Homer1a upregulation via intravenous injection of cell-membrane-permeable TAT-Homer1a elicits rapid antidepressant effects in various tests. Similar to ketamine and SD, in vitro and in vivo application of TAT-Homer1a enhances mGlu5 signaling, resulting in increased mTOR pathway phosphorylation, and upregulates synaptic AMPA receptor expression and activity. The antidepressant action of SD and Homer1a induction depends on mGlu5 activation specifically in excitatory CaMK2a neurons and requires enhanced AMPA receptor activity, translation, and trafficking. Moreover, our data demonstrate a pronounced therapeutic potential of different TAT-fused peptides that directly modulate mGlu5 and AMPA receptor activity and thus might provide a novel strategy for rapid and effective antidepressant treatment.
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http://dx.doi.org/10.1016/j.neuron.2019.07.011DOI Listing
October 2019

Hippocampal theta phases organize the reactivation of large-scale electrophysiological representations during goal-directed navigation.

Sci Adv 2019 07 3;5(7):eaav8192. Epub 2019 Jul 3.

Department of Neuropsychology, Institute of Cognitive Neuroscience, Faculty of Psychology, Ruhr University Bochum, Bochum, Germany.

Humans are adept in simultaneously following multiple goals, but the neural mechanisms for maintaining specific goals and distinguishing them from other goals are incompletely understood. For short time scales, working memory studies suggest that multiple mental contents are maintained by theta-coupled reactivation, but evidence for similar mechanisms during complex behaviors such as goal-directed navigation is scarce. We examined intracranial electroencephalography recordings of epilepsy patients performing an object-location memory task in a virtual environment. We report that large-scale electrophysiological representations of objects that cue for specific goal locations are dynamically reactivated during goal-directed navigation. Reactivation of different cue representations occurred at stimulus-specific hippocampal theta phases. Locking to more distinct theta phases predicted better memory performance, identifying hippocampal theta phase coding as a mechanism for separating competing goals. Our findings suggest shared neural mechanisms between working memory and goal-directed navigation and provide new insights into the functions of the hippocampal theta rhythm.
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http://dx.doi.org/10.1126/sciadv.aav8192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609163PMC
July 2019

Machine learning-aided personalized DTI tractographic planning for deep brain stimulation of the superolateral medial forebrain bundle using HAMLET.

Acta Neurochir (Wien) 2019 08 30;161(8):1559-1569. Epub 2019 May 30.

Department of Stereotactic and Functional Neurosurgery, Neurocenter - University Medical Center, Breisacher Straße 64, 79106, Freiburg i.Br., Germany.

Background: Growing interest exists for superolateral medial forebrain bundle (slMFB) deep brain stimulation (DBS) in psychiatric disorders. The surgical approach warrants tractographic rendition. Commercial stereotactic planning systems use deterministic tractography which suffers from inherent limitations, is dependent on manual interaction (ROI definition), and has to be regarded as subjective. We aimed to develop an objective but patient-specific tracking of the slMFB which at the same time allows the use of a commercial surgical planning system in the context of deep brain stimulation.

Methods: The HAMLET (Hierarchical Harmonic Filters for Learning Tracts from Diffusion MRI) machine learning approach was introduced into the standardized workflow of slMFB DBS tractographic planning on the basis of patient-specific dMRI. Rendition of the slMFB with HAMLET serves as an objective comparison for the refinement of the deterministic tracking procedure. Our application focuses on the tractographic planning of DBS (N = 8) for major depression and OCD.

Results: Previous results have shown that only fibers belonging to the ventral tegmental area to prefrontal/orbitofrontal axis should be targeted. With the proposed technique, the deterministic tracking approach, that serves as the surgical planning data, can be refined, over-sprouting fibers are eliminated, bundle thickness is reduced in the target region, and thereby probably a more accurate targeting is facilitated. The HAMLET-driven method is meant to achieve a more objective surgical fiber display of the slMFB with deterministic tractography.

Conclusions: The approach allows overlying the results of patient-specific planning from two different approaches (manual deterministic and machine learning HAMLET). HAMLET shows the slMFB as a volume and thus serves as an objective tracking corridor. It helps to refine results from deterministic tracking in the surgical workspace without interfering with any part of the standard software solution. We have now included this workflow in our daily clinical experimental work on slMFB DBS for psychiatric indications.
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http://dx.doi.org/10.1007/s00701-019-03947-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616222PMC
August 2019

Simultaneous Frame-assisted Stereotactic Placement of Subdural Grid Electrodes and Intracerebral Depth Electrodes.

J Neurol Surg A Cent Eur Neurosurg 2019 Sep 13;80(5):353-358. Epub 2019 May 13.

Medical Faculty, Freiburg University, Freiburg, Germany.

Background And Study Aims:  In complex cases of drug-resistant focal epilepsy, the precise localization of the epileptogenic zone requires simultaneous implantation of depth and subdural grid electrodes. This study describes a new simple frame-assisted method that facilitates the simultaneous placement of both types of intracranial electrodes.

Material And Methods:  Ten consecutive patients were evaluated and divided into two groups. Group A included patients with simultaneous frame-assisted placement of depth and subdural grid electrodes. In group B, depth electrodes were implanted stereotactically; grid electrodes were implanted in a separate surgery.

Results:  The placement of the subdural grid was accurate as individually designed by the epileptologists in all five patients from group A. In group B, one patient showed a slight and another one a significant deviation of the subdural grid position postoperatively. The mean surgical time in group A was shorter (280±62 minutes) compared with the mean duration of the surgical procedures in group B (336±51 minutes).

Conclusion:  The frame-assisted placement of subdural grid electrodes facilitates the surgical procedure for invasive video-electroencephalography monitoring in complex cases of drug-resistant focal epilepsy in which a combination of depth electrodes and subdural grid electrodes is needed, by reducing the surgical time and guaranteeing highly accurate electrode localizations.
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http://dx.doi.org/10.1055/s-0039-1685193DOI Listing
September 2019

Superolateral medial forebrain bundle deep brain stimulation in major depression: a gateway trial.

Neuropsychopharmacology 2019 06 13;44(7):1224-1232. Epub 2019 Mar 13.

Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Short- and long-term antidepressant effects of deep brain stimulation (DBS) in treatment-resistant depression (TRD) have been demonstrated for several brain targets in open-label studies. For two stimulation targets, pivotal randomized trials have been conducted; both failed a futility analysis. We assessed efficacy and safety of DBS of the supero-lateral branch of the medial forebrain bundle (slMFB) in a small Phase I clinical study with a randomized-controlled onset of stimulation in order to obtain data for the planning of a large RCT. Sixteen patients suffering from TRD received DBS of the slMFB and were randomized to sham or real stimulation for the duration of 2 months after implantation. Primary outcome measure was mean reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) during 12 months of DBS (timeline analysis). Secondary outcomes were the difference in several clinical measures between sham and real stimulation at 8 weeks and during stimulation phases. MADRS ratings decreased significantly from 29.6 (SD +/- 4) at baseline to 12.9 (SD +/- 9) during 12 months of DBS (mean MADRS, n = 16). All patients reached the response criterion, most patients (n = 10) responded within a week; 50% of patients were classified as remitters after 1 year of stimulation. The most frequent side effect was transient strabismus. Both groups (active/sham) demonstrated an antidepressant micro-lesioning effect but patients had an additional antidepressant effect after initiation of stimulation. Both rapid onset and stability of the antidepressant effects of slMFB-DBS were demonstrated as in our previous pilot study. Given recent experiences from pivotal trials in DBS for MDD, we believe that slow, careful, and adaptive study development is germane. After our exploratory study and a large-scale study, we conducted this gateway trial in order to better inform planning of the latter. Important aspects for the planning of RCTs in the field of DBS for severe and chronic diseases are discussed including meaningful phases of intra-individual and between-group comparisons and timeline instead of single endpoint analyses.
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http://dx.doi.org/10.1038/s41386-019-0369-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785007PMC
June 2019

Automatic Segmentation of the Subthalamic Nucleus: A Viable Option to Support Planning and Visualization of Patient-Specific Targeting in Deep Brain Stimulation.

Oper Neurosurg (Hagerstown) 2019 11;17(5):497-502

Department of Stereotactic and Functional Neurosurgery, University of Freiburg, Freiburg, Germany.

Background: Automatic segmentation is gaining relevancy in image-based targeting of neural structures.

Objective: To evaluate its feasibility, we retrospectively analyzed the concordance of magnetic resonance imaging (MRI)-based automatic segmentation of the subthalamic nucleus (STN) and intraoperative microelectrode recordings (MERs).

Methods: Electrodes (n = 60) for deep brain stimulation were implanted in the STN of patients (n = 30; median age 57 yr) with Parkinson disease (n = 29) or rapid-onset dystonia parkinsonism (n = 1). Elements (Brainlab, Munich, Germany) were used to segment the STN, using 2 volumetric T1 (±contrast) and volumetric T2 images as input. The stereotactic computed tomography was coregistered with the imaging, and the original stereotactic coordinates were imported. MERs (0.5-1 mm steps) along the anterior, central, and lateral trajectories were used to determine differences between the image-segmented STN boundary and MER-based STN entry and exit.

Results: Of 175 trajectories, 105 penetrated or touched (≤0.7 mm) the STN. The overall median deviation between the segmented STN boundary and electrophysiological recordings was 1.1 mm for MER-based STN entry and 2.0 mm for STN exit. Regarding the entry point of the STN, there was no statistically significant difference between MRI-based automatic segmentation and the electrophysiological trajectories analyzed with intraoperative MER. The exit point was significantly different between both methods in the central and lateral trajectories.

Conclusion: MRI-based automatic segmentation of the STN is a viable, patient-specific targeting approach that can be used alongside traditional targeting methods in deep brain stimulation to support preoperative planning and visualization of target structures and aid postoperative optimization of programming.
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http://dx.doi.org/10.1093/ons/opz015DOI Listing
November 2019

Atypical Presentation of Rapid-onset Dystonia-parkinsonism (DYT12) Unresponsive to Deep Brain Stimulation of the Subthalamic Nucleus.

Mov Disord Clin Pract 2018 Jul-Aug;5(4):427-429. Epub 2018 Apr 1.

Department of Neurology and Neuroscience, Medical Center - University of Freiburg, Medical Faculty University of Freiburg, Breisacher Straße 64 D-79106, Freiburg Germany.

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http://dx.doi.org/10.1002/mdc3.12605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6336285PMC
April 2018

A novel rescue therapy for cerebral vasospasm: Cisternal Nimodipine application via stereotactic catheter ventriculocisternostomy.

J Clin Neurosci 2019 May 5;63:244-248. Epub 2019 Feb 5.

Department of Stereotactic and Functional Neurosurgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Str. 64, 79106 Freiburg, Germany.

Delayed Cerebral Infarction (DCI) due to Cerebral Vasospasm (CVS) is an important contributor to poor outcome after aneurysmal subarachnoid haemorrhage (aSAH). Despite established risk factors CVS and DCI are unpredictable at the individual patient level. Efficient treatments are lacking. We report a novel rescue therapy for DCI: Access to the basal cisterns by stereotactic catheter ventriculocisternostomy (STX-VCS) and direct cisternal application of the spasmolytic agent Nimodipine. On the basis of individual treatment decisions three aSAH patients who developed CVS underwent STX-VCS. Continuous lavage with Nimodipine was performed. CVS was assessed by daily transcranial doppler ultrasonography. Neurological outcome at 3 months was assessed by modified Rankin scale. STX-VCS was performed without complications in all patients. CVS rapidly resolved upon cisternal application of Nimodipine. CVS recurred in two patients upon interruption of Nimodpine application and resolved upon restart of Nimodipine. DCI did not occur in all three cases. STX-VCS and cisternal Nimodipine application is a novel rescue therapy for CVS treatment and DCI-prevention in patients with aSAH.
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http://dx.doi.org/10.1016/j.jocn.2019.01.039DOI Listing
May 2019

Integrity Assessment of a Hybrid DBS Probe that Enables Neurotransmitter Detection Simultaneously to Electrical Stimulation and Recording.

Micromachines (Basel) 2018 Oct 10;9(10). Epub 2018 Oct 10.

Laboratory for Biomedical Microtechnology, Department of Microsystems Engineering (IMTEK), University of Freiburg, Georges-Kohler-Allee 102, 79110 Freiburg, Germany.

Deep brain stimulation (DBS) is a successful medical therapy for many treatment resistant neuropsychiatric disorders such as movement disorders; e.g., Parkinson's disease, Tremor, and dystonia. Moreover, DBS is becoming more and more appealing for a rapidly growing number of patients with other neuropsychiatric diseases such as depression and obsessive compulsive disorder. In spite of the promising outcomes, the current clinical hardware used in DBS does not match the technological standards of other medical applications and as a result could possibly lead to side effects such as high energy consumption and others. By implementing more advanced DBS devices, in fact, many of these limitations could be overcome. For example, a higher channels count and smaller electrode sites could allow more focal and tailored stimulation. In addition, new materials, like carbon for example, could be incorporated into the probes to enable adaptive stimulation protocols by biosensing neurotransmitters in the brain. Updating the current clinical DBS technology adequately requires combining the most recent technological advances in the field of neural engineering. Here, a novel hybrid multimodal DBS probe with glassy carbon microelectrodes on a polyimide thin-film device assembled on a silicon rubber tubing is introduced. The glassy carbon interface enables neurotransmitter detection using fast scan cyclic voltammetry and electrophysiological recordings while simultaneously performing electrical stimulation. Additionally, the presented DBS technology shows no imaging artefacts in magnetic resonance imaging. Thus, we present a promising new tool that might lead to a better fundamental understanding of the underlying mechanism of DBS while simultaneously paving our way towards better treatments.
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http://dx.doi.org/10.3390/mi9100510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215126PMC
October 2018

Discontinuation of Superolateral Medial Forebrain Bundle Deep Brain Stimulation for Treatment-Resistant Depression Leads to Critical Relapse.

Biol Psychiatry 2019 03 22;85(6):e23-e24. Epub 2018 Sep 22.

Division of Interventional Biological Psychiatry, Department of Psychiatry and Psychotherapy, Freiburg University Medical Center, Freiburg, Germany; Department of Psychiatry and Mental Health, Johns Hopkins University, Baltimore, Maryland. Electronic address:

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http://dx.doi.org/10.1016/j.biopsych.2018.07.025DOI Listing
March 2019

Tractography-assisted deep brain stimulation of the superolateral branch of the medial forebrain bundle (slMFB DBS) in major depression.

Neuroimage Clin 2018 14;20:580-593. Epub 2018 Aug 14.

Department of Stereotactic and Functional Neurosurgery, Freiburg University Medical Center, Germany; Medical Faculty, Freiburg University, Freiburg, Germany; Philips GmbH DACH, Hamburg, Germany.

Background: Deep brain stimulation (DBS) of the superolateral branch of the medial forebrain bundle (slMFB) emerges as a - yet experimental - treatment for major depressive disorder (MDD) and other treatment refractory psychiatric diseases. First experiences have been reported from two open label pilot trials in major depression (MDD) and long-term effectiveness for MDD (50 months) has been reported.

Objective: To give a detailed description of the surgical technique for DBS of the superolateral branch of the medial forebrain bundle (slMFB) in MDD.

Methods: Surgical experience from bilateral implantation procedures in  = 24 patients with MDD is reported. The detailed procedure of tractography-assisted targeting together with detailed electrophysiology in 144 trajectories in the target region (recording and stimulation) is described. Achieved electrode positions were evaluated based on postoperative helical CT and fused to preoperative high resolution anatomical magnetic resonance imaging (MRI; Philips Medical Systems, Best, Netherlands), including the pre-operative diffusion tensor imaging (DTI) tractographic information (StealthViz DTI, Medtronic, USA; Framelink 5.0, Medtronic, USA). Midcommissural point (MCP) coordinates of effective contact (EC) location, together with angles of entry into the target region were evaluated. To investigate incidental stimulation of surrounding nuclei (subthalamic nucleus, STN; substantia nigra, SNr; and red nucleus, RN) as a possible mechanism, a therapeutic triangle (TT) was defined, located between these structures (based on MRI criteria in T2) and evaluated with respect to EC locations.

Results: Bilateral slMFB DBS was performed in all patients. We identified an electrophysiological environment (defined by autonomic reaction, passive microelectrode recording, acute effects and oculomotor effects) that helps to identify the proper target site on the operation table. Postoperative MCP-evaluation of effective contacts (EC) shows a significant variability with respect to localization. Evaluation of the TT shows that responders will typically have their active contacts inside the triangle and that surrounding nuclei (STN, SNr, RN) are not directly hit by EC, indicating a predominant white matter stimulation. The individual EC position within the triangle cannot be predicted and is based on individual slMFB (tractography) geometry. There was one intracranial bleeding (FORESEE I study) during a first implantation attempt in a patient who later received full bilateral implantation. Typical oculomotor side effects are idiosyncratic for the target region and at inferior contacts.

Conclusion: The detailed surgical procedure of slMFB DBS implantation has not been described before. The slMFB emerges as an interesting region for the treatment of major depression (and other psychiatric diseases) with DBS. So far it has only been successfully researched in open label clinical case series and in 15 patients published. Stimulation probably achieves its effect through direct white-matter modulation of slMFB fibers. The surgical implantation comprises a standardized protocol combining tractographic imaging based on DTI, targeting and electrophysiological evaluation of the target region. To this end, slMFB DBS surgery is in technical aspects comparable to typical movement disorder surgery. In our view, slMFB DBS should only be performed under tractographic assistance.
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http://dx.doi.org/10.1016/j.nicl.2018.08.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120598PMC
January 2019

Combination of CT angiography and MRI in surgical planning of deep brain stimulation.

Neuroradiology 2018 Nov 22;60(11):1151-1158. Epub 2018 Aug 22.

Department of Stereotactic and Functional Neurosurgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Purpose: For safe deep brain stimulation (DBS) planning, an accurate visualization and localization of vessels is mandatory. Contrast enhanced (ce) MRI depicts both arteries and veins. Computed tomography angiography (CTA) detects arteries with high geometric accuracy. We routinely combine both modalities for DBS planning.

Methods: A total of 222 trajectories in a consecutive series of 113 patients who underwent DBS operations were included. In all trajectories, the number of veins and arteries in a 10-mm diameter around the planned trajectory were counted in a ceMRI and a CTA. If a vessel was visible in both modalities, the distance was measured.

Results: A total of 370 vessels were counted. Two hundred forty vessels (65%) were visible in both modalities. With 134 of the vessels, we detected a difference of the vessel's location with an average distance of 1.24 mm (SD 0.58). Eighty vessels (22%) were visible only in the ceMRI, 50 vessels (13%) only in the CTA. We had four bleedings (1.8% per lead) of which one was symptomatic (0.45%).

Conclusion: The majority of vessels were visible in both modalities; however, in more than half of these cases, the location was not identical. Here, the location in the CTA can be regarded as the ground truth. Moreover, both the CTA and the ceMRI depicted vessels not seen in the other imaging modality. We therefore assume that the combination of both imaging modalities for DBS planning increases the chance to detect vascular conflicts along the trajectory, thus reducing the risk of intracranial bleeding.
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http://dx.doi.org/10.1007/s00234-018-2079-0DOI Listing
November 2018

Development of a Standardized Cranial Phantom for Training and Optimization of Functional Stereotactic Operations.

Stereotact Funct Neurosurg 2018 13;96(3):190-196. Epub 2018 Jun 13.

Department of Stereotactic and Functional Neurosurgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Background: In recent years, simulations based on phantom models have become increasingly popular in the medical field. In the field of functional and stereotactic neurosurgery, a cranial phantom would be useful to train operative techniques, such as stereo-electroencephalography (SEEG), to establish new methods as well as to develop and modify radiological techniques. In this study, we describe the construction of a cranial phantom and show examples for it in stereotactic and functional neurosurgery and its applicability with different radiological modalities.

Methods: We prepared a plaster skull filled with agar. A complete operation for deep brain stimulation (DBS) was simulated using directional leads. Moreover, a complete SEEG operation including planning, implantation of the electrodes, and intraoperative and postoperative imaging was simulated.

Results: An optimally customized cranial phantom is filled with 10% agar. At 7°C, it can be stored for approximately 4 months. A DBS and an SEEG procedure could be realistically simulated. Lead artifacts can be studied in CT, X-ray, rotational fluoroscopy, and MRI.

Conclusions: This cranial phantom is a simple and effective model to simulate functional and stereotactic neurosurgical operations. This might be useful for teaching and training of neurosurgeons, establishing operations in a new center and for optimization of radiological examinations.
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http://dx.doi.org/10.1159/000489581DOI Listing
April 2019