Volker A. Coenen

Three-dimensional visualization of the pyramidal tract in a neuronavigation system during brain tumor surgery: first experiences and technical note.

OBJECTIVETo integrate spatial three-dimensional information concerning the pyramidal tracts into a customized system for frameless neuronavigation during brain tumor surgery. METHODSFour consecutive patients with intracranial tumors in eloquent areas underwent diffusion-weighted and anatomic magnetic resonance imaging studies within 48 hours before surgery. Diffusion-weighted datasets were merged with anatomic data for navigation purposes. The pyramidal tracts were segmented and reconstructed for three-dimensional visualization. The reconstruction results, together with the fused-image dataset, were available during surgery in the environment of a customized neuronavigation system. RESULTSIn all four patients, the combination of reconstructed data and fused images was a helpful additional source of information concerning the tumor seat and topographical interaction with the pyramidal tract. In two patients, intraoperative motor cortex stimulation verified the tumor seat with regard to the precentral gyrus. CONCLUSIONDiffusion-weighted magnetic resonance imaging allows individual estimation of large fiber tracts applicable as important information in intraoperative neuronavigation and in planning brain tumor resection. A three-dimensional representation of fibers associated with the pyramidal tract during brain tumor surgery is feasible with the presented technique and is a helpful adjunct for the neurosurgeon. The main drawbacks include the length of time required for the segmentation procedure, the lack of direct intraoperative control of the pyramidal tract position, and brain shift. However, mapping of large fiber tracts and its intraoperative use for neuronavigation have the potential to increase the safety of neurosurgical procedures and to reduce surgical morbidity.

Human Medial Forebrain Bundle (MFB) and Anterior Thalamic Radiation (ATR): Imaging of Two Major Subcortical Pathways and the Dynamic Balance of Opposite Affects in Understanding Depression

The medial forebrain bundle (MFB), a key structure of reward-seeking circuitry, remains inadequately characterized in humans despite its vast importance for emotional processing and development of addictions and depression. Using Diffusion Tensor Imaging Fiber Tracking (DTI FT) the authors describe potential converging ascending and descending MFB and anterior thalamic radiation (ATR) that may mediate major brain reward-seeking and punishment functions. Authors highlight novel connectivity, such as supero-lateral-branch MFB and ATR convergence, caudally as well as rostrally, in the anterior limb of the internal capsule and medial prefrontal cortex. These anatomical convergences may sustain a dynamic equilibrium between positive and negative affective states in human mood-regulation and its various disorders, especially evident in addictions and depression.

Fiber tracking with distinct software tools results in a clear diversity in anatomical fiber tract portrayal.

BACKGROUND Fiber tract portrayal, based on diffusion tensor imaging (DTI), is becoming more and more important in functional neuronavigation. No standard exists to guarantee anatomically correct fiber tract depiction for neurosurgical purposes. Therefore, showing the anatomically correct extension of fiber tracts beyond the pure connection of functional areas remains an area of important research and investigation. Standards for fiber tracking software applications are elusive. The purpose of this study was to compare the performance of different fiber tracking software tools (FT-tools). We tested the software performance, comparability and anatomical accuracy of the tracking results of several programs. MATERIAL AND METHODS A single DTI dataset of a healthy control subject was submitted to four different fiber tracking software applications (two commercial, two freeware), three of them based on Fiber Assignment by Continuous Tracking, one based on the Tensorline Propagation Algorithm. The corticospinal tract (CST) was investigated. The tracking procedure was controlled by the following input variables: single regions of interest (ROIs): brain stem, or internal capsule, or subcortical white matter of the precentral gyrus; background threshold, fractional anisotropy (FA) threshold, maximum fiber angulation and fiber length. Tracking results were compared for 2-D correlated triplanar images (axial, coronal, sagittal) and in 3-D. For all FT-tools, the time used to generate the CST was measured. The inter-rater variability for tracking time and for the tracked CST volumes was recorded for two of the four FT-tools. RESULTS AND CONCLUSIONS Distinct FT-tools performed very differently with respect to the time required to achieve CST portrayal (track generation time varied between 16 and 50 min). None of the software applications was able to display the CST in its full anatomical extent. Especially the lateral precentral areas were not pictured. Surprisingly, the application of the four distinct FT-tools did not lead to comparable tracking results. As very similar or identical tracking algorithms were used, this difference cannot be easily explained. Clearly, neurosurgeons have to be cautious about applying fiber tracking results intraoperatively, especially when dealing with an abnormal or distorted fiber tract anatomy. The authors recommend the use of adjunct strategies such as intraoperative electrophysiology to enhance patient safety and improve anatomical accuracy when using tracking results for surgical procedures.

Deep Brain Stimulation of the Human Reward System for Major Depression—Rationale, Outcomes and Outlook

Deep brain stimulation (DBS) as a putative approach for treatment-resistant depression (TRD) has now been researched for about a decade. Several uncontrolled studies—all in relatively small patient populations and different target regions—have shown clinically relevant antidepressant effects in about half of the patients and very recently, DBS to a key structure of the reward system, the medial forebrain bundle, has yielded promising results within few days of stimulation and at much lower stimulation intensities. On the downside, DBS procedures in regions are associated with surgical risks (eg, hemorrhage) and psychiatric complications (suicidal attenuation, hypomania) as well as high costs. This overview summarizes research on the mechanisms of brain networks with respect to psychiatric diseases and—as a novelty—extrapolates to the role of the reward system in DBS for patients with treatment-resistant depression. It further evaluates relevant methodological aspects of today’s research in DBS for TRD. On the scientific side, the reward system has an important yet clearly under-recognized role in both neurobiology and treatment of depression. On the methodological side of DBS research in TRD, better animal models are clearly needed to explain clinical effects of DBS in TRD. Larger sample sizes, long-term follow-up and designs including blinded sham control are required to draw final conclusions on efficacy and side effects. Practical research issues cover study design, patient tracking, and the discussion of meaningful secondary outcome measures.

Sequential visualization of brain and fiber tract deformation during intracranial surgery with three-dimensional ultrasound: an approach to evaluate the effect of brain shift.

OBJECTIVE: We present a technique that allows intraoperative display of brain shift and its effects on fiber tracts. METHODS: Three patients had intracranial lesions (one malignant glioma, one metastasis, and one cavernoma) in contact with either the corticospinal or the geniculostriate tract that were removed microneurosurgically. Preoperatively, magnetic resonance diffusion-weighted imaging (DWI) was performed to visualize the fiber tract at risk. DWI data were fused with those obtained from anatomic T1-weighted magnetic resonance imaging. A single-rack three-dimensional ultrasound neuronavigation system, which simultaneously displays the MRI scan and the corresponding ultrasound image, was used intraoperatively for 1) navigation; 2) definition of fixed and potentially shifting ultrasound landmarks near the fiber tract; and 3) sequential image updating at different steps of resection. The result was time-dependent brain deformation data. With a standard personal computer equipped with standard image software, the brain shift-associated fiber tract deformation was assessed by use of sequential landmark registration. After surgery, DWI was performed to confirm the predicted fiber tract deformation. RESULTS: The lesions were removed without morbidity. Comparison of three-dimensional ultrasound with DWI and T1-weighted magnetic resonance imaging data allowed us to define fixed and potentially shifting landmarks close to the respective fiber tract. Postoperative DWI confirmed that the actual fiber tract position at the conclusion of surgery corresponded to the sonographically predicted fiber tract position. CONCLUSION: By definition and sequential intraoperative registration of ultrasound landmarks near the fiber tract, brain shift-associated deformation of a tract that is not visible sonographically can be assessed correctly. This approach seems to help identify and avoid eloquent brain areas during intracranial surgery.

Residual Tumor Volume as Best Outcome Predictor in Low Grade Glioma - A Nine-Years Near-Randomized Survey of Surgery vs. Biopsy.

Diffuse low grade gliomas (DLGG) are continuously progressive primary brain neoplasms that lead to neurological deficits and death. Treatment strategies are controversial. Randomized trials establishing the prognostic value of surgery do not exist. Here, we report the results of a nine-year near-randomized patient distribution between resection and biopsy. Until 2012, the Department of Neurosurgery and the Department of Stereotactic Neurosurgery at the University Medical Center Freiburg were organized as separate administrative units both coordinating DLGG patient treatment independently. All consecutive adult patients with a new diagnosis of DLGG by either stereotactic biopsy or resection were included. Pre- and post-operative tumor volumetry was performed. 126 patients, 87 men (69%), 39 women (31%), median age 41 years, were included. 77 (61%) were initially managed by biopsy, 49 (39%) by resection. A significant survival benefit was found for patients with an initial management by resection (5-year OS 82% vs. 54%). The survival benefit of patients with initial resection was reserved to patients with a residual tumor volume of less than 15 cm3. Maximum safe resection is the first therapy of choice in DLGG patients if a near-complete tumor removal can be achieved. Accurate prediction of the extent-of-resection is required for selection of surgical candidates.

Preoperative assessment of motor cortex and pyramidal tracts in central cavernoma employing functional and diffusion-weighted magnetic resonance imaging

BACKGROUND Functional MRI (fMRI) combines anatomic with functional information and has therefore been widely used for preoperative planning of patients with mass lesions affecting functionally important brain regions. However, the courses of functionally important fiber tracts are not visualized. We therefore propose to combine fMRI with diffusion-weighted MRI (DWI) that allows visualization of large fiber tracts and to implement this data in a neuronavigation system. METHODS DWI was successfully performed at a field strength of 1.5 Tesla, employing a spin-echo sequence with gradient sensitivity in six noncollinear directions to visualize the course of the pyramidal tracts, and was combined with echo-planar T2* fMRI during a hand motor task in a patient with central cavernoma. RESULTS Fusion of both data sets allowed visualization of the displacement of both the primary sensorimotor area (M1) and its large descending fiber tracts. Intraoperatively, these data were used to aid in neuronavigation. Confirmation was obtained by intraoperative electrical stimulation. Postoperative MRI revealed an undisrupted pyramidal tract in the neurologically intact patient. CONCLUSION The combination of fMRI with DWI allows for assessment of functionally important cortical areas and additional visualization of large fiber tracts. Information about the orientation of fiber tracts in normal appearing white matter in patients with tumors within the cortical motor system cannot be obtained by other functional or conventional imaging methods and is vital for reducing operative morbidity as the information about functional cortex. This technique might, therefore, have the prospect of guiding neurosurgical interventions, especially when linked to a neuronavigation system.

Affective neuroscience strategies for understanding and treating depression: From preclinical models to three novel therapeutics

Mammalian brains contain seven primary-process affective substrates for primal emotional feelings and behaviors. Scientific labels for these interactive systems are SEEKING, RAGE, FEAR, LUST, CARE, PANIC, and PLAY. Understanding these brain substrates could lead to new treatments of emotional disturbances that accompany mental illnesses. We summarize how understanding of such emotional affects—especially those of separation distress (PANIC, promoting excessive sadness and grief), SEEKING (promoting enthusiasm), and PLAY (promoting social joy)—may regulate depressive affect through a focus on the following: (a) reducing PANIC, namely, “psychic pain” with “safe opioids” such as buprenorphine; (b) facilitating enthusiasm with deep brain stimulation of the transdiencephalic medial forebrain bundle–based SEEKING urges; and (c) how studies of brain neurochemical pathways that facilitate social joy (PLAY) in animals have yielded novel neurochemical interventions (e.g., GLYX-13, a partial agonist of glycine receptors) currently in successful human testing. Affective neuroscience principles that have led to these advances are summarized.

Image-guided microneurosurgical management of small cerebral arteriovenous malformations: the value of navigated computed tomographic angiography.

In small arteriovenous malformations (AVM) with large hematomas, surgery remains the main therapeutic option. However, intraoperative identification of the AVM, feeders, and draining veins could be difficult in the environment of substantial intracerebral blood. In those selected cases, we use navigated computed tomographic angiography (CTA) for the microneurosurgical management. It is our objective to report our initial experiences. Prior to operation a conventional CTA with superficial skin fiducials placed on a patient’s head was acquired for diagnostic and neuronavigation purposes. Image data were transferred to a neuronavigation device with integrated volume rendering capacities which allows a three-dimensional reconstruction of the vascular tree and the AVM to be created. In all patients the AVM was removed successfully after having been localized with CTA-based neuronavigation. Navigated CTA is helpful for the operative management of small AVMs with large hematomas. The technique allows feeding arteries to be distinguished from draining veins thereby allowing the nidus of the AVM to be identified despite the presence of substantial intracerebral blood. CTA can be easily implemented into commercial neuronavigation systems.

On-demand deep brain stimulation for essential tremor: A report on four cases

Deep brain stimulation (DBS) is an established therapy for essential tremor (ET), but loss of efficacy due to tolerance can occur. Our objective was to evaluate if it is feasible to use DBS only on‐demand and if this would prevent tolerance. We report on the effects of left‐side thalamic DBS in 4 ET patients who were instructed to switch on stimulation only when using their right hand for motor tasks and were followed‐up to 30 months after surgery. The patients were capable of using DBS only on‐demand (DBS use of 22.0 ± 13.5%/day). DBS led to a stable suppression of right arm tremor throughout the follow‐up. No problems associated with tolerance such as tremor rebound or late therapy failure occurred. In comparison to publications stating that ET patients had been using DBS continuously during the daytime, the use of on‐demand DBS saves battery life, which delays surgical replacement of the stimulator. Thus, on‐demand DBS saves money, may help to prevent tolerance, and should be adopted for the long‐term treatment of ET patients.