Christian Doenitz

Magnetic Resonance Imaging Diffusion Tensor Tractography: Evaluation of Anatomic Accuracy of Different Fiber Tracking Software Packages

BACKGROUND Diffusion tensor imaging (DTI)-based tractography has become an integral part of preoperative diagnostic imaging in many neurosurgical centers, and other nonsurgical specialties depend increasingly on DTI tractography as a diagnostic tool. The aim of this study was to analyze the anatomic accuracy of visualized white matter fiber pathways using different, readily available DTI tractography software programs. METHODS Magnetic resonance imaging scans of the head of 20 healthy volunteers were acquired using a Siemens Symphony TIM 1.5T scanner and a 12-channel head array coil. The standard settings of the scans in this study were 12 diffusion directions and 5-mm slices. The fornices were chosen as an anatomic structure for the comparative fiber tracking. Identical data sets were loaded into nine different fiber tracking packages that used different algorithms. The nine software packages and algorithms used were NeuroQLab (modified tensor deflection [TEND] algorithm), Sörensen DTI task card (modified streamline tracking technique algorithm), Siemens DTI module (modified fourth-order Runge-Kutta algorithm), six different software packages from Trackvis (interpolated streamline algorithm, modified FACT algorithm, second-order Runge-Kutta algorithm, Q-ball [FACT algorithm], tensorline algorithm, Q-ball [second-order Runge-Kutta algorithm]), DTI Query (modified streamline tracking technique algorithm), Medinria (modified TEND algorithm), Brainvoyager (modified TEND algorithm), DTI Studio modified FACT algorithm, and the BrainLab DTI module based on the modified Runge-Kutta algorithm. Three examiners (a neuroradiologist, a magnetic resonance imaging physicist, and a neurosurgeon) served as examiners. They were double-blinded with respect to the test subject and the fiber tracking software used in the presented images. Each examiner evaluated 301 images. The examiners were instructed to evaluate screenshots from the different programs based on two main criteria: (i) anatomic accuracy of the course of the displayed fibers and (ii) number of fibers displayed outside the anatomic boundaries. RESULTS The mean overall grade for anatomic accuracy was 2.2 (range, 1.1-3.6) with a standard deviation (SD) of 0.9. The mean overall grade for incorrectly displayed fibers was 2.5 (range, 1.6-3.5) with a SD of 0.6. The mean grade of the overall program ranking was 2.3 with a SD of 0.6. The overall mean grade of the program ranked number one (NeuroQLab) was 1.7 (range, 1.5-2.8). The mean overall grade of the program ranked last (BrainLab iPlan Cranial 2.6 DTI Module) was 3.3 (range, 1.7-4). The difference between the mean grades of these two programs was statistically highly significant (P < 0.0001). There was no statistically significant difference between the programs ranked 1-3: NeuroQLab, Sörensen DTI Task Card, and Siemens DTI module. CONCLUSIONS The results of this study show that there is a statistically significant difference in the anatomic accuracy of the tested DTI fiber tracking programs. Although incorrectly displayed fibers could lead to wrong conclusions in the neurosciences field, which relies heavily on this noninvasive imaging technique, incorrectly displayed fibers in neurosurgery could lead to surgical decisions potentially harmful for the patient if used without intraoperative cortical stimulation. DTI fiber tracking presents a valuable noninvasive preoperative imaging tool, which requires further validation after important standardization of the acquisition and processing techniques currently available.

A mechanism for the rapid development of intracranial aneurysms: a case study.

BACKGROUND:Despite technical and diagnostic progress there are still open questions in the understanding of the pathophysiology of intracranial aneurysms. OBJECTIVE:Within 44 days we observed the de novo genesis and rupture of an aneurysm of the basilar artery in a patient. We performed computational fluid dynamics on 3-dimensional (3D) models of the inconspicuous vessel and the same vessel with aneurysm. Based on the simulations we propose a mechanism of genesis of fast-growing aneurysms. METHODS:Three-dimensional mesh models were built using computed tomography-angiography slices. Flow was modeled as a non-Newtonian blood model with shear-dependent dynamic viscosity. We investigated flow velocity, wall pressure, impingement point, wall shear stress (WSS), and asymmetric flows in 3D models of the vessel tree of the basilar artery. RESULTS:Impingement point and wall pressure had no clear relation to the origin of the aneurysm. The impingement point faded away during aneurysm growth. Instead we found an area of permanently low WSS in the original basilar artery. This location corresponded to the origin of the later developing aneurysm. Aneurysm growth was facilitated by an increasing overall expansion of the basilar tip and a constant decrease of WSS. CONCLUSION:Assuming a preexisting reduced resistibility of the vessel wall to pressure changes and an area of permanently low WSS, an increase in pressure induces geometrical changes. These cause changes of intravascular flow distribution, lowering the already low WSS in specific locations. This leads to endothelial damage in this area and to a decreasing stability of the vessel wall, causing aneurysm development, growth, and rupture.

Effects of spinal cord stimulation on cortical excitability in patients with chronic neuropathic pain: A pilot study

Background: Despite a broad clinical use, the mechanism of action of SCS is poorly understood. Current information suggests that the effects of SCS are mediated by a complex set of interactions at several levels of the nervous system including spinal and supraspinal mechanisms.

Recurrent subarachnoid hemorrhage caused by a de novo basilar tip aneurysm developing within 8 weeks after clipping of a ruptured anterior communicating artery aneurysm: Case report - Commentary

OBJECTIVEWell-documented case reports of the rapid formation and rupture of de novo aneurysms of the posterior circulation are rare. CLINICAL PRESENTATIONWe report a patient with subarachnoid hemorrhage caused by an aneurysm of the anterior communicating artery that was clipped consecutively. Forty-four days after the initial subarachnoid hemorrhage, the patient experienced a second subarachnoid hemorrhage after the rupture of a newly grown aneurysm of the basilar tip. Between the two hemorrhages, transcranial Doppler sonography and neuroimaging revealed a fulminant generalized vasospasm. INTERVENTIONTo our knowledge, this is the first report of the rapid development and rupture of a de novo aneurysm of the posterior circulation after the rupture of an initial aneurysm of the anterior circulation. CONCLUSIONWe review the pertinent literature and discuss possible reasons for the development and rupture of this second aneurysm.OBJECTIVE: Well-documented case reports of the rapid formation and rupture of de novo aneurysms of the posterior circulation are rare. CLINICAL PRESENTATION: We report a patient with subarachnoid hemorrhage caused by an aneurysm of the anterior communicating artery that was clipped consecutively. Forty-four days after the initial subarachnoid hemorrhage, the patient experienced a second subarachnoid hemorrhage after the rupture of a newly grown aneurysm of the basilar tip. Between the two hemorrhages, transcranial Doppler sonography and neuroimaging revealed a fulminant generalized vasospasm. INTERVENTION: To our knowledge, this is the first report of the rapid development and rupture of a de novo aneurysm of the posterior circulation after the rupture of an initial aneurysm of the anterior circulation. CONCLUSION: We review the pertinent literature and discuss possible reasons for the development and rupture of this second aneurysm.

The impact of sedation on brain mapping: a prospective, interdisciplinary, clinical trial.

BACKGROUND During awake craniotomies, patients may either be awake for the entire duration of the surgical intervention (awake-awake-awake craniotomy, AAA) or initially sedated (asleep-awake-asleep craniotomy, SAS). OBJECTIVE To examine whether prior sedation in SAS may restrict brain mapping, we conducted neuropsychological tests in patients by means of a standardized anesthetic regimen comparable to an SAS. METHODS We prospectively examined patients undergoing surgery either under total intravenous anesthesia (TIVA) or under regional anesthesia with slight sedation (RAS). The tests included the DO40 picture-naming test, the digit span, the Regensburg Word Fluency Test, and the finger-tapping test. Each test was conducted 3 times for every patient in the TIVA and RAS groups, once before surgery and twice within about 35 minutes after the end of sedation. Patients undergoing AAA were examined preoperatively and intraoperatively. RESULTS In the AAA group, no significant difference was found between preoperative and intraoperative test results. In the TIVA and RAS groups, postoperative tests showed worse results than preoperative tests. In most tests, patients improved from the first to the second postoperative test. CONCLUSION Cognitive and motor performance were significantly influenced by prior sedation in the TIVA and RAS groups, but not in the AAA group. Therefore, prior sedation may be assumed to cause a change in the baselines, which may compromise brain mapping and thus endanger a patients neurological outcome in the case of an SAS.

Relevance of correction for rotational targeting error in functional neurosurgery

Objective: A prospective study is presented on the amount of targeting error that is due to rotational deviations between the atlas and the stereotactic coordinate system. Materials and Methods: We investigated 14 volunteers with a stereotactic frame fixed to their heads by tight adhesive bands. Sagittal, coronal and axial T2-weighted MRI scans, as well as MPRage sequences, were performed. The anterior and posterior commissures and one additional point on the midline (the septum pellucidum) were determined on the axial T2-weighted images. Bilateral atlas coordinates for the subthalamic nucleus (STN), globus pallidus pars interna (GPi) and nucleus ventralis intermedius (Vim) were transformed to stereotactic frame coordinates, either without correction or by 2-point or 3-point correction. A total of 896 coordinates (x, y, z for the STN, GPi and Vim in both hemispheres) were calculated. Results: Although the mean differences between the two algorithms (0.24 ± standard deviation of 0.33 mm) were within the range of system-immanent inaccuracies in MRI-guided stereotaxy, deviations of up to 2.8 mm occurred. No significant correlation was found regarding the amount of rotational angle and the differences in x-, y-, or z-coordinates when 2-point and 3-point transformations were compared. Conclusions: The reliability of meticulous trajectory planning might be compromised significantly by using only 2-point-based correction or no calculations at all.

Evaluation of robot-guided minimally invasive implantation of 2067 pedicle screws

Objective Recent studies have investigated the role of spinal image guidance for pedicle screw placement. Many authors have observed an elevated placement accuracy and overall improvement of outcome measures. This study assessed a bi-institutional experience following introduction of the Renaissance miniature robot for spinal image guidance in Europe. Methods The medical records and radiographs of all patients who underwent robot-guided implantation of spinal instrumentation using the novel system (between October 2011 and March 2015 in Mainz and February 2014 and February 2016 in Regensburg) were reviewed to determine the efficacy and safety of the newly introduced robotic system. Screw position accuracy, complications, exposure durations to intraoperative radiation, and reoperation rate were assessed. Results Of the 413 surgeries that used robotic guidance, 406 were via a minimally invasive approach. In 7 cases the surgeon switched to conventional screw placement, using a midline approach, due to referencing problems. A total of 2067 screws were implanted using robotic guidance, and 1857 screws were evaluated by postoperative CT. Of the 1857 screws, 1799 (96.9%) were classified as having an acceptable or good position, whereas 38 screws (2%) showed deviations of 3-6 mm and 20 screws (1.1%) had deviations > 6 mm. Nine misplaced screws, implanted in 7 patients, required revision surgery, yielding a screw revision rate of 0.48% of the screws and 7 of 406 (1.7%) of the patients. The mean ± SD per-patient intraoperative fluoroscopy exposure was 114.4 (± 72.5) seconds for 5.1 screws on average and any further procedure required. Perioperative and direct postoperative complications included hemorrhage (2 patients, 0.49%) and wound infections necessitating surgical revision (20 patients, 4.9%). Conclusions The hexapod miniature robotic device proved to be a safe and robust instrument in all situations, including those in which patients were treated on an emergency basis. Placement accuracy was high; peri- and early postoperative complication rates were found to be lower than rates published in other series of percutaneous screw placement techniques. Intraoperative radiation exposure was found to be comparable to published values for other minimally invasive and conventional approaches.

The impact of white matter lesions on the cognitive outcome of subthalamic nucleus deep brain stimulation in Parkinson’s disease

OBJECTIVES White Matter lesions (WML) are a risk factor for cognitive impairment in Parkinsons disease. There is no clear evidence of reduced general cognitive function after DBS. However, a subgroup of patients develops dementia rapidly after DBS despite careful patient selection processes. The aim of this study was to evaluate the load of WML as a possible risk factor for cognitive decline following STN DBS. PATIENTS AND METHODS 40 PD-patients receiving bilateral STN-DBS were followed at least three years after surgery to detect dementia. All patients underwent comprehensive neuropsychological assessment and MRI before surgery. The extent of WML was assessed using an automated approach. WML volume was correlated to the onset of dementia and the decline of a cognitive composite score retrospectively. RESULTS Patients with a rapid onset of dementia within one, respective three following DBS showed significant higher WML volumes compared to cognitive normal and MCI patients (55.8cm3±18.836 vs. 9.3cm3±12.2; p=0.002). The same significant association was found in a multivariable model, including the covariables age, gender and PD disease duration (p=0.01). WML volume was associated to the rate of decline in cognitive composite score within three years after DBS surgery (p=0.006; R2=0.40) after correction for age. CONCLUSIONS Damaged white matter may lead to a reduced compensation of disconnections in cognitive circuits caused by the implantation of the DBS electrodes or by chronic stimulation. The role of WML as a prognostic factor for the cognitive outcome after DBS may be underestimated. The WML burden should be taken seriously in preoperative risk stratification.

Extent of Resection in Newly Diagnosed Glioblastoma: Impact of a Specialized Neuro-Oncology Care Center

Treatment of glioblastoma (GBM) consists of microsurgical resection followed by concomitant radiochemotherapy and adjuvant chemotherapy. The best outcome regarding progression free (PFS) and overall survival (OS) is achieved by maximal resection. The foundation of a specialized neuro-oncology care center (NOC) has enabled the implementation of a large technical portfolio including functional imaging, awake craniotomy, PET scanning, fluorescence-guided resection, and integrated postsurgical therapy. This study analyzed whether the technically improved neurosurgical treatment structure yields a higher rate of complete resection, thus ultimately improving patient outcome. Patients and methods: The study included 149 patients treated surgically for newly diagnosed GBM. The neurological performance score (NPS) and the Karnofsky performance score (KPS) were measured before and after resection. The extent of resection (EOR) was volumetrically quantified. Patients were stratified into two subcohorts: treated before (A) and after (B) the foundation of the Regensburg NOC. The EOR and the PFS and OS were evaluated. Results: Prognostic factors for PFS and OS were age, preoperative KPS, O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status, isocitrate dehydrogenase 1 (IDH1) mutation status and EOR. Patients with volumetrically defined complete resection had significantly better PFS (9.4 vs. 7.8 months; p = 0.042) and OS (18.4 vs. 14.5 months; p = 0.005) than patients with incomplete resection. The frequency of transient or permanent postoperative neurological deficits was not higher after complete resection in both subcohorts. The frequency of complete resection was significantly higher in subcohort B than in subcohort A (68.2% vs. 34.8%; p = 0.007). Accordingly, subcohort B showed significantly longer PFS (8.6 vs. 7.5 months; p = 0.010) and OS (18.7 vs. 12.4 months; p = 0.001). Multivariate Cox regression analysis showed complete resection, age, preoperative KPS, and MGMT promoter status as independent prognostic factors for PFS and OS. Our data show a higher frequency of complete resection in patients with GBM after the establishment of a series of technical developments that resulted in significantly better PFS and OS without increasing surgery-related morbidity.

The usefulness of the awake-awake-awake technique.

Dear Sirs, We appreciate the comments fromDr. Duffau [3] on our paper “Awake craniotomies without any sedation: the awakeawake-awake technique” [5]. We agree that an awake patient is the best candidate for intraoperative neurological testing, and it is obvious that the less the patient is mentally compromised by sedatives, the better the test results will be. Thus, in a recent publication we could demonstrate that patients show unimpaired alertness with our procedure, whereas higher cognitive functions were compromised for at least an hour in other patients with intermittent anesthesia or sedation with propofol [6]. We fully agree that during the purely surgical phases the patient should not follow this in the sense of focusing on the surgical procedure. Duffau here suggests the use of sedation in accordance with the common asleep-awake-asleep technique. As the sedatives and anesthetics in question are also called “hypnotics”, it is justified to ask if only a pharmacological “hypnosis” can protect the patient from “harmful” experiences, or if other approaches like our hypnotic communication [4] can have the same effect. We would say “yes” according to our experience. Utilizing the natural trance state of surgical patients [2] and by positive suggestions, dissociation to a “safe place”, reframing of disturbing noises or feelings, and adequate care, our patients did well without pharmacological sedation [5]. Our technique should not be discredited based on our reported rates of intraoperative seizures and neurological deficits, since these rates are comparable to those reported in the literature [1, 8]. It should furthermore be noted that our study was not restricted to patients with low-grade gliomas only involving the speech area with exclusive speech mapping, as in the studies mentioned by Duffau. In fact, we had a study population with 74 % high-grade astrocytomas (°III/IV) and only 17 % low-grade gliomas. Moreover, 59 % of our patients had exclusive or additional motor mapping because of involvement of the motor area, and seizures were only seen with motor mapping and mainly with high-grade gliomas (75 %). The high percentage of high-grade gliomas and the significant rate (30 %) of a preoperative deficit in our patients explains the rate of 2 % major and 14 % minor postoperative deficits, which were exclusively motor deficits [5]. Besides this, neurological outcome and the number of intraoperative seizures were not the main issues of this study and should not be misunderstood as effects of the awake-awake-awake technique. As an aside, it is well documented that propofol, while being antiepileptic at high dosage, is epileptogenic at low dosage as used for sedation [7]. Far away from comparing reported complications, it is indisputable that anesthetics have side effects and that these side effects can be reduced by avoiding these drugs. Dr. Duffau is right to stress the usefulness of a new technique and not only feasibility. But these two issues cannot be separated in serious clinical studies. The driving force of searching for improvement is the clinical usefulness for the medical doctors and even more for the patients. If this proposition is given, feasibility is tested. Our intent was not to break records or set up new ones for the record’s sake. This would be unethical in any circumstances. The avoidance of sedation was not a pre-setting in our study, but its result. We have not claimed that our patients have fear and anxiety on a regular basis. We wanted to emphasize that we take measures to reduce or abandon these emotional feelings, as C. Doenitz :A. Brawanski Department of Neurosurgery, University Hospital Regensburg, Regensburg, Germany