Christopher Nimsky

Intraoperative magnetic resonance imaging combined with neuronavigation: a new concept.

OBJECTIVE Intraoperative image data may be used not only to evaluate the extent of a tumor resection but also to update neuronavigation, compensating for brain shift. To date, however, intraoperative magnetic resonance imaging (MRI) can be combined only with navigation microscopes that are separated from the magnetic field, thus requiring time-consuming intraoperative patient transport. To help solve this problem, we investigated whether a new navigation microscope can be used within the fringe field of the MRI scanner. METHODS The navigation microscope was placed at the 5-G line of a 0.2 MRI device. Patients were positioned lying down directly on the table of the scanner, with their heads placed approximately 1.5 m from the center of the magnet, fixed in an MRI-compatible ceramic head holder. Standard operating instruments were used. For intraoperative imaging, we slid the table into the center of the magnet in less than 30 seconds. RESULTS By use of this setup, we operated on 22 patients. In all patients, anatomic neuronavigation could be used in combination with intraoperative MRI. In addition, in 12 patients, functional data from magnetoencephalographic or functional MRI studies were integrated, resulting in functional neuronavigation. We did not encounter adverse effects of the low magnetic field during navigation. Moreover, intraoperative imaging was not disturbed by the navigation microscope and vice versa. CONCLUSION Functional neuronavigation and intraoperative MRI can be used essentially simultaneously without the need for lengthy intraoperative patient transport. The combination of intraoperative imaging with functional neuronavigation offers the opportunity for more radical resections and fewer complications.

Small interfering RNA-mediated xCT silencing in gliomas inhibits neurodegeneration and alleviates brain edema

Neurodegeneration and brain edema are hallmarks of human malignant brain tumors. Here we show that genetic or pharmacological inhibition of the glutamate transporter xCT (Xc− system, encoded by SLC7a11) in vivo leads to abrogated neurodegeneration, attenuated perifocal edema and prolonged survival. These results show a crucial role for xCT in glioma-induced neurodegeneration and brain edema, corroborating the concept that edema formation may be in part a consequence of peritumoral cell death.

New approach to localize speech relevant brain areas and hemispheric dominance using spatially filtered magnetoencephalography

We used a current localization by spatial filtering‐technique to determine primary language areas with magnetoencephalography (MEG) using a silent reading and a silent naming task. In all cases we could localize the sensory speech area (Wernicke) in the posterior part of the left superior temporal gyrus (Brodmann area 22) and the motor speech area (Broca) in the left inferior frontal gyrus (Brodmann area 44). Left hemispheric speech dominance was determined in all cases by a laterality index comparing the current source strength of the activated left side speech areas to their right side homologous. In 12 cases we found early Wernicke and later Broca activation corresponding to the Wernicke‐Geschwind model. In three cases, however, we also found early Broca activation indicating that speech‐related brain areas need not necessarily be activated sequentially but can also be activated simultaneously. Magnetoencephalography can be a potent tool for functional mapping of speech‐related brain areas in individuals, investigating the time‐course of brain activation, and identifying the speech dominant hemisphere. This may have implications for presurgical planning in epilepsy and brain tumor patients. Hum. Brain Mapping 14:236–250, 2001.

Improved delineation of brain tumors: an automated method for segmentation based on pathologic changes of 1H-MRSI metabolites in gliomas

In this study, we developed a method to improve the delineation of intrinsic brain tumors based on the changes in metabolism due to tumor infiltration. Proton magnetic resonance spectroscopic imaging ((1)H-MRSI) with a nominal voxel size of 0.45 cm(3) was used to investigate the spatial distribution of choline-containing compounds (Cho), creatine (Cr) and N-acetyl-aspartate (NAA) in brain tumors and normal brain. Ten patients with untreated gliomas were examined on a 1.5 T clinical scanner using a MRSI sequence with PRESS volume preselection. Metabolic maps of Cho, Cr, NAA and Cho/NAA ratios were calculated. Tumors were automatically segmented in the Cho/NAA images based on the assumption of Gaussian distribution of Cho/NAA values in normal brain using a limit for normal brain tissue of the mean + three times the standard deviation. Based on this threshold, an area was calculated which was delineated as pathologic tissue. This area was then compared to areas of hyperintense signal caused by the tumor in T2-weighted MRI, which were determined by a region growing algorithm in combination with visual inspection by two experienced clinicians. The area that was abnormal on (1)H-MRSI exceeded the area delineated via T2 signal changes in the tumor (mean difference 24%) in all cases. For verification of higher sensitivity of our spectroscopic imaging strategy we developed a method for coregistration of MRI and MRSI data sets. Integration of the biochemical information into a frameless stereotactic system allowed biopsy sampling from the brain areas that showed normal T2-weighted signal but abnormal (1)H-MRSI changes. The histological findings showed tumor infiltration ranging from about 4-17% in areas differentiated from normal tissue by (1)H-MRSI only. We conclude that high spatial resolution (1)H-MRSI (nominal voxel size = 0.45 cm(3)) in combination with our segmentation algorithm can improve delineation of tumor borders compared to routine MRI tumor diagnosis.

Diffusion tensor imaging and optimized fiber tracking in glioma patients: Histopathologic evaluation of tumor-invaded white matter structures

Fiber tracking is increasingly used to plan and guide neurosurgical procedures of intracranial tumors in the vicinity of functionally important areas of the brain. However, valid data concerning the reliability of tracking with respect to the actual pathoanatomical situation are lacking. We retrospectively correlated fiber tracking based on magnetic resonance (MR) DT imaging with the histopathological data of 25 patients with WHO grade II and III gliomas. Fiber tracking using the Fiber Assignment by Continuous Tracking (FACT) method was performed to investigate the integrity of white matter tracts in the surrounding border zone of the lesions. The tracking procedure was stopped when fractional anisotropy (FA) thresholds = 0.1, 0.15, 0.2, 0.25, and 0.3, or a tract turning angle >60 degrees were encountered. In 9 patients we were able to reconstruct brain fiber tracts at biopsy loci (2-32% tumor infiltration) using an FA threshold of 0.15 and 0.2, but not for a threshold of 0.25 or 0.3. The neurological outcome demonstrated potential tumor cell infiltration of functionally intact brain fiber tracts in the range of 2-8%. These findings may be useful in planning therapeutic approaches to gliomas in the vicinity of eloquent brain regions.

Proton Magnetic Resonance Spectroscopic Imaging Integrated into Image-guided Surgery: Correlation to Standard Magnetic Resonance Imaging and Tumor Cell Density

OBJECTIVE: In this study, we attempted to improve the delineation of the infiltration zone in gliomas using proton magnetic resonance spectroscopic imaging (1H MRSI). In conventional magnetic resonance imaging (MRI), the boundaries of gliomas sometimes are underestimated. 1H MRSI is a noninvasive tool that can be used to investigate the spatial distribution of metabolic changes in brain lesions. The purpose was to correlate tumor cell density from histopathological specimens with metabolic levels and the coregistered metabolic maps. METHODS: We developed a method to integrate spectroscopic data depicted as metabolic maps of biochemically pathological tissue into frameless stereotaxy. In seven patients harboring gliomas, we performed 1H MRSI with high spatial resolution and evaluated the spectral data. An algorithm was developed for user-independent calculation of pathological voxels and for visualization as metabolic maps. These maps were integrated into a three-dimensional MRI data set used for frameless stereotaxy. Stereotactic biopsies were taken from three different areas in and around the tumor involving the maximum pathological change, the border zone, and an area from outside the spectroscopically suspicious area. These specimens were correlated to the exact voxel positions in the stereotactic image space and evaluated histopathologically. RESULTS: In all cases, the implementation of the metabolic maps into frameless stereotaxy was successful, and stereotactic biopsies were acquired by use of the spectral data. A relation could be demonstrated between the metabolic changes and tumor cell density ranging from 60 to 100% in the maximum pathological area to 5 to 15% in the border zone. Interestingly, the tumor areas defined by the metabolic maps and histopathologically confirmed by biopsy exceeded the T2-weighted signal change in all cases, ranging from 6 to 32% in the examined volume. CONCLUSION: Our preliminary data suggest that 1H MRSI may be useful in combination with frameless stereotaxy to define more exactly the tumor infiltration zone in glioma surgery compared with conventional anatomic MRI alone.

The stem cell marker prominin-1/CD133 on membrane particles in human cerebrospinal fluid offers novel approaches for studying central nervous system disease.

Cerebrospinal fluid (CSF) is routinely used for diagnosing and monitoring neurological diseases. The CSF proteins used so far for diagnostic purposes (except for those associated with whole cells) are soluble. Here, we show that human CSF contains specific membrane particles that carry prominin‐1/CD133, a neural stem cell marker implicated in brain tumors, notably glioblastoma. Differential and equilibrium centrifugation and detergent solubility analyses showed that these membrane particles were similar in physical properties and microdomain organization to small membrane vesicles previously shown to be released from neural stem cells in the mouse embryo. The levels of membrane particle‐associated prominin‐1/CD133 declined during childhood and remained constant thereafter, with a remarkably narrow range in healthy adults. Glioblastoma patients showed elevated levels of membrane particle‐associated prominin‐1/CD133, which decreased dramatically in the final stage of the disease. Hence, analysis of CSF for membrane particles carrying the somatic stem cell marker prominin‐1/CD133 offers a novel approach for studying human central nervous system disease.

Flat-panel detector volumetric CT for visualization of subarachnoid hemorrhage and ventricles: preliminary results compared to conventional CT

IntroductionThe aim of this study was to compare flat-panel volumetric CT (VCT) to conventional CT (cCT) in the visualization of the extent of subarachnoid hemorrhage (SAH) and the width of the ventricles in patients with acute SAH.MethodsIncluded in the study were 22 patients with an acutely ruptured cerebral aneurysm who received VCT during coil embolization. VCT image quality, the extent of SAH (using a modified Fisher score and total slice number with SAH visible) and the width of the ventricles (Evans index) were evaluated by two experienced neuroradiologists (RAD1 and RAD2) and compared to the findings on cCT. Ten patients undergoing VCT for reasons other than SAH served as negative controls.ResultsInterobserver agreement in rating image quality was excellent for cCT (Kendall W value 0.94) and good for VCT (0.74). SAH was identified by RAD1 and RAD2 on VCT images in all patients. The modified Fisher scores underestimated the extent of SAH on VCT images in comparison with cCT images. Pearson’s correlation coefficient (r) regarding the number of image slices with SAH visible on cCT images compared with the number on VCT images was 0.85 for RAD1 and 0.84 for RAD2. The r value for the degree of interobserver agreement for the number of slices with SAH visible was 0.99 for cCT, and 0.95 for VCT images (n = 19), respectively. The width of the ventricles measured in terms of the Evans Index showed excellent concordance between the modalities (r = 0.81 vs. 0.82).ConclusionOur preliminary results indicate that VCT is helpful in evaluating SAH in the angiography suite. Additionally, reliable evaluation of ventricle width is feasible. However, there are limitations with regard to the visibility of SAH on VCT images in comparison to cCT images.

Intraoperative magnetic resonance imaging in epilepsy surgery

The aim of this study was to investigate how intraoperative magnetic resonance imaging (MRI) can help in epilepsy surgery to asses immediately whether a resection or disconnection procedure is tailored to the individual needs of a patient, thus ideally meeting the treatment plan and enhancing the efficiency of the procedure. The recently proposed concept of an individually tailored procedure with as limited tissue removal as possible would support a more conservative resection than initially advocated by many centers; such limited removal would preserve as much brain as possible that is not necessarily epileptogenic or involved in propagation of seizures. For intraoperative imaging we used a Magnetom Open 0.2‐T scanner located in our “twin‐OR” in 61 patients with pharmacoresistant epilepsy. A three‐dimensional sequence was used, allowing free slice reformatting. In the nonlesional cases (n = 32) the extent of the tailored temporal resection (n = 28) or callosotomy (n = 4) could be documented exactly. In the 29 lesional cases the complete resection was primarily proved in 23 patients. In three glioma patients a lesion that extended into eloquent areas did not allow for complete removal. A second look (n = 3) could increase the rate of total resection in the lesional cases from 79% to 90%. Intraoperative MRI allowed a reliable evaluation of the extent of resection or disconnection in epilepsy surgery within the operative procedure. It also provided the possibility of a second look in cases of incomplete resection, especially in the lesional cases. Increased knowledge of structure‐function relationships as partially defined by intraoperative imaging may reduce the adverse neuropsychological sequelae of epilepsy surgery in the future. J. Magn. Reson. Imaging 2000;12:547–555.

Cellular characterization of the peritumoral edema zone in malignant brain tumors

Brain edema is a hallmark of human malignant brain tumors and contributes to the clinical course and outcome of brain tumor patients. The so‐called perifocal edema or brain swelling imposes in T2‐weighted MR scans as high intensity areas surrounding the bulk tumor mass. The mechanisms of this increased fluid attraction and the cellular composition of the microenvironment are only partially understood. In this study, we focus on imaging perifocal edema in orthotopically implanted gliomas in rodents and correlate perifocal edema with immunohistochemical markers. We identified that areas of perifocal edema not only include the tumor invasion zone, but also are associated with increased glial fibrillary acidic protein (GFAP) and aquaporin‐4 expression surrounding the bulk tumor mass. Moreover, a high number of activated microglial cells expressing CD11b and macrophage migration inhibitory factor (MIF) accumulate at the tumor border. Thus, the area of perifocal edema is mainly dominated by reactive changes of vital brain tissue. These data corroborate that perifocal edema identified in T2‐weighted MR scans are characterized with alterations in glial cell distribution and marker expression forming an inflammatory tumor microenvironment. (Cancer Sci 2009; 100: 1856–1862)