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Among spinal tumors that occur intradurally, meningiomas, nerve sheath tumors, ependymomas, and astrocytomas are the most common. While a spinal MRI is the state of the art to diagnose intradural spinal tumors, in some cases CT scans, angiography, CSF analyses, and neurophysiological examination can be valuable. The management of these lesions depends not only on the histopathological diagnosis but also on the clinical presentation and the anatomical location, allowing either radical resection as with most extramedullary lesions or less invasive strategies as with intramedullary lesions. Although intramedullary lesions are rare and sometimes difficult to manage, well-planned treatment can achieve excellent outcome without treatment-related deficits. Technical advances in imaging, neuromonitoring, minimally invasive approaches, and radiotherapy have improved the outcome of intradural spinal tumors. However, the outcome in malignant intramedullary tumors remains poor. While surgery is the mainstay treatment for many of these lesions, radiation and chemotherapy are of growing importance in recurrent and multilocular disease. We reviewed the literature on this topic to provide an overview of spinal cord tumors, treatment strategies, and outcomes. Typical cases of extra- and intramedullary tumors are presented to illustrate management options and outcomes.

Background The knowledge of exact tumor margins is of importance for the treating neurosurgeon, radiotherapist, and oncologist alike. The aim of this study was to investigate whether tumor volume and tumor margins acquired by magnetic resonance imaging (MRI) are congruent with the findings acquired by O-(2-(18F)-fluoroethyl)- l -tyrosine–positron emission tomography (FET-PET). Methods Patients received FET-PET and MRI before surgery for brain metastases. Metastases were quantified by calculating tumor-to-background uptake ratios using FET uptake. PET and MRI-based tumor volumes, as well as areas of intersection, were assessed. Results Forty-one patients were enrolled in the study. The maximum tumor-to-background uptake ratio measured in all of our patients harboring histologically proven viable tumor tissue was >1.6. Absolute tumor volumes acquired by FET-PET and MRI were not congruent in our patient cohort, and tumors identified in FET-PET and MRI only partially overlapped. The ratio of intersection (intersection of tumor defined by MRI and tumor defined by FET-PET at the ratio of tumor defined by FET-PET) was within a range of 0.27–0.68 when applying the different thresholds. Conclusions Our study therefore indicates that treatment planning based on MRI or PET only might have a substantial risk of undertreatment at the tumor margins. These findings could have important implications for the planning of surgery as well as radiotherapy, although they have to be validated in further studies.

Thrombus composition has been suggested to have a decisive impact on the outcome of patients treated by mechanical thrombectomy because of embolic stroke. The recent development of stent retrievers allows collection and, hence, histopathological analysis of fresh thrombus material. Against this background, the aim of this prospective study was to assess the impact of thrombus composition on mechanical recanalization, clinical outcome and stroke etiology. Thirty-four patients suffering from acute ischemic stroke due to occlusion of the distal internal carotid artery/carotid-T, anterior cerebral artery, or middle cerebral arteries were mechanically recanalized, and thrombus material was obtained. Histological thrombus composition was compared with imaging, clinical, and neurointerventional data. The main findings were that a higher percentage of white blood cells (WBCs) in the thrombus was associated with (i) cardioembolic etiology, (ii) extended mechanical recanalization time, and (iii) less favorable recanalization (Thrombolysis in Cerebral Infarction score) and clinical outcome (National Institute of Health Stroke Scale). Our results suggest that thrombi with a high WBC fraction are related to more organized thrombi of cardioembolic origin associated with less favorable recanalization and clinical outcome in acute ischemic anterior circulation stroke. WBC-mediated immunological and coagulatory processes may play a key role in thrombus formation and pathogenesis of stroke warranting further investigation.

The MR image quality after intracranial aneurysm clipping is often impaired because of artifacts induced by metal implants. The purpose of the present study was to evaluate the benefit of a new WARP sequence with slice-encoding metal artifact correction (SEMAC) and view-angle tilting (VAT) MR imaging as novel artifact reduction techniques. A new WARP TSE (a work-in-progress software package provided by Siemens Healthcare) sequence was implemented for cranial applications based on a turbo spin echo (TSE) sequence. T1- and T2-weighted images with standard and WARP TSE sequences were acquired from 6 patients with 11 clipping sites, and the images were compared based on artifact size and general image quality. T2- and T1-weighted WARP TSE sequences resulted in a highly significant reduction of metal artifacts compared with standard sequences (T2w- WARP TSE: 89.8 ± 1.4 %; T1w- WARP TSE: 84.9 ± 2.9 %; p

A blood oxygenation level-dependent (BOLD)-based apparent relative oxygen extraction fraction (rOEF) as a semi-quantitative marker of vascular deoxygenation has recently been introduced in clinical studies of patients with glioma and stroke, yielding promising results. These rOEF measurements are based on independent quantification of the transverse relaxation times T2 and T2* and relative cerebral blood volume (rCBV). Simulations demonstrate that small errors in any of the underlying measures may result in a large deviation of the calculated rOEF. Therefore, we investigated the validity of such measurements. For this, we evaluated the quantitative measurements of T2 and T2* at 3 T in a gel phantom, in healthy subjects and in healthy tissue of patients with brain tumors. We calculated rOEF maps covering large portions of the brain from T2, T2* and rCBV [routinely measured in patients using dynamic susceptibility contrast (DSC)], and obtained rOEF values of 0.63 ± 0.16 and 0.90 ± 0.21 in healthy-appearing gray matter (GM) and white matter (WM), respectively; values of about 0.4 are usually reported. Quantitative T2 mapping using the fast, clinically feasible, multi-echo gradient spin echo (GRASE) approach yields significantly higher values than much slower multiple single spin echo (SE) experiments. Although T2* mapping is reliable in magnetically homogeneous tissues, uncorrectable macroscopic background gradients and other effects (e.g. iron deposition) shorten T2*. Cerebral blood volume (CBV) measurement using DSC and normalization to WM yields robust estimates of rCBV in healthy-appearing brain tissue; absolute quantification of the venous fraction of CBV, however, is difficult to achieve. Our study demonstrates that quantitative measurements of rOEF are currently biased by inherent difficulties in T2 and CBV quantification, but also by inadequacies of the underlying model. We argue, however, that standardized, reproducible measurements of apparent T2, T2* and rCBV may still allow the estimation of a meaningful apparent rOEF, which requires further validation in clinical studies.

a b s t r a c t Introduction: Concerning the preoperative clinical diagnostic work-up of glioma patients, tumor hetero- geneity challenges the oncological therapy. The current study assesses the performance of a multimodal imaging approach to differentiate between areas in malignant gliomas and to investigate the extent to which such a combinatorial imaging approach might predict the underlying histology. Methods: Prior to surgical resection, patients harboring intracranial gliomas underwent MRIs (MR-S, PWI) and 18 F-FET-PETs. Intratumoral and peritumoral biopsy targets were defined, by MRI only, by FET-PET only, and by MRI and FET-PET combined, and biopsied prior to surgical resection and which then received separate histopathological examinations. Results: In total, 38 tissue samples were acquired (seven glioblastomas, one anaplastic astrocytoma, one anaplastic oligoastrocytoma, one diffuse astrocytoma, and one oligoastrocytoma) and underwent histopathological analysis. The highest mean values of Mib1 and CD31 were found in the target point "T' defined by MRI and FET-PET combined. A significant correlation between NAA/Cr and PET tracer uptake (−0.845, p < 0.05) as well as Cho/Cr ratio and cell density (0.742, p < 0.05) and NAA/Cr ratio and MIB-1 (−0761, p < 0.05) was disclosed for this target point, though not for target points defined by MRI and FET-PET alone. Conclusion: Multimodal-imaging-guided stereotactic biopsy correlated more with histological malig- nancy indices, such as cell density and MIB-1 labeling, than targets that were based solely on the highest amino acid uptake or contrast enhancement on MRI. The results of our study indicate that a combined PET-MR multimodal imaging approach bears potential benefits in detecting glioma heterogeneity.

Purpose: Magnetic resonance imaging (MRI) is the gold standard in visualizing brain tumors and their effects on adjacent structures. However, no reliable information concerning different tumor components and borders between perifocal edema and infiltration areas can be received. The aim of the study was to establish and evaluate a multimodal imaging concept, in order to differentiate different biological tumor components and to determine tumor borders. Materials and Methods: 12 patients with cerebral gliomas (four low and eight high grade) received a “morphological” MRI, a 3D MR spectroscopy and a T2* MR perfusion examination prior to surgery. Data was evaluated by defining different tumor components, which were entitled based upon their multimodal characteristics and histological data. Results: In high grade gliomas different components can be differentiated, which were described as: “true edema”, “cellular proliferation”, “vascular proliferation”, “cellular infiltration”, “tumor” and “necrosis”. In low grade gliomas, four different tumor components were found: “true edema”, “cellular infiltration”, “cellular proliferation” and “tumor”. Conclusion: With the applied multimodal imaging and a novel evaluation concept, it was possible to detect different tumor components, which could be helpful in detecting the optimal sites for tumor biopsy. Especially in morphological “edema appearing” sites, this knowledge could be important for the adaption of tumor resection borders and the planning of radiation therapy. Further studies with more patients and histological correlation are needed.

Object Brain metastases occur in 10% to 40% of patients harboring cancer. In cases of neurosurgical metastasis resection, all postoperative neurological deterioration should be avoided. Reasons for postoperative deficits can be direct tissue damage due to resection, hemorrhage, venous congestive infarcts, or arterial ischemic events leading to tissue infarction. The aim of this study was to evaluate whether postoperative ischemic infarctions occur in surgery for brain metastasis and to determine their influence on new postoperative neurological deficits. Methods Patients who underwent resection of brain metastases and had preoperative and early postoperative (within 48 hours) MRI scans, including diffusion-weighted imaging sequences and apparent diffusion coefficient maps, between January 2009 and May 2012 were included in this study. Clinical and histopathological data (histopathological results, pre- and postoperative neurological status, and previous tumor-specific therapy) were recorded. Results One hundred twenty-two patients (56 male, 66 female) who underwent resection of brain metastases were included. The patients' mean age was 60 years (range 21–89 years). The mean time span from initial tumor diagnosis to resection of brain metastasis was 44 months (range 0–338 months). The mean preoperative Karnofsky Performance Status was 80% (exact mean 76% ± 17% [SD]), and the mean postoperative value was 80% (exact mean 78% ± 17%). Twelve (9.8%) of the 122 patients had postoperative permanent worsening of a neurological deficit or a new permanent neurological deficit; 44 (36.1%) of the 122 patients had postoperative ischemic lesions. When comparing patients with and without previous brain irradiation, 53.8% of patients with previous brain irradiation had ischemic lesions on postoperative imaging compared with 31.3% of patients without previous brain irradiation (p = 0.033). There was a significant association between ischemia and postoperative neurological status deterioration (transient or permanent); 13 (29.5%) of 44 patients with ischemic lesions had deterioration of their neurological status compared with 7 (9%) of the 78 patients who did not have ischemic lesions (p = 0.003). Conclusions This study demonstrates a high prevalence of vascular incidents in patients undergoing resection for metastatic brain disease. Patients harboring postoperative ischemic lesions detected by MRI have a higher rate of neurological deficits (transient or permanent). Patients who had previous irradiation therapy are at higher risk of developing postoperative ischemic lesions. A large number of postoperative neurological deficits are caused by ischemic incidents.

Object The aim of surgical glioma treatment is the complete resection of tumor tissue while preserving neurological function. Surgery-related neurological deficits arise from direct damage to the cortical or subcortical structures or from ischemia. The authors aimed to assess the incidence of resection-related ischemia of newly diagnosed or recurrent supratentorial gliomas and the sensitivity of intraoperative neuromonitoring (IOM) of motor evoked potentials (MEPs) for detecting such ischemic events and their influence on neurological motor function. Methods Between January 2009 and December 2010, 70 patients with tumors in motor-eloquent brain areas underwent intraoperative MEP monitoring during glioma resection and were examined by early postoperative MRI including diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) mapping. Postoperative areas of restricted diffusion were assessed by investigators blinded to the course of intraoperative MEPs and the neurological course. Results Among the 70 enrolled patients, a MEP amplitude decline below 50% of the baseline level was observed in 21 patients (30%). Sixteen of these patients (76%) had ischemic lesions identified on postoperative MRI scans. Forty-nine patients (70%) showed no decline in MEP amplitude, and only 16 (33%) of these patients harbored ischemic lesions. Moreover, 9 (69%) of 13 patients with a permanent loss of MEP amplitude showed postoperative ischemic lesions. Factors that promoted the occurrence of postoperative infarction were previous radiotherapy and location of the tumor close to the central arteries. Conclusions Alterations in the MEP amplitude during tumor resection and postoperative ischemic lesions are associated with postoperative impairment of motor function. Rather than cortical or subcortical structural damage of eloquent brain tissue alone, peri- or postoperative ischemic lesions play a crucial role in the development of surgery-related motor deficits.

Hypoxia plays a central role in tumor stem cell genesis and is related to a more malignant tumor phenotype, therapy resistance (e.g. in anti-angiogenic therapies) and radio-insensitivity. Reliable hypoxia imaging would provide crucial metabolic information in the diagnostic work-up of brain tumors. In this study, we applied a novel BOLD-based MRI method for the measurement of relative oxygen extraction fraction (rOEF) in glioma patients and investigated potential benefits and drawbacks. Forty-five glioma patients were examined preoperatively in a pilot study on a 3T MR scanner. rOEF was calculated from quantitative transverse relaxation rates (T2, T2*) and cerebral blood volume (CBV) using a quantitative BOLD approach. rOEF maps were assessed visually and by means of a volume of interest (VOI) analysis. In six cases, MRI-targeted biopsy samples were analyzed using HIF-1α-immunohistochemistry. rOEF maps could be obtained with a diagnostic quality. Focal spots with high rOEF values were observed in the majority of high-grade tumors but in none of the low-grade tumors. VOI analysis revealed potentially hypoxic tumor regions with high rOEF in contrast-enhancing tumor regions as well as in the non-enhancing infiltration zone. Systematic bias was found as a result of non-BOLD susceptibility effects (T2*) and contrast agent leakage affecting CBV. Histological samples demonstrated reasonable correspondence between MRI characteristics and HIF-1α-staining. The presented method of rOEF imaging is a promising tool for the metabolic characterization of human glioma. For the interpretation of rOEF maps, confounding factors must be considered, with a special focus on CBV measurements in the presence of contrast agent leakage. Further validation involving a bigger cohort and extended immuno-histochemical correlation is required.

Object The aim of surgical treatment of glioma is the complete resection of tumor tissue with preservation of neurological function. Inclusion of diffusion-weighted imaging (DWI) in the postoperative MRI protocol could improve the delineation of ischemia-associated postoperative neurological deficits. The present study aims to assess the incidence of infarctions following resection of newly diagnosed gliomas in comparison with recurrent gliomas and the influence on neurological function. Methods Patients who underwent glioma resection for newly diagnosed or recurrent gliomas had early postoperative MRI, including DWI and apparent diffusion coefficient (ADC) maps. Postoperative areas of restricted diffusion were classified as arterial territorial infarctions, terminal branch infarctions, or venous infarctions. Tumor entity, location, and neurological function were recorded. Results New postoperative ischemic lesions were identified in 26 (31%) of 84 patients with newly diagnosed gliomas and 20 (80%) of 25 patients with recurrent gliomas (p < 0.01). New permanent and transient neurological deficits were more frequent in patients with recurrent gliomas than in patients with newly diagnosed tumors. Patients with neurological deficits had a significantly higher rate of ischemic lesions. Conclusions Postoperative infarctions occur frequently in patients with newly diagnosed and recurrent gliomas and do have an impact on postoperative neurological function. In this patient cohort there was a higher risk for ischemic lesions and for deterioration of neurological function after resection of recurrent tumors. Radiogenic and postoperative tissue changes could contribute to the higher risk of an ischemic infarction in patients with recurrent tumors.

An accurate characterization of glioma heterogeneity is essential when determining tumor grade and the most appropriate therapy target. Non-invasive imaging modalities such as MR perfusion imaging (PWI) and 2D proton MR spectroscopic imaging (MRSI) can provide functional and metabolic information about the tumor to assist in this task. Using a voxel-wise correlation we aimed at investigating whether both MRSI and PWI characterize brain tumor heterogeneity similarly, and, whether the regions of their most pathologic values coincide. In 31 patients with different primary brain tumors rCBV and rCBF were correlated to the metabolites Cho, Cr and NAA and the metabolite ratios Cho/Cr, NAA/Cr and Cho/NAA on a voxel-wise basis. Intraindividually, we tested for significant relationships and we recorded the reliability and the direction of these relationships by calculating the inter individual variance of Kendall's correlation coefficient τb. Additionally, the locations of the most pathologic values of PWI and MRSI were compared. Across all tumors we found no reliable relationship between perfusion and spectroscopic measures apart from a positive correlation of rCBV and rCBF with Cr, mainly based on a positive correlation in II° gliomas and glioblastomas but not in III° gliomas or lymphomas. The separate analysis of the tumor groups revealed consistent correlations of additional value pairs in II° gliomas and glioblastomas, but not in III° gliomas or lymphomas. The overall spatial concordance rate between the maximum perfusion values and the most pathological metabolite values was 34%. Our results suggest that brain tumors display heterogenous correlation pattern of the perfusion markers of malignancy to the spectroscopy-derived malignancy markers. As the single modality methods may display different kinds of tumor hot spots, PWI and MRSI should be fused to allow for more specific therapy planning of brain tumors.

Background Recently, mutations in an open-reading frame on chromosome 19 (C19orf12) were identified as a novel genetic factor in neurodegeneration with brain iron accumulation (NBIA). Because of the mitochondrial localization of the derived protein, this variant is referred to as mitochondrial membrane protein-associated neurodegeneration with brain iron accumulation (MPAN). Methods/Results We describe the clinical phenotype and MRI of 3 newly identified individuals with MPAN due to either previously reported or novel homozygous or compound heterozygous genetic alterations in C19orf12. Conclusions MPAN is characterized by a juvenile-onset, slowly progressive phenotype with predominant lower limb spasticity, generalized dystonia, and cognitive impairment. Typical additional features include axonal motor neuropathy and atrophy of the optic nerve. MRI showed iron deposition in the globus pallidus and substantia nigra without the eye-of-the-tiger sign, which is typical for PKAN, the most frequent form of NBIA. © 2012 Movement Disorder Society

Experimental treatment strategies using human umbilical cord blood mononuclear cells (hUCB MNCs) represent a promising option for alternative stroke therapies. An important point for clinical translation of such treatment approaches is knowledge on the therapeutic time window. Although expected to be wider than for thrombolysis, the exact time window for hUCB MNC therapy is not known. Our study aimed to determine the time window of intravenous hUCB MNC administration after middle cerebral artery occlusion (MCAO). Male spontaneously hypertensive rats underwent MCAO and were randomly assigned to hUCB MNC administration at 4, 24, 72, and 120 or 14 days. Influence of cell treatment was observed by magnetic resonance imaging on days 1, 8, and 29 following MCAO and by assessment of functional neurological recovery. On day 30, brains were screened for glial scar development and presence of hUCB MNCs. Further, influence of hUCB MNCs on necrosis and apoptosis in postischemic neural tissue was investigated in hippocampal slices cultures. Transplantation within a 72-h time window resulted in an early improvement of functional recovery, paralleled by a reduction of brain atrophy and diminished glial scarring. Cell transplantation 120 h post-MCAO only induced minor functional recovery without changes in the brain atrophy rate and glial reactivity. Later transplantation (14 days) did not show any benefit. No evidence for intracerebrally localized hUCB MNCs was found in any treatment group. In vitro hUCB MNCs were able to significantly reduce postischemic neural necrosis and apoptosis. Our results for the first time indicate a time window of therapeutic hUCB MNC application of at least 72 h. The time window is limited, but wider than compared to conventional pharmacological approaches. The data furthermore confirms that differentiation and integration of administered cells is not a prerequisite for poststroke functional improvement and lesion size reduction.

In Multiple Sclerosis (MS), detection of T2-hyperintense white matter (WM) lesions on magnetic resonance imaging (MRI) has become a crucial criterion for diagnosis and predicting prognosis in early disease. Automated lesion detection is not only desirable with regard to time and cost effectiveness but also constitutes a prerequisite to minimize user bias. Here, we developed and evaluated an algorithm for automated lesion detection requiring a three-dimensional (3D) gradient echo (GRE) T1-weighted and a FLAIR image at 3 Tesla (T). Our tool determines the three tissue classes of gray matter (GM) and WM as well as cerebrospinal fluid (CSF) from the T1-weighted image, and, then, the FLAIR intensity distribution of each tissue class in order to detect outliers, which are interpreted as lesion beliefs. Next, a conservative lesion belief is expanded toward a liberal lesion belief. To this end, neighboring voxels are analyzed and assigned to lesions under certain conditions. This is done iteratively until no further voxels are assigned to lesions. Herein, the likelihood of belonging to WM or GM is weighed against the likelihood of belonging to lesions. We evaluated our algorithm in 53 MS patients with different lesion volumes, in 10 patients with posterior fossa lesions, and 18 control subjects that were all scanned at the same 3T scanner (Achieva, Philips, Netherlands). We found good agreement with lesions determined by manual tracing (R2 values of over 0.93 independent of FLAIR slice thickness up to 6 mm). These results require validation with data from other protocols based on a conventional FLAIR sequence and a 3D GRE T1-weighted sequence. Yet, we believe that our tool allows fast and reliable segmentation of FLAIR-hyperintense lesions, which might simplify the quantification of lesions in basic research and even clinical trials.

Purpose: To investigate age-related regional perfusion changes focused on the medial temporal lobes and related parietal areas using a pulsed arterial spin labeling technique. Materials and Methods: Resting cerebral blood flow (CBF) maps were obtained from 44 healthy volunteers (18 male, 26 female; age range, 19 to 79 years) using a pulsed arterial spin labeling (PASL) MRI technique at 3 Tesla focused on the parietal and temporal lobes. Repeated measurements were performed in 20 subjects to assure the reliability and reproducibility of the applied PASL technique. Results: Focal age-related CBF decreases were detected in the parietal cortex, cuneus and caudate, whereas increases were seen in the lateral and medial temporal lobe such as hippocampus, the calcarine gyrus and the thalamus. Moreover, repeated measurements demonstrated a high reliability and reproducibility of the applied PASL technique. Conclusion: Data provide evidence for regionally dissociated patterns of perfusion increases and decreases during ageing in the temporal and parietal lobes. J. Magn. Reson. Imaging 2011;. © 2011 Wiley Periodicals, Inc.

Alzheimer's disease (AD) and mild cognitive impairment (MCI), the transitional clinical stage between cognition in normal aging and dementia, have been linked to abnormalities in brain perfusion. Pulsed arterial spin labeling (PASL) is a magnetic resonance imaging (MRI) technique for evaluating brain perfusion. The present study aimed to determine regional perfusion abnormalities in 19 patients with mild dementia in AD and 24 patients with MCI as compared to 24 cognitively healthy elderly controls using PASL. In line with nuclear imaging methods, lower perfusion in patients with MCI and AD was found mainly in the parietal lobe, but also in angular and middle temporal areas as well as in the left middle occipital lobe and precuneus. Our data imply that PASL may be a valuable instrument for investigating perfusion changes in the transition from normal aging to dementia and indicate that it might become an alternative to nuclear imaging techniques in AD diagnostics.

Experimental human fetal neural progenitor cell (hfNPC) transplantation has proven to be a promising therapeutic approach after traumatic brain injury (TBI). However the long-term efficacy and safety, which are both highly important for clinical translation of this approach, have not been investigated so far. This study investigated the effect of local (1x105 cells) (L) and systemic (5x105 cells) (S) administration of PKH-26-labeled pre-differentiated hfNPCs over a period of twelve weeks, twenty-four hours after severe controlled cortical impact TBI in Sprague-Dawley rats. Accelerating rotarod testing revealed a trend of functional improvement beginning one week after transplantation and persisting until the end of the experiment. The traumatic lesion volume as quantified by magnetic resonance imaging was smaller in both treatment groups when compared to control (C) animals (C = 54.50 mm3, L = 32 mm3, S = 37.50 mm3). Correspondingly, NeuN staining showed increased neuronal survival at the border of the lesion in both transplanted groups (S: 92.4%; L: 87.2%; 72.5%). Histological analysis of brain compartments revealed transiently increased angiogenesis and reduced astroglial reaction during the first four weeks post-transplantation. PKH-26-positive cells were detected exclusively after local transplantation without any evidence of tumor formation. However, graft differentiation was only observed in very rare cases. In conclusion, transplantation of hfNPCs improved the long-term functional outcome after TBI, diminished trauma lesion size and increased neuronal survival in the border zone of the lesion. This therapeutic effect was most unlikely due to cell replacement but was associated with transiently increased angiogenesis and reduced astrogliosis.

Objectives Different techniques for measuring of perfusion are clinically available, but these are usually applied to healthy brain tissue. Material and methods Five different techniques were used here in 12 patients with brain tumors to investigate the impact of tumor vascularization on the perfusion signal: three qualitative dynamic contrast-enhanced/susceptibility-contrast magnetic resonance imaging (DCE-MRI/DSC-MRI) techniques exploiting T1, T2, T 2 * contrast, and two quantitative techniques, pulsed arterial spin labeling (PASL) and H215O positron emission tomography (H215O-PET). Results In a first approximation, a linear correlation was found between all five imaging modalities regarding the perfusion signal of both, normal brain tissue and tumor. The estimated values for tumor perfusion differed significantly between the techniques (1 = methodical mean in arbitrary units): PASL: 0.83, H215O-PET: 0.62, T1-DCE: 1.73, T2-DCE: 0.69, T 2 * -DSC : 0.89. Conclusions The tumor perfusion values, determined with different techniques are not comparable. The T 2 * -DSC , here applied with contrast agent presaturation of extravascular space, and PASL depict median perfusion most reliably.

PURPOSE: With respect to the specific characteristic of rete mirabile epidurale rostrale in sheep, the aim of this study was to investigate the use of time of flight (TOF) magnetic resonance angiography (MRA) to observe vascular anatomy and to validate MCA occlusion in a new model of experimental focal cerebral ischemia by permanent middle cerebral artery (MCA) occlusion in sheep (designed to study stroke therapy using autologous stem cells from umbilical cord blood). Furthermore, we wanted to assess the extent and natural time course of ischemic focal brain injury in sheep using functional and morphological magnetic resonance imaging (MRI). MATERIALS AND METHOD: 13 Merino sheep were examined. In 4 of the animals all, in 5 sheep 1 or 2 MCA branches were occluded and in 1 one case touched (sham operation). 4 controls did not undergo a surgical procedure. 23 MRI sessions were performed in 10 sheep. These sessions included T1, T2, T2* sequences, diffusion-weighted imaging (DWI) and TOF MRA before and 2-46 days after the onset of stroke using a 1.5 T clinical MR scanner. Corrosion casts of the cerebral arteries of 3 sheep were prepared and compared to MRA. RESULTS: The MRA visualized the vessel anatomy or occlusion distal to the rete mirabile. Anatomical variants concerning the variant origin of the MCA and inconstant arteria choroidea rostralis and communicans rostralis were revealed. Sheep with occluded left MCA showed space occupying lesions with a drop in ADC values. Depending on the number of preserved MCA branches (0; 1; 2), highly significant (p< 0.001) differences in lesion size (21 +/- 5.7; 13; 1.7 +/- 1.3 ml) could be found. No indication of ischemia but minimal contusion damage was observed in the sham operated animal. Conclusions: In our study focal cerebral ischemia was generated in sheep and examined using MRI for the first time. Depending on the occlusion type, the model produced a reproducible lesion size. TOF-MRA proved to be able to clearly depict the anatomy, variants and occlusion type of cerebral arteries in sheep in a manner comparable to that of corrosion casts despite the upstream rete mirabile. MRI with MRA is a useful tool for assessing the extent of brain injury and the type of MCA occlusion and is therefore suitable for non-invasive monitoring of lesion development upon stroke.

Background We have recently shown that the presence of headache in ischemic stroke is associated with lesions of the insular cortex. The aim of this post-hoc subgroup analysis was to investigate the association of specific headache features with stroke location in patients with acute ischemic stroke. Methods In this observational study, patients (mean age: 61.5, 58% males) with ischemic stroke and acute headache (n = 49) were investigated. Infarcts were manually outlined on 3D diffusion weighted magnetic resonance imaging (MRI) scans and transformed into standard stereotaxic space; lesions of the left hemisphere were mirrored in the x-axis to allow a voxel-wise group analysis of all patients. We analyzed the association of lesion location and the following phenotypical characteristics by voxel-based symptom lesion mapping: Headache intensity, different qualities of headache (pulsating, tension-type like and stabbing), and the presence of nausea, of cranial autonomic symptoms and of light or noise sensitivity. Results Headache intensity was associated with lesions of the posterior insula, the operculum and the cerebellum. “Pulsating” headache occurred with widespread cortical and subcortical strokes. The presence of “tension-like” and “stabbing” headache was not related to specific lesion patterns. Nausea was associated with lesions in the posterior circulation territory. Cranial-autonomic symptoms were related to lesions of the parietal lobe, the somatosensory cortex (SI) and the middle temporal cortex. The presence of noise sensitivity was associated with cerebellar lesions, whereas light sensitivity was not related to specific lesions in our sample. Conclusion Headache phenotype in ischemic stroke appears to be related to specific ischemic lesion patterns.

Purpose To investigate whether and how the blood-oxygenation-level–dependent (BOLD) functional MRI (fMRI) signal is modified by brain tumors. Materials and Methods The BOLD signal depends on the perfusion, which in turn may be affected in the presence of a tumor. Some studies have demonstrated a reduced BOLD signal in the tumor-bearing hemisphere. The BOLD signal variation in the motor cortex area was studied with finger tapping in a brain tumor group and a control group. An a priori volume-of-interest (VOI)-based method was applied that allows quantification of the mean BOLD signal amplitude and extent of activated volume. BOLD signal amplitude and activated volume were correlated with the extent of edema, a mass effect on the central sulcus, tumor volume, distance of tumor to somatosensory cortex, and tumor blood volume. Results In the tumor group the ipsilateral activated volume was reduced by 21% (P = 0.025) and the mean signal amplitude was reduced by 16% (P = 0.004). The mean BOLD signal amplitude shows a significant correlation with the total intratumoral blood volume (P = 0.014). Conclusion We concluded that the peritumoral perfusion was reduced resulting due to a tumor aspirating perfusion (steal phenomenon). J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc.

Despite good neurological outcome after the treatment of ruptured or incidental cerebral aneurysms, many patients complain about mood disturbances such as anxiety and depression. The present study investigated the nature of these affective disorders, their trigger factors, and corresponding structural brain changes. We assessed 63 patients matched by history of previous subarachnoid hemorrhage (SAH) and treatment modality (clipping vs. coiling) by a test battery including the Hospital Anxiety and Depression Scale (HADS) and beck depression inventory-II (BDI-II). MR imaging for the evaluation of structural changes included H1-MR spectroscopy, hippocampal volumetry, and diffusion tensor imaging (DTI). The applied multimodal imaging revealed no significant differences between patients with previous SAH and patients with incidental aneurysms; there were also no substantial differences between patients with and without previous SAH with respect to depression and anxiety. However, we observed significantly higher mean HADS scores in patients treated surgically versus patients treated by coiling (p < 0.01). BDI-II tended to be higher in surgically treated patients, but this difference appeared statistically insignificant. Surgically treated patients displayed substantial hippocampal damage in all imaging techniques: reduction in mean concentrations of N-acetylaspartate (p = 0.04), hippocampal volume reduction (p = 0.012), and diffusion disorder (p = 0.02). The structural alterations correlated significantly with the increased HADS scores. In contrast to endovascular treatment, aneurysm surgery seems to be associated with an increased incidence of mood disorders corresponding to hippocampal neuronal loss, independent of preceding SAH.

BACKGROUND AND PURPOSE: In acute stroke, CTP is often used to visualize the endangered brain areas, including the ischemic core and the penumbra. Our goal was to assess the evolution of the infarct after mechanical thrombectomy and to analyze the interventional factors determining the fate of the penumbra. MATERIALS AND METHODS: All patients receiving mechanical thrombectomy in the anterior circulation and receiving CTP beforehand were identified. The infarct volume was specified. The clinical parameters, outcome, and interventional results were correlated with the CTP and the final infarct size. RESULTS: In total, 73 patients were included. After mechanical thrombectomy, 78.1% reached a TICI score of 3/2b. The final infarct volume was significantly smaller, with a TICI score of 3/2b compared with less sufficient recanalization (19.60 ± 3 cm(3) versus 38.1 ± 9 cm(3); P < .001). After TICI 3/2b recanalization, 81% ± 5.2% of the potential infarct size (calculated as the sum of infarct core and penumbra) could be rescued. In patients with TICI scores of 2a or worse, only 39 ± 28.3 were salvaged (P < .001). The Alberta Stroke Program Early CT Score after successful recanalization TICI score of 3/2b resulted in a decline of 1.9 ± 1.4 compared with the significantly higher degradation score of 3.7 ± 1.7 after recanalization, with a TICI score of 2a or worse. A recanalization TICI score of 3/2b resulted in an NIHSS improvement of 7.3 ± 0.8 NIHSS points, whereas a poorer recanalization improved on the NIHSS by only 2.5 ± 1.5 points (P < .01). CONCLUSIONS: Mechanical thrombectomy is a potent method to rescue large areas of penumbra in acute stroke.

Brain metastases occur in 10% to 40% of patients harboring cancer. In cases of neurosurgical metastasis resection, all postoperative neurological deterioration should be avoided. Reasons for postoperative deficits can be direct tissue damage due to resection, hemorrhage, venous congestive infarcts, or arterial ischemic events leading to tissue infarction. The aim of this study was to evaluate whether postoperative ischemic infarctions occur in surgery for brain metastasis and to determine their influence on new postoperative neurological deficits.Patients who underwent resection of brain metastases and had preoperative and early postoperative (within 48 hours) MRI scans, including diffusion-weighted imaging sequences and apparent diffusion coefficient maps, between January 2009 and May 2012 were included in this study. Clinical and histopathological data (histopathological results, pre- and postoperative neurological status, and previous tumor-specific therapy) were recorded.One hundred twenty-two patients (56 male, 66 female) who underwent resection of brain metastases were included. The patients' mean age was 60 years (range 21-89 years). The mean time span from initial tumor diagnosis to resection of brain metastasis was 44 months (range 0-338 months). The mean preoperative Karnofsky Performance Status was 80% (exact mean 76% ± 17% [SD]), and the mean postoperative value was 80% (exact mean 78% ± 17%). Twelve (9.8%) of the 122 patients had postoperative permanent worsening of a neurological deficit or a new permanent neurological deficit; 44 (36.1%) of the 122 patients had postoperative ischemic lesions. When comparing patients with and without previous brain irradiation, 53.8% of patients with previous brain irradiation had ischemic lesions on postoperative imaging compared with 31.3% of patients without previous brain irradiation (p = 0.033). There was a significant association between ischemia and postoperative neurological status deterioration (transient or permanent); 13 (29.5%) of 44 patients with ischemic lesions had deterioration of their neurological status compared with 7 (9%) of the 78 patients who did not have ischemic lesions (p = 0.003).This study demonstrates a high prevalence of vascular incidents in patients undergoing resection for metastatic brain disease. Patients harboring postoperative ischemic lesions detected by MRI have a higher rate of neurological deficits (transient or permanent). Patients who had previous irradiation therapy are at higher risk of developing postoperative ischemic lesions. A large number of postoperative neurological deficits are caused by ischemic incidents.

A blood oxygenation level-dependent (BOLD)-based apparent relative oxygen extraction fraction (rOEF) as a semi-quantitative marker of vascular deoxygenation has recently been introduced in clinical studies of patients with glioma and stroke, yielding promising results. These rOEF measurements are based on independent quantification of the transverse relaxation times T2 and T2* and relative cerebral blood volume (rCBV). Simulations demonstrate that small errors in any of the underlying measures may result in a large deviation of the calculated rOEF. Therefore, we investigated the validity of such measurements. For this, we evaluated the quantitative measurements of T2 and T2* at 3 T in a gel phantom, in healthy subjects and in healthy tissue of patients with brain tumors. We calculated rOEF maps covering large portions of the brain from T2, T2* and rCBV [routinely measured in patients using dynamic susceptibility contrast (DSC)], and obtained rOEF values of 0.63 ± 0.16 and 0.90 ± 0.21 in healthy-appearing gray matter (GM) and white matter (WM), respectively; values of about 0.4 are usually reported. Quantitative T2 mapping using the fast, clinically feasible, multi-echo gradient spin echo (GRASE) approach yields significantly higher values than much slower multiple single spin echo (SE) experiments. Although T2* mapping is reliable in magnetically homogeneous tissues, uncorrectable macroscopic background gradients and other effects (e.g. iron deposition) shorten T2*. Cerebral blood volume (CBV) measurement using DSC and normalization to WM yields robust estimates of rCBV in healthy-appearing brain tissue; absolute quantification of the venous fraction of CBV, however, is difficult to achieve. Our study demonstrates that quantitative measurements of rOEF are currently biased by inherent difficulties in T2 and CBV quantification, but also by inadequacies of the underlying model. We argue, however, that standardized, reproducible measurements of apparent T2, T2* and rCBV may still allow the estimation of a meaningful apparent rOEF, which requires further validation in clinical studies.

Background: In MS, the relationship between lesions within cerebral white matter (WM) and atrophy within deep gray matter (GM) is unclear. Objective: To investigate the spatial relationship between WM lesions and deep GM atrophy. Methods: We performed a cross-sectional structural magnetic resonance imaging (MRI) study (3 Tesla) in 249 patients with clinically-isolated syndrome or relapsing–remitting MS (Expanded Disability Status Scale score: median, 1.0; range, 0–4) and in 49 healthy controls. Preprocessing of T1-weighted and fluid-attenuated T2-weighted images resulted in normalized GM images and WM lesion probability maps. We performed two voxel-wise analyses: 1. We localized GM atrophy and confirmed that it is most pronounced within deep GM; 2. We searched for a spatial relationship between WM lesions and deep GM atrophy; to this end we analyzed WM lesion probability maps by voxel-wise multiple regression, including four variables derived from maxima of regional deep GM atrophy (caudate and pulvinar, each left and right). Results: Atrophy of each deep GM region was explained by ipsilateral WM lesion probability, in the area most densely connected to the respective deep GM region. Conclusion: We demonstrated that WM lesions and deep GM atrophy are spatially related. Our results are best compatible with the hypothesis that WM lesions contribute to deep GM atrophy through axonal pathology.

The aim of surgical treatment of glioma is the complete resection of tumor tissue with preservation of neurological function. Inclusion of diffusion-weighted imaging (DWI) in the postoperative MRI protocol could improve the delineation of ischemia-associated postoperative neurological deficits. The present study aims to assess the incidence of infarctions following resection of newly diagnosed gliomas in comparison with recurrent gliomas and the influence on neurological function.Patients who underwent glioma resection for newly diagnosed or recurrent gliomas had early postoperative MRI, including DWI and apparent diffusion coefficient (ADC) maps. Postoperative areas of restricted diffusion were classified as arterial territorial infarctions, terminal branch infarctions, or venous infarctions. Tumor entity, location, and neurological function were recorded.New postoperative ischemic lesions were identified in 26 (31%) of 84 patients with newly diagnosed gliomas and 20 (80%) of 25 patients with recurrent gliomas (p0.01). New permanent and transient neurological deficits were more frequent in patients with recurrent gliomas than in patients with newly diagnosed tumors. Patients with neurological deficits had a significantly higher rate of ischemic lesions.Postoperative infarctions occur frequently in patients with newly diagnosed and recurrent gliomas and do have an impact on postoperative neurological function. In this patient cohort there was a higher risk for ischemic lesions and for deterioration of neurological function after resection of recurrent tumors. Radiogenic and postoperative tissue changes could contribute to the higher risk of an ischemic infarction in patients with recurrent tumors.

Aiming at iron-related T2-hypointensity, which is related to normal aging and neurodegenerative processes, we here present two practicable approaches, based on Bayesian inference, for preprocessing and statistical analysis of a complex set of structural MRI data. In particular, Markov Chain Monte Carlo methods were used to simulate posterior distributions. First, we rendered a segmentation algorithm that uses outlier detection based on model checking techniques within a Bayesian mixture model. Second, we rendered an analytical tool comprising a Bayesian regression model with smoothness priors (in the form of Gaussian Markov random fields) mitigating the necessity to smooth data prior to statistical analysis. For validation, we used simulated data and MRI data of 27 healthy controls (age: [Formula: see text]; range, [Formula: see text]). We first observed robust segmentation of both simulated T2-hypointensities and gray-matter regions known to be T2-hypointense. Second, simulated data and images of segmented T2-hypointensity were analyzed. We found not only robust identification of simulated effects but also a biologically plausible age-related increase of T2-hypointensity primarily within the dentate nucleus but also within the globus pallidus, substantia nigra, and red nucleus. Our results indicate that fully Bayesian inference can successfully be applied for preprocessing and statistical analysis of structural MRI data.

Multiple sclerosis (MS) is a heterogeneous disease with respect to lesion pathology, course of disease, and treatment response. Imaging modalities are needed that allow better definition of MS lesions in vivo. The aim of this study was to establish an MRI- and PET/CT-based imaging modality and to evaluate approved and promising PET tracers in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. Methods: MRI and PET/CT scans were obtained in Dark agouti rats with EAE and healthy control rats. The PET tracers 2-18F-fluoro-2-deoxy-d-glucose (18F-FDG), 3′-deoxy-3′-18F-fluorothymidine (18F-FLT), and O-(2-18F-fluoro-ethyl)-l-tyrosine (18F-FET) were used as surrogate markers of glucose utilization, proliferative activity, and amino acid transport and protein biosynthesis. Immediately after the PET/CT scan, animals were sacrificed for autoradiography, histologic work-up, or RNA expression analysis. Results: EAE lesions were predominantly located in the spinal cord. With MRI, we were able to detect inflammatory lesions in diseased rats, which correlated well with inflammatory infiltrates as determined by histology. Increased 18F-FDG uptake was observed in spinal cord lesions in all diseased rats. Further investigation by volume-of-interest analysis demonstrated a correlation between the density of histologically proven cellular infiltrates and the 18F-FDG signal intensity in PET (FDF=3 = 5.9, P = 0.001) and autoradiography (FDF=3 = 4.2, P = 0.008). With 18F-FET and 18F-FLT, no definite uptake could be observed on PET scans, whereas autoradiography showed slight radiotracer accumulation in some lesions. Conclusion: Spinal cord inflammatory lesions in the EAE model can be noninvasively visualized in vivo using MRI and 18F-FDG PET/CT. Localized 18F-FDG uptake correlates better with a histologically proven abundance of inflammatory cells as a critical marker of disease activity than MRI. Neither 18F-FET nor 18F-FLT seems to be a suitable marker for the in vivo detection of inflammatory lesions.

We present the first report on familial pineocytoma. The propositus, a 31-year-old man, presented with incontinence due to a cystic and haemorrhagic tumour of the pineal region. His 34-year-old sister, who had suffered from tinnitus for several years, also had a pineal tumour. Histopathology following tumour resection revealed pineocytomas (WHO grade 1). Cerebral MRI examinations of the patient’s brother and father did not reveal any pineal region abnormalities. Their mother had developed breast cancer at the age of 43. Although not impossible, it is rather unlikely that pineocytomas occurring in siblings are pure coincidence because of the rarity of this type of tumour.

Recently, mutations in an open-reading frame on chromosome 19 (C19orf12) were identified as a novel genetic factor in neurodegeneration with brain iron accumulation (NBIA). Because of the mitochondrial localization of the derived protein, this variant is referred to as mitochondrial membrane protein-associated neurodegeneration with brain iron accumulation (MPAN).We describe the clinical phenotype and MRI of 3 newly identified individuals with MPAN due to either previously reported or novel homozygous or compound heterozygous genetic alterations in C19orf12.MPAN is characterized by a juvenile-onset, slowly progressive phenotype with predominant lower limb spasticity, generalized dystonia, and cognitive impairment. Typical additional features include axonal motor neuropathy and atrophy of the optic nerve. MRI showed iron deposition in the globus pallidus and substantia nigra without the eye-of-the-tiger sign, which is typical for PKAN, the most frequent form of NBIA.

HSV causes a wide range of pathologies in the human CNS including meningitis, myelitis, and encephalitis (HSE). Even with early initiation of antiviral treatment and advances in neurocritical care, HSE remains a life-threatening condition associated with high mortality and morbidity. Cerebrovascular complications contribute to the devastating prognosis and include brain edema, ischemic stroke, and intracerebral hemorrhage.1 Primary or secondary vasculitis related to an underlying disease may be restricted to the nervous system or involve multiple organs in the context of systemic disease. The list of pathogens that may cause vascular inflammation within the CNS is comprehensive.2 Among herpesviruses, a high frequency of vasculitic complications is reported for varicella zoster virus (VZV).3 Here, we report a case of cerebral HSV-2 vasculitis, which was masked by the initial presentation as thalamic hemorrhage and followed by an encephalitic syndrome and multifocal ischemic stroke. A 72-year-old immunocompetent man was referred with acute onset of nonfluent aphasia and right-sided weakness. CT scan revealed a 4 × 1.8 cm left thalamic hemorrhage. He was taking ramipril and a combination of pioglitazone/metformin due to hypertension and diabetes, respectively. Since he had been living alone, details on prior signs and symptoms were scarce and complicated by aphasia. Laboratory examinations including coagulation parameters …

Purpose. We analyzed our experience with the phenox clot retriever as part of a multimodal mechanical thrombectomy (MTE) approach in acute ischemic stroke.Methods. 56 patients were treated by MTE with the phenox clot retriever alone or in combination with other modalities.Results. Overall we achieved TICI 2b/3 reperfusion rates of 61,9%. In multimodally treated patients we achieved reperfusion rates of 72,8%. There were 3 (5,5%) severe adverse events, all symptomatic intracranial hemorrhages. The mean angio to reperfusion times (ART) were 74 minutes for phenox-only procedures and 51 minutes for multimodal procedures. A chronological analysis showed a reduction of ART from 70,5 to 49,4 minutes and an increase of TICI 2b/3 recanalizations from 53,8% to 81,8%. Throughout the observation period there was a significant shift towards multimodal procedures with simultaneous increase of TICI 2b/3 reperfusions. Both effects are partially attributable to our institutional learning curve. NIHSS improvement could be seen in 54% () overall and in 73% () of MCA recanalizations.Conclusions. The phenox clot retriever is a safe and effective tool for MTE in acute stroke patients, with faster and better reperfusion results when used as part of a multimodal strategy. Clinical improvement is more frequent in MCA recanalizations.

Background Pittsburgh Compound B ([ 11 C] PiB) is a specific positron emission tomography (PET) marker of cerebral amyloid deposits. Only few data have been published on in vivo longitudinal changes of amyloid load in Alzheimer's disease (AD) patients, with conflicting results. Therefore, little is known about the factors that influence these changes. Methods A group of 24 patients with probable AD diagnosed by combining established clinical criteria with an AD-typical pattern in [ 18 F] fluoro-deoxy-glucose PET underwent [ 11 C] PiB-PET examinations at baseline and after 24 months. The difference of amyloid load between the two examinations and the association with clinical and neurobiological variables was examined with a regions-of-interest approach and voxel-based analyses. Results Cerebral [ 11 C] PiB uptake ratio increased significantly by an annual rate of 3.92%. Although the increase occurred in all parts of the neocortex, no increase was detected in the archipallium. The increase was gene-dose-dependent (analysis of variance p = .012) to the number of apolipoprotein E e4 alleles. Progression of dementia symptoms was correlated to the [ 11 C] PiB increase in numerous regions associated with cognition. Conclusions The results of this study indicate that a significant increase of amyloid deposition occurs in patients with AD during a relatively short interval of its clinical course. The rate of amyloid aggregation rate is closely associated with the apolipoprotein E genotype, which might be important for the evaluation of antiamyloid drug treatment effects. The present study further emphasizes the value of amyloid-plaque imaging as a marker of disease progression and as a potential surrogate marker to be used in antiamyloid drug trials.

Background: It is well known that pituitary volume decreases with age; little is known about the influences of female cycle, intake of oral contraceptives, number of given births and duration of menopause on pituitary morphology. Furthermore, these contexts have never been examined with 3-tesla MRI, from which a high spatial resolution is expected. Methods: Ninety-four women from 18 to 80 years (mean 64 years) had to answer a questionnaire concerning their cycle situation, menopause, hormone intake and childbirths before receiving a 3-tesla MRI scan (Achieva, Philips, N.V.), including a T1-weighted TSE sequence of the sella turcica. Pituitary volumes and diameters were measured with the software iplan® (BrainLAB, Feldkirchen, Germany). Results: A significant reverse correlation was found between age and pituitary volume (p < 0.0001)/cranio-caudal diameter (p = 0.02). In addition, an age-independent influence of oral contraceptives was found, indicating smaller pituitary sizes with hormone intake (p = 0.003). Cycle phase, number of given births and onset or duration of menopause had no effects on pituitary size. Conclusion: Three-tesla MRI suggests that pituitary volume not only decreases with age, it also seems to be related to long-term hormonal changes such as intake of oral contraceptives.

In many centres both MRI and CT-myelography are performed for treatment planning of degenerative spine disease. More and more centres acquire 3-Tesla MRI scanners in which some artefacts, which lead to difficulties in image evaluation, are more pronounced than at 1.5 Tesla. Aim of this study was to compare spinal physiological and pathological anatomy between 3-Tesla MRI and CT-myelography and to review current imaging standards.In 47 spinal segments commonly used 3-Tesla T2-weighted sequences and CT-myelography studies were evaluated retrospectively. Spinal canal, neural foraminal, spinal cord and disc protrusion diameters were measured.The spinal canal was found to be 10% tighter with the utilized MRI sequences, in comparison to CT-M and foraminal diameters were found to be 19.7% tighter in MRI. This was more pronounced in narrowed than in healthy segments. Spinal cord size and size of disc protrusions displayed no significant difference between MRI and CT-myelography.The main advantage of CT-myelography, in comparison to 3-Tesla MRI, is the reliable information about the bony structures. Soft tissues like the spinal cord or disc protrusions were visualised equivalently with both modalities concerning diameters.

We evaluated the effect of hyperbaric oxygen therapy (HBO) on experimental brain contusions in rats using magnetic resonance imaging (MRI).Ten Sprague-Dawley rats were investigated at 24 h and 72 h after controlled cortical impact injury. One hour after trauma, 5 rats were treated for 60 min with 100% oxygen at 2.5 absolute atmosphere (ATA), 5 were kept at normobaric room air. MRI was performed longitudinally at 24 h and 72 h after injury. Lesion volume was determined in T2 weighted MRI scans. Relative apparent diffusion coefficient (ADC) changes were calculated in comparison to the contralateral side.Following HBO, T2 lesion volume was smaller at 24 h versus controls (63.1 +/- 16.5 mm3 vs. 87.4 +/- 13.8 mm3, p0.05), and decreased further at 72 h (46.8 +/- 17.8 mm3 vs. 92.5 +/- 13.1 mm3, p0.01). At 24 h, the mean relative ADC change in the lesion area decreased from + 26.8 +/- 2.3% in controls to + 2.3 +/- 12.2% in HBO animals (p0.01). At 72 h, the HBO effect on relative ADC values was less when compared to 24 h.A 60-minute exposure to hyperbaric oxygen starting 1 h after impact injury significantly attenuated lesion growth and relative increase of ADC values within the contused area for up to 72 h. Thus, a "single-shot" HBO treatment seems to have long-lasting neuroprotective effects on the contused brain and its penumbra.

As effective stroke treatment by thrombolysis is bound to a narrow time window excluding most patients, numerous experimental treatment strategies have been developed to gain new options for stroke treatment. However, all approaches using neuroprotective agents that have been successfully evaluated in rodents have subsequently failed in clinical trials. Existing large animal models are of significant scientific value, but sometimes limited by ethical drawbacks and mostly do not allow for long-term observation. In this study, we are introducing a simple, but reliable stroke model using permanent middle cerebral artery occlusion in sheep. This model allows for control of ischemic lesion size and subsequent neurofunctional impact, and it is monitored by behavioral phenotyping, magnetic resonance imaging, and positron emission tomography. Neuropathologic and (immuno)-histologic investigations showed typical ischemic lesion patterns whereas commercially available antibodies against vascular, neuronal, astroglial, and microglial antigens were feasible for ovine brain specimens. Based on absent mortality in this study and uncomplicated species-appropriate housing, long-term studies can be realized with comparatively low expenditures. This model could be used as an alternative to existing large animal models, especially for longitudinal analyses of the safety and therapeutic impact of novel therapies in the field of translational stroke research.

BACKGROUND We evaluated the effect of hyperbaric oxygen therapy (HBO) on experimental brain contusions in rats using magnetic resonance imaging (MRI). MATERIALS AND METHODS Ten Sprague-Dawley rats were investigated at 24 h and 72 h after controlled cortical impact injury. One hour after trauma, 5 rats were treated for 60 min with 100% oxygen at 2.5 absolute atmosphere (ATA), 5 were kept at normobaric room air. MRI was performed longitudinally at 24 h and 72 h after injury. Lesion volume was determined in T2 weighted MRI scans. Relative apparent diffusion coefficient (ADC) changes were calculated in comparison to the contralateral side. RESULTS Following HBO, T2 lesion volume was smaller at 24 h versus controls (63.1 +/- 16.5 mm3 vs. 87.4 +/- 13.8 mm3, p < 0.05), and decreased further at 72 h (46.8 +/- 17.8 mm3 vs. 92.5 +/- 13.1 mm3, p < 0.01). At 24 h, the mean relative ADC change in the lesion area decreased from + 26.8 +/- 2.3% in controls to + 2.3 +/- 12.2% in HBO animals (p < 0.01). At 72 h, the HBO effect on relative ADC values was less when compared to 24 h. DISCUSSION A 60-minute exposure to hyperbaric oxygen starting 1 h after impact injury significantly attenuated lesion growth and relative increase of ADC values within the contused area for up to 72 h. Thus, a "single-shot" HBO treatment seems to have long-lasting neuroprotective effects on the contused brain and its penumbra.

Different techniques for measuring of perfusion are clinically available, but these are usually applied to healthy brain tissue.Five different techniques were used here in 12 patients with brain tumors to investigate the impact of tumor vascularization on the perfusion signal: three qualitative dynamic contrast-enhanced/susceptibility-contrast magnetic resonance imaging (DCE-MRI/DSC-MRI) techniques exploiting T(1), T(2), T(2)(*) contrast, and two quantitative techniques, pulsed arterial spin labeling (PASL) and H(2)(15)O positron emission tomography (H(2)(15)O-PET).In a first approximation, a linear correlation was found between all five imaging modalities regarding the perfusion signal of both, normal brain tissue and tumor. The estimated values for tumor perfusion differed significantly between the techniques (1=methodical mean in arbitrary units): PASL: 0.83, H(2)(15)O-PET: 0.62, T(1)-DCE: 1.73, T(2)-DCE: 0.69, T(2)(*)-DSC: 0.89.The tumor perfusion values, determined with different techniques are not comparable. The T(2)(*)-DSC, here applied with contrast agent presaturation of extravascular space, and PASL depict median perfusion most reliably.

Functional magnetic resonance imaging based on blood-oxygenation-level-dependent (BOLD) signal variations is clinically used to investigate the impact of neurological disorders on brain function. Such disorders effect not only the localization but also the amplitude and extent of the BOLD signal. Statistical methods are useful to localize the BOLD signal but fail to quantify functional activity because they rely on arbitrary thresholds. This article presents a method that uses a priori defined VOI (volume of interest) and independently quantifies the mean BOLD signal and extent of the activated volume. The technique is based on the separation of the VOI signal difference distribution into a noise and an activation contribution. The technique does not require any threshold and is nearly independent of the preselected VOI size. The technique was verified in a test group of 17 subjects performing bilateral finger tapping. The results were compared with those of conventional analysis based on statistical tools. A standard imaging technique using FID-EPI (free induction decay echo-planar imaging, TR = 4000 ms, TE = 66 ms, 60 images activation, 60 images rest) was employed. The activated volume, V, and signal difference, deltaS, of the motor cortex were determined with an accuracy of sigma(V) = 17.1% and sigma(deltaS) = 3.6%, respectively. The activated volume of the left hemispheric motor area was significantly greater (P = 0.025) then in the right hemispheric, VL = 7.35 +/- 2.29 cm3 versus VR = 6.39 +/- 2.34 cm3. The result is consistent with the findings obtained by other techniques. On the other hand, the statistical methods did not yield any significant difference in activation between both hemispheres. The VOI-based method presented here is an additional tool to study the extent and amplitude of the BOLD signal.

In stroke, stem cell (SC) treatment is currently in the stage of translation from preclinical to clinical testing as a new therapy option. It is estimated to have the potential to overcome the therapeutic nihilism which exists in stroke apart from the 3-hours time window in which thrombolysis is effective. We have developed a new large-animal stroke model with the aim to apply this model for evaluation of the effect of autologous SCs cells on stroke outcome. This present study was initiated to test whether it is feasible to quantify sheep brain perfusion and glucose consumption (as a surrogate parameter of brain viability) after stroke by employing a clinical PET scanner. In adult male Merino sheep, stroke was induced by complete left middle cerebral artery occlusion (MCAO) using high-frequency bipolar forceps. 24h after MCAO, 4.0mio kg-1 autologous mononuclear bone-marrow cells (containing 1.5-2.0% stromal and hematopoietic SCs) were given i.v. Brain PET was carried ou t immediately before SC application, 2wks and 6wks after MCAO. For that purpose, the sheep were anesthetized, i.v. injected with 1000 and 370 MBq [15O]H2O and [18F]FDG, respectively, and dynamically scanned on a clinical high-resolution ECAT EXACT HR+ scanner. The PET imaging was paralleled by neurological investigations using an established clinical score as well as by MRI (1.5T Gyroscan Integra; T1, T2, T2*, diffusion-weighted sequences, MRA). The PET image data were co-registered with the individual MRI data employing the MultiModality software. The animals were sacrificed 7wks after MCAO and brain histology was obtained. So far, 13 PET investigations have been carried out in the animals. Radiotracer input function which is required for PET data modeling was no obtainable from arterial blood samples. This was due to the follow-up design of this study and the complex anatomy of the sheep vasculature. As an alternative it was verified that it is possible to derive the input function internally from