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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.

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.

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.

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.

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.

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.

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.

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.

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.

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 AND PURPOSE: Similar to digital subtraction angiography, dynamic spin labeling angiography (DSLA) provides time-resolved measurements of the influx of blood into the cerebral vascular tree. We determined whether DSLA may help in assessing the degree of stenosis and whether it provides information about intracerebral collateralization and allows us to monitor the hemodynamic effects of vascular interventions. METHODS: We developed a segmented DSLA sequence that allowed the formation of images representing inflow delays in 41-ms increments. Thirty patients with unilateral carotid artery stenosis and 10 control subjects underwent DSLA. Arrival times of the labeled arterial blood bolus were measured in the carotid siphon (CS) and the middle cerebral artery (MCA) on both sides, and the corresponding side-to-side arrival time differences (ATDs) were calculated. ATDs before and after carotid endarterectomy or percutaneous angioplasty were studied in 10 patients. RESULTS: The degree of stenosis was significantly correlated with ATD in the cerebral vessels. Receiver operating characteristic analysis yielded a cutoff CS ATD of 110 ms to separate stenoses

Pulsed arterial spin labeling (PASL) perfusion imaging is an MRI technique,relying on the detection of magnetically labelled water. The aim of the present study was to determine regional CBF abnormalities in patients with Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI), the transitional clinical stage between normal cognition and dementia, as compared with cognitively normal elderly controls using PASL.MRI was performed on a 3 T MR scanner. A multislice STAR sequence with WET presaturation and thin slice periodic saturation pulses was used for PASL: readout single-shot EPI; TR/TE/a = 2500ms/17ms/90°; TI1/TI1S/TI2 = 700ms/ 1200ms/1500ms; 11 slices ; 80 pairs of labeled-control; scan time 7min 18sec. For coregistration a single shot EPI and a T1-weighted TFE sequence were acquired. Resting CBF maps were obtained from 15 elderly cognitively normal controls, 13 MCI patients and 7 patients with AD. Analysis of variance was performed across groups using SPM5. Results were thresholded at p< 0.05, corrected for FWE.Lower perfusion was found in the left and right inferior parietal cortex and angular gyrus, in the left middle temporal and posterior cingulate cortex in patients. A small reduction of perfusion was detected in the left caudate in patients as compared with cognitively normal controls.These results confirm previous findings of hypoperfusion in parietal and temporal areas of patients with MCI and AD as compared to age matched controls. In addition, lower perfusion was detected in the left caudate. PASL may be a valuable tool for investigating the transition from normal ageing to dementia.