Stella Blasel

Diffusion tensor imaging in patients with adult chronic idiopathic hydrocephalus.

OBJECTIVEDiffusion tensor imaging (DTI) parameters were investigated in patients with chronic idiopathic hydrocephalus to evaluate microstructural changes of brain tissue caused by chronic ventricular dilatation. METHODSEleven patients fulfilling the criteria for possible or probable idiopathic normal pressure hydrocephalus and 10 healthy control subjects underwent MRI at 3 Tesla, including DTI with 12 gradient directions. Patients were scanned before lumbar cerebrospinal fluid (CSF) withdrawal tests. Differences in fractional anisotropy (FA) and mean diffusivity (MD) between patients and controls were assessed using 2 different methods: manual definition of regions of interest and a fully automated method, TBSS (Tract-Based Spatial Statistics). DTI parameters were correlated with clinical findings. RESULTSCompared with the control group, patients with chronic idiopathic hydrocephalus had significantly higher MD values in both the periventricular corticospinal tract (CST) and the corpus callosum (CC), whereas FA values were significantly higher in the CST but lower in the CC. DTI parameters of the CST correlated with the severity of gait disturbances. CONCLUSIONMicrostructural changes in periventricular functionally relevant white matter structures (CSF, CC) in chronic idiopathic hydrocephalus can be visualized using DTI. Further studies should investigate the change of DTI parameters after CSF shunting and its relation to neurologic outcome.

Influence of iMRI-guidance on the extent of resection and survival of patients with glioblastoma multiforme.

Intraoperative MRI (iMRI) is used in glioma surgery mainly to determine the extent of resection, allowing surgeons to immediately continue resection in case of residual tumor tissue. The aim of this study is to report on the influence of the use of iMRI on the extent of resection and survival of patients with glioblastoma multiforme (GBM). We analyzed our prospectively collected database of patients with GBM operated upon during the initial period after installation of an iMRI; between July 2004 and December 2005, all patients with GBM undergoing intended complete tumor resection were included in this study, while patients undergoing mere tumor biopsy or intended incomplete resection were not. In total, 43 Patients met the inclusion criteria. Of these, 10 patients (23.3%) were operated upon with the help of iMRI while 33 underwent conventional tumor resection. All patients underwent postoperative high-field MR imaging at 1.5 Tesla to determine the extent of resection. Subsequently, all patients received adjuvant treatment. Median patient age was 60.0 years; median overall survival was 70.7 weeks. Radiologically complete tumor resection (P < 0.001) and the administration of temozolomide chemotherapy (P < 0.01) were statistically significant prognostic factors in a multivariate analysis. The rate of complete tumor resections was significantly higher in the iMRI group than in the conventional surgery group (P < 0.05). Patient age was not a prognostic factor in our series of patients (P = 0.22). Intraoperative MRI is a helpful tool to increase the extent of resection in GBM surgery and thereby improve patient survival.

Distribution and prognostic relevance of tumor-infiltrating lymphocytes (TILs) and PD-1/PD-L1 immune checkpoints in human brain metastases

The activation of immune cells by targeting checkpoint inhibitors showed promising results with increased patient survival in distinct primary cancers. Since only limited data exist for human brain metastases, we aimed at characterizing tumor infiltrating lymphocytes (TILs) and expression of immune checkpoints in the respective tumors. Two brain metastases cohorts, a mixed entity cohort (n = 252) and a breast carcinoma validation cohort (n = 96) were analyzed for CD3+, CD8+, FOXP3+, PD-1+ lymphocytes and PD-L1+ tumor cells by immunohistochemistry. Analyses for association with clinico-epidemiological and neuroradiological parameters such as patient survival or tumor size were performed. TILs infiltrated brain metastases in three different patterns (stromal, peritumoral, diffuse). While carcinomas often show a strong stromal infiltration, TILs in melanomas often diffusely infiltrate the tumors. Highest levels of CD3+ and CD8+ lymphocytes were seen in renal cell carcinomas (RCC) and strongest PD-1 levels on RCCs and melanomas. High amounts of TILs, high ratios of PD-1+/CD8+ cells and high levels of PD-L1 were negatively correlated with brain metastases size, indicating that in smaller brain metastases CD8+ immune response might get blocked. PD-L1 expression strongly correlated with TILs and FOXP3 expression. No significant association of patient survival with TILs was observed, while high levels of PD-L1 showed a strong trend towards better survival in melanoma brain metastases (Log-Rank p = 0.0537). In summary, melanomas and RCCs seem to be the most immunogenic entities. Differences in immunotherapeutic response between tumor entities regarding brain metastases might be attributable to this finding and need further investigation in larger patient cohorts.

Phospholipid Metabolites in Recurrent Glioblastoma: In Vivo Markers Detect Different Tumor Phenotypes before and under Antiangiogenic Therapy

Purpose Metabolic changes upon antiangiogenic therapy of recurrent glioblastomas (rGBMs) may provide new biomarkers for treatment efficacy. Since in vitro models showed that phospholipid membrane metabolism provides specific information on tumor growth we employed in-vivo MR-spectroscopic imaging (MRSI) of human rGBMs before and under bevacizumab (BVZ) to measure concentrations of phosphocholine (PCho), phosphoethanolamine (PEth), glycerophosphocholine (GPC), and glyceroethanolamine (GPE). Methods 1H and 31P MRSI was prospectively performed in 32 patients with rGBMs before and under BVZ therapy at 8 weeks intervals until tumor progression. Patients were dichotomized into subjects with long overall survival (OS) (>median OS) and short OS (<median OS) survival time from BVZ-onset. Metabolite concentrations from tumor tissue and their ratios were compared to contralateral normal-appearing tissue (control). Results Before BVZ, 1H-detectable choline signals (total GPC and PCho) in rGBMs were elevated but significance failed after dichotomizing. For metabolite ratios obtained by 31P MRSI, the short-OS group showed higher PCho/GPC (p = 0.004) in rGBMs compared to control tissue before BVZ while PEth/GPE was elevated in rGBMs of both groups (long-OS p = 0.04; short-OS p = 0.003). Under BVZ, PCho/GPC and PEth/GPE in the tumor initially decreased (p = 0.04) but only PCho/GPC re-increased upon tumor progression (p = 0.02). Intriguingly, in normal-appearing tissue an initial PEth/GPE decrease (p = 0.047) was followed by an increase at the time of tumor progression (p = 0.031). Conclusion An elevated PCho/GPC ratio in the short-OS group suggests that it is a negative predictive marker for BVZ efficacy. These gliomas may represent a malignant phenotype even growing under anti-VEGF treatment. Elevated PEth/GPE may represent an in-vivo biomarker more sensitive to GBM infiltration than MRI.

Is the surgical repair of unruptured atherosclerotic aneurysms at a higher risk of intraoperative ischemia

BACKGROUND The incidence of ischemia might be increased in the surgical repair of atherosclerotic unruptured aneurysms compared to non-atherosclerotic aneurysms. The atherosclerotic wall might increase the occurrence of thrombembolic events or its rigidity might endanger the occlusion of perforators within the aneurysm vicinity. METHODS 87 patients (53 patients without and 34 patients with atherosclerotic unruptured aneurysms, 50.5 ± 9.7 years) were analyzed for severity of atherosclerosis within the aneurysm and the aneurysm bearing vessel, surgical maneuvers, intraoperative alterations in evoked potentials and clinical and neuroradiological results. RESULTS Temporary vessel occlusion (25% vs. 50%, p = 0.021), repositioning of a permanent clip (21% vs. 56%, p = 0.001) and aneurysm remnants (2% vs. 18%, p = 0.012) occurred more often in patients with atherosclerotic aneurysms. At 6 months, 3/34 patients with atherosclerosis (8.8%) had an unfavorable outcome, all patients without atherosclerosis had a favorable outcome (p = 0.056). CONCLUSION The surgical repair of unruptured aneurysms is safe but patients with atherosclerotic altered vessels and aneurysms accounted to a minor increase in unfavorable outcome and an increased risk of morbidity at 6 months postoperatively. This factor should be taken into consideration when performing surgery of atherosclerotic, unruptured aneurysms.

MR Imaging of Midbrain Pathologies

The spectrum of pathologic processes affecting the midbrain features some differences to other brain areas. The midbrain is exposed to traumatic alterations due to its position between the tentorial edges, and some neurodegenerative and metabolic-toxic diseases may typically involve the midbrain. Isolated midbrain ischemia is rare, whereas the midbrain is typically part of the “top of the basilar” syndrome. Primary midbrain tumors are also infrequent and often show a benign clinical course. Apart from multiple sclerosis other inflammatory autoimmune processes and some infectious agents predominantly affect the brainstem including the midbrain. This review discusses the different pathologic processes of the midbrain, i.e., infarction, hemorrhage and trauma, inflammation, toxic and metabolic diseases, neurodegeneration, neoplastic diseases, as well as pathologies typically involving the perimesencephalic cisterns.ZusammenfassungDas Spektrum pathologischer Mittelhirnprozesse weist gegenüber anderen Hirnregionen einige Besonderheiten auf. Die exponierte Lage im Tentoriumschlitz macht das Mittelhirn anfällig für traumatische Läsionen, zudem involvieren verschiedene neurodegenerative und metabolisch-toxische Erkrankungen in typischer Weise das Mittelhirn. Obschon regelhaft eine mesenzephale Beteiligung beim Basilarisspitzensyndrom vorliegt, sind isolierte Mittelhirninfarkte selten. Primäre Tumoren des Mittelhirns sind ebenfalls selten und haben meist einen gutartigen klinischen Verlauf. Neben der multiplen Sklerose befallen andere autoimmune oder erregerassoziierte Entzündungen vorwiegend den Hirnstamm einschließlich des Mittelhirns. Es werden verschiedene pathologische Mittelhirnprozesse wie ischämische Infarkte, Blutungen und Traumata, Entzündungen, toxische and metabolische Erkrankungen, Neurodegeneration und neoplastische Erkrankungen neben Pathologien, die typischerweise die perimesenzephalen Zisternen betreffen, auch unter differentialdiagnostischen Aspekten dargestellt.

Toxic leukoencephalopathy after heroin abuse without heroin vapor inhalation: MR imaging and clinical features in three patients.

Background and Purpose:Toxic leukoencephalopathy has been associated with illicit heroin vapor inhalation. Despite the nonspecific and variable clinical presentation of these patients, they show typical radiologic findings. Previous studies evaluated typical radiologic findings with symmetric infratentorial hyperintense signal changes and similar alteration in the posterior limb of the internal capsule, the splenium of corpus callosum, the medial lemniscus and the lateral brainstem. In context with the reviewed literature, a series of another three cases with toxic leukoencephalopathy after heroin abuse other than vapor inhalation is presented.Patients and Methods:All three patients underwent magnet resonance imaging (MRI) including additional diffusion- weighted imaging and apparent diffusion coefficient maps. Clinical and laboratory findings were recorded.Results:MRI of all three patients revealed similar symmetric supratentorial hyperintense signal changes involving the frontal, parietal, occipital and temporal lobes. The cortex was spared and the subcortical U fibers were partially involved. Further, the brainstem and the cerebellar white matter were not affected.Conclusion:Toxic leukoencephalopathy without involvement of the cerebellum and brainstem is a rare complication of heroin abuse. The pattern of heroin-induced toxic leukoencephalopathy on MRI might not only be related to an unknown adulterant, but also to the mode of drug administration.ZusammenfassungHintergrund und Ziel:Die toxische spongiforme Leukoenzephalopathie ist mit der Inhalation von Heroin assoziiert. Trotz variabler und unspezifischer klinischer Symptomatik finden sich typische Magnetresonanz-(MR-)tomographische Läsionsmuster. So haben frühere Studien symmetrische infratentorielle hyperintense Läsionen und zusätzliche Veränderungen im hinteren Schenkel der Capsula interna, im Centrum semiovale und im Balken aufgezeigt. In der vorliegenden Studie werden drei weitere Fälle mit toxischer Leukoenzephalopathie nach nichtinhalativem Heroinabusus präsentiert und diskutiert.Patienten und Methodik:Alle drei Patienten wurden sequentiell MR-tomographisch einschließlich diffusionsgewichteter Sequenzen untersucht und die klinischen sowie laborchemischen Befunde im Verlauf analysiert.Ergebnisse:MR-tomographisch zeigten alle drei Patienten ähnliche symmetrische, supratentoriell gelegene hyperintense Signalkonversionen im frontalen, parietalen, okzipitalen und temporalen Marklager. Der Kortex war komplett und die subkortikalen U-Fasern waren partiell ausgespart. Darüber hinaus waren der Hirnstamm sowie die zerebellären Marklagerstrukturen nicht betroffen.Schlussfolgerung:Die toxische Leukoenzephalopathie ohne Einbezug des Cerebellums und des Hirnstamms ist eine seltene Komplikation bei Heroinabusus. Das Muster der heroininduzierten toxischen Leukoenzephalopathie im MRT könnte somit nicht nur durch das Heroin selbst und mögliche Zusätze, sondern auch durch die Art der Drogenapplikation hervorgerufen werden.

Quantitative T2, T2*, and T2′ MR imaging in patients with ischemic leukoaraiosis might detect microstructural changes and cortical hypoxia

IntroductionQuantitative MRI with T2, T2*, and T2′ mapping has been shown to non-invasively depict microstructural changes (T2) and oxygenation status (T2* and T2′) that are invisible on conventional MRI. Therefore, we aimed to assess whether T2 and T2′ quantification detects cerebral (micro-)structural damage and chronic hypoxia in lesions and in normal appearing white matter (WM) and gray matter (GM) of patients with ischemic leukoaraiosis (IL). Measurements were complemented by the assessment of the cerebral blood flow (CBF) and the degree of GM and WM atrophy.MethodsEighteen patients with IL and 18 age-matched healthy controls were included. High-resolution, motion-corrected T2, T2*, and T2′ mapping, CBF mapping (pulsed arterial spin labeling, PASL), and segmentation of GM and WM were used to depict specific changes in both groups. All parameters were compared between patients and healthy controls, using t testing. Values of p < 0.05 were accepted as statistically significant.ResultsPatients showed significantly increased T2 in lesions (p < 0.01) and in unaffected WM (p = 0.045) as well as significantly increased T2* in lesions (p = 0.003). A significant decrease of T2′ was detected in patients in unaffected WM (p = 0.027), while no T2′ changes were observed in GM (p = 0.13). Both unaffected WM and GM were significantly decreased in volume in the patient-group (p < 0.01). No differences of PASL-based CBF could be shown.ConclusionNon-invasive quantitative MRI with T2, T2*, and T2′ mapping might be used to detect subtle structural and metabolic changes in IL. Assessing the grade of microstructural damage and hypoxia might be helpful to monitor disease progression and to perform risk assessment.

The striate sign: peritumoural perfusion pattern of infiltrative primary and recurrent gliomas

MR perfusion depicts angiogenesis as a key factor for growth and malignancy in gliomas by means of increased regional cerebral blood volume (rCBV). The rCBV increase is not limited to the tumour area, but may also produce a stripe-like pattern of peritumoural rCBV increase that we defined as the “striate sign”. We evaluated if prior radiochemotherapy influences perfusion values and pattern in and adjacent to malignant gliomas comparing rCBV of treated recurrent gliomas with untreated gliomas. Ninety-three patients with primary or recurrent WHO grades II–IV glial tumours underwent T2*-weighted dynamic susceptibility-weighted contrast-enhanced (DSC)-MRI. Differences of normalised rCBV and rCBVmax were evaluated using Kruskal−Wallis analysis with post hoc tests. The number of cases showing a hot spot of rCBV (rCBVmax) and/or a peritumoural striate pattern of rCBV increase (striate sign) was assessed and evaluated by Fisher’s exact test. Significance level was determined as p < 0.05. Normalised rCBV, rCBVmax and number of cases with the striate sign were significantly lower in recurrent (rCBV = 3.24 ± 1.22, rCBVmax = 5.05 ± 2.27 and striate sign = 10/24) compared to primary WHO grade IV tumours (rCBV = 4.44 ± 1.39, rCBVmax = 7.31 ± 3.0 and striate sign = 17/21, respectively). There were fewer cases with a striate sign in treated recurrent WHO grade III tumours than in untreated malignant transformed WHO grade II tumours. The pattern and degree of rCBV increase in and around gliomas differ between untreated and previously treated tumours. These differences might be due to post-therapeutic changes of the tumour-associated microvasculature by radiochemotherapy. Spectroscopic and susceptibility-weighted MR imaging may provide further insights into the tumour biology.

Perfusion MRI in the Evaluation of Suspected Glioblastoma Recurrence

Treatment‐related changes (TRC) often imitate tumor progression in glioblastomas. Increased regional cerebral blood volume (rCBV) can differentiate tumor progression from TRC after the standardized first‐line radiochemotherapy, but information about diagnostic accuracy of rCBV for patients without any clinical selection criteria is limited. Therefore, we aimed to evaluate if rCBV can differentiate between TRC and tumor progression irrespective of preceding therapies and number of tumor progressions.