No abstract available

[en] We present five cases of cerebral glioma that illustrate the benefit of functional CT imaging of blood-brain barrier permeability and cerebral blood volume. Functional CT uses Patlak analysis of a single location dynamic sequence to extract physiological information that is useful clinically in the assessment of cerebral gliomas. Functional CT offers distinct advantages over other functional modalities, including clearer delineation of tumour, tumour grading, measurement of tumour activity and monitoring response to therapy

[en] We report here our experience in treating high-flow arteriovenous fistulas (AVFs) of the brain and spine using balloon-assisted glue injection. During a 3-year period (2003-2005) five patients with high-flow AVFs were treated at our hospital using transarterial balloon-assisted glue injection. There were two pial AVFs, one dural AVF, one vein of Galen malformation and one perimedullary AVF of the cervical spine. All patients were clinically followed-up for 12-48 months. Immediate angiographic obliteration was achieved in all patients. The fistulas remained closed in all patients, as ascertained by follow up-angiograms. No new neurological deficits related to the procedure were detected. Clinically, one patient with severe pre-treatment neurological deficit experienced excellent recovery. Transarterial balloon-assisted glue embolization of high-flow AVFs is a feasible and efficient treatment. This technique affords more control in the glue injection and minimizes the risk of distal embolization. (orig.)

[en] Dynamic contrast-enhanced (DCE) imaging is a promising approach for in vivo assessment of tissue microcirculation. Twenty patients with clinical and routine computed tomography (CT) evidence of intracerebral neoplasm were examined with DCE-CT imaging. Using a distributed-parameter model for tracer kinetics modeling of DCE-CT data, voxel-level maps of cerebral blood flow (F), intravascular blood volume (v_i) and intravascular mean transit time (t₁) were generated. Permeability-surface area product (PS), extravascular extracellular blood volume (v_e) and extraction ratio (E) maps were also calculated to reveal pathologic locations of tracer extravasation, which are indicative of disruptions in the blood-brain barrier (BBB). All maps were visually assessed for quality of tumor delineation and measurement of tumor extent by two radiologists. Kappa (κ) coefficients and their 95% confidence intervals (CI) were calculated to determine the interobserver agreement for each DCE-CT map. There was a substantial agreement for the tumor delineation quality in the F, v_e and t₁ maps. The agreement for the quality of the tumor delineation was excellent for the v_i, PS and E maps. Concerning the measurement of tumor extent, excellent and nearly excellent agreement was achieved only for E and PS maps, respectively. According to these results, we performed a segmentation of the cerebral tumors on the base of the E maps. The interobserver agreement for the tumor extent quantification based on manual segmentation of tumor in the E maps vs. the computer-assisted segmentation was excellent (κ = 0.96, CI: 0.93-0.99). The interobserver agreement for the tumor extent quantification based on computer segmentation in the mean images and the E maps was substantial (κ = 0.52, CI: 0.42-0.59). This study illustrates the diagnostic usefulness of parametric maps associated with BBB disruption on a physiology-based approach and highlights the feasibility for automatic segmentation of cerebral tumors. (orig.)

[en] This article gives an overview over past and present studies concerning the acute management of stroke. Stroke trials involving intra-arterial thrombolytic agents, either alone or in combination with other therapies, are described. (orig.)

[en] Chemical analysis of brain tumour cyst contents has invalidated the concept of cyst formation being the result of tumour necrosis, and a common mechanism of vasogenic brain oedema and cyst formation, namely blood-brain barrier (BBB) disruption, has been suggested. To analyse a possible relationship between the occurrence of vasogenic oedema and the presence of cysts, we performed a volumetric analysis on the MRI and CT studies of 60 patients with primary or metastatic brain tumours. We compared four groups of tumours: 30 gliomas, of which 15 were cystic and 15 not and 30 metastatic brain tumours of which 15 were cystic and 15 not. Although the mean volume of oedema was similar for cystic and noncystic tumours, the ratio of oedema to tumour volume was approximately four times as high in cystic supratentorial tumours. This would support the view that cyst formation may be related to relatively greater production of oedema, possibly due to fusion of microcysts containing oedema fluid. The ratio of oedema to tumour volume is not greater in cystic cerebellar and intraventricular tumours. This may be due to the different anatomical organization of the cerebellar white matter, and the fact that the intraventricular tumours are bordered by subcortical grey matter. In these cases, spread of oedema is impeded. Formation of a large amount of brain oedema is therefore not an essential prerequisite for cyst formation. (orig.)

[en] Thrombolysis has been shown to improve neurological recovery in acute stroke. But the response to thrombolysis is variable across patients. We sought to investigate this variability by analyzing the lesion patterns following systemic thrombolysis with recombinant tissue plasminogen activator (rtPA) and tirofiban in middle cerebral artery (MCA) stroke. One hundred three consecutive stroke patients (67 ± 14 years) were grouped according to the site of MCA occlusion and successful or failed recanalization as assessed with magnetic resonance angiography. Infarct lesions were analyzed in T2-weighted magnetic resonance images after 10 days. Patients recovered markedly upon successful recanalization following thrombolysis (p < 0.05) but remained severely impaired when there was no recanalization within 24 h. Infarct lesions were smaller after successful than after failed recanalization (p < 0.005). They occurred throughout the cerebral cortex on the cerebral convexity in distal MCA occlusions with large individual heterogeneity. In contrast, there was a large lesion overlap in insular cortex, basal ganglia, internal capsule, and paraventricular white matter in proximal MCA occlusions. Systemic thrombolysis with rtPA and tirofiban of MCA occlusions resulted in early neurological recovery and preferentially peri-insular infarcts. In failed recanalization of the MCA stem there was a large lesion overlap in the hemispheric white matter and a lack of recovery. (orig.)

[en] The widespread use of silver nanoparticles (AgNPs) in medicine and in multiple commercial products has motivated researchers to investigate their potentially hazardous effects in organisms. Since AgNPs may easily enter the brain through the blood-brain barrier (BBB), characterization of their interactions with cellular components of the neurovascular unit (NVU) is of particular importance. Therefore, in an animal model of prolonged low-dose exposure, we investigate the extent and mechanisms of influence of AgNPs on cerebral microvessels. Adult rats were treated orally with small (10 nm) AgNPs in a dose of 0.2 mg/kg b.w. over a 2-week period. A silver citrate-exposed group was established as a positive control of ionic silver effects. Alterations in the expression of tight junction proteins claudin-5, ZO-1, and occludin, were observed. These effects are accompanied by ultrastructural features indicating enhanced permeability of microvessels such as focal edema of perivascular astrocytic processes and surrounding neuropil. We did not identify changes in the expression of PDGFβR which is a marker of pericytes. Ultrastructural alterations in these cells were not identified. The results show that altered integrity of cerebral vessels under a low-dose of AgNP-exposure may be the consequence of dysfunction of endothelial cells caused by disruption of tight junction proteins.

[en] Compelling evidences have shown that amyloid-β (Aβ) peptide is one of the major pathogenic factors resulting in blood-brain barrier (BBB) disruption in Alzheimer's disease (AD). However, the mechanism underlying BBB breakdown remains elusive. In our present study, we employed murine brain capillary endothelial cells (bEnd.3) as an in vitro BBB model to investigate the role of autophagy in Aβ_1–42 oligo induced BBB disruption. We first identified Aβ_1–42 oligo cytotoxicity to bEnd.3 cells as observed in the reduced cell viability and downregulation of ZO-1, Occludin and Claudin-5. Based on the observation that both downregulated expression of p-mTOR/m-TOR and upregulated ratio of LC3-II/β-actin were induced by Aβ_1–42 oligo, we then applied 3-MA, an inhibitor of autophagy, to test the role of autophagy in Aβ_1–42 oligo induced Tight junction (TJ) proteins damage. Results have shown that 3-MA partially reversed Aβ_1–42 oligo induced downregulation of ZO-1, Occludin and Claudin-5, which was further determined by LC3 siRNA. We also used rapamycin to activate autophagy and found that TJ proteins damage induced by Aβ1–42 was deteriorated even further. Given that the receptor of advanced glycation end-products (RAGE) is a pivotal receptor that mediates Aβ toxicity, RAGE siRNA was utilized to identify the involvement of RAGE in Aβ_1–42 oligo induced autophagy. The results demonstrated a suppressed autophagy with increased p-mTOR/m-TOR and decreased LC3-II/β-actin as well as increased ZO-1, Occludin and Claudin-5 in transfected cells after Aβ_1–42 oligo treatment, as compared to the non-transfected group. In summary, these results suggested that Aβ_1–42 oligo induced TJ proteins disruption via a RAGE-dependent autophagy pathway.

[en] The goal of the present study was to evaluate the reproducibility of cerebral A₁ adenosine receptor (A₁AR) quantification using [¹⁸F]CPFPX and PET in a test-retest design. Eleven healthy volunteers were studied twice. Eight brain regions ranging from high to low receptor binding were examined. [¹⁸F]CPFPX was injected as a bolus with subsequent infusion over 120 min. Various outcome parameters were compared based on either metabolite-corrected venous blood sampling [e.g. apparent equilibrium total distribution volume (DV_t')] or a reference region [ratio of specific to non-specific distribution volume (BP₂)]. Test-retest variability was low in the outcome measure BP₂ (on average 5.9%) and moderate in DV_t' (on average 13.2%). Regarding reproducibility, the outcome parameter BP₂ showed an intra-class correlation coefficient (ICC) of 0.94 ± 0.1. For DV_t' the between-subject coefficient of variation (%CV) was similar to the within-subject %CV (around 10%), resulting in a poor ICC of 0.06 ± 0.2. Our results suggest that quantification of [¹⁸F]CPFPX imaging is reproducible and reliable for PET studies of the cerebral A₁AR. Among the outcome parameters the non-invasive measures were of superior test-retest stability over the invasive. (orig.)