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Background: Amyloidopathy, one pathological hallmark of Alzheimer's disease (AD), results from dysbalanced amyloid‐β production and clearance. Therefore, disruptions in brain clearance may have a pivotal role as pathogenic drivers. Transgenic mice models of AD may serve to develop and establish minimally invasive in vivo measurement methods to observe brain clearance longitudinally. Method: We used magnetic resonance imaging (MRI) with intravenously administered gadolinium‐based contrast agent (GBCA) on a 7T small animal ultrahighfield MRI scanner to determine brain clearance efficacy. Imaging sessions were performed longitudinally in n = 9 APPswe/PS1dE9 (tg) mice and n = 9 wild type (wt) littermates at 6, 9 and 12 months of age with a scan protocol consisting of a highly T2w Inv. Rec. RARE (FLAIR) sequence. For a subsample of n = 6 wt and n = 6 tg at 9 and 12 months we used an additional T1w RARE sequence for evaluation of parenchymal changes. Both protocols were carried out every 5‐6.5 minutes for a total of 180 minutes. We determined mean voxel values in manually delineated volumes of interest in ventricles (in T2w images) and brain parenchyma (T1w images) using PMOD software. Result: We created intensity‐time‐curves and measured slopes for signal increase and decrease, derived from fitting with a model consisting of an exponential convoluted with another exponential and used to normalize area under the curve (AUC) values (Figure 1A‐C). Repeated measurements ANOVA revealed no differences in normalized AUC values regarding age in both lateral (p = 0.568, F(2, 28) = 0.577), 3rd (p = 0.306, F(1.903, 26.64) = 1.232) and 4th ventricles (p = 0.181, F(1.345, 18.83) = 1.924) and also no differences regarding genotype in both lateral (p = 0.684, F(1,16) = 0.172), 3rd (p = 0.737, F(1,16) = 0.117) and 4th ventricle (p = 0.186, F(1,16) = 1.910). Measurements of parenchymal clearance capacity are still ongoing and first results will be presented at the conference. Conclusion: Our first results showed no measurable difference in the brain clearance efficacy. This could have two possible reasons. Either ventricular clearance measurements are not sensitive enough to measure AD related changes in brain clearance or the used pathogenetic model shows no changes in clearance efficacy. Our still ongoing analyses of parenchymal brain could help to elucidate further on this question. [ABSTRACT FROM AUTHOR]

Magnetic resonance-guided focused ultrasound (MRgFUS) lesioning of the ventralis intermedius nucleus (VIM) has shown promise in treating drug-refractory essential tremor (ET). It remains unknown whether focal VIM lesions by MRgFUS have broader restorative effects on information flow within the whole-brain network of ET patients. We applied an information-theoretical approach based on intrinsic ignition and the concept of transfer entropy (TE) to assess the spatiotemporal dynamics after VIM-MRgFUS. Eighteen ET patients (mean age 71.44 years) underwent repeated 3T resting-state functional magnetic resonance imaging combined with Clinical Rating Scale for Tremor (CRST) assessments one day before (T0) and one month (T1) and six months (T2) post-MRgFUS, respectively. We observed increased whole brain ignition-driven mean integration (IDMI) at T1 (p < 0.05), along with trend increases at T2. Further, constraining to motor network nodes, we identified significant increases in information-broadcasting (bilateral supplementary motor area (SMA) and left cerebellar lobule III) and information-receiving (right precentral gyrus) at T1. Remarkably, increased information-broadcasting in bilateral SMA was correlated with relative improvement of the CRST in the treated hand. In addition, causal TE-based effective connectivity (EC) at T1 showed an increase from right SMA to left cerebellar lobule crus II and from left cerebellar lobule III to right thalamus. In conclusion, results suggest a change in information transmission capacity in ET after MRgFUS and a shift towards a more integrated functional state with increased levels of global and directional information flow. • For the first time, functional consequences of a focal VIM-lesion, are described by advanced information theory-based measures. • Information broadcasting between hubs of the tremor network is improved post-MRgFUS, correlating with tremor improvement. • VIM-MRgFUS improves global information transfer, as evidenced by increased mean integration, suggesting restorative effects. [ABSTRACT FROM AUTHOR]

Background: Recently, an orbital glymphatic system (GS) was described, that serves retinal homeostasis and clearance. In accordance to the brain GS, the orbital GS is supposed to be altered in a variety of disease, first and foremost Alzheimer's Disease (AD). Disturbances of the orbtial GS where suggested to serve as early (imaging) biomarker. Therefore it is highly desirable to visualize orbital GS function in vivo. This study investigated intravenously injected Gadolinium‐based contrast agent (GBCA) to visualize the orbital GS. We used a retrospective patient cohort of children suffering from retinoblastoma (RB) who are supposed to show altered orbital GS function to test the validity of this method. Method: This IRB approved retrospective single‐center study encompassed 539 orbital MRIs performed with an orbital coil and with the children in a state of general anesthesia. Differences of signal intensity ratios of the AC to the lens (∆SIRs) were determined between native and GBCA‐enhanced T1‐weighted images. Subsequently, ∆SIRs were correlated with histopathologic tumor features such as infiltration of the ON, choroid, ciliary body, sclera and AC. Result: ∆SIR of the RB eye was an independent, significant predictor for ON infiltration in multivariate analysis with adjustment for tumor size (p < 0.05) and increased with infiltration level (compare fig. 1A+B). ∆SIR was not predictive for any other assessed histopathologic tumor feature. Conclusion: GBCA enhancement of the AC predicts ON infiltration by RB. This might be caused by impairment of the orbital GS, which is supposed to clear toxic metabolites from the retina to the postlaminar ON (compare fig. 2). In RB with ON infiltration, this efflux path might be inhibited, which is supposed to result in disturbed retinal homeostasis, release of vascular endothelial growth factor and iris neovascularization with increased penetration of GBCA into the AC (compare fig. 3). We conclude, that GBCA‐enhanced MRI might enable visualization of (orbital) GS function in vivo and suggest assessment of this imaging approach in patients with neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: This retrospective single-center study aims to evaluate endovascular therapy (EVT) of cranial dural arteriovenous fistulas (dAVF) with ethylene vinyl alcohol (EVOH) copolymer (Onyx) regarding occlusion rates, complications, and recurrences.Material and Methods: From January 2008 to April 2018, 75 patients with dAVF (41 men, 34 women; mean age 56 years) underwent EVT with the nonadhesive liquid embolic agent as primary treatment. Patient records and angiograms were reviewed for demographic data, symptoms, fistula type and size, number of EVTs, amount of embolic material, occlusion rates, and recurrences.Results: Seventy-five patients with dAVFs were primarily embolized with EVOH in 96 EVTs. According to the Merland-Cognard classification the majority of dAVFs treated were type 4 (42.7%), followed by type 2a (18.7%), type 2a+b (17.3%), type 1 (8%), type 2b (5.3%), type 3 (5.3%), and type 5 (2.7%). Complete occlusion (CO) of the dAVF was achieved in 45/75 (60%) of cases after a single EVT and in 58 (77%) patients after one or several EVTs. Seven patients (9%) required additional surgical therapy for CO. Successful treatment was achieved for 70/75 (93%) patients including 10 (13%) patients with residual dAVFs type 1-2a. Recurrence after CO occurred in one (1.3%) patient and four (5.3%) patients remained refractory to therapy with dAVFs type > 2a. Procedure-related permanent morbidity occurred in 4/75 (5.3%) patients.Conclusion: For more than a decade transarterial EVOH embolization has established as the first-line treatment for cranial dAVFs with high cure rates and low rates of complications and recurrences. Additional neurosurgical therapy is rarely required for curative treatment. [ABSTRACT FROM AUTHOR]

Background: APPswe/PS1dE9 mice reproduce features of amyloid β (Aβ) pathology and neuronal dysfunction as reflected in electrophysiological recordings of neuronal hyperexcitability. This leads to changes in sleep‐wake‐rhythm, downstream affecting brain clearance functionality. Our objective is to investigate the effect of circadian rhythm and Aβ pathology on clearance efficacy in APPswe/PS1dE9 mice. Method: First, we examined the brain wide distribution of an intrahippocampal injected fluorescent dye. Dye was injected at 6 am (post wake period) or 6 pm (post sleep period) and sampled 1 or 3 h post injection for histological analysis (Figure 1A) in n = 3 transgenic mice and n = 3 non‐transgenic mice per group. Secondly, in an in vivo approach we analyzed the brain wide distribution of a gadolinium based contrast agent using a T2‐RARE sequence in a 7 Tesla small animal MRI scanner (Bruker BioSpin GmbH, Germany) (Figure 1B) in n = 4 transgenic mice and n = 4 non‐transgenic mice. We measured values for brightness in manually defined regions of interest with PMOD software (version 3.7; PMOD Technologies LLC, Switzerland). Result: In the first experiment, we were able to observe dye distribution in the brain parenchyma as surrogate for interstitial clearance net flux. Preliminary results point to an effect of circadian rhythm, as a trend of better dye distribution shortly after the sleep period was observed. Furthermore, a possible detrimental effect of the Aβ phenotype on clearance was observed in transgenic mice. In comparison to non‐transgenic mice they showed a trend of lesser dye distribution independent of day‐time. With the second approach, we were able to observe influx and efflux of applied contrast agent into cerebrospinal fluid. Preliminary data point to a trend of an increased slope of the influx as well as decreased slope of the efflux in transgenic mice. Conclusion: Histological analysis of a stereotactic injected dye is a feasible method for investigation of dye distribution outlining a possible effect of daytime and amyloid pathology. However, MR‐imaging is a promising tool as we will be able to observe the disease progression in mice longitudinally. Further experiments will be needed to ensure these preliminary results and maybe also point to underlying mechanistic basis. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: Mechanical thrombectomy is common practice in proximal anterior vessel occlusion. However, it remains unclear whether peripheral artery occlusions should be treated as well. This retrospective study aimed to prove the effectiveness of endovascular recanalization treatment for the M2 segment by comparison of intracranial internal carotid artery (ICA), M1 segment, and M2 segment thrombectomy.Materials and Methods: All patients who received endovascular treatment for distal ICA, M1, or M2 segment occlusions between January 2010 and July 2017 at our center were re-analyzed with respect to reperfusion success, interventional and clinical parameters. Statistical analysis was performed by Mann Whitney test, Chi square test, and Spearman correlation analysis.Results: A total of 261 patients (median age, 72 years), 100 with ICA, 137 with M1, and 24 with M2 segment occlusion, were included. Duration of endovascular treatment was significantly longer in ICA occlusions (median, 83 minutes, p < 0.001) compared to M1 (56 minutes) or M2 segment occlusions (49 minutes). Recanalization and reperfusion success and rate of endovascular complications did not differ between occlusion sites (AOL, p = 0.071; mTICI, p = 0.540; complications, p = 0.064). No significant difference in revascularization success was found between the different thrombectomy devices (direct thrombus aspiration, stent retrieving, or a sequential combined approach; p = 0.112). Successful M2 recanalization (mTICI 2b-3) correlated significantly with stronger posttherapeutic NIHSS reduction (r = 0.691, p < 0.001).Conclusion: We found endovascular treatment of M2 segment occlusions as safe and successful as endovascular therapy of the ICA or M1 segment, with stronger posttherapeutic NIHSS reduction after successful compared to insufficient M2 recanalization. [ABSTRACT FROM AUTHOR]

Parenchymal hemorrhage is considered a major risk factor for perioperative morbidity in patients undergoing stereotactic brain biopsy. Studies on patients undergoing surgical procedures have suggested that evaluation of prothrombin time (PT) and activated partial thromboplastin time (aPTT) is of limited value with regard to prevention of haemorrhagic complications. However, this issue has not yet been addressed in patients undergoing stereotactic biopsy of intracranial lesions. We retrospectively analysed the medical records of 159 consecutive patients undergoing stereotactic biopsy of supratentorial intracranial lesions during a three-year period. Laboratory values (PT, aPTT, platelet count) were reviewed as well as clinical characteristics, modalities of surgical treatment, histopathological results and the postoperative course of patients. The overall diagnostic yield was 93.7%. Histopathological examination revealed glioma (WHO°I: 5, WHO°II: 25, WHO°III: 23, WHO°IV: 65), lymphoma (n = 14), inflammation (n = 8) and other entities (n = 6). Surgery-associated neurological deficits occurred in 7 patients (4.4%) and completely resolved in 6 of these patients. CT-confirmed intracranial hemorrhage occurred in 2 patients (1.3%) and in both cases, histopathological examination revealed glioblastoma. Results of hemostatic parameters (PT: 99 ± 13%, aPTT: 24 ± 3s, platelet count: 274 ± 87 10 3 /μL) were within normal range values in all patients and did not correlate with postsurgical morbidity. Standard assessment of haemostasis seems to be of limited value in patients with intracranial lesions undergoing stereotactic biopsy. Further studies regarding the intratumoural vasculature’s impact on the risk of biopsy-related bleeding are necessary. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: The purpose of this study was to assess regional cerebral perfusion distribution in patients with Alzheimer disease (AD) or mild cognitive impairment (MCI) using dynamic susceptibility contrast magnetic resonance imaging. Materials and Methods: Regional changes of perfusion were evaluated in 34 patients with AD, 51 patients with MCI, and 23 healthy controls (HCs). Using region of interest analyses, regional cerebral blood flow (CBF), cerebral blood volume, and mean transit time were measured bilaterally in the hippocampus; the temporal, temporoparietal, frontal, and sensomotoric cortices; the anterior and posterior cingulate gyri; the lentiform nucleus; and the cerebellum. Results: A significant reduction of CBF in patients with AD compared to HCs was shown in the frontal and temporoparietal cortices bilaterally, the lentiform nuclei bilaterally, the left posterior cingulate gyrus, and the cerebellum. Compared with patients with MCI, patients with AD presented a reduction of CBF in the frontal cortices bilaterally, the left temporoparietal cortex, and the left anterior and posterior cingulate gyrus. In both hippocampi and the posterior cingulate gyrus, a trend to a slight increase of CBF in patients with MCI was noticed with a decrease in patients with AD. Conclusions: Using dynamic susceptibility contrast magnetic resonance imaging, pathologic alterations of regional brain perfusion can be demonstrated in patients with AD compared to patients with MCI or HCs. [ABSTRACT FROM AUTHOR]