Synthesis of human amyloid restricted to liver results in an Alzheimer disease-like neurodegenerative phenotype.

Several lines of study suggest that peripheral metabolism of amyloid beta (Aß) is associated with risk for Alzheimer disease (AD). In blood, greater than 90% of Aß is complexed as an apolipoprotein, raising the possibility of a lipoprotein-mediated axis for AD risk. In this study, we report that genetic modification of C57BL/6J mice engineered to synthesise human Aß only in liver (hepatocyte-specific human amyloid (HSHA) strain) has marked neurodegeneration concomitant with capillary dysfunction, parenchymal extravasation of lipoprotein-Aß, and neurovascular inflammation. Moreover, the HSHA mice showed impaired performance in the passive avoidance test, suggesting impairment in hippocampal-dependent learning. Transmission electron microscopy shows marked neurovascular disruption in HSHA mice. This study provides causal evidence of a lipoprotein-Aß /capillary axis for onset and progression of a neurodegenerative process.

Cerebral MR oximetry during acetazolamide augmentation: Beyond cerebrovascular reactivity in hemodynamic failure.

BACKGROUND: Oxygen extraction fraction (OEF) elevation predicts increased ischemic stroke incidence among patients with carotid steno-occlusive disease, and can be estimated from quantitative susceptibility mapping (QSM) MRI. PURPOSE: To explore QSM oximetry during acetazolamide (ACZ) challenge, hypothesizing that detectable OEF alterations will reflect hemodynamic compromise in unilateral cerebrovascular disease (CVD) patients. STUDY TYPE: Retrospective. SUBJECTS: Fourteen unilateral CVD patients, and 24 healthy controls (HC). FIELD STRENGTH/SEQUENCE: Multiecho gradient echo (GRE) and T1 -weighted images at 3T. ASSESSMENT: We constructed QSM images and R2* maps from multiecho GRE images. QSM-OEF maps were generated from the susceptibility difference between venous blood and background brain tissue. Intrasubject diseased/contralateral hemisphere OEF ratios in the middle cerebral artery (MCA) territories were calculated. Intravascular susceptibility in the straight sinus (SS) and MCA was also measured. STATISTICAL TESTS: The result significance was determined using t-tests and Pearson's correlation. RESULTS: Mean and standard deviation for the patient diseased/contralateral OEF ratios were 1.15 ± 0.14 at baseline and 1.23 ± 0.17 post-ACZ. Disease group R2* ratios were 0.95 ± 0.05 at baseline and 1.03 ± 0.08 post-ACZ. Left/right OEF and R2* ratios for the HC group were 0.98 ± 0.06 and 0.99 ± 0.038, respectively. Susceptibility (ppb) in the SS and MCA in patients was 162.63 ± 35.4 and -22.33 ± 13.70, respectively, at baseline, 124.56 ± 37.43 and -19.27 ± 23.14 post-ACZ. The HC group SS and MCA susceptibility was 146.10 ± 24.79 and -19.59 ± 12.37, respectively. Patient group OEF ratios were greater than 1.0 before and after ACZ challenge (P < 0.01 and < 0.001, respectively, one-sample t-test), and were greater than HC ratios (P < 0.001 unpaired t-test). OEF and R2* ratios increased from baseline to post-ACZ (P = 0.024, 0.004, respectively, paired t-test). Detectable blood oxygenation change was confirmed by finding SS susceptibility decreased from baseline to post-ACZ (P < 0.001, paired t-test), while MCA susceptibility did not change significantly (P = 0.67, paired t-test). DATA CONCLUSION: These results suggest QSM is sensitive to dynamic OEF modulation during hemodynamic augmentation. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:175-182.

Mechanisms and Risk Factors Contributing to Visual Field Deficits following Stereotactic Laser Amygdalohippocampotomy.

Selective laser amygdalohippocampotomy (SLAH) is a minimally invasive surgical treatment for medial temporal lobe epilepsy. Visual field deficits (VFDs) are a significant potential complication. The objective of this study was to determine the relationship between VFDs and potential mechanisms of injury to the optic radiations and lateral geniculate nucleus. We performed a retrospective cross-sectional analysis of 3 patients (5.2%) who developed persistent VFDs after SLAH within our larger series (n = 58), 15 healthy individuals and 10 SLAH patients without visual complications. Diffusion tractography was used to evaluate laser catheter penetration of the optic radiations. Using a complementary approach, we evaluated evidence for focal microstructural tissue damage within the optic radiations and lateral geniculate nucleus. Overablation and potential heat radiation were assessed by quantifying ablation and choroidal fissure CSF volumes as well as energy deposited during SLAH.SLAH treatment parameters did not distinguish VFD patients. Atypically high overlap between the laser catheter and optic radiations was found in 1/3 VFD patients and was accompanied by focal reductions in fractional anisotropy where the catheter entered the lateral occipital white matter. Surprisingly, lateral geniculate tissue diffusivity was abnormal following, but also preceding, SLAH in patients who subsequently developed a VFD (all p = 0.005).In our series, vision-related complications following SLAH, which appear to occur less frequently than following open temporal lobe -surgery, were not directly explained by SLAH treatment parameters. Instead, our data suggest that variations in lateral geniculate structure may influence susceptibility to indirect heat injury from transoccipital SLAH.

Variability of Resting-State Functional MRI Graph Theory Metrics across 3T Platforms.

BACKGROUND AND PURPOSE: Graph theory analysis of brain connectivity data is a promising tool for studying the function of the healthy and diseased brain. The consistency of resting-state functional MRI (rsfMRI) connectivity measures across multiple scanner types is an important factor in designing multi-institutional research studies and has important implications for the potential use of this technique in a heterogeneous clinical setting. We sought to quantitatively study the interscanner variability of rsfMRI graph theory metrics obtained from healthy volunteers scanned on three different scanner platforms. METHODS: In this prospective Institutional Review Board approved study, 9 healthy volunteers were enrolled for brain MRI on three 3T scanners (Magnetom Prisma, Skyra, and Trio, Siemens, Erlangen, Germany) in three separate scan sessions within approximately 1 week. Standard preprocessing of rsfMRI was performed with SPM12. Subject scans were normalized to Montreal Neurologic Institute (MNI) space, and connectivity of 116 regions-of-interests based on the automated anatomic labeling (AAL) atlas was calculated using Conn toolbox. Whole-network graph theory metrics were calculated using Brain Connectivity Toolbox, and intraclass correlation (ICC) across three scan sessions was assessed. RESULTS: A total of 25 rsfMRI exams were completed in 9 subjects with a median-intersession time of 3 days. Among all three sessions, there was good to excellent agreement in characteristic path length and global efficiency (ICC: .79, .79) and good agreement in the transitivity, local efficiency, and clustering coefficient (ICC = .72, .69, .62). CONCLUSIONS: There was high consistency of graph theory metrics of rsfMRI connectivity networks among healthy volunteers scanned on three different generation 3T MRI scanners.