Regional association of pCASL-MRI with FDG-PET and PiB-PET in people at risk for autosomal dominant Alzheimer's disease.

Autosomal dominant Alzheimer's disease (ADAD) is a small subset of Alzheimer's disease that is genetically determined with 100% penetrance. It provides a valuable window into studying the course of pathologic processes that leads to dementia. Arterial spin labeling (ASL) MRI is a potential AD imaging marker that non-invasively measures cerebral perfusion. In this study, we investigated the relationship of cerebral blood flow measured by pseudo-continuous ASL (pCASL) MRI with measures of cerebral metabolism (FDG PET) and amyloid deposition (Pittsburgh Compound B (PiB) PET). Thirty-one participants at risk for ADAD (age 39 ± 13 years, 19 females) were recruited into this study, and 21 of them received both MRI and FDG and PiB PET scans. Considerable variability was observed in regional correlations between ASL-CBF and FDG across subjects. Both regional hypo-perfusion and hypo-metabolism were associated with amyloid deposition. Cross-sectional analyses of each biomarker as a function of the estimated years to expected dementia diagnosis indicated an inverse relationship of both perfusion and glucose metabolism with amyloid deposition during AD development. These findings indicate that neurovascular dysfunction is associated with amyloid pathology, and also indicate that ASL CBF may serve as a sensitive early biomarker for AD. The direct comparison among the three biomarkers provides complementary information for understanding the pathophysiological process of AD

PET of Brain Prion Protein Amyloid in Gerstmann–Sträussler–Scheinker Disease

In vivo amyloid PET imaging was carried out on six symptomatic and asymptomatic carriers of PRNP mutations associated with the Gerstmann-Sträussler-Scheinker (GSS) disease, a rare familial neurodegenerative brain disorder demonstrating prion amyloid neuropathology, using 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([F-18]FDDNP). 2-Deoxy-2-[F-18]fluoro-d-glucose PET ([F-18]FDG) and magnetic resonance imaging (MRI) scans were also performed in each subject. Increased [F-18]FDDNP binding was detectable in cerebellum, neocortex and subcortical areas of all symptomatic gene carriers in close association with the experienced clinical symptoms. Parallel glucose metabolism ([F-18]FDG) reduction was observed in neocortex, basal ganglia and/or thalamus, which supports the close relationship between [F-18]FDDNP binding and neuronal dysfunction. Two asymptomatic gene carriers displayed no cortical [F-18]FDDNP binding, yet progressive [F-18]FDDNP retention in caudate nucleus and thalamus was seen at 1- and 2-year follow-up in the older asymptomatic subject. In vitro FDDNP labeling experiments on brain tissue specimens from deceased GSS subjects not participating in the in vivo studies indicated that in vivo accumulation of [F-18]FDDNP in subcortical structures, neocortices and cerebellum closely related to the distribution of prion protein pathology. These results demonstrate the feasibility of detecting prion protein accumulation in living patients with [F-18]FDDNP PET, and suggest an opportunity for its application to follow disease progression and monitor therapeutic interventions

Effects of Nanoporous and Microgrooved Substrates on Cell Morphology and Cell Migration of Hepatoma Cells

Understanding the mechanism of how surface topography influences mammalian cells is important for the development of medical implants and tissue engineering. Although variety of cell types have been used in cell-substrate studies for different purposes, hepatocytes have been paid relatively less attention. In this study, we investigated the influences of nanopores and microgrooves on the morphology and migration of hepatoma cell line, BEL-7402 cells. The cells were cultured on different synthetic substrates including flat cell culture plate, flat silicon wafer sputtered with alumina, nanoporous (140 nm in diameter) anodized aluminum membrane (AAM) surface, flat polydimethylsiloxane (PDMS), and PDMS patterned with microgrooves of various widths (10 μm, 30 μm and 50 μm in width, and 2 μm in depth). Cellular behaviour on these surfaces was studied using fluorescent microscopy, time lapse microscopy and scanning electron microscopy (SEM)

Effects of Nanoporous and Microgrooved Substrates on Cell Morphology and Cell Migration of Hepatoma Cells

Understanding the mechanism of how surface topography influences mammalian cells is important for the development of medical implants and tissue engineering. Although variety of cell types have been used in cell-substrate studies for different purposes, hepatocytes have been paid relatively less attention. In this study, we investigated the influences of nanopores and microgrooves on the morphology and migration of hepatoma cell line, BEL-7402 cells. The cells were cultured on different synthetic substrates including flat cell culture plate, flat silicon wafer sputtered with alumina, nanoporous (140 nm in diameter) anodized aluminum membrane (AAM) surface, flat polydimethylsiloxane (PDMS), and PDMS patterned with microgrooves of various widths (10 μm, 30 μm and 50 μm in width, and 2 μm in depth). Cellular behaviour on these surfaces was studied using fluorescent microscopy, time lapse microscopy and scanning electron microscopy (SEM)