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• W2896694002 abstract "Evidence suggests that impaired rates of clearance increase amyloid-β (Aβ) accumulation in Alzheimer's disease (AD). Brain aquaporin-4 (AQP4) water channels appear to play a key role in Aβ clearance, possibly via the glymphatic pathway. To address the lack of non-invasive tools available to assess brain clearance pathways, we have developed an MRI technique (multi-TE ASL) able to measure rates of vascular water delivered across BBB to the mouse brain parenchyma [Ohene et al. ISMRM(2017)]. We hypothesise that AQP4-deficient (AQP4−/-) mice will demonstrate slower transfer of vascular water into the brain parenchyma. This may provide a novel tool to better understand the dynamic role of AQP4 in brain protein clearance, working towards new and clinically viable biomarkers for early diagnosis of AD. Images were acquired using an Agilent 9.4T MR system in nine AQP4−/- mice and nine C57/B6 WT controls. A multi-TE FAIR ASL sequence was used with parameters: TE = 15, 18, 23, 30, 40, 50, 65ms; TI = 1500ms. Analysis was performed on a manually defined cortical ROI using Matlab R2015a. A kinetic perfusion model was applied to generate measurements of cerebral perfusion and the cortical exchange time i.e. time for magnetically labelled vascular water to exchange into brain tissue. The mean cortical exchange time was significantly longer in AQP4−/- mice (536 ± 92ms) relative to WT mice (377 ± 89ms) (p = 0.004), Figure 1B. This reflects slower movement of vascular water into the extravascular cortical tissue in the absence of AQP4 channels. Table 1 shows no significant difference in cortical arterial arrival time (δa), Cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) between animal groups, which indicates preserved cerebral haemodynamics and microstructure . Average exchange time maps across all animals (scale bar shown) and an anatomical reference of the cortical brain region for individual animal analysis. The mean cortical exchange time measurements for individual animals with group mean parameter and associated error (± std) indicated on the plot. We have developed the first non-invasive imaging technique to assess AQP4-mediated water transport at the brain-blood interface. Previous studies suggest that the capacity of this water transport system is a key determinant of Aβ clearance from the brain. The emerging importance of the AQP4-mediated clearance pathways, such as the glymphatic system, makes this technique a promising and clinically applicable tool for better understanding the role of AQP4-mediated Aβ clearance in AD." @default.
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• W2896694002 date "2018-07-01" @default.
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• W2896694002 title "IC‐06‐02: NON‐INVASIVE IMAGING OF BRAIN CLEARANCE PATHWAYS USING MULTIPLE ECHO TIME ARTERIAL SPIN LABELLING: AN AQUAPORIN‐4 STUDY" @default.
• W2896694002 doi "https://doi.org/10.1016/j.jalz.2018.06.2055" @default.
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