Non-invasive MRI of brain clearance pathways using multiple echo time arterial spin labelling: an aquaporin-4 study
Non-invasive MRI of brain clearance pathways using multiple echo time arterial spin labelling: an aquaporin-4 study
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DOI：
10.1016/j.neuroimage.2018.12.026
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发表时间：
2019-03-01
期刊：
影响因子：
5.7
通讯作者：
Wells, Jack A.
中科院分区：
文献类型：
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作者：
Ohene, Yolanda;Harrison, Ian F.;Wells, Jack A.
目前缺乏非侵入性工具来评估健康和病理脑组织中的水运输。水通道蛋白-4（AQP 4）水通道是许多水转运机制的核心，新出现的证据也表明AQP 4可能通过胶质淋巴系统在淀粉样蛋白-13（A13）清除中发挥关键作用。在这里，我们提出了第一个非侵入性技术敏感的AQP 4通道极化的血脑界面（BBI）。我们将多回波时间（多TE）动脉自旋标记（ASL）MRI技术应用于小鼠大脑，通过计算交换时间（T-ex（w））（磁标记血管内水交换通过BBI的时间）来评估BBI水渗透性。我们观察到AQP 4缺陷（Aqp 4（-/-））小鼠的交换时间（452 +/- 90 ms）比野生型小鼠（343 +/- 91 ms）增加了31%（p = 0.01），证明了该技术对缺乏AQP 4水通道的敏感性。更确定的定量MRI参数：动脉通过时间（delta（a））脑血流量（CBF）和表观扩散系数（ADC）检测到AQP 4的去除没有显着变化。这种临床相关工具对于更好地了解AQP 4在BBI水运输中的作用以及清除阿尔茨海默病等神经退行性疾病中的蛋白质至关重要。
There is currently a lack of non-invasive tools to assess water transport in healthy and pathological brain tissue. Aquaporin-4 (AQP4) water channels are central to many water transport mechanisms, and emerging evidence also suggests that AQP4 plays a key role in amyloid-13 (A13) clearance, possibly via the glymphatic system. Here, we present the first non-invasive technique sensitive to AQP4 channels polarised at the blood-brain interface (BBI). We apply a multiple echo time (multi-TE) arterial spin labelling (ASL) MRI technique to the mouse brain to assess BBI water permeability via calculation of the exchange time (T-ex(w)), the time for magnetically labelled intravascular water to exchange across the BBI. We observed a 31% increase in exchange time in AQP4-deficient (Aqp4(-/-)) mice (452 +/- 90 ms) compared to their wild-type counterparts (343 +/- 91 ms) (p = 0.01), demonstrating the sensitivity of the technique to the lack of AQP4 water channels. More established, quantitative MRI parameters: arterial transit time (delta(a)) cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) detected no significant changes with the removal of AQP4. This clinically relevant tool may be crucial to better understand the role of AQP4 in water transport across the BBI, as well as clearance of proteins in neurodegenerative conditions such as Alzheimer's disease.