Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR.
Department of Neurology, Oregon Health & Science University, Portland, OR.
J Neuroimaging. 2020 Sep;30(5):658-665. doi: 10.1111/jon.12744. Epub 2020 Jun 17.
Transvascular water exchange plays a key role in the functional integrity of the blood-brain barrier (BBB). In white matter (WM), a variety of imaging modalities have demonstrated age-related changes in structure and metabolism, but the extent to which water exchange is altered remains unclear. Here, we investigated the cumulative effects of healthy aging on WM capillary water exchange.
A total of 38 healthy adults (aged 36-80 years) were studied using 7T dynamic contrast enhanced MRI. Blood volume fraction (v ) and capillary water efflux rate constant (k ) were determined by fitting changes in the H O longitudinal relaxation rate constant (R ) during contrast agent bolus passage to a two-compartment exchange model. WM volume was determined by morphometric analysis of structural images.
R values and WM volume showed similar trajectories of age-related decline. Among all subjects, v and k averaged 1.7 (±0.5) mL/100 g of tissue and 2.1 (±1.1) s , respectively. While v showed minimal changes over the 40-year-age span of participants, k declined 0.06 s (ca. 3%) per year (r = -.66; P < .0005), from near 4 s at age 30 to ca. 2 s at age 70. The association remained significant after controlling for WM volume.
Previous studies have shown that k tracks Na , K -ATPase activity-dependent water exchange at the BBB and likely reflects neurogliovascular unit (NGVU) coupled metabolic activity. The age-related decline in k observed here is consistent with compromised NGVU metabolism in older individuals and the dysregulated cellular bioenergetics that accompany normal brain aging.
血管内水交换在血脑屏障（BBB）的功能完整性中起着关键作用。在白质（WM）中，多种成像方式已经证明了与年龄相关的结构和代谢变化，但水交换改变的程度尚不清楚。在这里，我们研究了健康衰老对 WM 毛细血管水交换的累积影响。
对 38 名健康成年人（年龄 36-80 岁）进行了 7T 动态对比增强 MRI 研究。通过拟合对比剂团注通过时 H O 纵向弛豫率常数（R ）的变化来确定血容量分数（v ）和毛细血管水流出率常数（k ）。WM 体积通过结构图像的形态计量分析确定。
R 值和 WM 体积表现出相似的与年龄相关的下降轨迹。在所有受试者中，v 和 k 的平均值分别为 1.7（±0.5）mL/100g 组织和 2.1（±1.1）s 。尽管 v 在参与者 40 年的年龄跨度内变化很小，但 k 每年下降 0.06 s（约 3%）（r = -.66；P <.0005），从 30 岁时的近 4 s 下降到 70 岁时的约 2 s。在控制 WM 体积后，这种相关性仍然显著。
先前的研究表明，k 追踪 BBB 上 Na + ，K -ATPase 活性依赖性水交换，可能反映神经胶质血管单元（NGVU）偶联代谢活性。这里观察到的 k 与年龄相关的下降与老年个体中 NGVU 代谢受损以及伴随正常大脑衰老的细胞能量代谢失调一致。
