Institute for Biomedical Engineering, Swiss Federal Institute of Technology and University of Zurich, CH-8093 Zurich, Switzerland.
J Neurosci. 2012 Feb 1;32(5):1705-13. doi: 10.1523/JNEUROSCI.5626-11.2012.
Amyloid-β (Aβ) deposition in the cerebral vasculature is accompanied by remodeling which has a profound influence on vascular integrity and function. In the current study we have quantitatively assessed the age-dependent changes of the cortical vasculature in the arcAβ model of cerebral amyloidosis. To estimate the density of the cortical microvasculature in vivo, we used contrast-enhanced magnetic resonance microangiography (CE-μMRA). Three-dimensional gradient echo datasets with 60 μm isotropic resolution were acquired in 4- and 24-month-old arcAβ mice and compared with wild-type (wt) control mice of the same age before and after administration of superparamagnetic iron oxide nanoparticles. After segmentation of the cortical vasculature from difference images, an automated algorithm was applied for assessing the number and size distribution of intracortical vessels. With CE-μMRA, cerebral arteries and veins with a diameter of less than the nominal pixel resolution (60 μm) can be visualized. A significant age-dependent reduction in the number of functional intracortical microvessels (radii of 20-80 μm) has been observed in 24-month-old arcAβ mice compared with age-matched wt mice, whereas there was no difference between transgenic and wt mice of 4 months of age. Immunohistochemistry demonstrated strong fibrinogen and Aβ deposition in small- and medium-sized vessels, but not in large cerebral arteries, of 24-month-old arcAβ mice. The reduced density of transcortical vessels may thus be attributed to impaired perfusion and vascular occlusion caused by deposition of Aβ and fibrin. The study demonstrated that remodeling of the cerebrovasculature can be monitored noninvasively with CE-μMRA in mice.
脑内血管中的淀粉样β（Aβ）沉积伴随着重塑，这对血管完整性和功能有深远影响。在本研究中，我们定量评估了脑淀粉样变性的 arcAβ 模型中皮质血管的年龄依赖性变化。为了估计皮质微血管的密度，我们使用了对比增强磁共振微血管造影（CE-μMRA）。在 4 个月和 24 个月大的 arcAβ 小鼠中获取具有 60μm 各向同性分辨率的三维梯度回波数据集，并在施用超顺磁性氧化铁纳米颗粒前后与同龄的野生型（wt）对照小鼠进行比较。在从差异图像中分割皮质血管后，应用自动算法评估了脑内血管的数量和大小分布。通过 CE-μMRA，可以可视化直径小于标称像素分辨率（60μm）的脑动脉和静脉。与年龄匹配的 wt 小鼠相比，24 个月大的 arcAβ 小鼠的功能性皮质微血管（半径为 20-80μm）数量随年龄显著减少，而 4 个月大的转基因和 wt 小鼠之间没有差异。免疫组织化学显示，24 个月大的 arcAβ 小鼠的小血管和中等大小血管中存在强烈的纤维蛋白原和 Aβ 沉积，但在大的脑动脉中没有。因此，跨皮质血管密度的降低可能归因于 Aβ 和纤维蛋白沉积引起的灌注受损和血管闭塞。该研究表明，CE-μMRA 可在小鼠中无创监测脑血管重塑。
