Tutino Vincent M, Rajabzadeh-Oghaz Hamidreza, Chandra Anusha R, Gutierrez Liza C, Schweser Ferdinand, Preda Marilena, Chien Aichi, Vakharia Kunal, Ionita Ciprian, Siddiqui Adnan, Kolega John
Canon Stroke and Vascular Research Center, University at Buffalo, Buffalo, NY 14260, United States.
Department of Biomedical Engineering, University at Buffalo, Buffalo, NY 14260, United States.
Curr Neurovasc Res. 2018;15(4):312-325. doi: 10.2174/1567202616666181127165943.
The neurovasculature dynamically responds to changes in cerebral blood flow by vascular remodeling processes. Serial imaging studies in mouse models could help characterize pathologic and physiologic flow-induced remodeling of the Circle of Willis (CoW).
We induced flow-driven pathologic cerebral vascular remodeling in the CoW of mice (n=3) by ligation of the left Common Carotid Artery (CCA), and the right external carotid and pterygopalatine arteries, increasing blood flow through the basilar and the right internal carotid arteries. One additional mouse was used as a wild-type control. Magnetic Resonance Imaging (MRI) at 9.4 Tesla (T) was used to serially image the mouse CoW over three months, and to obtain threedimensional images for use in Computational Fluid Dynamic (CFD) simulations. Terminal vascular corrosion casting and scanning electron microscope imaging were used to identify regions of macroscopic and microscopic arterial damage.
We demonstrated the feasibility of detecting and serially measuring pathologic cerebral vascular changes in the mouse CoW, specifically in the anterior vasculature. These changes were characterized by bulging and increased vessel tortuosity on the anterior cerebral artery and aneurysm- like remodeling at the right olfactory artery origin. The resolution of the 9.4T system further allowed us to perform CFD simulations in the anterior CoW, which showed a correlation between elevated wall shear stress and pathological vascular changes.
In the future, serial high-resolution MRI could be useful for characterizing the flow environments corresponding to other pathologic remodeling processes in the mouse CoW, such as aneurysm formation, subarachnoid hemorrhage, and ischemia.
神经血管系统通过血管重塑过程对脑血流量的变化做出动态反应。在小鼠模型中进行系列成像研究有助于表征 Willis 环(CoW)病理性和生理性血流诱导的重塑。
我们通过结扎小鼠(n = 3)的左颈总动脉(CCA)、右颈外动脉和翼腭动脉,增加通过基底动脉和右颈内动脉的血流量,从而在小鼠的 CoW 中诱导血流驱动的病理性脑血管重塑。另外一只小鼠用作野生型对照。使用 9.4 特斯拉(T)的磁共振成像(MRI)对小鼠的 CoW 进行为期三个月的系列成像,并获取用于计算流体动力学(CFD)模拟的三维图像。使用终端血管铸型腐蚀和扫描电子显微镜成像来识别宏观和微观动脉损伤区域。
我们证明了检测和系列测量小鼠 CoW 中病理性脑血管变化的可行性,特别是在前循环血管中。这些变化的特征是大脑前动脉出现膨出和血管迂曲增加,以及右嗅动脉起始处出现动脉瘤样重塑。9.4T 系统的分辨率进一步使我们能够在前 CoW 中进行 CFD 模拟,结果显示壁面剪应力升高与病理性血管变化之间存在相关性。
未来,系列高分辨率 MRI 可能有助于表征与小鼠 CoW 中其他病理性重塑过程相对应的血流环境,如动脉瘤形成、蛛网膜下腔出血和缺血。