Hossain Shaolie S, Zhang Yongjie, Fu Xiaoyi, Brunner Gerd, Singh Jaykrishna, Hughes Thomas J R, Shah Dipan, Decuzzi Paolo
Department of Translational Imaging, Houston Methodist Hospital Research Institute, Houston, TX, USA Department of Nanomedicine, Houston Methodist Hospital Research Institute, Houston, TX, USA
Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA.
J R Soc Interface. 2015 May 6;12(106). doi: 10.1098/rsif.2015.0001.
Peripheral arterial disease (PAD) is generally attributed to the progressive vascular accumulation of lipoproteins and circulating monocytes in the vessel walls leading to the formation of atherosclerotic plaques. This is known to be regulated by the local vascular geometry, haemodynamics and biophysical conditions. Here, an isogeometric analysis framework is proposed to analyse the blood flow and vascular deposition of circulating nanoparticles (NPs) into the superficial femoral artery (SFA) of a PAD patient. The local geometry of the blood vessel and the haemodynamic conditions are derived from magnetic resonance imaging (MRI), performed at baseline and at 24 months post intervention. A dramatic improvement in blood flow dynamics is observed post intervention. A 500% increase in peak flow rate is measured in vivo as a consequence of luminal enlargement. Furthermore, blood flow simulations reveal a 32% drop in the mean oscillatory shear index, indicating reduced disturbed flow post intervention. The same patient information (vascular geometry and blood flow) is used to predict in silico in a simulation of the vascular deposition of systemically injected nanomedicines. NPs, targeted to inflammatory vascular molecules including VCAM-1, E-selectin and ICAM-1, are predicted to preferentially accumulate near the stenosis in the baseline configuration, with VCAM-1 providing the highest accumulation (approx. 1.33 and 1.50 times higher concentration than that of ICAM-1 and E-selectin, respectively). Such selective deposition of NPs within the stenosis could be effectively used for the detection and treatment of plaques forming in the SFA. The presented MRI-based computational protocol can be used to analyse data from clinical trials to explore possible correlations between haemodynamics and disease progression in PAD patients, and potentially predict disease occurrence as well as the outcome of an intervention.
外周动脉疾病（PAD）通常归因于脂蛋白和循环单核细胞在血管壁中的渐进性血管内蓄积，导致动脉粥样硬化斑块的形成。已知这受局部血管几何形状、血流动力学和生物物理条件的调节。在此，提出了一种等几何分析框架，用于分析循环纳米颗粒（NP）在一名PAD患者股浅动脉（SFA）中的血流和血管沉积情况。血管的局部几何形状和血流动力学条件源自于在基线和干预后24个月进行的磁共振成像（MRI）。干预后观察到血流动力学有显著改善。由于管腔扩大，体内测量的峰值流速增加了500%。此外，血流模拟显示平均振荡剪切指数下降了32%，表明干预后紊乱血流减少。相同的患者信息（血管几何形状和血流）用于在计算机模拟中预测全身注射纳米药物的血管沉积情况。针对包括血管细胞黏附分子-1（VCAM-1）、E-选择素和细胞间黏附分子-1（ICAM-1）等炎症血管分子的纳米颗粒，预计在基线配置下会优先在狭窄部位附近蓄积，其中VCAM-1的蓄积量最高（分别比ICAM-1和E-选择素的浓度高约1.33倍和1.50倍）。纳米颗粒在狭窄部位的这种选择性沉积可有效用于检测和治疗SFA中形成的斑块。所提出的基于MRI的计算方案可用于分析临床试验数据，以探索PAD患者血流动力学与疾病进展之间的可能相关性，并潜在地预测疾病的发生以及干预结果。
