Early Detection of Vascular Dysfunction Using Biomarkers from Lagrangian Carotid Strain Imaging

摘要 目前治疗动脉粥样硬化斑块或动脉粥样硬化的临床标准主要集中在 血管狭窄的百分比。然而，闭塞的测量(狭窄百分比)并不能确定 容易破裂的斑块，可能会释放栓子进入供血敏感的大脑 脉管系统。一种新的方法，拉格朗日颈动脉应变成像，其中组织位移精确地 在通过动脉的血液搏动过程中测量的数据已经被开发出来。我们建议测量‘应变’ 指数，包括估计的心脏的最大轴向、侧向和剪切应变 循环，探讨早期斑块的详细力学性质。我们相信这些应变指数将证明 是指示血管老化和可能的斑块脆弱性的有价值的血管生物标志物。 我们的初步结果显示了区分斑块软硬区的能力。 在体内的临床成像条件下。我们对‘脆弱斑块’或‘脆弱患者’的定义依赖于 识别脂质沉积或较软的斑块，即那些经历大的轴向或侧向的斑块 心动周期期间的变形和/或大的剪切应变。应变张量成像能力和 从斑块早期阶段到成熟斑块病变特征的血管生物标志物将是 评估和量化。 还提出了一项针对无症状志愿者和患者的研究。志愿者将提供价值 对于与年龄相关的血管硬化归一化的血管应变指数。结果将使我们能够确定 血管硬度与年龄相关的变化趋势，并确定可能建立血管的偏差 老化标准。然后可以使用逆转血管老化的干预措施，例如改变生活方式 以及常见的医学疗法。应变成像结果将由三个人验证和赞扬- 一组选定的高危志愿者的三维颈动脉磁共振成像(MRI) 用3D颈动脉MRI和3D组织病理学分析对患者切除的整个斑块进行更好的 了解斑块的组成和结构。对我们结果的验证将促进实时非侵入性 超声应变成像作为筛选工具识别易受血管老化影响的受试者 和/或形成容易破裂的斑块或微栓塞术，这可能导致“无症状性卒中”和 血管认知障碍。患者研究还将使应变指数与颈动脉MRI进行比较 真相，也就是切除的斑块。

Abstract Current clinical criteria for treatment of atherosclerotic plaque, or atheromas, have focused primarily on percent stenosis of the vessel. However, measures of occlusion (percent stenosis) do not identify those plaques that are prone to rupture, which may release emboli into the blood stream feeding sensitive cerebral vasculature. A novel approach, Lagrangian carotid strain imaging, where tissue displacements are precisely measured during pulsation of blood through the artery has been developed. We propose to measure `strain indices,' that include the maximum accumulated axial, lateral, and shear strain estimated over the cardiac cycle, to probe the detailed mechanical properties of early plaque. We believe these strain indices will prove to be valuable vascular biomarkers to indicate vascular aging and possible plaque vulnerability. Our preliminary results demonstrate the ability to differentiate between soft and stiff regions in plaque under in-vivo clinical imaging conditions. Our definition of `vulnerable plaque' or `vulnerable patient' relies on the identification of lipidic depositions or softer plaques, i.e., those that undergo large axial or lateral deformations and/or large shearing strains during the cardiac cycle. Capability of strain tensor imaging and vascular biomarkers to characterize plaque severity from its early stages to a mature plaque lesion will be evaluated and quantified. A study on asymptomatic volunteers and patients also is proposed. The volunteer will provide values for vascular strain indices normalized to age-related vascular stiffening. The results will enable us to establish trends in age-related variations in vascular stiffness and to determine deviations that could establish vascular aging criteria. Interventions to reverse vascular aging might then be used, for example lifestyle modifications and common medical therapies. Strain imaging results will be validated and complimented by three- dimensional (3D) carotid magnetic resonance imaging (MRI) on a selected group of high-risk volunteers, along with 3D carotid MRI and 3D histopathological analysis of the entire excised plaque on patients to better understand plaque composition and structure. Validation of our results will foster use of real-time noninvasive ultrasound strain imaging as a screening tool for identifying human subjects susceptible to vascular aging and/or developing plaque prone to rupture or micro-embolization that could lead to `silent strokes' and possible vascular cognitive impairment. The patient study will also enable comparison of strain indices and carotid MRI to the ground truth, namely the excised plaque.