Radiotracer-Based Imaging for Quantitative Assessment of Angiosome Perfusion Following Lower Extremity Revascularization

基于放射性示踪剂的成像对下肢血运重建后血管灌注的定量评估

• 批准号: 9220154
• 负责人: Mitchel R Stacy
• 金额: $ 41.88万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-13 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9220154
• 关键词: Affect; American; Amputation; Animal Model; Arteries; Atherosclerosis; Blood Vessels; Blood flow; Cardiovascular Diseases; CdZnTe; Cessation of life; Chronic; Clinical Trials; Complications of Diabetes Mellitus; Data; Detection; Diabetes Mellitus; Dimensions; Distal; Evaluation; Family suidae; Foot Ulcer; Functional disorder; Future; Goals; Heterogeneity; Hybrids; Image; Imaging Device; Imaging Techniques; Impaired wound healing; Impairment; Intervention; Ischemia; Leg Ulcer; Limb Salvage; Limb structure; Lower Extremity; Magnetic Resonance Imaging; Medical; Microcirculation; Microvascular Dysfunction; Modeling; Monitor; Morphology; Muscle; Outcome; Patients; Perfusion; Peripheral; Peripheral Vascular Diseases; Physiological; Play; Procedures; Process; Resolution; Rest; Risk; Role; Shapes; Skeletal Muscle; Source; Stress; Stress Tests; Technology; Tissue Viability; Tissues; Translating; Treatment Efficacy; Treatment outcome; Ulcer; Work; Wound Healing; X-Ray Computed Tomography; artery occlusion; base; clinically relevant; disability; endothelial dysfunction; foot; high risk; imaging approach; improved; indexing; limb amputation; macrovascular disease; mortality; non-healing wounds; non-invasive imaging; novel; novel strategies; outcome forecast; perfusion imaging; public health relevance; quantitative imaging; radiotracer; response; restenosis; single photon emission computed tomography; stress tolerance; success; targeted treatment; tool; treatment response; wound

Project Abstract The long-term goal of this work is to non-invasively evaluate regional changes in foot tissue perfusion following lower extremity revascularization to better predict efficacy of targeted treatment and future rates of wound healing and limb salvage. Peripheral vascular disease (PVD) is an atherosclerotic disease of the lower limbs that affects 8 to 10 million Americans, and is more prevalent and progresses more quickly in patients with diabetes mellitus (DM). In addition to macrovascular complications, DM patients commonly present with microvascular disease of the lower extremities, which may contribute to high rates of foot ulceration, limb amputation, and poor treatment outcomes that exist in the setting of DM. Current imaging tools have limitations for assessing underlying microvascular disease and there is no standard non-invasive approach to evaluate changes in microvascular perfusion in three-dimensional (3D) vascular territories of the feet, or angiosomes, following medical treatment in PVD patients. We propose a novel approach for evaluating angiosome microvascular perfusion under resting conditions in DM patients with critical limb ischemia (CLI) who are undergoing revascularization. Using hybrid SPECT/CT imaging, we will evaluate microvascular perfusion within 3D angiosomes of the foot that are targeted for direct revascularization due to pre-existing non-healing wounds, and relate changes in relative and absolute angiosome perfusion to rates of wound healing and limb salvage. The central hypothesis of this work is that radiotracer-based imaging of microvascular perfusion can detect sensitive changes in underlying pathophysiology of the foot in specific vascular territories, which can assist clinicians with targeted revascularization while also predicting treatment efficacy and limb salvage outcomes. In Aim 1 we will quantify relative changes in resting microvascular perfusion within 3D angiosomes of the foot using SPECT/CT imaging to evaluate revascularization procedures targeted at non-healing wounds in DM patients with CLI, and relate changes in angiosome perfusion to wound healing and limb salvage outcomes. Aim 2 will validate the utility of dynamic SPECT/CT imaging for quantifying serial changes in absolute skeletal muscle perfusion in a large animal model of peripheral artery occlusion. Finally, Aim 3 will translate dynamic SPECT/CT imaging into patients to evaluate the repeatability of this approach and to assess the value of absolute quantitative perfusion in 3D angiosomes in DM patients undergoing revascularization. We believe that radiotracer-based imaging will allow for high sensitivity detection of impaired foot tissue perfusion under resting conditions at baseline and following revascularization. Therefore, this imaging approach may help to identify patients at risk for wound progression or limb loss and assist in predicting treatment outcomes in PVD patients.

项目摘要 这项工作的长期目标是非侵入性地评估足部组织灌注的区域变化 下肢血运重建以更好地预测靶向治疗的疗效和未来的伤口发生率 愈合和肢体抢救。周围血管疾病（PVD）是一种下肢动脉粥样硬化性疾病 影响 8 至 1000 万美国人，在患有以下疾病的患者中更为普遍且进展更快 糖尿病（DM）。除了大血管并发症外，DM 患者还常见以下症状： 下肢微血管疾病，可能导致足部溃疡、肢体溃疡的高发生率 糖尿病患者中存在截肢和治疗效果不佳的情况。当前的成像工具有局限性 用于评估潜在的微血管疾病，并且没有标准的非侵入性方法来评估 足部三维 (3D) 血管区域或血管小体中微血管灌注的变化， PVD 患者接受治疗后。我们提出了一种评估血管小体的新方法 患有严重肢体缺血（CLI）的糖尿病患者静息条件下的微血管灌注 正在进行血运重建。使用混合 SPECT/CT 成像，我们将评估微血管灌注 由于先前存在的不愈合，在足部的 3D 血管体内进行直接血运重建 伤口，并将相对和绝对血管灌注的变化与伤口愈合和肢体的速度联系起来 打捞。这项工作的中心假设是基于放射性示踪剂的微血管灌注成像可以 detect sensitive changes in underlying pathophysiology of the foot in specific vascular territories, which can 协助临床医生进行有针对性的血运重建，同时预测治疗效果和保肢 结果。在目标 1 中，我们将量化 3D 血管体内静息微血管灌注的相对变化 使用 SPECT/CT 成像评估足部针对不愈合伤口的血运重建手术 患有 CLI 的 DM 患者，并将血管灌注的变化与伤口愈合和保肢联系起来 结果。目标 2 将验证动态 SPECT/CT 成像在量化连续变化方面的效用 大型动物外周动脉闭塞模型中的绝对骨骼肌灌注。最后，目标 3 将 将动态 SPECT/CT 成像转化为患者，以评估该方法的可重复性并评估 接受血运重建的 DM 患者 3D 血管体中绝对定量灌注的价值。我们 相信基于放射性示踪剂的成像将能够高灵敏度地检测受损的足部组织灌注 在基线和血运重建后的休息条件下。因此，这种成像方法可能 帮助识别有伤口进展或肢体丧失风险的患者，并协助预测治疗结果 在PVD患者中。