Microvascular Perfusion Assessment of Ischemic Diabetic Ulcers Using MRI

使用 MRI 评估缺血性糖尿病溃疡的微血管灌注

• 批准号: 8984912
• 负责人: Gerd Brunner
• 金额: $ 15.56万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8984912
• 关键词: 5 year old; Age; Amputation; Ankle; Area; Atherosclerosis; Award; Blood Vessels; Body mass index; Bypass; Cardiology; Cardiovascular Diseases; Caring; Characteristics; Clinic; Clinical; Clinical Research; Comorbidity; Data; Development; Diabetes Mellitus; Diabetic ulcer; Diagnosis; Disease; Doctor of Philosophy; Environment; Funding; Future; Gender; Glomerular Filtration Rate; Goals; Grant; Healed; Health; Healthcare Systems; Hospitals; Hypertension; Image; Incidence; Individual; International; Ischemia; K-Series Research Career Programs; Leg; Legal patent; Lipoproteins; Lower Extremity; Magnetic Resonance Imaging; Manuscripts; Measures; Medical center; Medicine; Mentors; Methodist Church; Microcirculation; Microvascular Dysfunction; Muscle; Obesity; Operative Surgical Procedures; Oxygen; Partial Pressure; Participant; Patient Recruitments; Patients; Pattern; Perfusion; Peripheral arterial disease; Phase; Physics; Play; Productivity; Protocols documentation; Public Health; Publications; Publishing; Raja; Recruitment Activity; Research; Research Personnel; Research Training; Resources; Risk; Role; Scientist; Secure; Site; Skeletal Muscle; Smoking; Techniques; Testing; Texas; Time; Toes; Training; Training and Education; Ulcer; Ultrasonography; United States National Institutes of Health; Veterans; Work; Wound Healing; Writing; base; biomedical Computer science; cardiovascular imaging; career; career development; college; contrast enhanced; diabetic; diabetic patient; experience; foot; healing; improved; indexing; interest; macrovascular disease; mid-career faculty; mortality; multidisciplinary; post intervention; primary outcome; professor; programs; secondary outcome; skeletal; skills; tenure track; wound

 DESCRIPTION (provided by applicant): The candidate, Gerd Brunner, MS/PhD is a quantitative researcher trained in cardiovascular imaging and biomedical computer science who is a second year tenure track Assistant Professor at the Division of Atherosclerosis and Vascular Medicine, Department of Medicine at Baylor College of Medicine, Houston, Texas. The candidate's career goal is to become an independent investigator in the field of cardiovascular imaging. The K25 Quantitative Career Development Award is of critical importance for transitioning to independence. The award will provide additional training, mentoring and protected time for research to develop a clear understanding of the causes, mechanisms, and clinical aspects of atherosclerosis and diabetes mellitus, enhance Dr. Brunner's grantsmanship skills, and to gain advanced experience in performing clinical imaging studies. The K25 award will provide Dr. Brunner with the necessary experience to develop a strong independent program in cardiovascular imaging. Dr. Brunner's preliminary studies, recent publications, and new data since the first submission and multidisciplinary training form the basis of this application and present a logical continuation of his previous research and training. The Texas Medical Center is a superb environment that provides the necessary facilities and educational resources for Dr. Brunner to pursue a targeted mentoring phase in order to develop into an independent investigator. Mentoring Team and Career Development: Dr. Brunner and his primary mentor Christie Ballantyne MD, an internationally recognized leader in atherosclerosis, peripheral arterial disease (PAD), and lipoprotein research, have assembled an outstanding mentoring team including Lawrence Lavery, DPM, MPH, an international expert in wound healing and diabetic ulcers; Dipan Shah, MD a national expert in clinical cardiovascular imaging; Ashok Balasubramanyam, MD an international expert in diabetes and cardiovascular disease; Raja Muthupillai, PhD a national leader in magnetic resonance imaging (MRI) and MRI physics; Vijay Nambi, MD/PhD a national expert in cardiology, atherosclerosis and ultrasonography; and Joel Morrisett, PhD an internationally known leader in vascular imaging and atherosclerosis. Dr. Brunner's mentors have tremendous experience in research and mentoring junior investigators, as evident by NIH funded projects including an institutional T32 training grant for +15 years. His mentoring team and Dr. Brunner have agreed on metrics for every year of his career development. Based on past productivity, Dr. Brunner will publish 5 manuscripts in the first 2 years, 3-5 articles annually in years 3 and 4, and 4-8 in the last year. Dr. Brunner will be the fist author on at least 50% of his published work. Dr. Brunner's immediate career goal is to obtain a funded career development award. His 3-year goal is to complete education and training. His 4-year goal is to write an RO1 NIH grant to secure continuous funding. His 6-7 year goal is to be promoted to Associate Professor with tenure and his 10-year goal is to be a national leader in cardiovascular imaging and to mentor junior scientists. Research Plan: Diabetes mellitus is a multi-facetted disease associated with macrovascular (large vessel disease) complications such as PAD and microvascular complications (small vessel disease). Up to 40% of ischemic diabetic ulcers do not heal after 1-year following either open bypass surgery or endovascular revascularization. This presents a conundrum, i.e., lower extremity ischemia persists in what otherwise appears to be a patent vessel. Several studies suggest that alterations in the microcirculation may contribute to the poor wound healing of ischemic diabetic ulcers. However, the association of microcirculation with wound healing in diabetics with ischemia remains unknown. Identifying patients who are unlikely to achieve wound healing at the outset, would likely benefit patients and the health care system. This field is severely hampered by the lack of clinical measures to quantify microvascular circulation. Therefore, this proposal will elucidate th role that skeletal foot muscle microcirculation plays in diabetics with ischemic ulcers. Dr. Brunner has previously demonstrated the feasibility of a magnetic resonance imaging (MRI) protocol to assess muscle perfusion (microvascular circulation) in healthy controls and PAD patients. The applicant's latest data show that skeletal muscle perfusion, as measured with contrast-enhanced (CE)-MRI is markedly reduced in PAD patients (including diabetics) compared to healthy controls, confirming results by other groups. His data also reveal that muscle perfusion shows heterogeneous patterns across muscle compartments indicating perfusion abnormalities, and CE-MRI skeletal muscle perfusion characteristics correlate inversely with estimated glomerular filtration rate (eGFR), a known marker of microvascular disease. This proposal will test the hypothesis that microvascular circulation (skeletal muscle perfusion), as measured with CE-MRI in the foot, is impaired in diabetics with ischemic ulcers compared to comorbidity matched controls and that baseline microvascular circulation is more impaired in diabetics with non-healing ulcers at 1 year after clinically indicated lower-extremity revascularization. The proposed non-invasive MRI studies will, for the first time, provide quantitative data on the skeletal foot muscle microcirculation in diabetics with ischemic ulcers. These studies will advance our understanding of the role that microvascular circulation plays in diabetics with ischemia before and after clinically indicated arterial revascularization.

 描述（由申请人提供）：候选人Gerd Brunner，MS/PhD是一名接受心血管成像和生物医学计算机科学培训的定量研究员，他是德克萨斯州休斯顿贝勒医学院医学系动脉粥样硬化和血管医学部的第二年终身助理教授。候选人的职业目标是成为心血管成像领域的独立研究者。K25定量职业发展奖对于过渡到独立至关重要。该奖项将为研究提供额外的培训，指导和保护时间，以明确了解动脉粥样硬化和糖尿病的原因，机制和临床方面，提高Brunner博士的granitarian技能，并获得进行临床成像研究的先进经验。K25奖将为Brunner博士提供必要的经验，以开发强大的心血管成像独立项目。Brunner博士的初步研究，最近的出版物，以及自首次提交以来的新数据和多学科培训构成了本申请的基础，并提出了他以前的研究和培训的逻辑延续。德克萨斯州医疗中心是一个极好的环境，为布伦纳博士提供必要的设施和教育资源，以追求有针对性的指导阶段，以发展成为一名独立的调查员。指导团队和职业发展：Brunner博士和他的主要导师Christie Ballantyne医学博士，一位国际公认的动脉粥样硬化，外周动脉疾病（PAD）和脂蛋白研究的领导者，组建了一个杰出的指导团队，包括Lawrence Lavery，医学博士，MPH，伤口愈合和糖尿病溃疡的国际专家; Dipan Shah，医学博士，临床心血管成像的国家专家; Ashok Balasubramanyam，医学博士，糖尿病和心血管疾病的国际专家; Raja Muthupillai，博士，磁共振成像（MRI）和MRI物理学的国家领导人; Vijay Nambi，医学博士/博士，心脏病学，动脉粥样硬化和超声检查的国家专家; Joel Morrisett，博士，血管成像和动脉粥样硬化的国际知名领导人。Brunner博士的导师在研究和指导初级研究人员方面拥有丰富的经验，NIH资助的项目包括15年以上的机构T32培训补助金。他的指导团队和Brunner博士就他职业发展的每一年的指标达成了一致。根据以往的生产力，Brunner博士将在前2年发表5篇手稿，第3年和第4年每年发表3-5篇文章，最后一年发表4-8篇文章。Brunner博士将是他至少50%已发表作品的第一作者。Brunner博士的直接职业目标是获得资助的职业发展奖。他的三年目标是完成教育和培训。他的4年目标是写一个RO 1 NIH赠款，以确保持续的资金。他的6-7年目标是晋升为终身副教授，他的10年目标是成为心血管成像领域的国家领导者，并指导初级科学家。研究计划：糖尿病是一种多方面疾病，与大血管（大血管疾病）并发症（如PAD）和微血管并发症（小血管疾病）相关。在开放性旁路手术或血管内血运重建术后1年，高达40%的缺血性糖尿病溃疡未愈合。这提出了一个难题，即，下肢局部缺血持续存在于否则看起来是开放的血管中。一些研究表明，微循环的改变可能导致缺血性糖尿病溃疡的伤口愈合不良。然而，微循环与糖尿病缺血患者伤口愈合的关系仍不清楚。从一开始就识别出不太可能实现伤口愈合的患者，可能会使患者和医疗保健系统受益。由于缺乏量化微血管循环的临床措施，这一领域受到严重阻碍。因此，这一建议将阐明骨骼肌足部微循环在糖尿病患者缺血性溃疡中的作用。Brunner博士先前已经证明了磁共振成像（MRI）方案评估健康对照和PAD患者肌肉灌注（微血管循环）的可行性。申请人的最新数据显示，与健康对照组相比，PAD患者（包括糖尿病患者）的骨骼肌灌注（使用对比增强（CE）-MRI测量）显著降低，证实了其他组的结果。他的数据还显示，肌肉灌注显示出跨肌肉隔室的异质模式，表明灌注异常，CE-MRI骨骼肌灌注特征与估计的肾小球滤过率（eGFR）呈负相关，eGFR是微血管疾病的已知标志物。本提案将检验以下假设：与合并症匹配的对照组相比，患有缺血性溃疡的糖尿病患者的足部CE-MRI测量的微血管循环（骨骼肌灌注）受损，并且在临床指征下肢血运重建后1年，患有非愈合性溃疡的糖尿病患者的基线微血管循环受损更严重。拟议的非侵入性MRI研究将首次提供糖尿病患者缺血性溃疡骨骼肌微循环的定量数据。这些研究将促进我们对微血管循环在糖尿病患者临床指征动脉血运重建前后缺血中所起作用的理解。