MRI Detection of Skeletal Muscle Microvascular Dysfunction

描述（由申请人提供）：2型糖尿病（T2DM）的长期并发症包括微血管结构和功能损伤。在骨骼肌中，这些导致用于葡萄糖处理和支持身体活动的血流量减少，危及局部组织和整体健康。然而，在常规临床实践中，还没有专门研究骨骼肌微血管功能的无创方法。提出的研究的总体目标是发展质子密度和血氧水平依赖（BOLD）敏感的磁共振成像（MRI）技术，用于无创研究骨骼肌微血管功能。具体目的1是验证质子密度加权MRI信号的等长收缩后变化分析将可重复和可靠地区分患有微血管疾病的T2DM患者和健康受试者的假设。我们目前使用短梯度和长梯度回声MRI信号来跟踪短暂的最大等长收缩后的血容量和氧合变化。我们对目前的方案进行了调整，以便对T2DM患者减弱的总血流反应和延迟的血流动力学提供更高的敏感性。具体目标2是利用质子密度加权MRI信号瞬态的收缩后变化来评估T2DM患者在初始诊断后和根据现行护理标准进行3个月临床干预期间的微血管功能。这将使我们能够在不干扰患者护理的情况下，检验使用这些措施评估微血管对改善血糖控制的反应的可行性。成功实现这些目标将通过提供新的非侵入性外周微血管功能评估技术来改善T2DM患者的健康状况。2型糖尿病是一种严重的疾病，身体不能正常调节血糖水平。2型糖尿病的长期并发症之一是流向肌肉的血流量减少。这会导致更糟糕的血糖控制，并可能导致非常严重的并发症，如截肢。在这些研究中，我们将开发新的方法来研究无创血液流向肌肉。

DESCRIPTION (provided by applicant): The long-term complications of Type 2 Diabetes Mellitus (T2DM) include structural and functional impairments to the microvasculature. In skeletal muscle, these result in reduced blood flow for glucose disposal and to support physical activity, imperiling both local tissue and overall health. However, there are no non-invasive methods for specifically studying skeletal muscle microvascular function used in routine clinical practice. The overall objective of the proposed studies is to develop proton density- and blood oxygenation level-dependent (BOLD)- sensitive magnetic resonance imaging (MRI) techniques for studying skeletal muscle microvascular function non-invasively. Specific Aim 1 is to test the hypothesis that analysis of post-isometric contraction changes in proton density-weighted MRI signals will reproducibly and reliably distinguish between T2DM patients with microvascular disease and healthy subjects. We currently use short- and long- gradient echo MRI signals to follow blood volume and oxygenation changes following brief maximal isometric contractions. We have adapted our current protocols so as to provide greater sensitivity to the attenuated total blood flow responses and delayed blood flow kinetics in T2DM. Specific Aim 2 is to use post-contraction changes in proton density-weighted MRI signal transients to assess microvascular function in T2DM patients after initial diagnosis and during 3 months of clinical intervention according to current standards-of-care. This will allow us to examine the feasibility of using these measures to assess microvascular responses to improved glycemic control without interfering with patient care. Successfully accomplishing these aims will improve the health of persons with T2DM by providing new non-invasive techniques for assessing peripheral microvascular function. Type 2 diabetes is a serious disorder in which the body can not regulate blood sugar levels properly. One of the long-term complications of Type 2 diabetes is reduced blood flow to the muscles. This leads to even worse blood sugar control and possibly to very serious complications such as limb amputation. In these studies we will be developing new methods for studying blood flow to muscles non-invasively.