MRI Detection of Skeletal Muscle Microvascular Dysfunction

描述(申请人提供)：2型糖尿病(T2 DM)的长期并发症包括微血管的结构和功能损害。在骨骼肌中，这会导致用于葡萄糖处置和支持体力活动的血流量减少，危及局部组织和整体健康。然而，在常规的临床实践中，还没有非侵入性的方法来专门研究骨骼肌微血管功能。这项研究的总体目标是开发质子密度和血氧水平依赖(BOLD)敏感的磁共振成像(MRI)技术，用于非侵入性研究骨骼肌微血管功能。具体目的1是验证这样一种假设，即对质子密度加权MRI信号的等长收缩后变化的分析将重现并可靠地区分T2 DM合并微血管疾病的患者和健康受试者。我们目前使用短梯度和长梯度回波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。我们已经调整了我们目前的方案，以便对T2 DM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是利用收缩后质子密度加权MRI信号瞬变的变化来评估T2 DM患者在初步诊断后以及根据目前的护理标准进行临床干预3个月期间的微血管功能。这将使我们能够研究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，而不会干扰患者的护理。成功实现这些目标将为评估外周微血管功能提供新的非侵入性技术，从而改善T2 DM患者的健康。2型糖尿病是一种严重的疾病，身体不能适当调节血糖水平。2型糖尿病的长期并发症之一是流向肌肉的血液减少。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，我们将开发非侵入性研究肌肉血流的新方法。

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.