Multinuclear MRI Assessment of Diabetic Peripheral Neuropathy

糖尿病周围神经病变的多核 MRI 评估

• 批准号: 9091515
• 负责人: Prodromos Parasoglou
• 金额: $ 43.53万
• 依托单位: NEW YORK UNIVERSITY SCHOOL 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: 2015-07-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9091515
• 关键词: Affect; Amputation; Area; Bioenergetics; Blood Glucose; Blood Vessels; Blood capillaries; Blood flow; Clawtoe; Clinical; Clinical assessments; Cross-Sectional Studies; Development; Diabetes Mellitus; Diabetic Foot Ulcer; Diagnosis; Disease Progression; Early Diagnosis; FDA approved; Health; Image; Impairment; Lead; Leg; Limb structure; Link; Longitudinal Studies; Magnetic Resonance; Magnetic Resonance Imaging; Measurement; Measures; Medical; Metabolic; Metabolic Pathway; Methods; Mitochondria; Molecular; Muscle; Muscular Atrophy; Nerve; Neuromuscular Diseases; Neuropathy; Noise; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Oxidative Phosphorylation; Pathogenesis; Patients; Perfusion; Peripheral; Peripheral Nerves; Peripheral Nervous System Diseases; Phosphorus; Physiologic pulse; Resolution; Risk Factors; Role; Severities; Signal Transduction; Skeletal Muscle; Staging; Techniques; Testing; Therapeutic; Ulcer; Work; angiogenesis; blood glucose regulation; blood oxygen level dependent; capillary; cost; design and construction; diabetic; diabetic patient; effective therapy; foot; improved; insight; novel therapeutics; pressure; prevent; wound

 DESCRIPTION (provided by applicant): Approximately 15% of type 2 diabetes mellitus (T2DM) patients will develop a diabetic foot ulcer (DFU). Despite several therapeutic approaches for wound treatment, approximately 15-20% of all DFUs ultimately require amputation. A major risk factor for the development of DFUs is diabetic peripheral neuropathy (DPN), which affects between 30-50% of all diabetic patients. The underlying mechanisms that cause DPN are not fully understood, and there are no FDA-approved therapies to prevent or reverse its progress. DPN is characterized by impaired metabolic and microvascular functions, which damage the endoneural capillaries that supply the peripheral nerves. Therefore understanding the diverse roles of bioenergetics and the microvasculature in the pathogenesis of DPN might facilitate the search for novel therapeutic compounds to prevent and treat DPN. Importantly, both metabolic and microvascular functions can be assessed using multinuclear MRI. Whereas phosphorus (31P) magnetic resonance (MR) can noninvasively assess skeletal muscle bioenergetics, microvascular function in muscle can be measured using post-contractile changes in blood oxygenation level dependent (BOLD) MRI signals. While typical 31P-MR approaches are limited by low sensitivity and poor spatial resolution, we have developed 31P-MRI methods that yield extensive muscle coverage and up to 30-fold increased spatial resolution compared with existing methods. This development in high-resolution 31P imaging allows us to examine focal areas of metabolic impairment, which are likely to occur in DPN. In this study we propose continued development of the 31P-MR acquisition to further improve the sensitivity of our measurements on a clinical (3T) MRI scanner and determine if our 31P-MR techniques, combined with BOLD-MRI, can i) detect presence and severity of DPN and ii) predict DFU formation. Our main working hypothesis is that multinuclear MRI will enable early detection of DPN and provide new insights into the vascular and metabolic impairments in the diabetic lower leg muscles that lead to complications, such as DFU formation. The proposed study has three specific aims: 1.) To enhance the sensitivity of 31P-MR metabolic outcomes through improved design and construction of a highly sensitive 3T dual-tuned (31P/1H) multi-channel array coil; 2) To perform a cross-sectional study and determine whether co-localized multinuclear MRI at 3T detects presence of DPN; and 3.) To perform a 2-year longitudinal study to determine if changes in multinuclear MRI measures of muscle perfusion and metabolic function at 3T indicate DPN progression and whether they can predict DFU formation. This proposal has a high likelihood of establishing multinuclear MRI as a non-invasive method for the early diagnosis and staging of DPN. It promises to enable new insights into the diverse roles of bioenergetics and microvascular factors responsible for the onset and progression of the disease. Multinuclear MRI might emerge as a key imaging approach to guide the diagnosis and therapy of DPN.

 描述(申请人提供)：大约15%的2型糖尿病(T2 DM)患者会发展为糖尿病足溃疡(DFU)。尽管有几种创面治疗方法，但大约15%-20%的DFU最终需要截肢。糖尿病周围神经病变(DPN)是DFU发生的主要危险因素，在所有糖尿病患者中有30%-50%受到影响。引起DPN的潜在机制尚不完全清楚，也没有FDA批准的治疗方法来阻止或逆转其进展。DPN的特点是代谢和微血管功能受损，损害供应周围神经的神经内毛细血管。因此，了解生物能量学和微血管在DPN发病机制中的不同作用，有助于寻找新的治疗药物来预防和治疗DPN。重要的是，代谢和微血管功能都可以用多核磁共振进行评估。虽然磷(31P)磁共振(MR)可以无创地评估骨骼肌的生物能量学，但肌肉的微血管功能可以通过收缩后血氧水平依赖(BOLD)MRI信号的变化来测量。虽然典型的31P-MR方法受限于低灵敏度和低空间分辨率，但我们开发了31P-MRI方法，与现有方法相比，31P-MRI方法产生了广泛的肌肉覆盖范围和高达30倍的空间分辨率。高分辨率31P成像的这一进展使我们能够检查DPN中可能发生的代谢损伤的焦点区域。在这项研究中，我们建议继续开发31P-MR采集，以进一步提高我们在临床(3T)MRI扫描仪上测量的灵敏度，并确定我们的31P-MR技术与BOLD-MRI相结合是否可以：i)检测DPN的存在和严重程度；ii)预测DFU的形成。我们的主要工作假设是，多核MRI将使DPN的早期检测成为可能，并为糖尿病小腿肌肉中导致并发症(如DFU形成)的血管和代谢损伤提供新的见解。拟议的研究有三个具体目标：1)通过改进设计和构造高灵敏度的3T双调谐(31P/1H)多通道阵列线圈来提高31P-MR代谢结果的灵敏度；2)进行横断面研究，并确定3T共定位多核MRI是否检测到DPN的存在；以及进行一项为期两年的纵向研究，以确定3T时肌肉灌注和代谢功能的多核MRI测量的变化是否预示着DPN的进展，以及它们是否可以预测DFU的形成。这一建议很有可能建立多核MRI作为DPN早期诊断和分期的无创性方法。它有望使人们对生物能量学和微血管因素在疾病发生和发展中的不同作用有新的见解。多核MRI可能成为指导DPN诊断和治疗的关键影像手段。