Non invasive measurements of muscle microstructure assessed by diffusion tensor imaging

通过扩散张量成像评估肌肉微观结构的无创测量

基本信息

批准号：
9982046
负责人：
LAWRENCE R FRANK
金额：
$ 45.82万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-11 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9982046
关键词：
3-Dimensional 3D Print Address Affect Animal Model Area Atrophic Biology Biopsy Carrageenan Cell Membrane Permeability Cells Characteristics Chronic Clinical Complex Computer Simulation Denervation Dermatomyositis Diagnosis Diffusion Diffusion Magnetic Resonance Imaging Disease Edema Engineering Excision Extracellular Matrix Fascicle Fatty acid glycerol esters Fiber Fibrosis Geometry Goals Gold Health Health Care Costs Histology Hypertrophy Image Imaging Techniques Impairment Inclusion Body Myositis Individual Inflammation Injections Injury Isometric Exercise Knowledge Magnetic Resonance Imaging Measurement Measures Membrane Metabolism Methods Microscopic Modeling Monitor Morphology Muscle Muscle Fibers Muscle function Muscular Atrophy Muscular Dystrophies Myopathy Needles Neuromuscular Diseases Pain Pathology Patients Performance Permeability Physiologic pulse Polymyositis Production Property Quality of life Recovery Resolution Sampling Errors Sarcolemma Sarcomeres Signal Transduction Skeletal Muscle Skeletal muscle injury Specificity Sterility Structural Biochemistry Structure Structure-Activity Relationship Techniques Testing Time Tissue Model Tissues Water base cardiovascular health clinical translation cost design diagnosis standard experimental study extracellular improved in silico in vivo injured innovation muscular structure nanofabrication novel phantom model pre-clinical simulation tool water diffusion

项目摘要

Skeletal muscle exemplifies structure-function relationships in biology. The organization of sarcomeres follow hierarchical ordering to form long contractile cells, bundled in extra-cellular matrix, to form larger fascicles and ultimately whole muscles. The tight relationship between structure and function allows muscle performance (and disease) to be inferred from its microstructure. For example, fiber area is directly related to isometric force production in muscle. With injury, microstructural changes in muscle fiber area (size), fibrosis (accumulation of extracellular matrix), membrane damage (permeability), and inflammation (edema) are observed, and impair muscle function. Muscle biopsy, followed by microscopic examination of the tissue (histology), is the gold standard to diagnose and monitor muscle health and disease. This tool is invasive, requiring a large bore needle and tissue removal under sterile conditions, which makes it painful and costly. Therefore, biopsy is not conducive to serial monitoring of muscle health. It is also semi-quantitative, and often difficult to extrapolate to the entire muscle, limiting its scientific and clinical value. For these reasons, there is a need for noninvasive assessment of muscle microstructure, which would facilitate the quantitative examination of muscle injury over time. Magnetic resonance imaging (MRI) has been used to noninvasively quantify changes in volume, fat distribution, and water content in muscle. Diffusion tensor imaging (DTI) is a version of MRI that measures anisotropic diffusion of water, which is related to tissue microstructure, but tends to yield non-specific changes regardless of the injury or disease state. The key reason for this lack of specificity is that the explicit relationships between microstructure and diffusion have not been rigorously studied, nor carefully calibrated. To address this gap in knowledge, the purpose of this proposal is to compare muscle microstructure and MRI diffusion properties of muscle in novel and tightly controlled computer simulations, precision engineered phantoms, and animal models of muscle injury and disease. Our central hypothesis is that DT-MRI can be directly related to muscle microstructural changes, when appropriate pulse sequences are used to uncouple complex pathology. Aim #1 will use computer-based simulations of muscle structure and biochemistry to carefully understand how diffusion is related to multiple muscle microstructural changes. Aim #2 will utilize 3D precision-engineered models to relate diffusion to muscle structure in real-world DT-MRI experiments. These experiments will be integrated into a final in vivo set of experiments (Aim #3), which are designed to test the accuracy of DT-MRI to uncouple complex microstructural changes in the presence of muscle atrophy, inflammation, and degeneration. These experiments will elucidate the understudied relationships between microstructure and diffusion in muscle. The long-term goal is to serially quantify muscle microstructure non- invasively. This approach is innovative in that it combines state-of-the art imaging, simulation, nanofabrication, and morphology methods to generate a clinically meaningful measurement tool.

骨骼肌例证了生物学中的结构 - 功能关系。肉瘤的组织关注分层秩序形成长的收缩细胞，捆绑在细胞外基质中，形成较大的束和最终整个肌肉。结构和功能之间的紧密关系使肌肉性能（和疾病）可以从其微观结构中推断出来。例如，纤维区域与等距力直接相关肌肉产生。受伤，肌肉纤维区域的微观结构变化（尺寸），纤维化（积累观察到细胞外基质），膜损伤（渗透率）和炎症（水肿），并损害肌肉功能。肌肉活检，然后对组织学（组织学）进行微观检查，是金诊断和监测肌肉健康和疾病的标准。该工具具有侵入性，需要大量孔无菌条件下的针和组织去除，这使其疼痛和昂贵。因此，活检不是有利于肌肉健康的连续监测。它也是半定量的，通常很难推断整个肌肉，限制了其科学和临床价值。由于这些原因，需要无创肌肉微观结构的评估，这将促进肌肉损伤的定量检查时间。磁共振成像（MRI）已用于非侵入性量化体积的变化，脂肪分布和肌肉中的水含量。扩散张量成像（DTI）是MRI的一个版本，用于测量水的各向异性扩散与组织微结构有关，但倾向于产生非特异性变化不管受伤或疾病状态如何。缺乏特异性的关键原因是明确微观结构和扩散之间的关系尚未经过严格研究，也没有仔细校准。为了解决这一知识的差距，该建议的目的是比较肌肉微观结构和MRI 肌肉在小说和紧密控制的计算机模拟中的扩散特性，精密设计幻影以及肌肉损伤和疾病的动物模型。我们的中心假设是DT-MRI可以是与肌肉微观结构变化直接相关，当使用适当的脉冲序列解开时复杂的病理。 AIM＃1将使用基于计算机的肌肉结构和生物化学模拟仔细了解扩散与多种肌肉微结构变化有何关系。 AIM＃2将使用3D 精确工程模型将扩散与现实世界DT-MRI实验中的肌肉结构相关联。这些实验将集成到最终的体内实验集中（AIM＃3），旨在测试 DT-MRI在肌肉萎缩存在下取消复杂的微结构变化的精度，炎症和变性。这些实验将阐明微观结构和肌肉扩散。长期目标是串行量化肌肉微观结构非 - 侵入性。这种方法具有创新性，因为它结合了最先进的成像，模拟，纳米制作，和形态学方法是生成临床上有意义的测量工具。