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:
- 金额:$ 45.82万
- 依托单位:
- 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:
- 关键词:3-Dimensional3D PrintAddressAffectAnimal ModelAreaAtrophicBiologyBiopsyCarrageenanCell Membrane PermeabilityCellsCharacteristicsChronicClinicalComplexComputer SimulationDenervationDermatomyositisDiagnosisDiffusionDiffusion Magnetic Resonance ImagingDiseaseEdemaEngineeringExcisionExtracellular MatrixFascicleFatty acid glycerol estersFiberFibrosisGeometryGoalsGoldHealthHealth Care CostsHistologyHypertrophyImageImaging TechniquesImpairmentInclusion Body MyositisIndividualInflammationInjectionsInjuryIsometric ExerciseKnowledgeMagnetic Resonance ImagingMeasurementMeasuresMembraneMetabolismMethodsMicroscopicModelingMonitorMorphologyMuscleMuscle FibersMuscle functionMuscular AtrophyMuscular DystrophiesMyopathyNeedlesNeuromuscular DiseasesPainPathologyPatientsPerformancePermeabilityPhysiologic pulsePolymyositisProductionPropertyQuality of lifeRecoveryResolutionSampling ErrorsSarcolemmaSarcomeresSignal TransductionSkeletal MuscleSkeletal muscle injurySpecificitySterilityStructural BiochemistryStructureStructure-Activity RelationshipTechniquesTestingTimeTissue ModelTissuesWaterbasecardiovascular healthclinical translationcostdesigndiagnosis standardexperimental studyextracellularimprovedin silicoin vivoinjuredinnovationmuscular structurenanofabricationnovelphantom modelpre-clinicalsimulationtoolwater 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.
骨骼肌体现了生物学中的结构与功能关系。肌节的组织如下
分层排序形成长收缩细胞,捆绑在细胞外基质中,形成更大的束和
最终完整的肌肉。结构和功能之间的紧密关系保证了肌肉的表现
(和疾病)可以从其微观结构推断出来。例如,纤维面积与等长力直接相关
肌肉的生产。随着损伤,肌纤维面积(大小)的微观结构发生变化,纤维化(纤维的积累)
观察到细胞外基质)、膜损伤(渗透性)和炎症(水肿),并损害
肌肉功能。肌肉活检,然后进行组织显微镜检查(组织学),是黄金
诊断和监测肌肉健康和疾病的标准。该工具是侵入性的,需要大孔径
在无菌条件下去除针头和组织,这使得过程痛苦且昂贵。因此,活检不
有利于肌肉健康的连续监测。它也是半定量的,并且通常很难推断
整个肌肉,限制了其科学和临床价值。由于这些原因,需要非侵入性的
肌肉微观结构的评估,这将有助于定量检查肌肉损伤
时间。磁共振成像(MRI)已被用于无创地量化体积、脂肪的变化
分布和肌肉中的水分含量。扩散张量成像 (DTI) 是 MRI 的一种版本,可测量
水的各向异性扩散,与组织微观结构有关,但往往会产生非特异性变化
无论受伤或疾病状态如何。缺乏特异性的主要原因是明确的
微观结构和扩散之间的关系尚未经过严格研究,也没有经过仔细校准。
为了解决这一知识差距,该提案的目的是比较肌肉微观结构和 MRI
新颖且严格控制的计算机模拟中肌肉的扩散特性,经过精密设计
肌肉损伤和疾病的幻影和动物模型。我们的中心假设是 DT-MRI 可以
当使用适当的脉冲序列来解耦时,与肌肉微观结构的变化直接相关
复杂的病理学。目标#1将使用基于计算机的肌肉结构和生物化学模拟来
仔细了解扩散与多种肌肉微观结构变化的关系。目标 #2 将利用 3D
精密设计的模型可将扩散与真实 DT-MRI 实验中的肌肉结构联系起来。这些
实验将被整合到最终的体内实验组中(目标#3),旨在测试
DT-MRI 的准确性可解开肌肉萎缩时复杂的微观结构变化,
炎症、变性。这些实验将阐明之间尚未研究的关系
肌肉的微观结构和扩散。长期目标是连续量化肌肉微观结构非
侵入性地。这种方法的创新之处在于它结合了最先进的成像、模拟、纳米加工、
和形态学方法来生成有临床意义的测量工具。
项目成果
期刊论文数量(0)
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会议论文数量(0)
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{{ truncateString('LAWRENCE R FRANK', 18)}}的其他基金
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
- 批准号:
10229536 - 财政年份:2017
- 资助金额:
$ 45.82万 - 项目类别:
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
- 批准号:
9763318 - 财政年份:2017
- 资助金额:
$ 45.82万 - 项目类别:
HIGH ANGULAR RESOLUTION DIFFUSION IMAGING W/ MAGNETIC RESONANCE
磁共振高分辨率扩散成像
- 批准号:
7722319 - 财政年份:2008
- 资助金额:
$ 45.82万 - 项目类别:
HIGH ANGULAR RESOLUTION DIFFUSION IMAGING W/ MAGNETIC RESONANCE
磁共振高分辨率扩散成像
- 批准号:
7601666 - 财政年份:2007
- 资助金额:
$ 45.82万 - 项目类别:
Software for the Analysis and Visualization of High Angular Resolution DTI Data
用于高角分辨率 DTI 数据分析和可视化的软件
- 批准号:
7123677 - 财政年份:2006
- 资助金额:
$ 45.82万 - 项目类别:
Software for the Analysis and Visualization of High Angular Resolution DTI Data
用于高角分辨率 DTI 数据分析和可视化的软件
- 批准号:
7477670 - 财政年份:2006
- 资助金额:
$ 45.82万 - 项目类别:
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