Probing Osteoarthritis Pathogenesis by Noninvasive Imaging of Cartilage Strain
通过软骨应变的无创成像探讨骨关节炎的发病机制
基本信息
- 批准号:10339486
- 负责人:
- 金额:$ 22.26万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-09-19 至 2023-03-31
- 项目状态:已结题
- 来源:
- 关键词:AftercareAnimalsAnterior Cruciate LigamentArthroscopyBenchmarkingBiological AssayBiological MarkersBiological ModelsBiological Response Modifier TherapyBiologyBiomechanicsBody mass indexCartilageCartilage DiseasesCellsClinicalCollagen Type IICommunitiesCoupledDataDegenerative polyarthritisDiagnosisDigestionDiseaseEnzymesFoundationsFunctional disorderGenderGoldGrantHealthHumanImageImaging TechniquesIn VitroInflammatoryInterventionJoint repairJointsLigamentsMagnetic Resonance ImagingMeasurementMeasuresMechanicsMethodsModelingModulusMonitorMonte Carlo MethodNoiseOperative Surgical ProceduresOrthopedic SurgeryOutcomeOutcome MeasurePainPathogenesisPatient Outcomes AssessmentsPatientsPatternPopulationPropertyRadiology SpecialtyReproducibilityResearchRuptureSeveritiesSheepSignal TransductionStatistical ModelsStructureStructure-Activity RelationshipSurveysTechniquesTestingTimeTissuesTranslatingTraumaUncertaintyValidationWorkaggrecananterior cruciate ligament rupturearticular cartilagebasecytokineefficacy evaluationelastographyfirst-in-humanfunctional outcomesimaging biomarkerimaging modalityimaging systemimplantationimprovedin vivoinjury and repairjoint functionjoint injuryligament injurymacromoleculenon-invasive imagingnoninvasive diagnosisnovelpatient subsetspredictive markerreconstructionrepairedstandard of caretendon grafttoolvolunteer
项目摘要
PROJECT SUMMARY / ABSTRACT
The objective of this proposal is to predict osteoarthritis (OA) pathogenesis in vivo using a novel noninvasive
MRI-based method of measuring articular cartilage biomechanics. Recent advances in magnetic resonance
imaging (MRI) have been introduced with exciting potential to diagnose and predict the progression of OA, the
most common degenerative joint disease. MRI methods have sought to discover early changes in OA, when
emerging disease-modifying interventions (e.g. cell implantation) may be most effective. OA pathophysiology
often involves joint injury (e.g. ligament rupture) and a degenerative cascade of increased expression of
inflammatory cytokines and enzymes. Moreover, the breakdown and loss of major macromolecules such as
aggrecan and type II collagen leads to altered strains and material properties (e.g. moduli) within the tissue,
suggesting MRI of cartilage biomechanics may be sensitive to degeneration. Unfortunately, noninvasive
diagnosis of OA remains poor, especially in early disease stages, and several challenges remain, including the
need for sensitive and specific imaging biomarkers that predict OA outcomes, and the need to relate imaging
biomarkers to tissue function and biomechanics. In our original grant (AR063712), we pioneered dualMRI
(displacements under applied loading by MRI) for cartilage biomechanics to monitor joint health. We
discovered that dualMRI is robust to detect strain increases following controlled enzyme digestions or
mechanical trauma to excised tissues, and in an in vivo time-course meniscectomy study in sheep. Compared
to quantitative MRI (qMRI, e.g. T1ρ mapping), shear strains better correlated with OA severity in human
cartilage. We also recently performed first-in-human in vivo and intra-tissue cartilage strain measures on a
clinical 3 Tesla (T) MRI system. In this renewal application, we will establish a workflow to measure strains and
moduli (i.e. elastography), and validate this workflow in multiple model systems. In humans, we will also
identify biomechanics-based MRI metrics and biomarkers that predict time-course cartilage function and
symptomatic pain following ligament reconstruction in a subset of patients. We will pursue three related
specific aims. In Aim 1, we will establish a routine, clinical workflow for dualMRI measures of intra-tissue strain
and properties. We will extend our existing dualMRI sequence to accelerate clinical measurement of strain
within 15 minutes, and coupled to inverse modeling, automate measurement of in vivo elastography. In Aim 2,
we will validate dualMRI intra-tissue strain and properties against gold-standard benchmarks, confirming
reproducibility for in vivo time course analyses by quantifying numerous error metrics. In Aim 3, we will predict
functional outcomes and cartilage health in patients following ligament reconstruction. We will determine the
extent that MRI metrics at six months predict patient-reported outcomes and tissue health at one and two years
post treatment. If successful, we will establish a routine method for functional assessment of cartilage, and
support a new paradigm targeting cartilage biomechanics as specific indicators of joint damage and repair.
项目摘要/摘要
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('Corey P Neu', 18)}}的其他基金
Development and Translation of Granulated Human-Derived Biomaterials for Integrative Cartilage Repair
用于综合软骨修复的颗粒状人源生物材料的开发和转化
- 批准号:
10718170 - 财政年份:2023
- 资助金额:
$ 22.26万 - 项目类别:
Probing Osteoarthritis Pathogenesis by Noninvasive Imaging of Cartilage Strain
通过软骨应变的无创成像探讨骨关节炎的发病机制
- 批准号:
9321780 - 财政年份:2016
- 资助金额:
$ 22.26万 - 项目类别:
Probing Osteoarthritis Pathogenesis by Noninvasive Imaging of Cartilage Strain
通过软骨应变的无创成像探讨骨关节炎的发病机制
- 批准号:
9221761 - 财政年份:2016
- 资助金额:
$ 22.26万 - 项目类别:
Intervertebral Disc Mechanics Measured by dualMRI In Vivo
通过体内双核磁共振成像测量椎间盘力学
- 批准号:
9294854 - 财政年份:2016
- 资助金额:
$ 22.26万 - 项目类别:
Intervertebral Disc Mechanics Measured by dualMRI In Vivo
通过体内双核磁共振成像测量椎间盘力学
- 批准号:
9034951 - 财政年份:2016
- 资助金额:
$ 22.26万 - 项目类别:
Biomechanics of Human Articular Cartilage Measured In Vivo
体内测量的人体关节软骨的生物力学
- 批准号:
8682517 - 财政年份:2014
- 资助金额:
$ 22.26万 - 项目类别:
Biomechanics of Human Articular Cartilage Measured In Vivo
体内测量的人体关节软骨的生物力学
- 批准号:
8825423 - 财政年份:2014
- 资助金额:
$ 22.26万 - 项目类别:
Probing Osteoarthritis Pathogenesis by Noninvasive Imaging of Cartilage Strain
通过软骨应变的无创成像探讨骨关节炎的发病机制
- 批准号:
10377980 - 财政年份:2013
- 资助金额:
$ 22.26万 - 项目类别:
Probing Osteoarthritis Pathogenesis by Noninvasive Imaging of Cartilage Strain
通过软骨应变的无创成像探讨骨关节炎的发病机制
- 批准号:
8737724 - 财政年份:2013
- 资助金额:
$ 22.26万 - 项目类别:
Probing Osteoarthritis Pathogenesis by Noninvasive Imaging of Cartilage Strain
通过软骨应变的无创成像探讨骨关节炎的发病机制
- 批准号:
9918150 - 财政年份:2013
- 资助金额:
$ 22.26万 - 项目类别:
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