# Probing Osteoarthritis Pathogenesis by Noninvasive Imaging of Cartilage Strain

> **NIH NIH R01** · UNIVERSITY OF COLORADO · 2021 · $222,564

## Abstract

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 heal...

## Key facts

- **NIH application ID:** 10339486
- **Project number:** 3R01AR063712-09S1
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** Corey P Neu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $222,564
- **Award type:** 3
- **Project period:** 2013-09-19 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10339486

## Citation

> US National Institutes of Health, RePORTER application 10339486, Probing Osteoarthritis Pathogenesis by Noninvasive Imaging of Cartilage Strain (3R01AR063712-09S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10339486. Licensed CC0.

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