# MR Biomarkers of Inflammation in Knee Osteoarthritis

> **NIH VA I01** · VA SAN DIEGO HEALTHCARE SYSTEM · 2023 · —

## Abstract

Osteoarthritis (OA) is highly prevalent in U.S. military service members and Veterans due to the impact of
joint trauma and overuse injury. Its socioeconomic impact is substantial, estimated to approach $60 billion
per year, and no disease-modifying treatments exist. Collaborative programs (such as CaRe-AP) have been
proposed to develop a treatment for post-traumatic osteoarthritis (PTOA) that will relieve pain and improve
function. The hypothesis that PTOA is caused by maladaptive repair responses including activation of the
pro-inflammatory pathways of innate immunity that in turn result in pain, loss of function and structural
decline have been broadly accepted. To this end, OA has long been characterized as a ‘wear and tear’
disease but is now considered a cell-mediated condition involving low-grade innate inflammation affecting
all tissues of the joint (cartilage, bone, synovium, fat pads). Inflammatory processes increase the risk of
knee OA (kOA) onset and progression, though the role of inflammation in the kOA, and as a determinant in
successful treatments is unclear. Further, correlation of structural changes that result in progression of
degeneration in kOA with those that serve as pain generators in this disease is crucial. Opioid prescriptions
due to acute and chronic musculoskeletal pain visits increased by 50% between 2006 and 2010.
MRI of kOA has historically focused on tissue specific drivers of OA, most notably cartilage evaluation. Our
past work has pioneered a whole-joint approach to kOA, taking into consideration interactions between
cartilage, meniscus and subchondral bone. The current MRI literature on the synovium, synovial fluid,
infrapatellar fat pad (IFP) and bone marrow are limited, presenting a significant gap in MRI evaluation of
kOA. The overwhelming majority of MRI literature addressing synovitis/effusion involves intravenous
contrast-based protocols. In a patient population prone to peripheral vascular disease (affecting contrast
delivery) and requiring longitudinal follow-up, contrast administration is suboptimal. Given the histologic
elements of the inflammatory pathway in synovium, IFP and bone marrow, non-invasive identification and
characterization of cellular infiltrates as well as their distinction from synovial hyperplasia, fibrosis and
vascularity in tissues would represent a revolutionary step in understanding the role of inflammation in OA
progression and response to therapy. Restriction Spectrum Imaging (RSI) is a novel diffusion-weighted
technique that has been used to distinguish restricted diffusion within cells from other water compartments,
has higher resolution than standard diffusion sequences, and has the potential to be standardized across
institutions. Ultrashort Echo Time Dual Echo Steady State (UTE-DESS) combines UTE and DESS to
characterize tissues with a range of intrinsic MR properties and allows quantitative evaluation of those
properties (T1 and T2) as well as diffusion data. We hypothes...

## Key facts

- **NIH application ID:** 10476943
- **Project number:** 2I01CX000625-09A1
- **Recipient organization:** VA SAN DIEGO HEALTHCARE SYSTEM
- **Principal Investigator:** CHRISTINE B CHUNG
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2023
- **Award amount:** —
- **Award type:** 2
- **Project period:** 2022-10-01 → 2026-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10476943

## Citation

> US National Institutes of Health, RePORTER application 10476943, MR Biomarkers of Inflammation in Knee Osteoarthritis (2I01CX000625-09A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10476943. Licensed CC0.

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