Early cartilage degenerative changes in individuals with chronic ankle instability

Research Team Members: Kyeongtak Song (PhD Student in Human Movement Science), Dr. Brian Pietrosimone, and Dr. Erik Wikstrom

Why did you do this study?

kt1Lateral ankle sprains are an extremely common musculoskeletal injury and about 40% of individuals who sprain their ankle develop chronic ankle instability (CAI), a condition characterized by recurrent ankle sprains and instability of the ankle joint. Additionally, recurrent ankle sprains are a common etiology for ankle post-traumatic osteoarthritis (PTOA). Roughly 12% of symptomatic OA is attributable to lower extremity PTOA and 80% of all ankle OA cases are post-traumatic in nature. Previous studies indicate that up to 78% of those with CAI develop ankle PTOA.

However, these data were obtained via arthroscopic visualization (i.e. during surgery) or using standard MRI at the end stage of OA. There is no cure for OA; thereby no therapy exists which can repair joint damage after OA has caused joint damage. Earlier detection techniques are needed if, early treatment strategies to slow the progression of PTOA are to be applied.  Therefore, it is important to detect degenerative changes at the earliest stage (molecular level) before irreversible tissue damage occurs.  Previous studies have shown that decreased proteoglycan density and increased water content are representative of early degenerative changes of the cartilage.  However, these changes are difficult to capture with plain radiography (X-ray), arthroscopy, or conventional MRI. Proteoglycans are one of the main components of the extracellular matrix of the cartilage. One of their functions is to bind with water and provide the basis for absorbing high compressive loads. Therefore, decreased proteoglycan density within articular cartilage indicate worse cartilage health.


The T1ρ MRI technique is a specialized sequence that has been developed for predominantly for cartilage imaging. The T1ρ MRI method can quantify proteoglycan density in the cartilage and provides the earliest possible detection of PTOA pathogenesis. Patients with CAI are at an increased risk of ankle PTOA, suggesting that CAI represents an important contribution to the early stages of ankle joint degeneration. Therefore, the purpose of this study was to determine if early degenerative changes of the talar cartilage were present in those with CAI compared to the healthy controls using T1ρ MRI.

What did you do and what did you find in this study?

We completed ankle MRI scans for 16 CAI patients and 16 healthy controls. They arrived at our biomedical-imaging center 30 minutes prior to the scan and remained seated to unload the ankle cartilage. We used a high resolution T1ρ relaxation time mapping technique, which quantified the interaction between water molecules and cartilage with the surrounding environment. Then, we manually segmented the talar cartilage of the t1rho image and identified four regions of interest (ROI): anteriomedial (AM), anteriolateral (AL), posteriomedial (PM), and posteriolateral (PL). Our main outcomes were the mean T1ρ relaxation times, an indicator of proteoglycan density, in each region of interest and compared these values between the CAI and control groups. Greater T1ρ relaxation times is interpreted as being associated with reduced proteoglycan density and worse cartilage health.


We found that those with CAI had higher mean T1ρ relaxation times relative to uninjured controls for all ROI, particularly in the AL region. This shows decreased proteoglycan density in talar cartilage in individuals with CAI compared to the healthy individuals and indicates that early cartilage degenerative changes are present in those with CAI.

KT Fig2

How do these findings impact the public?

Our findings suggest individuals with CAI have signs of early talar cartilage degeneration, which may be a key mediator driving the progression to PTOA. Ankle sprains are often erroneously deemed as an innocuous injury and many individuals do not seek appropriate care. However, evidence clearly shows a high prevalence of CAI and long-term negative consequences among those whom have sustained a lateral ankle sprain. Therefore, it is important to have proper treatment to prevent the development of CAI and ankle PTOA after you have sustained a lateral ankle sprain.

Our next step will be to understand how to slow the progression of ankle PTOA in those with CAI. Therefore, further research will focus on determining if early intervention programs restore appropriate biomechanics and maximize cartilage health to slow the progression of ankle PTOA in those with CAI.