Osteoarthritis (OA) affects over 30 million people and is the most common cause of disability in adults in the U.S. The Arthritis Foundation has set the goal of advancing OA treatments as one of its highest priorities, making it one of the Foundation’s four scientific initiatives. To do this, we have created the OA Center of Excellence (COE), where researchers from around the county can join the Clinical Trial Network to work together to accelerate the development of new OA therapies.
The OA COE is currently funding three Clinical Trial Network demonstration studies that may lead to better diagnosis and earlier treatments. Researchers from six different institutions will collaborate in various aspects of these cutting-edge studies. We will look at each of these studies in a series of blogs.
Dr. Xiaojuan Li is the principal investigator of the study “Multi-site Multi-Vendor Cross-validation of Cartilage T1rho and T2 imaging”. The team, made up investigators from four sites (the Cleveland Clinic Foundation [CCF] in Ohio, the University of California San Francisco, the University of Kentucky, and the University Hospital for Albert Einstein College of Medicine in New York) are working to quantify biomarker assessments in cartilage images obtained through magnetic resonance imaging (MRI). The study will take about six months to complete.
MRI has the advantage over other imaging method in being able to view cartilage, in addition to muscles, tendons, and bones. Articular (joint) cartilage is very thin and made up of cells (chondrocytes), proteins, water, and other molecules that help it retain water and maintain its structure. Retaining water is critical for the cartilage to maintain joint health and protect bones.
The most common MRI images are collected from two types of scans: T1-weighted and T2-weighted scans. Generally, T1-weighted images look at only fat tissue, while T2-weighted images look at fat and water in the tissue (cartilage). These currently used techniques are limited to evaluate structural changes of cartilage (like cartilage thinning and fissuring).
Dr. Li and the investigative team are evaluating new techniques with T1rho and T2 imaging which can detect biochemical changes within the cartilage matrix before structural changes can be seen. These biochemical changes represent promising biomarkers that are more sensitive for detecting the very early stages of OA, and for evaluating cartilage changes after treatment (treatment response).
T1rho and T2 measures and test result interpretation can vary based on many factors. Things like the positioning of the patient, the temperature of the room where the images are taken, and many other factors can affect results. Test results can also vary from radiologist to radiologist, partially due to the differences in the equipment made by different manufacturers for these tests. The team will standardize procedures (like patient positioning, room temperature, etc.) and will compare the imaging results obtained from three different imaging manufacturers commonly used around the U.S. (Siemens, Philips, and GE). The team is interested in seeing how much difference there may be between test results obtained.
The team will use T1rho and T2 measures as imaging biomarkers. They plan to do scans of 5 subjects at each site. There will also be 2 or 3 traveling subjects who will be imaged at all four sites (to compare sites). The first human subject was recently enrolled and scanned at CCF. The team expects to complete scans of all human subjects by May 2018.
Each site will also have man-made “phantom” joints made from material similar to human cartilage. This will allow them to calibrate and standardize the imaging machines across sites. The phantoms also allow each site to take multiple images with a joint with known parameters, as often as needed.
Dr. Li and her team will attempt to quantify these imaging biomarkers to create algorithms to standardize the measures. Once this is done, the standard measures can become automated, making test result interpretations consistent.
Dr. Li works in the biomedical engineering department, and directs the program of advanced musculoskeletal imaging (PAMI) of the CCF in Ohio.
- Arthritis Foundation: Advancing Osteoarthritis Treatments
- Researchers on the Path to a Cure – Spotlight on Dr. Caroline Jefferies
- Researchers on the Path to a Cure – Spotlight on Dr. Edward Doherty