SP #4: Genetic and imaging biomarkers of OA incidence and progression

Genetic and imaging biomarkers of OA incidence and progressiontest

Significance:

While osteoarthritis (OA) is not generally considered an inflammatory joint disease, there is evidence that a high level of expression of inflammatory genes promotes cartilage degradation and OA progression. For example, synovitis, or inflammation of the synovial membrane, has been associated with greater risk of cartilage loss in patients with knee OA. In a previous study, we have observed that Peripheral Blood Leukocyte (PBL) inflammatory gene expression is associated with pain, radiographic severity and progression of symptomatic knee OA (SKOA).

Aims:

In this study, we will determine whether various genomic, genetic, and protein/lipid biomarkers can be used to predict risk, progression, and severity of SKOA, as evaluated by high-field MRI. 

Approach:

Biomarkers to be as­sessed include PBL gene expression profiles (e.g. PBL IL-1b, COX-2, TNFa), plasma protein/lipid markers (e.g. tMMP-9, IL-1Ra, PGE2), and SNPs that map to inflammatory genes of interest.  We will use 3T and 7T MRI to perform multifaceted assessment of anatomical changes from baseline, including cartilage volume and thickness, subchondral bone marrow edema, synovium grading, assessment of osteophytes, etc.  In previous col­laborations with Radiology, we have used gadolinium-enhanced 3T MRI to show that quantitative assessment of synovial proliferation correlated with radiographic severity of knee osteoar­thritis (Figure 1) [1].  Further anal­yses of the MRI and scintigraphy data are ongoing, and to date 3 manuscripts have been published [2-4].  In one recent manuscript, we demonstrated the ability of T1rho imaging at 3 Tesla to identify changes in the molecular composition of menisci in subjects with varying stages of OA. 

In this Service Project, we will recruit and longitudinally follow a new cohort of 100 SKOA patients [5].  We will advance the field of combinatorial prognostic biomarkers by combining novel inflammatory biomarkers with MRI in this well-characterized knee OA population followed prospectively.

BTRC Resources Utilized:

TR&D #1: The ability to image these patients more rapidly would: 1) increase patient comfort and clinical throughput; 2) improve image quality by decreasing the chance of motion artifact during the acquisition of high-resolution proton microstructural images, which are currently time-consuming; and 3) allow additional physiologic and functional musculoskeletal imaging sequences to be performed within the same scan session (e.g., 23Na MRI in collaboration with Dr. Chang and Dr. Regatte).  Overall, rapid MR data acquisition will allow us to more easily determine a combined radiologic, genetic, and proteomic risk profile predictive of SKOA progression.  The achievement of this goal will allow us to identify the individuals who are best-suited for planned future clinical trials of disease modifying osteoarthritis drugs.

TR&D#2: The development of improved imaging hardware and safety monitoring at 7 Tesla will provide us with an unprecedented opportunity to determine in a well-defined patient cohort in vivo 1) the early changes in the molecular composition of cartilage, menisci, and other tissues during joint degeneration and 2) the early microstructural changes in cartilage, subchondral bone, and other tissues during joint degeneration.  The ability to identify these early molecular and microstructural changes at 7 Tesla will allow us to detect early disease.  Such a capability will accelerate clinical OA drug trials, which are currently time-consuming and expensive, requiring years for the onset of macroscopic structural changes on conventional MRI before the efficacy of a novel intervention can be assessed.  We would like to note that we are one of the few centers in the world with access to both a well-defined knee OA patient cohort and state-of-the art 7 Tesla imaging equipment.  We also already have on-site the clinical (rheumatology, radiology), translational (MSK imaging), and basic science (RF engineering, MR physics) expertise to carry out the project.

Principal Investigator: 

Sponsors

Latest Updates

10/31/2017 - 11:54
10/31/2017 - 11:37

Philanthropic Support

We gratefully acknowledge generous support for radiology research at NYU Langone Medical Center from:
 
• The Big George Foundation
• Raymond and Beverly Sackler
• Bernard and Irene Schwartz

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