Osteoarthritis (OA) is the most common form of arthritis in synovial joints and a leading cause of chronic disability, mainly in the elderly population. It currently affects 9% of the US population and is expected to affect 19% of Americans by 2030. OA is a degenerative disease of articular cartilage and is mainly characterized by a loss of glycosaminoglycans (GAG), change in size and organization of collagen fibers, and increased water content. There is no known cure for OA and present treatments focus mainly on pain management and ultimately, joint replacement. There are many obstacles to studying OA (heterogeneity in etiology, variability in progression of disease, long time periods required to see morphological joint changes), and consequently we currently lack the ability to predict the course of the disease. The limitation of identifying OA patients at riskfor progression and the lack of available non-invasive early biochemical markers have impeded the clinical development of potential disease modifying OA drugs (DMOAD). Specifically, hip osteoarthritis has a prevalence from 3 to 11% in Western population over 35 years old, and it is the main cause of hip pain in older adults. Quantitative sodium magnetic resonance imaging (MRI) is a non-invasive technique that is highly specific to the GAG content in cartilage that could be used to assess the degree of biochemical degradation of cartilage in OA. However, due to the low sodium concentration in vivo, its low sensitivity and fast relaxation, detecting the sodium signal in cartilage requires high fields (>3T), specific coils and specific 3D non-Cartesian sequences with ultrashort echo time. To the best of our knowledge, no study on sodium MRI of the hip was published to date. The recent acquisition of a dual-tuned body coil for imaging at 3T by our research team will allow us to acquire co-registered proton and sodium images of the hip within the same session. Quantitative sodium MRI could therefore provide a unique endogenous assessment of cartilage GAG content in clinically feasible scan times (20-25 min), and allow detection of OA in articular cartilage before morphological damage occurs and help assessing the effect of DMOAD treatments.
The aims of this pilot study are: 1) to develop and optimize the acquisition and reconstruction of quantitative sodium MRI of the hip joint in vivo (to optimize the acquisition sequence parameters for minimizing the acquisition time, increasing the signal-to-noise ratio and spatial resolution, to measure relaxation times and B1 maps, and to optimize synovial fluid suppression) and, 2) to apply quantitative sodium MRI to subjects with and without hip OA (to assess repeatability, sensitivity, specificity of the method, with and without fluid suppression). This method could profoundly affect how we diagnose OA in the hip joint and may allow the identification of high risk individuals and also assess DMOAD treatment follow-ups. Successful completion of this pilot project would allow us to apply to a R01 grant for improving the speed of sodium data acquisition (using compressed sensing) and investigating the clinical value of quantitative sodium MRI for assessing different degrees of OA in comparison to other proton-based imaging techniques such as dGEMRIC, T1? mapping or diffusion imaging.
Osteoarthritis (OA) is a degenerative joint disease that leads to chronic disability and for which there is no known cure. In this pilot study, we aim to develop quantitative sodium magnetic resonance imaging (MRI) method which is sensitive to biochemical degradation of the articular cartilage, for assessing OA in the hip joint. The proposed method could therefore allow detection of hip OA in patients at risk and help develop potential disease modifying OA drugs (DMOAD).
|Nunes Neto, Lucidio P; Madelin, Guillaume; Sood, Terlika Pandit et al. (2018) Quantitative sodium imaging and gliomas: a feasibility study. Neuroradiology 60:795-802|
|Khegai, Oleksandr; Madelin, Guillaume; Brown, Ryan et al. (2018) Dynamic phosphocreatine imaging with unlocalized pH assessment of the human lower leg muscle following exercise at 3T. Magn Reson Med 79:974-980|
|Madelin, Guillaume; Xia, Ding; Brown, Ryan et al. (2018) Longitudinal study of sodium MRI of articular cartilage in patients with knee osteoarthritis: initial experience with 16-month follow-up. Eur Radiol 28:133-142|
|Lakshmanan, Karthik; Brown, Ryan; Madelin, Guillaume et al. (2018) An eight-channel sodium/proton coil for brain MRI at 3 T. NMR Biomed 31:|
|Gilles, Alina; Nagel, Armin M; Madelin, Guillaume (2017) Multipulse sodium magnetic resonance imaging for multicompartment quantification: Proof-of-concept. Sci Rep 7:17435|
|Brown, Ryan; Lakshmanan, Karthik; Madelin, Guillaume et al. (2016) A flexible nested sodium and proton coil array with wideband matching for knee cartilage MRI at 3T. Magn Reson Med 76:1325-34|
|Lee, Jae-Seung; Xia, Ding; Madelin, Guillaume et al. (2016) Sodium inversion recovery MRI on the knee joint at 7 T with an optimal control pulse. J Magn Reson 262:33-41|
|Madelin, Guillaume; Babb, James; Xia, Ding et al. (2015) Repeatability of quantitative sodium magnetic resonance imaging for estimating pseudo-intracellular sodium concentration and pseudo-extracellular volume fraction in brain at 3 T. PLoS One 10:e0118692|
|Madelin, Guillaume; Poidevin, Frederick; Makrymallis, Antonios et al. (2015) Classification of sodium MRI data of cartilage using machine learning. Magn Reson Med 74:1435-48|