Monitoring the disease status of autoimmune disorders such as rheumatoid and juvenile idiopathic arthritis requires better quantitative, objective, and noninvasive biomarkers. Our goal is to develop and study non-invasive imaging biomarkers for the detection and treatment monitoring of autoimmune disease. One potential biomarker is carbon-13 (13C) lactate. 13C-pyruvate can be hyperpolarized and then the amount of its conversion into its downstream metabolite, 13C-lactate can be quantified using 13C magnetic resonance spectroscopic imaging (13C-MRSI). Preliminary data generated for this K08 proposal suggest that elevated lactate production may indicate presence of inflammatory arthritis. The proposed research has three specific aims: (1) optimize 13C-MRSI to detect and quantify disease severity in mouse models of inflammatory arthritis, (2) study how well 13C-lactate concentrations correlate with other measures of arthritis that may be more established but more invasive or subjective; (3) study how well 13C-lactate levels correlate with changes in the progression of disease over time and in response to therapy. Our long-term goal is to translate this imaging strategy in large animal models and ultimately in clinical trials examining patients with rheumatoid arthritis and juvenile idiopathic arthritis. This project will also serve n important training role for the PI, who is a board certified radiologist with subspecialty trainingin both pediatric and musculoskeletal imaging. The training component of the K08 will consist of a unique integration of formal coursework, practical research experience, and one-on-one mentorship with senior academic leaders in the fields of rheumatology/immunology and biomedical imaging. The training and research will occur in a well-established institution for biomedical science and imaging research and is designed to provide the PI with training and preliminary data to achieve independence as an investigator.
Autoimmune diseases such as rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) are widely prevalent diseases with high costs to the health car sector. Disease monitoring remains challenging. The clinical rationale is that RA and JIA demonstrate a tremendous range in presentation and progression, and an urgent need exists to develop non-invasive imaging biomarkers for improved patient-specific treatment planning and early assessment of therapeutic success and failure.
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