Pharmacokinetic modeling of dynamic MR imaging in the knee of children with juvenile rheumatoid arthritis

Imaging with nuclear magnetic resonance (NMR) is an application of classical and quantum physics with unparalleled breath and relevance in modern health care. The two basic magnetic resonance imaging (MRI) tissue contrast sources, the spin-lattice (T1) and spin-spin (T2) relaxation rates can be enhanced by paramagnetic relaxation chemical agents such as, gadolinium-diethylenetraiame pentaacetic (Gd-DTPA). After intravenous administration, Gd-DTPA passes into the extracellular-extravasccular space at a rate dependent on the local capillary permeability and tissue perfusion. Therefore, looking for a physiologic model that can predict these processes is important to investigate the disease activities at the earliest stage, in our case juvenile rheumatoid arthritis (JRA). The aim of this thesis is to develop a quantitative dynamic contrast enhanced MRI (DCE-MRI) method based on a two-compartmental pharmacokinetic (PK) model and investigate the capability of the PK parameters in predicting the JRA disease activity. Color-coded pixel-by-pixel parametric maps were also developed for visual comparisons.; The signal enhancement time course from the spin-lattice (T1) relaxation rate weighted perfusion images were characterized based on a pharmacokinetic modeling method. Including the bolus part of the arterial input function (AIF) from popliteal artery was shown to be important. The three pharmacokinetic parameters, Ktrans, (or Ktrans), kep, and Vp' (or nup), in both the synovium and physes, showed significant variations. In addition, during a 12 months longitudinal study these parameters showed significant decrease. This result was supported by the significant decrease of the clinical outcome measures and synovial volume, particularly at 12 months. A phantom which simulates capillary perfusion from DCE-MRI protocols was developed and was able to mimic the signal enhancement from the synovium and physes of knees in children with JRA.; Decreases in the pharmacokinetic parameters might reflect diminution in disease activity. The pixel-by-pixel color-coded parameterc maps could be used to follow JRA treatment outcomes. In addition, an improved HFC perfusion phantom, with better representation of the synovium, can be used as a tool to investigate the feasibility of quantitative methods to monitor disease activity in JRA. This method can also be applied for similar purposes in adults with rheumatoid arthritis and other disorders.