Carpal tunnel syndrome (CTS) is among the most important of the family of musculoskeletal disorders caused by chronic peripheral nerve compression. Generically, mechanical insult to the median nerve is well recognized as the proximate cause. However, despite the existing large body of research in many disciplinary areas, objective characterization of the local biomechanical insult directly responsible for the disorder remains conspicuously absent. The central paradigm of the proposed research is that local mechanical stress on the median nerve can be meaningfully quantified. This mechanical stress is due to fluid pressure within the confines of the tunnel, and direct physical contact of the median nerve with adjacent anatomic structures. Both of these types of interactions can be quantified - in tandem - by finite element (FE) analysis, using an anatomically based, three-dimensional, fluid immersion multi-body contact formulation, which has been developed in preliminary work. The long-term goal of the study is to establish an objective mechanistic framework for linking CTS with quantifiable biomechanical influence factors. An interdisciplinary approach will be adopted, integrating research team member expertise in the areas of biomechanical stress analysis, hand surgery, and musculoskeletal magnetic resonance imaging (MRI). The project has three specific aims: (1) Refine and physically validate the numerical model, and use it to explore the relative importance of fluid pressure versus solid contact on median nerve stress in normal subjects and CTS patients. (2) Based on clinical measurement, systematically study the effects of individual anatomic and functional parameters on median nerve stresses, and perform logistic regression analysis to identify the most important influence factor(s) or group(s) of factors. (3) Test for association between FE-identified factors most predisposing to elevated median nerve mechanical stress, and the presence and severity of CTS symptoms, in an affected patient group and in a negative control group of matched normal subjects. [unreadable] [unreadable] [unreadable]