Characterization of soft-tissue response to mechanical loading using nuclear magnetic resonance (NMR) and functional magnetic resonance imaging (fMRI) of neuronal activity during sustained cognitive-stimulus paradigms

by Wellen, Jeremy W.

Research applications of nuclear magnetic resonance (NMR) span a broad range of fields and disciplines. The work presented in this dissertation attests to this fact. Specifically, the research topics discussed in the body of this work employ NMR spectroscopy and imaging to characterize the water diffusion and NMR relaxation times ex vivo in rabbit Achilles tendon and, in a clinical setting, employ functional magnetic resonance imaging (fMRI) to investigate the behavior of different neural networks over a period of sustained activity. In the ex vivo in rabbit Achilles tendon work, a series of studies were performed. First, the diffusion-time dependence of the water apparent diffusion coefficient (ADC) was characterized in a spectroscopic mode with the samples subjected to different states of tensile loading. The results of this study demonstrated: (1) the anisotropy of the diffusion of water through tendon; (2) the ADC is diffusion-time dependent; (3) the values of the ADC(tdif) curve increased with tensile loading; (4) a change at the short diffusion-time points that is consistent with the interpretation of a load-induced increase in the collagen fibril packing density; and (5) an increase in the water ADC at long diffusion times, hypothesized to be due to T1 editing. To further investigate these issues, another series of ex vivo in rabbit Achilles tendon experiments was performed that employed NMR imaging to spatially characterize the water ADC, T1 and T2 relaxation time constants. As with the spectroscopic work, these studies were also conducted with the tendon samples subjected to different states of tensile loading. The results from these imaging experiments demonstrated: (1) two regions with distinct differences in signal intensity across the tendon: a thin region of - ix - high signal intensity at the peripheral rim of the tendon that encircles a region of low signal intensity in the central core of the tendon; (2) a higher diffusion anisotropy ratio in the tendon central core relative to the peripheral rim; (3) upon tensile loading, significant increases in the ADC of water in the peripheral rim region and a corresponding increase in a measure of the change in proton density in the rim region, consistent with the hypothesis that tensile loading causes extrusion of water from the core to the rim region of the tendon; (4) this water extrusion is not uniformly distributed throughout the tendon rim region; and (5) the long-diffusion-time ADC behavior is consistent with the T1 spin editing hypothesis of the spectroscopic work. From the clinical fMRI studies, an analysis method was presented for observing dynamic changes in brain regions involved in different neural network processes during a period of sustained activity. The results from these studies are consistent with the idea that over time, brain regions adapt to the given task demands through either recruitment or discharge of adjacent areas of tissue. These results also indicate that traditional analysis of block design fMRI studies may underestimate dynamic changes in brain regions during a sustained task. The analysis method may be useful as an exploratory tool to observe region specific variations in activation that may allow inferences to be made regarding how different brain regions adapt to and interact with one another during periods of extended activity. - x - - xi -