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Preface
mind of God.
From the beginning, I had the great fortune of adopting one of my predecessor’s final
not only as an initial project, but more so because of the experience of working with an
adept NMR scientist. The preliminary hypothesis of this study was to observe changes in
murine tumor oxygenation with radiotherapy. In preceding works, it was shown that the
oxygen tension. This relationship between fluorine relaxation and oxygenation, along
with NMR imaging techniques, allowed for evaluation of therapeutic interventions using
perfluorocarbons.
During this time, a parallel experiment was in progress to observe the effects of
oxygenation on the diffusion of water molecules in murine tumors. Other groups had
shown that there was a highly positive correlation between tumor oxygenation and the
apparent diffusion coefficient (ADC) of water in the tumor. These findings were
troubling because intuitively, if there were any correlation between tumor oxygenation
and ADC, we would expect to see a negative rather than a positive correlation. To
PREFACE iv
rewarding experiment because our intuition served us correctly. Despite the findings by
other groups, our studies showed that no apparent correlation existed between ADC
Studies in animals brought up questions about the behavior of water in the brain
following the onset of stroke. During cerebral ischemia, ionic imbalances in the brain
result in changes in cellular water distribution and give rise to edema (cellular swelling).
Although it is clear that the properties of diffusing water are correlated with the swelling
of cells, it was difficult to understand the intricacies behind the relationship of water to its
surroundings. The answer to this basic question of what is happening to the water in a
complicated two-compartment system has been one of the motivating factors for my
others have shown non-monoexponential diffusion signal attenuation, which has been
be a possibility, previous works have shown that even in single compartment systems,
compartment systems cast doubt on the interpretation of the data from the two-
compartment system. Not only are there compartmental effects on diffusion, but the
diffusion behavior is also confounded by restriction effects. One of the premises behind
PREFACE v
the work done in yeast-cell suspensions was that a deconvolution of the compartmental
effects could provide valuable information on the behavior of water. With this goal in
mind, a majority of my research efforts was devoted to investigating model systems for
experiments should serve merely as a stepping stone to other experiments which further
characterize the model system and, ultimately, carry over to in vivo experiments to
The last experiment in this dissertation deals with diffusion of water in excised rabbit
Achilles tendon. The initial set of experiments on tendon gave very promising results and
investigation into the behavior of the tendon revealed that these observed effects were no
more than an artifact of the storage medium. The initial discovery of this fact was
disappointing, but at the same time opened up another avenue for the direction of these
most of the groundwork has been laid for future studies. Although these results are not
completely revealing, we are still of the belief that the viscoelastic properties of tendons
change with tensile load. Whether this phenomenon is observable via NMR is still to be
determined.
PREFACE vi
Although diverse in nature, all of these experiments have taught one common lesson.
Ask the good question and seek the right answer. I hope that the writings herein will be a