14 Summary Chapter 7

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Chapter 7 Summary In the study involving radiotherapy of murine tumors, the scientific question being addressed is that of tumor oxygenation, its relation to radiation therapy, and the ability to noninvasively measure the effects of radiation on tumor oxygenation. The importance of such a study is that the behavior of tumors in response to radiation will allow for strategic use of such therapies in the treatment of human cancers. During the course of these experiments, we found that there was a discrepancy between the spectroscopic and imaging data. My contribution to this study was in reconciling the differences between the spectroscopic and imaging data, allowing for a direct comparison between these two different modalities. This work was presented at the IEEE conference where it took first place. This study was a collaboration between Drs. Sotak, Dardzinski, and myself.

The study involving the correlation between D(t) of tumor 1H2O and pO2 derived its significance from the fact that it challenged an existing theory. While it is difficult to challenge peer reviewed published work, this study showed on a larger scale that theories evolve as information accumulates.

Although this work was not the effort of one

individual, the insight of the principal investigator (Dr. Karl Helmer) and his direction in the study proved to be rewarding. This set an example of the need for good direction and

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clear vision in science. I was the second author on this paper, and my contribution was in the animal care, data acquisition, and part of the data processing.

On the surface, the study involving yeast cell suspensions appears to be a validation of a method.

Indeed, this is true, but the importance of these experiments lie in the

application of the method. Due to the complexity of interpreting data obtained from animal experiments, it often becomes necessary to take a step back and find an analogous model to answer questions arising from the animal experiments.

Specifically, the

question that vexed us was the diffusion behavior of water in a two-compartment system. During cerebral ischemia, the brain water apparent diffusion coefficient (ADC) decreases, and there are many plausible explanations behind this phenomena. Others have done studies involving intra- and extracellular metabolites to infer the behavior of the water diffusion coefficient from the behavior of these metabolites, but it is not evident a priori that the diffusion characteristics of these metabolites track those of water. Not only so, but metabolites that are constrained to only one compartment cannot accurately represent water, which can move between the two compartments. This study was a stepping stone to answering the perplexing question of what is really happening to the brain water at the onset of ischemia. I was responsible for working out the specific theory behind the experiments, designing the experiments, writing the pulse sequences, acquiring the data, and analyzing the data. Although this work was a collaborative effort of many, I was the one who set the direction of these experiments and analyzed the data to answer the underlying question of compartmental 1H2O ADC behavior. The future direction of this

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particular study would be to further characterize the water behavior in yeast by measuring the time-dependence of the ADC to extract structural parameters from the cellular compartments. Once this is done, in vivo measurements of compartmental water ADC in the rat brain under different pathological conditions would need to be done.

The rabbit Achilles tendon experiment showed the true multi-faceted nature of some NMR studies. The characterization of a system that is not well known is not a trivial task, and in this case, it was especially necessary to collaborate with scientists from multi-disciplinary backgrounds. Since the mechanical response to a biological system was under observation using NMR, mechanical engineers, physiologists, biomedical engineers, and NMR scientists were all involved in every step of these experiments. Although many people collaborated in this study, I was the one who set the direction for these studies. Since the system was not well characterized, there was a need to narrow the overall scope of this study and specify which questions needed to be addressed. I was responsible for forming the main scientific questions that needed to be addressed and working out the specific experiments necessary to characterize the system. I also wrote the pulse sequences necessary for the data acquisition and wrote the code to analyze all of the data. Since this study involving the rabbit Achilles tendon is fairly new, there is much that can be done with this and also many different directions in which this study can go. One point of interest is that the behavior of visco-elastic solids is different for dynamic loading conditions that for static loading conditions. The study of the water behavior to dynamic loading would be an interesting avenue to explore. Furthermore,

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due to the highly structured fiber orientation of the tendon, it would be interesting to know if there are any directional susceptibility artifacts that manifest themselves as a function of the tendon’s orientation in the static magnetic field.