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SUMMARY 150

Chapter 7

Summary

In the study involving radiotherapy of murine tumors, the scientific question beingaddressed is that of tumor oxygenation, its relation to radiation therapy, and the ability tononinvasively 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 strategicuse of such therapies in the treatment of human cancers. During the course of theseexperiments, we found that there was a discrepancy between the spectroscopic andimaging data. My contribution to this study was in reconciling the differences betweenthe spectroscopic and imaging data, allowing for a direct comparison between these twodifferent modalities. This work was presented at the IEEE conference where it took firstplace. This study was a collaboration between Drs. Sotak, Dardzinski, and myself.The study involving the correlation between

(

) of tumor

O and

derived itssignificance from the fact that it challenged an existing theory. While it is difficult tochallenge peer reviewed published work, this study showed on a larger scale that theoriesevolve as information accumulates. Although this work was not the effort of oneindividual, the insight of the principal investigator (Dr. Karl Helmer) and his direction inthe study proved to be rewarding. This set an example of the need for good direction and

SUMMARY 151

clear vision in science. I was the second author on this paper, and my contribution was inthe 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 amethod. Indeed, this is true, but the importance of these experiments lie in theapplication of the method. Due to the complexity of interpreting data obtained fromanimal experiments, it often becomes necessary to take a step back and find an analogousmodel to answer questions arising from the animal experiments. Specifically, thequestion 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 donestudies involving intra- and extracellular metabolites to infer the behavior of the waterdiffusion 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 representwater, which can move between the two compartments. This study was a stepping stoneto answering the perplexing question of what is really happening to the brain water at theonset of ischemia. I was responsible for working out the specific theory behind theexperiments, 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 theone who set the direction of these experiments and analyzed the data to answer theunderlying question of compartmental

ADC

behavior. The future direction of this

SUMMARY 152

particular study would be to further characterize the water behavior in yeast by measuringthe time-dependence of the

ADC

to extract structural parameters from the cellularcompartments. Once this is done,

in vivo

measurements of compartmental water

ADC

inthe rat brain under different pathological conditions would need to be done.The rabbit Achilles tendon experiment showed the true multi-faceted nature of someNMR studies. The characterization of a system that is not well known is not a trivialtask, and in this case, it was especially necessary to collaborate with scientists frommulti-disciplinary backgrounds. Since the mechanical response to a biological systemwas under observation using NMR, mechanical engineers, physiologists, biomedicalengineers, 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 forthese studies. Since the system was not well characterized, there was a need to narrowthe overall scope of this study and specify which questions needed to be addressed. I wasresponsible for forming the main scientific questions that needed to be addressed andworking out the specific experiments necessary to characterize the system. I also wrotethe 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 ismuch that can be done with this and also many different directions in which this studycan go. One point of interest is that the behavior of visco-elastic solids is different fordynamic loading conditions that for static loading conditions. The study of the waterbehavior to dynamic loading would be an interesting avenue to explore. Furthermore,