Mapping viability and oxygen concentration in spheroids: A noninvasive approach with EPR imaging
Woods, Ronald Kent
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https://hdl.handle.net/2142/20340
Description
Title
Mapping viability and oxygen concentration in spheroids: A noninvasive approach with EPR imaging
Author(s)
Woods, Ronald Kent
Issue Date
1991
Doctoral Committee Chair(s)
Swartz, Harold M.
Department of Study
Biophysics
Discipline
Biophysics
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Health Sciences, Radiology
Biophysics, Medical
Language
eng
Abstract
The multicellular spheroid embodies many of the physiological and anatomical characteristics of in vivo tumors and provides an appropriate context for investigating the phenomenon of reoxygenation and the interplay of local (O$\sb2$) and cellular viability in the response of tumors to various therapeutic regimens. There are, however, certain limitations of the methodology currently used to measure local (O$\sb2$) and viability in spheroids. The goal of this thesis was to overcome these limitations by developing a single noninvasive technique, based on Electron Paramagnetic Resonance Imaging (EPRI), which would provide simultaneous measurements of the distribution of (O$\sb2$) and viability. The approach is based on (1) the homogeneous distribution throughout the spheroid of an aqueous nitroxide with a lineshape (linewidth) responsive to local (O$\sb2$); and (2) the selective exclusion from cells with intact plasma membranes (viable cells) of a contrast agent which broadens the lineshape of the nitroxide. Therefore, it is necessary to recover from the net EPR signal the narrow lineshape (or relevant spectral parameters) for each respective region in the spheroid. Two independent approaches were developed to accomplish the spectral localization--4D spectral-spatial imaging and projection based modeling (PBM). Based on the results of feasibility tests, it was decided to pursue to completion only PBM. This technique employs a highly constrained downhill simplex method to minimize $\chi\sp2$ for two parameter spaces, characterizing, respectively, the viability and (O$\sb2$). One-dimensional projections, collected at 2$\sp\circ$C and 37$\sp\circ$C, are required experimental output functions for step (space) 1 and step 2 minimizations, respectively. Experimental results for step 1 confirm the capability to quantitate morphology and viability. Step 2, however, was unsuccessful due most likely to toxicity of the nitroxide and (or) contrast agent at higher temperatures.
As a preface to the more specific theoretical and experimental work in Chapters 3-6, Chapters 1 and 2 provide instructional discussion on projection reconstruction in conjunction with a complete software package for 2-4D image reconstruction documented in the Appendices.
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