Mapping viability and oxygen concentration in spheroids: A noninvasive approach with EPR imaging

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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biophysics

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2011

Author dc:creator

• Woods, Ronald Kent

Contributors dc:contributor

• Swartz, Harold M.

• Health Sciences, Radiology
• Biophysics, Medical

Statement dc:rights

• Copyright 1991 Woods, Ronald Kent

Language dc:language

eng

Identifier

AAI9211041
(UMI)AAI9211041

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/20340