{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/20340"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/20340","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Mapping viability and oxygen concentration in spheroids: A noninvasive approach with EPR imaging","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.","abstract_html":"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.","abstract_has_math":true,"creators":["Woods, Ronald Kent"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Biophysics","degree_department":null,"school":null,"contributors":["Swartz, Harold M."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-05-07T12:36:25Z","date_published":"2011-05-07T12:36:25Z","updated_at":"2026-07-22T22:25:15Z","subjects":["Health Sciences, Radiology","Biophysics, Medical"],"languages":["eng"],"rights":["Copyright 1991 Woods, Ronald Kent"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["AAI9211041","(UMI)AAI9211041"],"render_values":[{"text":"AAI9211041","href":null,"code":true},{"text":"(UMI)AAI9211041","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2142/20340","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Swartz, Harold M."]},{"key":"dc:creator","label":"Author","values":["Woods, Ronald Kent"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2011-05-07T12:36:25Z","10000-01-01","1991"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biophysics"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Health Sciences, Radiology","Biophysics, Medical"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 1991 Woods, Ronald Kent"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["AAI9211041","(UMI)AAI9211041","http://hdl.handle.net/2142/20340"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["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.","Made available in DSpace on 2011-05-07T12:36:25Z (GMT). No. of bitstreams: 2 license.txt: 4922 bytes, checksum: 910b249b4beec47e7ab768910c8f966f (MD5) 9211041.pdf: 10629981 bytes, checksum: d40205c3fcb033ff9f1fb6a0b8b498e7 (MD5) Previous issue date: 1991","Item marked as restricted to the 'UIUC Users [automated]' Group (id=2) by Howard Ding (hding2@illinois.edu) on 2011-05-07T14:43:14Z Item is restricted indefinitely.","Restriction data tranferred 2014-07-01T11:18:53-05:00 Original Data Group with Access UIUC Users [automated] Release Date: none Reason: ETDs are only available to UIUC Users without author permission","ETDs are only available to UIUC Users without author permission","U of I Only"]},{"key":"dc:title","label":"Title","values":["Mapping viability and oxygen concentration in spheroids: A noninvasive approach with EPR imaging"]}]}],"canonical_facts":{"dc:contributor":["Swartz, Harold M."],"dc:creator":["Woods, Ronald Kent"],"dc:date":["2011-05-07T12:36:25Z","10000-01-01","1991"],"dc:description":["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.","Made available in DSpace on 2011-05-07T12:36:25Z (GMT). No. of bitstreams: 2 license.txt: 4922 bytes, checksum: 910b249b4beec47e7ab768910c8f966f (MD5) 9211041.pdf: 10629981 bytes, checksum: d40205c3fcb033ff9f1fb6a0b8b498e7 (MD5) Previous issue date: 1991","Item marked as restricted to the 'UIUC Users [automated]' Group (id=2) by Howard Ding (hding2@illinois.edu) on 2011-05-07T14:43:14Z Item is restricted indefinitely.","Restriction data tranferred 2014-07-01T11:18:53-05:00 Original Data Group with Access UIUC Users [automated] Release Date: none Reason: ETDs are only available to UIUC Users without author permission","ETDs are only available to UIUC Users without author permission","U of I Only"],"dc:identifier":["AAI9211041","(UMI)AAI9211041","http://hdl.handle.net/2142/20340"],"dc:language":["eng"],"dc:rights":["Copyright 1991 Woods, Ronald Kent"],"dc:subject":["Health Sciences, Radiology","Biophysics, Medical"],"dc:title":["Mapping viability and oxygen concentration in spheroids: A noninvasive approach with EPR imaging"],"dc:type":["text"],"thesis:degree_discipline":["Biophysics"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:25:15Z"}