Myocardial perfusion imaging (MPI) with positron emission tomography (PET) is an emerging clinical tool for diagnosis and characterization of ischemic heart disease. The increasing use of PET introduces an opportunity, as it is capable of providing quantitative images that can be analyzed with pharmacokinetic modeling to estimate regional blood flow to the myocardium. Estimating myocardial blood flow (MBF) could provide increased clinical value over MPI alone, particularly if it could be combined with the clinical protocol used in clinical MPI. In this project, we investigated, designed and evaluated methods for MBF estimation that would enable a clinical protocol combining MPI and MBF.
We focused on two aspects of the PET data. First, we characterized the adequacy of an existing clinical PET/CT scanner in providing quantitatively-accurate, dynamic 82Rb-PET data over the wide range of radioactivity required for MBF estimation. Activity measurements were biased at early times in the data, so we then developed and validated a method for correcting image bias due to event losses in the detection process. Based on this investigation, we proposed opportunities for improvements to the scanner and later evaluated the performance of a prototype scanner with those improvements. Second, we addressed low counting statistics at late times in the data by quantifying the effect of using the coincidence time-of-flight difference, in particular the precision of its measurement, to reduce image variance. Having generated images with low bias and good precision, we then developed methods to accurately and precisely estimate MBF. We built on existing techniques for compartment modeling by investigating optimal and robust design of the acquisition and reconstruction, and by developing a fast and robust method for calculating flow. Altogether, these investigations have enabled a prospective, human-subjects study to provide data to demonstrate the accuracy of image data, robustness of the flow estimation and practicality of the combined clinical procedure. In future work, we expect that a larger-scale clinical evaluation of the combined MPI and MBF protocol may demonstrate improvements to diagnostic accuracy for coronary artery disease over the use of MPI alone.
","abstract_html":"<p>Myocardial perfusion imaging (MPI) with positron emission tomography (PET) is an emerging clinical tool for diagnosis and characterization of ischemic heart disease. The increasing use of PET introduces an opportunity, as it is capable of providing quantitative images that can be analyzed with pharmacokinetic modeling to estimate regional blood flow to the myocardium. Estimating myocardial blood flow (MBF) could provide increased clinical value over MPI alone, particularly if it could be combined with the clinical protocol used in clinical MPI. In this project, we investigated, designed and evaluated methods for MBF estimation that would enable a clinical protocol combining MPI and MBF.</p> <p>We focused on two aspects of the PET data. First, we characterized the adequacy of an existing clinical PET/CT scanner in providing quantitatively-accurate, dynamic <sup>82</sup>Rb-PET data over the wide range of radioactivity required for MBF estimation. Activity measurements were biased at early times in the data, so we then developed and validated a method for correcting image bias due to event losses in the detection process. Based on this investigation, we proposed opportunities for improvements to the scanner and later evaluated the performance of a prototype scanner with those improvements. Second, we addressed low counting statistics at late times in the data by quantifying the effect of using the coincidence time-of-flight difference, in particular the precision of its measurement, to reduce image variance. Having generated images with low bias and good precision, we then developed methods to accurately and precisely estimate MBF. We built on existing techniques for compartment modeling by investigating optimal and robust design of the acquisition and reconstruction, and by developing a fast and robust method for calculating flow. Altogether, these investigations have enabled a prospective, human-subjects study to provide data to demonstrate the accuracy of image data, robustness of the flow estimation and practicality of the combined clinical procedure. In future work, we expect that a larger-scale clinical evaluation of the combined MPI and MBF protocol may demonstrate improvements to diagnostic accuracy for coronary artery disease over the use of MPI alone.</p>","abstract_has_math":false,"creators":["Kolthammer, Jeffrey A."],"institution":"Case Western Reserve University School of Graduate Studies","degree_name":"Doctor of Philosophy","degree_level":"doctoral","degree_discipline":"Biomedical Engineering","degree_department":null,"school":null,"contributors":["Muzic, Raymond F.","Saidel, Gerald M."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-08-19","date_published":"2013-08-19","updated_at":"2026-07-24T03:37:16Z","subjects":["Biomedical Engineering","Medical Imaging","Radiology","positron emission tomography","PET","optimal experiment design","pharmacokinetic modeling","myocardial blood flow","myocardial perfusion imaging"],"languages":["English"],"rights":["unrestricted","This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://rave.ohiolink.edu/etdc/view?acc_num=case1365007300","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Muzic, Raymond F.","Saidel, Gerald M."]},{"key":"dc:creator","label":"Author","values":["Kolthammer, Jeffrey A."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2013-08-19"]},{"key":"dc:publisher","label":"Institution","values":["Case Western Reserve University School of Graduate Studies / OhioLINK"]},{"key":"dc:type","label":"Dc Type","values":["Electronic Thesis or Dissertation"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biomedical Engineering"]},{"key":"thesis:degree_level","label":"Degree Level","values":["doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Case Western Reserve University School of Graduate Studies"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Biomedical Engineering","Medical Imaging","Radiology","positron emission tomography","PET","optimal experiment design","pharmacokinetic modeling","myocardial blood flow","myocardial perfusion imaging"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English"]},{"key":"dc:rights","label":"Dc Rights","values":["unrestricted","This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://rave.ohiolink.edu/etdc/view?acc_num=case1365007300"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Myocardial perfusion imaging (MPI) with positron emission tomography (PET) is an emerging clinical tool for diagnosis and characterization of ischemic heart disease. The increasing use of PET introduces an opportunity, as it is capable of providing quantitative images that can be analyzed with pharmacokinetic modeling to estimate regional blood flow to the myocardium. Estimating myocardial blood flow (MBF) could provide increased clinical value over MPI alone, particularly if it could be combined with the clinical protocol used in clinical MPI. In this project, we investigated, designed and evaluated methods for MBF estimation that would enable a clinical protocol combining MPI and MBF.
We focused on two aspects of the PET data. First, we characterized the adequacy of an existing clinical PET/CT scanner in providing quantitatively-accurate, dynamic 82Rb-PET data over the wide range of radioactivity required for MBF estimation. Activity measurements were biased at early times in the data, so we then developed and validated a method for correcting image bias due to event losses in the detection process. Based on this investigation, we proposed opportunities for improvements to the scanner and later evaluated the performance of a prototype scanner with those improvements. Second, we addressed low counting statistics at late times in the data by quantifying the effect of using the coincidence time-of-flight difference, in particular the precision of its measurement, to reduce image variance. Having generated images with low bias and good precision, we then developed methods to accurately and precisely estimate MBF. We built on existing techniques for compartment modeling by investigating optimal and robust design of the acquisition and reconstruction, and by developing a fast and robust method for calculating flow. Altogether, these investigations have enabled a prospective, human-subjects study to provide data to demonstrate the accuracy of image data, robustness of the flow estimation and practicality of the combined clinical procedure. In future work, we expect that a larger-scale clinical evaluation of the combined MPI and MBF protocol may demonstrate improvements to diagnostic accuracy for coronary artery disease over the use of MPI alone.
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We focused on two aspects of the PET data. First, we characterized the adequacy of an existing clinical PET/CT scanner in providing quantitatively-accurate, dynamic 82Rb-PET data over the wide range of radioactivity required for MBF estimation. Activity measurements were biased at early times in the data, so we then developed and validated a method for correcting image bias due to event losses in the detection process. Based on this investigation, we proposed opportunities for improvements to the scanner and later evaluated the performance of a prototype scanner with those improvements. Second, we addressed low counting statistics at late times in the data by quantifying the effect of using the coincidence time-of-flight difference, in particular the precision of its measurement, to reduce image variance. Having generated images with low bias and good precision, we then developed methods to accurately and precisely estimate MBF. We built on existing techniques for compartment modeling by investigating optimal and robust design of the acquisition and reconstruction, and by developing a fast and robust method for calculating flow. Altogether, these investigations have enabled a prospective, human-subjects study to provide data to demonstrate the accuracy of image data, robustness of the flow estimation and practicality of the combined clinical procedure. In future work, we expect that a larger-scale clinical evaluation of the combined MPI and MBF protocol may demonstrate improvements to diagnostic accuracy for coronary artery disease over the use of MPI alone.
"],"dc:format":["application/pdf","p.215","9.38 MB"],"dc:identifier":["http://rave.ohiolink.edu/etdc/view?acc_num=case1365007300"],"dc:language":["English"],"dc:publisher":["Case Western Reserve University School of Graduate Studies / OhioLINK"],"dc:rights":["unrestricted","This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws."],"dc:subject":["Biomedical Engineering","Medical Imaging","Radiology","positron emission tomography","PET","optimal experiment design","pharmacokinetic modeling","myocardial blood flow","myocardial perfusion imaging"],"dc:title":["Quantitative Positron Emission Tomography for Estimation of Absolute Myocardial Blood Flow"],"dc:type":["Electronic Thesis or Dissertation"],"thesis:degree_discipline":["Biomedical Engineering"],"thesis:degree_level":["doctoral"],"thesis:degree_name":["Doctor of Philosophy"],"thesis:institution_name":["Case Western Reserve University School of Graduate Studies"]},"updated_at":"2026-07-24T03:37:16Z"}