Early detection of pancreatic ductal adenocarcinoma (PDAC) is challenging due to asymptomatic nature and deep location of the malignancy within the abdomen. The development of PDAC consists of three different pathways but two arise from the duct, Pancreatic Intraepithelial Neoplasia (PanIN) and Intraductal Papillary Mucinous Neoplasm (IPMN). During these premalignant stages, there is evidence of dysregulated metabolism present in these early lesions, including an increase in lactate production. The overarching goal of this dissertation is to develop the capability of non-invasively detecting these premalignant precursor lesions in the pancreas prior to invasive disease by harnessing a non-invasive imaging modality called hyperpolarized magnetic resonance (HP MR) metabolic imaging. HP MR increases the signal of conventional MRI by over 10,000-fold and can interrogate the dynamic metabolic flux (lactate-to-pyruvate ratio) in vivo in real time. Concurrently, the therapeutic efficacy of a preventative treatment was assessed non-invasively with HP MR. Ex vivo metabolomics based on NMR spectroscopy and histology were employed to validate and compliment the in vivo imaging data. These studies revealed that HP MR was sensitive to detect the altered metabolism non-invasively in the premalignant stages, specific to determine progression towards cancer against pancreatitis, a known confounder and has the potential for non-invasively determine the therapeutic efficacy of preventative measures in vivo.
","abstract_html":"<p>Early detection of pancreatic ductal adenocarcinoma (PDAC) is challenging due to asymptomatic nature and deep location of the malignancy within the abdomen. The development of PDAC consists of three different pathways but two arise from the duct, Pancreatic Intraepithelial Neoplasia (PanIN) and Intraductal Papillary Mucinous Neoplasm (IPMN). During these premalignant stages, there is evidence of dysregulated metabolism present in these early lesions, including an increase in lactate production. The overarching goal of this dissertation is to develop the capability of non-invasively detecting these premalignant precursor lesions in the pancreas prior to invasive disease by harnessing a non-invasive imaging modality called hyperpolarized magnetic resonance (HP MR) metabolic imaging. HP MR increases the signal of conventional MRI by over 10,000-fold and can interrogate the dynamic metabolic flux (lactate-to-pyruvate ratio) <em>in vivo</em> in real time. Concurrently, the therapeutic efficacy of a preventative treatment was assessed non-invasively with HP MR. <em>Ex vivo</em> metabolomics based on NMR spectroscopy and histology were employed to validate and compliment the <em>in vivo</em> imaging data. These studies revealed that HP MR was sensitive to detect the altered metabolism non-invasively in the premalignant stages, specific to determine progression towards cancer against pancreatitis, a known confounder and has the potential for non-invasively determine the therapeutic efficacy of preventative measures <em>in vivo</em>.</p>","abstract_has_math":false,"creators":["Enriquez, Jose S","Early detection of pancreatic ductal adenocarcinoma (PDAC) is challenging due to asymptomatic nature and deep location of the malignancy within the abdomen. The development of PDAC consists of three different pathways but two arise from the duct, Pancreatic Intraepithelial Neoplasia (PanIN) and Intraductal Papillary Mucinous Neoplasm (IPMN). During these premalignant stages, there is evidence of dysregulated metabolism present in these early lesions, including an increase in lactate production. The overarching goal of this dissertation is to develop the capability of non-invasively detecting these premalignant precursor lesions in the pancreas prior to invasive disease by harnessing a non-invasive imaging modality called hyperpolarized magnetic resonance (HP MR) metabolic imaging. HP MR increases the signal of conventional MRI by over 10,000-fold and can interrogate the dynamic metabolic flux (lactate-to-pyruvate ratio) in vivo in real time. Concurrently, the therapeutic efficacy of a preventative treatment was assessed non-invasively with HP MR. Ex vivo metabolomics based on NMR spectroscopy and histology were employed to validate and compliment the in vivo imaging data. These studies revealed that HP MR was sensitive to detect the altered metabolism non-invasively in the premalignant stages, specific to determine progression towards cancer against pancreatitis, a known confounder and has the potential for non-invasively determine the therapeutic efficacy of preventative measures in vivo.
"]},{"key":"dc:title","label":"Title","values":["Sensitivity and Specificity of Detecting Premalignant Pancreatic Lesions by Hyperpolarized Magnetic Resonance"]}]}],"canonical_facts":{"dc:contributor":["Pratip K. Bhattacharya, Ph.D.","Mary C. Farach-Carson, Ph.D.","Niki M. Zacharias Millward, Ph.D."],"dc:creator":["Enriquez, Jose S","Early detection of pancreatic ductal adenocarcinoma (PDAC) is challenging due to asymptomatic nature and deep location of the malignancy within the abdomen. The development of PDAC consists of three different pathways but two arise from the duct, Pancreatic Intraepithelial Neoplasia (PanIN) and Intraductal Papillary Mucinous Neoplasm (IPMN). During these premalignant stages, there is evidence of dysregulated metabolism present in these early lesions, including an increase in lactate production. The overarching goal of this dissertation is to develop the capability of non-invasively detecting these premalignant precursor lesions in the pancreas prior to invasive disease by harnessing a non-invasive imaging modality called hyperpolarized magnetic resonance (HP MR) metabolic imaging. HP MR increases the signal of conventional MRI by over 10,000-fold and can interrogate the dynamic metabolic flux (lactate-to-pyruvate ratio) in vivo in real time. Concurrently, the therapeutic efficacy of a preventative treatment was assessed non-invasively with HP MR. Ex vivo metabolomics based on NMR spectroscopy and histology were employed to validate and compliment the in vivo imaging data. These studies revealed that HP MR was sensitive to detect the altered metabolism non-invasively in the premalignant stages, specific to determine progression towards cancer against pancreatitis, a known confounder and has the potential for non-invasively determine the therapeutic efficacy of preventative measures in vivo.
"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1497"],"dc:subject":["Metabolic Imaging","Hyperpolarized Magnetic Resonance","Magnetic Resonance Imaging","NMR Metabolomics","Pancreatic Cancer","Early Detection","Therapeutic Efficacy","Non-Invasive Imaging","Texas Medical Center","Biochemistry","Other Biochemistry, Biophysics, and Structural Biology","Other Chemistry","Radiochemistry"],"dc:title":["Sensitivity and Specificity of Detecting Premalignant Pancreatic Lesions by Hyperpolarized Magnetic Resonance"],"thesis:degree_level":["Dissertation (PhD)"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:50:47Z"}