Author ORCID Identifier

0000-0002-9119-8176

Date of Graduation

12-2025

Document Type

Dissertation (PhD)

Program Affiliation

Molecular and Translational Biology

Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Pratip K. Bhattacharya, Ph.D.

Committee Member

Mary C. Farach-Carson, Ph.D.

Committee Member

Niki M. Zacharias Millward, Ph.D.

Committee Member

Livia S. Eberlin, Ph.D.

Committee Member

Rachael D. Sirianni, Ph.D.

Committee Member

Daniel E. Frigo, Ph.D.

Abstract

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.

Keywords

Metabolic Imaging, Hyperpolarized Magnetic Resonance, Magnetic Resonance Imaging, NMR Metabolomics, Pancreatic Cancer, Early Detection, Therapeutic Efficacy, Non-Invasive Imaging, Texas Medical Center

Available for download on Saturday, December 05, 2026

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