The overarching goal of this project is to develop, translate, and apply magnetic resonance fingerprinting (MRF), a novel, quantitatively robust magnetic resonance imaging (MRI) technique, for steady-state imaging of pancreatic ductal adenocarcinoma (PDAC) microvasculature using magnetic nanoparticles (MNP). MRF is a novel pattern matching based imaging method, which allows for simultaneous quantitative mapping of multiple parameters in a much shorter time than conventional imaging methods. Our experience in preclinical murine models of PDAC has revealed that MR imaging of ferumoxytol (an FDA-approved MNP) enables quantitative measurement of tumor microvasculature (e.g., vascular volume fraction (VVF), vessel size imaging (VSI) and vessel density index (VDI)). These measurements are all derived from changes in the quantitative MRI derived relaxation parameters, T2 and T2*. More importantly, we have shown that changes in these microvascular parameters can be a surrogate to therapeutic response following therapeutic manipulation of the tumor microenvironment through collagen disruption (e.g., angiotensin receptor blockade). Currently, MRF has not been optimized for abdominal imaging, nor is there a solution for T2* quantification. Our goal is to develop, translate, and apply MRF for improved and co-localized quantification of T2 and T2* in the human pancreas, prior to and following administration of MNP. The T2 and T2* values will then be used to quantify PDAC microvascularity and these results will be compared to histology. In order to complete this task, we have formed a multi-disciplinary team that includes expertise in MRI, quantitative imaging, surgical oncology, pathology, cancer biology, statistics, and pancreatic cancer. The team will conduct the following aims: 1) develop and optimize MR fingerprinting sequence for T1, T2 and T2* quantification in the pancreas; 2) validate T1, T2 and T2* MRF sequence in the pancreas of healthy volunteers; and 3) apply MRF T1, T2 and T2* sequences in patients with PDAC and correlate with pathology. An unmet need for imaging with high spatial resolution microvessel parameters following MNP (most notably, VSI) in pancreatic cancer is a technique that allows for simultaneous measures of T2 and T2*. We hypothesize that MRF, which is a quantitatively robust novel MR methodology, will be the most robust means of calculating T2 and T2* in the human pancreas following MNP, but secondary to its spiral technique, will provide these measures with a free breathing, highly reproducible and high image quality examination.
In the United States, pancreatic cancer is the fourth most common cause of death from cancer in both men and women largely due to the poor efficacy of chemotherapeutic options with this disease, which remains poorly understood. Our laboratory has demonstrated, in preclinical models of pancreatic cancer, that MRI of tumor microvasculature using magnetic nanoparticles is a surrogate for treatment response in novel targeted strategies. Magnetic resonance fingerprinting (MRF) for quantification of pancreatic tumor microvasculature, a project conducted at Oregon Health & Science University, will use innovative MRF imaging techniques to improve the quantification of microvascular biomarkers, thus fulfilling an unmet need in pancreatic cancer producing a more accurate picture of chemotherapeutic response that involves fewer artifacts and results in improved patient outcomes.