Objective
The objective of this project is to harness new advances in MRI technology that permit higher resolution imaging to assess glucose-induced changes in pancreas perfusion. We will optimize these technical advances for pancreas imaging and apply them to detect changes in perfusion in people with and without type 1 diabetes. The high-resolution imaging technique we develop will allow us to not only measure average perfusion throughout the pancreas, but examine spatial differences in pancreas perfusion across the entire pancreas.
Background Rationale
In type 1 diabetes, the insulin producing cells in the pancreas are destroyed by an aberrant immune system. However, the pancreas is not directly measured in current diagnosis and management of type 1 diabetes. MRI can image the pancreas of people without any harmful radiation or having to inject any substances. Thus, MRI is safe to image children and image repeatedly over time. Changes to the pancreas found using imaging may reflect aspects of type 1 diabetes that are not captured by measurements of body fluids. Other imaging studies have demonstrated that the movement of fluids (or perfusion) in the pancreas is different in models of type 1 diabetes. We seek to test if this is possible in people with type 1 diabetes. Ultimately, MRI of pancreas perfusion may improve diabetes prediction, monitoring, and development of therapies intended to arrest T1D progression.
Description of Project
Medical imaging has found that the pancreas is altered in people with type 1 diabetes. Our work has demonstrated that the pancreas is smaller not only in people with type 1 diabetes but also people who are at higher risk for getting type 1 diabetes. The degree of pancreas loss in T1D (~30%) far exceeds the percentage of the pancreas composed of the pancreatic islet (1-2%). These unexpected findings raise fundamental questions that challenge our understanding of diabetes pathogenesis, implicating exocrine pancreas involvement in diabetes. MRI can image not only pancreas size (or anatomy), but also the function (or physiology) of the pancreas. For example, MRI can measure the perfusion (or flow) of fluids through the pancreas. Using new MRI technology that allows us to see smaller spatial details in the pancreas, we will image perfusion throughout the pancreas. We will ask people with and without type 1 diabetes to drink a glucose gel while in the MRI scanner and image the resulting increases in pancreas perfusion. We believe the perfusion in the pancreas and the spatial patterns in this perfusion may be different in people with type 1 diabetes due to both beta cell destruction and altered exocrine secretion. This study will increase our understanding of changes in the pancreas in type 1 diabetes. Additionally, the MRI tool developed may be useful for predicting which individuals get type 1 diabetes and evaluating the effectiveness of therapeutics.
Anticipated Outcome
Our preliminary evidence demonstrates our capability to perform high resolution pancreas perfusion imaging, but it is unknown if this technique will detect altered perfusion in people with type 1 diabetes. Previous studies have found conflicting results imaging perfusion in the pancreas. Our proposal improves upon prior pancreas imaging studies by employing state-of-the-art reduced field-of-view imaging. We will generate the highest spatial resolution maps of entire human pancreas perfusion available to our knowledge, which may power new hypotheses regarding pancreas spatial heterogeneity. We anticipate that the pancreas of individuals with type 1 diabetes will exhibit a different temporal and spatial response to glucose, with a lower overall increase in perfusion.
Relevance to T1D
Successful completion of this project will yield a new, non-invasive tool for non-invasive human pancreas assessment and determine its sensitivity to pancreas pathology in T1D. This tool can then provide valuable insight into diabetes pathogenesis and may improve diabetes prediction, monitoring, and development of therapies seeking to induce beta cell proliferation. For example, pancreas perfusion can be imaged longitudinally in patients with T1D or those at risk for the disease to assess changes correlated with disease progression. Pancreas perfusion can also be assessed during therapeutic trials to see whether it reflects (or predicts) therapeutic outcomes.