New Noninvasive Biomarkers for the Diagnosis and Treatment of Pancreatic Disorders
Abstract
Diseases of the pancreas are common and include pancreatitis, pancreatic cancer, and type 1 and type 2 diabetes (T1D and T2D). It would be very beneficial to discover and implement new technologies to monitor pancreatic cells in health and disease states. Magnetic resonance imaging (MRI) uses magnetic fields, radio waves, and computer analysis to noninvasively and safely obtain detailed anatomical information. Magnetic resonance spectroscopy (MRS) can be performed together with MRI using conventional hospital MRI scanners in order to provide detailed biochemical information on the constituents within a region of interest. MRS has been clinically applied to noninvasively characterize changes in small molecules levels in the brain, breast, and prostate that are associated with disease. MRS, however, has not been well-developed to monitor small molecules in the pancreas that could provide new biomarkers of pancreatic diseases and read-outs of the efficacy of therapeutic interventions. We will for the first time, utilize advanced high-resolution two-dimensional (2D)-MRS to noninvasively measure the small molecule constituents of the pancreas (i.e., define the pancreatic “MRS-ome”) in a living large animal model. Next, as a proof-of-principle, we will determine whether 2D-MRS can detect the loss of the insulin-producing beta-cells, which underlies T1D in this large animal model. Currently, there is no clinically applicable mechanism to noninvasively image the beta-cells, and individuals only become aware of having developed T1D or T2D following the appearance of overt hyperglycemia. We anticipate that 2D-MRS will provide new noninvasive biomarkers of beta-cell mass. Such biomarkers are currently highly sought after in order to aid in the evaluation of therapeutics designed to inhibit or reverse T1D and T2D. Because MRS is safe, it can be repeatedly used to monitor disease progression and the efficacy of therapeutics. Additionally, the technology can be applied to aid in the diagnosis and treatment of other pancreatic disorders such as pancreatitis and pancreatic cancers. We anticipate that by providing clinicians with an entirely new noninvasive read-out of the abundance of an array of pancreatic small molecules, it will lay a foundation for better understanding the molecular basis of many pancreatic diseases. It will also provide new noninvasive biomarkers that could revolutionize medical treatments of pancreatic disorders by allowing early diagnosis and detailed read-outs of pancreatic constituents that may allow better personalized treatments.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010097
Entities
People
- Daniel Kaufman
Organizations
- United States Army
- University of California, Los Angeles