The use of MRI imaging as a non-invasive tool to assess encapsulated pancreatic beta cell viability is proposed. The immunoisolation of transplanted islets has emerged as a promising method of treating Type I Diabetes, and is potentially the only strategy that provides both the safety of avoiding immunosuppressant drugs and the effectiveness of measuring blood glucose as accurately as only living cells can. Since the device functions as an implantable homeostatic sensor-release system, it is fundamental for the encapsulated cells to be able to respond promptly to fluctuations in glucose concentrations of the interstitial fluid in order to retain a physiologic dynamic response. Currently, efficacy of the biocapsule is assessed indirectly by measuring serum glucose levels, and although insulin secretion may remain constant, levels of ATP, glucose consumption and lactate production may change, and may be indicators of irreversible damage to the encapsulated cells. In this proposal, NMR spectroscopy and microimaging will be used to analyze the physical and physiological status of the pancreatic beta cells. A novel MR imaging method is proposed to non-invasively assess cell activation. Pancreatic b-cells activated by increased glucose levels induce Ca2+ uptake through L-type voltage-gated Ca2+ channels. Mn2+ acts as a Ca2+ analog and enters cells through L-type voltage gated channels. Additionally, Mn2+ is a MR relaxation agent and reduces the T1 of water, resulting in a change in image contrast. Therefore beta cells activated by increased glucose in the presence of Mn2+ will demonstrate a change in MR signal intensity compared to non-activated cells. Using the high spatial resolution abilities of MRI, this approach will allow us to directly image beta cell function and viability. Simultaneously it will be possible to apply localized spectroscopic techniques to construct metabolic profiles of activated versus non-activated regions. In concert, these techniques will provide means to understand beta cell function, factors influencing successful islet transplantation, and the further development of encapsulated pancreatic beta cells necessary for a bioartificial pancreas.
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