Longitudinal three-dimensional visualisation of autoimmune diabetes by functional optical coherence imaging

Aims/hypothesis It is generally accepted that structural and functional quantitative imaging of individual islets would be beneficial to elucidate the pathogenesis of type 1 diabetes. We here introduce functional optical coherence imaging (FOCI) for fast, label-free monitoring of beta cell destruction and as- sociated alterations of islet vascularisation. Methods NOD mouse and human islets transplanted into the anterior chamber of the eye (ACE) were imaged with FOCI, in which the optical contrast of FOCI is based on intrinsic vari- ations of the index of refraction resulting in a faster tomo- graphic acquisition. In addition, the phase sensitivity allows simultaneous label-free acquisition of vascularisation. Results We demonstrate that FOCI allows longitudinal quan- tification of progressive autoimmune insulitis, including the mation and vascularisation. The substantially increased back- scattering of islets is dominated by the insulin–zinc nanocrystals in the beta cell granules. This translates into a high specificity for the functional beta cell volume of islets. Applying FOCI to a spontaneous mouse model of type 1 diabetes, we quantify the modifications of the pancreatic mi- crovasculature accompanying the progression of diabetes and reveal a strong correlation between increasing insulitis and density of the vascular network of the islet. Conclusions/interpretation FOCI provides a novel imaging technique for investigating functional and structural diabetes-induced alterations of the islets. The label-free detec- tion of beta cell volume and infiltration together with vascu- larisation offers a unique extension to study ACE-transplanted