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

Abstract

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 associated 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 variations of the index of refraction resulting in a faster tomographic acquisition. In addition, the phase sensitivity allows simultaneous label-free acquisition of vascularisation. Results We demonstrate that FOCI allows longitudinal quantification of progressive autoimmune insulitis, including the three-dimensional quantification of beta cell volume, inflammation and vascularisation. The substantially increased backscattering 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 microvasculature 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 detection of beta cell volume and infiltration together with vascularisation offers a unique extension to study ACE-transplanted Diabetologia (2016) 59:550-559 DOI 10.1007 Corinne Berclaz, Anja Schmidt-Christensen and Daniel Szlag contributed equally to this study. Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-015-3819-x) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Visible spectrum extended-focus optical coherence microscopy for label-free sub-cellular tomography

“…Although the exact nature of this particular contrast remains unknown, the presence of metals (such as Fe) in amyloid plaque cores, as described by Plascencia-Villa et al [23], might provide a first hint into the cause of this phenomenon. In fact, a previous study from our group showed that the contrast of the Langerhans islets in OCM images originated from the presence of Zn crystals [24]. Alternatively, this contrast could also arise from polarization effects as the plaques have been shown to have birefringent properties [25].…”

Label-free fast 3D coherent imaging reveals pancreatic islet micro-vascularization and dynamic blood flow

“…For instance, it has been shown that a modification of the vascularization is associated with the early onset of both type I and II diabetes [2][3][4][5]. Using functional optical coherence imaging (FOCI), we found that there is a strong correlation between the increasing inflammation of the islets and the density of their vascular network [6]. In addition, there are indications that the glucose intolerance observed in aged mice is due to a vascular impairment rather than β-cell defect [7].…”

“…For pancreas imaging, 6 to 8 B-scans were taken to perform averaging depending on the stabilization achieved, whereas for ACE imaging, 8 B-scans were averaged. Extraction of the islet and vascular volumes were done using algorithms described in previous papers [6,30]. The vascular density is defined as the ratio between the vascular volume and the islet volume.…”

“…3(a-c) intrinsic OCM contrast for the β-cells is caused by the zinc-insulin nanocrystals [6,39], providing a strongly enhanced light scattering. Vascularization imaging can be achieved by extracting the scattering of moving red blood cells.…”

“…Therefore, there is a need for an alternative imaging technique having a good spatial resolution, high sensitivity, sufficient penetration depth, and fast image acquisition rate to study longitudinally and non-invasively the vascularization and blood flow of islets of Langerhans. Extended-focus Optical Coherence Microscopy (xfOCM) [29] has been applied to image islets of Langerhans in vivo and ex vivo [6,[30][31][32]. In OCM, the axial resolution is determined by the spectral width of the broadband light source whereas the lateral resolution and depth of field are determined by the classical Abbe criteria.…”