title: Longitudinal three-dimensional visualisation of autoimmune diabetes by functional optical coherence imaging.
abstract: OBJECTIVE
  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
  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 human islets. These results are contributing to a deeper understanding of human islet transplant rejection and label-free in vivo monitoring of drug efficacy.
authors.affiliation: Laboratoire d'Optique Biomédicale, Ecole Polytechnique Fédérale de Lausanne, CH1015, Lausanne, Switzerland.
authors.forename: Corinne
authors.initials: C
authors.lastname: Berclaz
authors.affiliation: EMV - Immunology, Lund University, BMC, D14, 221 84, Lund, Sweden.
authors.forename: Anja
authors.initials: A
authors.lastname: Schmidt-Christensen
authors.affiliation: Laboratoire d'Optique Biomédicale, Ecole Polytechnique Fédérale de Lausanne, CH1015, Lausanne, Switzerland.|Institute of Physics, Faculty of Physics, Astronomy and Informatics, Nicolaus Copernicus University, Torun, Poland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Szlag
authors.affiliation: Laboratoire d'Optique Biomédicale, Ecole Polytechnique Fédérale de Lausanne, CH1015, Lausanne, Switzerland.|Hepia, University of Applied Science of Western Switzerland, Genève, Switzerland.
authors.forename: Jerome
authors.initials: J
authors.lastname: Extermann
authors.affiliation: EMV - Immunology, Lund University, BMC, D14, 221 84, Lund, Sweden.
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Hansen
authors.affiliation: Laboratoire d'Optique Biomédicale, Ecole Polytechnique Fédérale de Lausanne, CH1015, Lausanne, Switzerland.
authors.forename: Arno
authors.initials: A
authors.lastname: Bouwens
authors.affiliation: Laboratoire d'Optique Biomédicale, Ecole Polytechnique Fédérale de Lausanne, CH1015, Lausanne, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Villiger
authors.affiliation: Swiss Institute for Experimental Cancer Research, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Joan
authors.initials: J
authors.lastname: Goulley
authors.affiliation: Gene Expression Unit, Department of Molecular and Cellular Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Frans
authors.initials: F
authors.lastname: Schuit
authors.affiliation: DanStem, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Grapin-Botton
authors.affiliation: Laboratoire d'Optique Biomédicale, Ecole Polytechnique Fédérale de Lausanne, CH1015, Lausanne, Switzerland. theo.lasser@epfl.ch.
authors.forename: Theo
authors.initials: T
authors.lastname: Lasser
authors.affiliation: EMV - Immunology, Lund University, BMC, D14, 221 84, Lund, Sweden. dan.holmberg@med.lu.se.
authors.forename: Dan
authors.initials: D
authors.lastname: Holmberg
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology*; D004195:Disease Models, Animal; D005838:Genotype; D006801:Humans; D050417:Insulin-Secreting Cells / Q000473:pathology; D007515:Islets of Langerhans / Q000473:pathology; D016381:Islets of Langerhans Transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout
keywords: 3D visualisation; Beta cell volume; Human islets; Inflammation; Label-free; Longitudinal; NOD mouse; Non-invasive; OCM; Quantification; Vasculature