Longitudinal three-dimensional visualisation of autoimmune diabetes by functional optical coherence imaging
Longitudinal three-dimensional visualisation of autoimmune diabetes by functional optical coherence imaging
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DOI：
10.1007/s00125-015-3819-x
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发表时间：
2016-03-01
期刊：
影响因子：
8.2
通讯作者：
Holmberg, Dan
中科院分区：
文献类型：
--
作者：
Berclaz, Corinne;Schmidt-Christensen, Anja;Holmberg, Dan
目的/假设-它是普遍接受的，结构和功能的定量成像的个别胰岛将是有益的，以阐明1型糖尿病的发病机制。我们在这里介绍功能性光学相干成像（FOCI）的快速，无标记的β细胞破坏和相关的胰岛vascularisation.Methods的变化监测NOD小鼠和人类胰岛移植到眼前房（ACE）成像与FOCI，其中FOCI的光学对比度是基于内在的折射率的变化，从而导致更快的断层扫描采集。此外，相位灵敏度允许同时无标记收购vascularisation.Results我们证明，FOCI允许纵向量化进行性自身免疫性胰岛炎，包括β细胞体积，炎症和vascularisation的三维量化。胰岛的显著增加的背散射由β细胞颗粒中的胰岛素-锌纳米晶体主导。这转化为对胰岛的功能性β细胞体积的高特异性。应用FOCI的自发性小鼠模型1型糖尿病，我们量化的修改胰腺微血管伴随着糖尿病的进展，并揭示了强烈的相关性增加胰岛炎和密度的血管网络的islands.Conclusions/interpretation FOCI提供了一种新的成像技术，调查功能和结构糖尿病引起的改变的胰岛。无标记检测β细胞体积和浸润以及血管形成为研究ACE移植的人胰岛提供了独特的延伸。这些结果有助于更深入地了解人类胰岛移植排斥反应和无标记体内监测药物疗效。
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 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 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 human islets. These results are contributing to a deeper understanding of human islet transplant rejection and label-free in vivo monitoring of drug efficacy.