Molecular 3D imaging of the developing and diabetic pancreas

The endocrine component of the pancreas (including the insulin producing beta-cells) is organised into the islets of Langerhans, thousands of which are scattered throughout the exocrine tissue. Therefore, attempts to calculate the pancreatic beta-cell content has proven to be a great challenge. Optical Projection Tomography (OPT) is a relatively a new technique for three-dimensional (3D) imaging of biological specimen. We have recently adapted and optimised this technique to allow for 3D modelling and quantification of the intact adult mouse pancreas. Hereby, we possess the ability to obtain quantitative (volumetric) measurements and spatial coordinates for (specifically labelled) objects throughout the pancreatic volume. This ability has implications for a number of diabetes related research areas and allows us to address a number of questions regarding cellular ratios and cellular distributions in normal and diabetic mice. We are currently using this technology to study the spatio-temporal dynamics of beta-cell destruction and the insulitis process during the development of type 1 diabetes and different aspects of the normal islet mass distribution. Further we are exploring the use of the methodology for as a tool for the screening of rare events or cell niches during different pathologic and genetically induced conditions pertinent to both type 1 and type 2 diabetes. Other projects are includes the use of the technique for studying different aspects of normal and disturbed pancreas development and further development/optimisation of the technique itself for pancreas imaging