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Mapping microscopic worlds

Maurice Wilkins Centre researchers have used unique microscopic imaging techniques to peer into the three-dimensional structure of blood vessel networks – and new computational techniques to reveal how they are organised.

Maurice Wilkins Centre scientists have provided an unprecedented glimpse into the microscopic networks of tubes that keep tissues alive – creating 3D maps of the 16,000 blood vessel segments that supply the oxygen and nutrients to an entire lymph node.

LN Vasculature Web

The highly detailed 3D images and videos they published reveal the dizzying hydroslide ride taken by blood cells as they journey through a labyrinth of twists, loops and turns inside an organ as small as a grain of rice. This intricate network of tubes comprises a single incoming artery and outgoing vein connected by branches that become smaller and smaller to finally feed capillaries so narrow only one blood cell can pass through at a time. The stunning detail on this complete set of blood vessels was only possible because of a unique microscope designed and built at the University of Auckland.

Affiliate Investigator, and former Maurice Wilkins Centre PhD student, Dr Inken Kelch says the research developed new imaging and computational techniques capable of mapping even the smallest blood vessels in the tissues. “The special microscope developed by Associate Professor Ian LeGrice and his team at the University of Auckland allowed us to take 63,706 high resolution images of a lymph node only millimetres wide.” The precise control within the microscopy system allowed all these images to be seamlessly combined into one large 3D image – a feat not feasible on previous systems.

Dr Gib Bogle from the Auckland Bioengineering Institute then developed image processing tools to analyse the images and measure how all the microscopic blood vessels are arranged. “With computer analysis we were able to take detailed measurements of the network, including each blood vessel’s diameter, distances between vessels, and the number of branches along each path.” The precise measurements enabled the team to colour-code specific structures and re-visualise the network using 3D computer models. These methods allow the researchers to view the blood network from different angles, zoom into regions of interest, and compare structures.

Professor Rod Dunbar, Director of the Maurice Wilkins Centre, says the work is a completely new and detailed view of a critical immune environment at a microscopic scale. “These maps help us understand how lymph nodes work – these small cell factories are crucial for generating immune attack on both infectious agents and cancer. But the new information about how blood vessel networks are constructed has much wider use – from understanding diseases where blood vessel networks are abnormal, to understanding how different drugs flow from the blood into the tissues.” The techniques established in this project have already been used to image the disordered blood vessels in tumours, and Inken is using similar methods to image other networks of tubes in immune tissues – with similarly spectacular results.

Image: The 3D volume image of a mouse lymph node (left) was used to generate a 3D topology map of the continuous blood vessel system (right) and facilitated the quantification of vessel parameters. The display on the right shows colour-coded vessel diameters, whereby small vessels appear blue and the large vessels appear red.
Image courtesy of Dr Inken Kelch