Exquisite networks (2011)

Swollen lymph nodes (or “glands”) are a sign the immune system is fighting disease. Immune cells cluster and grow in the lymph nodes, and during an immune response, they balloon in size. However, unlike a balloon, the inside of a lymph node is criss-crossed by a dense network of tubes and fibres – and it’s unclear how this web of internal connections copes as the lymph node swells. 

To clarify this fundamental process, Inken Kelch, a Maurice Wilkins Centre PhD student in Director Professor Rod Dunbar’s laboratory, is creating a 3D “road map” of the connected tubes, fibres and spaces within lymph nodes. Inken’s work uses a unique microscope system that was designed and built in New Zealand. 

University of Auckland physiologist Associate Professor Ian LeGrice and colleagues originally built this system so they could stitch together very large numbers of overlapping images into a single 3D picture of heart tissue. Their machine combines a powerful microscope with a precision-engineered milling platform, so it can gradually remove thin layers of tissue, taking overlapping images as it goes – all accurately aligned so they can be seamlessly combined in 3D. 

In a major cross-disciplinary effort within the Maurice Wilkins Centre, Inken has worked with Ian’s team and surgeon Dr Anthony Phillips to adapt their imaging techniques for lymph nodes. Inken’s first 3D images show the entire blood vessel network of a lymph node, and she and Dr Gib Bogle, from the Auckland Bioengineering Institute, have now turned these images into a 3D computer model. This computer model allows the blood vessel network to be measured precisely, so now the team will be able to measure how all the blood vessels change when a lymph node swells. 

The cross-disciplinary links don’t stop there. It became clear that the same approach to map blood vessel networks in 3D could be used by Maurice Wilkins Centre colleagues at the Auckland Cancer Society Research Centre (ACSRC). 

Blood vessel networks form abnormally in tumours, resulting in uneven blood supply, and zones where there is little oxygen (hypoxia). So the lymph node team is now working with Drs Frederik Pruijn and Kevin Hicks from the ACSRC to precisely map both the blood vessels and the hypoxic zones in tumours. 

Models of the tumour blood vessels have already been used by Kevin and ACSRC colleagues, led by Professor Bill Wilson, to help design drugs that “switch on” only in hard-to-treat hypoxic zones (see page 9). The new 3D techniques developed at the Maurice Wilkins Centre offer the opportunity to produce much better models of tumour blood vessels, with potential to improve drug design – a useful practical outcome from some very innovative fundamental research.

Image: PhD student Inken Kelch using the microscope. Photograph courtesy of Godfrey Boehnke