Development of a 3D mouse atlas tool for improved non-invasive imaging of orthotopic mouse models of pancreatic cancer

Genetically engineered mouse models (GEMMs) are a vital tool in cancer research but their use has led to an increase in total animals bred due to the typically low percentage obtained per litter having the correct genotype. In addition, similar to the human disease, these animals develop spontaneous orthotopic tumours deep within the body over long periods of time and tumour burden can be extremely difficult to assess non-invasively. GEMMs of pancreatic cancer in particular are challenging to use as the mouse pancreas itself is soft and diffuse in comparison to human cancers and tumours develop in the abdominal area where they can be difficult to distinguish from other tissues especially intestine. Currently screening is done by ultrasound imaging (US), however this is a difficult, time consuming and extremely operator dependent technique, it can be stressful for the animal as it requires fur removal and the images cannot be co-registered with those of other imaging modalities such as MRI, CT, PET and SPECT.

We aim to use a low field (1T) small animal MRI instrument to develop a mouse atlas to define the pancreas and development of pancreatic cancer in a GEMM (the KPC model). This data will be validated using autoradiography, PET/MRI and SPECT/MRI and used to develop pancreatic/pancreatic cancer autosegmentation functionality for an existing digital 3-D mouse atlas tool in collaboration with our industrial partner, inviCRO. This accurate staging of deep tissue disease will reduce variability of results and lead to a decrease in group size (generally ten to 12 per group, down to five to seven per group. Every animal saved represents five animals bred in this model). Improved data readouts will increase the adoption of longitudinal imaging, which is already being used in our Institute to monitor response to therapy. Improved screening techniques will also lead to a reduction in suffering due to tumours being detected earlier, studies starting at a lower level of tumour burden and ending sooner. The 3D atlas tool is already commercially available and the pancreatic/pancreatic atlas data will be made available for the benefit of all users.

• 2019 Research Review: MRI and pancreatic cancer
• Engagement Activities: Pint of Science 2017