High performance in vivo imaging equipment to facilitate infectious disease research

Lead Research Organisation: London School of Hygiene & Tropical Medicine
Department Name: Infectious and Tropical Diseases

Abstract

Research at LSHTM is focused on infectious diseases that impact on some of the poorest people on the planet, with the long-term aim of developing more effective drugs and vaccines. However, progress in this area has been impeded by gaps in our knowledge of pathogen biology and how interactions with the host result in disease progression. Our research strategy is to address these issues, hand-in-hand with drug development.

In vivo imaging is a key technology in infectious disease research. It allows parasitic and bacterial infections in experimental mice to be monitored long-term in a non-invasive manner, and can be further adapted to provide data on tissue-specific and cell-specific infection and disease pathology. Scientists at LSHTM have been leaders in the application of these procedures. However, after a decade of heavy usage, our current equipment is reaching the end of its life-span, and has been overtaken by a new generation of imaging systems with enhanced technical specifications, resolution and sensitivity. The ultra-high resolution optical system, produced by MILabs, for which we are seeking funding is cutting edge technology. It will allow highly sensitive in vivo imaging and the monitoring of disease progression in 3 dimensions (tomography), ultimately at single cell resolution. The new equipment will be housed in a dedicated containment level 3 facility, where it will enable LSHTM researchers to take our research on globally important pathogens to a new level of detail. In addition, it will allow us to expand further collaborations on drug development with the pharmaceutical sector, and provide new opportunities to engage with researchers from disease endemic countries.

Technical Summary

LSHTM researchers have been leaders in the application of in vivo imaging techniques to trypanosome infections. The systems they have developed for Chagas disease (Trypanosoma cruzi) and African trypanosomiasis (Trypanosoma brucei) are the most sensitive available. They have made significant contributions to the study of parasite biology, host:parasite interactions, disease pathogenesis and drug development. One of our goals is to extend this technology into the areas of leishmaniasis and bacterial infections. However, our current imaging system has been in continuous use for more than 12 years, and is approaching the end of its life. A system failure would leave several of our research programmes at risk, and replacement of the current machine is thus a priority. Replacement would also represent a major opportunity to further develop our research capabilities, since the new generation of imaging systems have enhanced technical specifications which will add considerable value to research output.

We are seeking funds to purchase a MILabs ultra-high resolution optical imaging system. Its specifications include highly sensitive 2D fluorescence and bioluminescence in vivo imaging, 3D fluorescence and bioluminescence tomography, and X-ray computed tomography (CT) imaging. A key component is the advanced tomographic 3D-reconstruction algorithms that correct for differential absorption/scattering by different organs/tissues. These features are crucial for enabling real-time, tissue and cell-specific monitoring of pathogen dissemination, survival and recrudescence. The new system will also allow us to expand our collaborations with drug-development consortia and pharma, particularly in the area of Neglected Tropical diseases.

Publications

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