Implanted optical imaging laboratories for deep-tissue in vivo imaging

Aims

This project aims to reduce animal use across a number of research areas, including tracking cell fate and biodistribution of macromolecules, by developing a miniaturised implantable microscope for long term longitudinal imaging in the same mouse or rat. 

Background

In vivo microscopic imaging is widespread for fundamental research using animal models in biomedicine, for drug discovery and tracking disease progression. Deep-tissue imaging is highly invasive and so animals are normally killed after each measurement. In long term experiments involving measurements taken at multiple time points, for example, cell migration studies, groups of animals are used at each time point, resulting in large numbers of animals being used to achieve a reliable research outcome. 

This project will develop a miniaturised self-contained microscope suitable for in vivo implantation for long term longitudinal deep-tissue imaging. This will enable the same animal to be imaged at multiple time points, reducing the total number of animals needed per study. 

Research details and methods

This research will take advantage of recent technological advances in engineering and miniaturisation. The microscope will enable epifluorescence imaging employing a 5Mpixel ST camera module optimised for the low-light performance that is required for fluorescence microscopy. The development and utility of the device will be assessed initially in rat and mouse cadavers. Subsequent in vivo validation will be demonstrated by tracking the migration of neural stem cells within the spinal cord of mice in real-time.

Related Content

In vivo microscopic imaging on mice and rats is widespread and increasing: animal models are used in fundamental science, biomedicine, for drug discovery and tracking disease progression. The number of animals experimented upon continues to rise year on year; approximately 79% of the four million animals annually being rats or mice. Deep-tissue imaging is, however, highly invasive and so termination of the animal normally occurs after each measurement. In experiments involving testing with multiple timepoints, for example, the study of disease progression or cell migration, termination of an animal at each timepoint can require the use of a large number of animals to achieve a reliable research outcome. Furthermore this provides only snapshots of phenomena, hampering understanding of cell fate and function. We propose to develop in vivo imaging technology that has the promise to reduce the number of animals terminated in these experiments by a factor of ten.

We will develop a miniaturised self-contained microscope-technology platform suitable for in vivo implantation for long-term longitudinal fluorescence and hyperspectral deep-tissue imaging on single animals that will enable a step-change in the approach to animal-based research. We believe that this will be the smallest microscope system yet demonstrated. The technology promises to enable longitudinal studies on a single animal thereby yielding an overall reduction in the number of animals required to be terminated to achieve high quality research outcomes and refining the experiments on each animal through reduced need for anaesthesia.

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Strategic grant

Grant reference number

NC/L001969/1

Award date:

Mar 2015 - Nov 2018

Grant amount

£352,774 (Funded by EPSRC)