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NC3Rs: National Centre for the Replacement Refinement & Reduction of Animals in Research
Strategic grant

Ultrasound mediated bioluminescence tomography for high sensitivity, high spatial resolution 3D imaging

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At a glance

Award date
September 2014 - May 2018
Grant amount
£349,668 (Co-funded by EPSRC)
Principal investigator
Professor Stephen Morgan


University of Nottingham


  • Reduction



This project aims to reduce the number of animals needed in long time course studies by combining ultrasound with bioluminescence imaging to improve 3D spatial resolution and maximise the quantitative data that can be obtained from each animal.


Traditional approaches for long term in vivo studies, for example, to track disease progression require groups of animals (up to ten) to be killed at defined time points and tissues removed for analysis (e.g. cell count, pathogen numbers). Longitudinal imaging offers an opportunity to reduce animal use in these studies, but due to optical scattering, current state of the art optical imaging systems lack quantitative accuracy and spatial resolution. This project will combine ultrasound with bioluminescence imaging (BLI) to create a new imaging platform to enable non-invasive, long term longitudinal imaging within the same group of animals. Combining these technologies will improve spatial resolution of the images, increasing the amount and quality of the data generated using this approach.

A traditional six time point experiment would use 18-60 animals, but the current approach would require up to eight animals. Multiple imaging of the same animal throughout an experiment allows long term studies to be followed accurately with less variability.

Research details and methods

This project will build on initial efforts to combine ultrasound and BLI to develop a small animal ultrasound-mediated BLI platform capable of providing (i) ultrasound images of the tissue structure; (ii) 3D maps of bioluminescence from the ultrasound modulated signals; and (iii) unmodulated bioluminescence images. Professor Morgan will collaborate with Dr Hamid Dehghani at the University of Birmingham to modify the widely used NIRFAST software for reconstructing images to allow quantitative mapping of the signals from the new BLI platform. The development of the imaging system and the accuracy of the reconstruction algorithm will be tested in specially constructed tissue phantoms with known optical and acoustic properties. The validity of the system for in vivo imaging will be assessed in a variety of in vivo experiments already ongoing within the Morgan laboratory. This will include tracking mesenchymal stem cells in vivo and imaging bacterial infection/colonisation of indwelling devices, such as catheters.


  1. Ahmad J et al. (2018). Ultrasound-mediation of self-illuminating reporters improves imaging resolution in optically scattering media. Biomed. Opt. Express 9(4):1664-1679. doi: 10.1364/BOE.9.001664
  2. Jayet B et al (2018). Incorporation of an ultrasound and model guided permissible region improves quantitative source recovery in bioluminescence tomography. Biomed. Opt. Express 9(3):1360-1374. doi: 10.1364/BOE.9.001360
  3. Zhang Q et al. (2017). Nanoscale Ultrasound-Switchable FRET-Based Liposomes for Near-Infrared Fluorescence Imaging in Optically Turbid Media. Small 13(33). doi: 10.1002/smll.201602895
  4. Zhang Q et al. (2016). Ultrasound Induced Fluorescence of Nanoscale Liposome Contrast Agents. PloS ONE 11(7):e0159742. doi: 10.1371/journal.pone.0159742
  5. Zhang Q et al. (2015). Numerical investigation of the mechanisms of ultrasound-modulated bioluminescence tomography. IEEE Trans Biomed Eng. 62(9):2135-43. doi: 10.1109/TBME.2015.2405415