Malaria in 3D: bioluminescence imaging

In a recent Plos One paper, Ploemen and colleagues (Nijmegen Medical Centre) use previously generated luciferase-bearing malaria parasites (PbGFP-Luccon) to study the spatio-temporal development of malaria infection in liver of living infected mice. The final aim of the paper is to propose 3D-imaging to explore the effect of drug and vaccines on P. falciparum infection without surgery and other invasive methodologies in the mouse. Interestingly, they report good tri-dimensional plasmodium tracking in the liver, which can be followed over time.

Modified from Ploemen et al., Plos ONE 2009

A 3D approximation is obtained through rotational axis bioluminescence imaging through a CaliperLS workstation: eight imaging views from different advantage points are determined. At each angle view, both the picture of the mouse and its luciferase signal at 3 different wavelengths are acquired. Then, the algorithm tries, from surface data, to reconstruct what is happening inside the mouse by providing an approximate 3D-reconstruction. Last, a digital mouse atlas is overlaid onto the 3D diffuse tomography reconstruction to obtain anatomical reference points. The Caliper algorithm is longer to be perfect (see 2008 post on new developments in 3D-bioluminescence) in fact it is based on the assumption that the mouse is optically homogeneous. However, it seems to perform pretty well at least for a parenchimal organ like the liver (see picture). Indeed, also fluorescence tomography works well in liver (see post on infrared fluorescent protein).

In conclusion, at least for liver, it is possible to follow a reporter with enhanced spatio-temporal resolution. Since in liver, contrarily to the whole mouse, genetic engineering can be successfully performed with simple hydrodynamic injections, one would expect lot of progress in the future of molecular hepatology.

Ploemen, I., PrudĂȘncio, M., Douradinha, B., Ramesar, J., Fonager, J., van Gemert, G., Luty, A., Hermsen, C., Sauerwein, R., Baptista, F., Mota, M., Waters, A., Que, I., Lowik, C., Khan, S., Janse, C., & Franke-Fayard, B. (2009). Visualisation and Quantitative Analysis of the Rodent Malaria Liver Stage by Real Time Imaging PLoS ONE, 4 (11) DOI: 10.1371/journal.pone.0007881