In vivo optical imaging is becoming a powerful tool for monitoring infections. Developments in preclinical studies are leading us to ever more sophisticated ways to diagnose, track and understand infections in the body.
How in vivo optical imaging works
In vivo optical imaging is the name for a range of technologies that allow the non-invasive visualization or quantification of events within a whole animal or person. These systems have been used in a range of studies including oncology, inflammation and neuroscience.
In the field of infectious disease they are enabling us to see the effects of pathogens inside the bodies of small, living animals.
In vivo optical imaging uses two forms of labelling to visualize structures and cells within the body – bioluminescence and fluorescent probes – with the latter surpassing the former in popularity.
A number of instruments for imaging are now available and light-based imaging can be combined with other modalities, such as computed tomography (CT) and positron emission tomography (PET).
Detection of Inflammation induced myeloperoxidase activity after Microbial Infection. Luminescent Detection of Inflammation with X-Ray overlay. Image courtesy of Bruker BioSpin.
Identifying imaging agents
Current methods for imaging bacterial infection within the body are limited. One of the main strategies used is to radiolabel a patient or animal’s own white blood cells and then use imaging to observe which sites in the body the white blood cells are drawn to.
However, this technique has a number of drawbacks. Primarily, it is not very specific and cannot be used to distinguish between general inflammation and active infection, nor between the types of infectious agent, such as bacteria, fungi or parasite.
Imaging agents that can specifically monitor in vivo infections would therefore be very useful and are being explored in preclinical research.
One example is a molecule called dipicolylamine-Zinc(II) (DPA-Zn), which is the most well-studied candidate. In 2006, it was discovered that this cationic molecule has an affinity for the typically anionic membranes of bacteria. Since then multiple studies have characterized its use as a bacterial infection imaging agent with different fluorescent reporters.
Tracking cell migration
In vivo optical imaging has also been used to track bacterial cell migration and group movement (swarming) in culture, which could be particularly useful for helping understand treatment-resistant infections.
A recent study by Du et al. (2012) using fluorescently labelled Pseudomonas aeruginosa – an opportunistic pathogen – showed how the bacterium used a wave movement to efficiently colonize new territory. The researchers used multispectral 3D imaging to visualize the bacterial growth on agar over time.
Tracking therapeutic agents
Another use for in vivo imaging in infectious diseases has been to track potential therapeutic agents. For example, Jasmin et al. (2012, 2014) used a mouse model of Chagas disease – caused by the protozoan parasite Trypanosoma cruzi – to study a stem cell treatment for cardiomyopathy, one of the features of the disease.
By tagging the mesenchymal stem cells with nanoparticles and using small animal positron emission tomography (microPET), the researchers were able to show that the mesenchymal cells travelled to the heart in infected animals. Using magnetic resonance imaging, they then showed that this correlated with improved heart function.
Cardiovascular - Full body in vivo scan of a mouse using contrast agent. Image courtesy of Bruker BioSpin.
Understanding host-agent interaction
Researchers have also explored the host immune system response to infection, as well as the mechanisms that infectious agents use in turn to evade it. One study by Xu et al. (2012) looked at a type of virulence factor released by orthopoxviruses, such as smallpox, called type-1 interferon binding protein (T1-IFnbp). T1-IFnbp suppresses the host immune response by acting as a decoy receptor for interferons.
The researchers labelled the mousepox virus with a bioluminescent signal before infecting the animals. Using this to visualize viral load, they were able to show that monoclonal antibody treatment could cure mousepox.
Optical imaging systems
Since their development, in vivo optical imaging systems have become indispensable tools in both preclinical and clinical research. There are several recent trends in the field that are part of an overall progression towards the improved accuracy and utility of the technology. The first is multiplexing – the use of two or more probes or reporters within one animal. The second is a move towards 3D reconstructive multimodal imaging, allowing researchers to co-register images from multiple modalities, such as optical imaging and CT.
One example of an imaging system incorporating such developments is the Bruker MS FX PRO. It combines fluorescence, luminescence, radioisotopic and high-resolution X-ray imaging in one system and can produce high-quality small animal X-ray images in just 3 seconds. The system can also be coupled with the Bruker Albira PET/SPECT/CT system or with the multimodal animal rotation system for 360° imaging, bringing the broadest range of imaging applications from one system.
- Chi KR. (2015) Picturing Infection. Available at: http://www.the-scientist.com/?articles.view/articleNo/41699/title/Picturing-Infection/ Last accessed: 07th April 2015.
- Du H, et al. High density waves of the bacterium Pseudomonas aeruginosa in propagating swarms result in efficient colonization of surfaces. Biophysics Journal 2012;103:601-609.
- Glaser V. (2013) Improving In Vivo Small Animal Imaging. Available at http://www.genengnews.com/gen-articles/improving-in-vivo-small-animal-imaging/4699/ Last accessed: 08th April 2015.
- Jasmin J, et al. Mesenchmal bone marrow cell therapy in mouse model of Chagas disease. Where do the cells go? PLoS Neglected Tropical Diseases 2012;6:e1971.
- Jasmin J, et al. Molecular imaging, biodistribution and efficacy of mesenchymal bone marrow cell therapy in a mouse model of Chagas disease. Microbes & Infection 2014;16:923-935.
- McKenna N. (2012) In Vivo Imaging Expands Niche. Available at http://www.genengnews.com/gen-articles/in-vivo-imaging-expands-niche/3984/ Last accessed: 08th April 2015
- Sasser T, et al. Bacterial infection probes and imaging strategies in clinical nuclear medicine and preclinical molecular imaging. Current Topics in Medicinal Chemistry 2013; 13:479-487.
- Xu RH, et al. Antibody inhibition of a viral type 1 interferon decoy receptor cures a viral disease by restoring interferon signaling in the liver. PLoS Pathogens 2012;8:e1002475.
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