Development of a Multimodal Imaging Platform for the non-invasive assessment of the pathogenesis and antifungal treatment efficacy in experimental models of cryptococcus infection.
Cryptococcosis is a life-threatening fungal disease caused by the encapsulated yeast Cryptococcus neoformans or C. gattii. The main route of infection is by inhalation, whereby the lungs can be affected, but cryptococci can also spread from the lung to the brain, causing meningitis or brain lesions. The exact mechanism of cryptococci breaching through the blood-brain barrier and disseminating to the brain is still unknown. Traditional techniques in preclinical cryptococcosis research such as histology and fungal load quantification by colony-forming unit counts are limited to single-time point information per animal due to their invasive character. In this project, different and complementary imaging modalities such as magnetic resonance (MR) imaging and MR spectroscopy, and optical imaging techniques including bioluminescence imaging and fibered confocal fluorescence microscopy will be combined to allow non-invasive and longitudinal studies of the infection in experimental animal models of this disease. The dynamic information on disease progression could contribute to the unraveling of the pathogenesis of cryptococcosis in vivo. In addition, the project aims to validate new approaches to better diagnose cryptococcosis. This combination of techniques will also be used for the assessment of antifungal treatment efficacy by studying the in vivo effects on cell viability.