Cellular or systemic imaging is a central methodology applied in all animal model experiments performed within CRC1009, which has the central aim to investigate cell behaviour and cellular barriers. Fluorescence microscopy is the method of choice for cell cultures and tissue slices due to its excellent sensitivity and specificity. In vivo, however, it is destructive and provides only a “keyhole view” of a spatially confined target area. Non-invasive imaging is an asset to established biochemical and microscopic methods and adds a new level of understanding, which cannot be reached with conventional microscopy methods only. Among the non-invasive imaging methods, MRI is a particularly versatile tool to image cellular populations and integrity of barriers in vivo, because it provides high spatial resolution, diverse contrasts, static and dynamic data in 2D and 3D at full penetration depth. MRI methods are therefore developed and provided in a central project in the CRC. It is important to note that this is not designed as a service project, but as a project with its own scientific aims, developing novel methods for imaging cells and barriers. In the previous funding periods, we have shown that time lapse MRI can resolve single labelled immune cells and track those moving inside the vasculature of the brain. The number of observed cells differed significantly in healthy animals compared to mice after the onset of an immune response6. To assess the fate and barrier crossing of iron oxide nanoparticles (IONP), which were used for cell labelling, we have devised a novel approach. We designed novel IONP composed of 57Fe, and tracked those by a multimodal approach, combining MRI with mass spectrometric imaging4. For assessment of barrier-breaking in cancer, tumour microstructure characterization could be achieved with oscillating gradient diffusion measurements. For the characterisation of blood-brain-barrier leakage and contrast agent distribution across barriers, we have implemented a novel animal model, which allows for the accurate determination of individual arterial input functions of contrast agents. Yet, methods to characterize cell migration, bacterial dynamics, and tissue microstructure, remain limited in terms of temporal and spatial resolution. Therefore, the general aim of this central project remains to develop and apply improved imaging methods. For this purpose, we are developing (i) novel labelling protocols and improved detection schemes for single-cell detection and tracking with MRI, MR sequences for the characterisation of tissue microstructure, and (iii) dedicated methods for bacteria tracking in models requiring up to biosafety level 2 (bsl2) conditions. We will specifically strive for increasing temporal resolution of time lapse MRI to resolve single rolling leukocytes, to improve microstructural characterisation of tumours and white matter in the brain, and to develop bacteria tracking tools for abdominal imaging. These novel methods will be used to setup tailored imaging protocols for non-invasive cell tracking and systemic MRI, according to the specific needs of all projects within the CRC using animal models. Our efforts will continue to close the gap between systemic imaging and microscopy methods and thus, improve diagnostic and analytic options within this CRC.
Funding Period: 07/2020 – 06.2024