The central goal of CRC1450 is to develop and use novel imaging tools to understand which cellular processes in which organs are decisive indicators of how an inflammation will progress. In our project, a combined approach using MRI and mass spectrometric imaging will be developed. The aim of our project is to answer the overarching question, how quantitative MR parameters depend on elemental and molecular patterns in tissues, and how this dependence evolves during inflammatory responses. The novel methods will be applied to detect cell-type-specific signatures, to characterize immune response by non-invasive imaging with retrospective calibrations for quantitation.
MRI parametric mapping can provide quantitative measures of tissue parameters at high spatial resolution, independent of tissue depth. Yet, the exact relation between these tissue parameters and molecular concentrations of the actual substrate remains elusive. Molecular concentrations, however, are required for exact characterisation of (patho)physiological processes such as barrier leakage, molecular deposition, or immune cell extravasation and tissue infiltration occurring in inflammatory processes. This project aims to develop combined in vivo MRI and ex vivo mass spectrometry imaging (MSI) methods including both, laser ablation-inductively coupled plasma-mass spectrometry imaging (LA-ICP-MSI) and matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI). MSI shall additionally be used as an important milestone towards developing fully quantitative MRI methods as part of our comprehensive multiscale imaging strategy to analyse immune responses in disease models and patients in vivo. Making use of MR-compatible contrast agents, biorthogonal click reagents, BODYPIs and nanocapsules provided by other CRC1450 projects, calibrated MRI methods for investigation of vascular permeability will be developed. We will investigate if MRI methods can provide fully quantitative cell tracking and characterisation of immune response in response to bacterial infections and in ischemia-reperfusion in the heart and kidney.
For this purpose, we will establish calibrated relations between the in vivo accessible MR parameter relaxivity R1/2 and elemental concentration of the contrast agent (Gd, Fe) in dependence of its physicochemical state, develop novel MSI methods to quantify elements (LA-ICP-MSI) and to acquire metabolic profiles (MALDI-MSI), to include physicochemical parameters of the surrounding in relaxation modeling, implement robust coregistration algorithms for MRI and MSI, develop protocols to distinguish different populations of immune cells in vivo by combined MRI and MSI, and finally apply and validate these methods to characterise immune cell dynamics in a kidney ischemia/reperfusion model, vascular permeability models, in cardiac I/R, and in sepsis models.
Funding Period: 01.2021 – 12.2024