WP1: AD and Inflammation: The work will involve functional in vivo MRI of transgenic AD mice models, e.g. APP/PS1, at the age before plaque load appears and soluble amyloid is expected to steadily increase. Resting state fMRI will be used to assess changes in functional connectivity. Cerebrovascular response function will be defined using arterial spin labelling both with and without a vascular challenge. Chemical profiling of brain metabolites will be performed by 1H MRS chemical shift imaging protocols at ultra-high field to provide spatial maps. Amyloid load will be studies with optical imaging as well (either nanoparticle-based conventional optical imaging or MSOT approaches). A subset of mice will be imaged by ex vivo MSI to generate protein maps and identify biomolecules (biomarkers) related to the disease. Advanced co-registration tools will be employed and further developed to obtain perfect matching between MRI, MRS, optical imaging and MSI voxels. WP1 will be led by the group of Prof. van der Linden with two ESRs/ERs to be sent to partner institutions and three incoming ESRs/ERs brought to the University of Antwerp. WP1 has a requirement for a co-registration and analysis workflow of the multimodality imaging data. Furthermore, there is a need for bed and coil systems that can be used both for MRI and optical imaging. Medres and icoMetrix have been identified as partners where one ER and one ESR from the Antwerp laboratory will work and be trained in the respective host SME institutes. There will also be one new recruit and two incoming scientists from industry (icoMetrix and PERC) to assist with MSI and correlation of in vivo data to identify spatial metabolite maps.