F-MR imaging of perfluorocarbon (PFC)-labeled macrophages can provide a unique insight into their participation and spatio-temporal dynamics of inflammatory events, such as the biodegradation of an extracellular matrix (ECM) hydrogel implanted into a stroke cavity. To determine the most efficient acquisition strategy for F-MR imaging, five commonly used sequences were optimized using a design of experiment (DoE) approach and compared based on their signal-to-noise ratio (SNR). The fast imaging with steady-state precession (FISP) sequence produced the most efficient detection of a F signal followed by the rapid acquisition with relaxation enhancement (RARE) sequence. The multi-slice multi-echo (MSME), fast low angle shot (FLASH), and zero echo time (ZTE) sequences were significantly less efficient. Imaging parameters (matrix/voxel size; slice thickness, number of averages) determined the accuracy (i.e. trueness and precision) of object identification by reducing partial volume effects, as determined by analysis of the point spread function (PSF). A 96 × 96 matrix size (0.35 mm) produced the lowest limit of detection (LOD) for RARE (2.85 mM PFPE; 119 mM F) and FISP (0.43 mM PFPE; 18.1 mM F), with an SNR of 2 as the detection threshold. Imaging of a brain phantom with PFC-labeled macrophages invading an ECM hydrogel further illustrated the impact of these parameter changes. The systematic optimization of sequence and imaging parameters provides the framework for an accurate visualization of F-labeled macrophage distribution and density in the brain. This will enhance our understanding of the contribution of periphery-derived macrophages in bioscaffold degradation and its role in brain tissue regeneration.
