A systematic optimization of 19F MR image acquisition to detect macrophage invasion into an ECM hydrogel implanted in the stroke-damaged brain

Abstract

19F-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 19F-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 19F 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 mm3) produced the lowest limit of detection (LOD) for RARE (2.85 mM PFPE; 119 mM 19F) and FISP (0.43 mM PFPE; 18.1 mM 19F), 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 19F-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.