Elucidating the role of the immune response tobioscaffold-implantation using multi-color 19F MRI

/Abstract A robust host immune response to inductive bioscaffolds is essential for their biodegradation. Specifically, peripheral macrophages are thought to be the key effector of this process, which is essential for tissue regeneration. The trafficking of immune cells to the bioscaffold nevertheless remains poorly understood, especially in the brain. It is hypothesized here that immune cells accumulate in the peri-lesional tissues prior to their invasion into the bioscaffold. The spatio-temporal dynamics of this invasion at the tissue/bioscaffold interface is crucial to understand and potentially control this process. Histological time course studies are limited in their ability to visualize this process, especially in tissue cavities with a diverse topology, such as a stroke. We therefore here propose to use 19F Magnetic Resonance (MR) based imaging techniques to non- invasively visualize the distribution of ECM hydrogel using perfluorotertbutyl-cyclohexane (PFTBC), as well as perfluorocrownether (PFCE) invading immune cells and more specifically macrophages during different phases of the immune response. This multi-color 19F MRI is unique in its ability to distinctly visualize the bioscaffold and the acute peripheral immune cell invasion in the same animal over time. We aim to: 1) visualize non- invasively the spatio-temporal dynamics of immune cells accumulation and invasion into hydrogels implanted into brain tissue cavities formed by stroke; 2) to timestamp different phases of the peripheral immune cell invasion by 19F MRI and 3) to monitor in vivo the ablation of immune cells and investigate their contribution to hydrogel biodegradation and tissue regeneration. The goal of this work is to improve our mechanistic understanding of immune cell trafficking between the host and bioscaffold. We expect that these studies will lead to novel methods to monitor and manipulate the contribution of peripheral immune cells to biodegradation and tissue restoration. Project Number: 1R01NS142114-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Neurological Disorders and Stroke (NINDS) | Principal Investigator: Michel Modo | Institution: UNIVERSITY OF PITTSBURGH AT PITTSBURGH, PITTSBURGH, PA | Award Amount: $587,678 | Activity Code: R01 | Study Section: Imaging Technology for Neuroscience Study Section[ITN] View on NIH RePORTER: https://reporter.nih.gov/project-details/11295846