Quantitative imaging of astrogliosis and neuroinflammation

National Institute On Aging

Investigators

Linked publications, trials & patents

Abstract

As indicated in the Goals and Objectives section, the main goals of this research initiative are to discover diagnostic imaging biomarkers for astrogliosis and neuroinflammation by investigating the relationships between advanced multidimensional MRI signal signatures and increased glial fibrillary acidic protein (GFAP) deposition. Significant progress has been achieved during the last fiscal year: 1. We investigated ex vivo cerebral cortical tissue specimens derived from seven subjects who sustained blast induced injuries, which resulted in scar-border forming astrogliosis without being accompanied by other types of neuropathologic abnormality, and from seven control brain donors. By performing a combined postmortem radiology and histopathology correlation study we found that astrogliosis induces microstructural and chemical changes that are robustly detected with multidimensional MRI, and which can be attributed to astrogliosis because no axonal damage, demyelination, or tauopathy were histologically observed in any of the cases in the study. Importantly, we showed that no one-dimensional T1, T2, or diffusion MRI measurement can disentangle the microscopic alterations caused by this neuropathology. 2. Based on these finding, we developed a within-subject anomaly detection procedure that generates MRI-based astrogliosis biomarker maps ex vivo, which were significantly and strongly correlated with co-registered histological images of increased GFAP deposition. Our findings elucidate the underpinning of MRI signal response from astrogliosis, and the demonstrated high spatial sensitivity and specificity in detecting reactive astrocytes at the individual level, and if reproduced in vivo, will significantly impact neuroimaging studies of injury, disease, repair, and aging, in which astrogliosis has so far been an invisible process radiologically. 3. A clinical version of the multidimensional MRI sequence has been developed and tested on phantoms and on a small number of volunteer participants. Further control participants are being scanned to establish the multidimensional MRI response from normative brain tissue and to create a baseline dataset.