Arterial spin labeling perfusion predicts longitudinal decline in semantic variant primary progressive aphasia

The objective of the study was to evaluate the prognostic value of regional cerebral blood flow (CBF) measured by arterial spin labeled (ASL) perfusion MRI in patients with semantic variant primary progressive aphasia (svPPA). We acquired pseudo-continuous ASL (pCASL) MRI and whole-brain T1-weighted structural MRI in svPPA patients (N = 13) with cerebrospinal fluid biomarkers consistent with frontotemporal lobar degeneration pathology. Follow-up T1-weighted MRI was available in a subset of patients (N = 8). We performed whole-brain comparisons of partial volume-corrected CBF and cortical thickness between svPPA and controls, and compared baseline and follow-up cortical thickness in regions of significant hypoperfusion and hyperperfusion. Patients with svPPA showed partial volume-corrected hypoperfusion relative to controls in left temporal lobe and insula. svPPA patients also had typical cortical thinning in anterior temporal, insula, and inferior frontal regions at baseline. Volume-corrected hypoperfusion was seen in areas of significant cortical thinning such as the left temporal lobe and insula. Additional regions of hypoperfusion corresponded to areas without cortical thinning. We also observed regions of hyperperfusion, some associated with cortical thinning and others without cortical thinning, including right superior temporal, inferior parietal, and orbitofrontal cortices. Regions of hypoperfusion and hyperperfusion near cortical thinning at baseline had significant longitudinal thinning between baseline and follow-up scans, but perfusion changes in distant areas did not show progressive thinning. Our findings suggest ASL MRI may be sensitive to functional changes not readily apparent in structural MRI, and specific changes in perfusion may be prognostic markers of disease progression in a manner consistent with cell-to-cell spreading pathology.