Early-Frame [18F]Florbetaben PET/MRI for Cerebral Blood Flow Quantification in Patients with Cognitive Impairment: Comparison to an [15O]Water Gold Standard

Cerebral blood flow (CBF) may be estimated from early -frame PET imaging of lipophilic tracers, such as amyloid agents, enabling measurement of this important biomarker in participants with dementia and memory decline. Although previous methods could map relative CBF, quantitative measurement in absolute units (mL/100 g/min) remained challenging and has not been evaluated against the gold standard method of [15O]water PET. The purpose of this study was to develop and validate a minimally invasive quantitative CBF imaging method combining early [18F]florbetaben (eFBB) with phase -contrast MRI using simultaneous PET/MRI. Methods: Twenty participants (11 men and 9 women; 8 cognitively normal, 9 with mild cognitive impairment, and 3 with dementia; 10 P-amyloid negative and 10 P-amyloid positive; 69 +/- 9 y old) underwent [15O]water PET, phasecontract MRI, and eFBB imaging in a single session on a 3-T PET/MRI scanner. Quantitative CBF images were created from the first 2 min of brain activity after [18F]florbetaben injection combined with phasecontrast MRI measurement of total brain blood flow. These maps were compared with [15O]water CBF using concordance correlation (CC) and Bland-Altman statistics for gray matter, white matter, and individual regions derived from the automated anatomic labeling (AAL) atlas. Results: The 2 methods showed similar results in gray matter ([15O]water, 55.2 +/- 14.7 mL/100 g/min; eFBB, 55.9 +/- 14.2 mL/100 g/min; difference, 0.7 +/- 2.4 mL/100 g/min; P = 0.2) and white matter ([15O]water, 21.4 +/- 5.6 mL/100 g/min; eFBB, 21.2 +/- 5.3 mL/100 g/min; difference, -0.2 +/- 1.0 mL/100 g/min; P = 0.4). The intrasubject CC for AALderived regions was high (0.91 +/- 0.04). Intersubject CC in different AAL-derived regions was similarly high, ranging from 0.86 for midfrontal regions to 0.98 for temporal regions. There were no significant differences in performance between the methods in the amyloid-positive and amyloid-negative groups as well as participants with different cognitive statuses. Conclusion: We conclude that eFBB PET/MRI can provide robust CBF measurements, highlighting the capability of simultaneous PET/MRI to provide measurements of both CBF and amyloid burden in a single imaging session in participants with memory disorders.