Protein-based amide proton transfer-weighted MR imaging of amnestic mild cognitive impairment

Abstract

Amide proton transfer-weighted (APTw) MRI is a novel molecular imaging technique that can noninvasively detect endogenous cellular proteins and peptides in tissue. Here, we demonstrate the feasibility of protein-based APTw MRI in characterizing amnestic mild cognitive impairment (aMCI). Eighteen patients with confirmed aMCI and 18 matched normal controls were scanned at 3 Tesla. The APTw, as well as conventional magnetization transfer ratio (MTR), signal differences between aMCI and normal groups were assessed by the independent samples t-test, and the receiver-operator-characteristic analysis was used to assess the diagnostic performance of APTw. When comparing the normal control group, aMCI brains typically had relatively higher APTw signals. Quantitatively, APTw intensity values were significantly higher in nine of 12 regions of interest in aMCI patients than in normal controls. The largest areas under the receiver-operator-characteristic curves were 0.88 (gray matter in occipital lobe) and 0.82 (gray matter in temporal lobe, white matter in occipital lobe) in diagnosing aMCI patients. On the contrary, MTR intensity values were significantly higher in only three of 12 regions of interest in the aMCI group. Additionally, the age dependency analyses revealed that these cross-sectional APTw/MTR signals had an increasing trend with age in most brain regions for normal controls, but a decreasing trend with age in most brain regions for aMCI patients. Our early results show the potential of the APTw signal as a new imaging biomarker for the noninvasive molecular diagnosis of aMCI. Keywords: Alzheimer's disease, Mild cognitive impairment, Magnetic resonance imaging, Molecular imaging, Biomarkers