Amide Proton Transfer-Weighted MR Imaging Of Human Brain Aging And Amnestic Mild Cognitive Impairment

As a novel molecular magnetic resonance imaging(MRI)technique,amide proton transfer-weighted MRI(APTw MRI)is based on chemical exchange saturation transfer(CEST)and magnetization transfer(MT),which is able to noninvasively detect mobile endogeneous peptides and proteins in biological tissue.Normal brain aging means brain aging without any diseases,which presents few changes of brain function associated with increasing ages in the elderly.Mild cognitive impairment(MCI)is a neurodegenerative disease between normal brain aging and dementia.Patients with MCI,whose hypomnesia is not matched to their age,have mild impairment of cognitive function,which does not meet standards of dementia.The APTw MRI research about normal brain aging and MCI is still an open topic until now.This study,was designed to explore the feasibility and potential of using the APTw signal,as a new promising imaging biomarker,to evaluate normal brain aging and to noninvasively diagnose MCI at the molecular level.Part 1.Amide Proton Transfer-Weighted MR Imaging of Human Brain AgingBackgroundAmide proton transfer-weighted(APTw)imaging has revealed the great potential in the diagnosis of several brain diseases.The purpose of this proof-of-concept study was to evaluate the feasibility and value of APTw MRI to characterize normal brain aging.MethodsThere were 106 healthy subjects who were recruited and scanned at 3.0 Tesla,with APTw and conventional magnetization transfer(MT)sequences.Quantitative image analyses were performed in 12 regions of interest(ROIs)for each subject.The APTw or MT ratio(MTR)signal differences among five age groups(young,mature,middle-aged,young-old,and middle-old)were assessed using the one-way analysis of variance,with the Benjamini-Hochberg correction for multiple comparisons.The relationship between APTw and MTR signals and the age dependencies of APTw and MTR signals were assessed using the Pearson correlation and non-linear regression.ResultsThere were no significant differences between the APTw or MTR values for males and females in all 12 ROIs analyzed.Among the five age groups,there were significant differences in the three white matter regions in the temporal,occipital,and frontal lobes.Overall,the mean APTw values in the older group were higher than those in the younger group.The positive correlations with age were observed in most brain regions,including four with significant positive correlations(r=0.2065?0.4182)and five with increasing trends.As a comparison,the mean MTR values did not appear to be significantly different among the five age groups.In addition,the mean APTw and MTR values revealed significant positive correlations in 10 ROIs(r=0.2214?0.7269)and a significant negative correlation in one ROI(entorhinal cortex,r=-0.2141).ConclusionsOur early results show that the APTw signal can be used as a promising and complementary imaging biomarker,with which normal brain aging can be evaluated at the molecular level.Part 2.Amide Proton Transfer-Weighted MR Imaging of Amnestic MildCognitive ImpairmentBackgroundAmide 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 and value of protein-based APTw MRI in characterizing amnestic mild cognitive impairment(aMCI).MethodsEighteen 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.ResultsWhen 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.ConclusionsOur early results show the potential of the APTw signal as a new imaging biomarker for the noninvasive molecular diagnosis of aMCI.