阿尔茨海默病海马亚区水通道蛋白磁共振分子成像研究

Research on aquaporin magnetic resonance molecular imaging of hippocampal subfields in Alzheimer's disease

目的利用水通道蛋白磁共振分子成像(aquaporin magnetic resonance molecular imaging,AQP-MRMI)技术对海马亚区进行定量分析,探讨AQP-MRMI技术在阿尔茨海默病(Alzheimer's disease,AD)诊断中的应用价值。材料与方法本研究共纳入59名受试者,包括AD组16名、轻度认知障碍(mild cognitive impairment,MCI)组22名和正常对照(normal control,NC)组21名。分析三组间海马亚区水通道蛋白表观扩散系数(aquaporin apparent diffusion coefficient,AQP-ADC)值差异是否具有统计学意义,并与认知评分进行相关性分析。绘制AQP-ADC值受试者工作特征(receiver operating characteristic,ROC)曲线分析其诊断效能。结果对比NC组,MCI组仅表现为左侧海马角(cornu ammonis,CA)1的AQP-ADC值升高(P<0.05),AD组则表现为双侧齿状回(dentate gyrus,DG)-CA4、双侧CA1-3、左侧下托、双侧海马旁回及左侧内嗅皮层的AQP-ADC值升高(P<0.05);对比MCI组,AD组表现为双侧DG-CA4、双侧CA1-3、右侧下托及右侧海马旁回AQP-ADC值升高(P<0.05)。除右侧下托外,各海马亚区的AQP-ADC值均与简易精神状态检查量表(Mini-Mental State Examination,MMSE)评分呈负相关,其中左侧DG-CA4(r=-0.607,P<0.001)、左侧CA1-3(r=-0.633,P<0.001)与MMSE评分表现出较显著的相关性。通过ROC曲线的分析发现,多个海马亚区感兴趣区(region of interest,ROI)的AQP-ADC值可用于鉴别NC与AD、MCI,其中以左侧DG-CA4及左侧CA1-3的AQP-ADC值在NC与AD组间的曲线下面积(area under the curve,AUC)最大(AUC=0.905、0.940),并且具有较高的敏感度和特异度。结论本研究中多个海马亚区的AQP-ADC值与认知功能存在一定相关性,特别是左侧DG-CA4及左侧CA1-3亚区有助于评估认知障碍的严重程度,在鉴别AD与认知正常老年人上具有较优越的诊断效能,可以作为检测AD的生物标志物。左侧海马CA1亚区AQP-ADC值或许有望成为AD早期的潜在生物标记物。AQP-MRMI作为新兴水通道蛋白分子成像技术,可以在一定程度上反映AD的病理生理变化,在分子水平上为AD的诊断、治疗和预后评估提供更多的信息。

Objective:This study applied aquaporin magnetic resonance molecular imaging(AQP-MRMI)technology to quantitatively analyze the hippocampal subfield,aiming to explore the application value of AQP-MRMI technology in the diagnosis of Alzheimer's disease(AD).Materials and Methods:A total of 59 subjects were included in this study,including 16 subjects in the AD group and 22 subjects in the mild cognitive impairment(MCI)group,and 21 subjects in the normal control(NC)group.Aquaporin apparent diffusion coefficient(AQP-ADC)values were measured and recorded to analyze whether the differences in AQP-ADC values among the three groups were statistically significant,and correlation analysis was conducted with cognitive scores.The receiver operating characteristic(ROC)curve of AQP-ADC values was drawn,and the area under the sensitivity and specificity curve and diagnostic threshold were analyzed.Results:There were statistical differences in AQP-ADC values of all hippocampal subfields except the right entorhinal cortex among the three groups(P<0.05).Compared with the NC group,the MCI group only showed increased AQP-ADC value of cornu ammonis-1(CA1)on the left side(P<0.05),the AD group showed increased AQP-ADC values of bilateral dentate gyrus(DG)-CA4,bilateral CA1-3,bilateral para-hippocampus and left entorhinal cortex(P<0.05);compared with the MCI group,the AQP-ADC values of bilateral DG-CA4,bilateral CA1-3,right subiculum and right para-hippocampus in AD group were increased(P<0.05).The AQP-ADC values of all hippocampal subfields were negatively correlated with the total score of Mini-Mental State Examination(MMSE),except for the right subiculum,and the left DG-CA4(r=-0.607,P<0.001)and the left CA1-3(r=-0.633,P<0.001)showed a significant correlation with MMSE.The ROC curve analysis showed that AQP-ADC values of multiple hippocampal subfields region of interest(ROI)could be used to identify NC and AD,MCI,among which the AQP-ADC values of left DG-CA4 and left CA1-3 had the largest area under the curve(AUC=0.905,0.940)between NC and AD group with high sensitivity and specificity.Conclusions:In this study,AQP-ADC values in several hippocampal subfields were correlated with cognitive function,especially the left DG-CA4 and left CA1-3 subregions,which helped evaluate the severity of cognitive impairment and had superior diagnostic efficacy in distinguishing AD from cognitively normal elderly people,and could be used as biomarkers for the detection of AD.The AQP-ADC values of the left CA1 may be expected to be a potential biomarker for early AD.AQP-MRMI,as an emerging aquaporin molecular imaging technology,can reflect the pathophysiological changes of AD,and provide more information for the diagnosis,treatment,and prognosis assessment of AD at the molecular level.