轻度认知损害患者大脑MR海马体积及其波谱分析
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摘要
目的：利用磁共振成像技术对aMC I患者、AD患者及相匹配的正常老年人的临床表现同脑结构和代谢变化进行相关的研究,为aMCI和AD的早期诊断、鉴别诊断及监测其转归提供依据,为痴呆的早期诊断与干预提供参考。
方法：采用德国SIEMENS公司生产的Novu s 1.5T磁共振成像系统,对入选的研究对象行相应的常规MRI扫描,脑内感兴趣区的1H-MRS采集和／或海马体积扫描.
单体素1H-MRS检查：采用单体素序列为SVS-SE-30序列,双内侧颞叶的采集体素大小为1.2×1.2×1.2(cm3),左后扣带回体素大小为1.5×1.5×1.5(cm3), TR 1500ms,TE 30ms,间隔时间(TM)13.7ms,256次采样,8次相位循环,频宽2500Hz.。测得这些部位的N-乙酰天门冬氨酸(NAA),胆碱(Cho)和肌醇(mI)与肌酸(Cr)的值,并计算其各自相应的比值,包括NAA/Cr, NAA/mI,Cho/Cr及mI/Cr.
海马体积的测定：在常规扫描的基础上对海马进行定位,并行垂直于海马长轴的斜冠状IR-PDWI-Tf 13D序列扫描：TI 1100ms；TR 1830ms；TE 3.93ms；采集次数3次、层厚1.2 mm. FOV 25 cm.矩阵256×256,无间隔连续扫描。扫描范围包括杏仁核前部及侧脑室后角。
比较NC. aMC I和AD各组间NAA/Cr, NAA/mI, Cho/Cr, mI/Cr比值的差别,并分析各代谢物比值与认知功能的相关性,比较各组间海马体积的差别及与各部位代谢物比值的相关性,同时基于核磁共振代谢组学分析方法,探讨aMCI两个主要证型(肾虚证,痰浊证)的1H-MRS代谢物比值的相关特征。
结果：
1.左内侧颞叶aMCI和AD组的NAA/Cr均明显低于NC组(P＜0.05),AD组与aMCI组比较无显著性改变(P>0.05);aMC I组和AD组的NAA/mI低于NC组(P＜0.05),AD组与aMCI组比较无显著变化(P＞0.05)。右内侧颞叶AD组和aMCI的NAA/mI显著低于NC组(P<0.05)。aMCI. AD和NC组左扣带回后部NAA/Cr. Cho/Cr. mI/Cr及NAA/mI差异均无显著变化。双内侧颞叶aMCI组与Nc组代谢物不对称指数比较发现,aMCI组与Nc组有显著改变(p<0.05.),余代谢物比值差异无显著变化(P>0.05)。
2.(1)aMCI.AD组的MMSE评分与1H-MRS相关性：aMCI组与左后扣带回NAA/Cr呈负相关(r=-0.709,(P＜0.05),而与其它代谢物比值无明显相关。(2)aMCI和AD组的DSR评分与1H-MRS相关性：aMCI组与左内侧颞叶NAA/Cr呈正相关(r=0.648,P<0.05), AD组与左后扣带回的NAA/mI呈正相关(r=0.673,P<0.05),(3)aMCI和AD组的ISR评分与1H-MRS相关性：aMCI组与左内侧颞叶NAA/Cr有正相关趋势((r=0.629,P=0.051),与Cho/Cr正相关(r=0.660,P<0.05),AD组与左后扣带回的NAA/mI呈正相关(r=0.658,P<0.05)。
3.三组双侧校正后海马体积比较,NC. aMCI组和AD组两侧海马体积比较差异有显著改变(p<0.05),NC和aMCI组的两侧海马体积差异无显著改变(p>0.05)；AD组与aMCI组各自的左右侧海马体积与三个部位的代谢物比值无明显相关。
4. aMCI患者痰浊组左内侧颞叶代谢物NAA/Cr与MMSE正相关(r=0.498,P<0.05)；NAA/mI与MMSE正相关(r=0.462,P<0.05)；而与右内侧颞叶各代谢物比值无明显相关；aMCI患者肾虚组的MMSE与右内侧颞叶NAA/mI呈正相关(r=0.585,P<0.05),而与左内侧颞叶各代谢物比值无明显相关。
结论：
本研究发现海马体积测定在鉴别诊断aMCI和AD有重要价值,1H-MRS诊断及鉴别aMCI和NC有相对高的敏感性,两者结合对NC→aMCI→AD的病程追踪和病理的演变的监测相互补充,同时也是aMCI和AD诊断、鉴别诊断的最佳选择。
在对aMCI和AD的认知功能测评中,三个神经心理学量表(简易精神状态检查)MMSE、(延迟故事回忆)DSR及(即刻故事回忆)ISR中, DSR及ISR与左内侧颞叶的NAA/Cr有相关性,而以DSR的相关性最明显,提示延迟故事回忆(DSR)与脑影像学检查结合可作为aMCI和AD早期诊断及鉴别的重要辅助工具,左后扣带回的NAA/mI,及NAA/Cr与AD关联密切,可作为AD诊断的参考依据。
aMCI患者痰浊证的MMSE量表得分与左内侧颞叶的NAA/Cr、NAA/mI明显正相关,而肾虚组的MMSE量表得分与右内侧颞叶的NAA/mI明显正相关。不同证型aMCI出现代谢异常变化的部位可能不同,痰浊证以累及左内侧颞叶为主,肾虚证以累及右内侧颞叶为主。认知功能异常的中医证侯特征与代谢组学方法结合的研究,将成为今后的重要研究方向之一。
Objective:Using MR to find the relativity between the changes of 1H magnetic resonance spectroscopy (1H-MRS),structure of brain in aMCI, AD patients and normal control group.These can be used as an assistant tool to diagnosis aMCI and AD in early stage,to differential diagnosis,and to monitor the develop of disease.
Methods:Normal scanning,1H-MRS and Hippocampus volume measurements of VOI are acquired by siemens Novus 1.5T MRI system.
Single voxel 1H-MRS examination:using single voxel sequence of SVS-SE-30 sequence, the acquisition voxel size in medial temporal lobe is 1.2×1.2×1.2(cm3), the acquisition voxel size in left posterior cingulate is 1.5×1.5×1.5(cm3), TR 1500ms, TE 30ms, interval time(TM) is 13.7ms,256 samples,8-phase cycle, bandwidth 2500Hz.. N-acetyl aspartate (NAA), choline (Cho) and myo-inositol (mI) and creatine (Cr) was measured, and calculate the ratio of NAA/Cr, NAA/ml and ml/Cr.
Hippocampal volume measurement:location on the basis of the routine scan of hippocampus. IR-PDWI-Tfl3D sequence was taken in the oblique-coronal position of hippocampal long axis:TI 1100ms; TR 1830ms; TE 3.93ms; scanning:three times, slice thickness 1.2 mm, FOV 25CM, matrix 256×256, continuous scanning with no interval. Scan range:including amygdala, anterior and posterior horn of lateral ventricle.
Comparing difference of the ratio of NAA/Cr, NAA/mI, Cho/Cr, mI/Cr in these three groups (NC, aMCI and AD).analysis of the correlation of metabolite ratios and cognitive function,comparison the differences of hippocampal volume in each group, the relevance of metabolite ratios and hippocampal volume,the Features of metabolite of two major type symptoms of TCM (Shenjingkuixu, Tanzhuo)are all included.
Results:
1.NAA/Cr of left medial temporal lobe in aMCI and AD groups were lower than NC group with statistical significance(P<0.05), AD group and the aMCI group has not statistically significant difference (P>0.05); NAA/ml in aMCI and AD group lower than NC group with statistically significance(P<0.05), There was not statistically significant differdnce in AD group and the aMCI group (P>0.05). NAA/mI of right medial temporal lobe in AD and aMCI group lower than NC group with statistically significant (P<0.05).There are no statistical significance difference of NAA/Cr, Cho/Cr, ml/Cr and NAA/mI located in left posterior cingulate gyrus of aMCI, AD and NC groups. Metabolites asymmetry index of two sides of medial temporal lobe of aMCI group and NC group was statistically significant difference (p<0.05), metabolites asymmetry index of other position have no significant difference.
2. (1) relevance of MMSE score and 1H-MRS of aMCI, AD Group:NAA/ Cr located in left posterior cingulate gyrus was negative-related (r=-0.709, (P <0.05) with MMSE in aMCI group, while there was no significant correlation with other metabolic. (2) relevance of DSR scales and 1H-MRS of aMCI and AD group, the NAA/Cr of left medial temporal lobe was positively correlated with DSR(r= 0.648, P<0.05) in aMCI, the NAA/mI of the left posterior cingulate gyrus were positively correlated (r= 0.673, P<0.05)with DSR in AD group, (3) relevance between ISR score and 1H-MRS in aMCI and AD Group:NAA/Cr were positively correlated with ISR in left medial temporal lobe of aMCI group (r= 0.629, P= 0.051), and Cho/Cr were positively correlated with ISR (r= 0.660, P<0.05), the NAA/mI in the left posterior cingulate gyrus of positive correlate with ISR in AD group (r= 0.658, P<0.05).
3.comparation hippocampal volume among three groups:both sides of the hippocampal volume in AD group was significant differdent with NC and aMCI group (p<0.05).There is no significant difference in NC and aMCI groups on both sides of hippocampal volume (p>0.05); both sides of hippocampal volume of AD and aMCI groups did not significantly associated with the metabolite ratios in these three position.
4. NAA/Cr and MMSE has positive correlation in the left medial temporal lobe of the Tanzhuo group (r= 0.498, P<0.05); NAA/mI and MMSE has positive correlation (r=0.462, P<0.05),while this correlation was not exist in right medial the temporal lobe; NAA/mI were positively correlated (r=0.585, P<0.05)with MMSE in the right medial temporal lobe of the Shenjingkuixu group, but not exist in the left medial temporal.
Conclusion:The study found that hippocampal volume measurement has important value in identifying aMCI and AD,1H-MRS have a relatively high sensitivity in detection and identification of aMCI and NC.Combining these two kinds of Methods can monitoring pathology change of the course of NC→aMCI→AD and it is the best choice to identify aMCI and AD.
DSR and ISR have relevance with NAA/Cr in the left medial temporal lobe, DSR is more Significantly, in these three kinds of scales MMSE(mini-mental state examination), DSR (delayed story recall), and ISR(instant story story recall). It suggest that delayed story recall (DSR) can be used to diagnosis aMCI and mild AD. NAA/mI,NAA/Cr in the left posterior cingulate gyrus closely associated with AD suggesting it can be used as reference for the diagnosis of AD.
The study found that NAA/Cr, NAA/ml in left medial temporal lobe has positive correlation with MMSE in the Tanzhuo group, while NAA/ml in right medial temporal lobe has significant positive correlation with MMSE in the Shenjingkuixu group. Metabolism changes in different TCM type of aMCI. Which obviously involved in the left medial temporal lobe in the Tanzhuo group, involved in the right medial temporal lobe in the Shenjingkuixu. The study of combining metabolic and syndromes in Chinese medicine in cognitive dysfunction patients, will become an important research direction in the future.
方法：采用德国SIEMENS公司生产的Novu s 1.5T磁共振成像系统,对入选的研究对象行相应的常规MRI扫描,脑内感兴趣区的1H-MRS采集和／或海马体积扫描.
单体素1H-MRS检查：采用单体素序列为SVS-SE-30序列,双内侧颞叶的采集体素大小为1.2×1.2×1.2(cm3),左后扣带回体素大小为1.5×1.5×1.5(cm3), TR 1500ms,TE 30ms,间隔时间(TM)13.7ms,256次采样,8次相位循环,频宽2500Hz.。测得这些部位的N-乙酰天门冬氨酸(NAA),胆碱(Cho)和肌醇(mI)与肌酸(Cr)的值,并计算其各自相应的比值,包括NAA/Cr, NAA/mI,Cho/Cr及mI/Cr.
海马体积的测定：在常规扫描的基础上对海马进行定位,并行垂直于海马长轴的斜冠状IR-PDWI-Tf 13D序列扫描：TI 1100ms；TR 1830ms；TE 3.93ms；采集次数3次、层厚1.2 mm. FOV 25 cm.矩阵256×256,无间隔连续扫描。扫描范围包括杏仁核前部及侧脑室后角。
比较NC. aMC I和AD各组间NAA/Cr, NAA/mI, Cho/Cr, mI/Cr比值的差别,并分析各代谢物比值与认知功能的相关性,比较各组间海马体积的差别及与各部位代谢物比值的相关性,同时基于核磁共振代谢组学分析方法,探讨aMCI两个主要证型(肾虚证,痰浊证)的1H-MRS代谢物比值的相关特征。
结果：
1.左内侧颞叶aMCI和AD组的NAA/Cr均明显低于NC组(P＜0.05),AD组与aMCI组比较无显著性改变(P>0.05);aMC I组和AD组的NAA/mI低于NC组(P＜0.05),AD组与aMCI组比较无显著变化(P＞0.05)。右内侧颞叶AD组和aMCI的NAA/mI显著低于NC组(P<0.05)。aMCI. AD和NC组左扣带回后部NAA/Cr. Cho/Cr. mI/Cr及NAA/mI差异均无显著变化。双内侧颞叶aMCI组与Nc组代谢物不对称指数比较发现,aMCI组与Nc组有显著改变(p<0.05.),余代谢物比值差异无显著变化(P>0.05)。
2.(1)aMCI.AD组的MMSE评分与1H-MRS相关性：aMCI组与左后扣带回NAA/Cr呈负相关(r=-0.709,(P＜0.05),而与其它代谢物比值无明显相关。(2)aMCI和AD组的DSR评分与1H-MRS相关性：aMCI组与左内侧颞叶NAA/Cr呈正相关(r=0.648,P<0.05), AD组与左后扣带回的NAA/mI呈正相关(r=0.673,P<0.05),(3)aMCI和AD组的ISR评分与1H-MRS相关性：aMCI组与左内侧颞叶NAA/Cr有正相关趋势((r=0.629,P=0.051),与Cho/Cr正相关(r=0.660,P<0.05),AD组与左后扣带回的NAA/mI呈正相关(r=0.658,P<0.05)。
3.三组双侧校正后海马体积比较,NC. aMCI组和AD组两侧海马体积比较差异有显著改变(p<0.05),NC和aMCI组的两侧海马体积差异无显著改变(p>0.05)；AD组与aMCI组各自的左右侧海马体积与三个部位的代谢物比值无明显相关。
4. aMCI患者痰浊组左内侧颞叶代谢物NAA/Cr与MMSE正相关(r=0.498,P<0.05)；NAA/mI与MMSE正相关(r=0.462,P<0.05)；而与右内侧颞叶各代谢物比值无明显相关；aMCI患者肾虚组的MMSE与右内侧颞叶NAA/mI呈正相关(r=0.585,P<0.05),而与左内侧颞叶各代谢物比值无明显相关。
结论：
本研究发现海马体积测定在鉴别诊断aMCI和AD有重要价值,1H-MRS诊断及鉴别aMCI和NC有相对高的敏感性,两者结合对NC→aMCI→AD的病程追踪和病理的演变的监测相互补充,同时也是aMCI和AD诊断、鉴别诊断的最佳选择。
在对aMCI和AD的认知功能测评中,三个神经心理学量表(简易精神状态检查)MMSE、(延迟故事回忆)DSR及(即刻故事回忆)ISR中, DSR及ISR与左内侧颞叶的NAA/Cr有相关性,而以DSR的相关性最明显,提示延迟故事回忆(DSR)与脑影像学检查结合可作为aMCI和AD早期诊断及鉴别的重要辅助工具,左后扣带回的NAA/mI,及NAA/Cr与AD关联密切,可作为AD诊断的参考依据。
aMCI患者痰浊证的MMSE量表得分与左内侧颞叶的NAA/Cr、NAA/mI明显正相关,而肾虚组的MMSE量表得分与右内侧颞叶的NAA/mI明显正相关。不同证型aMCI出现代谢异常变化的部位可能不同,痰浊证以累及左内侧颞叶为主,肾虚证以累及右内侧颞叶为主。认知功能异常的中医证侯特征与代谢组学方法结合的研究,将成为今后的重要研究方向之一。
Objective:Using MR to find the relativity between the changes of 1H magnetic resonance spectroscopy (1H-MRS),structure of brain in aMCI, AD patients and normal control group.These can be used as an assistant tool to diagnosis aMCI and AD in early stage,to differential diagnosis,and to monitor the develop of disease.
Methods:Normal scanning,1H-MRS and Hippocampus volume measurements of VOI are acquired by siemens Novus 1.5T MRI system.
Single voxel 1H-MRS examination:using single voxel sequence of SVS-SE-30 sequence, the acquisition voxel size in medial temporal lobe is 1.2×1.2×1.2(cm3), the acquisition voxel size in left posterior cingulate is 1.5×1.5×1.5(cm3), TR 1500ms, TE 30ms, interval time(TM) is 13.7ms,256 samples,8-phase cycle, bandwidth 2500Hz.. N-acetyl aspartate (NAA), choline (Cho) and myo-inositol (mI) and creatine (Cr) was measured, and calculate the ratio of NAA/Cr, NAA/ml and ml/Cr.
Hippocampal volume measurement:location on the basis of the routine scan of hippocampus. IR-PDWI-Tfl3D sequence was taken in the oblique-coronal position of hippocampal long axis:TI 1100ms; TR 1830ms; TE 3.93ms; scanning:three times, slice thickness 1.2 mm, FOV 25CM, matrix 256×256, continuous scanning with no interval. Scan range:including amygdala, anterior and posterior horn of lateral ventricle.
Comparing difference of the ratio of NAA/Cr, NAA/mI, Cho/Cr, mI/Cr in these three groups (NC, aMCI and AD).analysis of the correlation of metabolite ratios and cognitive function,comparison the differences of hippocampal volume in each group, the relevance of metabolite ratios and hippocampal volume,the Features of metabolite of two major type symptoms of TCM (Shenjingkuixu, Tanzhuo)are all included.
Results:
1.NAA/Cr of left medial temporal lobe in aMCI and AD groups were lower than NC group with statistical significance(P<0.05), AD group and the aMCI group has not statistically significant difference (P>0.05); NAA/ml in aMCI and AD group lower than NC group with statistically significance(P<0.05), There was not statistically significant differdnce in AD group and the aMCI group (P>0.05). NAA/mI of right medial temporal lobe in AD and aMCI group lower than NC group with statistically significant (P<0.05).There are no statistical significance difference of NAA/Cr, Cho/Cr, ml/Cr and NAA/mI located in left posterior cingulate gyrus of aMCI, AD and NC groups. Metabolites asymmetry index of two sides of medial temporal lobe of aMCI group and NC group was statistically significant difference (p<0.05), metabolites asymmetry index of other position have no significant difference.
2. (1) relevance of MMSE score and 1H-MRS of aMCI, AD Group:NAA/ Cr located in left posterior cingulate gyrus was negative-related (r=-0.709, (P <0.05) with MMSE in aMCI group, while there was no significant correlation with other metabolic. (2) relevance of DSR scales and 1H-MRS of aMCI and AD group, the NAA/Cr of left medial temporal lobe was positively correlated with DSR(r= 0.648, P<0.05) in aMCI, the NAA/mI of the left posterior cingulate gyrus were positively correlated (r= 0.673, P<0.05)with DSR in AD group, (3) relevance between ISR score and 1H-MRS in aMCI and AD Group:NAA/Cr were positively correlated with ISR in left medial temporal lobe of aMCI group (r= 0.629, P= 0.051), and Cho/Cr were positively correlated with ISR (r= 0.660, P<0.05), the NAA/mI in the left posterior cingulate gyrus of positive correlate with ISR in AD group (r= 0.658, P<0.05).
3.comparation hippocampal volume among three groups:both sides of the hippocampal volume in AD group was significant differdent with NC and aMCI group (p<0.05).There is no significant difference in NC and aMCI groups on both sides of hippocampal volume (p>0.05); both sides of hippocampal volume of AD and aMCI groups did not significantly associated with the metabolite ratios in these three position.
4. NAA/Cr and MMSE has positive correlation in the left medial temporal lobe of the Tanzhuo group (r= 0.498, P<0.05); NAA/mI and MMSE has positive correlation (r=0.462, P<0.05),while this correlation was not exist in right medial the temporal lobe; NAA/mI were positively correlated (r=0.585, P<0.05)with MMSE in the right medial temporal lobe of the Shenjingkuixu group, but not exist in the left medial temporal.
Conclusion:The study found that hippocampal volume measurement has important value in identifying aMCI and AD,1H-MRS have a relatively high sensitivity in detection and identification of aMCI and NC.Combining these two kinds of Methods can monitoring pathology change of the course of NC→aMCI→AD and it is the best choice to identify aMCI and AD.
DSR and ISR have relevance with NAA/Cr in the left medial temporal lobe, DSR is more Significantly, in these three kinds of scales MMSE(mini-mental state examination), DSR (delayed story recall), and ISR(instant story story recall). It suggest that delayed story recall (DSR) can be used to diagnosis aMCI and mild AD. NAA/mI,NAA/Cr in the left posterior cingulate gyrus closely associated with AD suggesting it can be used as reference for the diagnosis of AD.
The study found that NAA/Cr, NAA/ml in left medial temporal lobe has positive correlation with MMSE in the Tanzhuo group, while NAA/ml in right medial temporal lobe has significant positive correlation with MMSE in the Shenjingkuixu group. Metabolism changes in different TCM type of aMCI. Which obviously involved in the left medial temporal lobe in the Tanzhuo group, involved in the right medial temporal lobe in the Shenjingkuixu. The study of combining metabolic and syndromes in Chinese medicine in cognitive dysfunction patients, will become an important research direction in the future.
引文
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