阻塞性睡眠呼吸暂停综合征病人脑组织结构及代谢改变MRI评价
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摘要
目的：
探讨VBM、扩散加权成像ADC图及MRS在评价OSAS脑结构及代谢改变中的价值。
材料和方法：
OSAS重度组(AHI>40次/小时)21例、OSAS轻中度组(5次/小时 扫描方法为：1.T1WI-RF-FAST序列容积扫描(扫描参数：TR/TE=12 ms/4.5 ms,视野FOV 25 cm2,层厚1.2 mm,间隔0 mm,矩阵256×256,采集次数1次,FLIP 20°)。2.扩散加权像SE-EPI-DWI的横断面扫描(扫描参数：TR/TE=6000 ms/94.9 ms,层厚5.0mm,间隔1 mm,矩阵100×100,翻转角90°,1次激励,b=0 s/mm2和b=1000 s/mm2)。3.所有受试者在双侧额叶及左侧颞-顶-枕叶交界区(兴趣区20mmx20mmx20mm)、左侧海马(兴趣区15mmx15mmx20mm)行单体素氢质子波谱—点分辨自旋回波波谱序列(point-resolved echo spin spectroscopy, PRESS)扫描(扫描参数：TR/TE=1500ms/35ms,翻转角900,采集次数为192次)。
统计学分析：1.采用VBM1.5 toolkit进行单因素方差分析。采用p<0.01(FDR校正),或p<0.0001(未校正),体素大于50为差别具有统计学意义。2.获得ADC图后,在SPM5软件上进行图像的分析。采用单因素方差分析寻找两组间差异,采用t检验观察差异的方向性,阈值为p<0.001(未校正),体素大于50个认为有统计学意义。3.MRS所测数据采用SPSS13软件进行统计分析与处理,主要的统计学方法包括,方差齐性检验,方差齐性数据采用方差分析及benoffen校正多重比较,方差不齐数据采用多组独立样本的秩和检验,P<0.05为有统计学意义。
结果：
1.VBM测量显示：(1)在总体积测量中,灰质总体积OSAS轻中度组(p=0.24)及OSAS重度组(P=0.32)小于健康对照组,提示：OSAS病人组脑灰质总体积缩小较其他成份改变明显。(2).在各脑区的测量中,在以双侧额叶、边缘叶、颞中回、楔前叶及小脑为主的脑区,①灰质密度及体积OSAS病人组小于健康对照组,OSAS轻中度组小于OSAS重度组,考虑OSAS病人有神经元的丢失及胶质细胞的增生；②白质密度及体积除脑干区OSAS重度组小于健康对照组外,其它脑区OSAS病人组均大于健康对照组,OSAS轻中度组大于重度组,考虑OSAS病人有白质轴索损伤及胶质细胞的增生、肥大并在此基础上进一步出现白质稀疏。
2.ADC图分析显示：(1)OSAS轻中度组ADC值较健康对照组升高主要发生于以灰质为主的脑区,此结果与VBM测量所推测的OSAS轻中度时灰质发生轻度神经原丢失,造成灰质细胞间隙增大,而白质此期多处于胶质细胞的增生、肥大阶段的假设相符合；(2) OSAS重度组ADC值较健康对照组升高发生于以以右侧额叶、左侧楔前叶及双侧小脑前叶脑区为主的灰质和白质,且胼胝体右侧枕钳ADC值也明显升高,此结果与VBM测量所推测的OSAS重度时,灰质神经元进一步丢失、胶质细胞增生及白质内在胶质细胞增生、肥大基础上发生白质稀疏的假设相对应；(3)OSAS重度组脑干区ADC值较轻中度组增高,且VBM显示OSAS病人脑干白质密度小于健康对照组、脑干白质体积OSAS重度组小于轻中度组,提示OSAS病人组脑干区有微观结构上的改变。
3.(1)左侧额叶NAA/CrOSAS重度组明显小于健康对照组(F=6.003,p=0.004)；右侧额叶NAA/Cr, OSAS轻中度组及重度组均小于健康对照组(χ2=11.677,p=0.003)；另外,OSAS病人组左侧海马NAA/Cr较健康对照组差异虽无统计学意义,但显示有减低的趋势,提示OSAS病人组神经元的减少以双侧额叶为主,且首先发生于右侧额叶,额叶的改变先于海马区的改变；(2)右侧额叶MI/Cr, OSAS轻中度组及重度组均大于健康对照组(χ2=16.518,p=0.000),提示OSAS病人有神经胶质细胞的增生；(3)左侧额叶Glx/CrOSAS重度组明显小于健康对照组(F=4.381,p=0.019),右侧额叶Glx/CrOSAS重度组较健康对照组差异虽无统计学意义,但显示有减低的趋势,这与重度OSAS病人兴奋性低、反应能力差等的临床症状相吻合。
结论：VBM测量、应用SPM分析软件的ADC图及MRS对显示OSAS引起的脑组织结构的改变是敏感的,在评价OSAS脑部病变中起重要作用。
Objective:
To study the changes of cerebral structure in patients of obstructive sleep apnea syndrome (OSAS) by using voxel-based morphometry (VBM), ADC map and magnetic resonance spectroscopy (MRS).
Materials and methods:
21 severe OSAS (AHI> 40/h) patients,14 mild-moderate OSAS (5/h Scanning parameter:1.T1 WI-RF-FAST sequence (TR/TE=12 ms/4.5ms, FOV 25 cm2, thickness 1.2 mm, interval 0m, matrix 256*256, FLIP 20°). VBM was calculated on SPM5 (statistic parameter mapping 5).2.SE-EPI-DWI (TR/TE=6000 ms/94.9 ms, thickness 5.0 mm, interval 1 mm, matrix 100x100, FLIP 90°, b=1000 s/mm2). All the ADC maps were calculated on SPM5.3. the MRS by using the point-resolved echo spin spectroscopy (PRESS) (TR/TE=1500ms/35ms, FLIP 90°). Proton volumes of interest (VOIs) were placed in the bilateral frontal lobes and left temporal-parietal-occipital cortex.(VOI:20mmx20mm><20mm), left hippocampus(VOI:15mmxl5mmx20mm). NAA, Cho, Mi, Glx/Gln were calculated.
Results:
l.VBM showed:(1)The bulk volume of gray matter (GM) showed decreased in OSAS patients. It indicated changes of GM was more sensitive than other structure. (2)In separate encephalic region:①The density and volume of GM in OSAS patients reduced compared to the control group.In the mild-moderate OSAS group, the density and volume of GM reduced could be related to neural loss, only. In the severe OSAS group, the reduced density and volume of GM could be related to neural loss and reactive gliosis.②There was increased in the density and volume of white matter (WM) in OSAS patients, the mild-moderate OSAS group was higher than the severe OSAS group. Increase in the density and volume of WM could be interpreted as hyperplasia. Decrease in the density and volume of WM in the severe OSAS group could be interpreted as evidence of WM rarefaction, respectively, secondary to repeated episodes of hypoxia in OSAS.
2.ADC map showed:(1)The increase of ADC value was seen mostly in GM in the mild-moderate OSAS group. It was corresponded with VBM, which had neural loss only at this time. (2)The increase of ADC value was found in GM and WM in the severe OSAS group. The changes was mainly located in right frontal lobe, left precuneus, both side of anterior lobe of cerebellum, and right occipital forceps. The manifestation was accorded with neural loss and reactive gliosis in GM,and rarefaction in WM.3. Changes in the brain stem was detected on both ADC map and VBM, indicating microstructural pathology.
3. (1)Significantly lower values of the N-acetylaspartate (NAA)/creatine (Cr) ratio (F=6.003, p=0.004) was found in left frontal lobe in the severe OSAS group compared to controls. In the right frontal lobe, NAA/Cr X2=11.677,P=0.003) ratio was also showed reduced in the OSAS patients. The apparence could be related to neural loss. (2)A significant increase in the myo-inositol (mI)/Cr ratio X2=16.518, p=0.000) was evident in right frontal regions. It could be interpreted as evidence of reactive gliosis, consequent to repeated episodes of hypoxia in OSAS. (3)Glutamine-glutamite (Glx/Gln)/Cr ratio (F=4.381, p=0.019) values were also significantly smaller in left frontal regions. It was coincidence with clinical apparence.
Conclusion:. VBM, ADC map and MRS were sensitive in evaluating cerebral structural changes in OSAS patients.
探讨VBM、扩散加权成像ADC图及MRS在评价OSAS脑结构及代谢改变中的价值。
材料和方法：
OSAS重度组(AHI>40次/小时)21例、OSAS轻中度组(5次/小时
统计学分析：1.采用VBM1.5 toolkit进行单因素方差分析。采用p<0.01(FDR校正),或p<0.0001(未校正),体素大于50为差别具有统计学意义。2.获得ADC图后,在SPM5软件上进行图像的分析。采用单因素方差分析寻找两组间差异,采用t检验观察差异的方向性,阈值为p<0.001(未校正),体素大于50个认为有统计学意义。3.MRS所测数据采用SPSS13软件进行统计分析与处理,主要的统计学方法包括,方差齐性检验,方差齐性数据采用方差分析及benoffen校正多重比较,方差不齐数据采用多组独立样本的秩和检验,P<0.05为有统计学意义。
结果：
1.VBM测量显示：(1)在总体积测量中,灰质总体积OSAS轻中度组(p=0.24)及OSAS重度组(P=0.32)小于健康对照组,提示：OSAS病人组脑灰质总体积缩小较其他成份改变明显。(2).在各脑区的测量中,在以双侧额叶、边缘叶、颞中回、楔前叶及小脑为主的脑区,①灰质密度及体积OSAS病人组小于健康对照组,OSAS轻中度组小于OSAS重度组,考虑OSAS病人有神经元的丢失及胶质细胞的增生；②白质密度及体积除脑干区OSAS重度组小于健康对照组外,其它脑区OSAS病人组均大于健康对照组,OSAS轻中度组大于重度组,考虑OSAS病人有白质轴索损伤及胶质细胞的增生、肥大并在此基础上进一步出现白质稀疏。
2.ADC图分析显示：(1)OSAS轻中度组ADC值较健康对照组升高主要发生于以灰质为主的脑区,此结果与VBM测量所推测的OSAS轻中度时灰质发生轻度神经原丢失,造成灰质细胞间隙增大,而白质此期多处于胶质细胞的增生、肥大阶段的假设相符合；(2) OSAS重度组ADC值较健康对照组升高发生于以以右侧额叶、左侧楔前叶及双侧小脑前叶脑区为主的灰质和白质,且胼胝体右侧枕钳ADC值也明显升高,此结果与VBM测量所推测的OSAS重度时,灰质神经元进一步丢失、胶质细胞增生及白质内在胶质细胞增生、肥大基础上发生白质稀疏的假设相对应；(3)OSAS重度组脑干区ADC值较轻中度组增高,且VBM显示OSAS病人脑干白质密度小于健康对照组、脑干白质体积OSAS重度组小于轻中度组,提示OSAS病人组脑干区有微观结构上的改变。
3.(1)左侧额叶NAA/CrOSAS重度组明显小于健康对照组(F=6.003,p=0.004)；右侧额叶NAA/Cr, OSAS轻中度组及重度组均小于健康对照组(χ2=11.677,p=0.003)；另外,OSAS病人组左侧海马NAA/Cr较健康对照组差异虽无统计学意义,但显示有减低的趋势,提示OSAS病人组神经元的减少以双侧额叶为主,且首先发生于右侧额叶,额叶的改变先于海马区的改变；(2)右侧额叶MI/Cr, OSAS轻中度组及重度组均大于健康对照组(χ2=16.518,p=0.000),提示OSAS病人有神经胶质细胞的增生；(3)左侧额叶Glx/CrOSAS重度组明显小于健康对照组(F=4.381,p=0.019),右侧额叶Glx/CrOSAS重度组较健康对照组差异虽无统计学意义,但显示有减低的趋势,这与重度OSAS病人兴奋性低、反应能力差等的临床症状相吻合。
结论：VBM测量、应用SPM分析软件的ADC图及MRS对显示OSAS引起的脑组织结构的改变是敏感的,在评价OSAS脑部病变中起重要作用。
Objective:
To study the changes of cerebral structure in patients of obstructive sleep apnea syndrome (OSAS) by using voxel-based morphometry (VBM), ADC map and magnetic resonance spectroscopy (MRS).
Materials and methods:
21 severe OSAS (AHI> 40/h) patients,14 mild-moderate OSAS (5/h
Results:
l.VBM showed:(1)The bulk volume of gray matter (GM) showed decreased in OSAS patients. It indicated changes of GM was more sensitive than other structure. (2)In separate encephalic region:①The density and volume of GM in OSAS patients reduced compared to the control group.In the mild-moderate OSAS group, the density and volume of GM reduced could be related to neural loss, only. In the severe OSAS group, the reduced density and volume of GM could be related to neural loss and reactive gliosis.②There was increased in the density and volume of white matter (WM) in OSAS patients, the mild-moderate OSAS group was higher than the severe OSAS group. Increase in the density and volume of WM could be interpreted as hyperplasia. Decrease in the density and volume of WM in the severe OSAS group could be interpreted as evidence of WM rarefaction, respectively, secondary to repeated episodes of hypoxia in OSAS.
2.ADC map showed:(1)The increase of ADC value was seen mostly in GM in the mild-moderate OSAS group. It was corresponded with VBM, which had neural loss only at this time. (2)The increase of ADC value was found in GM and WM in the severe OSAS group. The changes was mainly located in right frontal lobe, left precuneus, both side of anterior lobe of cerebellum, and right occipital forceps. The manifestation was accorded with neural loss and reactive gliosis in GM,and rarefaction in WM.3. Changes in the brain stem was detected on both ADC map and VBM, indicating microstructural pathology.
3. (1)Significantly lower values of the N-acetylaspartate (NAA)/creatine (Cr) ratio (F=6.003, p=0.004) was found in left frontal lobe in the severe OSAS group compared to controls. In the right frontal lobe, NAA/Cr X2=11.677,P=0.003) ratio was also showed reduced in the OSAS patients. The apparence could be related to neural loss. (2)A significant increase in the myo-inositol (mI)/Cr ratio X2=16.518, p=0.000) was evident in right frontal regions. It could be interpreted as evidence of reactive gliosis, consequent to repeated episodes of hypoxia in OSAS. (3)Glutamine-glutamite (Glx/Gln)/Cr ratio (F=4.381, p=0.019) values were also significantly smaller in left frontal regions. It was coincidence with clinical apparence.
Conclusion:. VBM, ADC map and MRS were sensitive in evaluating cerebral structural changes in OSAS patients.
引文
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