儿童屈光不正性弱视视中枢功能激活的fMRI研究
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摘要
目的：临床上普遍认为弱视治愈后继续坚持治疗1～2年为弱视治疗的终点,然而,很多病例仍然出现了视力回退。因此,何时才是弱视治疗的真正终点?,这个问题是一个很具有实际意义的提问,可指导临床更好地防治弱视的复发。但以往的各项研究措施无法很好的应用于弱视儿童,fMRI技术在探测活体大脑皮层对视觉运动刺激的激活方面具有无创、准确、快速等优点,能很好的评价弱视治疗过程中大脑视觉中枢对视觉刺激的反应差异,在中枢水平对弱视进行更进一步的研究。本研究采用3.OT高场强超导型功能磁共振成像(Blood-oxygenation level dependent functional MRI, fMRI)技术,评价屈光不正性弱视儿童在规范弱视训练后,大脑皮层视中枢功能重建的情况。
材料与方法：初诊屈光不正性弱视患儿9例(男5例,女4例),年龄7.2～11岁,平均(9.1±1.90)岁。均为中度屈光不正性弱视,球镜屈光度范围在-6.50D～-7.75D、+4.00D～+5.OOD,柱镜度数在-2.25D～-3.00D、+2.00D～+2.50D。所有被试无特殊眼部疾病及神经系统病史；MRI检查时排除由视网膜至外侧膝状体核间的疾病。所有被试均为远视性弱视,中心凹注视,右利手。规范弱视治疗后1周、2周及1月时定期复查功能磁共振检查。
实验数据由IEMENS MAGNETOM Verio3T超导型磁共振扫描系统获取。视觉刺激呈现采用脑功能视听觉刺激系统(SAMRTEC, SA-9900).任务设计程序均采用E-Prime2.0(Psychology Software Tools Inc.)软件编写。MRI扫描启动时的射频脉冲触发与刺激系统相连的同步系统,刺激模式采用对比度接近100%的旋转圆环形黑白棋盘格,频率为8Hz,背景为棋盘格的平均亮度。采用Block设计方案,共扫描3min38s,分两个组块：激活状态和控制状态,每个状态组块持续时间为21s,此期间共有7次采集,两种组块交替进行,每个组块共重复5次。为避免磁饱和效应的影响,先用控制状态预扫描8s,不记录其数据,总有效扫描时间210s、得36幅功能图像。
数据处理采用基于MATLAB7.12(The MathWorks, Inc.)的SPM8(Statistical Parametric Mapping)软件包进行离线处理。首先对数据进行预处理,包括进行头动校正、配准、分割、标准化及高斯空间平滑处理。将SPM的MNI坐标系统转换为Talairach标准坐标,进行功能区定位。阈值设定为P<0.005,未多重校正；对被试在治疗前及治疗后1周、2周及4周时相关脑皮层激活范围及强度的差异进行自身前后配对t检验。
结果：弱视训练1周时,无显著性激活差异；2周时,双侧枕叶(右侧BA18区Mean T=1.2361;左侧BA18区Mean T=1.5211；右侧BA19区Mean T=1.6845;左侧BA19区Mean T=1.5917, P<0.005)激活强度增加,视觉联合区,即V5区(右侧BA37区激活.Mean T=1.2014;右侧BA21区激活、Man T=1.1450,P<0.005)开始激活,至第4周时,激活范围及程度较前下降(右侧BA18区Mean T=1.0024;左侧BA18区Mean T=1.7431;右侧BA19区Mean T=1.2253；左侧BA19区MeanT=1.1813,P<0.005)。
结论：
1.儿童屈光不正性弱视对视中枢的功能损害较严重。
2.中颞区的功能恢复困难于初级视中枢。
3.大龄儿童屈光不正性弱视在功能训练早期,重建视中枢视觉运动觉功能较困难,且不稳定。
Objective:It's generally suggested that continue to treatment1～2years for the end point of the treatment of amblyopia after amblyopia cure clinically, however, many cases still appeared vision back. So, when is the real end of amblyopia treatment?, this problem is a very practical questions, it can guide clinical better to prevent and cure recurrence of amblyopia. But previous studies hadn't very well applied to children with amblyopia, fMRI technology possessed non-invasive, accurate and fast, it can be a very good to evaluate the response difference about the visual central reacted to visual stimuli when children were cured. This study used3.0T high field strength and superconducting type functional magnetic resonance imaging (fMRI) technology to evaluate the functional reconstruction about the visual cortex, after children with ametropic amblyopic were trainied in the standardization.To research the recovery of the visual cortical function mediating visual motion perception in ametropic amblyopia after regular amblyopia treatment using3.0Tesla functional MRI (fMRI).
Methods:In this study,9children with ametropic amblyopia aged from7.2to11years for the first time, five males and four females, average age was9.1±1.90years; all were moderate ametropic amblyopia, the spherical equivalent range was-6.50D～-7.75D,+4.00D～+5.00D and spherical cylindrical range was-2.25D～-3.00D,+2.00D～+2.50D. They didn't have eye and neurologica disease except for amblyopia. All were not have any disease that was from retina to corpus geniculatum laterale after MRI inspection. They were all hyperopic amblyopia, central vision type and right handedness. Review fMRI inspection after regular amblyopia treatment one week, two weeks and one month.
Data were acquired by SIEMENS MAGNETOM Verio3.0Tesla MR imaging system, carried out by the visual stimulus system (SAMRTEC, SA-9900). Visual stimulus was designed using E-Prime2.0(Psychology Software Tools Inc.). When MRI system scanning activated, the radio frequency pulse triggered synchronization systems which connected to stimulation system. The contrast ratio of the rotating checkerboard was approximate100%, and its frequency approach to8Hz, the average brightness of checkerboard for background. Blocks design mode was used by the activation state and control state composition, every state time was21s, and the scanning time was3min38s. During this time,7times data acquisition were collected, alternating between two state, each state repeated5times. To avoid the influence of magnetic saturation effect, used first control state to scanning8s, don't to record those data. The total effective scanning time was210s and36functional image data were acquired.
All data were processed offline by using the SPM8package (Statistical parametric mapping) which based on the MATLAB7.12(The Mathworks, Inc.). Fist, the pretreatment, it included realignment, coregister, segment, normalize, and gaussian space smooth. Next, the SPM's MN1coordinate system were transformed into Talairach standard coordinates, and the function orientation were carried out. At the last, The matrix data of each treatment stage were acquired by hypothesisdriven research, and before and after self-control study (matched t-test) was performed in each group to acquire average cerebral cortex activated functional images data. The different mapping between each group during visual motion stimulus was also acquired (set to Threshold P <0.005, and not multiple correction).
Results:When amblyopia treated one week, there was not significant differences between activation; The functional area that is bilateral occipital lobe (Mean T of the right BA18=1.2361; Mean T of the left BA18=1.5211; Mean T of the right BA19=1.6845; Mean T of the left BA19=1.5917, P<0.005) and the visual association area (V5)(The right BA37was activated and Mean T=1.2014; The right BA21was activated and Mean T=1.1450, P<0.005) expanded in different levels after amblyopia treatment two weeks; After four weeks, the bilateral occipital lobe (Mean T of the right BA18=1.0024; Mean T of the left BA18=1.7431; Mean T of the right BA19=1.2253; Mean T of the left BA19=1.1813, P<0.005) showed activation on the small area compare with two weeks ago.
Conclusion:(1) The function of visual central were damaged severely by the ametropic amblyopia.(2) The functional recovery of middle temporal area was more difficulty than other basic visual center.(3) In the early functional training of the older children's ametropic amblyopia, reconstruction the visual cortical function mediating visual motion perception was more difficulty and unstable.
材料与方法：初诊屈光不正性弱视患儿9例(男5例,女4例),年龄7.2～11岁,平均(9.1±1.90)岁。均为中度屈光不正性弱视,球镜屈光度范围在-6.50D～-7.75D、+4.00D～+5.OOD,柱镜度数在-2.25D～-3.00D、+2.00D～+2.50D。所有被试无特殊眼部疾病及神经系统病史；MRI检查时排除由视网膜至外侧膝状体核间的疾病。所有被试均为远视性弱视,中心凹注视,右利手。规范弱视治疗后1周、2周及1月时定期复查功能磁共振检查。
实验数据由IEMENS MAGNETOM Verio3T超导型磁共振扫描系统获取。视觉刺激呈现采用脑功能视听觉刺激系统(SAMRTEC, SA-9900).任务设计程序均采用E-Prime2.0(Psychology Software Tools Inc.)软件编写。MRI扫描启动时的射频脉冲触发与刺激系统相连的同步系统,刺激模式采用对比度接近100%的旋转圆环形黑白棋盘格,频率为8Hz,背景为棋盘格的平均亮度。采用Block设计方案,共扫描3min38s,分两个组块：激活状态和控制状态,每个状态组块持续时间为21s,此期间共有7次采集,两种组块交替进行,每个组块共重复5次。为避免磁饱和效应的影响,先用控制状态预扫描8s,不记录其数据,总有效扫描时间210s、得36幅功能图像。
数据处理采用基于MATLAB7.12(The MathWorks, Inc.)的SPM8(Statistical Parametric Mapping)软件包进行离线处理。首先对数据进行预处理,包括进行头动校正、配准、分割、标准化及高斯空间平滑处理。将SPM的MNI坐标系统转换为Talairach标准坐标,进行功能区定位。阈值设定为P<0.005,未多重校正；对被试在治疗前及治疗后1周、2周及4周时相关脑皮层激活范围及强度的差异进行自身前后配对t检验。
结果：弱视训练1周时,无显著性激活差异；2周时,双侧枕叶(右侧BA18区Mean T=1.2361;左侧BA18区Mean T=1.5211；右侧BA19区Mean T=1.6845;左侧BA19区Mean T=1.5917, P<0.005)激活强度增加,视觉联合区,即V5区(右侧BA37区激活.Mean T=1.2014;右侧BA21区激活、Man T=1.1450,P<0.005)开始激活,至第4周时,激活范围及程度较前下降(右侧BA18区Mean T=1.0024;左侧BA18区Mean T=1.7431;右侧BA19区Mean T=1.2253；左侧BA19区MeanT=1.1813,P<0.005)。
结论：
1.儿童屈光不正性弱视对视中枢的功能损害较严重。
2.中颞区的功能恢复困难于初级视中枢。
3.大龄儿童屈光不正性弱视在功能训练早期,重建视中枢视觉运动觉功能较困难,且不稳定。
Objective:It's generally suggested that continue to treatment1～2years for the end point of the treatment of amblyopia after amblyopia cure clinically, however, many cases still appeared vision back. So, when is the real end of amblyopia treatment?, this problem is a very practical questions, it can guide clinical better to prevent and cure recurrence of amblyopia. But previous studies hadn't very well applied to children with amblyopia, fMRI technology possessed non-invasive, accurate and fast, it can be a very good to evaluate the response difference about the visual central reacted to visual stimuli when children were cured. This study used3.0T high field strength and superconducting type functional magnetic resonance imaging (fMRI) technology to evaluate the functional reconstruction about the visual cortex, after children with ametropic amblyopic were trainied in the standardization.To research the recovery of the visual cortical function mediating visual motion perception in ametropic amblyopia after regular amblyopia treatment using3.0Tesla functional MRI (fMRI).
Methods:In this study,9children with ametropic amblyopia aged from7.2to11years for the first time, five males and four females, average age was9.1±1.90years; all were moderate ametropic amblyopia, the spherical equivalent range was-6.50D～-7.75D,+4.00D～+5.00D and spherical cylindrical range was-2.25D～-3.00D,+2.00D～+2.50D. They didn't have eye and neurologica disease except for amblyopia. All were not have any disease that was from retina to corpus geniculatum laterale after MRI inspection. They were all hyperopic amblyopia, central vision type and right handedness. Review fMRI inspection after regular amblyopia treatment one week, two weeks and one month.
Data were acquired by SIEMENS MAGNETOM Verio3.0Tesla MR imaging system, carried out by the visual stimulus system (SAMRTEC, SA-9900). Visual stimulus was designed using E-Prime2.0(Psychology Software Tools Inc.). When MRI system scanning activated, the radio frequency pulse triggered synchronization systems which connected to stimulation system. The contrast ratio of the rotating checkerboard was approximate100%, and its frequency approach to8Hz, the average brightness of checkerboard for background. Blocks design mode was used by the activation state and control state composition, every state time was21s, and the scanning time was3min38s. During this time,7times data acquisition were collected, alternating between two state, each state repeated5times. To avoid the influence of magnetic saturation effect, used first control state to scanning8s, don't to record those data. The total effective scanning time was210s and36functional image data were acquired.
All data were processed offline by using the SPM8package (Statistical parametric mapping) which based on the MATLAB7.12(The Mathworks, Inc.). Fist, the pretreatment, it included realignment, coregister, segment, normalize, and gaussian space smooth. Next, the SPM's MN1coordinate system were transformed into Talairach standard coordinates, and the function orientation were carried out. At the last, The matrix data of each treatment stage were acquired by hypothesisdriven research, and before and after self-control study (matched t-test) was performed in each group to acquire average cerebral cortex activated functional images data. The different mapping between each group during visual motion stimulus was also acquired (set to Threshold P <0.005, and not multiple correction).
Results:When amblyopia treated one week, there was not significant differences between activation; The functional area that is bilateral occipital lobe (Mean T of the right BA18=1.2361; Mean T of the left BA18=1.5211; Mean T of the right BA19=1.6845; Mean T of the left BA19=1.5917, P<0.005) and the visual association area (V5)(The right BA37was activated and Mean T=1.2014; The right BA21was activated and Mean T=1.1450, P<0.005) expanded in different levels after amblyopia treatment two weeks; After four weeks, the bilateral occipital lobe (Mean T of the right BA18=1.0024; Mean T of the left BA18=1.7431; Mean T of the right BA19=1.2253; Mean T of the left BA19=1.1813, P<0.005) showed activation on the small area compare with two weeks ago.
Conclusion:(1) The function of visual central were damaged severely by the ametropic amblyopia.(2) The functional recovery of middle temporal area was more difficulty than other basic visual center.(3) In the early functional training of the older children's ametropic amblyopia, reconstruction the visual cortical function mediating visual motion perception was more difficulty and unstable.
引文
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