1.帕金森病磁共振成像研究 2.术前语言功能磁共振成像技术在神经外科的应用

【作者】 张久权；

【导师】 冯华；

【作者基本信息】 第三军医大学 ， 外科学， 2010， 博士

【摘要】 研究目的和意义1.评估磁敏感加权成像技术在测量帕金森病脑部铁含量的可行性;2.探索脑部铁含量与帕金森病病情之间的关系。材料与方法1.受试者一般资料采集40例帕金森病患者和26例健康对照的脑部磁敏感加权成像数据。采用SPIN软件对相位像进行分析,获得帕金森病组和健康对照组的红核、黑质、尾状核、苍白球、壳核、丘脑和额叶白质相位改变数据,作为这些部位的铁含量值。在两组之间进行比较,并探索帕金森病患者这些感兴趣区铁含量与临床病情之间的相关性。2. MRI扫描方法所有MRI数据均采集于配置有八通道相控阵线圈的Siemens Trio 3.0T磁共振成像系统(Siemens Medical Systems, Erlangen, Germany)。扫描时,受试者头部采用泡沫垫固定于头线圈内。所有参与研究的健康志愿者和帕金森病患者均同时采集T1WI、T2WI、T2-weighted FLAIR和磁敏感加权成像图像。经T1WI、T2WI、T2-weighted FLAIR发现异常影像学表现的受试者排除出本研究。3.感兴趣区的确定将感兴趣区确定为红核、黑质、尾状核、苍白球、壳核、丘脑和额叶白质。所有的皮层下核团感兴趣区的确定均基于解剖学知识进行,额叶白质感兴趣区为圆形,不低于100个体素。4.铁含量的测定方法所有数据的处理均采用SPIN((signal processing in NMR))软件(http://www.mrc.wayne.edu/download.htm)完成。在进行感兴趣区的勾画之前将以感兴趣区为中心的图像部分放大16倍,在放大的磁敏感加权相位像上采用手动的方法勾画感兴趣区。由此得到各感兴趣区内的信号强度值的平均值和标准差。然后,将各个感兴趣区内的强度值转换为弧度值。采用此弧度值作为该感兴趣区的铁含量的推定值。5.统计学分析所有统计学分析均采用PASW Statistics 18软件(SPSS Inc., Chicago, Illinois, USA)进行。对于健康对照组不同感兴趣区左右之间铁含量的比较采用配对样本t检验;将健康对照组双侧感兴趣区铁含量左右平均后与以往文献中的数据进行Pearson相关分析;帕金森病受累明显侧与对侧对应感兴趣区之间的比较采用配对样本t检验;帕金森病患者受累明显侧与健康志愿者对应感兴趣区之间的比较采用独立样本t检验;帕金森病患者评价受累明显侧对应黑质区域铁含量分别与病程和UPDRS运动评分值之间的关系采用Pearson相关分析;早发型和晚发型帕金森病之间在黑质部位铁含量的关系和帕金森病不同性别之间黑质部位铁含量差异均采用独立样本t检验。以P<0.05为具有显著统计学差异。结果分析磁敏感加权成像技术所测得的相位位移值与先前文献中所报道的脑铁含量具有很好的相关性;帕金森病患者受累明显侧对应黑质部位铁含量显著增加,其他感兴趣区铁含量增加不明显。黑质部位铁含量增加量与病程长短之间不存在相关性,但是,与UPDRS运动评分呈显著相关。早发型和晚发型以及不同性别帕金森病黑质部位铁含量不存在显著差异。结论1.磁敏感加权成像技术所测得的相位位移值与先前文献中所报道的脑铁含量具有很好的相关性,是一种新的可靠的在体研究脑铁代谢异常相关疾病的无创手段。2.帕金森病患者受累明显侧对应黑质部位铁含量显著增加,其他感兴趣区铁含量增加不明显。黑质部位铁含量增加量与病程长短之间不存在相关性,但是与UPDRS运动评分呈显著相关。早发型和晚发型以及不同性别帕金森病黑质部位铁含量不存在显著差异。磁敏感加权成像技术能够成功检测帕金森病患者脑部铁含量。帕金森病黑质铁含量与UPDRS运动评分之间相关,表明其可以用来作为一个在体客观判断帕金森病病情的生物学标志。研究目的和意义采用静息态功能磁共振成像研究帕金森病脑部局部一致性改变及其与相关临床指标之间的相关性。材料与方法1.受试者一般资料收集于我院就诊的帕金森病患者34例。帕金森病的诊断采用英国脑库标准。采用统一帕金森病评定量表UPDRS对帕金森病患者的病情进行评定。同时,收集34例健康体检者作为健康对照组。2.MRI扫描方法所有MRI数据均采集于配置有八通道相控阵线圈的Siemens Trio 3.0T磁共振成像系统。扫描时,被试头部采用泡沫垫固定于头线圈内。所有参与研究的健康志愿者和帕金森病患者均同时采集T1WI、T2WI、FLAIR和静息态脑功能成像数据。经T1WI、T2WI、FLAIR发现异常影像学表现的被试排除出本研究。3.数据分析所有数据处理均基于Matlab 7.1 R14 SP3平台的SPM5、静息态功能磁共振数据处理工具包V1.4、Data Processing Assistant for Resting-State fMRI (DPARSF) V1.0等软件进行。4.局部一致性分析在REST软件上计算KCC值。因此,从每个人的fMRI数据得到此人的KCC图像,即ReHo图像。5.统计学分析首先分别对正常对照组和帕金森病组的ReHo图像分别进行单样本t检验;然后对正常对照组和帕金森病组的ReHo图像进行双样本t检验。以经过多重比较校正后P < 0.05为有统计学差异。多重比较校正采用AFNI的AlphaSim程序,通过Monte Carlo模拟获得。最后,将帕金森病组ReHo图像和临床指标之间进行相关分析,以期发现帕金森病组ReHo和帕金森病病程以及其严重程度之间的相关性。结果分析1.正常对照组和帕金森病组的单样本t检验见在正常对照组和帕金森病组在静息状态下,扣带回后部、楔前叶、前额叶内侧部ReHo值较其他脑区明显增高(P < 0.05,多重比较校正后),说明ReHo能够反映默认神经网络的神经元的自发活动。2.正常对照组和帕金森病组ReHo图的双样本t检验与正常对照组比较,帕金森病组在以下脑区ReHo值增高:双侧楔前叶、左侧枕中回、左侧距状皮层、右侧中央前回和右侧舌回;在以下脑区ReHo值减低:左侧角回、左侧嗅皮层、右侧额中回、右侧梭状回、右侧距状皮层、右侧小脑、右侧颞中回、右侧海马旁回、左侧辅助运动区和左侧颞下回。3.帕金森病组ReHo图与UPDRS之间的相关性帕金森病组ReHo值与其严重程度UPDRS在以下区域呈现正相关:右侧梭状回、左侧直回、右侧顶下小叶、右侧海马旁回、右侧额叶眶上皮层、右侧缘上回、左侧额叶下三角区;在以下区域呈现负相关:右侧小脑8区和9区。4.帕金森病组ReHo图与病程长短之间的相关性帕金森病组ReHo值与其病程长短在以下区域呈现正相关:左侧中央前回、右侧颞下回、左侧小脑脚、左侧额中回、左侧小脑后叶、右侧楔前叶和扣带回后部右侧;在以下区域呈现负相关:左侧脑干和右侧顶下小叶。结论本研究采用静息态功能磁共振成像手段对帕金森病进行了初步的研究,发现帕金森病患者在静息状态下存在异常的脑部神经活动,这些异常的脑部神经活动可能和帕金森病认知和行为功能障碍相关。对认识帕金森病的脑功能状态和这些改变与其临床病情之间的关系提供了新的思路和手段。语言区的病变既要做到全部切除又要同时保留语言功能对神经外科医生来说一直是一种挑战。语言区的准确定位是解决语言功能保留与病变切除程度之间矛盾的最有效的方法。脑功能成像技术是一种无创的脑功能定位方法,将它应用于临床需要解决两方面的问题,首先需要筛选出适用于中国人运动性语言区与感觉性语言区激活的任务模式,其次需要明确语言区功能定位的敏感性与准确性如何。研究目的和意义评价语言区脑功能成像的敏感性与准确性,了解语言功能区在颅内病变时的变化特点,确定语言激活脑区与病变切除的相对安全距离,并评价语言区功能导航的临床应用价值。材料与方法本研究选择功能区附近肿瘤患者术前行脑功能成像检查,通过神经导航将结构像、功能像行影像融合定位后,术中在唤醒状态下通过皮层电刺激来判断激活脑区与语言区的吻合度,并分析激活的核心脑区、辅助脑区以及参与脑区在汉语语言中的具体作用;通过比较术前术后脑功能成像特点与语言功能状态的变化,来了解语言区在颅内病变时的变化特点以及语言功能状态与激活脑区变化的关系;初步确定语言激活脑区与病变切除的相对安全距离,并评价语言区功能导航的临床应用价值。结果分析1.术前语言fMRI结果:本组31例患者共执行47项语言任务,其中20项(42.5%, 20/47)成像效果非常好,激活信号清楚明确;20项(42.5%, 20/47)成像效果清楚; 7项(15%, 7/40)未得到任务相关脑区激活。23项运动性语言任务中,5项(21.7%, 5/23)非常好,13项(56.5%, 13/23)清楚;24项感觉性语言任务中,15项(62.5%, 15/24)非常好,7项(29.2%, 7/24)清楚。2.术中电刺激结果:本组神经导航的系统误差小于2mm,病人唤醒时间10- 50min,平均19 min,23例患者在清醒状态完成语言任务。由于开颅骨窗限制或唤醒不理想,共进行了26项激活功能区与皮层电刺激结果的相关性比较,结果如下:12例(46.2%, 12/26)为重叠关系,差距在1cm之内;14例(53.8%, 14/26)为邻近关系,差距在2cm之内;未发现距离大于2cm的矛盾关系者。3.手术效果及神经功能障碍:本组31例患者,术前20例(64.5%, 20/31)语言功能正常,11例(35.5%, 11/31)有不同程度语言功能障碍。手术切除程度:全切12例(38.7%, 12/31),次全切除8例(25.8%, 8/31),大部切除11例(35.5%, 11/31)。术后语言功能变化:7例(22.6%, 7/31)较术前好转,19例(61.3%, 19/31)无变化,5例(16.1%, 5/31)出现短暂性运动性失语,未出现永久性语言功能损害者。4.皮层切除边界与fMRI功能脑区之间的关系:激活脑区与皮层切除边界距离大于10 mm者均未造成语言功能恶化;5例(16.1%, 5/31)出现运动性失语者,激活脑区与皮层切除的距离均小于10 mm(2例在5-10 mm之间,3例小于5mm),手术后即出现失语,在1周左右语言功能基本恢复正常,未遗留永久语言功能损害。结论1.脑部语言功能区病变对fMRI结果影响较小;无论是在1.5T还是3.0T的磁共振扫描仪上,术前语言功能区成像均具有较高的成功率;对功能区附近病变语言脑功能成像;术前语言功能区成像与术中电刺激具有良好的一致性,能够有效的降低语言区附近病变术后语言功能损害的发生率。2.fMRI导航条件下,若皮层激活脑区与皮层切除边界距离大于10 mm者,可以不必实施术中唤醒电刺激;皮层激活脑区与皮层切除边界距离在5～10 mm之间者,应该在术中实施唤醒电刺激;对于皮层激活脑区与皮层切除边界距离小于5mm者,应该在非常谨慎地实施术中唤醒电刺激。但是,此时暂时性的语言功能损害常常无法避免。更多还原

【Abstract】 Objectives1. To evaluate the feasibility of characterizing iron deposition in PD using susceptibility-weighted imaging (SWI).2. To investigate the correlation of brain iron accumulation with the clinical status in patients with PD.Subjects and MethodsForty patients with PD without dementia and 26 age- and sex-matched healthy controls underwent high-resolution susceptibility-weighted magnetic resonance (MR) imaging. The phase shift values of the bilateral red nucleus (RN), substantia nigra (SN), caudate nucleus (CA), globus pallidus (GP), putamen (PU) thalamus (TH) and frontal white matter (FWM) were examined for their relationship with the clinical status.Results1. Previously published regional iron concentrations vs. we observed SWI phase shift valuesIn healthy controls, we observed a positive correlation (r = 0.903, P = 0.005) between SWI phase shift values and previously published regional iron concentrations. (Hallgren and Sourander, 1958) This validates our application of SWI as a viable MRI method for the noninvasive estimation of regional brain iron content.2. Hemispheric differences in the healthy controlsThere were no significant hemispheric differences with regards to phase shift values in the healthy human brain.3. The most affected vs. the least affected brain side in PD The most affected body side of symptoms is assessed with Unified Parkinson’s Disease Rating Scale (UPDRS) motor score. The contralateral brain side is referred as“the most affected brain side”; the ipsilateral brain side referred as“the least affected brain side”. The paired-sample t test showed a difference between the controls and the patients in the SN (P = 0.000), but not in the other regions studied.4. The most affected brain side in PD vs. the healthy controlsIndependent t-tests showed that there were no significant phase shift value differences in other regions of interest (ROIs) except for the SN (P = 0.001).5. The least affect brain side in PD vs. the healthy controlsIndependent t-tests showed that there were no significant phase shift value differences in the regions of interest (ROIs).6. Correlations between the phase shift values in the SN of the most affected and least affected brain side in PD and its durationNo relationship was found between the phase shift values and the disease duration in the SN of the clinically most affected side or the least side (the most affected side, r = 0.142, P = 0.381; the least affected side, r= 0.287, P = 0.073).7. Correlations between the phase shift values in the SN of the most affected and least affected brain side in PD and the UPDRS motor scorePearson’s correlation analysis showed that there was a positive correlation between the phase shift values in the SN of the clinically most affected and least affected brain side in PD and the UPDRS motor score (the most affected side, r = 0.412, P = 0.008; the least affected side, r= 0.361, P = 0.022).8. Difference in the phase shift values of the SN between earlier-onset and later-onset PDThere were 15 cases of earlier-onset PD (the mean phase shift value in the SN = 0.14401±0.06205) and 25 cases of later-onset PD (the mean phase shift value in the SN = 0.16430±0.04776). No significant difference was detected between earlier- and later-onset PD (P = 0.253). ConclusionsBrain iron concentration can be evaluated by SWI. Also, the brain iron concentration in the SN correlated with UPDRS motor score, indicating that iron concentration can function as an in vivo biomarker to objectively evaluate the status of PD. ObjectivesTo explore the Regional Homogeneity alterations in patients with Parkinson’s disease and to investigate the correlation between these changes and clinical index. Subjects and MethodsThirty-four patients with PD without dementia and 34 healthy controls underwent resting-state functional magnetic resonance (MR) imaging. After the data preprocessing, the Regional Homogeneity alterations were calculated with the DPARSF and REST software package.Results1. The ReHo maps of the healthy controls and the patients with Parkinson’s disease( one-sample t test)The default mode network including the posterior cingulate cortex (PCC)/precuneus, medial prefrontal cortex (MPFC), and bilateral inferior parietal lobe (IPL) exhibited significant higher ReHo than other brain areas, which indicates that the ReHo method could reflect the spontaneous neuronal activity of the default mode network.2. Comparison of the ReHos between the healthy controls and the patients with Parkinson’s disease (two-sample t test)Compared with the healthy controls, the patients with PD at off state showed significant ReHo increases in the bilateral precuneus, left occipital middle gyrus, left calcarine cortex, right precentral gyrus and right lingual gyrus and significant ReHo decrease in the left angular gyrus, left olfactory cortex, right frontal middle gyrus, right fusiform area, right calcarine, right cerebellum, right temporal middle gyrus and left temporal inferior gyrus, right parahippcampal gyrus and left supplemental motor area.3. Correlations between ReHo and UPDRS in patients with PD Correlation analysis of ReHo at each voxel in the whole brain against the UPDRS in the patients with PD at off state revealed significantly positive correlation in the right fusiform area,left rectus gurus, right parietal inferior lobe, right parahippocampla gyrus, right frontal superior orbital gyrus, right supramarginal gyrus and right frontal inferior triangular area and revealed significant negative correlation in the right cerebelun 8 and 9 area.4. Correlations between ReHo and disease duration in patients with PDCorrelation analysis of ReHo at each voxel in the whole brain against the disease duration in the patients with PD at off state revealed significantly positive correlation in the left precentral gyrus, right temporal middle gyrus, left cerebellum crus, left frontal middle gyrus, left cerebellum posterior lobe, right precuneus and right cungulum posterior part; and revealed significant negative correlation in the left brainstem and right inferior parietal lobe.ConclusionsThe current study demonstrates that neural activity in the resting state is changed in patients with PD. This change is related to the severity and the duration of the disease, which provided new perspective and tool to explore the pathophysiology of the Parkinson’s disease. Objective1. To evaluate the sensitivity and accuracy of preoperative language cortex functional MRI localization.2. To characterize the alteration of language function under the circumstances of intracranial lesion around the language area.3. To determine the safety distance between the core activation of language functional region and the lesion during the resection.4. To assess the clinical value of functional neuronavigation during the resection of language area around lesions.MethodsThirty-one patients who had lesions in or around the language cortex were recruited in the study. As the help of neuronavigation we integrated the conventional MRI and fMRI images together and localized the position of the language cortex and lesion. In the course of operation the patients were awaked, the technique of direct cortical stimulation was performed to assess the sensitivity and accuracy of preoperative language cortex functional MRI localization. We compared the results of preoperative and postoperative fMRI in patients, and compared the language status before and after operation.Results1. The results of each fMRI paradigm in patients: The outcome of each fMRI paradigm was rated by‘very good’,‘fair’and‘unsuccessful’. Forty-seven language tasks were implemented in 31 patients, 20 tasks were rated‘very good’, 20 tasks rated were‘fair’, 4 tasks were rated‘unsuccessful’. In total 23 Broca’s area activations, 5 tasks were rated‘very good’, 13 tasks were rated‘fair’. In total 24 Wernicke’s area activations, 15 tasks were rated‘very good’, 7 tasks were rated‘fair’. 2. The consistence of fMRI activation area and direct cortical stimulation: The distance between the fMRI core activation and direct cortical stimulation was rated as overlapping (<1cm distance), adjacent (<2cm distance), discrepancy (>2cm distance). We performed 26 cases measurement, 12 cases were rated overlapping, 14 cases were rated adjacent, no cases showed discrepancy.3. The outcome of the fMRI neuronavigation assisted operation: Total lesion resection was achieved in 12 cases, subtotal resection in 8 cases, partial resection in 11 cases. Postoperatively the neurologic functions were improved in 7 cases, unchanged in 19 cases, temporary worsen in 5 cases, no persisting deficits.4. Correlation between the distance of resection border-to-language cortex and outcome: Resection border more than 10mm from the functional areas is safe. All the patients the neurologic functions were improved or unchanged. Three cases caught the temporary worsen, the distances were less than 10mm, and resumed in a week.Conclusions1. The influence of the language cortex around lesion on the outcome of the fMRI is limited; the successes rate of preoperative language cortex localization fMRI is high either on 1.5T or 3.0T MRI scanner; the outcome of preoperative language cortex localization fMRI is consistent well with that of intra-operative electrical stimulation, which could effectively decrease the incidence rate of language function damage during the resection the lesion around the language cortex.2. Under the circumstances of fMRI neuronavigation, if the distance between the core activation and the lesion is more than 10mm, it is unnecessary to implement intra-operative awaked electrical stimulation; if the distance between the core activation and the lesion is between 5mm and 10mm, intra-operative awaked electrical stimulation should been applied; if the distance between the core activation and the lesion is less than 5mm, intra-operative awaked electrical stimulation should been implemented very cautiously. But temporary language function damage is often unavoidable at this moment.更多还原