多模态MRI影像在矿难创伤后应激障碍研究中的应用
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摘要
创伤后应激障碍(Post-traumatic Stress Disorder, PTSD)指由突发性、威胁性或灾难性事件引起人体延迟出现并长期持续存在的精神障碍。常常表现为再度体验创伤，易激惹和回避行为，并常伴有睡眠障碍、注意力难以集中、警觉性过高、过度惊吓反应等症状。大部分人在创伤后数天至六个月内发病，经过一段时间调整后都可以恢复正常。据报道，在美国，约有3.6%的人曾患有PTSD，而其中7.8%的患者终身患病。引发创伤的事件包括战争、暴力犯罪、性侵害、交通事故、失业、离婚、自然灾害等，PTSD患者多为直接或间接接触创伤事件的幸存者、目击者和救援者。有研究表明，不同类型的创伤可能影响PTSD严重程度和症状表现。目前，PTSD已成为流行病学、心理学、社会医学等多个学科的研究热点。尤其是，近年来，矿难、地震、海啸、恐怖袭击频发，这些突发的灾难性事件所引起的PTSD越来越受到人们的关注。
目前，各国科学家已通过遗传、神经、生化、内分泌、心理及社会等多方面的研究，对PTSD病理、病因学机制进行了探讨，但具体机制仍不甚明晰。同时，由于对介导PTSD症状的大脑环路缺乏清晰的认识，目前仍未有针对PTSD的有效治疗方法。
近年来，影像医学的发展为脑部疾病的研究提供了新的手段。特别是磁共振成像(Magnetic Resonance Imaging, MRI)已逐渐从结构成像扩展到功能成像，从单模态成像发展到多模态成像。从多方面来分析患者的结构变化、血流灌注、功能代谢和功能连接等信息，将MRI的多种模态相结合，并应用到脑部疾病的诊断和评价，是目前的研究热点和难点。现已有研究通过影像手段，初步发现了PTSD患者在脑部结构和功能方面不同程度的病理性损害。
对于精神类疾病，在疾病引发实质性病变之前，往往会先出现功能代谢、血流灌注和功能区形状(如脑皮层厚度)的改变。因此，对脑皮层厚度和脑血流的分析往往可以检测出疾病发生早期对人体结构和功能的影响。各向异性分数(fractional anisotropy，FA)和表面弥散系数(apparent diffusion coefficient,ADC)可以有效反映微结构及分子水平的病理、生理学改变，能够检测早期的病变引起的脑损伤。但目前，尚未见基于MRI影像，对矿难创伤后PTSD所引起脑皮层厚度、血流及DTI指标变化的研究。
本研究针对上述问题，利用矿难幸存者的MRI结构、灌注和弥散张量成像(Diffusion Tensor Imaging, DTI)数据，进行脑皮层厚度、脑血流及DTI指标分析，检测矿难创伤后早期PTSD(MRI扫描时间为事故发生后6个月)对脑部结构和功能的影响；并进一步研究这些结构和功能的变化与PTSD症状的严重程度的相关关系及相关程度。
本研究被试者为2007年河南省三门峡市东风井，因河床水通过采空区涌入井下，而被困1400米深地下72小时的幸存者。参加本研究的20名幸存者中10人满足DSM-IV中描述的PTSD指标，为PTSD组；另外10人不满足，为非PTSD组。PTSD病情的严重程度通过创伤后应激障碍量表(Clinician-administered PTSD Scale, CAPS)进行评价。
本研究主要包含以下研究内容：
1、脑皮层厚度的准确测量及分析
在已有研究的基础上，本文构建了基于拉普拉斯方程的脑皮层三维厚度检测流程和方法，提高了计算速度和测量的准确性。首先考虑到DARTEL标准化算法对脑部细微结构进行配准具有更高的准确性，检测细微结构的异常变化具有更高的敏感性，本研究中利用VBM-DARTEL工具包对MRI的T1序列图像进行预处理，得到分割后的脑灰质、白质和脑脊液数据。并在预处理结果的基础上，采用改进的基于拉普拉斯偏微分方程的三维厚度测量方法测量脑皮层厚度，该方法通过在脑皮层内部构建势能场，并利用垂直等势面场线的长度来定义皮层厚度，使内、外表面具有唯一可逆对应点，避免了最短欧氏距离引起的测量误差，是目前脑皮层厚度测量最准确、有效的测量方法之一。但由于大脑脑沟区域的复杂形态变化和数据采集过程中各种因素的影响，容易造成分割误差。因此，在测量脑皮层三维厚度之后，采用脑沟厚度校正方法对可能存在误分割的脑沟区域进行校正，并根据校正后的灰质图像，重新测量脑皮层厚度，从而得到更准确的三维厚度值，并构建三维脑皮层厚度图像。
在构建脑皮层结构和三维厚度图像的基础上，利用SPM对两组间的体积及皮层厚度进行统计学分析。由于在人口学特征分析中，两组除年龄外，其他特征都不存在统计学差异，因此，本研究以年龄作为协变量，通过两样本t检验进行分析，未发现两组的体积存在统计学差异的区域。但对脑皮层厚度的统计分析表明，较非PTSD组，PTSD组在左脑顶叶、右脑额下回和右脑海马旁回区域脑皮层厚度明显变薄。
为了探索PTSD严重程度与脑皮层厚度间的相关关系，本研究采用穿过厚度变薄区域的场线上的所有体素，作为感兴趣区域(Regional of Interest,ROI)。通过ROI分析发现，PTSD组的10名被试者的右脑额下回的平均厚度与PTSD症状的严重程度(CAPS值)明显负相关。
2、脑血流(Cerebral Blood Flow, CBF)的准确测量及分析
通过灌注成像扫描序列的筛选，本研究使用无创、标记效率高的脉冲式动脉自旋标记(Pulsed Artery Spin Labeling, PASL)扫描序列来分析矿难后早期PTSD患者的CBF变化。为此，本研究在已有研究的基础上，构建了PASL序列CBF准确测量方法。
首先，由于PASL序列图像成像速度快，图像分辨率较低，本研究利用SPM分别对PASL序列图像和T1序列结构图像进行预处理，并将结构像信息应用到功能像当中，提高标准化的准确性和功能图像的分辨率。经过预处理后，图像分辨率有所提高，但仍受到部分容积效应(Partial Volume Effect,PVE)的严重影响。为此，本研究首次利用PASL序列的时间信息，构建了PASL时间序列，并使用MAP-EM算法分析时间序列中每个体素点中的混合组织参数，并结合CBF的测量方法，在对图像进行部分容积校正的基础上，获得更准确的CBF分布图。
获得CBF分布图后，通过分析，未发现两组的平均CBF统计学差异。但考虑到年龄对CBF的影响，本研究以年龄作为协变量，采用SPM进行两样本t检验，发现PTSD组，较非PTSD组，在右脑额叶区域CBF明显增高。但通过ROI分析，未发现PTSD组在该区域的平均CBF值与PTSD症状严重程度(CAPS值)存在相关关系。
3、DTI数据分析
本研究使用DTI Studio和SPM联合分析了矿难幸存者的DTI序列数据，发现PTSD组，较非PTSD组，在右脑侧脑室、右脑梭状回、右脑颞上回和右脑颞中回区域FA值明显降低，在右脑颞上回和右脑胼胝体区域ADC值明显增高。但通过ROI分析，未发现PTSD组在这些区域的平均FA值或ADC值与PTSD症状严重程度(CAPS值)存在相关关系。这可能是由于PTSD早期引起的结构及功能变化不明显，FA和ADC指标尚无显著变化所导致的。
4、小结
本研究首先构建了基于拉普拉斯方程的脑皮层厚度检测流程和方法，提高了计算速度和测量的准确性；考虑到灌注成像的分辨率低及PVE对CBF测量的影响，将基于MAP-EM算法的部分容积校正理论与CBF测量方法相结合，得到更准确的CBF分布图，上述方法为研究神经系统或脑部疾病引起的脑皮层厚度和血流变化提供了有效的手段。
基于提出的方法，本研究对经历矿难的20名幸存者构成的PTSD组和对照组的脑皮层厚度和CBF分布进行了统计分析，发现了多个厚度或CBF存在差异的的区域。同时，使用DTI Studio和SPM联合分析了DTI序列数据，发现了多个FA和ADC值异常的脑区。以上结果一方面可为进一步理解PTSD病理、病因学机制奠定基础，另一方面，提出的区域或指标，有望进一步成为早期PTSD临床诊断和评价的依据。
Post-traumatic stress disorder (PTSD) is an anxiety disorder that developsafter exposure to a terrifying event or ordeal in which grave physical harmoccurred or was threatened. Its features persist for a long duration. The commonsymptoms of PTSD are re-experience trauma, irritability, and avoidance behavior,accompanied by sleep disorders, lack of concentration, high alertness, excessivescare, etc. In general, the symptom is occurred in several days to six months afterexposure to the trauma. It’s reported that about3.6%Americans have sufferedfrom PTSD, and7.8%of them cannot be cured. The PTSD may be induced bywarfare, violent crime, sexual abuse, traffic accident, unemployment, divorce,natural disaster, etc. The patients of PTSD are the survivors, witnesses, andrescue workers of the trauma. At present, PTSD is hot topic of epidemiology,psychology, social medicine. A recent study reported that different types oftraumatic experiences may result in different levels of PTSD severity and displaydistinct PTSD symptom patterns. Especially, in recent years, the coal minedisaster, earthquakes, tsunamis, terrorist attack occur frequently. Therefore, thekind of PTSD induced by the sudden disaster is more and more concerned.
Currently, many researches have investigated the pathological andetiological mechanism, according to genetics, nerve, biochemistry, incretion,psychology and sociology studies. However, the detailed mechanism of PTSDremains unclear. Due to lack of clear understanding the alteration of braininduced by PTSD, there is no effectively therapeutic method for PTSD.
With the development of medical imaging, it provides a new method to thestudy of brain diseases. Especially, Magnetic Resonance Imaging (MRI) hasgradually developed from structural imaging to functional imaging, fromsingle-modality to multi-modality imaging. To analyze the alteration of structure,blood perfusion, metabolism and connection information in patients with PTSDfrom a range of directions, and combine multi-modality of MRI to diagnosis andevaluate the brain disease, is the hot and difficult topic at present. It is reportedthat different degree of pathological damage was preliminary found in thepatients with PTSD, based on the medical imaging.
For psychiatric diseases, the alterations of metabolism, perfusion and theshape of cortical cortex (cortical thickness) are usually occurred before thesubstantive lesions. So the cortical thickness and cerebral blood flow (CBF)analysis are often used to detect the effect of brain disease on the structure andfunction at early stage of disease. Fractional anisotropy (FA) and apparentdiffusion coefficient (ADC) are thought to reflect the microstructural alteration,physiological and pathological changes at the molecular level. However, to ourknowledge, no studies have investigated the effect of PTSD induced by coal minedisaster on the cortical thickness, CBF, FA and ADC value.
In view of above questions, the present study analyzed the difference incortical thickness, CBF, FA and ADC of whole brain in patient with recent onsetPTSD due to a mining disaster. The elapsed time between the traumatic event and MRI scans was ranged from187to190days. After the comparison of corticalthickness and CBF between subjects with and without PTSD, the relationship ofcortical thickness and CBF of identified regions with the PTSD symptom severitywas investigated.
In2007, a severe coalmine-flooded disaster occurred at Sanmenxia of HenanProvince. Sixty-nine male miners were trapped in a nearly1400m undergroundcoal pit. All the twenty subjects in this study are the survivors from this suddendisaster. Ten of them met the diagnostic criteria for PTSD, while the other tenpersons didn’t meet. With the constructed PTSD and non-PTSD groups in thisstudy, each group had10male subjects. The severity of their symptoms wasassessed with the Chinese version of the Clinician-Administered PTSD Scale(CAPS)
1. Cortical thickness measurement and analysis
In this study, the pipeline for cortical thickness measurement and analysiswas proposed, which improved computation speed and the accuracy of thicknessmeasurement. Considering DARTEL has a higher sensitivity in detecting subtleabnormalities of structures and accurate realignment of subtle structure, in thisstudy, the VBM-DARTEL was used to preprocess the T1sequence of MRI andsegment the normalized data into gray matter, white matter and cerebrospinalfluid (CSF) with signal intensity and prior probability information. Based on thesegmented gray matter, white matter and CSF, the3D cortical thickness wasestimated by the Laplacian approach. According to building series ofequipotential surfaces, the cortical thickness is defined as the arc length of thestreamlines which is perpendicular to the equipotential surfaces. This methodavoided the measurement error from Euclidean distance with unique andreversible corresponding points between two surfaces, and is regarded as one of most accurate and efficient thickness measurement method currently. Due to thetopological shell of the cerebral cortex and various influence factors in dataacquisition, it is hard to classify the tissues perfectly, especially in sulci regions.In this study, the algorithm developed for sulci detection and thickness correctionwas employed to further improve the brain segmentation after the thicknessestimation. After the correction of the segmentation, the cortical thickness wasre-calculated accordingly and more accurate result was obtained for the wholebrain.
Based on the image of cortical thickness, the difference of thickness can beanalyzed with statistical parametric mapping (SPM). Group differences indemographic variables were examined with independent t-tests. All subjects inthis study came from the same community and did not differ significantly insocioeconomic status. The two groups (PTSD and non-PTSD) significantlydiffered in age. Thus, group comparisons of cortical thickness were performedusing analysis of two sample t-test in SPM8with age as covariates to account forthe age effect. Comparisons of cortical thickness in survivors experienced miningdisaster indicated that in left parietal lobe, right inferior frontal gyrus, and rightparahippocampal gyrus, cortical thickness of subjects with PTSD was obviouslythinner than those without PTSD.
To investigate the relation between thickness and s PTSD symptom severity,the region that consists of all the voxels on the streamline across the significantlythinner region was used for ROI analysis in this study. ROI-based correlationalanalysis was performed in the patients with PTSD. The mean cortical thickness ofright inferior frontal gyrus tended to correlate negatively with the CAPS score inthe identified regions from thickness analysis.
2. CBF measurement and analysis
According to selection of MRI perfusion sequences, in this study, the pulsedartery spin labeling (PASL) sequence was used to investigate the alteration ofCBF for the patients of PTSD induced by coal mine disaster, which isnon-invasive with high efficiency. In this study, an accurate CBF measurementmethod of PASL sequence was proposed.
Due to fast imaging of PASL, the resolution of image is relative low. For thisreason, SPM was used to preprocess the PASL and T1sequences, respectively.With the information of structural images applied to the functional images, theaccuracy of normalization and resolution of functional images were improved.Though the resolution of images had been improved, the images were stillaffected by partial volume effect (PVE). In this study, the acquired time of PASLsequence was used to construct the time sequence, and the MAP-EM algorithmwas used to estimate the mixed tissue model parameters. Moreover, combinedwith this PVE correction, the CBF measurement method was used to acquire thedistribution image of CBF.
Based on the CBF image, no significant difference of mean CBF was foundbetween the PTSD and non-PTSD groups. Considering the effect of age on theCBF, group comparisons of CBF were performed using analysis of two samplet-test in SPM8with age as covariates to account for the age effect. Comparisonsof CBF in survivors experienced mining disaster indicated that in right frontallobe, CBF of subjects with PTSD was obviously higher than those without PTSD.However, based on ROI analysis in patients with PTSD, no significant correlationof the CAPS score with mean CBF in right frontal lobe was observed.
3. DTI analysis
Based on the software of DTI studio and SPM, the DTI sequence wasanalyzed. Comparisons of FA and ADC in survivors experienced mining disaster indicated that in the right lateral ventricle, right fusiform gyrus, right superiortemporal gyrus, and right middle temporal gyrus, FA value of subjects with PTSDwas obviously lower than those without PTSD, and ADC value of subjects withPTSD was obviously higher in the right superior temporal gyrus and right corpuscallosum. However, based on ROI analysis in patients with PTSD, no significantcorrelation of the CAPS score with mean FA and/or ADC in above identifiedregions was observed. That may be due to subtle alteration of cortical thicknesscaused by early stage of PTSD.
4. Summary
In this study, the pipeline for cortical thickness measurement and analysiswas proposed, which improved computation speed and the accuracy of thicknessmeasurement. Meanwhile, considering the relatively low resolution and the effectof PVE on images, the PVE correction method based on MAP-EM algorithm wascombined with CBF measurement method to keep the accuracy of the CBF.These proposed methods may provide an efficient method for the corticalthickness and CBF analysis for nerve system or brain diseases.
Based on proposed methods, in this study, a series of regions withsignificant difference between PTSD and non-PTSD groups were identified.Meanwhile, based on the software of DTI studio and SPM, the DTI sequence wasanalyzed. According to multiple regression analysis, the advantage ofmulti-modality image analysis is preliminarily confirmed. These results lay asolid foundation for the further study of pathological and etiological mechanism.Furthermore, the identified regions or indexes are hopeful to be the objective andquantitative indexes to diagnosis and evaluate PTSD in clinic.
目前，各国科学家已通过遗传、神经、生化、内分泌、心理及社会等多方面的研究，对PTSD病理、病因学机制进行了探讨，但具体机制仍不甚明晰。同时，由于对介导PTSD症状的大脑环路缺乏清晰的认识，目前仍未有针对PTSD的有效治疗方法。
近年来，影像医学的发展为脑部疾病的研究提供了新的手段。特别是磁共振成像(Magnetic Resonance Imaging, MRI)已逐渐从结构成像扩展到功能成像，从单模态成像发展到多模态成像。从多方面来分析患者的结构变化、血流灌注、功能代谢和功能连接等信息，将MRI的多种模态相结合，并应用到脑部疾病的诊断和评价，是目前的研究热点和难点。现已有研究通过影像手段，初步发现了PTSD患者在脑部结构和功能方面不同程度的病理性损害。
对于精神类疾病，在疾病引发实质性病变之前，往往会先出现功能代谢、血流灌注和功能区形状(如脑皮层厚度)的改变。因此，对脑皮层厚度和脑血流的分析往往可以检测出疾病发生早期对人体结构和功能的影响。各向异性分数(fractional anisotropy，FA)和表面弥散系数(apparent diffusion coefficient,ADC)可以有效反映微结构及分子水平的病理、生理学改变，能够检测早期的病变引起的脑损伤。但目前，尚未见基于MRI影像，对矿难创伤后PTSD所引起脑皮层厚度、血流及DTI指标变化的研究。
本研究针对上述问题，利用矿难幸存者的MRI结构、灌注和弥散张量成像(Diffusion Tensor Imaging, DTI)数据，进行脑皮层厚度、脑血流及DTI指标分析，检测矿难创伤后早期PTSD(MRI扫描时间为事故发生后6个月)对脑部结构和功能的影响；并进一步研究这些结构和功能的变化与PTSD症状的严重程度的相关关系及相关程度。
本研究被试者为2007年河南省三门峡市东风井，因河床水通过采空区涌入井下，而被困1400米深地下72小时的幸存者。参加本研究的20名幸存者中10人满足DSM-IV中描述的PTSD指标，为PTSD组；另外10人不满足，为非PTSD组。PTSD病情的严重程度通过创伤后应激障碍量表(Clinician-administered PTSD Scale, CAPS)进行评价。
本研究主要包含以下研究内容：
1、脑皮层厚度的准确测量及分析
在已有研究的基础上，本文构建了基于拉普拉斯方程的脑皮层三维厚度检测流程和方法，提高了计算速度和测量的准确性。首先考虑到DARTEL标准化算法对脑部细微结构进行配准具有更高的准确性，检测细微结构的异常变化具有更高的敏感性，本研究中利用VBM-DARTEL工具包对MRI的T1序列图像进行预处理，得到分割后的脑灰质、白质和脑脊液数据。并在预处理结果的基础上，采用改进的基于拉普拉斯偏微分方程的三维厚度测量方法测量脑皮层厚度，该方法通过在脑皮层内部构建势能场，并利用垂直等势面场线的长度来定义皮层厚度，使内、外表面具有唯一可逆对应点，避免了最短欧氏距离引起的测量误差，是目前脑皮层厚度测量最准确、有效的测量方法之一。但由于大脑脑沟区域的复杂形态变化和数据采集过程中各种因素的影响，容易造成分割误差。因此，在测量脑皮层三维厚度之后，采用脑沟厚度校正方法对可能存在误分割的脑沟区域进行校正，并根据校正后的灰质图像，重新测量脑皮层厚度，从而得到更准确的三维厚度值，并构建三维脑皮层厚度图像。
在构建脑皮层结构和三维厚度图像的基础上，利用SPM对两组间的体积及皮层厚度进行统计学分析。由于在人口学特征分析中，两组除年龄外，其他特征都不存在统计学差异，因此，本研究以年龄作为协变量，通过两样本t检验进行分析，未发现两组的体积存在统计学差异的区域。但对脑皮层厚度的统计分析表明，较非PTSD组，PTSD组在左脑顶叶、右脑额下回和右脑海马旁回区域脑皮层厚度明显变薄。
为了探索PTSD严重程度与脑皮层厚度间的相关关系，本研究采用穿过厚度变薄区域的场线上的所有体素，作为感兴趣区域(Regional of Interest,ROI)。通过ROI分析发现，PTSD组的10名被试者的右脑额下回的平均厚度与PTSD症状的严重程度(CAPS值)明显负相关。
2、脑血流(Cerebral Blood Flow, CBF)的准确测量及分析
通过灌注成像扫描序列的筛选，本研究使用无创、标记效率高的脉冲式动脉自旋标记(Pulsed Artery Spin Labeling, PASL)扫描序列来分析矿难后早期PTSD患者的CBF变化。为此，本研究在已有研究的基础上，构建了PASL序列CBF准确测量方法。
首先，由于PASL序列图像成像速度快，图像分辨率较低，本研究利用SPM分别对PASL序列图像和T1序列结构图像进行预处理，并将结构像信息应用到功能像当中，提高标准化的准确性和功能图像的分辨率。经过预处理后，图像分辨率有所提高，但仍受到部分容积效应(Partial Volume Effect,PVE)的严重影响。为此，本研究首次利用PASL序列的时间信息，构建了PASL时间序列，并使用MAP-EM算法分析时间序列中每个体素点中的混合组织参数，并结合CBF的测量方法，在对图像进行部分容积校正的基础上，获得更准确的CBF分布图。
获得CBF分布图后，通过分析，未发现两组的平均CBF统计学差异。但考虑到年龄对CBF的影响，本研究以年龄作为协变量，采用SPM进行两样本t检验，发现PTSD组，较非PTSD组，在右脑额叶区域CBF明显增高。但通过ROI分析，未发现PTSD组在该区域的平均CBF值与PTSD症状严重程度(CAPS值)存在相关关系。
3、DTI数据分析
本研究使用DTI Studio和SPM联合分析了矿难幸存者的DTI序列数据，发现PTSD组，较非PTSD组，在右脑侧脑室、右脑梭状回、右脑颞上回和右脑颞中回区域FA值明显降低，在右脑颞上回和右脑胼胝体区域ADC值明显增高。但通过ROI分析，未发现PTSD组在这些区域的平均FA值或ADC值与PTSD症状严重程度(CAPS值)存在相关关系。这可能是由于PTSD早期引起的结构及功能变化不明显，FA和ADC指标尚无显著变化所导致的。
4、小结
本研究首先构建了基于拉普拉斯方程的脑皮层厚度检测流程和方法，提高了计算速度和测量的准确性；考虑到灌注成像的分辨率低及PVE对CBF测量的影响，将基于MAP-EM算法的部分容积校正理论与CBF测量方法相结合，得到更准确的CBF分布图，上述方法为研究神经系统或脑部疾病引起的脑皮层厚度和血流变化提供了有效的手段。
基于提出的方法，本研究对经历矿难的20名幸存者构成的PTSD组和对照组的脑皮层厚度和CBF分布进行了统计分析，发现了多个厚度或CBF存在差异的的区域。同时，使用DTI Studio和SPM联合分析了DTI序列数据，发现了多个FA和ADC值异常的脑区。以上结果一方面可为进一步理解PTSD病理、病因学机制奠定基础，另一方面，提出的区域或指标，有望进一步成为早期PTSD临床诊断和评价的依据。
Post-traumatic stress disorder (PTSD) is an anxiety disorder that developsafter exposure to a terrifying event or ordeal in which grave physical harmoccurred or was threatened. Its features persist for a long duration. The commonsymptoms of PTSD are re-experience trauma, irritability, and avoidance behavior,accompanied by sleep disorders, lack of concentration, high alertness, excessivescare, etc. In general, the symptom is occurred in several days to six months afterexposure to the trauma. It’s reported that about3.6%Americans have sufferedfrom PTSD, and7.8%of them cannot be cured. The PTSD may be induced bywarfare, violent crime, sexual abuse, traffic accident, unemployment, divorce,natural disaster, etc. The patients of PTSD are the survivors, witnesses, andrescue workers of the trauma. At present, PTSD is hot topic of epidemiology,psychology, social medicine. A recent study reported that different types oftraumatic experiences may result in different levels of PTSD severity and displaydistinct PTSD symptom patterns. Especially, in recent years, the coal minedisaster, earthquakes, tsunamis, terrorist attack occur frequently. Therefore, thekind of PTSD induced by the sudden disaster is more and more concerned.
Currently, many researches have investigated the pathological andetiological mechanism, according to genetics, nerve, biochemistry, incretion,psychology and sociology studies. However, the detailed mechanism of PTSDremains unclear. Due to lack of clear understanding the alteration of braininduced by PTSD, there is no effectively therapeutic method for PTSD.
With the development of medical imaging, it provides a new method to thestudy of brain diseases. Especially, Magnetic Resonance Imaging (MRI) hasgradually developed from structural imaging to functional imaging, fromsingle-modality to multi-modality imaging. To analyze the alteration of structure,blood perfusion, metabolism and connection information in patients with PTSDfrom a range of directions, and combine multi-modality of MRI to diagnosis andevaluate the brain disease, is the hot and difficult topic at present. It is reportedthat different degree of pathological damage was preliminary found in thepatients with PTSD, based on the medical imaging.
For psychiatric diseases, the alterations of metabolism, perfusion and theshape of cortical cortex (cortical thickness) are usually occurred before thesubstantive lesions. So the cortical thickness and cerebral blood flow (CBF)analysis are often used to detect the effect of brain disease on the structure andfunction at early stage of disease. Fractional anisotropy (FA) and apparentdiffusion coefficient (ADC) are thought to reflect the microstructural alteration,physiological and pathological changes at the molecular level. However, to ourknowledge, no studies have investigated the effect of PTSD induced by coal minedisaster on the cortical thickness, CBF, FA and ADC value.
In view of above questions, the present study analyzed the difference incortical thickness, CBF, FA and ADC of whole brain in patient with recent onsetPTSD due to a mining disaster. The elapsed time between the traumatic event and MRI scans was ranged from187to190days. After the comparison of corticalthickness and CBF between subjects with and without PTSD, the relationship ofcortical thickness and CBF of identified regions with the PTSD symptom severitywas investigated.
In2007, a severe coalmine-flooded disaster occurred at Sanmenxia of HenanProvince. Sixty-nine male miners were trapped in a nearly1400m undergroundcoal pit. All the twenty subjects in this study are the survivors from this suddendisaster. Ten of them met the diagnostic criteria for PTSD, while the other tenpersons didn’t meet. With the constructed PTSD and non-PTSD groups in thisstudy, each group had10male subjects. The severity of their symptoms wasassessed with the Chinese version of the Clinician-Administered PTSD Scale(CAPS)
1. Cortical thickness measurement and analysis
In this study, the pipeline for cortical thickness measurement and analysiswas proposed, which improved computation speed and the accuracy of thicknessmeasurement. Considering DARTEL has a higher sensitivity in detecting subtleabnormalities of structures and accurate realignment of subtle structure, in thisstudy, the VBM-DARTEL was used to preprocess the T1sequence of MRI andsegment the normalized data into gray matter, white matter and cerebrospinalfluid (CSF) with signal intensity and prior probability information. Based on thesegmented gray matter, white matter and CSF, the3D cortical thickness wasestimated by the Laplacian approach. According to building series ofequipotential surfaces, the cortical thickness is defined as the arc length of thestreamlines which is perpendicular to the equipotential surfaces. This methodavoided the measurement error from Euclidean distance with unique andreversible corresponding points between two surfaces, and is regarded as one of most accurate and efficient thickness measurement method currently. Due to thetopological shell of the cerebral cortex and various influence factors in dataacquisition, it is hard to classify the tissues perfectly, especially in sulci regions.In this study, the algorithm developed for sulci detection and thickness correctionwas employed to further improve the brain segmentation after the thicknessestimation. After the correction of the segmentation, the cortical thickness wasre-calculated accordingly and more accurate result was obtained for the wholebrain.
Based on the image of cortical thickness, the difference of thickness can beanalyzed with statistical parametric mapping (SPM). Group differences indemographic variables were examined with independent t-tests. All subjects inthis study came from the same community and did not differ significantly insocioeconomic status. The two groups (PTSD and non-PTSD) significantlydiffered in age. Thus, group comparisons of cortical thickness were performedusing analysis of two sample t-test in SPM8with age as covariates to account forthe age effect. Comparisons of cortical thickness in survivors experienced miningdisaster indicated that in left parietal lobe, right inferior frontal gyrus, and rightparahippocampal gyrus, cortical thickness of subjects with PTSD was obviouslythinner than those without PTSD.
To investigate the relation between thickness and s PTSD symptom severity,the region that consists of all the voxels on the streamline across the significantlythinner region was used for ROI analysis in this study. ROI-based correlationalanalysis was performed in the patients with PTSD. The mean cortical thickness ofright inferior frontal gyrus tended to correlate negatively with the CAPS score inthe identified regions from thickness analysis.
2. CBF measurement and analysis
According to selection of MRI perfusion sequences, in this study, the pulsedartery spin labeling (PASL) sequence was used to investigate the alteration ofCBF for the patients of PTSD induced by coal mine disaster, which isnon-invasive with high efficiency. In this study, an accurate CBF measurementmethod of PASL sequence was proposed.
Due to fast imaging of PASL, the resolution of image is relative low. For thisreason, SPM was used to preprocess the PASL and T1sequences, respectively.With the information of structural images applied to the functional images, theaccuracy of normalization and resolution of functional images were improved.Though the resolution of images had been improved, the images were stillaffected by partial volume effect (PVE). In this study, the acquired time of PASLsequence was used to construct the time sequence, and the MAP-EM algorithmwas used to estimate the mixed tissue model parameters. Moreover, combinedwith this PVE correction, the CBF measurement method was used to acquire thedistribution image of CBF.
Based on the CBF image, no significant difference of mean CBF was foundbetween the PTSD and non-PTSD groups. Considering the effect of age on theCBF, group comparisons of CBF were performed using analysis of two samplet-test in SPM8with age as covariates to account for the age effect. Comparisonsof CBF in survivors experienced mining disaster indicated that in right frontallobe, CBF of subjects with PTSD was obviously higher than those without PTSD.However, based on ROI analysis in patients with PTSD, no significant correlationof the CAPS score with mean CBF in right frontal lobe was observed.
3. DTI analysis
Based on the software of DTI studio and SPM, the DTI sequence wasanalyzed. Comparisons of FA and ADC in survivors experienced mining disaster indicated that in the right lateral ventricle, right fusiform gyrus, right superiortemporal gyrus, and right middle temporal gyrus, FA value of subjects with PTSDwas obviously lower than those without PTSD, and ADC value of subjects withPTSD was obviously higher in the right superior temporal gyrus and right corpuscallosum. However, based on ROI analysis in patients with PTSD, no significantcorrelation of the CAPS score with mean FA and/or ADC in above identifiedregions was observed. That may be due to subtle alteration of cortical thicknesscaused by early stage of PTSD.
4. Summary
In this study, the pipeline for cortical thickness measurement and analysiswas proposed, which improved computation speed and the accuracy of thicknessmeasurement. Meanwhile, considering the relatively low resolution and the effectof PVE on images, the PVE correction method based on MAP-EM algorithm wascombined with CBF measurement method to keep the accuracy of the CBF.These proposed methods may provide an efficient method for the corticalthickness and CBF analysis for nerve system or brain diseases.
Based on proposed methods, in this study, a series of regions withsignificant difference between PTSD and non-PTSD groups were identified.Meanwhile, based on the software of DTI studio and SPM, the DTI sequence wasanalyzed. According to multiple regression analysis, the advantage ofmulti-modality image analysis is preliminarily confirmed. These results lay asolid foundation for the further study of pathological and etiological mechanism.Furthermore, the identified regions or indexes are hopeful to be the objective andquantitative indexes to diagnosis and evaluate PTSD in clinic.
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