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 Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 1  |  Issue : 1  |  Page : 23-27

Diffusion tensor imaging study of brain structural integrity in patients with posttraumatic stress disorders


1 Department of Radiology, Southwest Hospital; Institute of Digital Medicine, Third Military Medical University, Shapingba, Chongqing 400038, China
2 Department of Medical Image, College of Biomedical Engineering, Third Military Medical University, Shapingba, Chongqing 400038, China
3 Institute of Digital Medicine, Third Military Medical University, Shapingba, Chongqing 400038, China

Date of Web Publication30-Sep-2015

Correspondence Address:
Mingguo Qiu
Department of Medical Image, College of Biomedical Engineering, Third Military Medical University, Shapingba, Chongqing 400038
China
Shaoxiang Zhang
Institute of Digital Medicine, Third Military Medical University, Shapingba, Chongqing 400038
China
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Source of Support: The National High-Tech Research and Development Projects of China (863) (2012AA021105); the National Natural Science Foundation of China (Grant No.U1401254); the Major Science and Technology Projects of Guangdong province (Grant No.2012A080203013), Conflict of Interest: None declared.


DOI: 10.4103/2226-8561.166367

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  Abstract 

Objective: To explore the changes of brain structural integrity in patients with posttraumatic stress disorders (PTSD) using diffusion tensor imaging (DTI). Patients and Methods: Twenty PTSD patients who underwent a traffic accident and 20 non-PTSD patients were selected from the Department of Rehabilitation, Southwest Hospital of the Third Military Medical University in Chongqing, China, between January 2007 and December 2013. Using voxel-based analysis, we investigated fractional anisotropy (FA) and mean diffusivity (MD) in PTSD patients. Linear correlation analysis was employed to detect the relationship between FA and MD in regions of interest, and to obtain PTSD Checklist-Civilian Version scores. Results: When compared with the non-PTSD group, the FA of PTSD patients significantly decreased in bilateral middle frontal gyrus, right superior frontal gyrus, and left putamen (P < 0.005). The MD of PTSD patients increased mainly in bilateral middle frontal gyrus, anterior cingulate cortex, left amygdala, left insula, and left globus pallidus (P <0.005). Pearson correlation analysis revealed that the FA value of right middle frontal cortex (MFC) had a significant negative correlation with the PTSD score (r = −0.628, P = 0.039), while the MD value of right MFC and left amygdala had a significant positive correlation with the PTSD score (r = 0.630, P = 0.047; r = 0.632, P = 0.041, respectively). Conclusion: The abnormalities of structural integrity in the amygdala and middle frontal gyrus may be the structural foundation of emotional and memory dysfunction in PTSD.

Keywords: Diffusion tensor imaging, fractional anisotropy, mean diffusivity, posttraumatic stress disorder


How to cite this article:
Xie B, Zhang J, Zhang Y, Zhang S, Qiu M. Diffusion tensor imaging study of brain structural integrity in patients with posttraumatic stress disorders. Digit Med 2015;1:23-7

How to cite this URL:
Xie B, Zhang J, Zhang Y, Zhang S, Qiu M. Diffusion tensor imaging study of brain structural integrity in patients with posttraumatic stress disorders. Digit Med [serial online] 2015 [cited 2021 Dec 8];1:23-7. Available from: http://www.digitmedicine.com/text.asp?2015/1/1/23/166367


  Introduction Top


Posttraumatic stress disorder (PTSD) is classified as a postponed and long-lasting psychological disorder resulting from suddenly threatening or catastrophic life events.[1] It is clinically characterized by pathological re-experiencing, constant avoidance, selective amnesia of traumatic events, and sustained alertness increase. Traffic accident often happens in a short time, with an irritative scene. It makes the traumatic patients easily have a psychological illness, and 18–23% of these people will have PTSD within 6 months after suffering the traffic accidents.[2] It is important and essential to evaluate the effects of PTSD after the traffic accidents on the microstructure of brain integrity and neurobehavioral outcomes.

Neuroimaging studies have suggested that structural and functional changes exist in the brains of PTSD patient, mostly in cerebral areas relative to emotion and memory including prefrontal lobe, limbic system, and paralimbic system (e.g., anterior cingulate cortex [ACC], hippocampus, amygdala, insula). These studies mainly focused on functional activation of the brain area and density abnormalities of gray matter and white matter.[3],[4],[5],[6] Findings from the functional and structural neuroimaging studies have yielded tremendous advances in understanding the neural mechanisms underlying PTSD.[7] Lyoo et al.[8] found that trauma-exposed PTSD individuals recovering from a South Korean subway disaster had greater dorsolateral prefrontal cortical (DLPFC) thickness 1.42 years after trauma than controls, and the greater DLPFC thickness was associated with greater PTSD symptom reductions and better recovery. Using the resting functional magnetic resonance imaging (fMRI), Bluhm et al.[9] have compared women with early-life trauma to healthy women, and found that spontaneous low-frequency activity in the default network during rest was altered in patients with PTSD, and that spontaneous activity in the PCC/precuneus was more strongly correlated with activity in other areas of the default network in healthy controls than in patients with PTSD.

A newer magnetic resonance imaging (MRI) method and diffusion tensor imaging (DTI) can characterize tissue microstructure quantitatively.[10],[11],[12],[13] It has been shown that DTI is sensitive to microstructural alterations in a range of psychiatric disorders [14],[15],[16],[17] including PTSD patients.[18],[19],[20],[21] However, the studies on micro-change and integrity of cerebral structure in PTSD patients lack a consistent conclusion. Therefore, the present study aims to investigate cerebral structure changes in PTSD patients after traffic trauma, and to further analyze whether the structure changes would be related with the clinical signs.


  Patients and Methods Top


In our study, the patients were selected from the Department of Rehabilitation, Southwest Hospital, the Third Military Medical University in Chongqing, China, between January 2007 and December 2013. Twenty PTSD patients with traffic trauma rehabilitation were included in our study (12 males, eight females, right-handiness, aging from 21 to 42 years, mean age = 26.4 ± 15.6 years). According to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, PTSD diagnosis was made by a psychiatrist and psychotherapeut. Twenty non-PTSD patients with traffic trauma rehabilitation were included in the control group (13 males, seven females, right-handiness, aging from 20 to 40 years, mean age = 25.3 ± 14.7 years). There were no significant differences in age, gender, and education levels between the two groups. The patients in both groups had lower extremity or spine injury, definitely without brain trauma, medication overuse, and nervous system diseases (e.g. epilepsy). Before the examination, each subject signed written informed consent and completed a self-evaluation using PTSD Checklist-Civilian Version (PCL-C).

Ethics statement

This study was approved by Ethics Committee of the Third Military Medical University.

Data acquisition

The imaging data were collected on 3.0T MRI scanner (Trio, Siemens Medical Erlangen, Germany). A three-dimensional T1-weighted imaging (T1WI) in sagittal view was acquired using a magnetization prepared rapid gradient-echo sequence (TR = 1900 ms, TE = 2.34 ms, FOV = 256 mm × 256 mm, thickness = 1.0 mm, 166 slices). The diffusion tensor images covering the whole brain were acquired using a DTI-echo planar imaging sequence (TR = 9000 ms, TE = 106 ms, FOV = 240 mm × 240 mm, matrix = 128 × 128, thickness = 3 mm, 45 slices, continuous scan, 30 diffusion gradient directions, b values of 0, and 1000 s/mm 2). The subjects were required to keep quiet and still at the supine position during scanning. The T1WI data were assessed by an experienced radiologist. All the subjects were found to have no morphological abnormalities.

Data processing and analysis

DTI data were preprocessed and analyzed by FMRIB Software Library (FSL, Version 4.1.0 http://www.fmrib.ox.ac.uk/fsl/) and SPM8 (http://www.fil.ion.ucl.ac. uk/spm/). First, the data preprocessing was as follows: (1) Segregation of brain tissue from non-brain tissue using the Brain Extraction Tool;[22] (2) eddy current and head movement correction using eddy correct from FMRIB's Diffusion Toolbox;[23] (3) rotation of the gradients according to the corrected parameters from steps (2); (4) local fitting of diffusion tensors and construction of individual fractional anisotropy (FA) maps and mean diffusivity (MD) maps using DTIFIT from FMRIB's Diffusion Toolbox;[23] (5) normalization of the individual FA maps into a standard space (Montreal Neurological Institute) using SPM8, and these transformations were then also applied to MD maps; (6) FA maps and MD maps were smoothed with a Gaussian kernel of 6 mm full width at half maximum by SPM8. Then, general linear models were applied to the FA maps and MD maps, and the significance of the differences between the two groups was calculated by voxel-wise analysis. The brain areas with abnormal FA and MD in the PTSD patients were detected. Finally, we extracted the average FA and MD in the abnormal regions, and further investigated the relationship between FA and MD in the abnormal regions and PCL-C scores with Pearson correlation analysis.


  Results Top


Posttraumatic stress disorders Checklist-Civilian version evaluation results

The PCL-C score of the PTSD group ranged from 38 to 63 (mean = 47.7), and that of the non-PTSD group from 18 to 31 (mean = 25.6). The results revealed that the PCL-C score of the PTSD group was significantly higher than that of the non-PTSD group (t = 6.901, P<0.01).

Abnormal cerebral structural regions of posttraumatic stress disorder patient

In the PTSD patients, the FA values of bilateral middle frontal cortex (MFC), right superior prefrontal cortex (SPFC), and left putamen were significantly decreased (P<0.005, voxel>15) [Figure 1]a and [Table 1]. The MD values of bilateral MFC, left amygdala, ACC, left insula, and left globus pallidus (GP) were significantly increased (P<0.005, voxel>15) [Figure 1]b and [Table 2].
Figure 1: The brain areas of posttraumatic stress disorder patients with significant changes of fractional anisotropy and mean diffusivity. (a) Significant decrease of fractional anisotropy, (b) significant increase of mean diffusivity

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Table 1: The brain areas with significant decrease of FA in the PTSD group comparing to the non-PTSD group (P < 0.005)

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Table 2: The brain areas with significant increase of MD in the PTSD group comparing to the non-PTSD group (P < 0.005)

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Correlation analysis

Pearson correlation analysis revealed that the FA value of right MFC had a significant negative correlation with PTSD score (r = −0.628, P = 0.039) [Table 3], and the MD values of right MFC and left amygdala had significant positive correlations with PTSD score (r = 0.630, P = 0.047; r = 0.632, P = 0.041, respectively) [Table 4]. However, the FA and MD values of the other abnormal cerebral areas had no significant correlations with PTSD score [Table 3] and [Table 4].
Table 3: Correlation analysis between decreased FA and PTSD score

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Table 4: Correlation analysis between increased MD and PTSD score

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  Discussion Top


In the present study, we investigated the brain structural integrity in PTSD patients using DTI. By comparing FA and MD values between PTSD patients and non-PTSD controls, we found that PTSD patients exhibited decreased FA values in the bilateral MFC, right SPFC and left putamen, and increased MD values in the bilateral MFC, left amygdala, ACC, insula, and GP. Our findings might provide structural evidence for dysfunctional emotion and memory in PTSD patients. FA and MD, respectively, reflect direction and intensity of water molecular diffusion in vivo. Being subject to restriction by biomembrane (e.g. cytomembrane), the water molecular diffusion shows obvious anisotropy. FA basically describes the diffusion starting from cerebral areas longitudinally along fibers, and MD is the mean value of three diffusions (X-direction, Y-direction, and Z-direction). FA and MD are useful and comprehensive to evaluate cerebral microstructure. When brain tissue is invaded, the integrity is destructed with FA decrease and MD increase.[24] Our study found that the MD of bilateral MFC in PTSD patients increased and the FA decreased, which suggested somewhat of MFC's nonintegrity. Our study also found that the MD values of ACC, left amygdala and insula in the PTSD group were significantly higher than those in the control group while there were no significant differences for the FA values. We speculated that some pathological changes could exist in these areas (e.g., myelinoclasis, Wallerian degeneration), resulting in an increase of the diffusion horizontally perpendicular to fiber, but without obvious influence on that longitudinally along the fiber. Thus, FA change in these regions was not obvious, but MD increase was. Our results from the perspective of cerebral integrity may provide a reliable objective evidence for the early radiological diagnosis of traumatic PTSD patients.

Voxel-based analysis (VBA) can be used to explore diffusion change of different areas in the whole brain, which is useful for finding new lesions and positioning the area with the lesion. Based on the prior information and results of VBA, we extracted regions with abnormal FA and MD values in PTSD patients as region of interests (ROIs), and further quantitatively analyzed the relationship between FA/MD of ROIs and PCL-C, which could increase the accuracy and targeting. The results showed that FA value of right MFC had a significant negative correlation with PTSD score (r = −0.628, P = 0.039), the MD values of right MFC and left amygdala had significant positive correlations with PTSD score (r = 0.630, P = 0.047; r = 0.632, P = 0.041, respectively). These findings indicated that amygdala and MFC play important roles in the pathophysiologic mechanism of PTSD.

Amygdala is the most important area, processing memory and fear. Previous fMRI studies have suggested that with stimulations of trauma-related images, sounds, and words, the amygdala in PTSD patients significantly gets activated, presenting as abnormal activation.[3],[25] Some studies have indicated that there is a positive correlation between amygdala activation and PTSD severity.[26] In addition, Rogers et al.[27] found that amygdala volumes of PTSD patient were significantly smaller. Medial prefrontal cortex (MPFC) is considered to correlate with emotion regulation. MPFC was reported to have functional and structural abnormalities in some previous studies.[3] Britton [28] used positron emission tomography to study 16 PTSD patients suffering from wars and found that the MPFC activation decreased during trauma-related imagination. Gold et al.[29] found the MPFC was significantly inactive during nontrauma-related stress task imagination. In the present study, we found the decreased integralities of amygdala and MFC, as well as the significant correlations with clinical signs of PTSD. These findings suggested the pathological changes in amygdale and MFC might play important roles in the emotional disorder of PTSD. We speculated that the decreased integralities of amygdala and MFC might be the structural basis of functional disorders of emotion and memory of PTSD patient.


  Conclusion Top


The findings of our study confirmed the previous neuroimaging results of PTSD. Furthermore, we found a structural specific change of amygdala and MFC in PTSD pathology, which might be the structural foundation of dysfunctional emotion and memory in PTSD patients. One of the limitations of this study is a shortage of samples. In future work, we will increase samples and explore the anatomy relative to emotion-processing of PTSD to further reveal the correlation between structural change and clinical sign and provide imaging basis for PTSD treatment.

 
  References Top

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    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]


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