| Part 1 The Research of Functional Magnetic Resonance Imaging in DepressionObjective:To investigate the abnormal brain regions inpatients with depression using functional magnetic resonance imaging (fMRI) with the algorithm of fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) and to explore the role of these abnormal brain regions in depressive patients, in order to offers imaging grounds for diagnosis, pathogenesis and drug development.Materials and Methods1.Research Objects:36 patients (8 men and 28 women) coming to the Guangzhou Brain Hospital diagnosed with depression by The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) and Hamilton Depression Scale 24 item (HAMD-24) and 20 healthy volunteers sharing the similar age, gender and education years (5 men and 15 women) were collected. The age range of diseases group is 19 to 45 and average is 30.17 with 13.24 of average education years. The age range of control group is 19 to 42 and average is 30.00 with 14.58 of average education years. All the objects were right-handedness without other psychiatric illnesses, drug dependence, organic brain disorder and MRI contraindication.2.Data Collection:Data was acquired using Philips Intera Achieva 3.0Tesla MRI and 8-channel bird-cage-like array head coil. EPI was used to obtain the resting-state fMRI data, and theparameters as follows:TR=2000ms, TE=30ms, FOV=220×220× 150, Voxel size=3.44×3.44×3.44mm, Flip Angle=90°, matrix=64 X 64, Slice number is 33 with layer-by-layer, Slice thickness=4mm, Slice gap=0.6mm, NEX=1, Time Points=240, Scanning times=8 minutes. In additional, FSPGR was used during the structure phase scanning, and the parameters as follows:TR=8.2ms, TE=3.7ms, FOV=256 X 256mm, Voxel size=1×1×1mm, matrix=256, Slice number=188, NEX=1, Scanning times=11 minutes.3. Data Analysis:DPARSFA4.0 which based on MATLAB(R2012a) was applied to data preprocessing. The preprocessing steps of fALFF include data arrangement, data format conversion, rejecting first 10 time points, slice timing, realign, regression out covariates, normalize, smooth, calculating ALFF and fALFF value. While the processing steps of ReHo involve data organizing, data format conversion, rejecting first 10 time points, slice timing, realign, regression out covariates, filter, normalize, calculating ReHo value and smooth. In realign step, those subjects whose head movements exceeded 2.0mm maximum displacement and 2° maximum rotation in any direction of x, y and z. All of the subjects met the standard.4. Statistical analysis:The differences of age, gender, education years, height and weight between two groups were compared by SPSS 20.0 and a p<0.05 was deemed significant. The fALFF and ReHo documents of two groups were statistically analyzed with one-sample t-test by REST 1.8 respectively. In addition, two-sample t-test was performed for fALFF and ReHo documents of two groups. Multiple comparison correction was accomplished by AlphaSim in REST, the FWHM=6 and p value=0.05. After Monte carlo simulation of1000 times, the threshold value ofclusters size of fALFF was 76 while ReHo was 69. The differential brain regions were showed by Viewer in REST. Voxels with a p value<0.05 (after correcting) were considered to show significant differences.Results:There was no significant difference for age (t=0.081,p>0.05), gender (x2=0.55, p >0.05), height (t=1.938, p>0.05), weight (t=1.946, p>0.05) and education years (t=1.238, p>0.05) between two groups.Compared with the controls, the diseases group showed significantly increased fALFF in the left orbital part middle frontal gyrus, the right precuneus, the right opercular part inferior frontal gyrus and the right middle temporal gyrus without any brain regions’ fALFF value decreased. Besides, the ReHo in diseases group was significantly increased in the right middle temporal gyrus and decreased in the right precentral gyrus and the left postcentral gyrus.Conclusion:1. Compared with controls, these were abnormal several brain regions in which fALFF and ReHo value changes. fALFF increased significantly in the left orbital part middle frontal gyrus, the right precuneus, the right opercular part inferior frontal gyrus and the right middle temporal gyrus. There were no any brain regions which fALFF value decreased. The ReHo value of diseases group was significantly increased in the right middle temporal gyrus and decreased in the right precentral gyrus and the left postcentral gyrus.2. Combining the results of fALFF and ReHo, there were abnormal in depression patients in the frontal lobe, the right middle temporal gyrus, precuneus, the precentral gyrus and the postcentral gyrus. We found the frontal lobe especiallythe prefrontal lobe and precuneus are related to depressive pathogenesis and symptoms. What roles do the middle temporal gyrus, the precentral gyrus and the postcentral gyrus played needs further discussion. Part 2 The Research of Functional Magnetic Resonance Imaging of Sertraline and Xiaoyaosan in Treatment of DepressionObjective:To investigate the alterative brain regions in patients with depression after western medicine ortraditional Chinese medicine treatmentusing the fMRI with fALFF and ReHo, and to explore theareas of the brainon which these two medicine act, in order to offers imaging grounds for drug researchand application.Materials and Methods1. Research Objects:All the patients coming to the Guangzhou Brain Hospital diagnosed with depression by The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) and Hamilton Depression Scale 24 item (HAMD-24) was randomly divided to two groups:western medicine group (Sertraline, once per day, 50mg every time) andtraditional Chinese medicine group (Xiaoyaosan, twice per day, 9g every time). MRI scans and HAMD scale assessments were performed before and after 6 weeks treatment respectively. All the objects were right-handedness without other psychosis, drug dependence, organic brain disorder and MRI contraindication.2. Data Collection:Data was acquired using Philips Intera Achieva 3.0Tesla MRI and 8-channel bird-cage-like array head coil. The scanning sequence and theparameters were same as part 1.3. Data Analysis:DPARSFA 4.0 which based on MATLAB (R2012a) was applied to data preprocessing. The preprocessing steps of fALFF and ReHo were same as part 1. In realign step, those subjects whose head movements exceeded 2.0mm maximum displacement and 2° maximum rotation in any direction of x, y and z. Two objects of tradition Chinese group were removed.4. Statistical analysis:The fALFF and ReHo documents of two groups were statistically analyzed with one-sample t-test by REST 1.8 respectively. In addition, paired t-test was performed for fALFF and ReHo documents of two groups. Multiple comparison correction was accomplished by AlphaSim in REST, the FWHM=6 and p value=0.01. After Monte carlo simulation of1000 times, in western medicine group, the threshold value ofclusters size of fALFF was 30 while ReHo was 28, and in traditional Chinese medicine group were 29 and 28 respectively. The differential brain regions were showed by Viewer in REST. Voxels with a p value<0.05 (after correcting) were considered to show significant differences.Results:Before the medicine treatment, the HAMD scale scores of all the objects exceeded 20.In the western medicine group, the scale scores were ranged from 21 to 37 and the median was 28, while the scale scores in the traditional Chinese medicine group were range from 22 to 39 and the median was 30. After pharmacological treatment, the HAMD scale scores of all the objects was below 20. The patients in the western medicine group were having the score which ranged from 4 to 15 and the median was 11. In the traditional Chinese medicine group, the scale scores were ranged from 4 to 15 and the median was 9. Compared with the fALFF and ReHo pictures, fALFF value was significantly increased in the left middle occipital gyres and the leftcerebellum and ReHo value was decreased in the left middle frontal gyrus after western medicine treatment. And there was no any region which fALFF value decreased or ReHo value increased. In the traditional Chinese group, the ReHo values in the left medial part middle frontal gyrus, the right orbital part superior frontal gyrus, the bilateral anterior cingulate and the left middle temporal gyrus were significantly increased after treatment. There was no any region which value ReHodecreased and fALFF changes.Conclusion:1. In western medicine group, the HAMD scale scores were significantly decreased after treatment, which prompted improvement of symptoms of depression. Compared with fMRI before treatment, there were changes in several regions. fALFF value was increased in the left middle occipital gyres and the left cerebellum and ReHo value was decreased in the left middle frontal gyrus.2. In traditional Chinese medicine group, the HAMD scale scores were significantly decreased after treatment too, and it prompted the medicine could reduce disease severity. Compared with fMRI before treatment, there were changes in several regions. the ReHo values in the left medial part middle frontal gyrus, the right orbital part superior frontal gyrus, the bilateral anterior cingulate and the left middle temporal gyrus were significantly increased after treatment. There was no any region which value ReHodecreased and fALFF changes.3.The cumulative results prompted that the target brain regions of Sertraline might include the left middle occipital gyres, the left cerebellum and the left middle frontal gyrus, all these regions are correlation with emotion and cognition. While the target regions of Xiaoyaosan werethe left medial part middle frontal gyrus, the right orbital part superior frontal gyrus, the bilateral anterior cingulate and the left middle temporal gyrus. Among these regions, the prefrontal cortex and theanterior cingulate are important part of the LCSPT circuit and are considered as the parts related to pathogenesis of depression. However, What role do the middle temporal gyrus played needs further discussion. |
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