本文選題：復(fù)發(fā)緩解型 + 多發(fā)性硬化��； 參考：《南方醫(yī)科大學(xué)》2014年碩士論文

【摘要】：[目的] 利用3.0T Philips磁共振擴(kuò)散張量成像技術(shù)(DTI)并采用基于纖維束示蹤的空間統(tǒng)計(jì)(TBSS)的方法觀察復(fù)發(fā)緩解型多發(fā)性硬化患者全腦白質(zhì)微結(jié)構(gòu)改變,評價(jià)DTI兩個(gè)參數(shù)(FA、 MD/ADC)值在多發(fā)性硬化患者腦白質(zhì)微結(jié)構(gòu)及視覺通路損傷中的應(yīng)用價(jià)值,探索全腦白質(zhì)、視覺通路纖維束損害的特點(diǎn)以及可能的發(fā)病機(jī)制,從而為多發(fā)性硬化患者的臨床診斷提供客觀的影像學(xué)依據(jù)。 [材料及方法] 1.研究對象 本研究搜集2012年8月至2014年3月在廣州南方醫(yī)科大學(xué)南方醫(yī)院影像中心接受MRI檢查的復(fù)發(fā)緩解型多發(fā)性硬化(Relapsing-remitting Multiple Sclerosis, RRMS)患者共21例,男6例,女15例,年齡27-61歲,平均45.48±12.87歲,受教育程度6-16年,平均12.85±3.55年；病程(首次發(fā)病到最近一次發(fā)病時(shí)間)0.04-15.5年,平均7.09±5.46年；復(fù)發(fā)緩解次數(shù)2-7次,平均3.71±1.85年。所有RRMS患者符合2010年McDonald的MS診斷標(biāo)準(zhǔn),磁共振檢查前兩個(gè)月內(nèi)未使用過糖皮質(zhì)激素、免疫抑制劑等藥物。 正常對照組21例(性別、年齡、文化程度與RRMS組差異無統(tǒng)計(jì)學(xué)意義),男9例,女12例,年齡26-60歲,平均年齡46.71±11.68歲,受教育程度6-16年,平均13.35±2.85年。無任何臨床不適癥狀,無顱內(nèi)疾病病史及外傷史,無認(rèn)知功能障礙,行常規(guī)MRI檢查頭顱及視覺通路未見異常信號(hào)改變。所有納入的研究對象對本實(shí)驗(yàn)均知情同意。 2.掃描設(shè)備及序列 磁共振數(shù)據(jù)采集使用飛利浦3.0T磁共振掃描儀(Philips, Achieva,the Netherlands)并采用標(biāo)準(zhǔn)8通道頭顱線圈接收核磁共振信號(hào)。DTI數(shù)據(jù)采集之前均進(jìn)行全腦軸位T1WI、T2WI、 FLAIR掃描。頭顱常規(guī)平掃參數(shù)如下：軸位TSET2WI (TR/TE=3000/80ms),軸位T1WI (TR/TE=2000/120ms),軸位FLAIR (TR/TE=9000/120ms);翻轉(zhuǎn)角(flip angle)=90°;矩陣(matrix size)=460×268;視野(FOV)=230mm×230mm;激勵(lì)次數(shù)(NEX)=1；層厚(thickness)=6.Omm;層數(shù)(slice)=20;層間距(slice gap)=0。 頭顱常規(guī)DTI掃描參數(shù)：采集使用單次激發(fā)自旋回波平面回波序列,SPIR壓脂掃描,掃描以大腦前-后聯(lián)合連線平面為參考平面。TR/TE=9000/85ms, FOV=230mm×230mm,矩陣=92x108,b=0,1000s/mm2,層厚=2mm,層間距0,NEX=2,擴(kuò)散方向32個(gè),共掃描60層,掃描時(shí)間9min27s。 視覺通路DTI掃描參數(shù)同常規(guī)DTI掃描參數(shù),掃描以視交叉-后聯(lián)合(CH-PC)連線平面為參考平面。掃描時(shí)受試者全程保持頭部固定,雙眼閉合。3.DTI數(shù)據(jù)處理 3.1全腦白質(zhì)數(shù)據(jù)處理 首先采用MRIcron(http://www.mccauslandcenter.sc.edu/mricro/mricron/install)將每個(gè)被試者的1組B0圖像與相應(yīng)的32組擴(kuò)散加權(quán)二維圖像的DICOM數(shù)據(jù)格式轉(zhuǎn)化為四維NIFTI數(shù)據(jù)格式,其中包含了三維影像,并代表不同的擴(kuò)散權(quán)重梯度場強(qiáng)方向。 DTI數(shù)據(jù)分析采用FSL (http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/FSL5.0.6)軟件包。具體處理步驟包括：①使用FSL軟件中的Eddy correct函式對轉(zhuǎn)換好的DTI數(shù)據(jù)進(jìn)行頭動(dòng)及渦流校正。②利用FSL軟件中的BET函式,以每個(gè)被試者的B0圖像作為依據(jù)產(chǎn)生各自的腦Mask。③通過FDT中的DTIFIT函式,將梯度磁場方向、磁場強(qiáng)度的數(shù)值以及四維NIFTI格式圖像,連同各個(gè)被試的Mask輸入DTIFIT函式進(jìn)行擴(kuò)散張量計(jì)算。輸出的結(jié)果將包含部分各向異性(fractional anisotropy, FA)、平均擴(kuò)散率(mean diffusivity、及相對應(yīng)的三個(gè)特征向量(V1、V2、V3)。然后按TBSS四部標(biāo)準(zhǔn)流程進(jìn)行分析,包括tbss_1_preproc、 tbss_2_reg-T、 tbss_3_postreg-S、tbss_4_prestat，利用Randomize函式對兩組的FA值進(jìn)行基于纖維素示蹤的全腦非參數(shù)統(tǒng)計(jì)比較,以P0.05作為統(tǒng)計(jì)檢驗(yàn)水準(zhǔn),加入無閾值簇增強(qiáng)(threshold-free cluster enhancement，TFCE)選項(xiàng)以校正多重比較中的I類錯(cuò)誤。再將所有受試者各自的FA圖非線性配準(zhǔn)到MD圖上,生成配準(zhǔn)后的參數(shù)圖,并將之投射到平均FA纖維骨架上,進(jìn)行基于纖維素示蹤的全腦非參數(shù)統(tǒng)計(jì)比較。 3.2雙側(cè)視神經(jīng)評價(jià) 將掃描的原始DTI圖像傳至Philips后處理工作站。使用Diffusion軟件獲得各向異性分?jǐn)?shù)(FA)圖、表觀彌散系數(shù)(ADC)圖及彩色編碼圖,結(jié)合T2WI序列,選取雙側(cè)視神經(jīng)球后段,在FA圖、ADC圖上畫感興趣區(qū)(region of interest,ROI),大小為5.5mm2,測量雙側(cè)視神經(jīng)球后段FA值及ADC值,測量三次取平均值。 4.統(tǒng)計(jì)學(xué)分析 所得數(shù)據(jù)均以均數(shù)±標(biāo)準(zhǔn)差(x±s)來表示,應(yīng)用SPSS13.0軟件兩獨(dú)立樣本t檢驗(yàn)的統(tǒng)計(jì)方法比較復(fù)發(fā)緩解型多發(fā)性硬化組與正常對照組之間年齡、受教育程度的差異,卡方檢驗(yàn)評價(jià)兩被試組之間性別差異。全腦白質(zhì)纖維骨架平均FA值、MD值圖組間基于體素的比較,采用Randomize函式進(jìn)行非參數(shù)統(tǒng)計(jì)閾值分析的統(tǒng)計(jì)方法,置換測試次數(shù)5000,采用以簇為基礎(chǔ)的校正方法進(jìn)行多重比較校正。P0.05且簇50個(gè)體素(體素大小：1×1×1mm3)認(rèn)為有統(tǒng)計(jì)學(xué)意義。P0.01認(rèn)為差異有顯著性統(tǒng)計(jì)學(xué)意義。采用偏相關(guān)分析方法,以患者年齡、復(fù)發(fā)緩解次數(shù)為協(xié)變量,比較病程與全腦有顯著性差異腦區(qū)的FA值、MD值的相關(guān)性；以年齡、病程為協(xié)變量,比較復(fù)發(fā)緩解次數(shù)與全腦有顯著性差異腦區(qū)的FA值、MD值的相關(guān)性,P0.05認(rèn)為有統(tǒng)計(jì)學(xué)意義。 [結(jié)果] 1.腦白質(zhì)分析結(jié)果 RRMS患者全腦雙側(cè)額葉、顳葉、頂葉及枕葉腦白質(zhì)區(qū)域纖維素呈廣泛性FA值減低,MD值升高,差異有統(tǒng)計(jì)學(xué)意義(P0.05)；左側(cè)上縱束、雙側(cè)下縱束、左側(cè)上枕額束、雙側(cè)下額枕束、胼胝體膝部、壓部、右側(cè)扣帶束、左側(cè)鉤束、右側(cè)內(nèi)囊前肢、雙側(cè)外囊FA值明顯減低,與對照組比較差異有顯著統(tǒng)計(jì)學(xué)意義(P0.01)；左側(cè)下縱束、雙側(cè)下枕額束、胼胝體膝部、壓部、右側(cè)扣帶束、左側(cè)鉤束、右側(cè)內(nèi)囊前肢、雙側(cè)外囊FA值顯著減低(P0.001)。左側(cè)上縱束、雙側(cè)下縱束、雙側(cè)上枕額束、雙側(cè)下額枕束、胼胝體膝部、壓部、雙側(cè)扣帶束、雙側(cè)鉤束、左側(cè)內(nèi)囊前肢、左側(cè)內(nèi)囊后肢、雙側(cè)外囊MD值明顯升高,差異有顯著統(tǒng)計(jì)學(xué)意義(P0.01)。雙側(cè)下縱束、雙側(cè)上枕額束、胼胝體膝部、壓部、左側(cè)扣帶束、雙側(cè)鉤束、左側(cè)內(nèi)囊后肢MD值較對照組顯著升高(P0.001)。RRMS組未發(fā)現(xiàn)FA值明顯增高、MD值明顯減低的纖維束。 偏相關(guān)性分析：以年齡及復(fù)發(fā)緩解次數(shù)為協(xié)變量,胼胝體膝部(r=-0.539,P=0.017)、右內(nèi)囊前肢(r=-0.524,P=0.016)的FA值與病程(首次發(fā)病至最近一次發(fā)病)呈負(fù)相關(guān)；胼胝體膝部(r=0.514,P=0.024)、左上縱束(r=0.479,P=0.038)的MD值與病程呈正相關(guān)(P0.05)。其余組間有差異的腦白質(zhì)區(qū)FA值、MD值與病程之間的相關(guān)性無統(tǒng)計(jì)學(xué)意義(P0.05)。以年齡及病程為協(xié)變量,各組間有差異的腦白質(zhì)區(qū)FA值、MD值與復(fù)發(fā)緩解次數(shù)之間的相關(guān)性無統(tǒng)計(jì)學(xué)意義(P0.05)。 2.視覺通路分析結(jié)果： RRMS組雙側(cè)視神經(jīng)、視束及視輻射FA值較正常對照組減低,差異有統(tǒng)計(jì)學(xué)意義(P0.05)；左側(cè)視神經(jīng)、雙側(cè)視束及視輻射FA值較正常對照組減低,差異有顯著性統(tǒng)計(jì)學(xué)意義(P0.01)。雙側(cè)視束及雙側(cè)視輻射MD值較正常對照組升高,差異有顯著統(tǒng)計(jì)學(xué)意義(P0.01),雙側(cè)視神經(jīng)MD值兩組間比較差異無統(tǒng)計(jì)學(xué)意義(P0.05)。 偏相關(guān)性分析：以年齡及復(fù)發(fā)緩解次數(shù)為協(xié)變量,RRMS患者右側(cè)視束(r=-0.545,P=0.016)的FA值與病程呈負(fù)相關(guān)。其余組間FA值、MD值與病程相關(guān)性無統(tǒng)計(jì)學(xué)意義(P0.05)。以年齡及病程為協(xié)變量,RRMS患者左側(cè)視輻射(r=-0.531,P=0.019)的FA值與復(fù)發(fā)緩解次數(shù)呈負(fù)相關(guān)(P0.05)。其余組間FA值、MD值與復(fù)發(fā)緩解次數(shù)之間的相關(guān)性無統(tǒng)計(jì)學(xué)意義(P0.05)。 [結(jié)論] l.RRMS患者雙側(cè)額葉、顳葉、頂葉及枕葉腦白質(zhì)區(qū)存在廣泛的腦白質(zhì)損傷,其中以左側(cè)上縱束、雙側(cè)下縱束、雙側(cè)上枕額束、雙側(cè)下額枕束、胼胝體膝部、壓部、雙側(cè)扣帶束、雙側(cè)鉤束、雙側(cè)內(nèi)囊前肢、左側(cè)內(nèi)囊后肢及雙側(cè)外囊損傷更明顯。 2.在RRMS患者白質(zhì)損傷區(qū)域中,胼胝體膝部、右側(cè)內(nèi)囊前肢的FA值與病程呈負(fù)相關(guān)：胼胝體膝部、左側(cè)上縱束的MD值與病程呈正相關(guān)。 3.RRMS患者視覺通路中雙側(cè)視神經(jīng)、雙側(cè)視束及雙側(cè)視輻射存在損傷。 4.RRMS患者右側(cè)視束的FA值與病程呈負(fù)相關(guān),左側(cè)視輻射的FA值與復(fù)發(fā)緩解次數(shù)呈負(fù)相關(guān)。 5.DTI在復(fù)發(fā)多發(fā)性硬化患者中有很高的診斷價(jià)值,TBSS后處理方法能夠能在活體細(xì)胞水平對腦白質(zhì)異常的區(qū)域進(jìn)行更準(zhǔn)確的定位,定量評估腦白質(zhì)的完整性及損傷,可監(jiān)測全腦的白質(zhì)及視覺通路的潛在性損傷,為臨床提供客觀定量的影像學(xué)依據(jù)。
[Abstract]:[Objective]
3.0T Philips magnetic resonance diffusion tensor imaging (DTI) and spatial statistics (TBSS) based on fiber bundle tracer (TBSS) were used to observe the changes in the white mass structure of the whole brain of the patients with relapsed remission multiple sclerosis, and evaluate the application of the two parameters of DTI (FA, MD/ADC) in the white mass structure and visual pathway damage of the patients with multiple hardened brain. To explore the characteristics of the white matter in the whole brain, the characteristics of the damage of the fiber bundle of the visual pathway and the possible pathogenesis, so as to provide an objective imaging basis for the clinical diagnosis of the patients with multiple sclerosis.
[materials and methods]
1. research objects
This study collected 21 cases of recurrent remission multiple sclerosis (Relapsing-remitting Multiple Sclerosis, RRMS) in the imaging center of Southern Hospital of Southern Medical University, Guangzhou, from August 2012 to March 2014. There were 6 males and 15 females, 27-61 years old, with an average of 45.48 + 12.87 years old. The average education level was 6-16 years, and the average was 12.85 + 3.55 years. The course of disease (first onset to the most recent onset time) was 0.04-15.5 years, average 7.09 + 5.46 years, relapse remission times 2-7 times, averaging 3.71 + 1.85 years. All RRMS patients were in line with the MS diagnostic criteria of McDonald in 2010, and no glucocorticoids and immunosuppressive drugs were used within two months before magnetic resonance examination.
There were 21 cases of normal control group (sex, age, education level and RRMS group), 9 men, 12 women, 26-60 years old, and the average age was 46.71 + 11.68 years old. The average age was 46.71 + 11.68 years old. The average age of education was 6-16 years, and the average was 13.35 + 2.85 years. There was no clinical discomfort symptoms, no history of intracranial disease and trauma, no cognitive dysfunction, routine MRI examination of skull and No abnormal signal changes were found in the visual pathway. All participants were informed and agreed with the experiment.
2. scanning equipment and sequence
Magnetic resonance data acquisition using the PHILPS 3.0T magnetic resonance scanner (Philips, Achieva, the Netherlands) and using a standard 8 channel head coil to receive NMR signal.DTI data collected before the.DTI data acquisition of all brain axis T1WI, T2WI, FLAIR scan. 2000/120ms), axis FLAIR (TR/TE=9000/120ms), turning angle (flip angle) =90 degree; matrix (matrix size) =460 x 268; visual field (FOV) =230mm x 230mm;
Routine DTI scan parameters of head: acquisition and use of single excited spin echo plane echo sequence, SPIR compression scan, scanning with front and back joint plane of brain as reference plane.TR/TE=9000/85ms, FOV=230mm x 230mm, matrix =92x108, b=01000s/mm2, layer thickness =2mm, interval 0, NEX=2, and diffusion direction 32, scanning 60 layers, scanning time 9min27 S.
The DTI scanning parameters of the visual pathway and the conventional DTI scanning parameters were scanned with the optic cross and post Union (CH-PC) line plane as the reference plane. The subjects kept the head fixed throughout the scan and the.3.DTI data processing in the eyes closed.
Data processing of 3.1 white matter in the whole brain
First, MRIcron (http://www.mccauslandcenter.sc.edu/mricro/mricron/install) is used to transform 1 groups of B0 images of each participant and the corresponding DICOM data format of 32 groups of diffusion-weighted images into four dimensional NIFTI data format, which contains three dimensional images and represents the different direction of the gradient field strength of the different diffusion weight.
The DTI data analysis uses the FSL (http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/FSL5.0.6) software package. The specific processing steps include: (1) using the Eddy correct function of the FSL software to carry out the head motion and eddy current correction of the converted DTI data. (2) using the BET function in FSL software to produce their respective brain Ma on the basis of the B0 images of each person. Sk. (3) through the DTIFIT function in FDT, the gradient magnetic field direction, the magnetic field intensity value and the four dimensional NIFTI format image are calculated with the Mask input DTIFIT function of each test. The output results will include the partial anisotropy (fractional anisotropy, FA), the average diffusivity (mean diffusivity, and the corresponding three). Feature vectors (V1, V2, V3). Then analyzed by four standard TBSS processes, including tbss_1_preproc, tbss_2_reg-T, tbss_3_postreg-S, tbss_4_prestat, using the Randomize function to carry out the non parametric statistical comparison of the two groups of FA values based on cellulose tracers, taking P0.05 as the statistical test level, adding no threshold cluster enhancement (threshold-). The free cluster enhancement, TFCE) option is used to correct the I class errors in multiple comparisons. Then, all the FA diagrams of all the subjects are registered on the MD graph, and the registration parameters are generated and projected onto the average FA fiber skeleton for non parametric statistical comparison of the whole brain based on cellulose tracers.
3.2 bilateral optic nerve evaluation
The scanned original DTI images were passed to the Philips post processing workstation. The Diffusion software was used to obtain the anisotropic fraction (FA), the apparent dispersion coefficient (ADC) and color coding, and the posterior segment of the bilateral optic nerve ball was selected with the T2WI sequence, and the region of interest (region of interest, ROI) was drawn on the FA map and ADC diagram, and the size was measured, and the bilateral optic gods were measured. The average FA value and ADC value of the posterior segment were measured three times.
4. statistical analysis
The data were all represented by mean mean standard deviation (x + s), and the statistical method of SPSS13.0 software two independent sample t test was used to compare the age between the relapsing remission multiple sclerosis group and the normal control group and the difference in education degree. The chi square test evaluated the gender difference between the two groups. The average FA value of the whole brain white matter fiber skeleton and the MD value group Based on the comparison of voxel, the statistical method of non parametric statistical threshold analysis was carried out by Randomize function. The number of replacement tests was 5000. The cluster based correction method was used for multiple comparison correction.P0.05 and cluster 50 elements (voxel size: 1 * 1 x 1mm3) considered statistically significant.P0.01. Using the method of partial correlation analysis, the patients' age and relapse remission times were co variables, the FA value and the correlation of MD value were compared between the course of the disease and the whole brain, and the age and the course of disease were co variables. The correlation of the FA value and the MD value of the relapse remission times with the whole brain was compared, and the P0.05 was statistically significant.
[results]
1. brain white matter analysis results
RRMS patients with bilateral frontal lobes, temporal lobes, parietal lobe and occipital lobes had extensive FA values and increased MD values, with significant differences (P0.05); left superior longitudinal fascicles, bilateral inferior longitudinal fascicles, bilateral inferior occipital fasciculus, the genu of the corpus callosum, the right buckle band, left hook bundle, right internal capsule forelimb, bilateral outer capsule, F. The A value was significantly lower than that in the control group (P0.01); the left inferior longitudinal fasciculus, bilateral inferior occipital fasciculus, the genu of the corpus callosum, the right cingulate bundle, the left hook bundle, the right inner capsule front, and the bilateral outer capsule FA value decreased significantly (P0.001). The left superior longitudinal fasciculus, bilateral inferior longitudinal fascicles, bilateral occipital fasciculus, corpus callosum Knee, pressure, bilateral buckle, bilateral hook, left internal capsule forelimb, left internal capsule hind limbs, bilateral outer capsule MD value increased significantly, the difference was significant (P0.01). Bilateral lower longitudinal fasciculus, bilateral upper occipital fasciculus, corpus callosum, pressure part, left cingulate bundle, double hook bundle, left internal capsule posterior limb MD value was significantly higher than the control group (P0.001).RRMS group (P0.001) group.RRMS No significant increase in FA value and significant decrease in MD value were observed.
Partial correlation analysis: the FA value of the corpus callosum (r=-0.539, P=0.017) and the anterior limb of the right internal capsule (r=-0.524, P=0.016) was negatively correlated with the course of disease (the first onset of the first onset), the corpus callosum (r=0.514, P=0.024), the MD value of the upper left longitudinal bundle (r=0.479, P=0.038) in the corpus callosum was positively correlated with the course of the disease (P0.05). There was no significant correlation between the FA value of the white matter area between the other groups and the correlation between the MD value and the course of disease (P0.05). With age and course of disease as covariate, there was a difference in the FA value of the white matter area between each group, and the correlation between the MD value and the remission times was not statistically significant (P0.05).
2. visual pathway analysis results:
The FA value of bilateral optic nerve, optic tract and optic radiation in group RRMS was lower than that of the normal control group (P0.05). The left optic nerve, bilateral optic tract and visual radiation FA were lower than those of the normal control group, the difference was statistically significant (P0.01). The MD value of bilateral optic tract and bilateral optic radiation was higher than that of the normal control group, the difference was statistically significant There was no significant difference in P0.01 (MD) between the two groups (P0.05).
Partial correlation analysis: the FA value of the right visual tract (r=-0.545, P=0.016) of RRMS patients was negatively related to the course of disease with age and relapse remission times. There was no statistical significance between the FA value of the other groups and the correlation between the MD value and the course of disease (P0.05). The FA value of the left visual radiation (r=-0.531, P=0.019) in RRMS patients and the relapse remission of the RRMS patients were associated with the age and course of disease. There was a negative correlation between the number of times (P0.05). There was no statistically significant correlation between the FA value, MD value and relapse remission frequency among the rest groups (P0.05).
[Conclusion]
There were extensive brain white matter injuries in the frontal lobe, temporal lobe, parietal lobe and occipital lobe of l.RRMS patients, including the left superior longitudinal fasciculus, bilateral inferior longitudinal fasciculus, bilateral occipital frontal fasciculus, bilateral inferior occipital fasciculus, the corpus callosum, bilateral buckle band, bilateral hook tract, bilateral internal capsule forelimb, left internal capsule hind limbs and bilateral outer capsule.
2. in the area of white matter injury in RRMS patients, the FA value of the corpus callosum and the right side of the right internal capsule was negatively correlated with the course of the disease: the MD value of the corpus callosum and the left superior longitudinal bundle was positively correlated with the course of disease.
The bilateral optic nerve, bilateral optic tract and bilateral optic radiation were damaged in the visual pathway of 3.RRMS patients.
The FA value of the right optic tract in 4.RRMS patients is negatively correlated with the course of disease. The FA value of the left visual radiation is negatively correlated with the number of remission times.
5.DTI has a high diagnostic value in patients with recurrent multiple sclerosis. TBSS post-processing can be able to accurately locate the area of abnormal white matter in the living cell level, evaluate the integrity and damage of the brain white matter, monitor the potential damage of the white matter and visual pathway in the whole brain, and provide an objective quantitative shadow for the clinical. As a basis for learning.

【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R744.51;R445.2

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