本文選題：正電子 + 發(fā)射型��； 參考：《第二軍醫(yī)大學(xué)》2016年博士論文

【摘要】：研究背景:癲癇是以一種由于神經(jīng)元興奮與抑制失衡并導(dǎo)致神經(jīng)元群同步異常放電為特征的中樞神經(jīng)系統(tǒng)功能失常綜合征。據(jù)流行病學(xué)統(tǒng)計,我國癲癇患病率約為3.6~7.0‰,在神經(jīng)系統(tǒng)病變中僅次于腦卒中為第二大常見疾病,其中顳葉癲癇(Temporal Lobe Epilepsy,TLE)約占60~70%。在大部分患者中,藥物治療可使得癥狀得以有效控制,但也有將近1/3的患者會發(fā)展為藥物難治性癲癇,其中,顳葉內(nèi)側(cè)硬化患者常為藥物難治性癲癇且對手術(shù)治療響應(yīng)較好、需要手術(shù)治療,手術(shù)治療主要以對癲癇發(fā)作區(qū)域的切除為主。對藥物難治性癲癇來講,完善的術(shù)前評估是保證其療效的基礎(chǔ),但常受到難以準(zhǔn)確勾畫致癇灶的困擾。目前來看,多種功能分子成像技術(shù)可能在判定致癇灶定側(cè)、定位方面提供一些補(bǔ)充信息,其中正電子發(fā)射型計算機(jī)斷層掃描(Positron Emission Computed Tomography,PET)腦顯像技術(shù)是一種無創(chuàng)性的、能夠提供定位、定量信息的腦功能代謝檢查技術(shù),在臨床已有較多應(yīng)用。既往PET腦顯像評價主要依靠視覺評價以及腦內(nèi)不對稱指數(shù)計算等方法,雖取得較好臨床診斷效果,但其主觀影響大,受診斷醫(yī)師水平影響較大,亟須一種更加客觀、準(zhǔn)確的分析方法,統(tǒng)計參數(shù)圖在顳葉癲癇上進(jìn)行分析既往國內(nèi)外有一定研究,但因研究對象及對照組例數(shù)較少、多方法綜合比較研究較少等原因,其診斷價值尚不確切、肯定,未能真正進(jìn)入臨床應(yīng)用。研究目的:本研究旨在利用統(tǒng)計參數(shù)圖(Statistical Parametric Mapping,SPM)方法對顳葉癲癇患者定側(cè)診斷進(jìn)行研究、開發(fā),以患者術(shù)后病理及隨訪結(jié)果為金標(biāo)準(zhǔn),對不同方式SPM處理方法診斷效能進(jìn)行比較分析,并將所采用的SPM方法分與臨床常規(guī)應(yīng)用的視覺分析方法、不對稱指數(shù)(Asymmetry Index,AI)分析法等所得結(jié)果進(jìn)行統(tǒng)計學(xué)比較分析,評價各方法診斷效能,選定并建立合適的SPM方法學(xué)、優(yōu)選相關(guān)參數(shù),在此基礎(chǔ)上評價SPM分析法的價值,此外,通過患者組與對照組間的組間比較,初步討論顳葉癲癇時的機(jī)制問題。其研究意義在于建立適當(dāng)、準(zhǔn)確的基于像素水平的統(tǒng)計參數(shù)圖對顳葉癲癇進(jìn)行定側(cè)診斷的方法,取得分析時應(yīng)采用的各項合理參數(shù),對SPM方法在顳葉癲癇中的診斷價值進(jìn)行評價。研究方法:對86例資料完整的難治性顳葉癲癇患者及37例健康志愿者進(jìn)行回顧性分析,分析方法包括三大部分:(1)、視覺分析方法,包括獨(dú)立雙盲目測法和視覺AI分析法閱片,記錄研究對象雙側(cè)顳葉SUVmean值并將患者組及健康對照組雙側(cè)顳葉SUVmean值進(jìn)行比較,將患者組患側(cè)SUVmean值與健康對照組相應(yīng)值進(jìn)行比較,將目測法和視覺AI分析法閱片所得準(zhǔn)確率進(jìn)行比較。此外,我們利用兩組研究對象的SUVmean值進(jìn)行ROC曲線分析。(2)、利用SPM分析方法對難治性顳葉癲癇進(jìn)行定側(cè)診斷研究,采用不同置信水平P值分別進(jìn)行兩方面研究,(1)將患者組的每個患者數(shù)據(jù)與健康對照組進(jìn)行基于像素水平兩樣本t檢驗;(2)與對照組內(nèi)存在的腦內(nèi)不對稱進(jìn)行比較,并藉此評價每個患側(cè)腦內(nèi)的不對稱情況。每個患者圖像及對照組沿著矢狀位進(jìn)行左右翻轉(zhuǎn)得到鏡像圖像,將患者組、對照組原始圖像及兩組反轉(zhuǎn)鏡像圖像進(jìn)行單因素方差分析;(3)分別對不同SPM方法診斷準(zhǔn)確率進(jìn)行分析,將兩組所得最優(yōu)置信水平的方法進(jìn)行比較,其后將最優(yōu)化SPM診斷方法與視覺分析方法進(jìn)行比較,評價相應(yīng)SPM診斷方法的診斷效能。(3)、將左側(cè)顳葉癲癇患者組、右側(cè)顳葉癲癇患者組及全部癲癇患者組分別與對照組進(jìn)行組間比較,評價前述各患者組與對照組間腦區(qū)代謝差異。結(jié)果:(1)目測方法準(zhǔn)確檢出70例患者致癇灶,視覺AI分析法中72例患者能夠明確定側(cè)診斷,兩組間診斷準(zhǔn)確率無統(tǒng)計學(xué)顯著差異;經(jīng)統(tǒng)計學(xué)分析,健康對照組雙側(cè)顳葉SUVmean比較無統(tǒng)計學(xué)顯著差異;TLE組患側(cè)SUVmean低于健側(cè)相應(yīng)值,有統(tǒng)計學(xué)顯著差異;TLE組患側(cè)SUVmean明顯低于健康對照組左、右側(cè)顳葉SUVmean,有統(tǒng)計學(xué)顯著意義;利用SUVmean作為致癇灶定側(cè)指標(biāo)行ROC曲線分析得:當(dāng)SUV值為4.35時,其對癲癇灶定側(cè)診斷的敏感度為87.5%,特異性為81.4%,曲線下面積0.844。(2)采用不同置信水平P值,將單個患者與對照組進(jìn)行兩樣本t檢驗,發(fā)現(xiàn)當(dāng)P0.05(FWE校正值)時診斷準(zhǔn)確率為79.07%(68/86),優(yōu)于其它置信水平,與視覺分析法相當(dāng);采用不同置信水平P值,利用SPM計算單個患者腦內(nèi)不對稱性,發(fā)現(xiàn)當(dāng)選取置信水平P0.05時診斷準(zhǔn)確率可達(dá)94.19%(81/86),優(yōu)于采用其它種置信水平所得結(jié)果,優(yōu)于視覺分析方法及單個患者與對照組進(jìn)行兩樣本t檢驗方法。(3)組分析研究發(fā)現(xiàn),除顳葉代謝減低外,其他部分腦區(qū)有代謝減低或增高改變,可部分反映顳葉癲癇發(fā)病機(jī)制,并有助于臨床醫(yī)生認(rèn)識癲癇典型影像變化特點(diǎn)。結(jié)論:總體來看,SPM是通過對腦內(nèi)所有象素進(jìn)行逐一進(jìn)行分析、比較而最終形成統(tǒng)計參數(shù)圖,故其對病變的探測級別可以達(dá)到象素水平,SPM腦內(nèi)不對稱分析的PET分析方法基于像素水平進(jìn)行統(tǒng)計分析,考慮了部分客觀因素,并排除了診斷醫(yī)師主觀因素等影響,可無創(chuàng)地、更加客觀、科學(xué)、全面、準(zhǔn)確地發(fā)現(xiàn)各腦區(qū)微小代謝變化,對致癇灶檢出率高、靈敏度、特異性強(qiáng)、可重復(fù)性強(qiáng),在難治性TLE定側(cè)診斷上有較高的臨床應(yīng)用價值,因其流程化操作特點(diǎn),有望進(jìn)入臨床實踐。
[Abstract]:Background: epilepsy is a central nervous system dysfunction syndrome characterized by the imbalance of neuronal excitability and inhibition and the synchronous abnormal discharge of the neurons. According to epidemiological statistics, the prevalence of epilepsy in China is about 3.6~7.0 per thousand. In the pathological changes of the nervous system, only stroke is second common diseases, of which the temporal lobe is in the temporal lobe. Temporal Lobe Epilepsy (TLE) accounts for about 60~70%. in most of the patients. Drug treatment can effectively control the symptoms, but there are also nearly 1/3 patients who will develop into drug refractory epilepsy. Among them, the patient with Chang Wei's medial temporal sclerosis is difficult to treat and responds well to the surgical treatment. Surgical treatment is needed and the operation is the main treatment. In the case of drug refractory epilepsy, a perfect preoperative assessment is the basis for the treatment of epilepsy, but it is often difficult to accurately describe the preeclampsia. At present, multiple functional molecular imaging techniques may provide some additional information for the determination of the localization of the epileptic foci and the location of the positron. Positron Emission Computed Tomography (PET) brain imaging technology is a noninvasive brain functional metabolic examination technique that provides location and quantitative information. It has been widely used in clinical practice. The evaluation of PET brain imaging is mainly based on visual evaluation and the calculation of asymmetric index in the brain. But it has a better clinical diagnosis effect, but its subjective influence is big and the diagnostic physician level is greatly influenced. It is urgent to have a more objective and accurate analysis method. The statistical parameter map has a certain research on the temporal lobe epilepsy, but the research object and the control group are few, and the multiple methods are comparatively few and so on. The purpose of this study is to study the lateral diagnosis of temporal lobe epilepsy by using the Statistical Parametric Mapping (SPM) method. The purpose of this study is to develop the diagnostic efficiency of different methods of SPM treatment by using the postoperative pathological and follow-up results as the gold standard. The comparative analysis was carried out, and the SPM method was compared with the visual analysis method of clinical routine application, the results of asymmetric index (Asymmetry Index, AI) analysis were compared, the diagnostic efficiency of each method was evaluated, and the appropriate SPM methodology was established and the relevant parameters were selected. On this basis, the price of the SPM analysis method was evaluated. In addition, the mechanism of temporal lobe epilepsy was preliminarily discussed by comparison between the patient group and the control group. The significance of this study was to establish a proper and accurate method for the lateral diagnosis of temporal lobe epilepsy based on the pixel level statistical parameter map, and to obtain various reasonable parameters for the analysis of temporal lobe epilepsy, and the SPM method was used in temporal lobe epilepsy. The diagnostic value of 86 cases of intractable temporal lobe epilepsy and 37 healthy volunteers were analyzed retrospectively. The analysis method included three parts: (1) the visual analysis method, including the independent double blind method and the visual AI analysis, to record the SUVmean value of the bilateral temporal lobe and the patient group. The SUVmean values of bilateral temporal lobes in the healthy control group were compared and compared with the corresponding values of the patients' affected side SUVmean and the healthy control group. The accuracy rate of the visual and visual AI analysis was compared. In addition, we used the SUVmean value of the two groups of subjects to analyze the ROC curve. (2) the treatment of intractable temporomandibular temporomandibular time was made by SPM analysis. Ye Dianxian carried out the study of lateral diagnosis with two different confidence level P values. (1) the data of each patient in the patient group was compared with the healthy control group based on the pixel level two sample t test, and (2) compared with the intracerebral asymmetry in the control group, and to evaluate each side of the affected side of the brain. The patient image and the control group flipped along the sagittal position to get the image image. The patient group, the original image of the control group and the two groups of reverse mirror images were analyzed by single factor variance analysis. (3) the diagnostic accuracy of different SPM methods was analyzed, and the optimal confidence level of the two groups was compared, and then the optimal SPM diagnosis was taken. Compared with the visual analysis method, the diagnostic efficiency of the corresponding SPM diagnosis method was evaluated. (3) the left temporal lobe epilepsy group, the right temporal lobe epilepsy group and all the epileptic patients were compared with the control group respectively, and the metabolic difference between the foregoing group and the control group was evaluated. Results: (1) the visual inspection method was accurate. 70 cases of patients with epileptic foci, 72 cases of visual AI analysis can be definite side diagnosis, the diagnostic accuracy rate between the two groups is not statistically significant difference. After statistical analysis, there is no statistically significant difference in the bilateral temporal lobe SUVmean in the healthy control group; the affected side of the TLE group is lower than the corresponding value of the healthy side, there is a statistically significant difference; the TLE group suffers from the side SUVmean. The left side of the right temporal lobe was significantly lower than that in the healthy control group. The SUVmean was statistically significant in the right temporal lobe, and the ROC curve was analyzed by SUVmean as an index of the epileptic focus side. When the SUV value was 4.35, the sensitivity to the localized diagnosis of epileptic foci was 87.5%, the specificity was 81.4%, and the area under the curve was 0.844. (2) using the P values of different confidence levels. The two sample t test showed that the diagnostic accuracy of the P0.05 (FWE correction value) was 79.07% (68/86), which was superior to the other confidence levels, and was equivalent to the visual analysis method. Using the P values of different confidence levels and using SPM to calculate the asymmetry in the brain of a single patient, it was found that the diagnostic accuracy of the elected level P0.05 was 94.19% (81/86), which was better than that adopted. The results obtained from other levels of confidence were better than the visual analysis method and the two sample t test for individual patients and the control group. (3) the analysis of group analysis found that the metabolism decreased or increased in other parts of the brain except the decrease of temporal lobe metabolism, which could partly reflect the mechanism of temporal lobe epilepsy and help clinicians to recognize typical images of epilepsy. Like change characteristics. Conclusion: in general, SPM is by analyzing all the pixels in the brain, comparing and finally forming a statistical parameter map, so the detection level of the disease can reach the level of pixels. The PET analysis method of SPM asymmetry analysis in the brain is based on the statistical analysis of pixel leveling, considering some objective factors and side-by-side. In addition to the influence of the doctor's subjective factors, it can be noninvasive, more objective, scientific, comprehensive and accurate to find small metabolic changes in the brain regions, high detection rate, sensitivity, specificity and repeatability of the epileptic foci. It has high clinical application value in the diagnosis of intractable TLE, and it is expected to enter clinical reality because of its flow operation characteristics. Practice.
【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R742.1;R817.4

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