本文選題：磁共振成像 + 動態(tài)對比增強��； 參考：《山東大學》2017年博士論文

【摘要】：研究背景及目的卵巢腫瘤是婦科手術(shù)的主要適應(yīng)癥。經(jīng)陰道超聲檢查是懷疑卵巢癌的首選的影像學檢查方法,其優(yōu)點是時間效率高,價格便宜,它可以對感興趣區(qū)域進行實時評價,包括組織血管的功能信息,但對于復(fù)雜的病變,它不能準確診斷。磁共振成像在盆腔成像中提供了以下優(yōu)點:它可以提供良好的軟組織對比度;無電離輻射,已被證明對評估復(fù)雜和不確定的卵巢腫瘤優(yōu)于CT。在MR增強序列某些形態(tài)學特征,如固體部分,乳頭狀突起,或不規(guī)則間隔增厚,都提示有惡性腫瘤。但是雖然傳統(tǒng)的MRI對卵巢腫瘤一些形態(tài)學特征已有描述,但卵巢腫瘤之間的形態(tài)學特征仍然有一些重疊的特點。動態(tài)增強磁共振成像(DCE-MRI)作為一種先進的技術(shù),不僅可用于無創(chuàng)性評估卵巢腫瘤的微循環(huán)灌注和血管通透性,還可以根據(jù)時間-信號曲線(TIC)、半定量和定量參數(shù)更全面對卵巢腫瘤進行鑒別診斷。在其他一些惡性腫瘤,包括乳腺癌,前列腺癌和腎癌,動態(tài)增強半定量和定量參數(shù)已被證明對診斷及鑒別診斷是很有價值的。動態(tài)增強MRI的半定量參數(shù)也被證明與卵巢腫瘤血管的生物標志物相關(guān)。DCE-MRI半定量參數(shù)包括時間-信號曲線及基于時間-信號曲線的半定量參數(shù)。時間-信號曲線:Thomassi等以子宮外肌層作為內(nèi)部相對參照物,與子宮外肌層相比,卵巢腫瘤的實性成分呈輕度逐漸強化,此類曲線被命名為"Type I型";實性成分呈中等強化,此類曲線被命名為"TypeⅡ型";當實性成分強化早于子宮外肌層強化,此類曲線被命名為"TypeⅢ型"。其中TypeⅢ型是侵襲性卵巢腫瘤特異性的。半定量參數(shù):Thomassin-Naggara等利用高時間分辨率采集數(shù)據(jù),提出三個半定量的參數(shù):增強幅度(Enhancement Amplitude,EA)、到達半峰值時間(Time of Half Rising,THR),上升斜率(Maximal Slope,MS)。使用子宮外肌層作為內(nèi)部參考,相對增強幅度(EAratio),相對到達半峰值時間(THRratio),和相對上升斜率(MSratio)在侵襲性惡性腫瘤中明顯高于良性和交界性腫瘤;Dilks等通過低的時間分辨率(30s)采集數(shù)據(jù),提出其他的半定量參數(shù),例如最大絕對信號強度(Slmax)、相對信號強度(Slrel)以及對比劑充填率(WIR)。Bernardin等報道,良性病變的最大信號強度(Slmax)、相對信號強度(Slrel)、對比劑充填率(WIR)均低于交界和惡性腫瘤;這些作者強調(diào)這種技術(shù)很簡單,因為影像后臺工作站軟件的很容易計算出這些參數(shù)。DCE-MRI也已顯示與卵巢癌中的腫瘤血管的生物標志物相關(guān)。卵巢癌的特征是含有大量不成熟的微血管。這些微血管的特征是缺乏覆蓋周細胞以及卵巢囊腺癌的內(nèi)皮細胞和上皮細胞血管內(nèi)皮生長因子(VEGF)受體(也稱為VEGFR-2)的高表達。這些病理生理學特點已被證明與MR動態(tài)掃描半定量變化一致。時間信號曲線和半定量的分析是基于信號強度的評估,然而,在MR圖像上信號強度主要取決于采集參數(shù),如翻轉(zhuǎn)角度和重復(fù)時間。注射對比劑后圖像對比度和信號強度和對比劑濃度之間的線性關(guān)系高度依賴這些參數(shù)。因此,許多作者認為我們需要獲得不依賴采集條件的可重復(fù)性的灌注參數(shù)。最近提出基于藥代動力學基礎(chǔ)的定量分析,其將信號強度轉(zhuǎn)換為對比劑釓的濃度。Tofts-Kety模型是由于其良好的重復(fù)性,是目前人們最為熟知和常用的藥代動力學模型;定量參數(shù)主要包括:容量轉(zhuǎn)移常數(shù)(Ktrans)、每單位體積組織中血管外組織外間隙(EES)的容積分數(shù)(Ve)、EES與血漿間速率常數(shù)Kep;目前DCE-MRI定量分析已經(jīng)成為臨床研究的熱點,已應(yīng)用在顱腦、乳腺、前列腺、宮頸等多個部位腫瘤評估當中,主要的研究方向為良、惡性腫瘤的鑒別、腫瘤惡性程度分級、療效的評估等方面。目前定量分析對卵巢腫瘤診斷價值的研究還比較少。本文主要研究目的:1、探討動態(tài)增強掃描MR半定量參數(shù)及定量參數(shù)對卵巢腫瘤鑒別診斷的價值;2、建立鑒別良、惡性腫瘤的半定量參數(shù)及定量參數(shù)最佳閾值;3、對半定量參數(shù)及定量參數(shù)對卵巢腫瘤鑒別診斷效能進行對照分析。方法對在本院行MR常規(guī)及動態(tài)增強的45例卵巢腫瘤患者進行研究。所有患者均經(jīng)病理學證實,其中良性腫瘤13例,惡性腫瘤32例。在動態(tài)對比增強成像之后,在腫瘤的實性部分畫出感興趣的區(qū)域,感興趣的選擇異常顯著增強的軟組織區(qū)域,避開壞死、出血、囊變及血管等。1、時間-信號曲線及半定量參數(shù):使用Mean Curve軟件包自動生成時間-時間-信號曲線(time intensity curve,TIC),將TIC類型分為3種類型:卵巢病變的實性成分呈輕度緩慢漸進性強化,此類曲線被命名為"緩慢上升型(I型)",實性成分呈中等強化并持續(xù)強化,此類曲線被命名為"平臺型(II型)";當實性成分早期明顯強化并迅速下降,此類曲線被命名為為"流出型(III型)"。根據(jù)TIC曲線,獲得半定量參數(shù):增強掃描后60s強化率(SI60%)及增強掃描后200s內(nèi)達峰時間(TTP200S);增強掃描后60S的強化率用以下公式計算:SI60%=(Slpost60s-Slpre)/Slpre×100%,Slpost60s:增強掃描后60s病灶最大的信號強度值;Slpre為增強掃描前信號強度值。2、定量參數(shù):采用Siemens TISSUE 4D軟件包獲得定量參數(shù),該軟件采用改良的Tofts血流動力學雙室模型。根據(jù)增強掃描前采集兩個翻轉(zhuǎn)角T1-mapping序列,計算獲得基線T1值,進而計算動態(tài)增強掃描后圖像的T1強化值,選取腫塊實質(zhì)成分作為感興趣區(qū)(ROI),獲得反映腫瘤微血管通透性的定量參數(shù):①Ktrans:是指每單位體積內(nèi)血漿與血管外細胞外空間(EES)之間的轉(zhuǎn)移常數(shù),單位為min-1;②Kep:指血管外組織間隙內(nèi)的對比劑返流到血管內(nèi)的速度常數(shù),單位為min-1S③Ve:是血管外細胞外間隙占整個體積的容積比,沒有單位。應(yīng)用MedCalc 15.2.2統(tǒng)計軟件對數(shù)據(jù)的結(jié)果進行統(tǒng)計分析,觀察比較良、惡性卵巢腫瘤實性成分的時間-信號曲線(TIC)類型,采用x2檢驗,分析不同類型TIC曲線在良、惡性卵巢腫瘤間是否存在差異。應(yīng)用Mann-WhitneyU檢驗,分析對良、惡性卵巢腫瘤的半定量參數(shù)及定量參數(shù)的差異。根據(jù)ROC曲線分析確定半定量參數(shù)及定量參數(shù)在鑒別良、惡性腫瘤的最佳閾值、敏感度、特異度、陽性預(yù)測值、陰性預(yù)測值;并對半定量參數(shù)及定量參數(shù)對卵巢腫瘤的診斷效能進行對照分析。認為p0.05差異有統(tǒng)計學意義。結(jié)果惡性腫瘤32例(包括漿液性囊腺癌17例,黏液性囊腺癌13例,支持細胞瘤1例,轉(zhuǎn)移癌1例),年齡32-76歲,平均58歲;良性腫瘤13例(包括卵泡膜纖維瘤9例,卵泡膜細胞瘤3例,囊性腺纖維瘤1例,年齡35-80歲,平均55歲。TIC曲線:32例惡性腫瘤中,12例(37.50%)為Ⅲ型曲線,20例(62.50%)為Ⅱ型曲線,未見Ⅰ型曲線;13例良性腫瘤中,9例(69.23%)為Ⅰ型曲線,3例(23.08%)為Ⅱ型曲線,1例(7.69%)為Ⅲ型曲線;良、惡性卵巢腫瘤的TIC類型之間的差異有統(tǒng)計學意義(P0.0001)。半定量參數(shù):惡性腫瘤Sl60%(126.43±17.90%)明顯高于良性腫瘤(69.62±33.12%),惡性腫瘤(72.93±22.24s)明顯早于良性腫瘤TTP200S(141.11±48.12s),SI60%及TTP200S兩者之間的差異有統(tǒng)計學意義(p=0.0002,p=0.0001)。在鑒別良、惡性腫瘤時,SI60%96.125%、TTP200s116s時,診斷惡性腫瘤的敏感性較高(敏感性分別為93.7%及96.87%,特異性分別為76.9%及69.23%)。定量參數(shù):惡性卵巢腫瘤的Ktrans值(0.352±0.114mm-1)、Kep 值(0.535±0.182 min-1)及 Ve 值(0.761±0.428)均高于良性腫瘤(分別為 0.116±0.068mm-1、0.293±0.106 min-1及0.367±0.123),Ktrans 值、Kep 值及 Ve 值之間的差異有統(tǒng)計學意義。在鑒別良、惡性腫瘤時,當Ktrans值0.234min-1時,診斷惡性腫瘤的特異性及敏感性均較高,敏感性為87.50%,特異性為100.00%;當Kep0.414 min-1敏感性為92.31%,特異性78.12%;當Ve0.512時,敏感性為68.75%,特異性92.31%。半定量參數(shù)(SI60%、TTP200S)與定量參數(shù)(Ktrans值、Kep值、Ve值)對鑒別卵巢良、惡性腫瘤診斷效能的差異無統(tǒng)計學意義。定量參數(shù)Ktrans值鑒別卵巢良、惡性腫瘤曲線下面積(0.974)高于半定量參數(shù)(曲線下面積分別為0.829,0.882)。結(jié)論我們的初步研究證實DCE-MRI根據(jù)時間-信號曲線(TIC),半定量和定量參數(shù)在卵巢良、惡性腫瘤的有較高鑒別診斷效能。根據(jù)TIC,半定量和定量參數(shù)的最佳閾值鑒別良、惡性腫瘤有較高的敏感性和特異性。半定量參數(shù)與定量參數(shù)對卵巢腫瘤的診斷效能之間差異無統(tǒng)計學差異,但定量參數(shù)Ktrans值鑒別卵巢良、惡性腫瘤曲線下面積高于半定量參數(shù),因此本研究認為定量參數(shù)Ktrans值是鑒別卵巢腫瘤最相關(guān)的因素�？傊�,半定量參數(shù)及定量參數(shù)允許放射科診斷醫(yī)生更有信心地診斷良性或者卵巢腫瘤;這些參數(shù)是常規(guī)形態(tài)MR診斷的重要補充,對于那些常規(guī)MRI診斷不確定的情況,定量及半定量參數(shù)尤其有用,可以避免不必要的根治性手術(shù)。
[Abstract]:Background and objective ovarian tumors are the main indications of gynecologic surgery. Transvaginal ultrasound is the first choice for imaging of ovarian cancer. Its advantages are high time efficiency and cheap price. It can be used to evaluate the region of interest in real time, including the functional information of tissue vessels, but it is not accurate for complex lesions. Accurate diagnosis. Magnetic resonance imaging provides the following advantages in pelvic imaging: it provides good soft tissue contrast; non ionizing radiation has proven to be superior to CT. in evaluating complex and uncertain ovarian tumors with some morphological features in the MR enhanced sequence, such as solid parts, breast head protuberances, or irregular interval thickening, which are suggestive of evil. But although some morphological features of ovarian tumors have been described by traditional MRI, the morphological features of ovarian tumors still have some overlapping characteristics. Dynamic enhanced magnetic resonance imaging (DCE-MRI), as an advanced technique, can not only be used for non-invasive assessment of microcirculation perfusion and vascular permeability in ovarian tumors, but also for noninvasive evaluation of ovarian tumors. The differential diagnosis of ovarian tumors can be made in a more comprehensive way based on the time signal curve (TIC), semi quantitative and quantitative parameters. In other malignant tumors, including breast, prostate and renal cancer, dynamic enhanced semi quantitative and quantitative parameters have been proved to be valuable for diagnosis and differential diagnosis. The semi quantitative parameters of dynamic enhanced MRI are also used. The.DCE-MRI semi quantitative parameters related to the biomarkers of the ovarian tumor vessels include the time signal curve and the semi quantitative parameters based on the time signal curve. The time signal curve: the Thomassi and the outer myometrium are used as the internal relative reference. Compared with the extrauterine myometrium, the real components of the ovarian tumor are slightly gradually strengthened. This kind of curve is named "Type I"; the real component is moderately strengthened, and this kind of curve is named "Type II". When the solid component is strengthened earlier than the extrauterine muscle layer, the curve is named "Type III". The Type III is an invasive ovarian tumor specific. Semi quantitative parameter: Thomassin-Naggara and so on using high time resolution. Collect data and propose 3.5 quantitative parameters: Enhancement Amplitude (EA), half peak time (Time of Half Rising, THR), rising slope (Maximal Slope, MS). Using the extrauterine layer as an internal reference, relative enhancement amplitude (EAratio), relative to half peak time, and relative rise slope It was significantly higher in invasive malignant tumors than in benign and borderline tumors; Dilks, etc. collected data through low time resolution (30s), and proposed other semi quantitative parameters, such as maximum absolute signal intensity (Slmax), relative signal intensity (Slrel) and contrast agent filling rate (WIR).Bernardin, and the maximum signal intensity of benign lesions (Slma X), relative signal intensity (Slrel), contrast agent filling rate (WIR) is lower than borderline and malignant tumor; these authors emphasize that this technique is very simple, because the image background workstation software is easy to calculate these parameters.DCE-MRI also has been shown to be associated with the biomarkers of the tumor blood tube in ovarian cancer. Immature microvessels. These microvessels are characterized by the lack of high expression of endothelial cells and epithelial cell vascular endothelial growth factor (VEGF) receptors (also known as VEGFR-2) that cover pericytes and ovarian cystadenocarcinoma. These pathophysiological features have been shown to be consistent with the semi quantitative changes in dynamic MR scanning. The analysis is based on the evaluation of signal intensity. However, the intensity of the signal in the MR image depends mainly on the acquisition parameters, such as the turning angle and the repetition time. The linear relationship between the contrast of the image and the intensity of the signal and the concentration of the contrast agent after the injection of contrast agent is highly dependent on these parameters. A quantitative analysis based on the basis of pharmacokinetics has recently been proposed. The.Tofts-Kety model, which converts signal intensity to the concentration of the contrast agent gadolinium, is the most familiar and commonly used pharmacokinetic model because of its good reproducibility. The quantitative parameters include the capacity transfer constant (Ktrans The volume fraction (Ve) of extravascular space (EES) and the rate constant between EES and plasma in each unit volume of tissue are Kep. The quantitative analysis of DCE-MRI has become a hot spot in the clinical research and has been used in the evaluation of brain, breast, prostate, and cervix. The main research direction is good, the differentiation of malignant tumor and the tumor. Grade of malignancy, evaluation of curative effect, and so on. Quantitative analysis of the diagnostic value of ovarian tumors is still less. The main purpose of this study is to study the value of the semi quantitative parameters and quantitative parameters of dynamic enhanced scan MR for the differential diagnosis of ovarian tumors; 2, to establish the semi quantitative parameters and quantitative parameters of the differential and malignant tumors. Good threshold value; 3. Comparative analysis of the differential diagnosis efficiency of ovarian tumors by semi quantitative parameters and quantitative parameters. Methods 45 cases of ovarian tumor patients with MR routine and dynamic enhancement in our hospital were studied. All patients were confirmed by pathology, of which 13 cases of benign tumors and 32 cases of malignant swelling. After dynamic contrast enhancement imaging, the tumor was in tumor. The real part draws a region of interest, which is interested in choosing an abnormal and significantly enhanced soft tissue area, avoiding.1, time signal curve and semi quantitative parameters, such as necrosis, bleeding, cystic change and blood vessels: using the Mean Curve software package to automatically generate the time time signal curve (time intensity curve, TIC), and divide the TIC type into 3 types: ovary: ovary The real components of the lesions were mild slowly progressive enhancement, and this kind of curve was named "I type". The real component was moderately strengthened and continued to strengthen. This kind of curve was named "II type". When the real component was obviously strengthened and descended quickly, the curve was named "III type". According to the TIC curve, Obtain semi quantitative parameters: 60s enhancement rate (SI60%) after enhanced scan and 200s internal peak time after enhanced scan (TTP200S); the enhancement rate of 60S after enhanced scan is calculated by the following formula: SI60%= (Slpost60s-Slpre) /Slpre x 100%, the maximum signal intensity of the 60s focus after Slpost60s: enhanced scan; Slpre is the intensity value.2, quantitative before enhanced scan. Parameters: using the Siemens TISSUE 4D software package to obtain quantitative parameters, the software uses a modified Tofts hemodynamic double chamber model. The baseline T1 value is obtained by collecting two turn angle T1-mapping sequences before enhanced scan, and then the T1 strengthening value of the image after dynamic enhanced scan is calculated, and the substance component of the mass is selected as the region of interest (ROI). To obtain quantitative parameters reflecting microvascular permeability of tumor: (1) Ktrans: refers to the transfer constant between plasma and extravascular extracellular space (EES) per unit volume, the unit is min-1, and Kep: refers to the rate constant of the contrast agent reflux into the blood vessel in the space of extravascular tissue, and the unit is min-1S Ve: is the outer space of the extravascular extracellular space. MedCalc 15.2.2 statistical software was used to analyze the results of the data, and to observe the time signal curve (TIC) of the malignant ovarian tumor, and to analyze the difference between the different types of TIC curves in the benign and malignant egg nests. The Mann-WhitneyU test was used. The difference between the semi quantitative parameters and quantitative parameters of benign and malignant ovarian tumors was analyzed. According to the analysis of the ROC curve, the semi quantitative parameters and quantitative parameters were determined to identify the best threshold, sensitivity, specificity, positive predictive value and negative predictive value of malignant tumor, and the diagnostic efficiency of ovarian tumors by semi quantitative parameters and quantitative parameters was compared. There were 32 cases of malignant tumor (including 17 cases of serous cystadenocarcinoma, 13 cases of mucinous cystadenocarcinoma, 1 cases of support cell tumor, 1 cases of metastatic carcinoma), age 32-76 years, average 58 years, 13 cases of benign tumor (including follicular fibroma 9, follicular cell tumor 3, cystic adenofibroma 1, age 35-80 years, 55 years, average 55). Age.TIC curve: of the 32 cases of malignant tumors, 12 cases (37.50%) were type III curves, 20 cases (62.50%) were type II curves, no type I curve, 9 cases (69.23%) were type I curves, 3 (23.08%) was type I curve, 3 (23.08%) was type II curve, 1 (7.69%) was type III curve in 13 cases of benign tumors, and the difference between benign and malignant ovarian tumors was statistically significant (P0.0001). Semidefinite difference between benign and malignant ovarian tumors. Parameters: Sl60% (126.43 + 17.90%) of malignant tumor (69.62 + 33.12%) was significantly higher than that of benign tumor (69.62 + 33.12%), malignant tumor (72.93 + 22.24s) was earlier than benign tumor TTP200S (141.11 + 48.12s), and the difference between SI60% and TTP200S was statistically significant (p=0.0002, p= 0.0001). In the identification of benign and malignant tumors, SI60%96.125%, TTP200s116s, diagnosis of evil The sensitivity of sexual tumors was higher (sensitivity 93.7% and 96.87%, specificity 76.9% and 69.23% respectively). Quantitative parameters: Ktrans value of malignant ovarian tumors (0.352 + 0.114mm-1), Kep value (0.535 + 0.182 min-1) and Ve value (0.761 + 0.428) were higher than those of benign tumors (0.116 + 0.068mm-1,0.293 + 0.106 min-1 and 0.367 + 0.123), Ktrans The difference between value, Kep value and Ve value is statistically significant. When identifying benign and malignant tumors, when Ktrans is 0.234min-1, the specificity and sensitivity of the diagnosis of malignant tumors are high, the sensitivity is 87.50%, the specificity is 100%, the sensitivity of Kep0.414 min-1 is 92.31%, the specificity is 78.12%, and when Ve0.512, the sensitivity is 68.75%, the specificity 92.3. 1%. semi quantitative parameters (SI60%, TTP200S) and quantitative parameters (Ktrans, Kep value, Ve value) have no statistical significance for the differential diagnosis of ovarian and malignant tumors. The quantitative parameters Ktrans value is good in identifying the ovary and the area under the malignant tumor curve (0.974) is higher than the semi quantitative parameter (the area under the curve is 0.829,0.882). Conclusion our preliminary research According to the time signal curve (TIC), DCE-MRI has high differential diagnostic efficiency in benign and malignant ovarian tumors based on the time signal curve (TIC). The diagnosis of malignant tumors is high sensitivity and specificity based on the optimal threshold of TIC, semi quantitative and quantitative parameters. The diagnostic efficiency of semi quantitative and quantitative parameters to ovarian tumors is between the semi quantitative parameters and quantitative parameters. The difference was not statistically significant, but the Ktrans value of quantitative parameters was better than that of half quantitative parameters. Therefore, the Ktrans value of quantitative parameters was the most relevant factor in the identification of ovarian tumors. Tumors; these parameters are an important complement to conventional morphological MR diagnosis. It is especially useful for the quantitative and semi quantitative parameters of conventional MRI diagnosis, which can avoid unnecessary radical surgery.
【學位授予單位】：山東大學
【學位級別】：博士
【學位授予年份】：2017
【分類號】：R445.2;R737.31

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