DCE-MRI半定量及定量参数对卵巢肿瘤诊断价值的研究

发布时间：2018-06-03 14:27

本文选题：磁共振成像 + 动态对比增强　；参考：《山东大学》2017年博士论文

【摘要】：研究背景及目的卵巢肿瘤是妇科手术的主要适应症。经阴道超声检查是怀疑卵巢癌的首选的影像学检查方法,其优点是时间效率高,价格便宜,它可以对感兴趣区域进行实时评价,包括组织血管的功能信息,但对于复杂的病变,它不能准确诊断。磁共振成像在盆腔成像中提供了以下优点:它可以提供良好的软组织对比度;无电离辐射,已被证明对评估复杂和不确定的卵巢肿瘤优于CT。在MR增强序列某些形态学特征,如固体部分,乳头状突起,或不规则间隔增厚,都提示有恶性肿瘤。但是虽然传统的MRI对卵巢肿瘤一些形态学特征已有描述,但卵巢肿瘤之间的形态学特征仍然有一些重叠的特点。动态增强磁共振成像(DCE-MRI)作为一种先进的技术,不仅可用于无创性评估卵巢肿瘤的微循环灌注和血管通透性,还可以根据时间-信号曲线(TIC)、半定量和定量参数更全面对卵巢肿瘤进行鉴别诊断。在其他一些恶性肿瘤,包括乳腺癌,前列腺癌和肾癌,动态增强半定量和定量参数已被证明对诊断及鉴别诊断是很有价值的。动态增强MRI的半定量参数也被证明与卵巢肿瘤血管的生物标志物相关。DCE-MRI半定量参数包括时间-信号曲线及基于时间-信号曲线的半定量参数。时间-信号曲线:Thomassi等以子宫外肌层作为内部相对参照物,与子宫外肌层相比,卵巢肿瘤的实性成分呈轻度逐渐强化,此类曲线被命名为"Type I型";实性成分呈中等强化,此类曲线被命名为"TypeⅡ型";当实性成分强化早于子宫外肌层强化,此类曲线被命名为"TypeⅢ型"。其中TypeⅢ型是侵袭性卵巢肿瘤特异性的。半定量参数:Thomassin-Naggara等利用高时间分辨率采集数据,提出三个半定量的参数:增强幅度(Enhancement Amplitude,EA)、到达半峰值时间(Time of Half Rising,THR),上升斜率(Maximal Slope,MS)。使用子宫外肌层作为内部参考,相对增强幅度(EAratio),相对到达半峰值时间(THRratio),和相对上升斜率(MSratio)在侵袭性恶性肿瘤中明显高于良性和交界性肿瘤;Dilks等通过低的时间分辨率(30s)采集数据,提出其他的半定量参数,例如最大绝对信号强度(Slmax)、相对信号强度(Slrel)以及对比剂充填率(WIR)。Bernardin等报道,良性病变的最大信号强度(Slmax)、相对信号强度(Slrel)、对比剂充填率(WIR)均低于交界和恶性肿瘤;这些作者强调这种技术很简单,因为影像后台工作站软件的很容易计算出这些参数。DCE-MRI也已显示与卵巢癌中的肿瘤血管的生物标志物相关。卵巢癌的特征是含有大量不成熟的微血管。这些微血管的特征是缺乏覆盖周细胞以及卵巢囊腺癌的内皮细胞和上皮细胞血管内皮生长因子(VEGF)受体(也称为VEGFR-2)的高表达。这些病理生理学特点已被证明与MR动态扫描半定量变化一致。时间信号曲线和半定量的分析是基于信号强度的评估,然而,在MR图像上信号强度主要取决于采集参数,如翻转角度和重复时间。注射对比剂后图像对比度和信号强度和对比剂浓度之间的线性关系高度依赖这些参数。因此,许多作者认为我们需要获得不依赖采集条件的可重复性的灌注参数。最近提出基于药代动力学基础的定量分析,其将信号强度转换为对比剂钆的浓度。Tofts-Kety模型是由于其良好的重复性,是目前人们最为熟知和常用的药代动力学模型;定量参数主要包括:容量转移常数(Ktrans)、每单位体积组织中血管外组织外间隙(EES)的容积分数(Ve)、EES与血浆间速率常数Kep;目前DCE-MRI定量分析已经成为临床研究的热点,已应用在颅脑、乳腺、前列腺、宫颈等多个部位肿瘤评估当中,主要的研究方向为良、恶性肿瘤的鉴别、肿瘤恶性程度分级、疗效的评估等方面。目前定量分析对卵巢肿瘤诊断价值的研究还比较少。本文主要研究目的:1、探讨动态增强扫描MR半定量参数及定量参数对卵巢肿瘤鉴别诊断的价值;2、建立鉴别良、恶性肿瘤的半定量参数及定量参数最佳阈值;3、对半定量参数及定量参数对卵巢肿瘤鉴别诊断效能进行对照分析。方法对在本院行MR常规及动态增强的45例卵巢肿瘤患者进行研究。所有患者均经病理学证实,其中良性肿瘤13例,恶性肿瘤32例。在动态对比增强成像之后,在肿瘤的实性部分画出感兴趣的区域,感兴趣的选择异常显著增强的软组织区域,避开坏死、出血、囊变及血管等。1、时间-信号曲线及半定量参数:使用Mean Curve软件包自动生成时间-时间-信号曲线(time intensity curve,TIC),将TIC类型分为3种类型:卵巢病变的实性成分呈轻度缓慢渐进性强化,此类曲线被命名为"缓慢上升型(I型)",实性成分呈中等强化并持续强化,此类曲线被命名为"平台型(II型)";当实性成分早期明显强化并迅速下降,此类曲线被命名为为"流出型(III型)"。根据TIC曲线,获得半定量参数:增强扫描后60s强化率(SI60%)及增强扫描后200s内达峰时间(TTP200S);增强扫描后60S的强化率用以下公式计算:SI60%=(Slpost60s-Slpre)/Slpre×100%,Slpost60s:增强扫描后60s病灶最大的信号强度值;Slpre为增强扫描前信号强度值。2、定量参数:采用Siemens TISSUE 4D软件包获得定量参数,该软件采用改良的Tofts血流动力学双室模型。根据增强扫描前采集两个翻转角T1-mapping序列,计算获得基线T1值,进而计算动态增强扫描后图像的T1强化值,选取肿块实质成分作为感兴趣区(ROI),获得反映肿瘤微血管通透性的定量参数:①Ktrans:是指每单位体积内血浆与血管外细胞外空间(EES)之间的转移常数,单位为min-1;②Kep:指血管外组织间隙内的对比剂返流到血管内的速度常数,单位为min-1S③Ve:是血管外细胞外间隙占整个体积的容积比,没有单位。应用MedCalc 15.2.2统计软件对数据的结果进行统计分析,观察比较良、恶性卵巢肿瘤实性成分的时间-信号曲线(TIC)类型,采用x2检验,分析不同类型TIC曲线在良、恶性卵巢肿瘤间是否存在差异。应用Mann-WhitneyU检验,分析对良、恶性卵巢肿瘤的半定量参数及定量参数的差异。根据ROC曲线分析确定半定量参数及定量参数在鉴别良、恶性肿瘤的最佳阈值、敏感度、特异度、阳性预测值、阴性预测值;并对半定量参数及定量参数对卵巢肿瘤的诊断效能进行对照分析。认为p0.05差异有统计学意义。结果恶性肿瘤32例(包括浆液性囊腺癌17例,黏液性囊腺癌13例,支持细胞瘤1例,转移癌1例),年龄32-76岁,平均58岁;良性肿瘤13例(包括卵泡膜纤维瘤9例,卵泡膜细胞瘤3例,囊性腺纤维瘤1例,年龄35-80岁,平均55岁。TIC曲线:32例恶性肿瘤中,12例(37.50%)为Ⅲ型曲线,20例(62.50%)为Ⅱ型曲线,未见Ⅰ型曲线;13例良性肿瘤中,9例(69.23%)为Ⅰ型曲线,3例(23.08%)为Ⅱ型曲线,1例(7.69%)为Ⅲ型曲线;良、恶性卵巢肿瘤的TIC类型之间的差异有统计学意义(P0.0001)。半定量参数:恶性肿瘤Sl60%(126.43±17.90%)明显高于良性肿瘤(69.62±33.12%),恶性肿瘤(72.93±22.24s)明显早于良性肿瘤TTP200S(141.11±48.12s),SI60%及TTP200S两者之间的差异有统计学意义(p=0.0002,p=0.0001)。在鉴别良、恶性肿瘤时,SI60%96.125%、TTP200s116s时,诊断恶性肿瘤的敏感性较高(敏感性分别为93.7%及96.87%,特异性分别为76.9%及69.23%)。定量参数:恶性卵巢肿瘤的Ktrans值(0.352±0.114mm-1)、Kep 值(0.535±0.182 min-1)及 Ve 值(0.761±0.428)均高于良性肿瘤(分别为 0.116±0.068mm-1、0.293±0.106 min-1及0.367±0.123),Ktrans 值、Kep 值及 Ve 值之间的差异有统计学意义。在鉴别良、恶性肿瘤时,当Ktrans值0.234min-1时,诊断恶性肿瘤的特异性及敏感性均较高,敏感性为87.50%,特异性为100.00%;当Kep0.414 min-1敏感性为92.31%,特异性78.12%;当Ve0.512时,敏感性为68.75%,特异性92.31%。半定量参数(SI60%、TTP200S)与定量参数(Ktrans值、Kep值、Ve值)对鉴别卵巢良、恶性肿瘤诊断效能的差异无统计学意义。定量参数Ktrans值鉴别卵巢良、恶性肿瘤曲线下面积(0.974)高于半定量参数(曲线下面积分别为0.829,0.882)。结论我们的初步研究证实DCE-MRI根据时间-信号曲线(TIC),半定量和定量参数在卵巢良、恶性肿瘤的有较高鉴别诊断效能。根据TIC,半定量和定量参数的最佳阈值鉴别良、恶性肿瘤有较高的敏感性和特异性。半定量参数与定量参数对卵巢肿瘤的诊断效能之间差异无统计学差异,但定量参数Ktrans值鉴别卵巢良、恶性肿瘤曲线下面积高于半定量参数,因此本研究认为定量参数Ktrans值是鉴别卵巢肿瘤最相关的因素。总之,半定量参数及定量参数允许放射科诊断医生更有信心地诊断良性或者卵巢肿瘤;这些参数是常规形态MR诊断的重要补充,对于那些常规MRI诊断不确定的情况,定量及半定量参数尤其有用,可以避免不必要的根治性手术。
[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.
【学位授予单位】：山东大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R445.2;R737.31

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