本文選題：神經(jīng)膠質(zhì)瘤 + 磁共振成像　； 參考：《第三軍醫(yī)大學(xué)》2014年碩士論文

【摘要】：膠質(zhì)瘤是最常見的原發(fā)腦腫瘤，根據(jù)2007年WHO中樞神經(jīng)系統(tǒng)分類，分為低級(jí)別膠質(zhì)瘤(WHOⅠ、Ⅱ級(jí))及高級(jí)別膠質(zhì)瘤(WHOⅢ、Ⅳ級(jí))。不同級(jí)別及類型的膠質(zhì)瘤具有不同的生物學(xué)行為及預(yù)后，為臨床診治研究的重點(diǎn)。研究證明，腫瘤微血管的生成和病理分級(jí)密切相關(guān)，已作為判斷預(yù)后的重要因素。磁共振灌注成像(perfusionweighted magnetic resonance imaging，PWI)是一種功能性成像手段，可以術(shù)前評(píng)估活體組織的微血管分布及血流灌注情況。活體檢測(cè)膠質(zhì)瘤的微血管生成情況不僅有助于術(shù)前分級(jí)、指導(dǎo)臨床治療方案，更有利于監(jiān)測(cè)抗腫瘤藥物的療效。其中，腦血容量(cerebral blood volume,CBV)已廣泛應(yīng)用于臨床，并對(duì)膠質(zhì)瘤術(shù)前分級(jí)顯示出一定的優(yōu)勢(shì)。近年來(lái)，動(dòng)物實(shí)驗(yàn)結(jié)果表明基于MR灌注成像的血管管徑指數(shù)(vessel size index, VSI)可以非侵入性地定量描述病變的血管重構(gòu)，VSI也稱微血管結(jié)構(gòu)成像(vesselarchitectural imaging，VAI)，優(yōu)于血容量(CBV)、血流量(CBF)等提供間接信息的指標(biāo)，但該技術(shù)應(yīng)用于臨床仍處于摸索階段，缺乏病理驗(yàn)證。本研究利用SE-GE-EPI灌注成像技術(shù)測(cè)量人腦膠質(zhì)瘤的微血管管徑，與CBV結(jié)果作比較，并與病理學(xué)免疫組化結(jié)果相對(duì)照，分析不同級(jí)別腦膠質(zhì)瘤微血管生成的特點(diǎn)及PWI-VSI測(cè)量的準(zhǔn)確性，明確微血管管徑與膠質(zhì)瘤分級(jí)的相關(guān)性。 目的： 研究采用磁共振灌注成像(MR-PWI)測(cè)量膠質(zhì)瘤微血管管徑的有效性、準(zhǔn)確性，分析不同級(jí)別膠質(zhì)瘤微血管的組織學(xué)特點(diǎn)，并探討膠質(zhì)瘤血管大小指數(shù)(VSI)、血容量(CBV)與膠質(zhì)瘤組織學(xué)分級(jí)的相關(guān)性，以期提高M(jìn)RI對(duì)膠質(zhì)瘤術(shù)前分級(jí)評(píng)估的準(zhǔn)確性及為臨床監(jiān)測(cè)膠質(zhì)瘤藥物治療效果提供更多的信息。 材料與方法： 1.研究對(duì)象 膠質(zhì)瘤組：經(jīng)病理證實(shí)的35例膠質(zhì)瘤患者。男15例，女20例，，年齡18~69歲,平均47.26±13.71歲。所有病例為首診病例，未接受過(guò)任何侵入性或非侵入性治療。根據(jù)WHO2007年中樞神經(jīng)系統(tǒng)腫瘤分類及分級(jí)方法，低級(jí)別腫瘤10例，其中星形細(xì)胞瘤7例(包括6例彌漫性星形細(xì)胞瘤及1例肥胖型星形細(xì)胞瘤)，少突膠質(zhì)細(xì)胞瘤3例；高級(jí)別腫瘤25例，其中間變性少突膠質(zhì)細(xì)胞瘤5例，間變性少突星形細(xì)胞瘤1例，間變性星形細(xì)胞瘤3例，膠質(zhì)母細(xì)胞瘤16例。 正常對(duì)照組：10例，取自切除膠質(zhì)瘤標(biāo)本的周圍正常腦組織。 2.掃描設(shè)備及數(shù)據(jù)測(cè)量 MR成像儀器：SIEMENS lagnetom Verio3.0T，完成常規(guī)磁共振掃描及SE灌注掃描，囑患者次日24小時(shí)后行SE-GE-EPI灌注，采用GE SIGNA HDX1.5T超導(dǎo)型MR掃描儀，八通道線圈。分別測(cè)定腫瘤區(qū)VSIMRI最大值、VSIMRI平均值、最大血容灌注值(CBVmax)。測(cè)定對(duì)側(cè)正常腦白質(zhì)病變區(qū)VSIMRI值、CBV值。 3.病理切片染色及測(cè)定指標(biāo) 將病理確診為膠質(zhì)瘤的35例患者的所有石蠟標(biāo)本(每名患者2-8塊)各制備一張切片，分別進(jìn)行HE染色及CD34免疫組織化學(xué)染色，利用計(jì)算機(jī)圖像分析軟件(Image-ProPlus5.0)定量分析膠質(zhì)瘤微血管密度、形態(tài)(包括微血管長(zhǎng)徑、短徑)。 4.數(shù)據(jù)分析 采用皮爾遜相關(guān)分析評(píng)價(jià)VSIMRI、CBV值與微血管長(zhǎng)徑、短徑兩兩之間的相關(guān)性。對(duì)不同級(jí)別膠質(zhì)瘤的VSIMRI最大值、VSIMRI平均值、rCBVmax值行Mann-Whitney U檢驗(yàn)，P0.05為差異有統(tǒng)計(jì)學(xué)意義。采用受試者工作特征(ROC)曲線分析VSIMRI最大值、VSIMRI平均值、rCBVmax值在膠質(zhì)瘤分級(jí)診斷中的價(jià)值并確定其最佳診斷界值和取該界值時(shí)的靈敏度、特異度。 結(jié)果： 1.不同級(jí)別膠質(zhì)瘤的免疫組化表現(xiàn)：CD34標(biāo)記微血管呈棕黃色，低級(jí)別膠質(zhì)瘤(II級(jí))的微血管管徑較均一，血管管徑較小(長(zhǎng)徑18.93±5.11μm，短徑9.62±2.68μm)，稍大于正常腦組織微血管(長(zhǎng)徑8.79±5.10μm，短徑5.51±2.63μm)。在低級(jí)別膠質(zhì)瘤中，少突膠質(zhì)瘤血管管徑(短徑8.06±0.51μm)普遍小于彌漫性星形細(xì)胞瘤(短徑10.41±3.03μm)，而MVD則大于后者。高級(jí)別膠質(zhì)瘤(III、IV級(jí))的微血管密集，管徑相對(duì)較大(長(zhǎng)徑43.59±13.26μm。短徑33.36±11.43μm)，尤其膠質(zhì)母細(xì)胞瘤有更多畸形血管、分支狀血管及發(fā)現(xiàn)腎小球樣血管。微血管管徑最大區(qū)域的微血管數(shù)量不多，即MVD最大值區(qū)域與微血管管徑最大值區(qū)域不一致。隨著膠質(zhì)瘤級(jí)別的增加，腫瘤微血管分布的異質(zhì)性增大。 2. VSIMRI表現(xiàn)：彌漫性星形細(xì)胞瘤及II級(jí)少突膠質(zhì)細(xì)胞瘤的VSI彩圖中色彩較均一，呈VSI值較低的藍(lán)綠色，同一患者不同興趣區(qū)測(cè)得的數(shù)據(jù)相差不大，其中少突膠質(zhì)瘤VSIMRI值小于彌漫性星形細(xì)胞瘤(VSIMRI平均值分別為20.80±3.83μm及56.70±15.69μm)。高級(jí)別膠質(zhì)瘤的VSI彩圖色彩不均一，可見到呈紅色(VSIMRI值較大，III級(jí)膠質(zhì)瘤118.03±22.53μm，膠質(zhì)母細(xì)胞瘤144.05±23.09μm)的區(qū)域，特別是膠質(zhì)母細(xì)胞瘤，病灶中央有明顯壞死區(qū)域，VSIMRI值為0，VSIMRI最大的區(qū)域多位于壞死病灶的邊緣，這與病理所見相符合。 3. VSIMRI值和組織學(xué)切片微血管管徑的相關(guān)性：通過(guò)皮爾遜相關(guān)分析得出，病理切片中測(cè)量的微血管長(zhǎng)徑、短徑與MRI測(cè)量的VSIMRI最大值、平均值兩兩之間都有良好的相關(guān)性(p值均小于0.01，r值均大于0.7)，在MRI與病理測(cè)值兩種方法之間，相關(guān)系數(shù)最高的為微血管短徑與VSIMRI平均值(r=0.8190)。 4.不同級(jí)別膠質(zhì)瘤VSIMRI值的比較及病理切片結(jié)果的比較：高級(jí)別膠質(zhì)瘤較低級(jí)別膠質(zhì)瘤管徑大，經(jīng)統(tǒng)計(jì)學(xué)兩兩比較發(fā)現(xiàn)，WHO Ⅱ級(jí)～WHO Ⅲ級(jí)，WHO Ⅱ級(jí)～WHO Ⅳ級(jí)，WHO Ⅲ級(jí)～WHO Ⅳ級(jí)膠質(zhì)瘤間的VSIMRI平均值差異均有統(tǒng)計(jì)學(xué)意義(p＜0.05)。低級(jí)別膠質(zhì)瘤(WHO II級(jí))與高級(jí)別膠質(zhì)瘤(WHO Ⅲ級(jí)和WHO Ⅳ級(jí))的VSIMRI最大值也有顯著差異(p＜0.05)，而WHO Ⅲ級(jí)和WHO Ⅳ級(jí)膠質(zhì)瘤間VSIMRI最大值差異無(wú)統(tǒng)計(jì)學(xué)意義。低級(jí)別膠質(zhì)瘤(WHO II級(jí))與高級(jí)別膠質(zhì)瘤(WHO III級(jí)和WHO IV級(jí))的管徑有顯著差異，WHO Ⅲ級(jí)～WHO Ⅳ級(jí)膠質(zhì)瘤的短徑差異有統(tǒng)計(jì)學(xué)意義，長(zhǎng)徑差異無(wú)統(tǒng)計(jì)學(xué)意義。WHO Ⅱ級(jí)～WHO Ⅳ級(jí)膠質(zhì)瘤的MVD差異有統(tǒng)計(jì)學(xué)意義。 5. ROC分析：ROC分析結(jié)果顯示VSIMRI平均值和最大值在鑒別Ⅱ級(jí)和Ⅲ、Ⅳ級(jí)膠質(zhì)瘤的曲線下面積為1，VSIMRI平均值取臨界值81.02μm，VSIMRI最大值取臨界值109μm，其鑒別Ⅱ級(jí)和Ⅲ、Ⅳ級(jí)膠質(zhì)瘤的敏感度及特異度均可達(dá)100％(P0.01)。VSIMRI平均值取142μm時(shí)，鑒別WHO Ⅲ級(jí)膠質(zhì)瘤與WHO Ⅳ級(jí)膠質(zhì)瘤的敏感性為68.75%，特異性為88.89%。 6. VSI與CBV比較：在同時(shí)行兩種灌注掃描的13例患者中，rCBV值與VSIMRI值呈正相關(guān)，VSIMRI平均值與病理學(xué)測(cè)量微血管管徑呈正相關(guān)，rCBV值與微血管管徑相關(guān)性無(wú)明顯統(tǒng)計(jì)學(xué)意義。根據(jù)ROC分析結(jié)果得出的cutoff值(VSIMRI平均值取81.12μm，VSIMRI最大值取109μm，rCBV值取3.4)對(duì)此組病例進(jìn)行高、低級(jí)別判定。VSIMRI平均值及VSIMRI最大值能準(zhǔn)確分辨出13例，準(zhǔn)確率為100%；rCBV值能準(zhǔn)確分辨出12例，準(zhǔn)確率為92%。 結(jié)論： 1. VSIMRI值與病理切片測(cè)量微血管管徑有良好相關(guān)性，這與動(dòng)物實(shí)驗(yàn)研究結(jié)果吻合，其中，短徑均值(200倍鏡下測(cè)得的所有微血管徑線均值)與VSIMRI平均值相關(guān)性最好，說(shuō)明MRI-VSI技術(shù)能很好反應(yīng)測(cè)定區(qū)域所有微血管直徑的平均值，從而反應(yīng)腫瘤微血管結(jié)構(gòu)變化。 2.不同級(jí)別膠質(zhì)瘤的VSIMRI值差異有統(tǒng)計(jì)學(xué)意義，VSIMRI值鑒別高、低級(jí)別膠質(zhì)瘤的敏感度及特異度可高達(dá)100%，更值得一提的是VSIMRI平均值可鑒別WHO Ⅲ級(jí)及WHO Ⅳ級(jí)膠質(zhì)瘤。因此，利用VSIMRI值能很好鑒別良、惡性膠質(zhì)瘤，有助于膠質(zhì)瘤術(shù)前分級(jí)。 3.微血管結(jié)構(gòu)(管徑)比微血管密度更能反應(yīng)膠質(zhì)瘤的惡性程度，因此我們推測(cè)MRI-VSI技術(shù)是優(yōu)于血容量等常規(guī)指標(biāo)描述微血管生成的方法，其對(duì)膠質(zhì)瘤分級(jí)診斷提供更多信息。
[Abstract]:Glioma is the most common primary brain tumor. According to the classification of WHO central nervous system in 2007, it is divided into low grade glioma (WHO I, grade II) and high grade glioma (WHO III, grade IV). Different grades and types of gliomas have different biological behavior and prognosis, which are the key points in the diagnosis and treatment of clinics. The PerfusionWeighted magnetic resonance imaging (PWI) is a functional imaging method, which can evaluate the microvascular distribution and blood flow of the living tissue before operation. The microvasculature of the glioma can not only be used to detect the microvasculature in the glioma. Preoperative classification, guiding clinical treatment plans, is more conducive to monitoring the efficacy of antitumor drugs. Cerebral blood volume (CBV) has been widely used in clinical, and shows a certain advantage for preoperative grading of glioma. In recent years, animal experimental results have shown that the vascular diameter index (vessel size index) based on MR perfusion imaging (vessel size index, VSI) can describe the vascular remodeling of the lesion noninvasively, and VSI also known as vesselarchitectural imaging (VAI), which is superior to blood volume (CBV) and blood flow (CBF) to provide indirect information. However, this technique is still in the stage of clinical exploration and lacks pathological examination. This study uses SE-GE-EPI perfusion imaging technology. The microvascular diameter of human glioma was measured, compared with the results of CBV, and compared with the results of pathological immunohistochemical staining, the characteristics of microvascular formation in different levels of glioma and the accuracy of PWI-VSI measurement were analyzed, and the correlation between the microvascular diameter and the grade of glioma was determined.
Objective:
To investigate the effectiveness and accuracy of magnetic resonance perfusion imaging (MR-PWI) to measure the microvascular diameter of glioma, the histological features of the microvessels of different levels of glioma were analyzed, and the correlation between the blood volume index (VSI) of glioma, the blood volume (CBV) and the histological grade of glioma was discussed in order to improve the accuracy of the evaluation of the preoperative grading of glioma by MRI. And provide more information for clinical monitoring of drug treatment effect of glioma.
Materials and methods:
1. research objects
Glioma group: 35 cases of glioma confirmed by pathology, 15 male and 20 female, age 18~69 years, average 47.26 + 13.71 years old. All cases were first diagnosed cases, without any invasive or noninvasive treatment. According to WHO2007 classification and classification of central nervous system tumor, 10 cases of low grade tumor, including 7 cases of astrocytoma. There were 6 cases of diffuse astrocytoma and 1 cases of obesity type astrocytoma, 3 cases of oligodendroglioma, 25 cases of high grade tumor, 5 cases of oligodendroglioma with intermediate degeneration, 1 cases of anaplastic oligodendroid astrocytoma, 3 cases of anaplastic astrocytoma, and 16 cases of glioblastoma.
Normal control group: 10 cases were taken from normal brain tissue around excised glioma specimens.
2. scanning equipment and data measurement
MR imaging instrument: SIEMENS lagnetom Verio3.0T, complete the routine magnetic resonance scan and SE perfusion scan, instruct the patient to perform SE-GE-EPI perfusion 24 hours after the next day, use the GE SIGNA HDX1.5T superconducting MR scanner and the eight channel coil. VSIMRI value and CBV value in white matter lesion area.
3. pathological section staining and measurement index
All paraffin specimens (2-8 blocks per patient) of 35 patients with glioma were prepared by HE staining and CD34 immunohistochemical staining respectively. The microvascular density, morphology (including microvascular length and short diameter) was quantitatively analyzed by computer image analysis software (Image-ProPlus5.0).
4. data analysis
Pearson correlation analysis was used to evaluate the correlation between VSIMRI, CBV value and microvascular diameter and short diameter 22. The maximum value of VSIMRI, the mean value of VSIMRI, the rCBVmax value of the glioma at different levels, Mann-Whitney U test, P0.05 were statistically significant. The maximum value of VSIMRI, VSIMRI average, R was analyzed by the working characteristics of the subjects (ROC). The value of CBVmax in grading diagnosis of glioma and determine its best diagnostic value and sensitivity and specificity.
Result錛

本文編號(hào)：1874265