【摘要】：背景和目的 腦血管病是嚴重危害人類健康的三大主要疾病之一，流行病學調(diào)查資料顯示，腦出血（intracerebral hemorrhage, ICH）的發(fā)病率、死亡率、致殘率極高，嚴重威脅著人們的健康和生活。腦出血最重要的病理改變是血腫本身和血腫周圍的繼發(fā)性損傷，如何應用影像學檢查方法，在腦出血的早期及時做出準確的診斷，并評估血腫周圍腦組織的繼發(fā)性改變，對腦出血的診斷、治療和預后評估具有重要的意義。 傳統(tǒng)的觀點認為，腦出血的首選檢查手段是CT，常規(guī)磁共振成像（magneticresonance imaging, MRI）對出血不敏感。近年來，隨著MRI設(shè)備的不斷更新與磁共振成像新技術(shù)的發(fā)展，如多回波采集的T2*WI三維梯度回波（enhanced T2starweighted angiography, ESWAN）、擴散加權(quán)成像（diffusion weighted imaging,DWI）、灌注加權(quán)成像（perfusion weighted imaging, PWI）、磁共振波譜成像（magnetic resonance spectroscopic imaging, MRSI）、擴散張量成像（diffusiontensor imaging, DTI）在腦出血的研究中已得到廣泛的應用。其中ESWAN序列是近年來新興起的MRI檢查技術(shù)，它對磁敏感性物質(zhì)尤其敏感，不僅可以及早的發(fā)現(xiàn)出血灶，還能檢出常規(guī)序列所不能發(fā)現(xiàn)的微出血灶，對臨床治療方式的選擇具有重要的參考價值。 本實驗的研究目的是通過MRI檢查，探討腦出血后血腫體積的演變與灶周水腫的變化情況，并與病理結(jié)果對照，分析影像資料與病理指標的相關(guān)性。 材料與方法 1.隨機選取清潔級健康雄性SD大鼠64只，體重250g~300g，平均(280.3±7.5) g。實驗動物均由河南省動物實驗中心提供。按照隨機數(shù)字表法將大鼠分為實驗組和對照組，實驗組48只，行開顱、鉆孔、進針并注血，對照組16只，除不注血外其他操作同實驗組。以上動物均于造模后1h、3h、12h、24h、48h、72h、1w、2w分別行MRI掃描，并于各個時間點取病理標本。 2.腦出血模型的制作過程：將大鼠固定于立體定位儀上，取前囟后0.3mm，向左旁開3mm處，采用顱骨鉆鉆一大小約1mm直徑的小孔，進針6mm。取自體左心室動脈血40ul注入（3分鐘內(nèi)），留針10分鐘后拔出，封閉骨孔，縫合，行MRI掃描。 3.磁共振掃描采用美國GE公司7503.0T超導高場磁共振掃描機和大鼠專用線圈。實驗組和對照組分別于造模后1h、3h、12h、24h、48h、72h、1w、2w行T1加權(quán)成像（T1-weighted imaging, T1WI）、T2加權(quán)成像（T2-weighted imaging,T2WI）、擴散加權(quán)成像（diffusion weighted imaging, DWI）、T2*WI及ESWAN序列掃描。根據(jù)磁共振掃描相應層面，，在各個時間點分別選取2只大鼠，斷頭取腦，進行干濕重分析和免疫組織化學MMP9、AQP4的半定量分析。 4.觀察不同時間點大鼠腦出血在ESWAN序列上相位弧度值、SWAN信號值的動態(tài)演變。經(jīng)圖像后處理測出血腫在T2WI、T2*WI、ESWAN序列上的體積，并與大體標本所測得體積進行比較，得出以上各個序列的放大率。觀察比較不同時間點大鼠出血灶灶周DWI圖像的變化情況，并記錄表觀擴散系數(shù)（apparentdiffusion coefficient, ADC）的變化。MRI檢查后取腦組織行腦組織含水量測量，并取腦組織切片觀察MMP9和AQP4的表達趨勢，分析ADC值、腦組織含水量與MMP9、AQP4的相關(guān)性。 5.所得結(jié)果使用SPSS17.0統(tǒng)計軟件包行統(tǒng)計學分析，計量結(jié)果使用均數(shù)±標準差表示。運用的統(tǒng)計學方法是獨立樣本的t檢驗、配對樣本的t檢驗、方差分析、相關(guān)性分析，以P0.05為檢驗水準。 結(jié)果 1.實驗組大鼠腦出血后，出血中心區(qū)域相位弧度值、SWAN信號值均降低。實驗組大鼠與對照組大鼠不同時間點相位弧度值、SWAN信號值對比，差異有統(tǒng)計學意義（P＜0.05）；實驗組大鼠出血側(cè)與鏡像側(cè)相位弧度值、SWAN信號值對比，差異有統(tǒng)計學意義（P＜0.05）。 2. T2WI、T2*WI、ESWAN序列及大體標本所測血腫體積顯示，血腫體積在1h~2w時間段均逐漸減小。其中，T2WI所測血腫體積與大體標本所得體積比較，無顯著性差異（P=0.125＞0.05），T2*WI、ESWAN序列所測血腫體積與大體標本所得體積比較，差異有統(tǒng)計學意義（P=0.025＜0.05）。即T2WI對血腫體積的顯示較確切，ESWAN、T2*WI序列對血腫的顯示均存在放大效應，平均放大率分別為1.707±0.086,1.332±0.050。 3.實驗組大鼠血腫周圍的腦組織在1h時ADC值無明顯變化，3~72h ADC值上升。實驗組大鼠與對照組大鼠各個時間點ADC值相比，除1h、7d、14d組外，差異均有統(tǒng)計學意義（P＜0.05）；實驗組大鼠各個時間點出血側(cè)ADC值與鏡像側(cè)相比，除1h、7d、14d組外，差異均有統(tǒng)計學意義（P＜0.05）。 4.實驗組大鼠MMP9在出血后3h即可見表達，24h明顯增多，48h達高峰，出血14天時仍有表達。除了1h外，實驗組大鼠與對照組大鼠各個時間點的IODMMP9比較，差異均有統(tǒng)計學意義（P＜0.05）。 5.實驗組大鼠AQP4在出血后1h可見陽性表達，12h表達增強，48h達高峰，14d仍可見表達。實驗組大鼠與對照組大鼠各個時間點IODAQP4的比較，差異均有統(tǒng)計學意義（P＜0.05）。 6.分析ADC值、干濕重結(jié)果與病理指標MMP9、AQP4的相關(guān)性，ADC值與MMP9呈正相關(guān)性，腦組織含水量與MMP9、AQP4也存在正相關(guān)性。 結(jié)論 1. ESWAN序列可以準確的識別出血灶，并且可以用于早期出血的檢查 2. ESWAN、T2*WI序列對血腫的顯示存在放大效應，而T2WI對血腫的顯示更接近于真實大小 3.大鼠腦出血后血腫周圍AQP4和MMP9的表達隨著時間的延長，呈逐步增加的趨勢
[Abstract]:Background and purpose
Cerebrovascular disease is one of the three major diseases that seriously endanger human health. Epidemiological investigation data show that the incidence, mortality and disability rate of intracerebral hemorrhage (ICH) are extremely high, which seriously threaten people's health and life. How to make an accurate diagnosis in the early stage of intracerebral hemorrhage and evaluate the secondary changes of brain tissue around the hematoma by imaging examination is of great significance to the diagnosis, treatment and prognosis evaluation of intracerebral hemorrhage.
In recent years, with the continuous updating of MRI equipment and the development of new MRI techniques, such as enhanced T2 * WI three-dimensional gradient angiography (ESWAN) with multi-echo acquisition, expanding. Diffusion weighted imaging (DWI), perfusion weighted imaging (PWI), magnetic resonance spectroscopic imaging (MRSI), diffusion tensor imaging (DTI) have been widely used in the study of cerebral hemorrhage. The rising MRI technology is particularly sensitive to magnetic sensitive substances. It can not only detect hemorrhagic foci early, but also detect micro-hemorrhagic foci which can not be found by conventional sequence. It has important reference value for the choice of clinical treatment.
The purpose of this study is to investigate the changes of hematoma volume and perifocal edema after intracerebral hemorrhage by MRI, and to compare with pathological results, and to analyze the correlation between imaging data and pathological indicators.
Materials and methods
1. Sixty-four healthy male SD rats of clean grade were randomly selected, weighing 250-300 g, with an average of (280.3 (+ 7.5) g. The experimental animals were provided by Henan Provincial Animal Experimental Center. According to the random number table method, the rats were divided into experimental group and control group. 48 rats in the experimental group were craniotomy, drilling, needling and blood injection. 16 rats in the control group were operated in the same way except without blood injection. All the above animals were scanned by MRI at 1h, 3h, 12h, 24h, 48h, 72h, 1W and 2W after modeling, and pathological specimens were taken at each time point.
2. The process of making cerebral hemorrhage model: Fixed the rat on the stereotactic positioner, 0.3 mm after the anterior fontanel, 3 mm to the left side, drilled a small hole about 1 mm in diameter with a skull drill, and needled 6 mm. The left ventricular artery blood 40 UL was injected (within 3 minutes), the needle was pulled out after 10 minutes, the bone hole was closed, sutured and MRI scanned.
3. Magnetic resonance scans were performed with 7503.0T superconducting high-field magnetic resonance scanner made by GE Company and special coils for rats. The experimental group and the control group were performed T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion weighted imaging (DWI) at 1 h, 3 h, 12 h, 24 h, 48 h, 72 h, 1 W and 2 W after modeling, respectively. Two rats were selected at each time point and their brains were cut off for dry-wet weight analysis and semi-quantitative analysis of immunohistochemical MMP9 and AQP4.
4. To observe the dynamic changes of phase radian and SWAN signal value of intracerebral hemorrhage on ESWAN sequence at different time points. The volume of hemorrhage on T2WI, T2*WI and ESWAN sequence was measured by image post-processing, and the magnification of each sequence was obtained by comparing with the volume measured by gross specimen. The changes of DWI images were recorded and the apparent diffusion coefficient (ADC) was recorded. After MRI examination, the water content of brain tissues was measured. The expression trend of MMP9 and AQP4 was observed and the correlation between ADC value, water content of brain tissues and MMP9 and AQP4 was analyzed.
5. The results were analyzed by SPSS17.0 statistical software package, and the measurement results were expressed by mean-standard deviation.
Result
1. After intracerebral hemorrhage, the phase radian and SWAN signal value of the hemorrhagic center decreased. The phase radian and SWAN signal value of the experimental group and the control group at different time points were significantly different (P < 0.05); the phase radian and SWAN signal value of the hemorrhagic side and the mirror side of the experimental group were significantly different (P < 0.05). Significance (P < 0.05).
2. The hematoma volume measured by T2WI, T2 * WI, ESWAN sequence and gross specimen showed that the hematoma volume decreased gradually in the period of 1 h to 2 w. There was no significant difference between the hematoma volume measured by T2WI and that obtained by the general specimen (P = 0.125 > 0.05), the hematoma volume measured by T2 * WI, ESWAN sequence and the volume obtained by the general specimen, the difference was statistically significant. Meaning (P = 0.025 < 0.05). T2WI showed the hematoma volume more accurately. Both ESWAN and T2 * WI showed magnification effects on hematoma. The average magnification rates were 1.707 (+ 0.086) and 1.332 (+ 0.050) respectively.
3. The ADC value of the brain tissue around the hematoma in the experimental group did not change significantly at 1 hour, but increased at 3-72 hours. The ADC value of the experimental group was significantly different from that of the control group at each time point except 1 hour, 7 days and 14 days (P < 0.05); the ADC value of the hemorrhagic side of the experimental group was significantly different from that of the mirror side at each time point except 1 hour, 7 days and 14 days. There was statistical significance (P < 0.05).
4. The expression of MMP-9 was observed at 3 hours after bleeding, increased significantly at 24 hours, reached the peak at 48 hours, and still expressed at 14 days after bleeding in the experimental group. Except for 1 hour, the difference between the experimental group and the control group was statistically significant (P < 0.05).
5. AQP4 positive expression was observed at 1 hour after bleeding, increased at 12 hours, peaked at 48 hours, and still expressed at 14 days in the experimental group and the control group. The difference was statistically significant (P < 0.05).
6. The ADC value, the results of dry and wet weight were correlated with pathological indexes MMP9 and AQP4, ADC value was positively correlated with MMP9, and brain water content was positively correlated with MMP9 and AQP4.
conclusion
1. ESWAN sequence can accurately identify bleeding foci, and can be used for early bleeding examination.
2. ESWAN and T2*WI sequences have magnification effect on the display of hematoma, while T2WI is closer to the real size of hematoma.
3. the expression of AQP4 and MMP9 around hematoma after cerebral hemorrhage in rats showed a trend of gradual increase with the extension of time.
【學位授予單位】：鄭州大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R743.34;R445.2

【參考文獻】

相關(guān)期刊論文 前7條

1 王葦,張新江,殷小平,李澄,常麗英,張?zhí)K明,姜亞平,方思羽;腦出血超早期血腫周圍病變的MRI研究及其臨床意義[J];第三軍醫(yī)大學學報;2005年05期

2 張新江,楊金升,常麗英,殷小平,王葦,張?zhí)K明,方思羽;豬腦出血動態(tài)彌散加權(quán)成像和血腫周圍組織質(zhì)子波譜分析[J];第四軍醫(yī)大學學報;2004年21期

3 張朋奇,朱賢立,趙甲山,喬嫻;一種大鼠腦內(nèi)出血模型的建立與評價[J];中國臨床神經(jīng)外科雜志;2005年01期

4 周劍;高培毅;李小光;胡平英;;腦出血亞急性及慢性期血腫周圍組織低灌注損傷的CT灌注成像研究[J];中華放射學雜志;2006年05期

5 張新江,殷小平,王葦,常麗英,張?zhí)K明,方思羽;腦出血超早期灶周水腫性質(zhì)的磁共振研究[J];中華神經(jīng)科雜志;2003年03期

6 Reiji Sugita;Kei Ito;Naotaka Fujita;Shoki Takahashi;;Diffusion-weighted MRI in abdominal oncology:Clinical applications[J];World Journal of Gastroenterology;2010年07期

7 王娟;周義成;鐘高賢;王承緣;夏黎明;朱文珍;;DWI和MRS對微創(chuàng)血腫清除術(shù)后的評估研究[J];中國醫(yī)學影像技術(shù);2007年03期

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