本文選題：左心發(fā)育不良綜合征 + 超聲心動圖�。� 參考：《中南大學》2014年博士論文

【摘要】：目的：應用超聲心動圖診斷胎兒左心發(fā)育不良綜合征(hypoplastic left heart syndrome,HLHS),重點研究HLHS胎兒卵圓孔(FO)、肺靜脈(PV)、主動脈峽部(AoI)、大腦中動脈(MCA)和臍動脈(UA)的血流動力學變化,并與胎齡相匹配的正常對照組胎兒進行比較,旨在為深入認識HLHS胎兒復雜而獨特的病理生理和循環(huán)特點提供更多有用信息,探討其對于產(chǎn)前早期診斷HLHS和評估胎兒預后的臨床意義。 應用時間—空間相關成像(spatio-temporal image correlation,STIC)技術結合虛擬器官計算機輔助分析(virtual organ computer-aided analysis,VOCAL)軟件測量HLHS胎兒右心室容積,計算出右心功能參數(shù),并與胎齡相匹配的正常對照組胎兒右心室容積及心功能參數(shù)進行對比分析,探討STIC技術評價HLHS胎兒右心室容積和右心功能的可行性、準確性、優(yōu)越性及臨床意義。 對象及方法：2007年6月至2013年1月來本院接受常規(guī)產(chǎn)前超聲檢查的49例24+0-37+6孕周HLHS胎兒和180例胎齡相匹配的正常對照組胎兒,均為單胎妊娠。應用Acuson Sequoia512、GE Voluson730Expert和GE Voluson E8彩色多普勒超聲診斷儀檢測上述胎兒FO、PV‘AoI、MCA和UA血流,并測量其PV、MCA和UA的血流參數(shù),包括：PV的心室收縮波(S波)、心室舒張波(D波)、心房收縮波(A波)、S/D比值、MCA和UA的搏動指數(shù)(PI)以及腦/臍血管比值(CPR),然后進行統(tǒng)計學分析比較,并與尸檢或產(chǎn)后追蹤結果相對照。 應用GE Voluson730Expert和GE Voluson E8超聲診斷儀的三維容積探頭采集上述所有胎兒的STIC心臟動態(tài)圖像,并結合VOCAL軟件進行后期脫機分析。通過回放功能,在房室瓣開放和關閉的瞬間停幀,心臟收縮末期近似為房室瓣即將開放前,心臟舒張末期為房室瓣剛剛關閉后。設定旋轉角度為150,對軟件自動生成12個旋轉層面的右心室內(nèi)膜面逐層進行手動描記,計算機自動總和各個層面的容積數(shù)據(jù)得到右心室舒張末期容積(RVEDV)和右心室收縮末期容積(RVESV),從而計算出右心每搏量(RSV)、右心輸出量(RCO)和右心射血分數(shù)(REF)。根據(jù)產(chǎn)前常規(guī)超聲檢查時所測量頭圍(HC)、腹圍(AC)、股骨長度(FL)和胎兒估測體重(EFW)來標準化右心輸出量(RCO),然后將所有測量參數(shù)進行統(tǒng)計學分析比較。 結果：本研究納入統(tǒng)計分析的46例經(jīng)尸檢證實的HLHS胎兒中,29例(63.04%)FO血流方向正常,為右向左分流；17例(36.96%)FO血流明顯異常,其中,14例(30.44%)FO血流反向,為限制性左向右分流；另外3例(6.52%)FO早閉,房間隔完整,房水平無分流。 46例HLHS胎兒的PV血流頻譜呈現(xiàn)三種不同類型。29例FO右向左分流和14例FO限制性左向右分流的HLHS胎兒PV血流頻譜呈三相波型：心室收縮期前向血流(S波)、心室舒張期前向血流(D波)和心房收縮期反轉血流(A波)；3例房間隔完整無分流的HLHS胎兒PV血流頻譜呈短而搏動明顯的雙向來回血流,即：心室收縮期前向血流(S波)和心房收縮期反轉血流(A波),心室舒張期血流(D波)缺失。HLHS胎兒組的PV血流頻譜A波反轉、S波和S/D比值均較胎齡相匹配的正常對照組胎兒明顯增高(P0.001)；其中,FO血流異常與FO右向左分流兩組HLHS胎兒之間進行比較,前者的PV血流頻譜反轉A波較后者更高(P0.001)、D波則較后者減低或缺失(P0.001)、S波和S/D比值較后者顯著增高(P0.001)。 28例(60.87%)嚴重HLHS胎兒的AoI出現(xiàn)反向血流。三血管—氣管切面彩色多普勒顯示主動脈弓部血流主要來自動脈導管經(jīng)由AoI逆行灌注,血流方向與肺動脈前向血流方向相反,血流色彩不同。 HLHS胎兒組的MCA-PI和CPR均較胎齡相匹配的正常對照組胎兒明顯減低(P0.001)、而UA-PI則較正常對照組胎兒明顯增高(P0.001)；其中,AoI反向供血與AoI無反向供血兩組HLHS胎兒之間進行比較,前者的MCA-PI和CPR較后者更低(MCA-PI：P0.001；CPR：P0.05)。 本研究納入統(tǒng)計分析的226例胎兒中,190例胎兒的STIC心臟動態(tài)圖像采集滿意,并成功應用VOCAL軟件分析測量了胎兒的RVEDV和RVESV。其中,HLHS胎兒39例,正常對照組胎兒151例：整體采集分析成功率為84.07%,且可重復性較好。 正常對照組胎兒的RVEDV、RVESV、RSV、RCO和根據(jù)胎兒生物學參數(shù)(HC、AC、FL)分別標準化后的RCO均隨孕周增長呈增加趨勢,REF和RCO/EFW測值則在一定范圍內(nèi)波動。 HLHS胎兒組的右心室容積較胎齡相匹配的正常對照組胎兒明顯增大(P0.001)。其中,左心室腔存在與左心室腔閉鎖兩組HLHS胎兒右心室容積和心功能參數(shù)測值之間的比較并無明顯差異(P0.05)；三尖瓣嚴重返流與輕度返流兩組HLHS胎兒之間進行比較,前者的RVEDV和RVESV均較后者增大,而RVESV較后者增大得更明顯(RVEDV：P0.05;RVESV：P0.001),前者的RSV、RCO和標準化后的RCO(RCO/EFW、RCO/HC、RCO/AC、RCO/FL)卻較后者降低(P0.05),REF測值則較后者降低得更明顯(P0.001)；三尖瓣輕度返流組HLHS胎兒的REF測值與胎齡相匹配的正常對照組胎兒比較無明顯差異(P0.05),三尖瓣嚴重返流組HLHS胎兒的REF測值則較胎齡相匹配的正常對照組胎兒明顯降低(P0.001)。 結論： 1.針對FO限制性左向右分流或房間隔完整無分流的HLHS胎兒,產(chǎn)前盡早明確診斷有助于臨床及時開展有效的宮內(nèi)干預,從而達到最終改善其預后之目的。 2.PV血流頻譜可作為一個間接預測左房高壓的有用指標。HLHS胎兒PV血流頻譜的三種不同類型反映了左房高壓的不同嚴重程度,這些信息對于評估胎兒預后和制定圍產(chǎn)期處理方案至關重要。 3.由于AoI反向供血所致三血管—氣管切面主動脈弓部與肺動脈血流方向相反的聲像特征可為產(chǎn)前診斷HLHS提供重要線索。 4.同時出現(xiàn)AoI反向供血、FO和PV血流異常的HLHS胎兒,病變通常更加嚴重,應通過產(chǎn)前早期診斷進行及時的臨床干預。 5.HLHS胎兒腦血流量明顯減少,自動調(diào)節(jié)機制將促進腦血管代償性擴張,以使得血管阻力有所降低；故HLHS胎兒MCA-PI和CPR較胎齡相匹配的正常胎兒減低,從而最大限度地滿足腦循環(huán)血流灌注。這可作為HLHS產(chǎn)前早期診斷的一項輔助性指標。 6.正常胎兒的RVEDV、RESV.RSV、RCO和根據(jù)胎兒生物學參數(shù)(HC、AC、FL)標準化后的RCO均隨孕周增長呈增加趨勢,REF和RCO/EFW測值則在一定范圍內(nèi)波動。 7.三尖瓣輕度返流組HLHS胎兒的RVEDV、RVESV、RSV、RCO和標準化后的RCO(RCO/EFW、RCO/HC、RCO/AC、RCO/FL)均較胎齡相匹配的正常對照組胎兒明顯增加：提示HLHS胎兒右心室收縮功能代償性增強。HLHS胎兒左心室腔的大小對其右心室功能的影響不明顯。三尖瓣嚴重返流與輕度返流兩組HLHS胎兒之間進行比較,前者的右心室容積較后者增大,而右心功能參數(shù)測值卻較后者降低：提示三尖瓣嚴重返流的HLHS胎兒在宮內(nèi)即出現(xiàn)右心室收縮功能受損,預后極差,臨床應及時干預。 8.應用STIC技術能夠比較準確、客觀地測量胎兒心室容積,有望成為臨床評價胎兒心臟功能的重要方法,可為早期評價HLHS胎兒的右心功能提供極為有用信息。
[Abstract]:Objective: to diagnose fetal left heart dysplasia syndrome (hypoplastic left heart syndrome, HLHS) by echocardiography, and to study the changes in blood flow mechanics of HLHS fetal oval foramen (FO), pulmonary vein (PV), aorta isthmus (AoI), middle cerebral artery (MCA) and umbilical artery (UA), and compare with fetal age matched normal control group. The purpose of this study is to provide more useful information for the understanding of the complicated and unique pathophysiology and circulation characteristics of HLHS fetus, and to explore the clinical significance of the early prenatal diagnosis of HLHS and the evaluation of fetal prognosis.
Spatio-temporal image correlation (STIC) technique was used to measure the right ventricular volume of HLHS fetus with the computer aided analysis (virtual organ computer-aided analysis, VOCAL), and the right ventricular function parameters were calculated and the right ventricular volume and heart work in the normal control group matched with the gestational age were matched. The feasibility, accuracy, superiority and clinical significance of STIC technique in evaluating right ventricular volume and right heart function of HLHS fetus were discussed.
Objects and methods: from June 2007 to January 2013, 49 24+0-37+6 gestational HLHS fetuses and 180 normal control groups matched with fetal age were treated with conventional prenatal ultrasound examination, all of which were single pregnancy. Acuson Sequoia512, GE Voluson730Expert and GE Voluson E8 color Doppler ultrasound diagnostic apparatus were used to detect the fetus FO, PV 'A. OI, MCA and UA blood flow, and measure the blood flow parameters of PV, MCA and UA, including: PV ventricular systolic wave (S wave), ventricular systolic wave (D wave), atrial systolic wave (A wave), S/D ratio, MCA and pulsatile index, and the ratio of brain to umbilical blood vessels, then compared statistically and compared with autopsy or postpartum tracing results.
The three-dimensional volume probe of GE Voluson730Expert and GE Voluson E8 ultrasonic diagnostic instrument was used to collect all the STIC cardiac dynamic images of all the above fetus, and combined with the VOCAL software to analyze the later off-line analysis. Through the replay function, the frame of the atrioventricular valve opened and closed, the end of the systole was approximate to the atrioventricular valve opening before the opening of the atrioventricular valve, and the heart diastole was diastolic. After the end of the atrioventricular valve was just closed. The rotation angle was set to 150, and the software automatically generated 12 rotation layers of the right ventricular endocardium by manual tracing. The computer automatically combined the volume data of each level to get the right ventricular end diastolic volume (RVEDV) and the right ventricular end systolic volume (RVESV), thus calculating the right heart stroke volume. (RSV), right cardiac output (RCO) and right cardiac ejection fraction (REF). According to the measured head circumference (HC), abdominal circumference (AC), femur length (FL) and fetal estimation weight (EFW), the right cardiac output (RCO) was standardized by prenatal routine ultrasound examination, and all the measured parameters were compared statistically.
Results: 46 cases of HLHS fetus confirmed by autopsy were included in this study. 29 cases (63.04%) FO blood flow was normal, right to left shunt; 17 (36.96%) FO blood flow was obviously abnormal, of which 14 cases (30.44%) FO blood flow reversed to the restricted left to right shunt; the other 3 cases (6.52%) FO early closed, the atrial septum was intact, the atrial level was no distributary.
The PV blood flow spectrum of 46 cases of HLHS fetus showed three different types of.29 cases FO right to left shunt and 14 cases of FO restrictive left to right shunt of HLHS fetal PV flow frequency spectrum: the anterior ventricular systolic blood flow (S wave), ventricular diastolic forward flow (D wave) and atrial systolic reverse flow (A wave); 3 cases of atrial septal complete and non distributary HLHS. The blood flow of the fetal PV blood flow is short and pulsating, that is, the anterior ventricular systolic blood flow (S wave) and the atrial systolic reverse flow (A wave), the PV flow of the ventricular diastolic blood flow (D wave) in the.HLHS fetal group with the A wave inversion, the S wave and the S/D ratio are significantly higher than those of the normal control group that match the gestational age (P0.001). Among them, FO blood flow abnormal and FO right to left shunt two groups of HLHS fetus were compared, the former PV blood flow reversal A wave is higher than the latter (P0.001), D wave is lower or missing than the latter (P0.001), S wave and S/D ratio is significantly higher than the latter (P0.001).
28 cases (60.87%) of severe HLHS fetus had reverse flow of AoI. Three vascular trachea face color Doppler showed that the aortic arch flow mainly came from the retrograde perfusion of the ductus arteriosus via AoI, and the direction of the blood flow was opposite to the direction of the anterior pulmonary artery, and the color of the blood flow was different.
The MCA-PI and CPR of the HLHS fetal group were significantly lower than those of the normal control group (P0.001), while UA-PI was significantly higher than that of the normal control group (P0.001). Among them, the AoI reverse blood supply and AoI without reverse blood supply were compared between the two groups of HLHS fetus, the MCA-PI and CPR of the former were lower than the latter.
In this study, the STIC cardiac dynamic images of 190 fetuses were collected in 226 fetuses with statistical analysis, and the RVEDV and RVESV. of the fetus were measured by VOCAL software, 39 cases of HLHS fetus and 151 normal controls: the success rate of the whole collection analysis was 84.07%, and the repeatability was better.
RVEDV, RVESV, RSV, RCO, and fetal biological parameters (HC, AC, FL) of normal controls were all increased with the growth of gestational age, and REF and RCO/EFW values fluctuated in a certain range.
The right ventricular volume in the HLHS fetus group was significantly increased (P0.001) in the normal control group matched with the gestational age. There was no significant difference between the left ventricular cavity and the left ventricle atresia in two groups of HLHS fetal right ventricular volume and cardiac function parameters (P0.05); the three apical regurgitation and the mild reflux of two groups of HLHS fetuses were entered. Compared with the latter, the former RVEDV and RVESV were larger than the latter, while RVESV was more obvious than the latter (RVEDV:P0.05; RVESV:P0.001). The former RSV, RCO and the standardized RCO (RCO/EFW, RCO/HC, RCO/AC, RCO/FL) were lower than those of the latter. There was no significant difference between F and fetal age matched normal controls (P0.05). The REF values of HLHS fetus in the three apical regurgitation group were significantly lower than those of the normal control group that matched the gestational age (P0.001).
Conclusion:
1. for the FO restrictive left to right shunt or the complete and distributary HLHS fetus of the atrial septum, the early and clear diagnosis of the prenatal is helpful to the timely and effective intrauterine intervention, so as to achieve the ultimate improvement of the prognosis.
The 2.PV blood flow spectrum can be used as a useful indicator for indirect prediction of left atrial pressure, the three different types of.HLHS fetal PV blood flow spectrum reflect the different severity of left atrial pressure. These information are essential for assessing fetal prognosis and perinatal treatment.
3. the ultrasonographic features of the three vascular endotracheal arch and the opposite direction of the pulmonary artery blood flow can provide an important clue for the prenatal diagnosis of HLHS, due to the reverse blood supply of AoI.
4. at the same time, AoI reverse blood supply, FO and PV abnormal blood flow HLHS fetus, the lesions are usually more serious, we should make timely clinical intervention through prenatal diagnosis.
5.HLHS fetal brain blood flow is significantly reduced. Automatic regulation mechanism will promote cerebral compensatory expansion to reduce vascular resistance, so HLHS fetus MCA-PI and CPR are less matched with fetal age than fetal age, thus maximizing cerebral circulation perfusion. This can be used as an auxiliary indicator of early prenatal diagnosis of HLHS.
6. normal fetal RVEDV, RESV.RSV, RCO, and fetal biological parameters (HC, AC, FL) standardized RCO all increased with the growth of gestational age, and REF and RCO/EFW fluctuated in a certain range.
7. the RVEDV, RVESV, RSV, RCO, and standardized RCO (RCO/EFW, RCO/HC, RCO/AC, RCO/FL) of the HLHS fetus of the three apex regurgitation group were significantly higher than those of the normal control group that matched the gestational age. It suggested that the right ventricular systolic function of the HLHS fetus increased the size of the left ventricular chamber in the fetus of the fetus, and the effect of the right ventricular function was not obvious. Three Compared with the two groups of HLHS fetuses with severe regurgitation and mild reflux, the right ventricular volume of the former was larger than that of the latter, but the right ventricular function parameters were lower than that of the latter. It suggested that the right ventricular systolic function in the HLHS fetus with severe reflux of the tip of the valve was impaired in the uterus, and the prognosis was very poor, and the clinical intervention should be done in time.
8. the application of STIC technology can be more accurate and objective measurement of fetal ventricular volume. It is expected to be an important clinical evaluation of fetal heart function. It can provide very useful information for the early evaluation of the right heart function of HLHS fetus.
【學位授予單位】：中南大學
【學位級別】：博士
【學位授予年份】：2014
【分類號】：R445.1

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