增强超高速MRI评价心脏首次通过和心肌血流灌注的实验研究

目的 评价Ｇｄ－ＤＴＰＡ的心脏的首次通过及心肌的血流灌注,材料与方法 健杂种犬７条,采用Ｓｅｌｄｉｎｇｅｒ技术以右股动脉分别向ＬＣＸ或ＬＡＤ送主干近端。术后５～１０个月行选择性左冠状动脉造影及心脏增强超高速ＭＲＩ。观察Ｇｄ－ＤＴＰＡ在心脏诸腔及胸部大血管显示顺序,测量左心室前壁,前乳头肌壁,外侧壁,后壁,后乳头肌壁及间隔等区域的相对信号强度,Ｐ〈０．０５具有显著差异,采用光电镜技术观察心肌的病理改     

Gated SPECT imaging to detect changes in myocardial blood flow during progressive coronary occlusion

Background: The ability to track dynamic changes in myocardial blood flow (MBF) and wall motion with serial gated perfusion imaging may be a limiting factor in assessing new therapies. The purpose of this study was to determine whether gated Tc-99 m sestamibi (MIBI) SPECT imaging can track small changes in MBF in a model of progressive ischemia. Methods: Eight pigs (20 kg) underwent lateral thoracotomy for placement of an ameroid constrictor on the left circumflex coronary artery (LCX) and indwelling femoral and left atrial catheters for serial microsphere determinations of absolute MBF. Animals underwent concurrent left atrial microsphere and Tc-99 m sestamibi (0.3 mCi/Kg IV) injections at weekly intervals over 6 weeks per animal. Gated SPECT imaging was acquired for each injection using high resolution collimation and standard processing. The animals were sacrificed on day 42. Mean signal intensity (SI) from regions of interest (ROI) corresponding to control and ischemic MBF by microspheres was measured for three SPECT short-axis images. Mean contrast ratio (MCR) was calculated from the ratio of ischemic to control SI per slice. Regional wall motion (RWM) from gated images was scored 1–5 using a 16 segment model and a score index (RWMI) was calculated. Results: MBF decreased progressively (27% below resting values [P < 0.0001]) but with a clear and significant partial recovery by day 42 (13% improvement from peak ischemia, [P < 0.01]). SPECT perfusion and gated RWM closely paralleled the dynamic pattern of MBF caused by the ameroid constrictor. SPECT MCR decreased 21% from baseline scans in the LCX territory (P < 0.0001) and improved 11% from peak ischemia (P < 0.01) while the gated RWMI (1.0 at baseline) peaked at 1.36 and improved to 1.13 by day 42. Conclusion: Gated SPECT-a technique readily available-tracks dynamic changes in MBF closely with both perfusion and RWM. For trials of new therapies for the alleviation of chronic ischemia, these findings have direct implications for measuring efficacy.     

直接心肌内注射血管内皮生长因子基因对慢性缺血心肌侧枝循环生成的影响

目的观察血管内皮生长因子基因(rAAV2-hVEGF165)直接心肌内注射促进慢性缺血心肌侧枝循环生成的作用。方法小型猪左冠状动脉回旋支放置血管缩窄环,建立慢性心肌缺血模型。5周后应用心电图、冠脉造影和心脏核磁共振成像确认左回旋支闭塞或相应心肌的缺血。动物随机分为实验组和对照组,分别在缺血心肌内直接注射rAAV2-VEGF165(1×1012virus genomeml)或同等量的磷酸盐缓冲液或rAAV2-LACZ(1×1012virus genomeml)。治疗后6个月,冠状动脉造影了解有无侧枝循环生成。结果放置血管缩窄环后5周,所有动物均出现左回旋支完全、次全闭塞和旋支供血区域的心肌缺血。治疗后3个月,缺血心肌内可检测到LACZ和VEGF蛋白的阳性表达;治疗后6个月,VEGF组缺血心肌内毛细血管和小动脉密度均高于对照组(P<0.05);结论直接在小型猪慢性缺血心肌内注射rAAV2-VEGF165,VEGF165基因可转染入心肌组织内,并可在缺血部位显著促进侧枝循环形成。     

Importance of wall motion analysis in the diagnosis of left main disease using stress nuclear myocardial perfusion imaging

We describe a case of a 54-year-old male who underwent exercise technetium-99m sestamibi myocardial perfusion imaging prior to his renal transplantation. With exercise, the patient's myocardial perfusion imaging did not show any transient or fixed myocardial perfusion abnormalities due to balanced ischemia. However, wall motion analysis showed a new global left ventricular systolic dysfunction on post-exercise images. Coronary angiography showed severe left main coronary lesion involving ostia of left anterior descending, ramus intermedius and left circumflex coronary arteries with moderate right coronary artery disease. If one had used the perfusion imaging alone in this patient, the severe multivessel disease including left main coronary disease could have been missed. In this article we emphasize the importance of wall motion analysis in patients undergoing myocardial perfusion imaging.     

MRI of myocardial perfusion.

An overwhelming number of myocardial perfusion studies are done by nuclear isotope imaging. Magnetic resonance imaging during the first pass of an injected, contrast bolus has some significant advantages for detection of blood flow deficits, namely higher spatial resolution, absence of ionizing radiation, and speed of the test. Previous clinical studies have demonstrated that excellent sensitivity and specificity can be achieved with MR myocardial perfusion imaging for detecting coronary artery disease, and assessment of patients with acute chest pain. Furthermore, an absolute quantification of myocardial blood flow is feasible, as was demonstrated by comparison of MR perfusion imaging, to measurements with isotope labeled microspheres in experimental models. An integrated assessment of perfusion, function, and viability, is thus feasible by MRI to answer important clinical challenges such as the identification of stunned or hibernating, but viable myocardium.     

MRI demonstration of acute myocardial infarction due to posttraumatic coronary artery dissection

A case of left ventricular lateral wall myocardial infarction in the distribution of circumflex coronary artery (LCX) was demonstrated by magnetic resonance imaging in a 55-year-old woman. Dissection of the proximal LCX due to blunt chest trauma was followed by percutaneous coronary artery stenting. MR (magnetic resonance) imaging of myocardial infarction is reviewed.     

Hyperemic stress myocardial perfusion cardiovascular magnetic resonance in mice at 3 Tesla: initial experience and validation against microspheres

Background

Dynamic first pass contrast-enhanced myocardial perfusion is the standard CMR method for the estimation of myocardial blood flow (MBF) and MBF reserve in man, but it is challenging in rodents because of the high temporal and spatial resolution requirements. Hyperemic first pass myocardial perfusion CMR during vasodilator stress in mice has not been reported.

Methods

Five C57BL/6 J mice were scanned on a clinical 3.0 Tesla Achieva system (Philips Healthcare, Netherlands). Vasodilator stress was induced via a tail vein catheter with an injection of dipyridamole. Dynamic contrast-enhanced perfusion imaging (Gadobutrol 0.1 mmol/kg) was based on a saturation recovery spoiled gradient echo method with 10-fold k-space and time domain undersampling (k-t PCA). One week later the mice underwent repeat anaesthesia and LV injections of fluorescent microspheres at rest and at stress. Microspheres were analysed using confocal microscopy and fluorescence-activated cell sorting.

Results

Mean MBF at rest measured by Fermi-function constrained deconvolution was 4.1 ± 0.5 ml/g/min and increased to 9.6 ± 2.5 ml/g/min during dipyridamole stress (P = 0.005). The myocardial perfusion reserve was 2.4 ± 0.54. The mean count ratio of stress to rest microspheres was 2.4 ± 0.51 using confocal microscopy and 2.6 ± 0.46 using fluorescence. There was good agreement between cardiovascular magnetic resonance CMR and microspheres with no significant difference (P = 0.84).

Conclusion

First-pass myocardial stress perfusion CMR in a mouse model is feasible at 3 Tesla. Rest and stress MBF values were consistent with existing literature and perfusion reserve correlated closely to microsphere analysis. Data were acquired on a 3 Tesla scanner using an approach similar to clinical acquisition protocols, potentially facilitating translation of imaging findings between rodent and human studies.     

Understanding physiology by using quantitative magnetic resonance perfusion imaging

Cardiac magnetic resonance (CMR) perfusion imaging enables precise quantitation of myocardial blood flow and has been validated in animal models. Myocardial perfusion imaging using a T1-sensitive imaging sequence during the first pass bolus injection of a gadolinium-based contrast agent remains the most robust and extensively studied to date. Myocardial blood flow could be calculated from signal intensity curves utilizing a tracer kinetic model or a model-independent deconvolution method. Quantitative CMR perfusion imaging has provided pathophysiologic insights in epicardial coronary artery disease, microvascular disease, and cardiomyopathy. Imaging at higher field strength, for both CMR first-pass perfusion and myocardial blood oxygen level-dependent imaging, is likely to advance quantitative myocardial perfusion in the future.     

Angiographic correlations of patients with small vessel disease diagnosed by adenosine-stress cardiac magnetic resonance imaging

Cardiac magnetic resonance imaging (CMR) with adenosine-stress myocardial perfusion is gaining importance for the detection and quantification of coronary artery disease (CAD). However, there is little knowledge about patients with CMR-detected ischemia, but having no relevant stenosis as seen on coronary angiography (CA). The aims of our study were to characterize these patients by CMR and CA and evaluate correlations and potential reasons for the ischemic findings. 73 patients with an indication for CA were first scanned on a 1.5T whole-body CMR-scanner including adenosine-stress first-pass perfusion. The images were analyzed by two independent investigators for myocardial perfusion which was classified as subendocardial ischemia (n = 22), no perfusion deficit (n = 27, control 1), or more than subendocardial ischemia (n = 24, control 2). All patients underwent CA, and a highly significant correlation between the classification of CMR perfusion deficit and the degree of coronary luminal narrowing was found. For quantification of coronary blood flow, corrected Thrombolysis in Myocardial Infarction (TIMI) frame count (TFC) was evaluated for the left anterior descending (LAD), circumflex (LCX) and right coronary artery (RCA). The main result was that corrected TFC in all coronaries was significantly increased in study patients compared to both control 1 and to control 2 patients. Study patients had hypertension or diabetes more often than control 1 patients. In conclusion, patients with CMR detected subendocardial ischemia have prolonged coronary blood flow. In connection with normal resting flow values in CAD, this supports the hypothesis of underlying coronary microvascular impairment. CMR stress perfusion differentiates non-invasively between this entity and relevant CAD.     

Intrapericardial delivery of fibroblast growth factor-2 induces neovascularization in a porcine model of chronic myocardial ischemia

Therapeutic angiogenesis is a novel approach to the treatment of myocardial ischemia based on the use of proangiogenic growth factors to induce the growth of new blood vessels to supply the myocardium at risk. This study was designed to assess the safety and efficacy of a single intrapericardial injection of basic fibroblast growth factor (FGF-2) in a porcine model of chronic myocardial ischemia. Yorkshire pigs underwent ameroid placement around the left circumflex coronary artery. At 3 weeks, animals were randomized to receive a single intrapericardial injection of either saline (n = 10), 3 mg of heparin (n = 9), 3 mg of heparin + 30 microgram of FGF-2 (n = 10), 200 microgram of FGF-2 (n = 10), or 2 mg of FGF-2 (n = 10). Coronary angiography, microsphere flow, magnetic resonance functional, and perfusion imaging were performed before and 4 weeks after treatment, at which time histologic analysis was also performed on 3 animals in each group. In ischemic pigs, FGF-2 treatment resulted in significant increases in left-to-left angiographic collaterals and left circumflex coronary artery blood flow. These benefits were accompanied by improvements in myocardial perfusion and function in the ischemic territory, as well as histologic evidence of increased myocardial vascularity without any adverse effects. Not one of these benefits was seen in saline- or heparin-treated ischemic animals. A single intrapericardial injection of FGF-2 in a porcine model of chronic myocardial ischemia results in functionally significant myocardial angiogenesis, without any adverse outcomes. This mode of FGF-2 administration may prove to be a useful therapeutic strategy for the treatment of patients with ischemic heart disease.     

MR first pass imaging: quantitative assessment of transmural perfusion and collateral flow

Recent advances with fast switching gradient coils, and the optimization of magnetic resonance techniques for multi-slice imaging have made it possible to apply models of contrast agent transit for the quantification of myocardial perfusion, and determination of the transmural distribution of blood flow. This article summarizes some of these recent developments and presents examples of quantitative, multi-slice myocardial perfusion imaging studies in patients and animal models. Multi-slice, true first pass imaging, with high temporal resolution, and T1-weighted, arrhythmia insensitive contrast enhancement is used for the quantification of perfusion changes accompanying mild to severe ischemia. The first pass imaging technique and the modeling approach are sufficiently robust for fitting of tissue residue curves corresponding to a wide, physiologically realistic range of myocardial blood flows. In animals this was validated by comparison to blood flow measurements with radiolabeled microspheres as gold standard. It is demonstrated that with the proposed modeling approach one can determine the myocardial perfusion reserve from two consecutive MR first pass measurements under resting and hyperemic conditions. In patients with microvascular dysfunction the MR studies show for the first time that the myocardial perfusion reserve correlates with Doppler flow measurements (linear regression with slope of 1.02±0.09; r=0.80). Since perfusion limitations usually begin in the subendocardium as coronary flow is gradually reduced, first pass imaging with the prerequisitie spatial and temporal resolution allows early detection of a mild coronary stenosis.     

心肌声学造影估测冠脉血流储备的实验研究

建立13条开胸犬冠脉左旋支临界狭窄模型，静脉注射潘生丁前后，主动脉根部注射声振Renografin-76行心肌声学造影，分析左室乳头肌短轴切面不同区域造影效应，并与放射性微球所测该部位区域性心肌血流量对比。结果显示静注潘生丁后左前降支灌注区心肌血流量及造影时间-强度曲线指标中的曲线下面积、峰值强度、最大上升斜率均明显增加，P＜0．01或p＜0．05；而左旋支灌区心肌血流量及造影分析指标在给潘生丁前后无明显变化，p＞0．05。说明心肌声学造影可定性、定量评价冠脉血流储备，有较理想的临床应用前景。     

利声显经静脉心肌声学造影评价心肌梗死后患者的心肌灌注

目的 心肌造影超声心动图（MCE）采用触发谐频能量多普勒显像模式并用静脉持续输液利声显,观察心肌梗死后患者的心肌灌注情况,方法,使用谐频频率1．8－3．6MHZ的能量多普勒模式,于心电图T波终末处,按1：4心动周期进行触发,利声显浓度为300mg/ml,采用微量输液泵将所配心肌造影剂于患者左肘静脉内持续输注4 min(2ml/min),25例心肌梗死后患者的血压和心率变化并对心肌灌注情况进行半定量分析。结果 （1）MCE前后,患者血压和心率改变无明显差异;（2）触发谐频能量多普勒显像模式并用静脉持续输液min的心肌显影效果,而后方衰减可以避免。结论 触发谐频能量多普显像并用静脉持续输注利声显,可以产生较好的心肌灌注显像效果。     

心肌声学造影定量急性心肌梗塞后心肌血流量的实验研究

目的　评价心肌声学造影定量心肌梗塞心肌血流灌注的价值。方法　对６条犬急性心肌梗塞模型进行心肌声学造影, 采用自身对照的方法分析缺血区和非缺血区心肌显影时间－强度曲线各参数之比与心肌血流量的关系。结果　梗塞区时间－强度曲线各参数中, 曲线下面积（ＡＵＣ）和峰值强度（ＰＩ）与心肌相对血流量高度相关（ｒ＝ ０．９２和０．８４, Ｐ＜ ０．０１）, 与心肌绝对血流量相关性良好（ｒ＝ ０．７７和０．７１, Ｐ＜ ０．０１）。不同水平心肌血流量间的ＡＵＣ、ＰＩ均存在显著性差异（Ｐ均小于０．０１）, 且随着血流量的减少而呈下降趋势。三项时间指标与心肌绝对血流量无直接关系。结论　心肌造影时间－强度曲线参数中的曲线下面积和峰值强度可准确定量心肌梗塞后局部心肌血流量。     

心肌灌注显像对心梗恢复期骨髓细胞移植效果估侧的实验研究

目的应用99Tcm-MIBI心肌灌注显像评价猪急性心梗恢复期自体骨髓细胞移植的治疗效果.方法结扎小型猪冠状动脉前降支创建心肌梗死动物模型,分两组,分别于结扎后2周经前降支注入自身骨髓干细胞和磷酸缓冲液(PBS).结扎后2周及第5周,同时对两组动物行99Tcm-MIBI心肌灌注显像.结果骨髓细胞移植组,移植后3周心肌灌注显像血流灌注较PBS组明显改善,两组显像评分结果有显著性差异[(42.4±5.0)和(29.8±9.5)(P＜0.05)].并与冠造及免疫组化结果一致.结论心肌灌注显像是评价骨髓干细胞移植后,心梗心肌血流灌注和心肌细胞活性的较好方法.骨髓干细胞移植可明显改善心肌血运供应及心肌活力.     

应用药物负荷心脏MRI探讨冠心病心肌收缩功能与心肌灌注的关系

目的本研究主要探讨心脏MRI(CMRI)结合药物(小剂量ATP)负荷试验中,心肌收缩功能与心肌灌注之间、心肌收缩功能储备与心肌灌注储备之间的关系。方法我们采用1.5T磁共振扫描仪对68例冠心病患者进行了心脏电影MR成像,其中19例患者冠状动脉造影证实有阳性结果(血管狭窄>50%)。真正快速稳态梯度回波(FIESTA)序列用于观察静息状态下和小剂量ATP负荷状态下的心肌运动;平面回波成像(EPI)序列用于ATP负荷前后的MR心肌灌注成像。各序列均采用左室短轴位成像。电影MRI图像采用MASS软件包对左室各节段室壁运动进行半定量计分,同时对灌注曲线进行定量分析。最后对各节段心肌灌注参数和室壁运动评分进行统计分析。结果在静息状态和负荷状态下,心肌灌注参数均随着室壁运动评分的增加而降低。在小剂量ATP负荷状态下室壁运动较负荷前改善的心肌节段较无改善者的心肌灌注储备值低。结论心肌灌注和心肌收缩功能具有很好的相关性,对两者的综合判断有助于提高CMRI评估心肌活性的价值。     

选择性心肌超声造影对冠状动脉介入治疗后即刻心肌灌注变化的初步研究

目的 采用选择性心肌超声造影（MCE）探讨冠状动脉介入（PCI）术后冠状动脉微循环改善情况。方法 对14例冠心病患者分别于PCI术前及冠状动脉开通后即刻经冠状动脉注射造影剂，在对比脉冲序列成像（CPS）条件下行MCE检查，对比观察心肌显影效果，并采用CUSQ软件进行脱机分析，计算心肌节段微血管灌注的平均灌注量（minivalue）。结果 冠状动脉内注入造影剂即刻能够获得清晰心肌显影，所有患者均获得较满意的左心室及心肌显影。14例患者中12例冠状动脉开通，2例冠状动脉慢性闭塞未能开通。13例于PCI术前MCE显示狭窄或闭塞冠状动脉的对应心肌节段显示节段性充盈减低或无造影剂充盈，1例慢性冠状动脉闭塞性病变患者冠状动脉造影显示侧支循环良好，MCE显示闭塞冠状动脉对应心肌节段充盈基本接近正常。冠状动脉成功开通的12例患者术后即刻MCE显示11例术前闭塞冠状动脉对应心肌节段充盈较术前改善，心肌节段微血管灌注的平均灌注量较术前增加（P〈0．05），1例改善不明显。结论 PCI能够有效改善病变心肌微循环，选择性MCE在CPS条件下能够准确、快速、有效地评价PCI后心肌再灌注情况。     

心肌灌注显像在女性冠心病诊断中价值

目的评价心肌灌注显像对女性冠心病患者的诊断价值。方法 344例有胸痛、胸闷症状女性患者,行静息+药物负荷心肌灌注显像检测,并与冠状动脉造影结果进行对比分析。结果冠状动脉狭窄178例患者中心肌灌注显示异常者130例;冠状动脉造影无异常或不规则166例中心肌灌注显像异常50例,无异常116例;以冠状动脉造影结果为标准,心肌灌注显像对女性冠心病诊断的敏感度、特异度、阳性预测值、阴性预测值分别为73.0%,69.9%,72.2%,70.7%。结论心肌灌注显像对女性冠心病患者的诊断及是否进一步行冠状动脉造影的筛选有一定价值。     

Increases in myeloperoxidase levels after exercise in myocardial perfusion scintigraphy are not induced by myocardial ischemia

BACKGROUND: Increased systemic levels of myeloperoxidase (MPO) have been reported in patients with acute myocardial ischemia. We studied the association between exercise-induced myocardial ischemia measured by myocardial perfusion scintigraphy (MPS) and the magnitude and time course of changes in MPO levels in humans. METHODS: One hundred and twenty six patients underwent symptom limited exercise MPS. Myocardial ischemia was assessed semi-quantitatively. Plasma samples were taken before the start of exercise (baseline), at maximum exercise and every hour up to 6 h after maximum exercise. RESULTS: Myocardial ischemia was present in 42 (33%) patients. MPO levels rapidly increased during exercise in patients with and without ischemia (to 131% (106-172%) and 145% (121-199%) of baseline, respectively). MPO levels and absolute changes in MPO did not differ between patients with and without ischemia at any time point. None of the patient characteristics, including presence of ischemia, was independently predictive of the absolute increase in MPO levels during exercise. CONCLUSIONS: Exercise related immediate increases in MPO levels do not reflect myocardial ischemia.     

Direct comparison of an intravascular and an extracellular contrast agent for quantification of myocardial perfusion

A direct comparison of extracellular and intravascular contrast agents for the assessment of myocardial perfusion was carried out in a porcine model (N = 5) with a flow-limiting occluder on the left anterior descending coronary artery. Rapid imaging during the first pass of an extracellular or intravascular contrast agent with a saturation-recovery-prepared TurboFLASH sequence showed comparable peak contrast-to-noise enhancements in myocardial tissue regions with flows averaging 1.1 ± 0.2 at baseline to 4.8 ± 0.6 ml/min/g during hyperemia. The coefficient of variation between the MR estimates of blood flow with Gadomer-17 and the microsphere blood flow measurements was 11 ± 11, while the corresponding coefficient of variation for blood flow estimates with the extracellular CA was 23 ± 11. Blood volume differences between rest and hyperemia observed with the intravascular tracer were significant (V _vasc(rest) = 0.078 ± 0.013 ml/g, versus V _vasc(hyperemia) = 0.102 ± 0.019 ml/g; p < 0.05). The effects of water exchange were minimized through the choice of pulse sequence parameters to provide blood volume estimates consistent with the changes expected between rest and hyperemia. This study represents the first application of multiple indicators in first pass imaging studies for the assessment of myocardial perfusion. The use of an intravascular instead of an extracellular contrast agent allows a reduction of the degrees of freedom for modeling tissue residue curves and results in improved accuracy of blood flow estimates.