Rapid assessment of myocardial infarct size in rodents using multi-slice inversion recovery late gadolinium enhancement CMR at 9.4T

Background

Myocardial infarction (MI) can be readily assessed using late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR). Inversion recovery (IR) sequences provide the highest contrast between enhanced infarct areas and healthy myocardium. Applying such methods to small animals is challenging due to rapid respiratory and cardiac rates relative to T₁ relaxation.

Methods

Here we present a fast and robust protocol for assessing LGE in small animals using a multi-slice IR gradient echo sequence for efficient assessment of LGE. An additional Look-Locker sequence was used to assess the optimum inversion point on an individual basis and to determine most appropriate gating points for both rat and mouse. The technique was applied to two preclinical scenarios: i) an acute (2 hour) reperfused model of MI in rats and ii) mice 2 days following non-reperfused MI.

Results

LGE images from all animals revealed clear areas of enhancement allowing for easy volume segmentation. Typical inversion times required to null healthy myocardium in rats were between 300-450 ms equivalent to 2-3 R-waves and ~330 ms in mice, typically 3 R-waves following inversion. Data from rats was also validated against triphenyltetrazolium chloride staining and revealed close agreement for infarct size.

Conclusion

The LGE protocol presented provides a reliable method for acquiring images of high contrast and quality without excessive scan times, enabling higher throughput in experimental studies requiring reliable assessment of MI.     

MRI增强延迟扫描在心肌梗塞后存活性评价中的价值探讨

目的探索评价MRI增强延迟扫描技术对判断心肌存活性的价值。方法 20例患者行MRI增强延迟扫描检查,分析心肌延迟扫描图像并探索评价心肌存活性。结果 17例左室心肌未见梗塞灶,增强延迟扫描MR表现为均匀一致低信号,心肌内无对比剂存留。3例陈旧性心肌梗死表现为左心室病变区局限性信号不均匀增高,对比剂存留。结论 MRI增强延迟扫描技术可对心肌存活性作出一定评价,为患者制订治疗方案和预后评价提供信息。     

Scan-rescan reproducibility of quantitative assessment of inflammatory carotid atherosclerotic plaque using dynamic contrast-enhanced 3T CMR in a multi-center study

Background

The aim of this study is to investigate the inter-scan reproducibility of kinetic parameters in atherosclerotic plaque using dynamic contrast-enhanced (DCE) cardiovascular magnetic resonance (CMR) in a multi-center setting at 3T.

Methods

Carotid arteries of 51 subjects from 15 sites were scanned twice within two weeks on 3T scanners using a previously described DCE-CMR protocol. Imaging data with protocol compliance and sufficient image quality were analyzed to generate kinetic parameters of vessel wall, expressed as transfer constant (K^trans) and plasma volume (v_p). The inter-scan reproducibility was evaluated using intra-class correlation coefficient (ICC) and coefficient of variation (CV). Power analysis was carried out to provide sample size estimations for future prospective study.

Results

Ten (19.6%) subjects were found to suffer from protocol violation, and another 6 (11.8%) had poor image quality (n = 6) in at least one scan. In the 35 (68.6%) subjects with complete data, the ICCs of K^trans and v_p were 0.65 and 0.28, respectively. The CVs were 25% and 62%, respectively. The ICC and CV for v_p improved to 0.73 and 28% in larger lesions with analyzed area larger than 25 mm². Power analysis based on the measured CV showed that 50 subjects per arm are sufficient to detect a 20% difference in change of K^trans over time between treatment arms with 80% power without consideration of the dropout rate.

Conclusion

The result of this study indicates that quantitative measurement from DCE-CMR is feasible to detect changes with a relatively modest sample size in a prospective multi-center study despite the limitations. The relative high dropout rate suggested the critical needs for intensive operator training, optimized imaging protocol, and strict quality control in future studies.     

Computer-assisted calculation of myocardial infarct size shortens the evaluation time of contrast-enhanced cardiac MRI

BACKGROUND: Delayed enhancement magnetic resonance imaging depicts scar in the left ventricle which can be quantitatively measured. Manual segmentation and scar determination is time consuming. The purpose of this study was to evaluate a software for infarct quantification, to compare with manual scar determination, and to measure the time saved. METHODS: Delayed enhancement magnetic resonance imaging was performed in 40 patients where myocardial perfusion single photon emission computed tomography imaging showed irreversible uptake reduction suggesting a myocardial scar. After segmentation, the semi-automatic software was applied. A scar area was displayed, which could be corrected and compared with manual delineation. The different time steps were recorded with both methods. RESULTS: The software shortened the average evaluation time by 12.4 min per cardiac exam, compared with manual delineation. There was good correlation of myocardial volume, infarct volume and infarct percentage (%) between the two methods, r = 0.95, r = 0.92 and r = 0.91 respectively. CONCLUSION: A computer software for myocardial volume and infarct size determination cut the evaluation time by more than 50% compared with manual assessment, with maintained clinical accuracy.     

Assessment of infarct size and myocardial function in mice using transesophageal echocardiography.

BACKGROUND: Because transthoracic echocardiography (TTE) has significant limitations in assessing changes consequent to myocardial infarction (MI) in mice, we studied two novel methods to characterize such infarcts. METHODS: Large MIs were produced by proximal left coronary artery ligation, and small MIs by distal left coronary artery ligation. Serum cardiac troponin I levels were measured 24 hours postoperatively. At 2 weeks, mice underwent transesophageal echocardiography (TEE) and TTE. Infarct sizes were determined histologically. RESULTS: Surviving mice were classified according to infarct size. TEE identified all histologically proven large infarcts, and 4 of 5 small infarcts. TTE identified 4 of 5 large infarcts, but only 1 of 5 small infarcts. TEE-derived fractional area change, but not TTE-estimated left ventricular fractional shortening, was significantly different among large, small, and sham infarcts. Cardiac troponin I showed excellent correlation with infarct size and mortality. CONCLUSIONS: Cardiac troponin I was found to predict infarct size and mortality, whereas TEE proved superior to TTE in determining infarct size and/or myocardial function in a murine MI model. These tools should provide more accurate assessments in preclinical studies of ischemic cardiomyopathy.     

磁共振延迟成像时间对急性心肌梗死测定的影响

目的 本研究探讨不同磁共振延迟成像(comrast-enhanced magnetic resonance imaging,CeM-砌)时间是否影响急性心肌梗死(acute myocardial infarctin,AMI)后梗死面积的测定.并探讨磁共振测定的射血分数与左窒造影测定的射血分数的相关性.方法 选择在2005年6月至2006年4月在复旦大学附属中山医院住院治疗的患者,27例首次确诊为急性心肌梗死的患者进行前瞻性研究,年龄(54.3±10.5)岁.所有患者均动态观察心肌酶谱的变化,并经冠脉造影明确,冠脉造影同时测定左室造影射血分数,磁共振(SIMENS 1.5T)检查时间为心肌梗死后(13.2±5.2)d,磁共振检查方法 是首先进行电影扫描,测定射血分数,然后经静脉以5 mL/秒注入0.05 mmol/kgGd-DTPA行首过成像,最后经高压注射器静脉以2 mL/s注入0.15 mmol/kg Gd-ffFPA行延迟成像,测定心肌梗死面积,在延迟注药后5 min开始延迟期采集.选择存在延迟增强高信号区的同一短轴层面,每间隔5 min成像一次测定梗夕匕面积,直至20 min.采用配对t检验进行统计,并进行相关分析.结果 27例患者在延迟CeMRI上均存在延迟增强区,27例患者测定的梗死面积为(17.9±9.8)%,测定CK峰值为(2003.5±1496.8)U/L,肌钙蛋白T峰值为(4.6±3.3)ng/mL.梗死面积与CK峰值的相关系数为r=0.819(P<0.01),梗夕匕面积与肌钙蛋白T相关系数为r=0.517(P<0.05).存在梗死心肌的同一层面测定的梗死而积百分比在5 min,10 min,15 min及20 min时分别为(7.2±6.2)%,(8.5±7.4)%,(7.3±6.3)%及(6.9±6.4)%(10 min与20 min相比,P<0.05).MR测定的左室射血分数与造影测定的射血分数相关系数为r=0.867(P<0.01).结论 CeMRI可以诊断心肌梗死和定量测定梗死范围.磁共振测定与左室造影测定的射血分数密切相关.测定梗死范围时,不同延迟成像的时间影响梗死范围的测定.     

Influence of contrast agent dose and image acquisition timing on the quantitative determination of nonviable myocardial tissue using delayed contrast-enhanced magnetic resonance imaging.

BACKGROUND: Delayed contrast-enhanced magnetic resonance imaging (ceMRI) has been shown to identify areas of irreversible myocardial injury due to infarction (MI) with high spatial resolution, allowing precise quantification of nonviable (hyperenhanced) myocardium. The aim of our study was to investigate the size of nonviable myocardium quantitatively as a function of time post-contrast when inversion time is held constant in patients post-myocardial infarction using two contrast agent (CA) doses. METHODS: Nine patients with chronic MI underwent two MR scans on a 1.5 Tesla system. Contrast-enhanced MRI data in two short-axis (SA) slices were continuously acquired until 40 minutes after CA injection [gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), 0.1 mmol/kg body weight = single dose] interrupted only for a complete stack of SA slices encompassing the entire left ventricle (LV) between minutes 20 and 28. Left ventricular mass showing hyperenhancement was determined. The measurement was repeated on the subsequent day with double dose CA (0.2 mmol/kg body weight). Differences of signal intensities for hyperenhanced, nonhyperenhanced myocardium, and LV cavity were calculated. RESULTS: Total mass of hyperenhancement from a complete SA stack acquired between minutes 20 and 28 was lower for single dose CA [9.0% vs. 14.2% for single and double dose, respectively (p = 0.03)]. Ten to 18 minutes after CA injection, there was no significant difference between the two doses and to an internal reference for both single and double dose. For single dose the image contrast between hyperenhancement and LV cavity was superior (minutes 10 to 16, p < 0.05) but inferior between hyperenhanced and nonhyperenhanced myocardium (minutes 6 to 16, p < 0.05). CONCLUSION: Myocardial infarct size measurements are a function of time postcontrast when inversion time is held constant regardless of the contrast agent dose. These data underscore the fact that a standardized imaging protocol that defines how the appropriate inversion time should be selected is needed for comparison of results obtained at various cMR sites.     

Rapid and accurate determination of relative infarct size in humans using contrast-enhanced magnetic resonance imaging

Background  In clinical routine, rapid infarct sizing techniques are warranted, as objective and precise infarct sizing is important for clinical decision-making. Accurate and objective measures of relative infarct size (rIS) using contrast-enhanced cardiac magnetic resonance (ceCMR) have been extensively demonstrated in experimental animals, but less in humans. The aim of this study was therefore to quantify rIS assessed by ceCMR in patients with chronic myocardial infarction using semi-automatic quantitation techniques. Methods  A total of 62 patients (mean age 66 ± 9 years) with ischemic cardiomyopathy (EF 24 ± 8%) underwent ceCMR for viability testing. rIS was obtained by two time-saving semi-automatic thresholding methods based on: (1) visual definition of a single signal intensity cutoff value (VISUAL) and (2) the full-width-at-half-maximum technique (FWHM). Results were compared to manual tracing (MANUAL) as the reference standard. Results  VISUAL showed better agreement [r = 0.99; intraclass correlation coefficient (ICC) = 0.98, limits of agreement ±3.2%] to MANUAL than the FWHM technique (r = 0.77, ICC = 0.76, limits of agreement ±12%). Infarct sizing using MANUAL was twice as time-consuming (3.1 ± 0.2 min) compared to VISUAL (1.6 ± 0.1 min) or FWHM (1.6 ± 0.2 min). Conclusions  Visual estimation of signal intensity cutoff values allows rapid and accurate determination of rIS in patients with chronic myocardial infarction using ceCMR and is superior to the FWHM technique.     

心肌病变延迟增强MRI的研究进展

心肌延迟增强MRI正迅速的成为评估梗死后心肌瘢痕的参考标准。Gd-DTPA对比剂注射后,使用反转恢复(IR)快速自旋回波序列扫描,正常心肌显示为低信号。对比剂滞留导致T1时间缩短,因而T1加权像上表现为相对正常心肌的高信号。在一些病理生理情况下可见心肌组织的不同对比增强。强化程度也依赖于对比剂注射后的延迟时间。延迟增强并不是心肌梗死的特异表现,也可以出现在各种其他疾病     

Close association between the reduction in myocardial energy metabolism and infarct size: dose-response assessment of cyclosporine

Cyclosporine protects the heart against ischemia/reperfusion injury, but its effect on cardiac metabolism is largely unknown. We assessed cyclosporine-induced metabolic changes in the rat heart prior to occlusion using magnetic resonance spectroscopy (MRS) and correlated effects with infarct size in a coronary occlusion/reperfusion model. The two study groups were cyclosporine and cyclosporine + coronary occlusion (n = 20/group). Rats were pretreated with cyclosporine (5, 10, 15, and 25 mg/kg/day) or the vehicle by oral gavage for 3 days (n = 4/dose). On day 4, hearts of rats in the cyclosporine group were excised, and extracted cell metabolites were measured using (1)H and (31)P MRS. The second group was subjected to 30 min of coronary artery occlusion followed by 24 h of reperfusion. Infarct size and area at risk were measured using a double staining method. In the cyclosporine group, cyclosporine reduced cardiac energy metabolism (ATP: r = -0.89, P < 0.001) via depression of oxidative phosphorylation and the Krebs' cycle in a dose-dependent manner. The decrease of ATP levels was positively correlated with changes of NAD(+) (r = 0.89), glutamate (r = 0.95), glutamine (r = 0.84), and glucose concentrations (r = 0.92, all P < 0.002). It was inversely correlated with lactate (r = -0.93, P < 0.001). In the coronary occlusion group, cyclosporine dose dependently reduced the ratio [area of infarct/area of the left ventricle] (r = -0.86, P < 0.01), with 15 mg/kg/day being the most effective cyclosporine dose. The reduction in infarct size correlated with the reduction in oxidative phosphorylation (ATP: r = 0.97; NAD(+): r = 0.82, P < 0.01). The reduction in cardiac energy metabolism before occlusion may be the cause of myocardial preservation during ischemia/reperfusion.     

MRI for the assessment of myocardial viability

Accurate distinction between viable and infarcted myocardium is important for assessment of patients who have cardiac dysfunction. Through the technique of delayed-enhancement MRI (DE-MRI), viable and infarcted myocardium can be simultaneously identified in a manner that closely correlates with histopathology findings. This article provides an overview of experimental data establishing the physiologic basis of DE-MRI-evidenced hyperenhancement as a tissue-specific marker of myocardial infarction. Clinical data concerning the utility of transmural extent of hyperenhancement for predicting response to medical and revascularization therapy are reviewed. Studies directly comparing DE-MRI to other viability imaging techniques are presented, and emerging applications for DE-MRI are discussed.     

The measurement and cotrrol of myocardial infarct size

Direct, chemical, electrocardiographic and radio-isotopic methods are described for the estimation of myocardial infarct size in animals and man. Their relative points and failings are discussed. The effects of interventions, physical, metabolic and pharmacological, upon the size of myocardial infarcts, are examined and work attempting to reduce myocardial infarct size in man reviewed.     

A quantitative comparison of regional myocardial motion in mice,rabbits and humans using in-vivo phase contrast CMR

Background

Genetically manipulated animals like mice or rabbits play an important role in the exploration of human cardiovascular diseases. It is therefore important to identify animal models that closely mimic physiological and pathological human cardiac function.

Methods

In-vivo phase contrast cardiovascular magnetic resonance (CMR) was used to measure regional three-directional left ventricular myocardial motion with high temporal resolution in mice (N=18), rabbits (N=8), and humans (N=20). Radial, long-axis, and rotational myocardial velocities were acquired in left ventricular basal, mid-ventricular, and apical short-axis locations.

Results

Regional analysis revealed different patterns of motion: 1) In humans and rabbits, the apex showed slower radial velocities compared to the base. 2) Significant differences within species were seen in the pattern of long-axis motion. Long-axis velocities during systole were fairly homogeneously distributed in mice, whereas humans showed a dominant component in the lateral wall and rabbits in the base. 3) Rotational velocities and twist showed the most distinct patterns in both temporal evolution and relative contribution of base, mid-ventricle and apex, respectively. Interestingly, a marked difference in rotational behavior during early-systole was found in mice, which exhibited clockwise rotation in all slice locations compared to counter-clockwise rotation in rabbits and humans.

Conclusions

Phase contrast CMR revealed subtle, but significantly different regional myocardial motion patterns in mice, rabbits and humans. This finding has to be considered when investigating myocardial motion pattern in small animal models of heart disease.     

Reduction in myocardial infarct size: prevention of heart cell death.

The course of myocardial necrosis, the clinical syndrome, and methods of treatment are presented. Heart cell death may be prevented by maintaining the balance between myocardial oxygen and energy supply and consumption. New technics of improving this balance by reducing myocardial energy demand, altering metabolism, increasing myocardial substrate supply, and protecting cellular integrity are discussed.     

心肌造影超声心动图与存活心肌的检测

研究表明,冠脉微血管的完整性是心肌存活的必备条件.由于心肌造影超声心动图在对心肌微循环灌注进行定性、定量评估的同时,还能检测局部室壁运动功能,因此,它在存活心肌的检测方面具有独到的应用价值.