Conventional methods to quantify infarct size after myocardial infarction in mice are not ideal, requiring either tissue destruction for histology or relying on nondirect measurements such as wall motion. We therefore implemented a fast, high-resolution method to directly measure infarct size in vivo using three-dimensional (3D) late gadolinium enhancement MRI (3D-LGE). Myocardial T1 relaxation was quantified at 9.4 Tesla in five mice, and reproducibility was tested by repeat imaging after 5 days. In a separate set of healthy and infarcted mice (n = 8 of each), continuous T1 measurements were made following intravenous or intraperitoneal injection of a contrast agent (0.5 micromol/g gadolinium-diethylenetriamine pentaacetic acid). The time course of T1 contrast development between viable and nonviable myocardium was thereby determined, with optimal postinjection imaging windows and inversion times identified. Infarct sizes were quantified using 3D-LGE and compared with triphenyltetrazolium chloride histology on day 1 after infarction (n = 8). Baseline myocardial T1 was highly reproducible: the mean value was 952 +/- 41 ms. T1 contrast peaked earlier after intravenous injection than with intraperitoneal injection; however, contrast between viable and nonviable myocardium was comparable for both routes (P = 0.31), with adequate contrast remaining for at least 60 min postinjection. Excellent correlation was obtained between infarct sizes derived from 3D-LGE and histology (r = 0.91, P = 0.002), and Bland-Altman analysis indicated good agreement free from systematic bias. We have validated an improved 3D MRI method to noninvasively quantify infarct size in mice with unsurpassed spatial resolution and tissue contrast. This method is particularly suited to studies requiring early quantification of initial infarct size, for example, to measure damage before intervention with stem cells.
AimsTo measure the activity of the key phosphotransfer enzymes creatine kinase (CK), adenylate kinase (AK), and glycolytic enzymes in two common mouse models of chronic heart failure. Methods and resultsC57BL/6 mice were subjected to transverse aortic constriction (TAC), myocardial infarction induced by coronary artery ligation (CAL), or sham operation. Activities of phosphotransfer enzymes CK, AK, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 3-phosphoglycerate kinase (PGK), and pyruvate kinase were assessed spectrophotometrically. Mice were characterized by echocardiography or magnetic resonance imaging 5-to 8-week post-surgery and selected for the presence of congestive heart failure. All mice had severe left ventricular hypertrophy, impaired systolic function and pulmonary congestion compared with sham controls. A significant decrease in myocardial CK and maximal CK reaction velocity was observed in both experimental models of heart failure. However, the activity of AK and its isoforms remained unchanged, despite a reduction in its protein expression. In contrast, the activities of glycolytic phosphotransfer mediators GAPDH and PGK were 19 and 12% higher in TAC, and 31 and 23% higher in CAL models, respectively. ConclusionChronic heart failure in the mouse is characterized by impaired CK function, unaltered AK, and increased activity of glycolytic phosphotransfer enzymes. This pattern of altered phosphotransfer activity was observed independent of the heart failure aetiology.--
MRI has become an important tool to noninvasively assess global and regional cardiac function, infarct size, or myocardial blood flow in surgically or genetically modified mouse models of human heart disease. Constraints on scan time due to sensitivity to general anesthesia in hemodynamically compromised mice frequently limit the number of parameters available in one imaging session. Parallel imaging techniques to reduce acquisition times require coil arrays, which are technically challenging to design at ultrahigh magnetic field strengths. This work validates the use of an eight-channel volume phased-array coil for cardiac MRI in mice at 9.4 T. Two- and three-dimensional sequences were combined with parallel imaging techniques and used to quantify global cardiac function, T1-relaxation times and infarct sizes. Furthermore, the rapid acquisition of functional cine-data allowed for the first time in mice measurement of left-ventricular peak filling and ejection rates under intravenous infusion of dobutamine. The results demonstrate that a threefold accelerated data acquisition is generally feasible without compromising the accuracy of the results. This strategy may eventually pave the way for routine, multiparametric phenotyping of mouse hearts in vivo within one imaging session of tolerable duration. Magn Reson Med, 2010. © 2010 Wiley-Liss, Inc.
MRI can accurately and reproducibly assess cardiac function in rodents but requires relatively long imaging times. Therefore, parallel imaging techniques using a 4-element RF-coil array and MR sequences for cardiac MRI in rats were implemented at ultra-high magnetic fields (9.4 Tesla [T]). The hypothesis that these developments would result in a major reduction in imaging time without loss of accuracy was tested on female Wistar rats under isoflurane anesthesia. High-resolution, contiguous short-axis slices (thickness 1.5 mm) were acquired covering the entire heart. Two interleaved data sets (i) with the volume coil (eight averages) and (ii) with the four-element coil array (one average) were obtained. In addition, two-, three-, and fourfold accelerated data sets were generated through postprocessing of the coil array data, followed by a TGRAPPA reconstruction, resulting in five data sets per rat (in-plane voxel size 100 ؋ 100 m). The rat has been a mainstay of basic cardiovascular research for several decades. For example, rats with naturally occurring mutations such as the spontaneously hypertensive rat (1), and surgical models of myocardial infarction (2), or pressure-overload hypertrophy (3) are commonly used to study pathological processes in the heart on a structural, functional, metabolic, and molecular level. Importantly, recent descriptions of transgenic (4) and mutagenesis techniques in the rat (5) are likely to increase the need for accurate and rapid throughput cardiac phenotyping in this species.MRI has become a routine tool to noninvasively assess cardiac function in rodent models of human heart disease. This technique has been applied on MR systems with magnetic field strengths up to 11.7 Tesla (T; 6 -10), using surface-(7,9), volume-type (8,9) radio frequency (RF) coils, or a combination of both (6,10). However, the requirement for maximal spatial (Յ 200 m in-plane) and temporal (Յ 5 ms) resolution results in long imaging times (50 -90 min), and limits the usefulness of this technique, particularly in models of heart failure, which may be inherently hemodynamically unstable under general anesthesia. Technical advances in MR hardware (i.e., RF-coil arrays and receiver technology) and acquisition methods (parallel imaging techniques [PAT]) on clinical MR systems with lower magnetic field strengths have substantially reduced scan-time.The aim of our study was to implement PAT techniques (hardware and MR sequences) for experimental cardiac MRI in rats at 9.4T. We therefore developed and characterized a four-element receive-only coil array optimized for cardiac MR on rats, implemented the PAT technique TGRAPPA (11) and quantified the impact of accelerated MR on the cardiac functional and structural parameter assessment. We demonstrate for the first time that it is possible to conduct a complete cardiac functional study in rats at 9.4T in less than 3 min without losing temporal or spatial resolution and with very low variability.
Purpose: To investigate the accuracy (vs. standard manual analysis) and precision (scan-rescan reproducibility) of three-dimensional guide-point modeling (GPM) for the assessment of left ventricular (LV) function in mice. Methods:Six male wildtype C57/Bl6 mice (weight 26.2 Ϯ 1.1 g) were scanned twice, 3 days apart. Each scan was performed twice, at 0.2 mm/pixel with one average and at 0.1 mm/pixel with two averages. The 24 studies were anonymized and analyzed in blinded fashion using GPM and standard manual slice summation. Results:The average error between GPM and standard analysis was 2.3 Ϯ 5.8 mg in mass, 1.7 Ϯ 3.2 L in enddiastolic volume, 2.3 Ϯ 3.1 L in end-systolic volume, Ϫ2.7 Ϯ 4.3% in ejection fraction, Ϫ0.6 Ϯ 3.3 L in stroke volume, and Ϫ0.31 Ϯ 1.56 ml ⅐ min Ϫ1 in cardiac output (mean difference Ϯ SD of differences, n ϭ 24). The average time taken was 8.0 Ϯ 2.5 minutes for 3D GPM and 48.5 Ϯ 8.9 minutes for standard analysis (n ϭ 24). Scan-rescan reproducibility results were similar to the standard analysis. No significant differences were found using linear mixed effects modeling in either accuracy or precision between scan resolutions or analysis method. Conclusion:3D GPM enables fast analysis of mouse LV function, with similar accuracy and reproducibility to standard analysis. An image resolution of 0.2 mm/pixel with one average is adequate for LV function studies.
Murine MRI studies are conducted on dedicated MR systems, typically equipped with ultra-high-field magnets (≥4.7 T; bore size: ∼12–25 cm), using a single transmit-receive coil (volume or surface coil in linear or quadrature mode) or a transmit-receive coil combination. Here, we report on the design and characterization of an eight-channel volume receive-coil array for murine MRI at 400 MHz. The array was combined with a volume-transmit coil and integrated into one probe head. Therefore, the animal handling is fully decoupled from the radiofrequency setup. Furthermore, fixed tune and match of the coils and a reduced number of connectors minimized the setup time. Optimized preamplifier design was essential for minimizing the noise coupling between the elements. A comprehensive characterization of transmit volume resonator and receive coil array is provided. The performance of the coil array is compared to a quadrature-driven birdcage coil with identical sensitive volume. It is shown that the miniature size of the elements resulted in coil noise domination and therefore reduced signal-to-noise-ratio performance in the center compared to the quadrature birdcage. However, it allowed for 3-fold accelerated imaging of mice in vivo, reducing scan time requirements and thus increasing the number of mice that can be scanned per unit of time. Magn Reson Med, 2010. © 2010 Wiley-Liss, Inc.
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