Magnetic resonance microimaging for noninvasive quantification of myocardial function and mass in the mouse

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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.

Section: Standard Analysismentioning

confidence: 99%

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confidence: 99%

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Fast left ventricular mass and volume assessment in mice with three‐dimensional guide‐point modeling

Young

Barnes

Davison

et al. 2009

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“…RECENT ADVANCES IN TRANSGENIC MOUSE technology have resulted in the increasing use of magnetic resonance (MR) techniques to gain important insights into the functional and metabolic basis of heart disease (1)(2)(3)(4)(5). In general, increasing the static magnetic field strength increases the signal-to-noise ratio (SNR) (6), and when combined with strong, fast switching gradient systems and fast data acquisition schemes, highspatial-resolution and high-temporal-resolution MR experiments can be performed.…”

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confidence: 99%

Assessment of motion gating strategies for mouse magnetic resonance at high magnetic fields

Cassidy

Schneider

Grieve

et al. 2004

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112

101

Purpose:To assess the performance of motion gating strategies for mouse cardiac magnetic resonance (MR) at high magnetic fields by quantifying the levels of motion artifact observed in images and spectra in vivo. Materials and Methods:MR imaging (MRI) of the heart, diaphragm, and liver; MR angiography of the aortic arch; and slice-selective 1 H-spectroscopy of the heart were performed on anesthetized C57Bl/6 mice at 11.75 T. Gating signals were derived using a custom-built physiological motion gating device, and the gating strategies considered were no gating, cardiac gating, conventional gating (i.e., blanking during respiration), automatic gating, and userdefined gating. Both automatic and user-defined modes used cardiac and respiratory gating with steady-state maintenance during respiration. Gating performance was assessed by quantifying the levels of motion artifact observed in images and the degree of amplitude and phase stability in spectra.Results: User-defined gating with steady-state maintenance during respiration gave the best performance for mouse cardiac imaging, angiography, and spectroscopy, with a threefold increase in signal intensity and a sixfold reduction in noise intensity compared to cardiac gating only. Conclusion:Physiological gating with steady-state maintenance during respiration is essential for mouse cardiac MR at high magnetic fields.

“…Although MRI has been elegantly applied by several groups to studies of the mouse heart (e.g., Refs. [2][3][4][5], it remains concentrated in relatively few centers. Cardiac MRI of the mouse, unlike of the rat (6), is not widespread in the pharmaceutical research setting, but that seems likely to change as the advantages of murine models increasingly outweigh their disadvantages.…”

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confidence: 99%

Dobutamine stress cine‐MRI of cardiac function in the hearts of adult cardiomyocyte‐specific VEGF knockout mice

Williams¹,

Gerber²,

Giordano³

et al. 2001

A mouse model of non-necrotic vascular deficiency in the adult heart was studied using cine-magnetic resonance imaging (MRI) and other techniques. The mice lacked cardiomyocyte-derived vascular endothelial growth factor (VEGF) following a targeted knockout in the ventricular cardiomyocytes. Quantitative endothelial labeling showed that the capillary density was significantly reduced in the hearts of knockout mice. Gene expression patterns suggested that they were hypoxic. Semiautomated MR image analysis was employed to obtain both global and regional measurements of left ventricular function at 10 or more time points through the cardiac cycle. MRI measurements showed a marked reduction in ejection fraction both at rest and under low-and high-dose dobutamine stress. Regional wall thickness, thickening, and displacement were all attenuated in the knockout mice. A prolonged high-dose dobutamine challenge was monitored by MRI. A maximal response was sustained for 90 minutes, suggesting that it did not depend on endogenous glycogen stores. J. Index terms: VEGF; cine; dobutamine; mouse; heart THE RECENT PROLIFERATION of murine models of human heart disease has been remarkable (1) and is likely to continue. Although MRI has been elegantly applied by several groups to studies of the mouse heart (e.g., Refs. 2-5), it remains concentrated in relatively few centers. Cardiac MRI of the mouse, unlike of the rat (6), is not widespread in the pharmaceutical research setting, but that seems likely to change as the advantages of murine models increasingly outweigh their disadvantages. There are important biological differences between the hearts of different mammals, such as in calcium handling (7) and vascular anatomy (8), yet many of the perceived disadvantages of using mice as opposed to larger animal species are essentially technical in nature. This has spurred great efforts in adapting radiological, surgical, and physiological techniques to the temporal and spatial scale of the mouse heart (9,10).This paper describes MRI of the left ventricle (LV) under resting and stressed conditions in a mouse model of a non-necrotic vascular deficiency in the adult heart. This model may be of some value in designing and evaluating angiogenic therapies (11), and in understanding the pathophysiology of chronic ischemic conditions associated with coronary artery disease (12). The generation and preliminary phenotypic characterization of this mouse model has recently been described (13). Briefly, the Cre/lox system (14) was employed to generate a targeted knockout of vascular endothelial growth factor A (VEGF A) specific to the ventricular cardiomyocytes. VEGF A is a potent cytokine and mitogen involved in the formation and maintenance of blood vessels (15). Attempts to generate VEGF A knockouts by the more common germ-line strategies were confounded by the highly unusual embryonic lethality seen in VEGF A heterozygotes (16).The effect of the gene knockout was monitored directly (changes in VEGF A mRNA) and indirectly. Anticipating microvasc...