Improved arterial spin labeling after myocardial infarction in mice using cardiac and respiratory gated look-locker imaging with fuzzy C-means clustering

Abstract

Experimental myocardial infarction (MI) in mice is an important disease model, in part due to the ability to study genetic manipulations. MRI has been used to assess cardiac structural and functional changes after MI in mice, but changes in myocardial perfusion after acute MI have not previously been examined. Arterial spin labeling noninvasively measures perfusion but is sensitive to respiratory motion and heart rate variability and is difficult to apply after acute MI in mice. To account for these factors, a cardiorespiratory-gated arterial spin labeling sequence using a fuzzy C-means algorithm to retrospectively reconstruct images was developed. Using this method, myocardial perfusion was measured in remote and infarcted regions at 1, 7, 14, and 28 days post-MI. Baseline perfusion was 4.9 6 0.5 mL/gÁmin and 1 day post-MI decreased to 0.9 6 0.8 mL/gÁmin in infarcted myocardium (P < 0.05 versus baseline) while remaining at 5.2 6 0.8 mL/gÁmin in remote myocardium. During the subsequent 28 days, perfusion in the remote zone remained unchanged, while a partial recovery of perfusion in the infarct zone was seen. This technique, when applied to genetically engineered mice, will allow for the investigation of the roles of specific genes in myocardial perfusion during infarct healing. Magn Reson Med 63:648-657, 2010. V C 2010 Wiley-Liss, Inc.Key words: arterial spin labeling; myocardial perfusion; myocardial infarction; fuzzy C-means; mouse Mice are widely used as models of human disease in biomedical research. Similarities in the cardiovascular systems of mice and humans, the low cost of mouse studies, the relative ease of genetic manipulation of mice, and improved surgical techniques have led to increased use of mouse models of myocardial infarction (MI) (1-3). Cardiac MRI has been used to study structural and functional left ventricular (LV) remodeling in mice following MI (3-5). However, measurement of myocardial perfusion in mice by MRI during acute MI and subsequently during the processes of infarct healing and post-MI LV remodeling has not previously been performed.Arterial spin labeling (ASL) provides quantitative measurements of blood flow and has been used for quantification of cerebral blood flow (6,7) and myocardial perfusion (8-11) in humans. In small animals, ASL has been performed in both mice (12-15) and rats (16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Prior murine studies have examined myocardial perfusion at baseline (12-15), with differing anesthesia (13), in response to a vasodilator (13,15), and for phenotyping of genetically altered mice (14,15). Only two prior studies have measured perfusion after MI in mice, and those measurements were restricted only to the remote myocardium at 4 weeks following MI (12,14). ASL has been more widely used in rats (22) and has been used to assess changes in myocardial perfusion in response to dobutamine (17), adenosine (25), methods of anesthesia (23,24), diabetes (18,19) and following coronary stenosis (20,21) and MI (20,21). Similar to mouse studies, measurements...

Monocyte and/or Macrophage Infiltration of Heart after Myocardial Infarction: MR Imaging by Using T1-shortening Liposomes

“…Myocardial R1 was calculated by using a least-squares fit to a Bloch equation T1-relaxation curve. Maps of myocardial R1 were calculated pixel-by-pixel and were filtered by using a mean crescent filter with a kernel of 2 pixels in the radial direction and 7 pixels in the circumferential direction (23). Filtering was used to smooth the R1 maps and to reduce noise.…”

Quantitative Dynamic PET Imaging of the Heart: From Mouse to Man

“…This compares well with the existing literature for measuring MBF in mouse heart at rest with quantitative first-pass [152] and arterial spin-labeling MRI [151]. Absolute MBF under vasodilator stress obtained from the second PET was 8.9 mL/ min/ g. The MFR in mouse heart was hence computed to be 1.9 (Flow at stress/Flow at rest).…”

Myocardial Ischemia Without Obstructive Coronary Artery Disease: Perfusion MRI in Mouse Models

“…Briefly, CMR has been used by prior studies to assess in vivo LV structure (70), contractile function (71,72), the presence and extent of myocardial infarction (MI) (73,74), myocardial viability, fibrosis in the heart (75), edema after MI (76) and myocardial perfusion (77). CMR in mice has also been used to track labeled cells in heart (78), to assess cardiac regeneration (79) and calcium function in the heart (80).…”

“…The use of this method in the heart is however limited in humans because of the relatively modest changes in signal due to spin labeling and cardiac motion artifacts. However, in mice, where MBF is higher than in humans, ASL has been used to measure myocardial perfusion at rest (77,(96)(97)(98)(99)(100)(101)(102), after vasodilation (77,98,102) and after MI (77,99,100).…”

“…Our group has previously implemented ASL using the FAIR preparation scheme combined with a cardio-respiratory Look-Locker spiral gradient echo (77). Shown below are example images obtained using this technique.…”