Background—
Recent results from animal studies suggest that stem cells may be able to home to sites of myocardial injury to assist in tissue regeneration. However, the histological interpretation of postmortem tissue, on which many of these studies are based, has recently been widely debated.
Methods and Results—
With the use of the high sensitivity of a combined single-photon emission CT (SPECT)/CT scanner, the in vivo trafficking of allogeneic mesenchymal stem cells (MSCs) colabeled with a radiotracer and MR contrast agent to acute myocardial infarction was dynamically determined. Redistribution of the labeled MSCs after intravenous injection from initial localization in the lungs to nontarget organs such as the liver, kidney, and spleen was observed within 24 to 48 hours after injection. Focal and diffuse uptake of MSCs in the infarcted myocardium was already visible in SPECT/CT images in the first 24 hours after injection and persisted until 7 days after injection and was validated by tissue counts of radioactivity. In contrast, MRI was unable to demonstrate targeted cardiac localization of MSCs in part because of the lower sensitivity of MRI.
Conclusions—
Noninvasive radionuclide imaging is well suited to dynamically track the biodistribution and trafficking of mesenchymal stem cells to both target and nontarget organs.
A breath-hold two-dimensional cine magnetic resonance (MR) pulse sequence based on displacement encoding with stimulated echoes (DENSE) for quantitative myocardial motion tracking was developed and evaluated. In the sequence, complementary spatial modulation of magnetization was used for time-independent artifact suppression, and echo-planar imaging was used for rapid data sampling. Twelve healthy volunteers underwent cine DENSE MR imaging, and six of them also underwent conventional MR imaging myocardial tagging. The circumferential shortening component of strain (E(cc)) was measured on cine DENSE MR images and conventional tagged MR images. With complementary spatial modulation of magnetization, 10% or less of the total cine DENSE MR image energy was attributed to an artifact-generating echo during systolic imaging. Two-dimensional intramyocardial displacement and strain were measured at cine DENSE MR imaging with spatial resolution and temporal resolution of 2.7 x 2.7 mm and 60 msec, respectively. E(cc) measured at cine DENSE MR imaging correlated well with that measured at conventional MR imaging tagging (slope = 0.88, intercept = 0.00, R = 0.87).
Background-The objective of this study was to noninvasively determine the effects of reperfused myocardial infarction (MI) on regional and global left-ventricular (LV) function 24 hours after MI in intact mice with contrast-enhanced cardiac MRI and a single, gradient-echo pulse sequence. Methods and Results-Twenty-three mice received baseline MRI scans followed by either 60 minutes of coronary occlusion (MI group, nϭ15) or thoracotomy without occlusion (sham group, nϭ8). Gadolinium-DTPA-enhanced magnetic resonance (MR) images were acquired 24 hours after surgery. Hearts were then excised for conventional infarct size determination via 2,3,5-triphenyl tetrazolium chloride (TTC) staining. In addition to infarct size, analysis of the MR images yielded left ventricular (LV) mass, LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV), LV ejection fraction (LVEF), cardiac output, and percent LV wall thickening (%WTh). Twenty-four hours after surgery, infarct size was 28.1Ϯ1.8% of LV mass by MRI and 27.5Ϯ1.7% by TTC (PϭNS). Bland-Altman analysis revealed close agreement between the results obtained by the 2 methods. MI had little effect on LVEDV but caused a 98% increase in LVESV (from 11.3 to 22.4 L, PϽ0.05), which resulted in a significant reduction in LVEF (from 70% to 37%, PϽ0.05). Compared with LV regional function at baseline, %WTh 24 hours after MI was significantly depressed, not only in infarcted myocardium but also in regions remote from the infarct zone. In contrast, sham-operated mice showed a small but significant increase in %WTh 24 hours after surgery (PϽ0.05). Conclusions-MRI can accurately assess both infarct size and cardiac function in intact mice early after large, reperfused MI, revealing the existence of contractile dysfunction in noninfarcted regions of the heart.
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