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Background-We investigated the potential of magnetic resonance imaging (MRI) to track magnetically labeled mesenchymal stem cells (MR-MSCs) in a swine myocardial infarction (MI) model. Methods and Results-Adult farm pigs (nϭ5) were subjected to closed-chest experimental MI. MR-MSCs (2.8 to 16ϫ10 Key Words: magnetic resonance imaging Ⅲ myocardial infarction Ⅲ cells Ⅲ contrast media B ecause of the limited regenerative capacity of the heart muscle, mesenchymal stem cells (MSCs), found in bone marrow, may have enormous therapeutic potential for limiting infarct size and restoring cardiac function after irreversible ischemic injury. Most techniques for the study of stem cell transplantation in animal models require histological analysis to determine the fate and migration of cells. [1][2][3][4][5] Thus, the number and location of MSCs delivered using intramyocardial delivery techniques can only be estimated postmortem. The recent ability to label MSCs 6 with magnetic resonance imaging (MRI)-visible contrast agents should enable serial tracking and quantification of MSC transplantation noninvasively with high spatial resolution. Thus, the purpose of this study was to determine whether magnetically labeled MSCs injected intramyocardially could be detected and tracked noninvasively by MRI in a swine model of myocardial infarction. Methods Animal ModelAnimal studies were approved by the Institutional Animal Care and Use Committee. The evening before creation of a myocardial infarction (MI), 5 farm pigs (25 to 35 kg; Archer Farms, Belcamp, Md) received aspirin (325 mg) and diltiazem (180 mg sustained release) orally. Animals were sedated with acepromazine, ketamine, and atropine; induced with thiopental; and then intubated and mechanically ventilated with oxygen and isoflurane. To create MI, cardiac catheterization was performed via a 9F carotid sheath, and a 2.0 or 2.5ϫ20-mm coronary angioplasty balloon (Cordis, Inc) was inflated in the left anterior descending (LAD) artery beyond the first diagonal branch to occlude LAD flow for 60 minutes, followed by reperfusion. After allowing for stabilization, allogeneic MSCs were given by intramyocardial injection using a deflectable guiding catheter and a helical needle (Biocardia, Inc). In 4 animals, MRMSCs were injected; 1 control animal received nonlabeled MSCs. Magnetically Labeled MSCsSwine mesenchymal stem cells were isolated and cultured as previously described. 7 The MSCs were culture-expanded 2 or 3 passages in vitro, yielding up to 400 million cells, which were frozen and thawed for use. In two studies, before freezing, the MSCs were fluorescently labeled with DiI (1,1Ј-dioctadecyl-3,3,3Ј3Ј-testramethylindocarbocyanine perchlorate) and DAPI (4Ј,6-Diamidino-2-phenylindole), which preferentially stain cells membranes and nuclei, respectively.The swine MSCs were magnetically labeled by incubation with ferumoxides injectable solution (25 g Fe/mL, Feridex, Berlex Laboratories) in culture medium for 24 to 48 hours with 375 ng/mL poly-L-lysine (PLL; average MWϭ275 kDa) added ...
A method is proposed to estimate signal-to-noise ratio (SNR) values in phased array magnitude images, based on a region-of-interest (ROI) analysis. It is shown that the SNR can be found by correcting the measured signal intensity for the noise bias effects and by evaluating the noise variance as the mean square value of all the pixel intensities in a chosen background ROI, divided by twice the number of receivers used. Estimated SNR values are shown to vary spatially within a bound of 20% with respect to the true SNR values as a result of noise correlations between receivers.
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