Labelling of mammalian cells for visualisation by MRI.

Through labelling of cells with magnetic contrast agents it is possible to follow the fate of transplanted cells in vivo with magnetic resonance imaging (MRI) as has been demonstrated in animal studies as well as in a clinical setting. A large variety of labelling strategies are available that allow for prolonged and sensitive detection of the labelled cells with MRI. The various protocols each harbour specific advantages and disadvantages. In choosing a particular labelling strategy it is also important to ascertain that the labelling procedure does not negatively influence cell functionality, for which a large variety of assays are available. In order to overcome the challenges still faced in fully exploiting the benefits of in vivo cell tracking by MRI a good understanding and standardisation of the procedures and assays used will be crucial.

Intracoronary delivery of umbilical cord blood derived unrestricted somatic stem cells is not suitable to improve LV function after myocardial infarction in swine.

Regeneration of infarcted myocardium by injecting stem cells has been proposed to prevent heart failure. We studied the i.c. administration of human umbilical cord blood stem cells (USSC) in a porcine model of myocardial infarction (MI) and reperfusion. In 15 swine, MI was induced by balloon-occlusion of the left circumflex coronary artery (LCX) for 2 h followed by reperfusion. Five swine served as healthy controls. One week later, magnetic resonance imaging (MRI) was performed to assess left ventricular (LV) function and infarct size. Then, under immune suppression, 6 of the 12 surviving MI swine received intracoronary injection of approximately 10(8) human USSC in the LCX while the other MI-swine received medium. Four weeks later all swine underwent follow-up MRI, and were sacrificed for histology. One week after MI, end-diastolic volume (92+/-3 mL) and LV mass (75+/-2 g) were larger, while ejection fraction (42+/-2%) was smaller than in healthy control (68+/-3 mL, 66+/-3 g and 55+/-3%, all P<0.05). Regional wall thickening (-7+/-2%) in the LCX area became akinetic. No difference in global and regional LV function at 5 weeks was observed between MI animals receiving USSC or medium. Infarct size after USSC treatment was significantly larger (20+/-3 g vs. 8+/-2 g, P<0.05). USSC survived only in the infarct border zone at 5 weeks and did not express cardiomyocyte or endothelial markers. Histology showed that intracoronary injection of USSC caused micro infarctions by obstructing blood vessels. In swine with a 1 week old MI, injection of USSC via the intracoronary route does not improve LV function 4 weeks later.

Assessment of acute reperfused myocardial infarction with delayed enhancement 64-MDCT.

OBJECTIVE: The purpose of this study was to evaluate the utility of delayed enhancement 64-MDCT in the assessment of myocardial infarct size in a porcine model of acute reperfused myocardial infarction. CT can be used for noninvasive assessment of coronary artery stenosis, but to our knowledge, evaluation of myocardial viability in the subacute phase of acute myocardial infarction has not been validated. We performed delayed enhancement imaging on six domestic swine 5 days after reperfused acute myocardial infarction and assessed the relation between delayed enhancement patterns in vivo and the extent of viable and nonviable myocardium at postmortem histochemical analysis. CONCLUSION: Delayed enhancement imaging with 64-MDCT can be used for accurate assessment of the size of reperfused acute myocardial infarcts.

Reduction in infarct size, but no functional improvement after bone marrow cell administration in a porcine model of reperfused myocardial infarction.

AIMS: Stem cell therapy after myocardial infarction (MI) has been studied in models of permanent coronary occlusion. We studied the effect of intracoronary administration of unselected bone marrow (BM) and mononuclear cells (MNC) in a porcine model of reperfused MI. METHODS AND RESULTS: In 34 swine, the left circumflex coronary artery was balloon-occluded for 2 h followed by reperfusion. Ten swine without MI served as controls. All swine underwent magnetic resonance imaging (MRI) 1 week post-MI. The next day, 10 of the 30 surviving MI swine received BM, 10 other MI swine received MNC, and the remaining MI swine received medium intracoronary. Four weeks later, all swine underwent a follow-up MRI. One week after MI, end-diastolic volume (92+/-16 mL) and left ventricular (LV) weight (78+/-12 g) were greater, whereas ejection fraction (40+/-8%) was lower than in controls (69+/-11 mL, 62+/-13 g, and 53+/-6%). Injection of BM or MNC had no effect on the MI-induced changes in global or regional LV-function. However, there was a significant reduction in infarct size 4 weeks after MNC injection (-6+/-3%) compared with the medium (-3+/-5%). CONCLUSION: Intracoronary injection of BM or MNC in swine does not improve regional or global LV-function 4 weeks after injection. However, a reduction in infarct-size was noted after MNC injection.

Multislice computed tomography and magnetic resonance imaging for the assessment of reperfused acute myocardial infarction.

OBJECTIVES: We evaluated the accuracy of in vivo delayed-enhancement multislice computed tomography (DE-MSCT) and delayed-enhancement magnetic resonance imaging (DE-MRI) for the assessment of myocardial infarct size using postmortem triphenyltetrazolium chloride (TTC) pathology as standard of reference. BACKGROUND: The diagnostic value of DE-MSCT for the assessment of acute reperfused myocardial infarction is currently unclear. METHODS: In 10 domestic pigs (25 to 30 kg), the circumflex coronary artery was balloon-occluded for 2 h followed by reperfusion. After 5 days (3 to 7 days), DE-MRI (1.5-T) was performed 15 min after administration of 0.2 mmol/kg gadolinium-DTPA using an inversion recovery gradient echo technique. On the same day, DE-MSCT (64-slice) was performed 15 min after administration of 1 gI/kg of iodinated contrast material. One day after imaging, hearts were excised, sectioned in 8 mm short-axis slices, and stained with TTC. Infarct size was defined as the hyperenhanced area on DE-MSCT and DE-MRI images and the TTC-negative area on TTC pathology slices. Infarct size was expressed as percentage of total slice area. RESULTS: Infarct size determined by DE-MSCT and DE-MRI showed a good correlation with infarct size assessed with TTC pathology (R2 = 0.96 [p < 0.001] and R(2) = 0.93 [p < 0.001], respectively). The correlation between DE-MSCT and DE-MRI was also good (R2 = 0.96; p < 0.001). The relative difference in CT attenuation value of infarcted myocardium compared to remote myocardium was 191 +/- 18%. The relative MR signal intensity between infarcted myocardium and remote myocardium was 554 +/- 156%. CONCLUSIONS: We demonstrated that DE-MSCT can assess acute reperfused myocardial infarction in good agreement with in vivo DE-MRI and TTC pathology.

Magnetic resonance imaging of haemorrhage within reperfused myocardial infarcts: possible interference with iron oxide-labelled cell tracking?

AIMS: Magnetic resonance imaging (MRI) has been proposed as a tool to track iron oxide-labelled cells within myocardial infarction (MI). However, infarct reperfusion aggravates microvascular obstruction (MO) and causes haemorrhage. We hypothesized that haemorrhagic MI causes magnetic susceptibility-induced signal voids that may interfere with iron oxide-labelled cell detection. METHODS AND RESULTS: Pigs (n = 23) underwent 2 h occlusion of the left circumflex artery. Cine, T2*-weighted, perfusion, and delayed enhancement MRI scans were performed at 1 and 5 weeks, followed by ex vivo high-resolution scanning. At 1 week, MO was observed in 17 out of 21 animals. Signal voids were observed on T2*-weighted scans in five out of eight animals, comprising 24 +/- 22% of the infarct area. A linear correlation was found between area of MO and signal voids (R2 = 0.87; P = 0.002). At 5 weeks, MO was observed in two out of 13 animals. Signal voids were identified in three out of seven animals. Ex vivo scanning showed signal voids on T2*-weighted scanning in all animals because of the presence of haemorrhage, as confirmed by histology. Signal voids interfered with the detection of iron oxide-labelled cells ex vivo (n = 21 injections). CONCLUSION: Haemorrhage in reperfused MI produces MRI signal voids, which may hamper tracking of iron oxide-labelled cells.