Dual manganese-enhanced and delayed gadolinium-enhanced MRI detects myocardial border zone injury in a pig ischemia-reperfusion model.

BACKGROUND: Gadolinium (Gd)-based delayed-enhancement MRI (DEMRI) identifies nonviable myocardium but is nonspecific and may overestimate nonviable territory. Manganese (Mn(2+))-enhanced MRI (MEMRI) denotes specific Mn(2+) uptake into viable cardiomyocytes. We performed a dual-contrast myocardial assessment in a porcine ischemia-reperfusion (IR) model to test the hypothesis that combined DEMRI and MEMRI identifies viable infarct border zone (BZ) myocardium in vivo. METHODS AND RESULTS: Sixty-minute left anterior descending coronary artery IR injury was induced in 13 adult swine. Twenty-one days post-IR, 3-T cardiac MRI was performed. MEMRI was obtained after injection of 0.7 mL/kg Mn(2+) contrast agent. DEMRI was then acquired after injection of 0.2 mmol/kg Gd. Left ventricular (LV) mass, infarct, and function were analyzed. Subtraction of MEMRI defect from DEMRI signal identified injured BZ myocardium. Explanted hearts were analyzed by 2,3,5-triphenyltetrazolium chloride stain and tissue electron microscopy to compare infarct, BZ, and remote myocardium. Average LV ejection fraction was reduced (30±7%). MEMRI and DEMRI infarct volumes correlated with 2,3,5-triphenyltetrazolium chloride stain analysis (MEMRI, r=0.78; DEMRI, r=0.75; P<0.004). MEMRI infarct volume percentage was significantly lower than that of DEMRI (14±4% versus 23±4%; P<0.05). BZ MEMRI signal-to-noise ratio (SNR) was intermediate to remote and core infarct SNR (7.5±2.8 versus 13.2±3.4 and 2.9±1.6; P<0.0001), and DEMRI BZ SNR tended to be intermediate to remote and core infarct SNR (8.4±5.4 versus 3.3±0.6 and 14.3±6.6; P>0.05). Tissue electron microscopy analysis exhibited preserved cell structure in BZ cardiomyocytes despite transmural DEMRI enhancement. CONCLUSIONS: The dual-contrast MEMRI-DEMRI detects BZ viability within DEMRI infarct zones. This approach may identify injured, at-risk myocardium in ischemic cardiomyopathy.

EVP-ABD-enhanced MRI to evaluate diffuse liver disease in a rat model.

PURPOSE: To evaluate the feasibility of using manganese-based MR imaging contrast agent EVP-ABD to detect diffuse liver disease in an established rat hepatitis model. MATERIALS AND METHODS: Hepatitis was induced by administration of CCl(4) in corn oil vehicle to rats intraperitoneally. MR images were acquired on a 3T scanner using a volume coil approximately 36 hours after the administration of CCl(4). EVP-ABD was administered via a tail vein at a dose of 10 mumol/kg. Multi-TI turboflash images were acquired to evaluate liver R1 (=1/T1) values before and after the EVP-ABD administration. Eighteen rats received various doses of CCl(4) and completed pre- and postcontrast MRI scans and liver histologic evaluation. RESULTS: The liver R1 after the EVP-ABD administration and the change of the liver R1 before and after the administration, DeltaR1, show significant correlations with the CCl(4) dose. A significant correlation was also found between the histologic scores and the CCl(4) doses despite known variability in the relationship of CCl(4) dose to histology. A significant correlation was found between the histologic score and DeltaR1. CONCLUSION: Our results indicate that EVP-ABD-enhanced MRI can detect diffuse liver disease generated by CCl(4) based on the significant correlation between proton R1 in liver following EVP-ABD and the CCl(4) doses as well as the histologic scores.

Magnetic resonance imaging of myocardial infarction using a manganese-based contrast agent (EVP 1001-1): preliminary results in a dog model.

PURPOSE: To investigate the MRI characteristics of an intracellular manganese-based contrast agent, EVP 1001-1 (Eagle Vision Pharmaceutical Corp.), in a canine model of myocardial infarction. MATERIALS AND METHODS: Three dogs were imaged 14-37 days following permanent ligation of the left anterior descending coronary artery (LAD). Measurements of the longitudinal relaxation rate R(1) were made prior to EVP 1001-1 administration (20 micromol/kg i.v.) and for one hour thereafter. Triphenyl tetrazolium chloride (TTC) staining was used to document infarction. RESULTS: In normal myocardium, EVP 1001-1 produced a substantial increase in the longitudinal relaxation rate, which remained fairly constant over the postcontrast imaging period (DeltaR1= 1.47 +/- 0.58 sec(-1) (mean +/- SD) at 35 minutes, P < 0.05). In the infarct, the response to EVP 1001-1 was small or negligible (DeltaR1= 0.27 +/- 0.28 sec(-1)). This resulted in a significant postcontrast difference in relaxation rate between normal and infarcted tissue (R1(normal) - R1(infarct) = 1.08 +/- 0.26 sec(-1), P < 0.05). The infarct remained clearly delineated in all animals throughout the steady-state imaging period, and qualitatively matched TTC results. CONCLUSION: The persistent enhancement pattern revealed by MRI following EVP 1001-1 administration may be beneficial for identifying and characterizing myocardial infarction.

Preliminary evaluation of EVP 1001-1: a new cardiac-specific magnetic resonance contrast agent with kinetics suitable for steady-state imaging of the ischemic heart.

RATIONALE AND OBJECTIVES: To investigate the potential of a novel manganese-based magnetic resonance (MR) contrast agent, EVP 1001-1 for the evaluation of myocardial ischemia. METHODS: MR imaging with EVP 1001-1 was performed on 6 Yorkshire pigs, and T1 relaxation times were calculated. One animal served as a control, 2 were subjected to an acute coronary artery occlusion and 3 provided a model of chronic ischemia. RESULTS: Administration of the agent in the control and acute coronary occlusion model demonstrated a short plasma half-life (approximately 1.5 minutes) and rapid myocardial uptake in nonoccluded regions, with long retention times in the myocardium (>1 hour) and no evidence of redistribution. In the chronic ischemia model, differential enhancement was observed between normal and ischemic tissue, particularly under dobutamine-induced stress. CONCLUSIONS: These properties suggest the use of EVP 1001-1 for steady-state imaging of myocardial perfusion. Contrast administration could be performed under stress conditions outside the scanner, with high-resolution MR images reflecting the stress condition acquired after the stress has subsided.