Simultaneous assessment of left‐ventricular infarction size, function and tissue viability in a murine model of myocardial infarction by cardiac manganese‐enhanced magnetic resonance imaging (MEMRI)

Abstract

Owing to its signal-enhancing characteristics in viable well-perfused tissue, divalent manganese (Mn 2þ ) has been used as a myocardial imaging contrast agent. Because Mn 2þ can enter excitable cells through the voltage-gated L-type calcium channels, manganese-enhanced MRI (MEMRI) has been used to determine the viability and the inotropic state of the heart. In this study, we examined the correlation between left ventricular infarction zone as assessed by cardiac MEMRI and function in mice with permanent coronary artery occlusion. At an Mn 2þ infusion dose of 1.72 AE 0.47 nmol/min/g body weight, the steady-state signal intensity (SI) enhancement 20-26 min post-Mn 2þ infusion of the normal septum and leftventricular wall during diastole was 128.2 AE 14.4 and 127.9 AE 26.5%, respectively, whereas the infarction zone was 56.0 AE 7.1%. During systole, the SI enhancement was 144.6 AE 33.0, 116.0 AE 18.7 and 48.3 AE 20.0% for the normal septum, left-ventricular wall and infarction zone, respectively. A good correlation was obtained between the MEMRI determined infarction volume and conventional histological TTC staining (r ¼ 0.9582, p < 0.01). There was also a strong negative correlation between MEMRI determined infarction percentage (compared with whole left ventricle) and ejection fraction (r ¼ À0.94, p < 0.05). These data suggest that the Mn 2þ concentration at steady state in the heart may reflect altered tissue viability in the infarcted tissue as well as surrounding region following myocardial infarction. In conclusion, in vivo cardiac MEMRI offers a manner in which functional, pathologic and viability data may be obtained simultaneously in myocardial tissue.

KATP channel knockout worsens myocardial calcium stress load in vivo and impairs recovery in stunned heart

“…Male (n ϭ 4 each) and female (n ϭ 4 each) Kir6.2-KO mice or WT counterparts were anesthetized via intraperitoneal administration of 2,2,2-tribromoethanol (Avertin) at a dose of 250 mg/kg body wt. Under sterile conditions, a heparinized 10-l total volume polyethylene-10 catheter was introduced into the right internal jugular and sutured in place for infusion of the Mn 2ϩ and dobutamine solutions, used for tracing calcium influx and stress induction, respectively (13,19,20,35,56). Anesthesia was then maintained with Ͻ1% inhaled isoflurane to allow for a constant and controllable level of anesthesia and heart rate during the manganeseenhanced cardiac MRI procedure.…”

“…The imaging parameters were as follows: matrix ϭ 128 ϫ 128; angle ϭ 90°; echo time ϭ 1.3 ms; repetition time ϭ 300 ms; slice thickness ϭ 1.00 mm; field of view ϭ 2.5 cm and eight averages. Image intensities in the midseptum, midanterior wall, and midlateral wall were averaged and normalized to an external gadolinium-spiked water phantom placed to the side of the mouse (19). Images were taken every 3 min to monitor signal changes during the experiment.…”

“…Manganese-induced enhancement of the magnetic resonance cardiac signal is indicative of calcium influx into the heart (13,19,20,35). Accordingly, manganese-enhanced cardiac MRI was employed to probe the consequence of K ATP channel deletion on calcium loading under stress in vivo.…”

“…Under dobutamine challenge (56), in vivo manganese-enhanced cardiac magnetic resonance imaging (13,19,20,35) captured excessive calcium accumulation in mice deficient in K ATP channels, precipitating poor recovery. Deficit in K ATP channels translated into compromised function in the stunned heart, with the knockout phenotype rescued by targeting alternative pathways of calcium handling.…”

Manganese-Enhanced MRI Reveals Early-Phase Radiation-Induced Cell Alterations In Vivo

“…The tumor cell uptake of Mn 2þ is linked to the proliferation rate in vitro of human tumor cells (18). In addition, Mn 2þ is considered to be a cell viability indicator in myocardial infarction (19,20). Therefore, it is possible that radiation-induced cell-cycle alteration and the associated suppression of cell proliferation can be detected from the alterations in MEMRI signal enhancement.…”