Abstract 593: Molecular MRI of Cardiomyocyte Apoptosis With Simultaneous Delayed Enhancement MRI Distinguishes Apoptotic and Necrotic Myocytes in vivo: Potential for Midmyocardial Salvage in Acute Ischemia
Background: A novel dual contrast molecular MRI technique to image both cardiomyocyte (CM) apoptosis and necrosis in-vivo within 4 – 6 hours of ischemia is presented. The technique utilizes the annexin-based nanoparticle AnxCLIO-Cy5.5 (apoptosis) and simultaneous delayed enhancement (DE) imaging with a novel gadolinium chelate, Gd-DTPA-NBD (necrosis).
Methods and Results: Mice with transient coronary ligation were injected at the onset of reperfusion with AnxCLIO-Cy5.5 (n=7) or the control probe Inact CLIO-Cy5.5 (n=6). T2* weighted MR images were acquired within 4 – 6 hours of reperfusion. The contrast-to-noise ratio (CNR) between injured and uninjured myocardium was measured. The mice were then injected with Gd-DTPA-NBD and DE imaging was performed within 10 –30 minutes. Uptake of AnxCLIO-Cy5.5 (Fig 1A) was most prominent in the midmyocardium and was significantly greater than that of (1B) Inact CLIO-Cy5.5 (CNR 8.82 +/− 1.5 versus 3.78 +/− 1.1, p < 0.05). Only 21 +/− 3% of the myocardium with uptake of AnxCLIO-Cy5.5 showed DE of Gd-DTPA-NBD. Wall thickening was significantly reduced in segments with DE and/or transmural accumulation of AnxCLIO-Cy5.5 (1E-F). Fluorescence microscopy (1C) and immunohistochemistry confirmed the presence of numerous apoptotic but potentially viable CMs (AnxCLIO-Cy5.5 +ve, GD-DTPA-NBD -ve) in the midmyocardium.
Conclusions: A novel technique to image CM apoptosis and necrosis in-vivo within 4 – 6 hours of injury is presented, and reveals large areas of apoptotic but viable myocardium in the midmyocardium. Strategies to salvage the numerous apoptotic but potentially viable CMs in the midmyocardium in acute ischemia should be developed.