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Articles by M Nahrendorf
Total Records ( 3 ) for M Nahrendorf
  P Nordbeck , W. R Bauer , F Fidler , M Warmuth , K. H Hiller , M Nahrendorf , M Maxfield , S Wurtz , W Geistert , J Broscheit , P. M Jakob and O. Ritter

Background— Cardiac MRI offers 3D real-time imaging with unsurpassed soft tissue contrast without x-ray exposure. To minimize safety concerns and imaging artifacts in MR-guided interventional electrophysiology (EP), we aimed at developing a setup including catheters for ablation therapy based on carbon technology.

Methods and Results— The setup, including a steerable carbon catheter, was tested for safety, image distortion, and feasibility of diagnostic EP studies and radiofrequency ablation at 1.5 T. MRI was performed in 3 different 1.5-T whole-body scanners using various receive coils and pulse sequences. To assess unintentional heating of the catheters by radiofrequency pulses of the MR scanner in vitro, a fluoroptic thermometry system was used to record heating at the catheter tip. Programmed stimulation and ablation therapy was performed in 8 pigs. There was no significant heating of the carbon catheters while using short, repetitive radiofrequency pulses from the MR system. Because there was no image distortion when using the carbon catheters, exact targeting of the lesion sites was possible. Both atrial and ventricular radiofrequency ablation procedures including atrioventricular node modulation were performed successfully in the scanner. Potential complications such as pericardial effusion after intentional perforation of the right ventricular free wall during ablation could be monitored in real time as well.

Conclusion— We describe a newly developed EP technology for interventional electrophysiology based on carbon catheters. The feasibility of this approach was demonstrated by safety testing and performing EP studies and ablation therapy with carbon catheters in the MRI environment.

  D. E Sosnovik , E Garanger , E Aikawa , M Nahrendorf , J. L Figuiredo , G Dai , F Reynolds , A Rosenzweig , R Weissleder and L. Josephson

Background— A novel dual-contrast molecular MRI technique to image both cardiomyocyte apoptosis and necrosis in vivo within 4 to 6 hours of ischemia is presented. The technique uses the annexin-based nanoparticle AnxCLIO-Cy5.5 (apoptosis) and simultaneous delayed-enhancement imaging with a novel gadolinium chelate, Gd-DTPA-NBD (necrosis).

Methods and Results— Mice with transient coronary ligation were injected intravenously 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 (9.4 T) were acquired within 4 to 6 hours of reperfusion. The contrast-to-noise ratio between injured and uninjured myocardium was measured. The mice were then injected with Gd-DTPA-NBD, and delayed-enhancement imaging was performed within 10 to 30 minutes. Uptake of AnxCLIO-Cy5.5 was most prominent in the midmyocardium and was significantly greater than that of Inact_CLIO-Cy5.5 (contrast-to-noise ratio, 8.82±1.5 versus 3.78±1.1; P<0.05). Only 21±3% of the myocardium with accumulation of AnxCLIO-Cy5.5 showed delayed-enhancement of Gd-DTPA-NBD. Wall thickening was significantly reduced in segments with delayed enhancement and/or transmural accumulation of AnxCLIO-Cy5.5 (P<0.001). Fluorescence microscopy of AnxCLIO-Cy5.5 and immunohistochemistry of Gd-DTPA-NBD confirmed the presence of large numbers of apoptotic but potentially viable cardiomyocytes (AnxCLIO-Cy5.5 positive, Gd-DTPA-NBD negative) in the midmyocardium.

Conclusions— A novel technique to image cardiomyocyte apoptosis and necrosis in vivo within 4 to 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 cardiomyocytes in the midmyocardium in acute ischemia should be investigated.

  D. E Sosnovik , M Nahrendorf , P Panizzi , T Matsui , E Aikawa , G Dai , L Li , F Reynolds , G. W Dorn , R Weissleder , L Josephson and A. Rosenzweig

Background— The ability to image cardiomyocyte (CM) apoptosis in heart failure could facilitate more accurate diagnostics and optimize targeted therapeutics. We thus aimed to develop a platform to image CM apoptosis quantitatively and specifically in heart failure in vivo. The myocardium in heart failure, however, is characterized by very low levels of CM apoptosis and normal vascular permeability, factors thought to preclude the use of molecular MRI.

Methods and Results— Female mice with overexpression of Gaq were studied. Two weeks postpartum, these mice develop a cardiomyopathy characterized by low levels of CM apoptosis and minimal myocardial necrosis or inflammation. The mice were injected with the annexin-labeled nanoparticle (AnxCLIO-Cy5.5) or a control probe (CLIO-Cy5.5) and imaged in vivo at 9.4 T. Uptake of AnxCLIO-Cy5.5 occurred in isolated clusters, frequently in the subendocardium. Myocardial T2* was significantly lower (7.6±1.5 versus 16.8±2.7 ms, P<0.05) in the mice injected with AnxCLIO-Cy5.5 versus CLIO-Cy5.5, consistent with the uptake of AnxCLIO-Cy5.5 by apoptotic CMs. A strong correlation (r2=0.86, P<0.05) was seen between in vivo T2* (AnxCLIO-Cy5.5 uptake) and myocardial caspase-3 activity.

Conclusions— The ability of molecular MRI to image sparsely expressed targets in the myocardium is demonstrated in this study. Moreover, a novel platform for high-resolution and specific imaging of CM apoptosis in heart failure is established. In addition to providing novel insights into the pathogenesis of CM apoptosis, the developed platform could facilitate the development of novel antiapoptotic therapies in heart failure.

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