TY - JOUR
T1 - Molecular MRI detects low levels of cardiomyocyte apoptosis in a transgenic model of chronic heart failure
AU - Sosnovik, David E.
AU - Nahrendorf, Matthias
AU - Panizzi, Peter
AU - Matsui, Takashi
AU - Aikawa, Elena
AU - Dai, Guangping
AU - Li, Ling
AU - Reynolds, Fred
AU - Dorn, Gerald W.
AU - Weissleder, Ralph
AU - Josephson, Lee
AU - Rosenzweig, Anthony
PY - 2009/11
Y1 - 2009/11
N2 - 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 (r= 20.86, 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. (Circ Cardiovasc Imaging. 2009;2:468-475.)
AB - 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 (r= 20.86, 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. (Circ Cardiovasc Imaging. 2009;2:468-475.)
KW - Apoptosis
KW - Cardiomyocyte
KW - Heart failure
KW - MRI
KW - Molecular imaging
UR - http://www.scopus.com/inward/record.url?scp=73449116808&partnerID=8YFLogxK
U2 - 10.1161/CIRCIMAGING.109.863779
DO - 10.1161/CIRCIMAGING.109.863779
M3 - Article
C2 - 19920045
AN - SCOPUS:73449116808
SN - 1941-9651
VL - 2
SP - 468
EP - 475
JO - Circulation: Cardiovascular Imaging
JF - Circulation: Cardiovascular Imaging
IS - 6
ER -