This Article Full Text Full Text (PDF) All Versions of this Article: 2/6/468    most recent CIRCIMAGING.109.863779v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Sosnovik, D. E. Articles by Rosenzweig, A. PubMed PubMed Citation Articles by Sosnovik, D. E. Articles by Rosenzweig, A. Related Collections Other myocardial biology Congestive Cardiovascular imaging agents/Techniques Apoptosis Heart failure - basic studies Imaging CT and MRI

Original Articles

Molecular MRI Detects Low Levels of Cardiomyocyte Apoptosis in a Transgenic Model of Chronic Heart Failure

David E. Sosnovik, MD; Matthias Nahrendorf, MD; Peter Panizzi, PhD; Takashi Matsui, MD, PhD; Elena Aikawa, MD, PhD; Guangping Dai, PhD; Ling Li, MD; Fred Reynolds, PhD; Gerald W. Dorn, II, MD; Ralph Weissleder, MD, PhD; Lee Josephson, PhD and Anthony Rosenzweig, MD

From the Center for Molecular Imaging Research (D.E.S., M.N., P.P., E.A., F.R., R.W., L.J.), the Cardiology Division (D.E.S.), and Martinos Center for Biomedical Imaging (D.E.S., G.D.), Massachusetts General Hospital, Harvard Medical School, Boston, Mass; the Cardiovascular Institute (T.M., L.L., A.R.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass; and the Center for Pharmacogenomics (G.W.D.), Washington University School of Medicine, St Louis, Mo.

Correspondence to David E. Sosnovik, MD, 5416, 149 13th St, Charlestown, MA 02129. E-mail sosnovik{at}nmr.mgh.harvard.edu

Received March 8, 2009; accepted August 24, 2009.

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.

Key Words: apoptosis • heart failure • MRI • molecular imaging • cardiomyocyte

---

 

CLINICAL PERSPECTIVE