Abstract 14483: Strain Analysis by 2D Speckle Tracking Imaging Sensitively Identifies Early Dystrophin Cardiomyopathy in Murine Duchenne Muscular Dystrophy Model: An Ultrasound Biomicroscopy and Histology Correlation Study
Introduction: Cardiomyopathy is a significant cause of mortality and morbidity in Duchenne muscular dystrophy (DMD). To develop novel safe and efficacious therapy for dystrophin cardiomyopathy in mouse models, sensitive and reliable measures for left ventricular (LV) remodeling and dysfunction are imperative but difficult to validate using histology clinically.
Hypothesis: We hypothesized that strain analysis using ultrasound biomicroscopy (UBM) based 2D speckle tracking imaging (STI) is more sensitive than conventional measures in a murine model using histology.
Methods: A total of 25 x-linked muscular dystrophy (mdx)(C57BL/10ScSn-Dmdmdx/J) and 25 control (C57BL) mice at 3, 6, 9, and 12 months were studied using UBM. Conventional M-mode, 2D and new strain analysis using UBM/STI was obtained. Histology was performed at each time point, including hematoxylin and eosin (HE), picric acid sirius red (PSR) staining, and terminal dUTP nick end-labeling (TUNEL). Collagen volume fraction (CVF) was calculated to quantify fibrosis. Results (see Figure): Compared with control mice, mdx mice at 9 and 12 months demonstrated LV dilatation (EDD) and diminished systolic function (FS). In contrast, mdx mice at 6, 9 and 12 months showed progressively diminished longitudinal, radial and circumferential peak strain. Histological studies showed increased CVF at 3, 6, 9, and 12 months with progressive myocyte hypertrophy, leukocyte infiltration, focal fibrosis and apoptosis. Peak strain correlated with EF (r=0.81; SEE=6.97; p<0.05) and CVF (r=-0.64, SEE=2.43; p<0.05). Intra- and inter-observer variability was 5.2±3.6% and 6.1±2.6%, respectively.
Conclusions: Peak strain by UBM/STI is feasible and reproducible for assess LV dysfunction in mdx mice. Peak strain is also more sensitive than conventional UBM measures of LV remodeling and dysfunction. These measures may become powerful tools for evaluating new therapy for DMD. .
- © 2010 by American Heart Association, Inc.