Tamer Mohamed1, Yu Huang1, Maythem Saeed2, Deepark Srivastava1, and Sergey Magnitsky3
1Gladstone Institute, San Francisco, CA, United States, 2UCSF, San Francisco, CA, United States, 3Radiology, UCSF, San Francisco, CA, United States
Synopsis
In this study we compared two in vivo imaging techniques to obtain anatomical and physiological parameters of mice hart. Our results suggest that measurements of enjection fraction and mass of left ventricle were easier and cheaper with
ultrasound echocardiography however evaluation of a scar tissue and
re-muscularization of infarcted myocardium are only possible with MRI methodIntroduction
Myocardial infarction remains
a leading cause of morbidity and mortality worldwide. To replace damaged cells
in myocardium, we created a novel approach that transdifferentiates fibroblasts
into cardiomyocyte-like cells by overexpressing three core transcription
factors involved in development—Gata4, Mef2C and TBX5 (GMT)—in vitro and in
vivo. Notably, the degree of reprogramming was significantly higher in vivo
than in vitro. Administration of these factors into an animal with myocardium
infarction increased lifespan of experimental animals. Histological studies
demonstrated transformation of fibroblasts into normal myocardium tissue. These
promising results initiate significant research interest and several research groups
conducting fibroblast reprogramming studies worldwide. In order to facilitate
this research noninvasive imaging method of myocardium monitoring is needed. In
the present study we compare results of in vivo imaging of cardiac anatomy and
functions using two noninvasive techniques: ultrasound echocardiography and MR
imaging. Taking into account very different level of complexity and price for
these two techniques, the goal of the study was to evaluate which method
provides sufficient amount of information about anatomy and functionality of myocardium
and more preferable in the research.
Material and Methods
Left anterior descending coronary artery was permanently
occluded for 12 weeks in twenty B6 black mice. Ten animals were treated with intomyocardium
administration of genetically engineered lentiviruses. Viruses provided a delivery
of Gata4, Mef2c and Tbx5 transcription factors
into genome of cells surrounded the injection site. Another ten mice
were not treated and used as control. Ultrasound imaging of myocardium were
performed once a week for twelve weeks, MR imaging was performed once, twelve
weeks after occlusion. Ultrasound
imaging was performed on Visual Sonic Vevo 770 scanner.
MR imaging was performed at 7T preclinical horizontal bore
magnet interfaced to Agilent console. Spin echo MR pulse sequence was
implemented with the following parameters: TR=1s, TE=10ms, in-plane image
resolution 200 um and slice thickness of 1mm, acquisition time ~20min (depends
on hart rate). Cardiac and breathing gating was employed. In order to evaluate the
ejection fraction, nine short axis slices of the heart were acquired at diastole
(zero delay after R-heart-peak) and systole (45% of the R-R interval delay from
the R-peak).
Results
Ultrasound and MR images of the infarcted myocardium are shown
in figure 1 (A and B respectively). Table 1 presents the results of ejection
fraction (EF), left ventricle mass (LVmass) measurements obtained with
ultrasound and MR methods. In addition to these two parameters, MR imaging
allowed to measure scar size.
Discussion and
Conclusion
Measurements of EF and LVmass with MR and ultrasound imaging
provide consistent results while the evaluation of scar size with ultrasound
technique is not feasible. We compared
MRI measurements of the infarction size with histological staining and observed
very strong correlation (). Results of our study suggest that measurements of EF
and mass of left ventricle were easier and cheaper to perform with ultrasound echocardiography
however evaluation of a scar tissue and re-muscularization of infarcted
myocardium are only possible with MRI method.
Acknowledgements
This work was supported by NIH (NHLBI U01 HL100406) and CIRM (TR3-05593) funding. References
No reference found.