Comprehensive MRI for the detection of subtle alterations in diastolic cardiac function in apoE/LDLR(-/-) mice with advanced atherosclerosis

Urszula Tyrankiewicz; Tomasz Skorka; Anna Orzylowska; Magdalena Jablonska; Krzysztof Jasinski; Agnieszka Jasztal; Anna Bar; Renata Kostogrys; Stefan Chlopicki

doi:10.1002/nbm.3524

Comprehensive MRI for the detection of subtle alterations in diastolic cardiac function in apoE/LDLR(-/-) mice with advanced atherosclerosis

NMR Biomed. 2016 Jun;29(6):833-40. doi: 10.1002/nbm.3524. Epub 2016 May 5.

Authors

Affiliations

¹ Department of Magnetic Resonance Imaging, Institute of Nuclear Physics, Polish Academy of Sciences, Krakow, Poland.
² Jagiellonian Center for Experimental Therapeutics (JCET), Jagiellonian University, Krakow, Poland.
³ Chair of Pharmacology, Jagiellonian University Medical College, Krakow, Poland.
⁴ Department of Human Nutrition, Faculty of Food Technology, University of Agriculture in Krakow, Krakow, Poland.

PMID: 27146203
DOI: 10.1002/nbm.3524

Abstract

ApoE/LDLR(-/-) mice represent a reliable model of atherosclerosis. However, it is not clear whether cardiac performance is impaired in this murine model of atherosclerosis. Here, we used MRI to characterize cardiac performance in vivo in apoE/LDLR(-/-) mice with advanced atherosclerosis. Six-month-old apoE/LDLR(-/-) mice and age-matched C57BL/6J mice (control) were examined using highly time-resolved cine-MRI [whole-chamber left ventricle (LV) imaging] and MR tagging (three slices: basal, mid-cavity and apical). Global and regional measures of cardiac function included LV volumes, kinetics, time-dependent parameters, strains and rotations. Histological analysis was performed using OMSB (orceine with Martius, Scarlet and Blue) and ORO (oil red-O) staining to demonstrate the presence of advanced coronary atherosclerosis. MR-tagging-based strain analysis in apoE/LDLR(-/-) mice revealed an increased frequency of radial and circumferential systolic stretch (25% and 50% of segments, respectively, p ≤ 0.012), increased radial post-systolic strain index (45% of segments, p = 0.009) and decreased LV untwisting rate (-30.3° (11.6°)/cycle, p = 0.004) when compared with control mice. Maximal strains and LV twist were unchanged. Most of the cine-MRI-based LV functional and anatomical parameters also remained unchanged in apoE/LDLR(-/-) mice, with only a lower filling rate, longer filling time, shorter isovolumetric contraction time and slower heart rate observed in comparison with control mice. The coronary arteries displayed severe atherosclerosis, as evidenced by histological analysis. Using comprehensive MRI methods, we have demonstrated that, despite severe coronary atherosclerosis in six-month-old apoE/LDLR(-/-) mice, cardiac performance including global parameters, twist and strains, was well preserved. Only subtle diastolic alterations, possibly of ischemic background, were uncovered. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: MR tagging; MRI; apoE/LDLR-/- mice; atherosclerosis; cardiac function.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cardiac Imaging Techniques*
Coronary Artery Disease / complications
Coronary Artery Disease / diagnostic imaging*
Coronary Artery Disease / physiopathology*
Disease Progression
Magnetic Resonance Imaging, Cine / methods*
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Reproducibility of Results
Sensitivity and Specificity
Severity of Illness Index
Stroke Volume*
Ventricular Dysfunction, Left / diagnostic imaging*
Ventricular Dysfunction, Left / etiology
Ventricular Dysfunction, Left / physiopathology*