quantification-mouse-heart-left-ventricular-function-myocardial

Quantification of Mouse Heart Left Ventricular Function, Myocardial Strain, and Hemodynamic Forces by Cardiovascular Magnetic Resonance Imaging

Mouse models have contributed significantly to understanding genetic and physiological factors involved in healthy cardiac function, how perturbations ...

University of Amsterdam

Atherosclerosis is a prevalent disease affecting a large portion of the population at one point in their lives. There is an unmet need for noninvasive diagnostics to identify and characterize at-risk plaque phenotypes noninvasively and in vivo, to improve the stratification of patients with cardiovascular disease, and for treatment evaluation. Magnetic resonance imaging is uniquely positioned to address these diagnostic needs. However, currently available magnetic resonance imaging methods for vessel wall imaging lack sufficient discriminative and predictive power to guide the individual patient needs. To address this challenge, physicists are pushing the boundaries of magnetic resonance atherosclerosis imaging to increase image resolution, provide improved quantitative evaluation of plaque constituents, and obtain readouts of disease activity such as inflammation. Here, we review some of these important developments, with specific focus on emerging applications using high-field magnetic resonance imaging, the use of quantitative relaxation parameter mapping for improved plaque characterization, and novel F magnetic resonance imaging technology to image plaque inflammation.

Emerging Magnetic Resonance Imaging Techniques for Atherosclerosis Imaging.

 F-MRI is gaining widespread interest for cell tracking and quantification of immune and inflammatory cells in vivo. Different fluorinated compounds can be discriminated based on their characteristic MR spectra, allowing in vivo imaging of multiple  F compounds simultaneously, so-called multicolor  F-MRI. We introduce a method for multicolor  F-MRI using an iterative sparse deconvolution method to separate different  F compounds and remove chemical shift artifacts arising from multiple resonances.

An iterative sparse deconvolution method for simultaneous multicolor  F-MRI of multiple contrast agents.

Tetracycline antibiotics act by inhibiting bacterial protein translation. Given the bacterial ancestry of mitochondria, we tested the hypothesis that doxycycline-which belongs to the tetracycline class-reduces mitochondrial function, and results in cardiac contractile dysfunction in cultured H9C2 cardiomyoblasts, adult rat cardiomyocytes, in  and in mice. Ampicillin and carbenicillin were used as control antibiotics since these do not interfere with mitochondrial translation. In line with its specific inhibitory effect on mitochondrial translation, doxycycline caused a mitonuclear protein imbalance in doxycycline-treated H9C2 cells, reduced maximal mitochondrial respiration, particularly with complex I substrates, and mitochondria appeared fragmented. Flux measurements using stable isotope tracers showed a shift away from OXPHOS towards glycolysis after doxycycline exposure. Cardiac contractility measurements in adult cardiomyocytes and  hearts showed an increased diastolic calcium concentration, and a higher arrhythmicity index. Systolic and diastolic dysfunction were observed after exposure to doxycycline. Mice treated with doxycycline showed mitochondrial complex I dysfunction, reduced OXPHOS capacity and impaired diastolic function. Doxycycline exacerbated diastolic dysfunction and reduced ejection fraction in a diabetes mouse model vulnerable for metabolic derangements. We therefore conclude that doxycycline impairs mitochondrial function and causes cardiac dysfunction.

Article	Year
Emerging Magnetic Resonance Imaging Techniques for Atherosclerosis Imaging. Arteriosclerosis, thrombosis, and vascular biology\| PubMed ID: 30917678	2019
An iterative sparse deconvolution method for simultaneous multicolor F-MRI of multiple contrast agents. Magnetic resonance in medicine\| PubMed ID: 31441541	2020
The Antibiotic Doxycycline Impairs Cardiac Mitochondrial and Contractile Function. International journal of molecular sciences\| PubMed ID: 33921053	2021

Mariah R. R. Daal

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