Myocardial Tissue Characterization in Preclinical Models
Katrien Vandoorne1
1Technion – Israel Institute of Technology, Haifa, Israel

Synopsis

Cardiac MR techniques have been applied in small animal cardiovascular disease research, resulting in quantifying several hallmarks of cardiovascular disease. Hallmarks such as muscularization, angiogenesis and vessel stability, fibrotic balance, as well as immunological balance will be addressed as they eventually contribute to organ decline, reduced cardiac function and death. The technological challenges emerging from the small size of heart as well as high-pace cardiac and respiratory rates, particularly in mice, have been tackled. Cardiac tissue characterization could help us understand the sequence of events and cardiac tissue changes in cardiovascular disease progression.

Over the past decade, the development of MR imaging and spectroscopic technologies has dramatically shifted our understanding of cardiac biology. This is the result of the remarkable advances in MR technologies together with other revolutionary technologies such as single-cell genomics, CRISPR–Cas9 gene editing, and novel regenerative medicine strategies. Our knowledge on cardiogenesis and the basics of gene regulatory networks have been improved, clarifying also the heterogeneity and plasticity of the resulting cardiac cell states. Cardiac tissue characterization by preclinical cardiac MRI allows not only identification and characterization of the spatiotemporal function of vital pathways involved in cardiomyocyte proliferation and survival, but we have progressed beyond the cardiomyocyte to increasingly understand the physiological importance and therapeutic potential of the epicardium, stroma, vasculature, and immune system. Cardiac MR techniques have been developed for characterizing cardiovascular disease research, quantifying various hallmarks of cardiovascular disease. These hallmarks include muscularization, angiogenesis and vessel stability, fibrotic balance, as well as immunological balance and can eventually determine organ decline, reduced cardiac function and death. The technological challenges emerging from the small size of heart as well as high-pace cardiac and respiratory rates, particularly in mice, for these MRI techniques have been tackled. MR techniques provide a noninvasive tool on the complete timeline of cardiovascular disease progression, ranging from delicate early energetic, vascular, inflammatory or fibrotic changes that frequently indicate disease onset towards severe myocardial dysfunction accompanying end-stage heart failure1. MR imaging and spectroscopy techniques play an important role in basic cardiovascular research and in cardiovascular disease diagnosis2 and regenerative therapy follow-up3. This is because a range of hallmarks in cardiovascular disease can be quantified by MR under in vivo conditions non-invasively. First, organ function of the heart has been measured by standard CINE MRI giving basic parameters of structure and function of the heart. Aside from this, tagging MRI offers quantitative, serial and non-invasive measurements of regional myocardial motion and deformation1,3. The energetic balance in the heart can be noninvasively probed with cardiac MR spectroscopic imaging techniques like 31P-MRI, quantifying ATP turnover kinetics in cardiac tissue. Vascular features in the heart have been measured with several techniques, including BOLD imaging and contrast-enhanced MRI4. Cardiac infiltration of inflammatory cells can be quantified by targeted or non-targeted nanoparticles using several MRI techniques. Finally, fibrosis in the heart has been assessed using several techniques including Chemical Exchange Saturation Trasfer5, and parametric cardiac mapping3,6.Thus, cardiac tissue characterization could help us understand the sequence of events and cardiac tissue changes in cardiovascular disease progression.

Acknowledgements

KV is supported by the Israel Science Foundation 446/21 and 660/21.

References

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Proc. Intl. Soc. Mag. Reson. Med. 30 (2022)