Clinical Translation & Applications of Molecular MRI in Cardiovascular Diseases
René Botnar1

1King's College London, United Kingdom

Synopsis

Molecular magnetic resonance imaging (MRI) is a promising tool to detect molecular and cellular changes in the carotid, aortic and coronary vessel wall including endothelial dysfunction, inflammation, vascular remodelling, enzymatic activity, intraplaque haemorrhage and fibrin deposition and thus may allow early detection of unstable lesions and improve the prediction of future coronary events. To increase the biological information obtained by MRI a variety of targeted-specific molecular probes have been developed for the non-invasive visualisation of particular biological processes at the molecular and cellular level. This presentation will discuss recent advances in molecular MRI of atherosclerosis, covering both pulse sequence development and also the design of novel contrast agents, for imaging atherosclerotic disease in vivo.

Cardiovascular disease (CVD) remains the leading cause of death in Western countries despite improvements in prevention, diagnosis and treatment. The majority of CVD death is caused by atherosclerosis which is a chronic inflammatory disease that remains clinically silent for many decades. Sudden rupture of “high-risk/vulnerable” plaques has been shown to be responsible for the majority of acute cardiovascular events, including myocardial infarction and stroke. Therefore, early detection of biological processes associated with atherosclerosis progression and plaque instability may improve diagnosis and treatment and help to better monitor the effectiveness of therapeutic interventions. Molecular magnetic resonance imaging (MRI) is a promising tool to detect molecular and cellular changes in the carotid, aortic and coronary vessel wall including endothelial dysfunction, inflammation, vascular remodelling, enzymatic activity, intraplaque haemorrhage and fibrin deposition and thus may allow early detection of unstable lesions and improve the prediction of future coronary events. Evaluation of atherosclerosis at both, the preclinical and clinical level includes non-contrast-enhanced (NCE) and contrast-enhanced (CE) MRI with and without the use of MR contrast agents. To increase the biological information obtained by MRI a variety of targeted-specific molecular probes have been developed for the non-invasive visualization of particular biological processes at the molecular and cellular level. This presentation will discuss the recent advances in molecular MRI of atherosclerosis including post infarct myocardial remodelling, covering both pulse sequence development and also the design of novel contrast agents, for imaging atherosclerotic and myocardial disease in vivo.

Acknowledgements

No acknowledgement found.

References

1. Abubakar I, Tillmann T, Banerjee A (2015) Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 385:117-171 doi:10.1016/S0140-6736(14)61682-2

2. Weber, C. & Noels, H (2011) Atherosclerosis: current pathogenesis and therapeutic options. Nature medicine 17, 1410-1422, doi:10.1038/nm.2538 .

3. Stone, G. W. et al (2011) A prospective natural-history study of coronary atherosclerosis. The New England journal of medicine 364, 226-235, doi:10.1056/NEJMoa1002358

4. Caravan, P., Ellison, J. J., McMurry, T. J. & Lauffer, R. B (1999) Gadolinium(III) Chelates as MRI Contrast Agents: Structure, Dynamics, and Applications. Chemical reviews 99, 2293-2352

5. Kooi, M. E. et al (2003) Accumulation of ultrasmall superparamagnetic particles of iron oxide in human atherosclerotic plaques can be detected by in vivo magnetic resonance imaging. Circulation 107, 2453-2458, doi:10.1161/01.CIR.0000068315.98705.CC

6. Lancelot, E. et al (2008) Evaluation of matrix metalloproteinases in atherosclerosis using a novel noninvasive imaging approach. Arteriosclerosis, thrombosis, and vascular biology 28, 425-432, doi:10.1161/ATVBAHA.107.149666

7. Makowski, M. R. et al (2011) Assessment of atherosclerotic plaque burden with an elastin-specific magnetic resonance contrast agent. Nature medicine 17, 383-388, doi:10.1038/nm.2310

8. Phinikaridou, A. et al (2012) Noninvasive magnetic resonance imaging evaluation of endothelial permeability in murine atherosclerosis using an albumin-binding contrast agent. Circulation 126, 707-719, doi:10.1161/CIRCULATIONAHA.112.092098

9. Noguchi, T. et al (2014) High-intensity signals in coronary plaques on noncontrast T1-weighted magnetic resonance imaging as a novel determinant of coronary events. Journal of the American College of Cardiology 63, 989-999, doi:10.1016/j.jacc.2013.11.034

Figures

Molecular imaging require several ingredients including target identification and development of novel imaging probes, pulse sequences, image processing techniques and finally pre-clinical and clinical validation.

Spectrum of cardiovascular diseases that may benefit from molecular imaging.

Examples of molecular imaging probes for the early detection of biological processes associated with atherosclerosis.

Example of molecular imaging probes for the assessment of post infarct myocardial remodelling.

Proposed technical advances to allow for clinical translation of molecular imaging.

Proc. Intl. Soc. Mag. Reson. Med. 26 (2018)