Contrasted Magnetic Resonance: New Imaging Tool as Noninvasive Alternative to Detect Myocardial Changes in the Assessment of Cardiac Fibrosis

• Grant number: 23/09574-1
• Support Opportunities: Regular Research Grants
• Duration: May 01, 2024 - April 30, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Radiology
• Principal Investigator: Carlos Eduardo Rochitte
• Grantee: Carlos Eduardo Rochitte
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Khallil Taverna Chaim ; Maria Concepción García Otaduy

Abstract

Cardiac magnetic resonance is a unique method due to its ability to provide several imaging modalities to determine the prognosis through myocardial viability assessment with predictive value for future cardiovascular events. In this scenario, disease staging by sequential imaging using more specific CMR modalities is not long-established. Recently, advances in studies of heart failure showed the importance of cardiac diastolic dysfunction and determined the existence of another form of heart failure with preserved ejection fraction. In heart failure with preserved ejection fraction (HFPEF), the left ventricular diastolic function is reduced as result of impaired myocardial compliance and increased ventricular filling pressures. These changes are also responsible for the development of congestive clinical signs which are the leading cause of hospitalization of these patients. The changes in diastolic function are based in the excessive deposition of collagen fibers in the extracellular matrix. To the present moment, no specific therapeutic approach to avoid excessive collagen deposition has shown satisfactory results. New researches suggested that the presence of cross-linked collagen fibers might be the reason of reduced response to the treatment. The broad question of this study is whether sequential imaging using contrasted CMR through enhancement by a new molecule of iron oxide-based contrast agent can detect early changes when compared to gadolinium-based agent which is routinely used in clinical CMR. Contrasted CMR using superparamagnetic iron oxide nanoparticle is a new promissing method under research which targets therapy and diagnosis, known as theranostic nanomedicine. Specific proteins expression in the tissue in which collagen production and cross-linking are increased may function as biomarkers and be tracked during the pathophysiological process. Therefore, the present study is an initial approach to stablish basis for imaging using CMR to understand deeply the pathophysiology mechanisms related to the HFPEF progression, and validate proofs of concept providing the background of this project. Specific objectives are: (1) Construct a contrast with superparamagnetic iron oxide-based nanoparticle to demonstrate cardiac fibrosis in HFPEF experimental model; (2) validate the new contrast agent by the detection of injured myocardium enhancement using the iron oxide-based contrast agent in comparison with the conventional gadolinium-based contrast at distinct phases of disease progression in experimental model; (3) Correlate CMR imaging markers described in (2) with changes in cardiac function detected in echocardiography and histology. This study may lead to advances in detection of early changes in the myocardial tissue which might demonstrate accurately diastolic dysfunction through a non-invasive method and lead to identification of an original imaging tool with translational potential. (AU)