Contrasted Magnetic Resonance: New Imaging Tool as Noninvasive Alternative for Detection of Myocardial Changes to Assess Myocardial Fibrosis

• Grant number: 23/08659-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2024
• End date: February 28, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Radiology
• Principal Investigator: Carlos Eduardo Rochitte
• Grantee: Telma Mary Nakata
• 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

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 existance 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 congestive symptoms which is the leading cause of hospitalization of these patients. The basis of changes in diastolic function are related to excessive deposition of collagen fibers in the extracellular matrix. To the present moment, no specific therapeutical approach to avoid excessive collagen deposition has shown satisfatory 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 cardiac MR utilizing a new contrast agent based in nanoparticle, usTiO2NP, can detect early myocardial fibrosis deposition when compared to gadolinium-based contrast which is routinely used in clinical MR. Contrasted CMR using a paramagnetic nanoparticle is a new promissing method under research which targets the association of 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 pathological process. Therefore, the present study is an initial approach to stablish basis for molecular imaging using CMR to understand deeply the pathophysiology related to the HFPEF progression, and validate proofs of concept providing the background of this project. Specific objectives are: (1) Utilize a paramagnetic nanoparticle based contrast agent, usTiONP, to demonstrate cardiac fibrosis in HFPEF experimental model; (2) validate the new contrast agent by the detection of injured myocardium enhancement in comparison with the conventional gadolinium-based contrast at distinct phases of disease progression; (3) Correlate CMR imaging markers described in (2) with changes in hemodynamics and myocardial structure detected in echocardiography and histology. This study may lead to advances in early detection of changes in the myocardial tissue which might demonstrate accurately diastolic dysfunction through a non-invasive method through validation and lead to identification of an original imaging tool as clinical strategy with translational potential, providing data for patent registration.