Project Details
Projekt
Non-invasive Monitoring of Hypertrophic Cardiomyopathy using Cardiac Magnetic Resonance Virtual Biopsy (cardiacMRBIOPSY)
Subject Area
Cardiology, Angiology
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 461017576
Currently HCM diagnoses are based on detecting an unexplained, large-scale left ventricular hypertrophy (LVH) through imaging. However, such changes are not unique to HCM, and imaging does not reveal underlying subclinical microstructural changes in myocardial remodeling that occur during the course of the disease. Observing such changes is important for making correct therapeutic decisions and monitoring the therapeutic efficacy. Cardiac MRI (CMR) could make a clear contribution for HCM management but currently has limited prognostic value, due to a lack of longitudinal data on microstructural changes and their progression during pathology. Potentially, CMR readouts can image early myocardial fibrosis, myofiber disarray, microvascular dysfunction and other features relevant to the disease. But these findings need to be temporally correlated with histological hallmarks of myocardial remodeling that are currently the gold standard for assessing HCM, to produce and validate predictive models that accurately characterize the disease. This proposal will conduct CMR-based “virtual biopsies” to track the kinetics of myocardial microstructural changes and to predict disease progression in animal models of HCM. We will test 3 hypotheses: 1) Myocardial microstructural changes can be detected by CMR (cardiacMRBIOPSY) and used as biomarker to assess the progression of HCM. 2) Application of machine learning (ML) approaches to systematic CMR measurements and critical histological markers will accurately predict the course of HCM. 3) Selected CMR biomarkers will be used to prospectively assess alterations in myocardial remodeling in response to experimental therapies, and then interpreted to determine the effectiveness of different therapeutic regimes. We aim to advance the field of CMR for imaging microstructural changes during HCM. We will gain new insights into measurable, early changes in CMR parameters that appear prior to macroscopic changes, with which earlier diagnostic methods of subclinical HCM can be developed in patients. We will investigate how the properties of myocardial tissue properties change over time in healthy and diseased animals, and correlate markers of CMR with myocardial fibrosis, myofiber disarray and microvascular dysfunction. We will apply a multimodal CMR approach to quantify intrinsic tissue-specific parameters. We will correlate these quantitative markers with comprehensive histological data, alongside an investigation of gene expression changes during HCM progression, to identify genes that are dysregulated in cardiac fibrosis and heart failure. We will apply innovative ML approaches to this systematic and longitudinal dataset to reveal new relationships between CMR markers and other parameters. We will use these findings to evaluate the effects of pharmacotherapies on HCM, as an example of a therapeutic intervention which can then be expanded to other types of treatments.
DFG Programme
Research Grants
International Connection
USA
Cooperation Partner
Christopher Nguyen, Ph.D.
