Genetics and Imaging

What we do

Genetics and imaging are highly synergistic with each other as genotyping and phenotyping are two signs of a coin. High quality phenotyping can greatly clarify the genetic causation of disease. Accurate genotyping can likewise allow the definition of the clinical phenotype. In this is section we use cutting edge technology in our research to tackle the latest barriers in healthcare. We seek to understand the genetic basis of cardiovascular disease in order to both reveal disease mechanisms, thereby identifying new therapeutic targets, and to interpret genomic information for application in the clinic. 

Our imaging work is mainly based around cardiovascular magnetic resonance (CMR), nuclear medicine, cardiac CT and echocardiography. We aim to gain a better understanding of cardiac disease so that we can develop appropriate treatments tailored to the needs of individual patients. We investigate and implement prevention strategies in cardiovascular medicine, particularly in conditions such as cardiomyopathy, congenital heart disease, and coronary disease.

Our research involves the integration of genome data with cutting-edge phenotypic characterisation. Using CMR, we are determining the nature of the 3-dimensional architecture of the heart using diffusion tensor imaging, as well as applying machine-based image processing and quantitative multi-dimensional feature extraction techniques, transciptomics and translatomics, and other large data sets including electronic health records, to make new insights into human disease. 

Why it is important

Genetics and imaging are highly synergistic with each other as genotyping and phenotyping are two signs of a coin. High quality phenotyping can greatly clarify the genetic causation of disease. Accurate genotyping can likewise allow the definition of the clinical phenotype. In this is section we use cutting edge technology in our research to tackle the latest barriers in healthcare. We seek to understand the genetic basis of cardiovascular disease in order to both reveal disease mechanisms, thereby identifying new therapeutic targets, and to interpret genomic information for application in the clinic. 

Our imaging work is mainly based around cardiovascular magnetic resonance (CMR), nuclear medicine, cardiac CT and echocardiography. We aim to gain a better understanding of cardiac disease so that we can develop appropriate treatments tailored to the needs of individual patients. We investigate and implement prevention strategies in cardiovascular medicine, particularly in conditions such as cardiomyopathy, congenital heart disease, and coronary disease.

Our research involves the integration of genome data with cutting-edge phenotypic characterisation. Using CMR, we are determining the nature of the 3-dimensional architecture of the heart using diffusion tensor imaging, as well as applying machine-based image processing and quantitative multi-dimensional feature extraction techniques, transciptomics and translatomics, and other large data sets including electronic health records, to make new insights into human disease. 

Why it is important

Inherited cardiac conditions affect more than 600,000 patients in the UK (~1% of the population) with up to 13,000 new referrals every year. Cardiomyopathies alone are the commonest cause of sudden death in the young, and the leading cause of heart transplantation. Understanding the genetic basis of these diseases is vital to management of the patient and their family, as the familial inheritance pattern typically results in a 50% risk for first degree relatives. Accurate genetic analysis is key for diagnosis, and for 21st century precision medicine. 

We use the different imaging modalities to look at diverse patient problems and each technique has particular research strengths. With our research, we help to develop new treatments for patients. The research 3T magnet at Royal Brompton Hospital is a valuable asset allowing us to work in completely novel areas such as the microstructure of the heart with diffusion tensor imaging.

Impact of our research

• Reduction in mortality in thalassaemia major of over 70 per cent using T2* CMR to measure when myocardial iron levels are raised.
• Identification of pathognomonic patterns to myocardial fibrosis in cardiomyopathies.
• Discovery that the extent of myocardial fibrosis predicts cardiac events in dilated cardiomyopathy and can be used as an indication to implant a defibrillator.
• Incorporation of many CMR findings into international guidelines for patient management.
• Recent advances in DNA sequencing technologies, medical imaging, and data science have enabled us to uncover new insights into cardiac disease, and to provide new tools and resources for genome interpretation.
• New theory to explain myocardial dysfunction in hypertrophic and dilated cardiomyopathy, identifying titin as a cause of ~25% of dilated cardiomyopathy, and identifying fibrosis in the right side of the heart in congenital heart disease to predict sudden death in the future.
• Identification of the giant gene Titin as the single most important cause of dilated cardiomyopathy (DCM) (see Titin publications and press coverage), and recognition that Titin mutations affect the hearts of 1% of the population (read article on Imperial News).
• Redefining the genetic architecture of cardiomyopathies, including dilated, hypertrophic, arrythmogenic, and peripartum (pregnancy-related) cardiomyopathies.
• Participation in the Exome Aggregation Consortium to produce the largest human genomic reference dataset in the world as reported in Nature.
• Development of a comprehensive DNA sequencing panel for inherited cardiac conditions, for research and clinical application.
• Developing widely-used software and web-resources for clinical genome interpretation.

Summary of current research

• Defining the 3-dimensional architecture of the normal heart using diffusion tensor CMR -Pennell
• Applying diffusion tensor CMR in inherited cardiac conditions to distinguish phenotypes and uncover new mechanisms of myocardial dysfunction
• Developing new CMR sequences to improve diffusion tensor CMR - Firmin, Nielles-Vallespin
• Identifying genes and variants that cause inherited cardiac conditions -Prasad, Ware, Cook
• Interpreting genetic variation in order to discriminate rare benign genetic polymorphisms from pathogenic mutations - Ware, Cook
• Translating “Next-Generation Sequencing” (NGS) technologies for molecular diagnosis - Ware, Cook
• The role of titin (TTN) in cardiomyopathy and interaction of titin with second environmental factors in disease manifestations (e.g. alcohol) - Ware
• The use of echocardiography in assessment of stem cell treatment - Nihoyannopoulos, Senior
• Nuclear Medicine in inflammatory cardiac conditions such as sarcoidosis - Underwood
• Cardiovascular CT scan in coronary artery disease - Nicol
• Artificial intelligence based fast imaging and analysis for cardiovascular disease - Yang

View a selection of publications from the Genetics and Imaging Section

Our researchers