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AI answers da Vinci heart mystery

Structures first described by the Renaissance artist Leonardo da Vinci 500 years ago have been found to be crucial in our understanding of how the heart works.

An international team of cross-disciplinary researchers, led by the Medical Research Council (MRC) London Institute of Medical Sciences, based at Imperial College London, is the first to show how a complex mesh of muscle fibres that line the inner surface of the heart play a vital role in its function by increasing the efficiency of blood flow through the organ. The team hopes the findings, published in the journal Nature, could help to identify those most at risk of heart failure, one of the leading causes of death worldwide, and inform research into new treatments for the disease.

The study, funded by the MRC with additional support from the British Heart Foundation and Wellcome, used artificial intelligence (AI) to analyse 25,000 MRI scans of the heart from the UK Biobank study. The scans reveal the intricate structure of these muscle fibres and allowed researchers to investigate their role in heart function.

The findings show how these muscles called ‘trabeculae’ form a repeating geometric pattern known as a fractal, which is seen in other structures from trees to snowflakes, and which helps us to understand their function in the heart.

Da Vinci was the first to sketch these muscles in the 16th Century, speculating at the time that they warm the blood as it flows through the heart, however their true importance has not been recognised until now.

These new findings show how this intricate meshwork of muscle fibres, that cover the internal surface of the heart’s chambers, are critical to the performance of the heart. The research suggests that these fibres allow blood to flow more efficiently during each heartbeat just like the dimples on a golf ball help it to travel further through the air.

Dr Declan O’Regan from the MRC London Institute of Medical Sciences, and leader of the study, said: “Leonardo da Vinci sketched these intricate muscles inside the heart half a millennium ago, and it is only now that we are beginning to understand how important they are to human health.

“Da Vinci was also intrigued by the link between maths and nature, so it’s fitting that we found that fractal patterns in the heart are so important for its function. This work

offers an exciting new direction for understanding the heart and shows the potential for bringing together ideas in maths and biology to medical research”.

The study also discovered six regions in our DNA that affect how the fractal patterns in these muscle fibres develop. Intriguingly, the researchers found two of these genes also regulate branching of nerve cells, suggesting a similar mechanism at work in the developing brain as well as the heart.

The researchers found that trabeculae may influence the risk of heart disease. Using genetics to analyse data from 50,000 patients, they found that different fractal patterns in these muscles affected the risk of developing heart failure. It is hoped this will enable future research on the disease, which currently affects around 920,000 people in the UK [BHF Statistics Factsheet 2020].

Dr O’Regan said: “This network of muscles lies between fast-flowing blood inside the heart and the contracting heart muscle. The next steps for our research are to understand how these fibres affect the ‘aerodynamics’ of blood flow in the heart and how this might inform research into new treatments for heart disease.

“We also found that these fibres influence how fast electrical impulses travel through the heart – so they may be important for more than one aspect of how the heart works.”

Dr Hannah Meyer, who collaborated with Dr O’Regan on the study from the Cold Spring Harbor Laboratory in the US, added: “Our work significantly advanced our understanding of the importance of myocardial trabeculae. But perhaps even more importantly, we also showed the value of a truly multi-disciplinary team of researchers.

“Only the combination of quantitative genetics, clinical research and bioengineering led us to discover the unexpected role of myocardial trabeculae in the function of the adult heart.”

Ewan Birney, Deputy Director General of the Laboratory "EMBL's European Bioinformatics Institute (EMBL-EBI)", who also collaborated on the study, said: “Our findings answer very old questions in basic human biology. As large-scale genetic analyses and artificial intelligence progress, we’re rebooting our understanding of physiology to an unprecedented scale.”

Dr Ivan Pavlov, Programme Manager at the Medical Research Council, which funded the study, said: “This is a fascinating example of a truly interdisciplinary study that combines genetics, imaging, biomechanics, mathematics, big data and AI to discover a new unexpected function of a structure in the human heart.

“The findings may explain some of the known associations in the risk of cardiovascular disease, and what’s more, may provide new insights into how a basic regulatory mechanism could contribute to the function of other organs.”

More research is now needed on these intricate muscles inside the heart, with the hope this could lead to new directions for understanding how common heart diseases develop and how they are treated.

Article: UKRS Medical Research Council - 19 August 2020


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