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Small blood vessels may reveal serious illness

Can changes in the tiniest branches of our cardiovascular system help doctors detect and prevent a number of diseases decades before they become serious?

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Monika Colombo develops detailed computer simulations of the human cardiovascular system and studies it from a mechanical perspective. She maps the fluid dynamic factors that influence the development of diseases and she hopes that she can help pave the way for better prevention, diagnostics and treatment. (Photo: AU Nicolai Hildebrand)
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A piece of 3D-printed in vitro model of the body's microvascular circulation. (Photo: Monika Colombo)

29-year-old Monika Colombo has come to Aarhus University with an interesting hypothesis. She develops computer models of the body's blood circulation and the tiny ends of the capillaries, and she is on the trail of knowledge that may be a breakthrough for heart research.

"I use clinical images to build computer models of our blood vessels, and then I study cardiovascular interactions from a mechanical perspective. I’m looking particularly at what characterises fluid dynamics, and it appears that this will provide a new perspective on known pathological issues," she says.

Monika Colombo has just been employed in a tenure-track position at the Department of Mechanical and Production Engineering at Aarhus University, where she will continue her work to develop a new form of diagnostics.

"In many ways, Denmark is a leader in heart research, and in collaboration with clinicians here in Aarhus, I want to produce precise simulations of cardiovascular dysfunctions in humans. This will give us a new understanding of diseases and new opportunities to prevent and treat them," she says.

A new path for research into heart disease

Since her PhD dissertation in bioengineering from Politecnico di Milano, Monika Colombo has worked with the tiny microvascular changes that could eventually lead to serious diseases such as blood clot (thrombosis), heart valve damage, hardening of the arteries (arteriosclerosis), brain haemorrhage (stroke) and sudden cardiac arrest.

"These diseases develop over many years, and today we have very little chance of discovering them before they cause symptoms or permanent injury. We don’t know much about what’s going on at microvascular level, and I’m entering unexplored territory with my research. It's all new, and I'm relatively alone," she says.

As part of her experimental work, Monika Colombo is reconstructing the human cardiovascular system with its branches of arteries, arterioles and small capillaries using clinical images. Afterwards she fabricates or prints her models in 3D to be able to verify their accuracy.

"This means that we can now model various defects in the cardiovascular system and study them from a mechanical perspective and not just from a physiological or biological perspective. We can study flow, permeability, pressure and characteristics of the body's smallest blood vessels, and thereby discover the molecular and cellular changes that form the basis for different types of disease development. This may pave the way for more nuanced pathology and a completely new type of diagnostics," she says.

The dream of better diagnostics

We do not currently have equipment that is sensitive enough to measure what happens in the body's small blood vessels. It is therefore virtually impossible for doctors to detect or treat the microvascular changes that will eventually lead to serious illness.

Coronary microvascular dysfunction is one of the diseases that Monika Colombo uses as a case in her experiments. The condition primarily affects women, and it is caused by a weakening of the body's endothelial cells, which are crucial for healthy circulation. The cells produce a substance that makes blood vessels flexible and elastic and helps transport nutrients and waste products between cells in the body and the bloodstream. The symptoms are chronic chest pain, and in the long term the dysfunction can become fatal, but it is very difficult for clinicians to diagnose and therefore treat.

"Clinicians simply have no chance of discovering the dysfunction using the technology they have at their disposal today," says Monika Colombo.

But what doctors cannot diagnose at hospitals, Monika Colombo can see on her computer simulations, where the hermodynamic changes are clearly expressed at microvascular level.

"The heart pumps oxygen-rich blood around in a network of veins and arteries and oxygen-poor blood flows back to the heart. In our modelling of the disease, we can observe changes in the biomechanical interaction between particles in the blood circulation and in the backflow through the capillaries. My basic idea is to try to understand how these changes occur, and how they lead to disease progression over time," she says.

In the long term, Monika Colombo hopes that she can use her knowledge from computer simulations, mechanical engineering and biochemistry to develop a screening tool that can predict and prevent cardiovascular diseases by means of non-invasive imaging and a simple blood sample.

Contact

Monika Colombo, Tenure Track assistant professor, Department of Mechanical and Production Engineering