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IEMR in cross-disciplinary project on fibrosis

Fibrotic diseases represent a significant health problem, and research in this area has received very little attention until now. IEMR is now part of a new collaborative project across disciplines, aiming to improve the disease course and treatment outcomes for patients with fibrotic diseases.

The research project FibroPET is one of several convergence environments at UiO: Life Science. With expertise in medicine, physics, radiochemistry, radiopharmacy, and education drawn from the University of Oslo, Oslo University Hospital, and industry, the project ticks all the collaboration boxes.

“We come from different disciplines and environments, and we use different methods and designs in our research, but in this project, we have the same goal. We mutually benefit from each other, and the project evolves with each other’s contributions,” says project leader and professor of medicine Mona-Elisabeth Rootwelt-Revheim.

New understanding of the disease

Previously, it was believed that fibrosis is a passive end stage of chronic inflammation, but new treatment possibilities have recently been identified, and the first medications to reverse the fibrosis process have entered the market.

“Even though treatments exist, it is not appropriate to treat all patients once the diagnosis is made. If the risk of severe disease is low, we will be cautious about initiating aggressive treatment,” says Håvard Halland Fretheim, a rheumatology specialist and postdoc in the FibroPET Convergence Environment.

“Today, we lack methods to predict the disease’s progression. We can often assess the extent of organ damage at the moment, but in clinical practice, we lack tools to see which processes are active at the molecular level and thus know more about the patient’s prognosis,” Fretheim continues.

One of the research goals of the project is to identify patients developing fibrosis earlier using the molecular imaging technique PET (positron emission tomography). PET is a nuclear medicine technique that provides detailed three-dimensional images of molecular and functional processes in the body. By using PET markers, researchers can now see early signs of the disease and better predict how the disease will progress.

“With chronic inflammatory diseases like this, some patients develop fibrosis more easily than others. But today, we don’t know who does and who doesn’t. We want to distinguish those who develop fibrosis and those diseases that are more inflammatory. By using PET scans, we can tailor the treatment more to each individual patient,” says Rootwelt-Revheim.

From left: Håvard Halland Fretheim, Emil Espe and Mona-Elisabeth Rootwelt-Revheim.
"We can make fibrosis activity light up! With a PET scanner, we can count the flashes of light, and thus quantify fibrosis activity much earlier than with MRI or ultrasound."
Emil Espe

Counting flashes of light

But how does this happen, exactly? Physicist Emil Espe, a researcher at the Institute of Experimental Medical Research (IEMF) and one of the project leaders in FibroPET explains the process:

“We inject a substance containing PET markers into the patient. These substances have two very interesting properties: firstly, they are designed to accumulate where there is high fibrosis activity. Secondly, they are radioactive, which makes them ‘light up’ where they accumulate. In other words, we can make fibrosis activity light up! With a PET scanner, we can count the flashes of light, and thus quantify fibrosis activity much earlier than with MRI or ultrasound. We get a number we can track in the further development of the disease,” says Espe.

Stiff heart

Fibrosis can affect all organs in the body, and in some cases, multiple organs simultaneously. Research on cardiac fibrosis, known as “stiff heart,” is a key focus area for IEMR.

“We know surprisingly little about when and how cardiac fibrosis occurs, and how it can be treated,” says Espe.

In addition to work with PET markers where experiments are currently conducted on animal models, Espe and his colleagues at IEMF use tissue samples from diseased hearts to learn more about why and how the heart forms connective tissue and becomes stiff.

“We collaborate with cardiologists and thoracic surgeons at Rikshospitalet and examine diseased hearts before and after transplantation. Together with the Intervention Center, we perform tests on the heart while it is still in the patient, and as soon as the patient is offered a new heart, one of our researchers or medical students comes to retrieve the old heart. We are ready around the clock, all year round.

The tissue samples from these hearts, along with all the information around each patient, form a unique biobank for other researchers.

“Here, one of IEMR’s strengths also comes to the fore: as Norway’s largest translational environment for heart research, we have access to some of the best methods for in-depth research on disease mechanisms,” says Espe.

Communication and jargon

The average time from symptoms and signs of fibrosis disease to diagnosis is now more than three years. This may be due to a lack of knowledge in the population and among healthcare professionals, and therefore the work of conveying correct information to patients, healthcare professionals, and society is central to the project. By working together with educators from the Department of Educational Sciences at the University of Oslo, the goal is to ensure better patient communication and patient compliance.

“The educators observe how we communicate with the patients and the way we convey things. Proper communication is crucial for patients to take responsibility for their illness and treatment. Therefore, we need to figure out what we are doing right – and not right,” says Rootwelt-Revheim with a smile.

“We benefit greatly from becoming aware of the language we use, and especially from abandoning the worst jargon,” says Fretheim.

The goal of the convergence environments is to gather people who work a bit differently and outside their own niche.

“We often say that we work multidisciplinary when we pair a doctor with a physicist. But even though these individuals have different fields of expertise, they will still think quite similarly. By bringing in someone from the humanities, they have a completely different way of looking at the issues, and that challenges us. The convergence project involves a full integration of diverse expertise from researchers with different scientific backgrounds. This leads to further synergies where the effect of collaboration is greater than the sum of the individual contributions,” Rootwelt-Revheim concludes.