PET-CT scans that show exactly in which joints macrophages are active or where new medicines take effect in the body. These are new developments in rheumatism research. Currently, these techniques are still in the research phase. But as far as professor of rheumatology Conny van der Laken (Amsterdam UMC) is concerned, this imaging technology is also promising for clinical practice in the future. In this interview she gives us an insight into her fascinating field of work.
On April 1, 2022, Van der Laken was appointed professor of rheumatology, in particular imaging in diseases of the musculoskeletal system. On November 25, 2022, she delivered her inaugural lecture at VU University Amsterdam entitled ‘Seeing more by looking further’. The approach of her research is to use imaging technology, such as PET-CT, MRI and ultrasound, for the early diagnosis of rheumatic diseases and for the development of tailor-made therapy. In addition, she uses imaging techniques for pathogenetic research in rheumatic diseases and for the development of new therapeutic agents. Finally, she compares different imaging techniques with each other. With this she wants to investigate which imaging techniques are most suitable to answer certain questions from clinical practice.
Early diagnosis
Van der Laken studies which cells and proteins play a role in the early phase of rheumatic diseases. For this she uses the PET-CT technique in combination with specific marker substances. “The most commonly used marker substance in PET-CT is fluorodeoxyglucose (FDG). This glucose derivative is mainly taken up in tissues with an increased metabolism, such as inflammation or tumours. For our research, we have developed marker substances that specifically target different components of the immune system, such as macrophages, B cells or the cytokine TNF-α. A radioactive label is attached to the marker substances. If they bind to their target in the body, we can visualize this on a PET-CT scan. In this way we can visualize very specifically, at a molecular level, where the inflammatory cells or inflammatory proteins are active in the body. This technique is fundamentally different from, for example, MRI or ultrasound, where you study anatomical changes at the tissue level.”
A physical examination or in the blood often shows nothing in an early phase of rheumatism. The PET-CT scan, with the specific marker substances, can already detect abnormalities. The advantage of a PET-CT scan is that you photograph the entire body. “That way you can not only look at the joints, but also at all organs, blood vessels and mucous membranes. In this way you not only collect information about which immune cells and substances play a role in an early phase of rheumatism, but also where in the body this process takes place.”
Customized therapy
PET-CT in combination with specific markers can also play a role in the development of tailor-made therapy. “If you know which cells or cytokines are active in a specific patient, you can also determine which form of therapy best suits this. For example, do you give rituximab because someone has a B-cell-driven disease or a TNF-α blocker because macrophages are mainly involved in the disease process? We can also investigate that with this technique.”
pathological mechanisms
The researchers often also take a biopsy of the abnormalities on the PET-CT scan. With this they collect more information about the underlying pathological mechanisms of the condition. “In a biopsy we can look at the entire setting. For example, if we see on the PET-CT scan that TNF-α is active in a tissue, we can find out in the biopsy what else is going on in that tissue. In this way we want to discover new targets that are expressed in the affected tissues. That in turn helps us to develop new diagnostics and therapeutics.”
Testing drugs
Finally, Van der Laken also uses the PET-CT technique to test the effectiveness of new medicines in collaboration with pharmaceutical companies. “We link a radioactive label to the medicine and inject it into a patient. This way we can see whether the drug actually ends up in the right place in the body. We do this in the context of scientific research.”
Algorithms and Artificial Intelligence
The PET-CT technique is still expensive and, due to the radioactively labeled marker substances, has radiation exposure. In addition, specific expertise is required to read the images. Before the technology can be used for regular patient care, a number of developments are still needed. “A recent development is that PET-CT scanners are scanning faster and more sensitively. As a result, the radiation exposure decreases and the applicability in clinical rheumatology practice increases. In addition, I do not expect that PET-CT scans will be required for all questions asked by rheumatic patients. Based on clinical and laboratory findings, I want to develop algorithms with which I can determine the place of additional PET-CT scans in subgroups of rheumatic patients. Finally, I want to investigate how artificial intelligence (AI) can help read the scans. At the moment we draw all the spots that light up on a PET-CT scan by hand on the computer and measure how active the disease is. This is very labour-intensive, especially if there are many deviations or if you take several consecutive measurements over time. In order to measure faster and more accurately in healthcare, we want to train computers to recognize and quantify those spots on the scans. We will be working on that for the next 3 years. We start with measurements in patients with spondyloarthritis (SpA). If that works well, we want to expand the technique to other rheumatic diseases.”
Compare techniques
Van der Laken’s research group has unique expertise in the field of PET-CT scans. However, this does not mean that this is the only imaging technique she focuses on. “In the coming years I also want to focus on determining the position of the various imaging techniques. I often get the question from the field: ‘With which imaging technique can I best answer the question I have about my patient?’ For some questions this is very clear. But sometimes it is also a bit of trial-and-error and you have to try several techniques before you have an answer. I see it as a mission for my group to clarify this with comparative studies.”
An example is the monitoring of patients with vasculitis of the great vessels. “If people still have complaints after we have treated them, we often don’t really know why. At the moment we also do not yet know how we can map out any remaining inflammatory processes. Is that with PET-CT, MRI or ultrasound? I would like to find out.”
Added value
Van der Laken is convinced that imaging technology can have added value, both for diagnosis and for monitoring therapy in various rheumatic diseases. “Ultimately, I want to use the developments we are currently working on in research to improve rheumatological care. And that for a whole range of rheumatic diseases.”
The different imaging techniques in rheumatology
How are the different imaging techniques currently applied in rheumatology practice? And what developments are there in the field of scientific research?
Positron Emission Tomography Computed Tomography (PET-CT)
In current rheumatology practice, doctors mainly use a PET-CT scan in the following situations:
- in diagnostic dilemmas where whole-body imaging has additional value;
- in case of unexplained elevated erythrocyte sedimentation rate or fever;
- in case of suspicion of – and monitoring of – large vessel vasculitis or other systemic inflammation;
- in case of suspected malignancy.
In the context of scientific research, doctors and researchers study the role PET-CT can have in early diagnosis, the prediction of therapy outcomes and the development of tailor-made therapy for various rheumatic inflammatory diseases such as rheumatoid arthritis (RA) and spondyloarthritis (SpA) .
Diagnostic computed tomography (CT) is mainly used for high-resolution imaging of abnormalities in bone and cartilage structures.
Magnetic Resonance Imaging (MRI)
MRI offers possibilities for diagnostics of pathology in soft tissue, bone and cartilage. MRI is often used in the diagnosis of SpA. Scientific research focuses on the question of whether MRI has added value in the early diagnosis and monitoring of RA and SpA. In addition, researchers are studying the role of whole-body MRI in, among other things, the detection of myositis.
Ultrasound
Many rheumatology practices already use low-threshold ultrasound to assess the presence of inflammation and other pathology in soft tissues, particularly in the synovium of joints. Ultrasound also allows the rheumatologist to assess erosions and the presence of crystals in joints. Scientific research is investigating whether ultrasound also has added value in the early diagnosis and monitoring of RA and peripheral SpA.
Register participants for research
Studies are currently underway on the value of PET-CT for the:
- early diagnosis of rheumatoid arthritis (RA) in anti-CCP-positive arthralgia patients;
- prediction of therapy outcomes in RA patients starting anti-TNF;
- early diagnosis and prediction of therapy outcomes in patients with psoriatic arthritis or Bechterew’s disease.
Do you have a patient who you think could benefit from early stage imaging or rheumatoid treatment? Then consult Prof. van der Laken (j.vanderlaken@amsterdamumc.nl) about the possibilities for participation in research.