Pioneering work in the field of Neurotraumatology
Professor Olli Tenovuo is an experienced researcher and neurotraumatologist at the University of Turku and Turku University Hospital. Since 1996 he has led a multidisciplinary research group on traumatic brain injuries (TBIs). The research group focuses on blood-based brain injury biomarkers, novel brain imaging methods, and diagnostics and prognostic modelling of TBI, and his research group includes more than 40 researchers of diverse backgrounds from postdocs to medical students. He was one of the first researchers in Europe to receive the professorship in Neurotraumatology, with 30 years of experience working with patients with TBI.
Medicine was not Olli’s only choice when he applied for the university, and he had to choose between economy, chemistry, and medicine before he finally decided to become a doctor.
“I submitted my application to the School of Economics and School of Chemistry at Åbo Akademi in addition to Faculty of Medicine at University of Turku, and I was admitted to all of them. However, I chose Faculty of Medicine because I thought being a doctor would be the best choice to have an interesting job and I have always been interested in research maybe partly because my father was also a scientist.”
In his PhD, Olli studied the neurobiochemistry of Parkinson’s and Alzheimer’s disease, with Professors Urpo Rinne and Matti Viljanen as supervisors. Shortly after he finished the PhD, he was appointed as a rehabilitation neurologist at Turku University Hospital. During this work, he met patients with TBI and found them very fascinating and interesting as every patient was so different. He became interested in the heterogeneity of this disease, and thus, he established the research group in 1996 to study the pathophysiology of TBI and its mechanisms.
“We started a collaboration with neuropsychologist Raija Portin who had earlier collected a group of 200 patients with TBI. Raija had made accurate neuropsychological examinations and we wanted to see how these people were 20 years later, which kind of life they had and which kind of medical problems they had developed.”
The group has been growing ever since, and currently his research group includes more than 40 researchers of diverse backgrounds. The focus of the group during recent years has been blood-based brain injury biomarker development, novel brain imaging methods, and diagnostics and prognostic modeling of TBI. In 2019, Olli was appointed as the first Professor of Neurotraumatology in Finland and only the second one in Europe.
Active Blood-Based Biomarker Development in Turku
Olli sees the development of the biomarkers as important, and he believes that one day we will have clinical biomarker tests for TBI diagnosis. More specifically he thinks that we will have panels of biomarkers. Olli’s group has studied a variety of blood-based biomarkers, such as the neurofilament light, glial fibrillary acidic protein, UCH-L1, amyloid proteins, tau, IL-10, etc. But the progress to the clinics takes time because of the individuality of TBI, and because different pathophysiological mechanisms affect differently the levels of the biomarkers.
“There are few biomarkers that are brain specific. None of them is fully brain specific but are almost solely coming from the brain. But we don’t know well enough how the biomarkers from the brain enter the bloodstream. Leakage of the blood-brain barrier or glymphatic flow are obviously the main mechanisms.”
“Every biomarker has its own kinetic profile and TBI is a very dynamic injury. So, it does affect at which time points you will take the blood samples. Therefore, we have to measure these biomarkers at several time points in different types of injuries to understand their potential clinical use.”
The group is doing pioneering work with researchers Matej Orešič and Alex Dickens in the metabolomic biomarker development, small molecules, which can be seen as fingerprints of the events that are going on in the brain. They recently published a paper in Nature Communications indicating that metabolites circulating in the blood associate with TBI severity and potentially improve the prediction of patient outcomes (https://doi.org/10.1038/s41467-022-30227-5).
New Brain Imaging Techniques as Promising Diagnostic Tools
Although brain imaging techniques are routine as diagnostic tools for different neurological disorders, novel more accurate methodologies are still uncommon in the clinical setting of TBI. Nevertheless, conventional brain imaging using CT and, to some extent, MRI have been used along the other clinical and neuropsychological examinations in diagnosing TBI.
“The tools we are clinically using to diagnose TBI are not satisfactory, and there are several problems. By far the most common mechanism of TBI is diffuse axonal injury, but our conventional neuroimaging techniques cannot show this injury in the brain.”
Diffusion Tensor Imaging (DTI) could be a promising tool that might replace or be combined with other conventional ways of diagnosing TBI. Yet, the ongoing dilemma lies within setting cut-off criteria to compare the findings of each imaging device and identify the standards to interpret the results. To set these values, the data from a healthy population of different age groups are collected to identify the normal values and then compare them with patients’ results to decide on the abnormal ones.
“Using DTI in the clinical diagnosis of TBI is still very rare. In Finland, Turku University Hospital is the only one adopting this approach with certain cases, in addition to some other centers in Europe, such as Imperial College London.”
National and International Multidisciplinary Collaboration Unleash New Opportunities
Collaboration comes in the essence of the TBI research group, leading to several successful research outcomes nationally and internationally.
In Finland, Olli and his group have worked alongside researchers from the Turku PET Centre to study the mechanisms of the cholinergic system in TBI and the opportunities for developing cholinergic agents to treat patients, in addition to their collaboration with the researchers from BioCity to study the metabolomic biomarkers. Outside Turku, the group has worked with researchers from the Tampere University Hospital.
On the international level, Olli has mostly collaborated with researchers from the University of Gothenburg, the University of Cambridge, the University of Geneva, and with many US universities, among many others. One of the major projects the group is involved in is the CENTER-TBI study, which includes representatives from around 20 countries under the lead of Professor Andrew Maas from the University of Antwerp in Belgium and Professor David Menon from the University of Cambridge in the UK. This has been a prospective study collecting detailed information about the patients, their injuries, treatments, and outcomes.
“The challenges in the research are usually so great that you are not able to cope with them alone and we also need large patient populations. If samples are collected only locally, they might not be representative of the whole population. That is why we have tried to be internationally as active as possible.”
Olli also partnered with the University of Cambridge to study the genetic background of TBI to create a global Biobank with the blood samples of the patients, which could explain the vast variability of the prognosis. In the long-term, Olli desires, through his international partnership, to better identify TBI prognosis and how it could lead to the progressive deterioration witnessed in some patients and the role of neuroinflammation in the disease progress.
Clinical Career and Establishment of Turku Brain Injury Centre
Olli’s research career started from clinical interests and everything that the research group does, is somehow connected to the clinical dilemmas.
“One of the main challenges of the clinical care of TBI has been that the responsibility of these patients has been spread between many specialties and thus the patients often fall in between the healthcare system and as a result, nobody takes care of them. That has been recognized as a major problem also in international working groups more than 10 years ago and they suggested that multidisciplinary team should take care of these patients.”
To respond to this challenge, Turku University Hospital launched a project to create a national Brain Injury Centre for clinical care and research of TBI patients. Even though the national project did not succeed as such, the initiative led to the organizational change and establishment of the Brain Injury Centre within Neurocenter of Turku University Hospital. This kind of center is still pretty unique worldwide and the Centre was chosen as one of the Centers of Excellence in the hospital district when they were established in 2017. The main advantage of the Centre is that all medical doctors and nurses working with patients with TBI are educated so that the chain of care goes as optimally as possible. Olli acted as the head of the Brain Injury Centre since its establishment until his recent retirement from the hospital. From August 2022 onwards, Docent Jussi Posti was appointed as the Head of the Centre.
Future Research Topics and TBI New Classification
TBI severity is currently classified as mild, moderate, or severe, based on assessing the level of consciousness and the duration of post-traumatic amnesia. However, as the pathophysiological mechanism is different from one patient to another and the pathophysiology of these clinical measures poorly known, this current classification has caused the patients often more problems than benefits. Specifically, it is hard to properly assess the level of consciousness or amnesia in patients using traditional methods because the injuries are dynamic and full of several potential confounders.
Next year will be an important year as the international TBI community will have a meeting in Maryland, where a new classification of patients with TBI will be launched. The new classification will be based on the work of CENTER-TBI and TRACK-TBI (US counterpart of CENTER-TBI) projects and the aim is that the patients will be more accurately diagnosed into different pathophysiological groups.
“Basically, all pharmacological intervention studies have failed as we have lumped together all patients who have, e.g., severe TBI thinking they are the same, but there are so many different pathophysiological mechanisms, that the patients haven’t benefited from the intervention as a whole. When we can classify the patients more accurately, we are able to get this field further and develop targeted therapies for different types of patients.”
Outside Work and Academia
Although Olli has spent a major part of his time working either in the hospital or in his research, he has also tried to find some time whenever possible to practice his hobbies. Since his teenage years, he has been interested in birdwatching and taking photos of them. Olli’s father was an ornithologist and Professor of Biology at the University of Turku, so it wasn’t strange for Olli and his brother, who is also a birdwatcher and photographer, to inherit that and follow their father’s steps.
“I can spend more time watching birds now after my retirement from the hospital, so I don’t have a problem to think what to do now with my spare time or even after retiring from research. I also like giving my time to my grandchildren.”