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Here you can read about everything that's happening in the ISB Group.

New students!

Uncategorised Posted by ISB GroupPosted on Tue, April 14, 2020 14:02:36

We have several master-thesis and internship students working in our group this spring. Here is a small introduction!

Gustav Magnusson
I’m a master student in Physics with a hope to contribute something to the world of Systems Biology. The aim of my master thesis is to work with the Digital Twin, to put together the various models produced here at ISB to form an interface for users such as patient and researchers to test various situations and hypothesis. The goal is also to work on my own model which could be a part of the Digital Twin, perhaps with focus towards phyisical training, atherosclerosis or the immune system.

Lucas Raihle
Hi! I’m Lucas and I will be interning at ISB group during March-September. My project will revolve around making a model that can describe how diet affects the progression of NAFLD (non-alcoholic fatty liver disease). NAFLD is the most common liver disease in the world and is heavily correlated with the metabolic syndrome. Understanding the progression of NAFLD could lead to more effective forms of treatment and diagnosing. I’m happy to join this group and excited to start my project.

Johanna Hansson
Hi, my name is Johanna Hansson and I have just started an internship at ISB group. I will be working on a project to describe the disease progression of atherosclerosis to stroke and how the consequential oxygen loss affects the brain function. First, I will develop a mechanistic atherosclerosis model and later connect it with existing models of e.g. blood flow and stroke. Understanding atherosclerosis and its relationship with stroke could help predict who is at risk of having one. With that knowledge, we may be able to prevent the stroke from happening and save lives. I will work on my project for 6 months and I am excited to see the result!

Jonatan Baggman
Hi! My name is Jonatan and I’m doing my master thesis here at ISB group this spring. For my master thesis I’m looking into imputations for the Digital Twin, how to estimate the input values which are not measured directly from the patient. I will look into different methods of imputation and will compare these. Hopefully, I will be able to present how to make the Digital Twin personalized without measuring all values from the patient!



Ph.D. defense of Markus Karlsson: MRI-based modelling of liver function

Events Posted by Gunnar CedersundPosted on Thu, January 30, 2020 11:26:55
Markus preparing for his Ph.D. defense.

Today there is a new Ph.D. defense in ISB group: that of Markus Karlsson. Markus has been working with usage of magnetic resonance imaging techniques to characterize the liver, and the formal title of the Ph.D. thesis is: “Non-Invasive Characterization of Liver Disease – by multimodal quantitative magnetic resonance”. Various techniques have been tested, MRS-PDFF (to measure liver fat), T1 relaxation (to estimate fibrosis), R2* (to estimate iron in the liver), etc. In three of the papers (Paper 1,2 and 4), normal MRI analysis has been done in different patient cohorts, and in two of the papers (Paper 3 and 5), mathematical modelling has been done in collaboration with ISB group. More specifically:

Paper 1 established a relationship between R2* and MRS-PDFF, and saw that liver fat distorts the R2* signal with about one R2* unit per MRS-PDFF unit. This could be used to device a simpe correction method when using R2* to estimate liver iron levels.

Paper 2 looked at the relationship between T1 and liver fibrosis in a cohort of approximately 100 patients with various degrees of diffuse liver disease, ranging from no fibrosis to cirrhosis. In the literature, different degrees of connection between T1 and liver fibrosis have been reported, and this paper unfortunately supports the conclusion that there is low correlation.

Paper 3 was the main paper deviced by us:

Model-inferred mechanisms of liver function from magnetic resonance imaging data: Validation and variation across a clinically relevant cohort. Forsgren MF, Karlsson M, Dahlqvist Leinhard O, Dahlström N, Norén B, Romu T, Ignatova S, Ekstedt M, Kechagias S, Lundberg P, Cedersund G. PLoS Comput Biol. 2019 Jun 25;15(6):e1007157.

In this paper, the data consists of DCI-MRI data, i.e. dynamic MRI images which have been enhanced by the contrast agent gadoxetate, which has been injected into the arm at the beginning of the time-series. By combining this data with a previously developed compartment transport model, we could estimate reliable uptake rates into the liver for all patient groups. Furthermore, in this paper we also showed that these estimated uptake rates, only accesible using the model, serve as new useful biomarkers for estimating liver function and fibrosis. In this paper, we also demonstrated how nonlinear mixed-effects modelling could be used to simplify the currently used protocol, to save money and time in the clinic.

Paper 4 looked at the relationship between magnetic resonance cholangiopancreatography (MRCP) and liver function estimated using DCI-MRI.

Paper 5 again looks at modelling of DCI-MRI data, to characterize the transport rates in and out of hepatocytes. In this paper, we compare uptake rates in humans and rats, and in rats with different exposures to a drug which impacts liver function. This allows us to establish a translational framework, that can predict the likely effect of a drug in humans, based on these available data and new data for the effect of the drug in rats. This is useful for drug development, when one wants to estimate the likely effect of a drug in humans based on available pre-clinical and clinical evidence.

Opponent for the defense is Steven Sourbron, who has worked with similar uptake and perfusion modelling in many of the central organs for many years, and who is one of the leading authorities in the field. In the examination committee sits Sven Månsson (Malmö), Lennart Blomqvist (Stockholm) and Zoltan Szabo (Linköping), who have complementary radiological and clinical competence.



Seminar day on non-animal perspectives in biomedicine and drug development with 3R

3R and animal experiments, Events, Systems biology and science Posted by ISB GroupPosted on Tue, January 14, 2020 19:28:05

Today, parts of the group participated at a seminar day with the Swedish 3R center in stockholm, both with posters, presentations and in discussions.

The day consisted of presentations from people doing research that can/could lead to replacement of animal testing – specifically on organs on a chip and mathematical modelling – and a panel discussions. In the panel discussions, among other things, the capabilities of the presented research to replace animal testing was discussed, what they can replace, and what the hurdels of making that happen are. All in all, the day gave a clearer vision on where we are, where we couldget, and how to do it.

From the panel discussion. From left to right, Per Artursson, Uppsala University, Karin Stenkula, Lund University, Lotte Martoft, AstraZeneca, Peter Gennemark, AstraZeneca, and Gunnar Cedersund chairing the discussions.



More grants to Systems Biology in Linköping

Uncategorised Posted by ISB GroupPosted on Thu, November 28, 2019 16:36:06

Elin has received two substantial grants, from the Swedish Research Council (VR) and from the Center for Industrial Information Technology (CENIIT). Both grants are given to young and promising researchers.

VR-NT From omics to patient specific simulations (950 000 SEK per year for 4 years)
CENIIT Executable models for drug development (450 000 SEK per year for up to 6 years)



Precise4Q meeting in Linköping

Events, News Posted by ISB GroupPosted on Tue, November 12, 2019 16:02:17

During 7th and 8th of the November, we have had meeting with our partners in the PRECISE4Q project here in Linköping. In PRECISE4Q, we are working wit developing hybrid models for a decision support for Stroke treatment together with scientists within health informatics, computer science, machine learning, medicine, etc.

During the meetings, we discussed our upcoming EU review (we are financed by EUs Horizon 2020 project), how we should move forward in general, and met with local scientists here in Linköping that are working with similar things.



Master thesis presentation

Uncategorised Posted by ISB GroupPosted on Fri, October 04, 2019 18:18:09

Today, Therese Alenvret presented here master thesis on how health information from the clinic and/or different mobile devices can be retrieved and modeled to be used by our digital twin. So now we now more about the posibilities and challanges with accessing personal data to the digital twin. Good job Therese!



Autumn update – two new PhDs and a Post-doc

Uncategorised Posted by ISB GroupPosted on Fri, October 04, 2019 15:19:28

With the summer long gone, and a new term in full swing, it is time for a very late and past-due update post! The autumn of 2019 was hectic, exciting and rewarding! The year started off with the addition of three new group members, two PhDs and a post-doc (more about this further down). We also started our to date most collaborative effort, which was to connect (almost) all of our existing models. The first phase of this project culminated in a fully packed event at the Almedalen week in the beginning of the summer, but more about this in a later blog post.

The group has grown. We have had several new (but old) additions. Both me (Christian Simonsson) and Nicolas Sundqvist, both previous master-thesis students in systems biology, started PhD-positions in the group. Here’s a short update from us. I’m finishing up my projects concerning the metabolic syndrome and I have just started new projects concerning disease progression in the liver (ASH/NASH).  Adding to this, I will spend half of my PhD working at the Division of Radiological Sciences (RAD) in the group of Peter Lundberg, doing clinical research. Right now, I am analyzing MRE data for patients with suspected liver fibrosis. Nicolas is continuing his work with metabolic flux modelling, but he has also branched out, and is now doing modelling of fMRI data and brain metabolism in the group of Maria Engstrom. Also, Belen Casas is doing her post-doc in our group. Her post-doc project concerns mechanistic modeling of MPS-systems.

Three talented internship-students have just ended their one year stay with us. Kajsa Tunedal has worked with several projects, including modelling of NEFA circulation and uptake in the liver, and modelling of cortisol levels in relation to stress. Henrik Podéus has worked with connecting several models describing the different aspects of the neurovascular coupling in collaboration with Sebastian Sten (PhD in Maria Engstroms group). Anton Tornerefelt has with collaborators from Örebro’s University created a model of Macrophages activation. You all have done great work and we wish you the best of luck in all your future endeavors!

Here is two of our latest group photos! The latter is from our latest group retreat, which took place at the beautiful Omberg eco-park.



Update from MTD

Uncategorised Posted by ISB GroupPosted on Fri, October 04, 2019 15:01:41

Two exciting days of biomedical engineering just ended after our division hosted the annual MTD conference. The purpose of MTD is to be the most important meeting place for medical technology in Sweden. Where all key stakeholders; researchers, company representatives and medical experts can meet and discuss important questions. Our presence was at the digitalization of healthcare track where our PI, Gunnar, held the opening talk. He presented our group vision of personalized medicine: digital twins – physiologically based, personalized, simulation models to be used in healthcare. Also, Elin and Tilda each had poster presentations representing modelling research. All in all, two good days where we could showcase our research vision to the Swedish biomedical community.



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