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Fusion makes a difference – also in the prostate!

ansattebilde.may-britt.tessemailin falkmo hansenBloggers:  Ailin Falkmo Hansen (PhD candidate) and May-Britt Tessem (Research Scientist), MR Cancer group


Movember is around with a “trøndersk” spirit on Facebook, Instagram, and the city is filled with mustaches in different shapes and varieties. The goal is increased awareness of men’s health and prostate cancer – a disease we in the MR cancer group want to understand better.

vevsbit og MR

Prostate tissue samples are stored in liquid nitrogen prior to MR spectroscopy analyses (photo: Geir Mogen/NTNU)

How can cancer metabolism provide important information about prostate cancer?

Scientists around the world have shown that changes in metabolism are important characteristics of cancer. We have studied how metabolism is altered due to cancer and how metabolism is changed owing to cancer aggressiveness. Previously, we have found that the two molecules citrate and spermine may be markers for prostate cancer and also can reveal information about aggressiveness.

Prostate cancer is a heterogeneous type of cancer, and this is of importance for treatment and prognosis of patients. However, today there are no reliable methods for assessment of type of prostate cancer. Researchers world-wide are therefore searching for new methods that may provide diagnostic and/or prognostic information. Presence of the fusion gene TMPRSS2-ERG have been suggested to be a candidate method for risk stratification, and in a recently published study we investigated the link between prostate cancer metabolism and TMPRSS2-ERG.

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CIUS fall conference day 2016

The second CIUS full-day conference held on 23 November 2016 in Trondheim, attracted near 80 participants representing CIUS researchers, partners, collaborators and international speakers.  The day had a varied programme and ample opportunity for networking across work packages, institutions, and fields of speciality.

CIUS director Asta Håberg opened the day before leaving the floor for the invited speakers Dr Alan Hunter from University of Bath, and Dr Hua Wang from MIT.

Presentations by Hunter and Wang. Photos: Kari Williamson/NTNU

Dr Hunter spoke on the topic “Underwater crime scene investigation for the London Metropolitan Police”, where the challenge is to develop an autonomous, compact, easy-to-use and affordable sonar vessel for finding missing persons and objects related to crime. He took us through the progress in the project so far, and future challenges, like identifying small objects.

Dr Wang’s presentation on “Seismic Propagation in Borehole Environment” took us through the use of wave dispersion characteristics by modelling of single and dual cased wells.  He presented a novel method for depicting and characterizing bore holes, even through double steel layers, using ultrasound.

After a quick update on plans for the CIUS website and intranet by web- and communications officer Kari Williamson, it was time for speed updates. The topics ranged from improving ultrasound technology and image analysis to clinical applications. See the programme below for details.

Speed updates. Photos: Kari Williamson/NTNU

The partner presentations ranged from open heart surgery applications and innovative projects, to the use of portable ultrasound at the patient bedside, also by non-expert users.

First speaker was Erik Swensen, Vice President R&D at Medistim, who talked about the use and challenges of developing reusable ultrasound probes for monitoring vessel patency in open heart, peripheral and transplant surgery. He was followed by Svein-Erik Måsøy, CEO Inphase Solutions, who talked about innovation projects including using ultrasound for wireless transfer of information and power as well as for use in quality assurance. The last speaker in this section was Håvard Dalen, Professor NTNU and Senior Consultant Cardiology St. Olavs Hospital, who showed how portable ultrasound devices can be used with great success by medical students, medical residents and nurses, and how it improves diagnostic accuracy, and thereby reducing time to treatment

Partner updates. Photos: Kari Williamson/NTNU

The final session saw updates from academia with Fabrice Prieur, Postdoc at UiO, talking about the use of 2nd harmonics, which is commonly used in medical ultrasound for SONAR imaging (non-linearity and its challenges). He demonstrated that the use of 2nd harmonics provides additional information also in SONAR.  Lasse Løvstakken, Professor NTNU, taking us through the latest in Doppler, software beamforming, functional ultrasound imaging and 3D tracking. CIUS Board Director and Programme Manager at GE Healthcare, Eva Nilssen, concluded the conference with a summary of the day.

Closing sessions. Photos: Kari Williamson/NTNU

The next CIUS conference day will be held in the last week of April and by request from our partners, the CIUS spring meeting will be extended to 1.5 day to get more time for workshops and partner-academia interaction.

The presentations will be made available on the CIUS intranet.

The programme:

  • Opening and presentation of CIUS’ results for 2016 and plans for 2017 (Professor Asta Håberg)
  • Underwater crime scene investigation for the London Metropolitan Police (Professor Alan Hunter, University of Bath, UK)
  • Seismic Propagation in borehole environment (Dr. Hua Wang, MIT, USA)
  • Presentation of CIUS intra- and internet pages (Kari Williamson, web- and communications, CIUS)
  • Speed updates:
    • Optimisation of Ultrasound Pulses for Second Harmonic Imaging, Thong Huynh, HSN
    • Experimental Evaluation of Broadband Wave Propagation in Plates, Andreas Talberg, NTNU
    • Deep learning, Erik Smistad, NTNU/SINTEF (Read Smistad’s blog on the same topic.)
    • 3D Vector Flow, Morten Smedsrud Wigen, NTNU
    • Improving Quality of Cardiac Ultrasound Images, Ali Fatemi, NTNU (Read Fatemi’s blog on the topic)
    • Ultrasound and Multimodal Image-Guided Interventions, Tormod Selbekk, SINTEF
    • VScan in Stroke Diagnosis and Follow-Up, Lars Mølgaard Saxhaug, NTNU/Levanger Community Hospital.
    • The Dynamic Range of Adaptive Beamformers, Andreas Austeng, UiO
  • Medistim (Erik Swensen, Vice President R&D)
  • Inphase Solutions (Svein-Erik Måsøy, CEO)
  • US cardiology in a non-expert setting (Nord-Trøndelag, HUNT) (Professor Håvard Dalen, St. Olavs Hospital and NTNU)
  • Non linearity in underwater acoustics, and other things (Postdoc Fabrice Prieur, UiO)
  • Ultrasound blood flow imaging – state of the art and future perspectives (Professor Lasse Løvstakken, NTNU)
  • Closing remarks (Eva Nilssen, CIUS Board Director and Programme Manager GE Healthcare, and Asta Håberg, NTNU)

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How to outsmart a prostate cancer cell

Siver MoestueBlogger: Siver Moestue, Associate Professor
MR Cancer Group, Department of circulation and medical imaging, NTNU



Cancer cells are notoriously difficult to deal with – partly because they have the ability to dodge the bullets we aim at them. They are inherently resistant to a lot of hostile conditions and therapies, but they can also activate compensatory mechanisms that rescue them when they are exposed to anticancer drugs. We have therefore tried to find a way to responsibly kill cancer cells (killing cancer cells without harming the normal cells in the body, that is) by identifying the crucial compensation mechanisms, and then applying a second drug that strikes the cancer cells where it hurts the most.

Essentially all the work that is performed inside our cells is carried out by proteins. Not all proteins work at the same time – most of them are responsive to cues from their surroundings that tell them when to work and when to take a break. One such cue is OGlcNacylation. Sounds difficult, but basically the cells put tiny “flags” consisting of amino sugars on proteins, thereby giving them new work orders (Figure 1).

Illustration of O-GlcNac Transferase (OGT)

Figure 1 Proteins can be activated, deactivated or otherwise change function when they are labelled with the amino sugar N-acetylglucosamine on specific amino acid residues. This process is called O-GlcNacylation, and may play an important role in cancer.

In cancer, it has been seen that an enzyme responsible for putting these amino sugar flags on proteins (OGT) is frequently over-activated. In a collaboration with Prof. Ian Mills (Norwegian Centre for Molecular Medicine) and Suzanne Walker (Harvard Medical School), we wanted to find out if a novel drug targeting OGT could be used to kill prostate cancer cells. To cut a long story short, they could – but only to a certain extent. The cells found a way to survive and continue to divide, just a little slower than before. To understand how the cancer cells escaped death, we took a deep dive into their metabolism using magnetic resonance spectroscopy.

Interestingly, we found that OGT inhibition made the cells reprogram metabolism. They stopped consuming glucose, instead turning to the common amino acid alanine as a new source of energy. Since OGlcNacylation is a process that normally allows cells to respond to starvation or altered supply of nutrients, this sort of makes sense. It also raised the question “What if we block the metabolism of the cells so they cannot use alanine anymore?”. Luckily, the well-known drug cycloserine (used to treat tuberculosis), does just that – by blocking the alanine-converting enzyme GPT2.

When we treated the prostate cancer cells with both the OGT inhibitor and cycloserine, the prostate cancer cells activated a self-destruct mechanism and died. Luckily, normal prostate cells tolerated the treatment very well.

MR spectrum of cells treated with an OGT inhibitor.

Figure 2 Left: MR spectrum showing how cells treated with an OGT inhibitor (black line) have low levels of glutamate and are virtually depleted of alanine. Right: Diagram demonstrating how LNCaP prostate cancer cells treated with a combination of an OGT inhibitor + cycloserine (blue bar) are far less viable than untreated control cells or cells treated with each of the drugs alone (grey bars).

What did we learn from all this? First, we demonstrated an important principle: Cancer cells may display metabolic ”soft spots” leaving them in a vulnerable position once they are under attack from anticancer drugs. Finding these – and attacking them with a second drug – could be a way of improving cancer therapy in the future. Second, we proved that it is possible to learn an old dog new tricks: cycloserine was developed to make it hard for tuberculosis bacteria to make their cell wall. However, as a side effect it also blocks the ability of mammalian cells to use alanine as an energy source. This does not seem to be a problem for normal cells, because they don´t depend on this mechanism at all. But under given conditions (such as when they are under attack from drugs blocking OGT), prostate cancer cells are addicted to it – and we can take advantage of that when we try to kill them.

The project was carried out with financial support from the Norwegian Cancer Society and the Research Council of Norway.

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Improving quality of cardiac ultrasound images

Ali FatemiBlogger: Ali Fatemi, PhD Candidate
Centre for Innovative Ultrasound Solutions (CIUS), Department of circulation and medical imaging



Cardiovascular diseases (CVDs) are the number-one cause of death globally. An estimated 17.5 million people died from CVDs in 2012, 31% of all global deaths. One important factor in preventing cardiovascular disease, is early diagnosis using technologies such as ultrasound echocardiography. In this project, we study the cause of certain defects in the current echocardiograms and will try to propose new processing methods to improve the image qualities.

The quality of cardiac ultrasound images (echocardiograms) has increased significantly in the last 20 years, making it possible to correctly diagnose the occurrence of CVDs in about 80% of patients. In the remaining 20% certain physical factors hinder a correct visualization of the heart and the assessment of its function.

One of the artefacts which is seen in the echocardiograms taken from some patients, is what we refer to as “haze” artefact. In the images with this artefact a haze-like noise can be seen over the heart. This haze-like noise normally disappears when imaging deeper than 10 cm into the body in the studied cases (see the hazy echocardiogram in the figure below). In the following figure a “non-hazy” echocardiogram is shown together with a “hazy” one.

Ultrasound images

Left: a ”clear” ultrasound image of heart. Right: a ”hazy” ultrasound image of heart

Echocardiography produces real-time images of the heart, by sending ultrasonic pulses (sound waves with higher frequency than audible frequency range) in between the ribs and down into the body. Ultrasonic pulses are then reflected back to the transducer (the transmitter and receiver of the ultrasonic pulses), which can be detected and transformed into an image. However that is not the only path that the signal can take. Sometimes the signal can be partially blocked by the ribs impacting the quality of the result images. Therefore, as a potential cause of the haze artefact, we investigate the geometry of rib bones and its effect on the received ultrasound signal from the heart.

To study this effect, we carried out an experiment out of the body, where we imaged an artificial ventricle in a water tank. A section of a pork ribcage was placed on top of it to simulate the ribs effect in human body (see figure below). We imaged the ventricle through the ribs with an M5Sc transducer and E95 GE scanner. We repeated the imaging after placing the tip of a metal needle under water about 10 cm away from the transducer. Figure below shows the setup with and without the needle and the corresponding ultrasound images. We observe that the needle tip is displayed in the ultrasound image at a depth of around 11 cm (see the lower right pane in the figure below). However the needle is not expected to be visible in the image since it is placed out of the transducer field of view or “imaging plane” (a cross section of the object which is being imaged).

Ultrasound images and pork ribs with artificial ventricle

Images of the setup and corresponding ultrasound images with and without the needle. Upper left pane: image of the setup without the needle. Lower left pane: ultrasound image without the needle. Upper right pane: image of the setup with the needle. Lower right pane: ultrasound image with the needle.

This experiment shows that if the ultrasound beam is partially blocked by the ribs, then part of the energy is reflected to unwanted directions. This deflected energy can then be reflected once more by the scatterers that are present in these directions (the needle tip in our experiment) and travels back to the transducer. Therefore, the scatterers out of the imaging plane can be observed in the ultrasound image as noise. The result of this experiment can be expanded to the haze artefact in the echocardiograms with the hypothesis being:

In some patients, with a specific shape and angle of the ribs, and depending on the heart position relative to the ribs, there is no way for all of the ultrasound beam to go through the ribs before hitting the desired cross section of the heart. This leads to the beam being partially reflected and any scattering tissue out of the imaging plane is then rendered as haze noise.

At this stage, we are collecting some live data from volunteers to check the haze level in their echocardiograms. At the same time, we record some data of the shape and distance of their ribs and compare the haze level with this information.

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Can a psoriasis drug be used to treat breast cancer? Targeting the link between inflammation and cancer

Hanna Maja TunsetEugene KimBloggers: Hanna Maja Tunset, PhD candidate, Eugene Kim, PostDoc,
MR Cancer group, Department of circulation and medical imaging



October is nearly over. The good news is that Christmas season is just around the corner. The bad news? This is the final post from the MR Cancer group in our blog series for breast cancer awareness month! If you missed the first two blogs, you can check them out here: A new cure for breast cancer? and Could breast cancer metabolism reveal new therapeutic targets?

Breast cancer is not just one disease, and different breast cancers need different treatment. Targeted treatment according to the type of tumor has increased breast cancer survival for a lot of patients.  However, around 15 % of breast cancer patient have what we call triple negative breast cancer (TNBC), which does not respond to currently available targeted therapies. This subtype also tends to be highly aggressive, develop at a younger age, and have poorer prognosis compared to other types. Going against the overall trend in breast cancer, survival rates for TNBC have not increased in the past few decades. So, new targeted therapies for TNBC are in high demand.

One way of finding a good therapeutic target is to look for something that is unique to that particular disease. We have previously identified that the inflammatory enzyme cytosolic phospholipase A2, or cPLA2, is overly active in TNBC as compared to other breast cancers. We wanted to see if inhibiting cPLA2 could be an effective treatment.  So we teamed up with Berit Johansen, a professor at the NTNU Department of Biology and CSO of Avexxin AS, a Trondheim-based start-up company developing a line of cPLA2 inhibitors intended to treat inflammatory diseases like psoriasis and rheumatoid arthritis.

We tested one of their drugs, AVX235, in a mouse model of TNBC, and the results look promising. Tumors in mice treated with the drug only reached 1/3rd of the size of untreated control tumors after 19 days of treatment.

But how does AVX235, an anti-inflammatory drug, inhibit tumor growth?

Targeting the link between inflammation, blood vessels, and cancer

Cytosolic phospholipase A2 is highly involved in both acute and chronic inflammation in the body. In 1863, Rudolf Virchow, the father of cellular pathology, theorized that cancer was caused by chronic inflammation. Over the years, research has revealed close links between inflammation and cancer. American pathologist Harold Dvorak  went as far as to describe tumors as “wounds that do not heal”. A major component of inflammation and wound healing is angiogenesis –  the growth of new blood vessels. Angiogenesis is a hallmark of cancer and is observed in most solid tumors. As a tumor grows, it produces blood vessels that deliver the oxygen and nutrients necessary to sustain it.

Our study suggests that cPLA2 plays an important role in angiogenesis in TNBC. We found that AVX235 reduced the amount and size of blood vessels in the tumors. High-resolution CT images showed that large portions of tumors treated with AVX235 did not have a blood supply.


CT images of breast cancer tumours

CT-based images of representative tumors from control (Ctrl) and treated (Tx) groups, color-coded for vessel caliber (VC), i.e. vessel diameter – the more yellow or red, the larger the vessel. Note the lack of vessels in large areas of the treated tumor (arrows).

We also examined tumor tissue under the microscope, after staining for certain factors that could reveal if blood vessel cells were dividing. Treated tumors had fewer actively growing blood vessels. This indicates that blocking cPLA2 activity hindered the cancer’s ability to produce new blood vessels, resulting in tumors that were under-fed and unable to grow as they normally would.

Next steps towards improving treatment of TNBC

We are still in the early phases, but our initial results show that inhibition of cPLA2 may be a strategy for targeted therapy of TNBC. Continuing our collaboration with Avexxin, we are currently trying to find out more about how this may work. By using breast cancer cells grown in a flask as a model system, we can detect responses on a cellular level, like alterations of metabolism, how fast the cells grow, and their ability to invade new tissues.

Over the past decade, there has been an increasing interest in cPLA2 as an important player in the progression of various cancers, including breast cancer. We hope our research in this field will contribute towards providing a much-needed targeted therapy for triple negative breast cancer patients.

The results from this study was published in BMC Cancer.

This work was funded by the liaison committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology (NTNU), the Norwegian Cancer Society, the Research Council of Norway, and Avexxin AS.

Group photo. Poto: Kari Williamson

From the back (left to righ): Astrid Jullumstrø Feuerherm, Siver Moestue, Jana Kim, Eugene Kim, Berit Johansen and Hanna Maja Tunset

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A new cure for breast cancer?

Portrettbilde SiverTrygve AndreassenBloggers: Trygve AndreassenSenior engineer, and Siver Moestue, Associate professor,
The MR Cancer Group, Department of circulation and medical imaging



Scientists all over the world are strenuously pursuing new ways of killing cancer cells. They look for so called “drug targets” – proteins the cancer cells need for rapid and uncontrolled proliferation. In collaboration with Karolinska Institutet in Sweden, we have discovered such a protein called CHPT1. Based on this discovery we think it may be possible to develop new drugs for treating breast cancer.

A needle in a haystack

Before we can develop a new cancer drug, we must have some idea about what the drug should do. We have to identify a “drug target” – a protein the drug must recognize, bind to and alter the function of. It is not as simple as it might sound – we have about 20,000 different protein coding genes in our DNA, and it has been estimated that they can produce up to 100,000 different proteins (Savage, Nature 2015). These proteins communicate with each other in various ways, which means that we are trying to find a needle in a pretty big haystack.

Cancer drugs are often designed to block processes that are important for cell division, or the copying of DNA that happens prior to every cell division. In our research group, we are interested in the metabolism of cancer cells (in order to grow and divide fast, the cancer cells will reprogram their metabolism), and therefore we have searched for possible target proteins in the biochemical pathways.

In collaboration with Karolinska Institutet in Sweden, we started out with some known characteristics of breast cancer cells: They often grow faster in the presence of oestrogen; and they have an abnormally high turnover of the molecule choline. In order to study the choline turnover we apply a technique called MR-spectroscopy.

Main suspect: CHPT1

First we identified about 18,000 oestrogen binding domains in DNA, and found that these domains control the expression of about 2500 genes. Next we found how many of these genes that could be involved in choline turnover – hereby reducing the number of candidate genes to 19. By interpreting MR-spectra of cancer cells grown with and without oestrogen, we found which metabolic changes that could be derived from oestrogen stimulation. This allowed us to further reduce the number of proteins – and eventually we suspected the protein CHPT1 of being heavily involved in transferring the stimulating effect of oestrogen to the metabolic machinery of cancer cells.

To make sure that our findings are not only valid for cancer cells grown in the lab, we investigated tumour tissue from 70 breast cancer patients. Here we found higher expression of CHPT1 in tumour tissue compared to normal breast tissue. Even more interesting, we could see that tumours classified as oestrogen sensitive had significantly higher CHPT1 expression than the other tumours. This implies that oestrogen actually activates CHPT1 in breast cancer patients.

The next step in proving that CHPT1 is a relevant drug target was to show what happens if we switch off this gene. In the laboratory we have molecular tools which allow us to stop the production of the CHPT1-protein in cancer cells, and we found that cancer cells grew much slower when CHPT1 was switched off (Figure 1).

Figur 1: Brystkreftceller i mikroskop.

Figure 1: The two pictures to the left show to different types of breast cancer, seen in a microscope when growing freely in a dish. In the pictures to the right (marked siCHPT1) we see the same cells, but here we have “switched off” CHPT1. There are clearly fewer cells, which indicates that the cells need CHPT1 to grow and divide.

Killing cells in a dish at the lab is fairly easy, so the next step was to see if we could influence tumour growth in a living organism. Our choice of organism was zebrafish (they are quite transparent which enables us to observe the cancer cells directly). By switching off CHPT1 we could see that both tumour growth, as well as the cancer cells’ ability to spread to other tissue and organs, was reduced (Figure 2).

Sebrafisklarve med svulster.

Figure 2: Above we see a zebrafish larva with implanted oestrogen sensitive MCF-7 cancer cells. They have developed a tumour at the injections site (red colour), and daughter tumours (metastases) have formed along the spine (marked with arrows (6). Below we see a zebrafish larva injected with the same type of cancer cells, but with CHPT1 switched off (siCHPT1). Here, there is no big tumour at the injection site, and there are clearly fewer daughter tumours along the spine (marked with arrows (3)).

All in all, we have presented several indicators suggesting that CHPT1 may be an important drug target for the treatment of oestrogen sensitive breast cancer. But there are still many things we haven’t found out yet: Is it possible to design drugs that block CHPT1? What are the side effects? Are they superior to existing drugs?

We have published our findings and hope that someone will take up the gauntlet and continue working on our ideas. And hopefully be able to develop a new drug based on our basic research.

The project has been partly funded by the Norwegian Cancer Society and the Research Council of Norway.

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Could breast cancer metabolism reveal new therapeutic targets?

Tonje Husby HaukaasBlogger: Tonje Husby Haukaas, Senior engineer
MR Cancer Group at the Department of circulation and medical imaging




Could there be a better day to write my first blog? Especially when it’s a “pink” one! The 1st of October marks the beginning of Breast cancer awareness month. This is a month that has the aim to improve knowledge among the population, show compassion for breast cancer patients, and raise funds for breast cancer research.

Rosa sløyfe. Foto: Deborah Hill/NTNU

In the coming days and weeks, the streets will be filled with pink ribbons, balloons, and accessories, and a variety of pink activities will be organized throughout the country. With this blog I hope to teach you something you didn’t know about breast cancer. I also want to show you what research funding can contribute to.

Breast cancer affects many lives, not only the people who are diagnosed. It is the most common cancer among women in Norway, and just today eight women will be diagnosed with breast cancer. Luckily, due to early detection and improved treatment, 90 % of women with breast cancer are still alive 5 year after the diagnosis. But no two tumors are exactly alike, which makes it hard to predict who will be in the 10 % that respond poorly to the current treatments and have short survival times. Also, even with a good response to treatment the patient can experience post treatment adverse effects and a poorer quality of life.

We wish to improve this.

To provide targeted and optimal treatment that has been tailored to each patient, we first have to learn as much as possible about the cancers’ properties and potential weaknesses. Some important targets are already well established in the clinic, like drugs that attack cancer cells that depend on the hormones estrogen or progesterone to grow. But there are still some cancers that don’t have established targets and researchers are working hard to uncover new ways to treat them.

Important differences can be hidden in cancer metabolism

One of the aims of the MR Cancer group has been to reveal potential treatment targets by exploring cancer metabolism.

Cancer cells grow and divide uncontrollably, which increases the need for energy and building blocks compared to normal cells. This can be observed when MR spectroscopy is used to study which small molecules, called metabolites, are present in tissue samples. The result of such an experiment is called a ‘spectrum’, where the peaks originate from different metabolites (see figure). Some of the metabolites are more common than others, such as glucose and lactate. Others are perhaps less known, such as glycerophosphocholine and glutathione, but are still important to study. The metabolites can tell us something about which processes are ongoing at the time the sample is taken.

Previous studies have shown that the cancer tissue’s metabolic fingerprint, meaning the metabolites present, is related to the tumor grade (how aggressive the cancer is), potential for metastasis, and 5 year survival.

By studying the metabolic fingerprint, it is possible to increase the knowledge about which types of breast cancer exist, how aggressive they are, and at the same time look for more biological markers that can identify new targets for treatment.

The figure shows some of the metabolites we can observe by performing MR spectroscopy on breast cancer tissue.

The figure shows some of the metabolites we can observe by performing MR spectroscopy on breast cancer tissue.

The Oslo2-study: A large-scale breast cancer study from multiple biological levels

In the Oslo2-study, a large-scale breast cancer study at the Oslo University Hospital, sample material from 228 patients has been sent to Trondheim and analyzed by MR spectroscopy. Based on the samples’ metabolic fingerprints we have identified three new subgroups of breast cancer. These three groups displayed differences in metabolism; understanding what makes them different helps us to identify more precise drug targets specific for each of the three groups.


Three new subgroups of breast cancer, called Mc1, Mc2 and Mc3, was found by comparing their metabolic fingerprint.


The unique feature of this study is that the sample materials from the same group of patients have been analyzed with multiple methods. Both the expression of genes and level of breast cancer related proteins have been analyzed. This gives us the possibility to look for new relationships between genes, proteins, and metabolites in breast cancer. By combining the levels of data, we saw that one group in particular expressed big differences in genes and proteins compared to the two other groups.


Tissue samples are stored in liquid nitrogen prior to MR spectroscopy. The samples are kept frozen while they are cut to fit the sample tubes. Photo: Geir Mogen/NTNU.

Based on this, we suspect that this group has a more aggressive cancer type, and would therefore benefit from a different type of treatment than the two other groups.

We will soon acquire follow-up data from the patients in this study, which will provide us with new information on survival and relapse. Based on our metabolic findings, the hypothesis is that the patient survival is different depending on which metabolic subgroup they belong to. If this hypothesis is correct, it means that the metabolic classification can indicate which patients need extra follow-up, and possibly more intensive treatment to get well.

Finally: Why not wear something pink today to show your appreciation for Breast cancer awareness month?

The research is financed by the K.G. Jebsen Center for Breast Cancer Research.


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Avoiding unnecessary coronary angiograms

Bjørn Olav HaugenBlogger: Bjørn Olav Haugen, Professor,
Centre for Innovative Ultrasound Solutions, Department of circulation and medical imaging

Angina is chest pain that occurs when the blood supply to the muscles of the heart is restricted. It usually happens because the coronary arteries supplying the heart become hardened and narrowed.

A coronary angiogram (CA) is an X-ray test done to find out if the coronary arteries are blocked or narrowed. If medication does not reduce the symptoms, it is usually recommended to do a coronary angiogram to help the cardiologist to see if you need treatment such as angioplasty with implantation of a stent (PCI), or coronary artery bypass surgery (CABG). Continue reading

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Interpreting ultrasound images with neural networks

Erik SmistadBlogger: Erik Smistad, PostDoc at Centre for Innovative Ultrasound Solutions (CIUS)




Neural networks have recently achieved incredible results for recognising objects such as cats, coffee cups, cars and plants in photographs. These methods are already used by companies like Facebook and Google to identify faces, recognize voice commands and even enable self-driving cars. At the Centre for Innovative Ultrasound Solutions (CIUS), we aim to use these methods to interpret ultrasound images. Ultrasound images can be challenging for humans to interpret and requires a lot of training. We believe neural networks can be used to make it easier to use ultrasound, interpret the images, extract quantitative information, and even help diagnose the patient. This may ultimately improve patient care, reduce complications and lower costs.

Low-level image representations learned by an artificial neural network.

Low-level image representations learnt by an artificial neural network.

Artificial neural networks are simplified versions of the neural networks in the human brain. These networks are able to learn directly from a set of images. By showing a neural network many images of a cat, the network is able to learn how to recognise a cat.

Neural networks are organized into several processing layers which learn different levels of image representation, from low-level representations such as edges, to high-level representations such as the shape of a cat. The image representations are used to distinguish one object from another. Over the years the trend has been to increase the number of layers and thus referred to as deep neural networks and deep learning.

Experiments have shown that deeper neural networks can learn to do even more advanced tasks. Recently, such a deep neural network beat the world champion in the game Go – a game more complex than chess.

One of the challenges with these methods is to collect enough data. Many images are required for the neural network to learn the anatomical variation present in the human population and how the objects appear in ultrasound images. Also, the data must be labelled by experts, which can be a time-consuming process.

In a recent study, we created a neural network able to detect and highlight blood vessels in ultrasound images as shown in the figure below. This was done by training a neural network with over 10,000 examples of images with and without blood vessels. When the neural network is presented with fresh images it is able to recognise blood vessels – it has learnt what a blood vessels looks like in an ultrasound image.

Blood vessels automatically located and highlighted by a neural network.

Blood vessels automatically located and highlighted by a neural network.

Currently, we are investigating how these neural networks can locate structures such as nerves in ultrasound images, which can be difficult even for humans. The figure below shows the femoral nerve of the thigh in yellow, located automatically by an artificial neural network. Identifying these nerves is crucial when performing ultrasound-guided regional anesthesia.

The femoral nerve (yellow) and femoral artery (red).

The femoral nerve (yellow) and femoral artery (red).

Erik Smistad is a PostDoc at CIUS working on machine learning and segmentation techniques for ultrasound image understanding. You can learn more about his research on his own website: Erik Smistad.

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Brain changes in U-2 pilots due to altitude exposure – NATO high altitude research at NTNU

Andreas MøllerløkkenMarianne Bjordal HavnesBloggers:
Marianne Bjordal Havnes, Post Doc
Andreas MøllerløkkenResearcher,
The Barophysiology group at the Department of circulation and medical imaging



Researchers are trying to find out why U-2 pilots operating in high altitude have  central nervous system changes in a NATO-led project involving researchers from the Barophysiology group at NTNU, researchers from the U.S. Air Force in Texas and from the Institute of Aviation Medicine in Oslo.

You have probably been in a passenger jet, and as you get ready for take-off, you register the cabin attendants going through the safety instructions, mentioning something about loss of cabin pressure and oxygen masks, but you don’t worry about it. 15 minutes later the captain announces that the airplane has reached its cruising altitude of 38,000 feet. At this altitude the barometric pressure is only 1/5 of sea level pressure.

U-2 aeroplane. Photo: Dr Stephen McGuire USAF.Inside the aircraft the pressurisation system ensures that the cabin altitude according to international regulations will never exceed 8000 feet = ¾ of sea level pressure. So while you are travelling, you are actually performing a little mountain-excursion to the same altitude as Norway’s highest mountain, Galdhøpiggen.

Now imagine that you are flying twice as high as your airliner. At an altitude of 70,000+ feet the barometric pressure is 1/25th of an atmosphere. You can see the curvature of the earth and the blackness of space above. This is where the U-2 pilots are working. If you lose the cabin pressure in this environment, an oxygen mask will be of no help. You need to wear a space suit that will instantly inflate to a pressure of 0.3 bar (corresponding to 30,000 feet) and supply you with a breathing gas of 100% oxygen.

The U-2 planes have been operating since the 50s and are still in active duty. In fact, U-2 pilots have actually been flying more the last 10 years as other high-altitude reconnaissance airplanes have retired. This has resulted in an increased number of neurologic decompression sickness episodes.

A US Air Force research team has published findings of what are called white matter hyperintensities in the brain on magnetic resonance imaging (MRI) of U-2 pilots (McGuire et al., 2013) . Recently they have discovered similar findings in U.S. Air Force altitude chamber instructors (McGuire et al., 2014). This group works inside hypobaric chambers, training aircrew including U-2 pilots, in the effect of loss of cabin pressure and lack of oxygen. The altitude exposure in hypobaric chamber training is usually much shorter and less severe than in U-2 operations. None of the other U.S. Air Force control groups they have tested so far, including Air Force doctors, have had similar changes.

The U.S. Air Force research team visited the Institute for Aviation Medicine, Oslo, Norway, and wanted to meet Norwegian research groups that might contribute to understanding the pathophysiology behind the findings. Members of the NTNU Barophysiology group were invited based on their merits for a long time commitment to research on man in extreme environments.

U-2 aeroplane. Photo: Dr Stephen McGuire USAF.U-2 aeroplane. Photo: Dr Stephen McGuire USAF.

Most of the work of the NTNU Barophysiology group has been related to the activity of diving and the adverse effects of working under water. Presently, the research is funded by the Norwegian Research Council through the Petromaks programme.

From left: Berit Holte Munkeby, MD, PhD, Norwegian Armed Forces, Dr Paul Sherman, USAF, Andreas Møllerløkken, PhD NTNU, Marianne Bjordal Havnes, PhD, NTNU, Dr Stephen McGuire USAF.

From left: Berit Holte Munkeby, MD, PhD, Norwegian Armed Forces, Dr Paul Sherman, USAF, Andreas Møllerløkken, PhD NTNU, Marianne Bjordal Havnes, PhD, NTNU, Dr Stephen McGuire USAF.

One of the technologies we are using in assessing possible stress after a dive is ultrasound detection of gas bubbles found in blood veins. These bubbles will form in nearly all diving activity, and it is recognised that the risk of decompression sickness increases with increasing amounts of bubbles.

Our way of observing vascular gas bubbles after diving has become a recognised method for evaluating procedures.  It has also been shown both in animals and humans that the bubbles themselves influence the endothelium lining all blood vessels. When going to high altitudes, the pressure changes are opposite of diving. But there are many similarities as well, and the formation of bubbles is thought to be involved in the formation of the white matter hyperintensities.

After the meeting in Oslo, the researchers from NTNU did some preliminary investigations, and were invited to Lackland Air Force Base in Texas where the main investigation is taking place. The results from the tests at NTNU have already been presented at a NATO high altitude exposure meeting this summer in Paris, and has gained a lot of attention within NATO. Together with the Institute of Aviation Medicine in Oslo, the researchers from the Department of circulation and medical imaging are eager to continue the investigations.

U-2 aeroplane. Photo: Dr Stephen McGuire USAF.

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