Tag Archives: ISB

Shutting off blood supply to an extremity to protect the heart

på operasjonssal

Foto: Geir Mogen

In a study just published in the International Journal of Cardiology, researchers from CERG and the Department of Cardiothoracic Surgery at the St. Olav’s Hospital have shown that shutting off the blood supply to an arm or leg before cardiac surgery protects the heart during the operation.

We wanted to see how the muscle of the left chamber of the heart was affected by a technique, called RIPC (remote ischemic preconditioning), during cardiac surgery. RIPC works by shutting off the blood supply to an arm or a leg before heart surgery. The goal is to reduce risk during cardiac surgery in the future.

Read more at CERG’s blog

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To treat or not to treat? The role of PET/MRI in prostate cancer

Mattijs ElschotBlog by: Mattijs Elschot
Postdoctoral Fellow at MR Cancer Group

Some prostate cancer patients need radical surgery to survive, whereas others can do without any form of treatment. The urologist determines to which group a patient belongs. Researchers at NTNU/St. Olavs Hospital investigate whether a PET/MRI scan can help making the correct decision.

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Early markers of a potentially dangerous type of prostate cancer

Morten Beck RyeBloggers: May-Britt Tessemansattebilde.may-britt.tessem and Morten Beck Rye

As we speak there are no accurate methods to diagnose potentially dangerous prostate cancer in an early stage of cancer.

From a pathologist’s point of view, aggressive cancers look totally similar to harmless subtypes in the beginning of development. As a consequence, the patients will be at high risk of overtreatment in the majority of cases where prostate cancer is detected. We urgently need new tools and markers to sort out the potentially dangerous types of prostate cancer from the non-dangerous in early disease. Most importantly, this will save the patients from reduced quality of life due to unnecessary surgical interventions, and also be economically beneficial for society.

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New method for characterizing brain tumors

Blogger: Morteza EsmaeiliMortezaE
Postdoctoral Fellow at MR Cancer Group, NTNU

 

A new non-invasive method can identify a special mutation in a type of brain tumor called gliomas. This unique test can assist in research towards new treatments that target cancer cells in glioma patients carrying this mutation. The new method is developed by my colleagues and me at MR Cancer Group at NTNU and researchers at the Departments of Radiology and Pathology of Radboud University Medical Center in Nijmegen. We believe it is an important step towards improved tools for the diagnosis and treatment evaluation of brain tumor patients.

Gliomas are common subtypes of primary brain tumors that originate from glial cells in the brain. There are different grades of gliomas, indicating their degree of aggressiveness; however, they are most often classified as “low-grade” or “high-grade” gliomas. Glioblastomas are the most aggressive type of gliomas. Various types of gliomas have been identified, and they have different clinical behavior and response to treatment. This means there is an urgent need for more accurate and precise diagnosis, prognosis, and therapy monitoring tools.

MR-bilde av en hjerne

Gliomas are common subtypes of primary brain tumors that originate from glial cells in the brain. A new non-invasive method can identify a special mutation in gliomas. (Photo: Geir Mogen/NTNU)

Conventional anatomical imaging methods, such as magnetic resonance imaging (MRI) (Figure 1), provide limited information on tumor characterization and prognosis. Advances in personalized patient management and new drug treatments for brain tumors have generated increasing demand for reproducible, non-invasive, quantitative imaging biomarkers.

Recent developments have concentrated on the role of physiological and metabolic MRI, such as magnetic resonance spectroscopy (MRS, see an example in Figure 2), and other molecular imaging methods in understanding the metabolic processes associated with tumor growth and progression. These studies have indicated that cancer cell metabolism, contrary to the metabolism in normal cells, is modulated and reprogrammed to facilitate additional/excessive demands for biomass generation and rapid cellular growth and proliferation. This particular characteristic of cancer cells can be targeted as a “weak point” to kill these cells.

This particular characteristic of cancer cells can be targeted as a “weak point” to kill these cells.

Furthermore, the utility of various techniques in distinguishing between aggressive and benign tumors, tumor grading, and treatment response evaluation and monitoring are also of interest.

Conventional MR imaging of glioblastoma

Figure 1: Conventional MR imaging of glioblastoma. Tumor regions can be identified by different MR contrasts; For example, (A) T1-weighted pre-contrast exhibit a low-intensity lesion in the left frontal lobe region (yellow arrow), (B) post-contrast MR image demonstrates a focus of enhancement in that area, (C) and T2-weighted MR image shows increased-intensity at the same region. These MR techniques enable non-invasive imaging and diagnosis of tumor lesions in the brain. Illustration is adapted from Ahmed R. et al. Cancer Manag Res, 2014 (with permission).

During our study, we uncovered a new imaging biomarker to identify glioma subtypes with different prognosis and therefore this biomarker may be used for a better clinical management, avoiding extra cost for patients and communities. More specifically the biomarker concerns metabolite levels associated with a mutated IDH gene found in more than 70% of the brain tumors classified as low-grade gliomas and secondary gliomas. Glioma patients with this mutation actually have a better prognosis.

In particular, with our MRS technique we observe the indirect effect of the mutation in the IDH1 gene on the level of some phospholipid metabolites, which can be considered a molecular “finger print” for this mutation. These metabolites are major components of phospholipid metabolism in the synthesis of cancer cell membranes.

MR spectroscopy provides information additional to conventional MRI

Figure 2: MR spectroscopy provides information additional to conventional MRI. T2-weighted MR images of a mouse brain with glioma tumor (top, A) and a healthy mouse brain (bottom, B), and corresponding MRS data from area of interest (blue circles, C and D). MRS detects signals for different metabolites in normal brain and tumor tissue. In particular phospholipid metabolites are of interest to characterize brain tumors. (from left to right); PE, phosphoethanolamine; PC, phosphocholine; GPE, glycerophosphoethanolamine; GPC, glycerophosphocholine. Adapted from Esmaeili M. et al. Cancer Res. 2014 (with permission).

To be a bit technical: IDH1 acts in an energy-generating pathway known as the citric-acid cycle, and the IDH1 mutations associated with cancer causes a metabolite called 2-hydroxyglutarate to accumulate. IDH1 catalyzes the conversion of isocitrate into α-ketoglutarate, a reaction that takes place in energy-generating metabolic pathways. Most remarkable is that the mutated IDH1 enzyme has acquired the capacity to produce 2-hydroxyglutarate, which can accumulate in high concentrations in gliomas with the mutation. 2-hydroxyglutarate is commonly called an oncometabolite. Our finding shows that the mutation also alters lipogenesis in brain cancer cells. Phospholipid metabolism is a major network supporting cellular lipogenesis and cell membrane turnover.

The discovery of the IDH1 mutation has generated such intense interest that pharmaceutical companies are keen to find drugs that target mutant IDH1 gliomas

The discovery of the IDH1 mutation has generated such intense interest that pharmaceutical companies are keen to find drugs that target mutant IDH1 gliomas, with some companies focusing exclusively on targeting cancer metabolism. The findings of this study and those published recently on IDH related metabolism could be used in the development of drugs for cancers with these mutations. In addition, these findings enable the detection through non-invasive imaging of the direct metabolic consequence of a genetic mutation in a cancer cell. This offers a potential new tool in the management of brain tumor patients.

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Spectacular images of tumor blood vessels

Jana CebullaBlogger: Jana Cebulla
PhD Candidate at MR Cancer group

 

Angiogenesis is the formation of new blood vessels from pre-existing vessels. This process takes place during wound healing, but is also essential during the development of certain diseases, such as cancer.

In order to grow beyond a size of 1-2mm, tumors send out chemical signals telling nearby blood vessels to send new vessels in the direction of the tumor. This way, the cancer cells can get sufficient supplies of oxygen and nutrients. Angiogenesis has also been found to help cancer spread to other parts of the body (i.e. metastasize).

Blood vessels that are recruited by a tumor

Blood vessels (orange) that are recruited by a tumor (white) which was grown on the leg of a mouse (surrounding “healthy” tissue in blue). Photo: Jana Cebulla

Hopefully, in the future the worldwide research on angiogenesis can help put together all the pieces in the puzzle and describe how angiogenesis in cancer is regulated and how we can influence it with drugs in order to treat cancer patients more effectively.

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Copenhagen next!

We’re off to Copenhagen! You can meet us at the Science in The City festival from tomorrow until Thursday 26. July.

This is what we are doing there: http://scienceinthecity.dk/en/event/6-can-u-hear-u-sound

On Saturday at 17:00 our researcher Garrett Newton Andersen will demonstrate a hand-held ultrasound machine (Vscan) on stage: http://scienceinthecity.dk/en/event/103-scan-your-heart-stage-can-u-hear-u-sound

ScienceintheCity

 

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Applied Human Physiology in Extreme Environments

Blogger: Andreas Møllerløkken Andreas Møllerløkken

 

 

 

The NTNU Barophysiology Group aims to promote safety and minimize the acute and long-term harmful effects of diving and other extreme environmental exposures. Our work covers the topics of both basic and applied research. Through a translational approach, we study animal models to provide novel and comprehensive knowledge of pathophysiological mechanisms. We also use human field and laboratory studies to obtain physiologically relevant data.

This week we arrange a course, “Enjoy the Cold – Health, Protection and Survival in the Cold – Adaptation and risk assessment of human activities in cold environments” in Ny-Ålesund, Svalbard. This course aims at giving people who are working and participating in activities related to cold environments proper training and insights on different equipment that exists which can be used to manage the different challenges one faces in the cold environment. Through a combination of lectures, discussions, practical work and use of equipment, the participants will gain an intimate knowledge on how to handle work situations as well as accidents.

Measuring oxygen consumption during field work

Measuring oxygen consumption during field work

The Arctic areas have become regions of global importance because of their enormous natural resources and their strategic position. These northern areas are cold, harsh and hostile to man. Working in them is difficult, expensive and demands high levels of technical, scientific, and physiological expertise. Cold weather exposure can cause immediate health problems. For people with ailments, cold exposure can lead to new symptoms, or aggravate those existing. Cold exposure may also cause pain and disease in healthy subjects.

A number of climatic factors are known to increase challenges related to work in the northern areas, such as temperature, wind, icing, the polar low, uncertain weather forecasts and polar night. In addition to climatic factors, regulation of body temperature is affected by activity, technical protective actions/systems and clothing. The climatic problems connected with activity in the arctic areas are not only limited to equipment and equipment function. Cold is one of the most dangerous environmental risk factors for man. Not only does the cold challenge day to day function in those prepared for such an environment, but if conditions become more extreme, then it may also challenge survival. Although the human body has a physiological control mechanism, homeostasis, to maintain a stable and optimal internal environment independent of a changing external environment, this mechanism is not protection enough in the sub-arctic areas. Man is totally dependent on personal protective equipment, established working procedures and training to perform the work within specified safety and efficiency limits.

 Man is totally dependent on personal protective equipment, established working procedures and training

Increasing development and human activity in the Arctic environment calls for increased research focus on the appropriate applied human physiology in order to increase our knowledge on how the organism adapts to extreme environments.

It is well recognized that cold environments have negative health effects on the human body, but an important question is are there any increased health risks due to the physiological stress and decreased performance associated with survival requirements, for example having to wear heavy protective clothing constantly?

The course participants gets to experience field testing of immersion suits

The course participants gets to experience field testing of immersion suits

As diving is likely to be an important activity in these regions, the long-term health effects for divers who undertake the majority of their work in cold water should also be considered. More knowledge is needed to understand which processes come into play when the body’s ability to adaptation is exceeded, why one human reacts differently to another when exposed to the same environments and stressors, and how we can prepare ourselves to be protected against adverse health effects of exposures to extreme environments both in the short and long term.

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In 1990 the course “Health, Protection and Survival in the Cold” was arranged at Svea, and this was the first course in a series of courses that have been held throughout the years since then. All in all, some 250 persons have participated the course since its beginning in 1990, to get a better understanding of the different elements one meets in extreme environments and how they influence our own physiology.

With the increasing activity in the arctic regions, research within the human physiology and its response in the cold environment is necessary and give bases for our course.

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Are you at PhD student or Supervisor within Cardiovascular Disease in Norway?

Blogger: Øivind RognmoØivind Rognmo2

Are you at PhD student or Supervisor within Cardiovascular Disease in Norway?

I will recommend you to be members of the Norwegian PhD School of Cardiovascular Research (NORHEART) as it may offer you a lot of benefits.

 Foto: Geir Mogen, Istockphoto.com

NORHEART members comprise PhD students in Norwegian cardiovascular research, their supervisors, as well as lecturers from Norway and abroad. Sign up today to be a part of the number one education network for cardiovascular scientists in Norway!

Who can become member of NORHEART? All students from PhD programs or Medical Students Research programs at Norwegian Universities with projects focused on cardiovascular research. Supervisors, postdocs and other researchers within the field of cardiovascular research are also encouraged to register as members. Previous student members are listed as NORHEART alumnis.

What are the benefits for NORHEART members?

  • Priority at NORHEART events
  • Opportunities for travel and exchange grants
  • Automatic e-mail updates on key NORHEART events

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Improving nanoparticles for battling cancer

Blogger: Sjoerd Haksjoerd hak

 

The Research Council of Norway has recently awarded grants under the funding scheme Independent Basic Research Projects – Medicine, Health Sciences and Biology (FRIMEDBIO). There is tough competition for this funding nationally, and only the best projects get through. The Faculty of Medicine, NTNU, has been awarded funding for three talented young researchers, three research projects and two post docs. You can read about all these projects on the blog over the coming weeks. Sjoerd Hak received FRIMEDBIO-funding for his post doc project: “Multimodal in vivo study of nanoparticle decomposition and targeting dynamics”

In the field of nanomedicine, the use of drug loaded nanoparticles to deliver drugs to tumours is now well established (see Figure 1).

Tumour bloodvessels are very leaky as compared to healthy vasculature. When drug loaded nanoparticles are injected into the bloodstream, they can leak from the leaky tumour bloodvessels into the tumour tissue; whereas leakage from the blood vessels in healthy tissue is limited.

Exciting developments in nanotechnology have allowed for the production of a wide variety of advanced nanoparticles.

As compared to conventional therapy without nanoparticles, this results in a larger part of the injected drugs ending up in the tumour and a reduction in side effects (Figure 1B).

Figure 1. A: General design of a nanoparticle loaded with drug. The core/shell/surface coating can be composed of a variety of different materials, which has resulted in an enormous diversity in the design, and hence properties, of different nanoparticles. B: When a drug loaded nanoparticle is injected into the blood, it can leak into the tumour tissue due to the leaky tumour blood vessels. C: General design of a targeted nanoparticle loaded with drug. D: Nanoparticles can be specifically targeted to the cells making up the tumour vasculature. When these are injected into the blood, they accumulate in the tumor vasculature. The targeting and subsequent disrupting of tumour blood vessels is a promising therapeutic strategy. E: Nanoparticles can also be specifically targeted to cancer cells. When these targeted nanoparticles are injected into the blood, they accumulate in the tumor and bind to tumor cells, increasing the amount of drug delivered to individual cancer cells.

Figure 1. A: General design of a nanoparticle loaded with drug. The core/shell/surface coating can be composed of a variety of different materials, which has resulted in an enormous diversity in the design, and hence properties, of different nanoparticles. B: When a drug loaded nanoparticle is injected into the blood, it can leak into the tumour tissue due to the leaky tumour blood vessels. C: General design of a targeted nanoparticle loaded with drug. D: Nanoparticles can be specifically targeted to the cells making up the tumour vasculature. When these are injected into the blood, they accumulate in the tumour vasculature. The targeting and subsequent disrupting of tumour blood vessels is a promising therapeutic strategy. E: Nanoparticles can also be specifically targeted to cancer cells. When these targeted nanoparticles are injected into the blood, they accumulate in the tumour and bind to tumour cells, increasing the amount of drug delivered to individual cancer cells.

Although this has improved therapy for a group of cancer patients, the full potential of nanoparticles in cancer therapy remains to be explored. Exciting developments in nanotechnology have allowed for the production of a wide variety of advanced nanoparticles.

One highly interesting development is the synthesis of so-called targeted nanoparticles: Nanoparticles equipped with molecules on their surface making them specifically recognise and accumulate in tumour tissue (Figure 1C). This is a very promising approach to deliver drugs specifically to tumours and to spare healthy tissue (Figure 1 D-E).

For the development and successful application of such targeted nanoparticles, detailed studies to learn about and understand the in vivo behaviour of these novel targeted nanoparticles are essential.

For example, it is not well known how fast targeted nanoparticles accumulate in tumour tissue after injection. Moreover, it is now becoming clear that certain nanoparticles readily disintegrate upon injection into the blood, resulting in drug release in the blood. As such, the drug may be released before the tumour is reached. Hence, knowledge of nanoparticle degradation and tumour targeting rates and dynamics are crucial for successful development and application of targeted nanoparticles. However, these dynamics remain largely unstudied, which may be compounded by the fact that suitable experimental in vivo tools to do so are lacking

Ultimately, we anticipate to fine-tune our nanoparticle design and increase their value in the battle against­­­ cancer.

Over the last four years, during my recently completed PhD project, we have established the synthesis of innovative nanoparticles of which such dynamics can be quantitatively monitored. Furthermore, combining in vivo microscopy and magnetic resonance imaging, we have developed a unique experimental set-up which is highly suitable to study in vivo nanoparticle dynamics.

Over the next years, this novel experimental approach will be exploited to study degradation and targeting dynamics of our nanoparticles at an unprecedented level of detail. Importantly, this will provide general knowledge applicable to a variety of targeted therapies. Ultimately, we anticipate to fine-tune our nanoparticle design and increase their value in the battle against­­­ cancer.

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Your moustache makes a difference

Blogger: Siver Moestue532136_10151252982417512_69966992_n

 

 

 

 

During last years “Movember” – an annual month-long event involving the growing of moustaches during the month of November to raise awareness of prostate cancer – the Movember Foundation and associated charities raised 839 million NOK worldwide.

As a result, the Norwegian Cancer Society (Movember’s collaborator in Norway) distributed NOK 3.6 mill to research on prostate cancer in Norway. One of the two projects receiving support is a project led by Prof. Tone Frost Bathen (MR Cancer Group, ISB) and Prof. Anders Angelsen (Dept. of Surgery, St. Olavs Hospital and NTNU). The project is entitled “PET/MR imaging for improved diagnosis and personalized treatment in prostate cancer”.

.. we are highly grateful for the support from the Movember Foundation and all those who contribute by growing a moustache or make a donation to somebody who did.

This funding (NOK 1.2 mill) will be used to conduct a clinical trial in patients with suspected recurrence after prostate cancer surgery. This is a MO13-Download-Styleguide-I-patient group where rapid and accurate diagnostic procedures are needed to improve the outcome of the disease.

In collaboration with the Dept. of Radiology at St. Olavs Hospital, we will compare the diagnostic performance of PET/MR imaging with that of the current diagnostic procedures (CT + bone scintigraphy). A novel radiotracer, 18FACBC, will be used as its pharmacokinetic profile is suitable for imaging of the pelvic area.

Using PET/MR as a “one-stop-shop” can potentially simplify patient logistics, thereby shortening the time needed for re-staging the disease.

In addition, this tracer can also detect skeletal metastases, and we can therefore compare the sensitivity of PET/MR imaging to that of bone scintigraphy. Our hypothesis is that PET/MR imaging both can provide more accurate clinical information and reduce the number of different examinations the patients need to go through. Using PET/MR as a “one-stop-shop” can potentially simplify patient logistics, thereby shortening the time needed for re-staging the disease.

The project team believes that the multidisciplinary approach and the use of new technology will contribute to improved health services for prostate cancer patients, and we are highly grateful for the support from the Movember Foundation and all those who contribute by growing a moustache or make a donation to somebody who did. For more information on the study, contact Prof. Tone F. Bathen or Prof.  Anders Angelsen.

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