‘Atrial fibrillation is thought to be responsible for 20 to 30 percent of all strokes in the United States,’ said Northwestern’s Michael Markl, the Lester B. and Frances T. Knight Professor of Cardiac Imaging. ‘While atrial fibrillation is easy to detect and diagnose, it’s not easy to predict who will suffer a stroke because of it.’

Markl, who is a professor of biomedical engineering in the McCormick School of Engineering and of radiology in the Feinberg School of Medicine, has developed a new imaging technique that can help predict who is most at risk for stroke. This breakthrough could lead to better treatment and outcomes for patients with atrial fibrillation.

Atrial fibrillation is linked to stroke because it slows the patient’s blood flow. The slow, sluggish blood flow can lead to blood clots, which can then travel to the brain and initiate stroke. Markl’s cardiac magnetic resonance (CMR) imaging test can detect the blood’s velocity through the heart and body. Called ‘atrial 4D flow CMR,’ the technique is non-invasive and does not require contrast agents. The imaging program, which images blood flow dynamically and in the three spatial dimensions, comes in the form of software that can also be integrated into current MRI equipment without the need of special hardware and scanners or equipment upgrades.

4D flow CMR can be employed to measure in-vivo 3D blood flow dynamics in the heart and atria. Derived flow stasis maps in the left atrium and left atrial appendage are a novel concept to visualize and quantify regions with low flow, known to cause clot formation and risk for stroke.
‘We simply programmed the scanner to generate information differently – in a way that wasn’t previously available,’ Markl said. ‘It allows you to measure flow, diffusion of molecules, and tissue elasticity. You can interrogate the human body in a very detailed manner.’

Historically, physicians have attempted to assess stroke risk in atrial fibrillation patients by using a risk scoring system, which takes risk factors, such as age, general health, and gender, into account. Higher risk patients are then given medicine to prevent blood clots that lead to stroke.

‘It’s very well accepted that these therapies significantly reduce the risk of stroke,’ Markl said. ‘But they also increase risk of bleeding complications. It’s a dilemma that physicians face. They want to reduce one risk without introducing another risk. It’s particularly difficult for younger patients who might be on these medications for a long period of time. Maybe the risk of bleeding is initially small. But after taking medication for 20 or 30 years, it’s more and more likely that they’ll experience complications.’

Markl’s 4D flow imaging technique can give a more precise assessment of who needs the medication, preventing physicians from over treating their patients. In a pilot study with 60 patients and a control group, Markl found that atrial fibrillation patients who would have been considered high risk for stroke by the traditional scoring system in fact had normal blood flow, while patients who were considered lower risk sometimes had the slow blood flow indicative of potential clotting.

‘About 50 or 60 percent of patients who you would consider high risk actually had normal flows,’ Markl said. ‘You could then hypothesize that those 50 percent don’t really need the treatment.’

Northwestern University www.mccormick.northwestern.edu/news/articles/2016/10/imaging-stroke-risk-in-4d.html

Researchers at ETH Zurich have developed a new marker substance for positron emission tomography (PET) that will allow them to monitor the progression of the degenerative muscle disease amyotrophic lateral sclerosis (ALS) in a patient’s brain. Many people will remember the Ice Bucket Challenge back in the summer of 2014. This social media campaign helped patient support groups to promote public awareness of the rare, but debilitating and incurable muscle disease, amyotrophic lateral sclerosis (ALS). The challenge involved one person nominating three others through social media, creating a snowball effect, to make a financial donation to an ALS support group, or – as a forfeit – to pour a bucket of ice-cold water over their heads. This action was supposed to give participants a brief insight into one of the symptoms experienced by someone suffering from degenerative muscle disease.
ALS induces progressive degeneration of the motor neurons that control the muscles. The patient suffers from muscular atrophy and paralysis, accompanied by symptoms such as difficulty walking, speaking and swallowing. At best, drugs can delay the progression of the disease, but oft en life expectancy is only a few years after the initial diagnosis. Very little is known about the causes of the disease.
A new marker substance developed by ETH researchers in collaboration with specialists at St. Gallen Cantonal Hospital and University Hospital Zurich could potentially make a vital contribution to ALS research. The new substance could perhaps make it possible to monitor the progression of ALS in patients using positron emission tomography (PET). The PET imaging technique renders specific molecules on the cell surface visible within the body tissue. The scan uses marker substances, known as PET ligands, that adhere to these molecules via the lock-and-key principle. The radiation emitted by the radioactive markers is very short lived, with a half-life between several minutes and a few hours. This radiation is measured during the PET scan.
The newly developed PET ligand binds to a receptor molecule in the body’s neurotransmitter system for cannabis-based substances, known as the cannabinoid receptor 2 (CNR2). This is very common in inflamed nerve tissue, and is also found in the central nervous system of patients suffering from ALS.
‘The big challenge we faced was to develop a PET ligand that only binds to CNR2, but not to the related cannabinoid receptor 1 (CNR1),’ explains Simon Ametamey, a professor at the Institute of Pharmaceutical Sciences at ETH Zurich. CNR1 occurs naturally in the human brain, where it elicits the pain-relieving and intoxicating effect of cannabis.
The researchers in Professor Ametamey’s group synthesized a series of molecules and performed an in vitro study to measure their ability to bind to the receptors CNR2 and CNR1. The team went on to successfully test the molecule with the most obvious preference for CNR2 in rats and mice with inflamed nerve tissue. Th e scientists have filed a patent for this molecule. The next step will be to perform clinical trials in humans.
‘The new PET ligand could help us to research ALS more effectively and to understand how the disease progresses,’ says Professor Ametamey. It could also improve the early diagnosis of the disease. It might also be potentially interesting for research and diagnosis of other neurological disorders such as Alzheimer’s, Parkinson’s or multiple sclerosis.

ETHZ http://tinyurl.com/gvnvsy5

The brain is the most temperature-sensitive organ in the body. Even small deviations in brain temperature are capable of producing profound effects-including behavioural changes, cell toxicity, and neuronal cell death. The problem faced by researchers and clinicians is how to measure and understand
these changes in the brain and how they are influenced by complex biochemical and physiological pathways that may be altered by disease, brain injury or drug abuse.
In a new paper Stefan Musolino of the University of Adelaide and the ARC Centre of Excellence for Nanoscale BioPhotonics, Australia, and his colleagues describe a new optical fibre-based probe capable of making pinpoint brain temperature measurements in moving lab animals.
‘Within our centre we house physicists, chemists, and medical researchers and one of the interests of our centre’s Origin of Sensation’ theme is temperature change in the central nervous system,’ Musolino said. ‘It is only recently that more studies in my area of research- drug-induced hyperthermia- have started looking at changes in brain temperature in addition to changes in core body temperature within drug-treated animals.
We wanted to further investigate these drug-induced brain temperature changes using centre-developed probes in order to develop a better understanding of the mechanisms driving them.’
The probe developed by Musolino and his colleagues consists of an optical fibre, sheathed within a protective sleeve and encased within a 4-millimeter-long 25-gauge needle. The end-face of the approximately 2-mm-long probe tip is dipped into molten glass made of tellurite, doped with a small amount of the rareearth oxide erbium. When inserted into the brain, the colour of the light emitted from the erbium ions will vary depending on the temperature of the surrounding tissue; the temperature of that tissue can thus be determined by monitoring the light of these colour changes. This method allows for measurements to be performed with a precision of a fraction of a degree (0.1degree CelsiusC).
‘The area that can measure temperature is less than 125 micrometers in size,’ said study co-author Erik Schartner ‘making it highly spatially precise and able to isolate temperature readings from very small brain areas.’ The researchers say it is possible to make the temperature-sensing area of the probe tip smaller still – as small as a few microns across – by modifying the probe’s design.
The probe’s immediate application will be to investigate changes in brain temperature within moving lab animals exposed to certain drugs of abuse, such as MDMA (or ecstasy’). ‘We will also look at the possible therapeutic properties of the tetracycline antibiotic minocycline and its ability to attenuate the changes in temperature caused by the administration of MDMA,’ said Musolino. ‘In the future we will also be looking into combining this probe with other optical sensors in the hopes of developing new optical fibre-based sensing techniques for use in medical science labs that are examining real-word medical problems.’
Eventually, a fully developed probe could be used in human brain temperature monitoring after traumatic brain injury, stroke or hemorrhage – times when the brain is extremely sensitive and small deviations in temperature can lead to additional brain injury.
‘Continuous monitoring of brain temperature after brain injury would allow for the effects of hyperthermia management techniques such as anti-pyretics – drugs that reduces fever – and hypothermia to be observed and evaluated by clinicians in real time,’ Musolino said. ‘These new tools and this deeper understanding will ultimately give us better understanding of the brain and how to more quickly react to brain injury.’

The Optical Society http://tinyurl.com/hkrqo9w

Carestream Health’s focus on the radiology profession has earned it the No. 1 market position for its DRYVIEW Laser Imaging Film, resulting in the production of more than one billion square meters of this and other specialty films at its White City, Oregon facility – enough film to circle the Earth 70 times. CARESTREAM DRYVIEW film for medical imaging use is sold in more than 140 countries. It contains more than 25 different components, including nanoparticles, with four layers coated simultaneously on the top of a PET film base and two layers on the back. The six-layer DRYVIEW film is coated in one pass at a rate of hundreds of feet per minute with in-line quality inspection to meet FDA-regulated Class 1 medical device requirements. The company’s manufacturing capabilities include its Contract Manufacturing operations that apply specialized manufacturing processes using high-technology coating assets to help contract-coating customers and partners develop better products at a competitive cost using coated or cast filmbased advanced materials. Carestream Contract Manufacturing offers optimal product design, technology integration, manufacturing support, distribution, and finishing (slitting and packaging) capabilities with facilities in Asia and North America. The company can create structures of up to 20 precision-coated layers in a single pass, with options for two-sided coating, radiation cure, on-line inspection and lamination. Carestream adheres to top global standards for quality and certification including ISO 9001, ISO 13485 and ISO 14001.

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