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

Researchers investigating a novel device to repair the mitral heart valve report 100 percent procedural success in a safety and performance study, the first such study done in humans. The image-guided device, based on technology developed at the University of Maryland School of Medicine, is deployed through a tiny opening in a beating heart, avoids open-heart surgery, automates a key part of the valve repair process, simplifies the procedure and reduces operating room time.
Traditional mitral valve repair is performed during open heart surgery, a lengthy operation in which the patient’s chest is opened, the heart is stopped and circulation is maintained with a heart-lung bypass machine. Recovery can take months, and patients face significant risks. As a result, there is considerable interest in finding less invasive mitral valve treatment options.
‘We think this is a safer approach than open heart surgery,’ says principal investigator James S. Gammie, MD, professor and chief of cardiac surgery at the University of Maryland School of Medicine. ‘We think the safety profile is going to be better and, ultimately, people will be able to go home from the hospital the next day.’
The device, known as the Harpoon TSD-5, made by Harpoon Medical Inc. of Baltimore, is an investigational device. At the present time, the US Food and Drug Administration has not approved the device for use in patients in the United States. It is designed to treat degenerative mitral regurgitation (MR), the most common type of heart valve disorder. In MR, a leaky valve lets blood travel in the wrong direction on the left side of the heart, causing shortness of breath, fluid retention, irregular heartbeats and fatigue. MR develops when the small fibrous cords that open and close the valve’s flaps, known as leaflets, are broken or stretched, preventing them from closing tightly and causing the leaflets to bulge or prolapse upward toward the left atrium. The natural cords connect the valve flaps to muscles inside the heart that contract to close the mitral valve, which gets its name because its two flaps resemble a bishop’s mitre.
The TSD-5 anchors artificial cords on the flaps to take the place of the natural cords. The artificial cords are made of expanded polytetrafluoroethylene (ePTFE), a polymer commonly used as sutures in cardiac surgery.
Surgeons insert the device into the beating heart through a tiny opening in the ribcage and, using echocardiographic imaging, guide it to the surface of the defective mitral flaps. When the surgeon determines the optimal placement for an artificial cord, the device is actuated and a specially designed needle wrapped with 50 coils of ePTFE makes a tiny hole and sends the cord material through the flap. An automated process makes a knot to hold the cord in place. The other end of the cord is adjusted for optimum length and tied to the outside layer of the heart, the epicardium. Three or four cords are required for most cases.
Gammie says the ability to make adjustments to the artificial cords while the heart is beating is a key advantage over open heart surgery: ‘The heart’s fully loaded and beating and we can just adjust the length of the cords to optimize the result, and only when we’re really happy do we tie it off.’

University of Maryland School of Medicine http://tinyurl.com/j5m9lmp

A team of Mayo Clinic researchers has, for the first time, successfully mapped patterns of prostate cancer recurrence, following surgery. Using C-11 choline PET imaging and multi-parametric MRI, researchers found an anatomically diverse pattern of recurrence, which may help optimize treatment of patients whose prostate cancer returns after surgery.
‘This study has important implications for men who have a rising prostate-specific antigen (PSA) test, also known as biochemical recurrence, after radical prostatectomy for prostate cancer,’ says Jeffrey Karnes, M.D., a urological surgeon at Mayo Clinic. ‘In men with biochemical recurrence, determining where the disease has recurred is quite challenging, especially when the PSA level is low.’
According to Dr. Karnes, in the U.S., approximately 30 percent of patients who have had an initial prostate cancer surgically excised will suffer a recurrence and seek treatment. ‘Current imaging tests like conventional bone and CT scans are not sensitive enough to identify sites of recurrence, especially when the PSA value is lower than 10,’ he says.
Dr. Karnes says the combination of C-11 choline PET scanning and multiparametric MRI, helps physicians accurately identify sites of recurrence at an average PSA of 2. More importantly, he says, ‘This type of staging allows us to identify sites of recurrent disease that can be potentially treated either surgically or with radiation.’
Dr. Karnes and his team also were able to describe patterns of prostate cancer recurrence. They found that nearly two-thirds of men in the study had recurrence limited to the pelvis, which potentially can be targeted for radiation therapy.

Mayo Clinic http://tinyurl.com/h9ot93x

Computer algorithms can automatically interpret echocardiographic images and distinguish between pathological hypertrophic cardiomyopathy (HCM) and physiological changes in athletes’ hearts, according to research from the Icahn School of Medicine at Mount Sinai (ISMMS).

HCM is a disease in which a portion of the myocardium enlarges, creating functional impairment of the heart. It is the leading cause of sudden death in young athletes. Diagnosing HCM is challenging since athletes can present with physiological hypertrophy, in which their hearts appear large, but do not feature the pathological abnormality of HCM. The current standard of care requires precise phenotyping of the two similar conditions by a highly trained cardiologist.

‘Our research has demonstrated for the first time that machine-learning algorithms can assist in the discrimination of physiological versus pathological hypertrophic remodeling, thus enabling easier and more accurate diagnoses of HCM,’ said senior study author Partho P. Sengupta, MD, Director of Cardiac Ultrasound Research and Professor of Medicine in Cardiology at the Icahn School of Medicine at Mount Sinai. ‘This is a major milestone for echocardiography, and represents a critical step toward the development of a real-time, machine-learning-based system for automated interpretation of echocardiographic images. This could help novice echo readers with limited experience, making the diagnosis rapid and more widely available.’

Using data from an existing cohort of 139 male subjects who underwent echocardiographic imaging at ISMMS (77 verified athlete cases and 62 verified HCM cases), the researchers analyzed the images with tissue tracking software and identified variable sets to incorporate in the machine-learning models. They then developed a collective machine-learning model with three different algorithms to differentiate the two conditions. The model demonstrated superior diagnostic ability comparable to conventional 2D echocardiographic and Doppler-derived parameters used in clinical practice.

‘Our approach shows a promising trend in using automated algorithms as precision medicine techniques to augment physician-guided diagnosis,’ said study author Joel Dudley, PhD, Director of the Institute for Next Generation Healthcare and Director of the Center for Biomedical Informatics at ISMMS. ‘This demonstrates how machine-learning models and other smart interpretation systems could help to efficiently analyse and process large volumes of cardiac ultrasound data, and with the growth of telemedicine, it could enable cardiac diagnoses even in the most resource-burdened areas.’

Mount Sinai Health System www.mountsinai.org/about-us/newsroom/press-releases/mount-sinai-researchers-demonstrate-ability-of-machine-learning-algorithms-in-echocardiographic-interpretation-and-diagnosis-of-hcm

Patients with a combination of left ventricular dysfunction and low aortic valve gradient, or reduced force of blood flow through the aortic valve, have higher mortality rates and a greater risk of recurrent heart failure after transcatheter aortic valve replacement (TAVR), with low aortic valve gradient the driving force behind their poor outcomes.
Patients with this profile, however, should still be considered for TAVR, especially since research on similar patients who had surgical valve replacement found that they could withstand the procedure, Suzanne J. Baron, M.D., M.Sc., the study’s lead author, said.
Low aortic valve gradient is a result of aortic stenosis, a narrowing of the opening of the aortic valve. This condition results in restricted blood flow from the left ventricle to the aorta. Stenosis can also lead to impaired left ventricular ejection fraction, meaning that the heart pumps an inadequate amount of blood with each beat.
To treat aortic stenosis, physicians typically replace the aortic valve, either through open heart surgery or through TAVR. During TAVR, a new valve is delivered to the heart through arteries in the leg or chest. For patients at high risk of surgical complications, TAVR has been shown to be at least as effective as open heart surgery.
Previous studies of valve replacement through surgery have shown that patients with impaired left ventricular ejection fraction and low aortic valve gradient do not do as well as those with better cardiac function and blood flow. In this study, researchers set out to determine the roles that left ventricular dysfunction and low aortic valve gradient play in rates of death and recurrent heart failure following this less invasive procedure.
Since left ventricular dysfunction and low aortic valve gradient are oft en seen together, researchers aimed to determine which of these factors was the driving force behind the poor clinical outcomes. Aft er adjusting for several clinical factors, including age, sex, previous cardiovascular bypass grafting, and previous angioplasty, only the presence of a low aortic valve gradient was associated with higher mortality rates and recurrent heart failure. The effect of left ventricular ejection fraction was no longer significant.
Baron, a cardiologist at Saint Luke’s Mid America Heart Institute, University of Missouri-Kansas City, in Kansas City, Missouri, said the finding that left ventricular dysfunction was not independently associated with long-term mortality after adjusting for clinical factors "provides important reassurance regarding the benefits of TAVR, even in patients with severe left ventricular dysfunction." The study results also suggest that patients with a low aortic valve gradient may be a subset of aortic stenosis patients who have less long-term benefit from this procedure, although the majority of these patients who were still alive one year after the procedure had improved quality of life. Baron concludes that "neither severe left ventricular dysfunction nor low aortic valve gradient alone or in combination provide sufficient prognostic discrimination to preclude treatment with TAVR in the absence of other adverse prognostic factors."

The American College of Cardiology http://tinyurl.com/zw28rc4