Virtual models can be created in the angiography room thanks to an approach developed by researchers at the University of Montreal Hospital Research Centre (CRCHUM) and the university’s departments of radiology, radiation oncology, and nuclear medicine. The latest advances were presented by Dr. Gilles Soulez at the Cardiovascular and Interventional Radiology Society of Europe (CIRSE).
For 25 years, Dr. Soulez has been involved in developing medical imaging technologies to prevent complication for, operate on, and monitor patients with abdominal aortic aneurysms. The main problem has been the ability to properly visualize the area to be treated. ‘Remarkable advances in imagery have improved surgery and helped to develop less invasive interventions. But the images are still far from being perfect. We want to develop new software to maximize the use of images generated with current ultrasound, scanning, and magnetic resonance imaging (MRI) technologies to ultimately provide more personalized treatments,’ he explained.
On the screen is a coloured image of an abdominal aorta. But there’s something wrong with the photo: an enlarged area that looks like a small balloon. It’s an abdominal aortic aneurysm, a disease caused by weakening of the vessel wall. Linked to atherosclerosis risk factors such as hypertension and smoking, the disease is the 13th cause of death in North America. It especially affects men. ‘If you have a ruptured aneurism, you have a one in two chance of dying,’ Dr. Soulez said.
Currently, a simple abdominal ultrasound or measurement of the aorta with a scanner can detect patients at risk of aneurysm rupture. Beyond 5 cm for women and 5.5 cm for men, surgery is usually recommended. But operations have their own risks, so researchers want to refine screening to provide the most appropriate treatments for patients who really need surgery.
To avoid rupturing the small balloon formed by the abdominal aortic aneurysm, two treatment options exist: open surgery to replace the diseased section or endovascular grafting, in which a catheter is inserted in the groin to deliver a stent-graft through the blood vessels to the aneurysm. This option is less invasive, but in some patients, the morphology of the aneurysm is not suited to this kind of treatment. Using scanner images, Soulez’s research provides three-dimensional images of all components of the aneurysm, i.e., the light, the thrombus or clot, the wall, and the calcification. ‘The grid is used to establish growth profiles of the aneurysm. We are now working to create simulations to better predict the risk of rupture, adding biomechanical properties such as tissue elasticity and connectivity at each pixel of the grid,’ he explained.
Currently, the operation is performed using static images taken by a scanner before the procedure. The procedure itself is done under fluoroscopy by injecting dye into the vessels to be treated. ‘The image produced by X-ray shows the dye in the vessels and the stent being inserted, but not the wall. This approach requires a lot of dye, which can be toxic for the patient if used in excessive amounts,’ said the radiologist.
It’s thanks to a grant from the Canadian Institutes of Health Research (CIHR), in partnership with Siemens, that Dr. Soulez’s laboratory has been able to develop this approach that combines all available data. ‘We superimpose the images, and this helps to visualize the area to be treated. But in reality, the tools we introduce into the body during the procedure deform the organs. We are testing at the CHUM and in Halifax right now a new approach that uses a computer to automatically recognize the tools introduced into the body and correct the deformities they cause,’ he said. ‘We hope this simulation-operation model will improve the accuracy of the procedure.’

University of Montreal Hospital Research Centrehttp://tinyurl.com/gmo8p4w

For the first time, researchers can provide early detection of plaques that have a high likelihood of clotting and/or rupture. Boston University School of Medicine (BUSM) scientists have observed the development and evolution of atherosclerotic plaques at the highest risk for thrombosis (clotting) by using non-invasive Magnetic Resonance Imaging (MRI).

Atherosclerosis is an important contributor to heart attacks and strokes, the leading causes of death in developed nations despite progress in their prevention. Atherosclerosis is a complex disease with many stages, ranging from plaques that can remain clinically silent for decades (‘stable’) to dangerous (‘vulnerable’) plaques that in their most highly advanced stage (‘highest risk’) can suddenly form a blood clot (thrombus) in the vessel, leading to myocardial infarction or stroke.

Researchers at BUSM, under the direction of James A. Hamilton, PhD, Professor of Physiology and Biophysics and Research Professor of medicine at BUSM, pioneered the use of MRI to identify high-risk plaques in a unique experimental model encompassing both atherosclerosis and thrombosis (atherothrombosis). The group established criteria for distinguishing vulnerable and stable plaques from analysis of in vivo (from a living organism) images of mature plaques. The plaques were then tested to determine their stability.

In the new study, images were obtained at monthly intervals to provide information about the pathways of progression (plaque history) of individual plaques in the vessel and to determine whether MRI can discriminate vulnerable and stable plaques at early times.

‘Vulnerable plaques and stable plaques showed different physiological progression patterns beginning after one month. Stable plaques exhibited no features of vulnerability at any time, whereas vulnerable plaques showed a progression of vulnerable features, especially in the last month,’ explained Hamilton, who is the corresponding author.

According to Hamilton, successive MRIs could provide a non-invasive means of identifying plaques that are evolving to become a high risk for rupture. ‘This work provides us a unique model for evaluating potential therapies after vulnerable plaques are clearly established.’ EurekAlert

By identifying new compounds that selectively block mitochondrial respiration in pathogenic fungi, Whitehead Institute scientists have identified a potential antifungal mechanism that could enable combination therapy with fluconazole, one of today’s most commonly prescribed fungal infection treatments. The approach could also prevent the development of drug resistance.

‘Our research adds weight to the idea that effective antifungal drugs can target even those mitochondrial proteins that are highly conserved in humans and fungi, and that this could be a way to make a broad spectrum antifungal combination therapy that would be less susceptible to resistance,’ says Benjamin Vincent, a former graduate student in Whitehead Member Susan Lindquist’s lab who is now a scientist at Yumanity Therapeutics.

Fungi cause bothersome diaper rashes, oral thrush, athlete’s foot, and vaginal yeast infections, but they are also responsible for life-threatening infections in the immune-compromised, including patients receiving transplants, people with HIV/AIDS, cancer patients, and the elderly. Severe invasive fungal infections have a mortality rate of 30-50% and cause an estimated 1.5 million deaths worldwide annually.

Doctors rely on three main drug classes-the azoles (e.g., fluconazole), the echinocandins, and amphotericin-to treat these severe infections, but often with limited success. Many strains of pathogenic yeast, such as Candida albicans (C. albicans) can develop resistance to these drugs. Although combining therapies is a potent method to combat drug resistance in bacteria, antifungal drugs often perform poorly when used in combination due to their complex pharmacology and antagonistic antifungal mechanisms. When used individually, current antifungal drugs can have significant toxicities that are markedly enhanced when the drugs are used in combination.

‘Pharmaceutical companies are abandoning the development of antifungals,’ says Lindquist, who is also a Howard Hughes Medical Institute investigator and a professor of biology at MIT. ‘Fungi are much more similar to us than bacteria, so it is hard to find agents that attack them but not us.’

To identify new potential antifungals that could be combined with fluconazole, a team of Whitehead and MIT scientists screened 300,000 compounds, selecting one with the most apparent potential-Inz-1-for further study. Their work is described online this week in the journal Cell Chemical Biology.

Inz-1 inhibits the growth of C. albicans in media lacking glucose but only partially impairs growth when glucose is present, indicating that Inz-1 interferes with mitochondrial function. Indeed, the researchers determined that Inz-1 targets the cytochrome B protein required for mitochondrial production of ATP. The authors then worked with synthetic chemist Jean-Baptiste Langlois in the laboratory of Stephen Buchwald in the MIT Department of Chemistry to iteratively synthesize and test analogs of Inz-1 to improve its properties. This work led to Inz-5, which exhibited dramatically improved potency and selectivity for fungal cytochrome B. Although cytochrome B is highly conserved across humans and many pathogenic fungi, including Cryptococcus neoformans, Aspergillus fumigatus, and Rhizopus oryzae, Inz-5 exploits important differences in the amino acid sequence of the protein that enable selectivity for fungi.

Because the compound is metabolized too rapidly for study in mice, the team mimicked its effects by knocking out cytochrome B in C. albicans and infecting mice with this mutant strain. Overall, the cytochrome B knock-out strain is much less virulent, and mice infected with it survive much longer than those with the wild-type strain. Curiously, the mutant yeast seems to cause more infections in the brain and central nervous system than unaltered C. albicans. Treatment with fluconazole effectively clears infection caused by this mutant, indicating that combination antifungal therapy could be highly effective when one of the agents targets mitochondrial respiration.

Not only does hitting cytochrome B disable C. albicans’ virulence, but the fungus’s altered mitochondrial function means that the yeast is unable to adapt to the nutrient-deprived conditions present within the host, particularly inside macrophages. Instead of punching its way out of a macrophage that has engulfed it, the yeast remains trapped and loses its fight against the immune system.

Although Inz-1’s therapeutic promise is limited by its poor stability in animals, the compound proves that conserved cellular processes can be viable targets for selective antifungal therapeutics and could provide targets for effective combination antifungal therapy.

Whitehead Institute wi.mit.edu/news/archive/2016/disrupting-mitochondrial-function-could-improve-treatment-fungal-infections

By cleverly combining two medical imaging techniques, A*STAR scientists have found a way to produce high-resolution images of the lungs that is both high resolution and accounts for lung movement due to breathing. The method is expected to greatly assist clinicians when they target tumours in the lungs during radiotherapy.
Cancerous tumours in the lungs are often treated by irradiating them with high-energy X-rays, but this therapy is complicated by the fact that tumours are moving targets, due to the expansion and contraction of the lungs as the patient breathes.
Currently, two biomedical imaging techniques are used to help clinicians locate tumours in the lungs, both of which have their advantages and disadvantages. Three-dimensional computed tomography (3D-CT) provides high-resolution images, but it can only provide snapshots in time and there are safety concerns surrounding exposure to X-rays. In contrast, four-dimensional magnetic resonance imaging (4D-MRI) does not employ ionizing radiation and allows continuous tracking of the lung motion, but its low spatial resolution yields blurred images.
Now, Soo Kng Teo and co-workers at the A*STAR Institute of High Performance Computing in Singapore have combined these two techniques to realize the best of both approaches – a high-resolution imaging method that accurately accounts for lung movement.
The researchers used 3D-CT to obtain a sharp static image of the lungs. They mathematically combined this static image with the four-dimensional (the three spatial dimensions plus time) information extracted from images obtained using 4D-MRI. This enabled them to achieve a high spatial resolution to realize excellent clarity and show movement of a lung tumour over several breathing cycles.
They tested their imaging technique on six lung-cancer patients and obtained impressive results: the average error was less than two millimetres.
As with all medical innovations, adoption of the technique in hospitals depends on obtaining the backing of medical equipment companies and meeting the many regulatory requirements. ‘The biggest hurdle will be convincing equipment manufacturers to adopt the imaging method,’ says Teo.

A*STAR http://tinyurl.com/hucefzb