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After suffering a heart attack, some patients develop a microvascular obstruction, an area of the injured heart with extremely poor blood flow. These patients are at an increased risk of developing heart failure in the future.

Medical imaging technologies such as magnetic resonance imaging (MRI) and positron emission tomography (PET) can be used to study the remodeling process after a heart attack that can lead to a microvascular obstruction. However, poor blood flow makes it difficult to get contrast agents into the obstruction. Contrast agents are used in medical imaging to show contrast between different types of tissue, such as damaged and healthy tissue.

Benjamin Wilk, a PhD candidate at Lawson Health Research Institute and Western University’s Schulich School of Medicine & Dentistry, will investigate whether a hybrid PET/MRI system and a new method of administering contrast agents can allow researchers to image microvascular obstructions and study these “hidden” regions in the heart.

Contrast agents are usually injected as a bolus, meaning the entire injection is administered immediately. In this study, participants will instead receive a constant infusion of an MRI contrast agent and PET tracer, which means the injection will be delivered over the course of an hour. The MRI contrast agent they are using is sensitive to blood flow and scar tissue, and the PET tracer is sensitive to inflammatory cells.

This will allow researchers to study the anatomy, blood flow and inflammatory processes in microvascular obstructions a week after heart attack. Participants will then be imaged again after six weeks to study the long-term effects on heart function.

“Studying the heart after a heart attack using novel contrast agent injection strategies with simultaneous PET/MRI could provide crucial information for treatment planning, helping us reduce the number of people affected by heart failure in the future,” says Wilk. “This project could also lead to further research into finding better ways to administer PET tracers and MRI contrast agents. These methods could be applied to different diseases as well.”

Wilk received a Lawson Internal Research Fund (IRF) Studentship to conduct the study, which will be supervised by Dr. Frank Prato, Assistant Director, Lawson and leader of the Lawson Imaging research program at St. Joseph’s Health Care London.

“Lawson's IRF is valuable for students for many reasons. It not only allows us to conduct further research, it also enriches our experience by giving us opportunities to write grants and attend conferences,” adds Wilk.

The IRF is designed to provide Lawson scientists the opportunity to obtain start-up funds for new projects with the potential to obtain larger funding, be published in a high-impact journal, or provide a clinical benefit to patients. Funding is provided by the clinical departments of London Health Sciences Centre and St. Joseph’s Health Care London, as well as the hospital foundations (London Health Sciences Foundation and St. Joseph’s Health Care Foundation).

Normally samples of bacteria must be removed from their microbiome environment for analysis, which can lead to changes in their metabolic activity and other behaviors, hindering our ability to accurately study the gut or urogenital microbiome.

“This could be avoided if we are able to observe the bacteria in the body using Magnetic Resonance Imaging (MRI),” says Sarah Donnelly, MSc student at Lawson Health Research Institute and the Department of Microbiology and Immunology and collaborative Molecular Imaging program at Western University’s Schulich School of Medicine & Dentistry.

She is investigating the possibility of using magnetically-labelled bacteria with MRI to more directly study microbial interactions in urological and other conditions.

“The hope is that in the future we can use imaging technologies to visualize aspects of the microbiome in its healthy state compared to diseased states to see the early signs of disease and take preventative measures or allow for early intervention,” she says.

Donnelly has received a Lawson Internal Research Fund (IRF) Studentship to conduct the study, which will be supervised by Dr. Jeremy Burton, scientist in Lawson’s Human Microbiome and Probiotics research program at St. Joseph’s Health Care London (St. Joseph’s) and appointed to the Departments of Surgery and Microbiology & Immunology at Schulich Medicine & Dentistry; and Dr. Donna Goldhawk, scientist in Lawson’s Imaging research program at St. Joseph’s and assistant professor in the Department of Medical Biophysics at Schulich Medicine & Dentistry.

Escherichia coli (E. coli) are a common bacterium found in the human gut microbiome and frequently cause non-intestinal conditions like urinary tract infections. The researchers will program E. coli to express an iron uptake gene, magA. This gene is taken from another type of bacteria called magnetotactic because of their response to Earth’s magnetic field. The researchers will study whether the increase in iron uptake caused by magA expression will allow MRI to detect the magnetic signal more clearly than it would in images of untransformed E.coli. This would make it possible to see the bacteria’s behavior in living subjects without removing the bacteria cells from the microbiome environment.

They will then use this technique to study how magA labelled bacteria affect biofilm on medical devices. A biofilm is a structure produced when certain bacteria adhere to a surface and then stick together.

They will also analyze how lithotripsy affects the bacteria’s spatial distribution and interactions in three-dimensional models of kidney stones. Lithotripsy uses shockwaves to break up kidney stones into smaller pieces that are able to pass naturally out of the body. However, these shockwaves not only affect kidney stones. The waves are sent throughout the tissue, and the bacteria living on these tissues may also be affected.

“While lithotripsy is effective in treating kidney stones, we don’t know the side effects of lithotripsy on the microbiome. The shockwaves could disturb the bacteria, potentially leading to diseases caused by an imbalance between helpful and harmful bacteria,” says Donnelly.

These laboratory models will allow the researchers to perform studies in vivo (in animal models) in the future.

“Health research is very important for the development of new technologies and treatments but it is often difficult to secure funding. The IRF program allows students to pursue research that would not otherwise be possible,” explains Donnelly.

The IRF is designed to provide Lawson scientists and students the opportunity to obtain start-up funds for new projects with the potential to obtain larger funding, be published in a high-impact journal, or provide a clinical benefit to patients. Funding is provided by the clinical departments of London Health Sciences Centre and St. Joseph’s Health Care London, as well as the hospital foundations (London Health Sciences Foundation and St. Joseph’s Health Care Foundation).

Wrist arthritis can cause debilitating pain, weakness and decreased range of motion. When patients are first diagnosed, the condition can often be managed with activity modification and pain medication. However, as symptoms progress, patients eventually require surgery.

Surgeons typically perform a procedure called four-corner fusion to preserve wrist motion and provide pain relief.  This surgery involves removing one of the carpal bones and fusing four of the remaining carpal bones. Although this procedure is one of the most common treatments for wrist arthritis, it is not known how the position of the fusion of the wrist bones affects range of motion and joint contact.

Lawson associate scientist Dr. Nina Suh is leading a study with the goal of improving the surgical technique for four-corner fusion to maximize wrist function and symptom relief, and delay wrist arthritis progression.

Dr. Suh and her team will use a customized active-motion wrist simulator to create different carpal bone fusion positions. They will then assess how these positions affect wrist motion and joint contact area.

“We hope this research will lead to new surgical techniques that will help us to more effectively manage wrist arthritis with four-corner fusion,” says Dr. Suh, who is also an orthopaedic surgeon at the Roth McFarlane Hand and Upper Limb Centre (HULC) at St. Joseph’s Health Care London and an assistant professor at Western University’s Schulich School of Medicine & Dentistry. “The project will also advance our understanding of wrist biomechanics, providing a foundation for the development of enhanced patient-specific surgical tools, such as custom wrist fusion devices and implants.”

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The study is being funded through the Lawson Internal Research Fund (IRF), designed to allow scientists the opportunity to obtain start-up funds for new projects with exciting potential.

“The IRF program is valuable for scientists as external funding sources routinely require preliminary data to strengthen applications,” says Dr. Suh. “Particularly for new scientists such as myself, these grants provide seed funding that allows us to demonstrate the validity of our methodology and the clinical usefulness of our results.”

The IRF is designed to provide Lawson scientists the opportunity to obtain start-up funds for new projects with the potential to obtain larger funding, be published in a high-impact journal, or provide a clinical benefit to patients. Funding is provided by the clinical departments of London Health Sciences Centre and St. Joseph’s Health Care London, as well as the hospital foundations (London Health Sciences Foundation and St. Joseph’s Health Care Foundation).

People who inject drugs are at a high risk for a number of health issues. In a new study from ICES, Lawson Health Research Institute and Western University, researchers discovered a significant rise in the risk of infective endocarditis, a serious heart infection, among Ontarians who inject drugs. When examining opioid prescriptions in the province, the research team discovered the increased risk of infective endocarditis may be related to the growing use of a specific opioid, hydromorphone.

The researchers looked at de-identified Ontario health data for 60,529 hospital admissions related to injection drug use between 2006 and 2015. Of the 60,529 admissions, 733 patients had infective endocarditis. Although hospital admission rates in people who inject drugs were stable over the study period, the risk of infective endocarditis increased from 13.4 admissions to 35.1 admissions every three months.

“Rates of infective endocarditis in people who inject drugs have been increasing around the world and our study shows this is true in Ontario,” says Dr. Matthew Weir, adjunct scientist at ICES, associate scientist at Lawson and assistant professor at Schulich School of Medicine & Dentistry, Western University. “We wondered if a change in the types of drugs people inject was responsible for this higher risk.”

Through further analysis of Ontario health data, the team discovered the increasing risk of infective endocarditis may be linked to a rise in prescriptions of the opioid hydromorphone. The number of hydromorphone prescriptions in Ontario increased from 16 per cent of all opioid prescriptions in 2006 to 53 per cent by 2015. This parallels the timing for increased risk of infective endocarditis among people who inject drugs. 

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The researchers initially suspected the increased risk for infective endocarditis would begin when controlled-release oxycodone was removed from the market in 2011. 

“We thought hydromorphone prescriptions would increase when controlled-release oxycodone was removed from the market, leading to increased risk of heart infection,” says Dr. Michael Silverman, associate scientist at Lawson and associate professor at Schulich Medicine & Dentistry. “However, while the study did show a substantial increase in risk for infective endocarditis, it began in 2010.”

Traditional controlled-release oxycodone was easily dissolvable and people who inject drugs did not save or reuse their injection equipment. Controlled-release hydromorphone, the more common form of the drug, is more difficult to dissolve. Since residue of the drug gets left in injection equipment, injection drug users save the equipment for future use or to share with others. Reusing injection equipment allows multiple opportunities for bacterial contamination, increasing the chances that bacteria will be injected when the equipment is next used.

Infective endocarditis occurs when the inner lining of the heart becomes infected. It can be a life-threatening illness and research suggests it can be caused by sharing or re-using injection equipment, possibly through the injection of bacteria.  

“While the timing was not what we expected, we did find a correlation between the rise in infective endocarditis and hydromorphone prescriptions,” says Dr. Sharon Koivu, Lawson scientist and associate professor at Schulich Medicine & Dentistry. “Our research is now focused on better understanding the potential relationship between the injection of hydromorphone and risk of infective endocarditis.”

The team is conducting ongoing studies that are looking at whether bacteria that cause infective endocarditis are more likely to survive in equipment used to prepare hydromorphone compared to other drugs. 

“The opioid crisis is one of the most pressing health issues of our time. Our findings not only confirm an increasing risk of infective endocarditis in persons who inject drugs but also offer the first evidence for why it might be happening,” says Dr. Weir. “Through research and collaboration, we hope to further collect the evidence needed to address this global problem.”

The study, “The risk of infective endocarditis among people who inject drugs: A retrospective, population-based time series analysis,” is published today in CMAJ (Canadian Medical Association Journal).