JDRF Research
Imaging Method Allows Researchers to Assess Islet Damage
JDRF-funded researchers at the Joslin Diabetes Center in Boston have discovered a way to assess damage in pancreatic islets in real time, potentially overcoming a major hurdle in the early detection and prevention of type 1 diabetes. In the September issue of the Journal of Clinical Investigation, the scientists reported using a noninvasive technology called Magnetic Resonance Imaging-Magnetic Nanoparticles (MRI-MNP), to visualize and measure inflammation as it occurs. They demonstrated that the technology can effectively monitor the progression of type 1 diabetes and predict its course. It has already been successfully used to monitor responses to experimental treatments in cancer patients.
Early detection of type 1 diabetes has been hindered by the lack of direct, noninvasive technologies to measure inflammation in pancreatic islets — an early indicator of the disease. To date, a pancreatic biopsy, a potentially risky approach, has been the only way to detect cellular infiltration and pancreatic damage. This limitation has hampered scientists’ ability to fully understand the disease process, to predict risk, and to monitor the effectiveness of therapies.
The Joslin study was led by Stuart Turvey, Ph.D., in the laboratory of JDRF-funded researchers Diane Mathis, Ph.D., and Christophe Benoist, M.D., Ph.D. “This is an important advance toward monitoring progression of type 1 diabetes because it may allow clinicians to test earlystage patients to see whether a treatment is working, and if not, to change tactics,” said Teo Staeva-Vieira, Ph.D., JDRF’s Acting Director of Immunology. “Until now, we had no way of assessing damage to islets except watching to see if the patient developed the disease. With MRI-MNP, we have visual evidence of this damage in real time.”
The researchers used MRI-MNP to study the islets of mice induced to develop diabetes. They tracked tiny particles of iron oxide, or MNPs, as they traveled through the blood vessels and ultimately made their way to the tiny vessels in its pancreas. The MNPs would accumulate at sites where inflammation occurred, which was picked up by the MRI-MNP scan. The scientists later examined biopsies of the animals’ islet tissue for immune cell infiltration. This step verified that the images accurately reflected the damage that accompanies development of type 1 diabetes.
The investigators then used MRI-MNP to scan mice that were induced to develop the disease but also received an anti-CD3 antibody for five days. (Anti-CD3 antibodies have been shown to significantly prevent the progression of type 1 diabetes in newly diagnosed patients who retained higher levels of beta cell mass.) They found that the imaging technique identified animals that had a favorable response to the treatment as early as three days after the treatment was completed.
“Three days is a remarkably short time to get an indication about whether a treatment is working,” Dr. Staeva-Vieira says. “Eventually, this could give researchers and physicians a chance to change to a more effective therapy or at least discontinue a therapy that could be harmful.”
According to Dr. Staeva-Vieira, this type of noninvasive imaging of the pancreas has two potential clinical applications:
1) identifying people at highest risk for developing clinical onset of type 1 diabetes and 2) following patients undergoing a treatment to identify who is responding to treatment — and who is not — so as to alter treatment strategies early in the course of the disease.