Canadian researchers have determined that using gene chips to read molecules during heart transplant biopsies is much safer and more effective than conventional methods.

Dr. Phillip Halloran, who developed the molecular microscope system, presented the preliminary findings earlier this month at the 2018 meeting of the International Society for Heart and Lung Transplantation in Nice, France. The system was created at the Alberta Transplant Applied Genomics Centre (ATAGC) at the University of Alberta, Edmonton, Canada.

"Heart biopsies are conventionally read by microscopes, but there is extensive disagreement between doctors reading the biopsies, and therefore, errors," said Halloran, a transplant physician and global leader in the field of transplantation. "The ATAGC team believes that biopsies should be read by their molecules, and has developed a molecular microscope method to do just that."

The molecular microscope uses microarrays, also called gene chips, to read the molecules in heart and lung transport biopsies. Software converts the chip readings into diagnoses rather than relying on humans to determine a diagnosis. The molecular microscope diagnoses T cell and antibody rejection, and requires less tissue than the conventional method with a standard microscope

Halloran said the system provides clinicians with information necessary for managing heart transplant rejection and treatment, but it also removes the confusion of unrecognized injury with rejection.

"Our findings suggest that, not infrequently, the current standard lacks the refinement to distinguish true rejection from other processes causing injury," said Dr. Daniel Kim, University of Alberta transplant cardiologist. "This implies that, at times, patients could be treated for a condition they don't have. The molecular microscope's ability to more accurately diagnose rejection, before structural damage has occurred in a patient's heart, provides us with an essential tool in the evolution towards true precision medicine."

Since the molecular microscope system has shown success in reading heart transplant biopsies, it's now being developed for use in lung transplant biopsies.

"Reading small lung transplant biopsies with a microscope is challenging — much more so than other transplantable organs — and that makes diagnosing rejection that much more difficult and prone to error," said Kieran Halloran, assistant professor of medicine at the University of Alberta. "This molecular diagnostic system is at an earlier stage in lung compared to heart and certainly to kidney, but is showing promising results that it can see similar information. That potential is very exciting for lung transplant clinicians."

Precision among lung transplant patients is extremely important since they often experience the shortest of all survival rates. According to the National Heart, Lung, and Blood Institute (NHLBI), the one-year survival rate for single-lung transplants is almost 80 percent while the five-year survival rate exceeds 50 percent.

"You can't hit what you can't see," Dr. Phillip Halloran said. "Transplant rejection can be going on, and we are missing it. And more commonly, rejection is way overdiagnosed, and patients are experiencing treatment complications for a condition they didn't have.

"Our system will change the approach to care."