A new super-resolution microscope could enable doctors to diagnose kidney diseases earlier and faster - and for less cost.
The discovery, made by researchers in the Department of Pathology at Montefiore Medical Center and Albert Einstein College of Medicine, in collaboration with physicists at the University of St. Andrews, in Scotland, UK, has led to a new method for diagnosing nephrotic syndrome in the kidney – a group of debilitating and sometimes lethal diseases in which the kidney loses its ability to retain proteins in the blood, which are then carried into the urine. The findings were published online in January 6, 2016 issue of Biomedical Optical Express.
A novel light microscope - the super-resolution structured illumination microscope, or “SIM” - overcomes physical laws of diffraction to visualize structures much smaller than would normally be expected. Such structures can only be seen otherwise using an illumination source with a smaller wavelength, such as the electrons in an electron microscope.
“It is important and exciting to show how advances in physics such as the SIM can benefit medicine and biology, and especially help people with kidney disease,” said Dr. James Pullman, director of surgical pathology and professor of pathology at Montefiore-Einstein.
In the United States, an estimated 26 million adults and children suffer from chronic kidney disease, with nephrotic syndrome as one of the most common forms.
A collaborative effort
Dr. James Pullman
Dr. Pullman and his collaborators conducted their research with the state-of-the-art microscope at St. Andrews, where it is currently used by scientists in the Schools of Physics & Astronomy, Biology, and Medicine. Professor Kishan Dholakia, who leads the team of physicists at the University of St Andrews, said: “This is an exciting advance and I'm very pleased by the synergy of our team of physicists, biologists and physicians to apply advances in optics for the diagnosis and treatment of kidney disease.”
The team demonstrated that the SIM can “see” the critical changes in the podocyte foot process – which needs to be observed for a diagnosis - that adversely affect kidney filtration and cause nephrotic diseases, and that the changes match those seen previously only with the electron microscope.
Changes in one part of the kidney filtration apparatus, the podocyte foot process, must be seen in detail in order to make a diagnosis of nephrotic disease. These foot processes, however, are so small that conventional light microscopes, which have been used for almost two hundred years to visualize cells and diagnose disease in tissue, cannot show them. Instead, pathologists have used a more time-consuming and expensive process with a different type of microscope, the electron microscope, which can resolve such smaller structures.
This discovery, Dr. Pullman said, paves the way for more rapid and less expensive diagnosis of kidney disease. And because SIM technology also allows specific proteins to be visualized within the kidney, it also has the potential to facilitate discovery of new structural changes of importance in kidney disease.
Dr. Kishan Dholakia, professor in the School of Physics and Astronomy, University of St. Andrews University
The next step, he said, is to study more nephrotic diseases in order to validate the technique in this study for clinical use. Dr. Pullman will pursue these validation studies using a similar super-resolution microscope - located in Einstein's Analytical Imaging Facility - and provide complete sample preparation utilizing a broad spectrum of techniques for examination by Transmission Electron Microscopy (TEM) or Scanning Electron Microscopy (SEM). In addition, he will continue to explore advanced biophotonic applications to clinical practice with Professor Dholakia at St. Andrews.
The future is looking bright. Dr. Pullman said, “I feel that our results represent the beginning of a new era in diagnostic pathology.”
The other authors of this work are Jonathan Nylk, Elaine C. Campbell, Frank J. Gunn-Moore and Michael B. Prystowsky, University Chair, Albert Einstein College of Medicine and Montefiore Medical Center.