April 2004

Weizmann Institute

Salty scans

Kidney disease may affect as many as one in twelve people, and causes millions of deaths each year. Currently, the diagnosis of kidney function relies mainly on blood and urine tests, an indirect means of figuring out how well they're working.

Standard MRI scanners, used to view many organs of the body, do not always show the whole picture for kidneys. This is because the MRI equipment found in hospitals and clinics works by imaging water molecules in the body. But in water-logged kidneys, the image may not distinguish between different functional parts. Now, Prof. Hadassa Degani of the Biological Regulation Department and her lab team have found a way to see into the kidneys using magnetic resonance imaging (MRI) that scans sodium ions rather than water.

Their method takes advantage of a unique feature of kidney function. Kidneys filter the blood and maintain steady levels of materials such as sodium and potassium in the bloodstream. To sustain control, these organs employ a gradient � a rising concentration of sodium from the outer layer, called the cortex, (where concentrations are around those of normal body tissues), towards the center, where levels reach up to five times the norm.

Prof. Degani, together with doctoral student Nimrod Maril and Raanan Margalit, was intrigued by a small number of MRI experiments that focus on sodium to attain images of various tissues, and wondered if the kidneys' sodium gradient could be imaged, and if so, what the image would reveal about kidney function. They enlisted the help of Dr. Joel Mispelter from the Institut Curie in France to help them build the special accessory needed to detect the sodium. Working at a high resolution allowed them to pick up the fine details of changing sodium concentration, particularly localized variations in the sodium gradient.

First the team imaged a healthy rat kidney, showing, for the first time, the shape of the sodium gradient as it rises in a smooth slope from the outer layers inward. Next, they continued their work on kidneys with altered function to see how effective a diagnostic tool the sodium imaging is. When the kidneys were treated with one of two commonly used diuretic drugs, which increase water out-flow, not only did they see the gradient flatten, but they were able to trace, in detail, the actions of each drug over time. Blocked kidneys showed disruptions in sodium patterns as well, and the team was able to identify sections of kidney that retained healthy functioning and could return to normal once the block was removed, as opposed to those that had permanent damage.

While todays' methods give estimates of kidney function in percentages, tomorrow's doctors, using this painless, non-invasive MRI technique, may be able to pinpoint exactly where a problem lies, reveal a disease before symptoms occur, or evaluate how a drug affects a patient. "If we were able to see so much in a tiny rat kidney, think of how much more we can see in a human kidney," says Degani. "The method is so logical, it's a wonder it had not been applied before."



Prof. Hadassa Degani's research is supported by the M.D. Moross Institute for Cancer Research; Sir David Alliance, CBE, UK; Mr. and Mrs. Lon Morton, Calabasas, CA; Mrs. Jackie Gee, Ms. Livia Meyer and Mr. Harry Woolf, UK; Ms. Lynne Mochon and Ms. Edith Degani, NY, USA; the Washington Square Health Foundation; the Estate of Mrs. Ilse Katz, Switzerland; Dr. and Mrs. Leslie Bernstein, El Macero, CA; and The Skirball Foundation, NY, USA. Prof. Degani is the incumbent of the Fred and Andrea Fallek Professorial Chair in Breast Cancer Research. She heads the Willner Family Center for Vascular Biology.




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