Possibilities and Risks in Ultrasound Operation Technion Researchers Develop a Model that Provides a Unique Explanation for the Way in Which Ultrasound Influences Living Cells Cell membranes absorb energy from the ultrasound, expanding and contracting during its operation Ultrasound is widely used in imaging devices. In the last decades, its use has increased also for treatment and therapy because it is non-invasive and can be pinpointed. But in most uses (at medium or low intensity) it is unclear how ultrasound heals and interacts with living cells. Over the past year, Technion researchers have developed a unique model that explains how ultrasound waves affect the living cell. The researchers claim that the cell membranes absorb mechanical energy from the ultrasound pressure wave, expanding and contracting during its operation. The model was published in the American journal “Proceedings of the National Academy of Sciences” (PNAS). “The model we developed predicts that the lipid bilayer membranes of the cell are capable of absorbing mechanical energy from the ultrasound field and translating it into expansion and contraction of the membrane’s internal space,” explains Prof. Eitan Kimmel of the Technion’s Faculty of Biomedical Engineering. “We have developed a unique model that is able to explain the interaction mechanism between ultrasound and biological tissue. The model integrates physics and bubble dynamics with the biomechanics of the cell and enables estimating the dynamic behavior of the bilayer membrane, which is made up of two layers of lipid molecules.” Fifteen years ago, Prof. Kimmel exposed anesthetized goldfish to low intensities of ultrasound together with Dr. Victor Frenkel (during his doctoral research) and then showed under an electronic microscope the spread of cell membranes in the fish skin. But only now he has succeeded in understanding the meaning, using a model he developed together with Prof. Shy Shoham and Dr. Boris Krasovitski. In their collaborated studies Kimmel and Shoham stimulate neuron cells using ultrasound, giving special attention to the cell membrane. “In the world of ultrasound, the common explanation is that during operation of the ultrasound machine tiny gas bubbles are produced (cavitation) which explode against the surface and are responsible for changes in the cells and tissue,” says Prof. Kimmel. “The FDA [US Federal Drug Administration] has determined a pressure amplitude limit under which bubbles are not anticipated and therefore, the assumption is that no damage is caused. Up until now, it was not known where the bubbles seen during high intensity ultrasound operation are produced in the body. We found the source of the bubbles. Where there are cells that are not entirely enclosed by dense tissue, there will be bubbles. If bubbles are seen in the blood vessels, we know that these are blood cells and their membranes have reacted to the ultrasound. Cell membranes under ultrasound look like layers of ‘bubble wrap.’ But this is a dynamic layer whose ‘bubble wrap’ expands and contracts with ultrasound operation.” 1 The Technion researchers have identified a wide range of medical uses such as drug introduction through the blood-brain barrier, stimulating nerves, pain suppression and facilitating blood vessel growth and shortening the healing times in wounds and fractured bones. On the other hand, it could be that it will be necessary to reevaluate the criteria for safe operation in order to reduce the risks of ultrasound. “When the membrane is opened and stretched – forces operate on the cell inside of it, on the cell skeleton and on the proteins found in the membrane,” states Prof. Kimmel. “Ultrasound interferes with their operations, which are vital for the life of the cell. At certain intensity, this can cause positive changes in the cell and at other intensities it could cause damage. Therefore, we recommend continuing investigation of the subject using the model we developed.” 2