Now scientists are finding many more advanced applications of sound in medicine. Acoustical energy can be focused and used for imaging and treating a variety of ailments, including cancer, stroke, and Parkinson's disease. Sound waves can be focused deep inside the body to control hemorrhages, they can assist doctors in delivering drugs to specific areas in tissues, and they can disrupt adverse bacterial biofilms.
Many of these applications will be discussed in presentations at the 154th meeting of the Acoustical Society of America (ASA), which takes place from Tuesday, Nov. 27 to Friday, Nov. 30 in New Orleans. Some highlights:
1) THERAPEUTIC ULTRASOUND FOR DRUG DELIVERY AND HEMORRHAGE CONTROL
Just as a magnifying glass can focus light on a point, a concave transducer can focus acoustical waves onto a small spot of intense energy about the size of a grain of rice. Such a high-intensity acoustical focus can be aimed almost anywhere in the body, even through the skin and into deep tissue (with some exceptions). The ability to penetrate deep within the body makes therapeutic ultrasound attractive for a variety of medical applications.
Vesna Zderic (http://www.gwu.edu) at George Washington University, Shahram Vaezy at the University of Washington, and their colleagues are exploring the use of high-intensity focused ultrasound to control bleeding. In this application, acoustical energy can be absorbed as heat by the tissue, which cauterizes the wound. The blood coagulates due to heating and also possibly due to mechanical tissue disruptions that may release clotting factors.
Zderic will make two presentations on this research in New Orleans. The first will look at studies by Vaezy and colleagues, who tested high-intensity focused ultrasound to control bleeding in a variety of deep-seated tissues, including the liver, spleen, kidneys, and blood vessels. They tested a range of ultrasound energies and found they can achieve faster coagulation if the ultrasound produces bubbles at the focus. They conclude that therapeutic ultrasound would be a safe and useful procedure for hemorrhage control because the acoustical waves can be focused deep within the body where the bleeding occurs. It also can be used with conventional ultrasound to guide the area of focus and precisely target the bleeding.
They are also looking to use therapeutic ultrasound to aid in delivering drugs. In this sort of application, ultrasound has to be much less energetic so that the heat does not damage the tissues. Rather than heating the tissue, the idea is to produce a highly localized area of microbubbles that essentially produce temporary holes in the membranes of cells in that area and allow drugs that are present there to diffuse more easily. Zderic and her colleagues are also currently conducting preclinical studies, producing these tiny bubbles in the cornea to deliver antibiotics and anti-inflammatory compounds to treat serious infections of the eye. The same principle could be used to enhance the absorption of drugs through the skin.
The talk "Acoustic hemostasis: underlying mechanisms" (2aBB3) will be at 9:15 a.m. on Wednesday, Nov 28.
The talk "Therapeutic potential of stable cavitation: from enhanced drug delivery to faster hemorrhage control" (4pBB3) will be at 2:10 p.m. on Friday, Nov 30.
2) BETTER DETECTION OF THYROID CANCER
Ultrasound is currently the most sensitive tool for detecting thyroid nodules and the most cost-effective imaging method for evaluating the thyroid gland. However, ultrasound and other imaging results are often ambiguous and cannot differentiate between malignant and benign thyroid nodules. The overwhelming majority of nodules discovered by ultrasound (as high as 95 percent) are benign.
Often, the only way to definitively rule out a cancer diagnosis is through fine needle aspiration and biopsy. More than half these biopsies prove benign. While that may be reassuring to the people who undergo the biopsies, it would be better if they could receive that reassurance without having an expensive, invasive, and (as it turned out) unnecessary procedure.
Azra Alizad (http://www.mayo.edu) of Mayo Clinic College of Medicine will be presenting data on a novel non-invasive imaging technique called vibro-acoustography (VA) for identifying thyroid nodules in excised human thyroids imbedded in tissue gel. In this method, ultrasound is used to vibrate tissue at low frequencies, and the resulting vibrations can be detected by a sensitive microphone. Harder tissues normally produce a significantly different acoustic field than softer tissues, and detecting the difference may reveal a more definitive diagnosis. Malignant lesions are stiffer than benign lesions; therefore it is reasonable to expect that VA will be a better tool for detection and differentiation of thyroid nodules than the conventional ultrasound imaging.
While the technique is not yet tested for actually detecting thyroid cancers in clinical trials, vibro-acoustography is currently undergoing clinical evaluation for detecting breast cancer lesions in people. If successful, this inexpensive and non-invasive imaging tool would represent a major advance in our ability to provide care for people with potential cancer.
The talk "Vibro-acoustography of the thyroid" (3pBB3) will be at 2:05 p.m. on Thursday, Nov. 29.
3) MRI-GUIDED ULTRASOUND THERAPY
The promise of therapeutic ultrasound is that it has the potential to treat a wide variety of diseases, including stroke, Parkinson's disease, internal bleeding, nausea, and cancer, with shorter recovery times and fewer side effects.
For instance, it could potentially remove cancerous tumors without invasive surgery. It is already an option for women approaching menopause who have severe complications due to uterine fibroids. In the past, the standard treatment option for these women was surgical removal of the fibroids or the entire uterus - a hysterectomy. Therapeutic ultrasound can potentially remove the fibroids non-invasively, reducing the recovery period from weeks to days.
What makes ultrasound especially attractive as a technology is that it is relatively cheap and clinically proven. Obstetricians and physical therapists have used it as an imaging and therapeutic tool for years. Sham Sokka (http://www.philips.com) and his colleagues at Philips Medical Systems are developing a system that uses MRI in conjunction with high-intensity focused ultrasound as a device to treat cancer. The system basically uses the MRI to guide the focus of acoustical waves so that the treatment can be monitored as it proceeds.
Depending on where the waves are directed, they can generate heat or cause cavitation??"the formation of microscopic bubbles. With the heat generated by acoustical waves or the formation and collapse of the micro-bubbles, tumors can be removed without ever piercing the skin. It can also help to deliver drugs locally in the brain or in other tissues. There is also the potential to load chemotherapy agents in bubbles and deliver these agents to certain parts of the body, amplifying their local concentration by focusing ultrasound on those areas.
High-intensity focused ultrasound is already in use in parts of Europe and Asia for treating people with a variety of malignant tumors, and several major clinical trials are underway in the United States, Europe, and Asia for treating an even wider range of cancers. Currently, Sokka and his colleagues are using their system in phase I safety trials for treating uterine fibroids and selected malignant tumors.
The talk "Cavitation-enhanced ultrasound heating in vivo: Mechanisms and implications in MR-guided high-intensity focused ultrasound therapy" (4pBB2) will be at 1:50 p.m. on Friday, Nov. 30.
4) BREAKING BIOFILMS
Single-celled organisms do not always go it alone, as anyone who has ever slipped on a rock at the bottom of a creek bed has experienced. The slippery slime on creek rocks is an example of a biofilm - a protective slick that single-celled organisms form when they clump together on a solid surface, communicate with one another, and secrete a mucus-like substance.
Biofilms are not just the bane of falling hikers, though. They can form inside pipes and foul the water supplies. Moreover, bacteria like Staph. aureus can form biofilms on medical devices implanted into the human body and cause severe infection - even death. Because of their mucus secretions, bacteria in biofilms can be harder to kill.
Now E. Carr Everbach (http://www.swarthmore.edu) and his colleagues at Swarthmore College have shown that acoustical waves can disrupt biofilms and destroy bacteria. They grew biofilms of a strain of fluorescing E. coli on microscope slides sandwiched between piezoelectric wafers. This allowed them to view the biofilm under a confocal microscope before, during and after charging the wafers, which set up standing acoustical waves on the biofilm. They observed changes in the biofilm structure that showed a mechanical destruction of the film and bacteria. The potential applications of this technique range from personalized water sterilization systems to better ways of protecting against hospital-acquired infections.
The talk "Effect of 810 kHz cw ultrasound on bacterial biofilms" (4aBB7) will be at 10:45 a.m. on Friday, Nov. 30.
5) ACOUSTICS AND BRAIN CANCER
Doctors often treat brain cancers with a combination of radiation therapy and surgery - basically removing part of the skull and excising the tumor. When tumors are surgically removed, doctors will often implant a thin, drug-encapsulated wafer before replacing the skull that diffuses chemotherapy agent over time to help ensure that no remaining tumor cells survive.
This approach is too often unsuccessful, and brain cancers like neuroblastomas and neurofibromatosis remain the leading cause of cancer-related death in people under the age of 35. Part of the problem may be that cancerous cells migrate beyond the range of the slowly diffusing drugs.
Now George Lewis Jr. (http://www.cornellbme.com) and his colleagues at Cornell University are testing the use of acoustic pulses to help brain tissue absorb chemotherapy drugs faster. Using various pulse sequences, they showed that focused ultrasound could enhance the uptake of cancer drugs in brain-like tissues. They believe that focused ultrasound agitates the tissues' matrices, causing enhanced permeability for the drug, and by mechanically pushing it with radiation forces where the acoustical waves are focused. The drugs can then spread further and faster into the tissues than by unassisted diffusion alone.
The talk "Acoustic targeted drug delivery in neurological tissue" (3aBB5) will be at 9:15 a.m. on Thursday, Nov. 29.
6) TISSUE STIFFNESS AS A MEASURE OF A HEALTH
Monitoring a tissue's material properties may not be as obvious a gauge of its health as looking at its biological or chemical properties, but changes to these properties can be a good indicator of disease. Areas of stiffness in a tissue, for instance, are often a good warning sign of cancer - the basic premise behind breast self-examination. Likewise when cancerous tumors form on the liver or another one of the body's organs, they are often stiffer than the surrounding tissues because there are more blood vessels to support the tumors. The problem is, how can you measure stiffness in tissues deep within the body" There is no such thing as a liver self-exam.
Matthew Urban (http://www.mayo.edu) and his colleagues at the Mayo Clinic College of Medicine are designing ways to measure the stiffness of tissues as a non-invasive diagnostic tool. Urban will present his latest experiments in which he and his colleagues used focused ultrasound waves to deliver tiny vibrations to a steel sphere encased in gelatin - a model of a tissue with a stiff lesion. They were able to measure the frequency response of the sphere to acoustical waves of multiple frequencies, which can be used to determine the stiffness of the tissue-mimicking material. The method also provides new ways to non-invasively cause vibration for assessment of tissue stiffness without the presence of the steel sphere.
Moreover, they were able to deliver the energy to the sphere without heating the surrounding gelatin. This is one of the challenges of using highly focused ultrasound, because acoustical energy can be absorbed by nearby tissues in the form of heat.
The talk, "Modulated ultrasound and multifrequency radiation force" (3pBB1) will be at 1:15 p.m. on Thursday, Nov. 29.
7) ACOUSTIC "MINISCALPELS" FOR NON-INVASIVE SURGERY
The idea of making surgical incisions inside the body without ever opening or puncturing the skin in any way might sound like something out of a science fiction novel, but the technology may be just around the corner. High-intensity ultrasound may someday allow acoustical waves to be focused into the world's tiniest scalpels.
Zhen Xu (http://www.eecs.umich.edu/) and colleagues at the University of Michigan are using high-intensity ultrasound pulses to test whether they can deliver power without heating to tissues deep within the body. The energetic waves delivered by the high-intensity ultrasound cause microbubbles to form at the focus. These bubbles expand and collapse forcefully and the energetic bubble activity can mechanically fragment tissues - presumably because cell membranes cannot withstand the pressure caused by the bubbles.
Currently the acoustical beams can be focused into a cluster of "miniscalpels" about the size of an individual cell. The action of these beams can be easily controlled and maneuvered electronically using a computer mouse or joystick. Moreover, the surgery can be precisely targeted and monitored in real time because the microbubbles themselves are easily spotted via conventional ultrasound or MRI.
The talk, "Image-guided cavitational ultrasound therapy histotripsy" (4pBB4) will be at 2:30 p.m. on Friday, Nov 30.
More information about the meeting is at http://asa.aip.org/neworleans/information.html.
ABOUT THE ACOUSTICAL SOCIETY OF AMERICA
The Acoustical Society of America is the premier international scientific society in acoustics devoted to the science and technology of sound. Its approximately 7000 worldwide members represent a broad spectrum of the study of acoustics. ASA publications include the Journal of the Acoustical Society of America, Acoustics Today magazine, books and standards on acoustics. ASA holds two major scientific meetings each year. It is a member society of the American Institute of Physics.
For more information about the Society, please visit ASA's Web site at http://asa.aip.org.
American Institute of Physics