New ultrasound treatment kills off cancer cells

It spares healthy cells while taking out cancerous ones

Cancer cells divide over and over, allowing them to grow rapidly — and spread. A new ultrasound treatment targets its cell-killing energy on these cells, sparing healthy ones.

By Alison Pearce Stevens April 10, 2020

Most cancer treatments involve surgery, chemical poisons or toxic radiation. Because they tend to take out healthy cells along with cancerous ones, these treatments can leave patients tired, hurting and more. So researchers are looking for new approaches that spare the healthy cells. One new idea would destroy cancer cells with ultrasound energy. Even this treatment, however, can sometimes damage healthy tissue. But a new development may help. It limits the ultrasound energy’s damage to only the cancer cells. Healthy cells should suffer little if any harm from it.

Explainer: What is ultrasound?

It’s exciting, says David Mittelstein of his team’s findings. Mittelstein is a biomedical engineer at the California Institute of Technology, in Pasadena. Low-intensity ultrasound, he says, “may allow physicians to target cancer cells based on their unique physical and structural properties.” Any spillover of the energy should cause little harm to healthy tissue.

The treatment sends out pulses of sound waves — energy — that have a frequency above 20,000 hertz (cycles per second). That’s too high for our ears to hear. (That’s also what makes it “ultra” sound.) Medical imaging relies on very short pulses of this low-intensity ultrasound.

Explainer: Understanding waves and wavelengths

Doctors had already used high-intensity ultrasound to kill cancer cells. These sound waves send lots of energy to a small, focused area. The waves vibrate water inside cells within that area. This causes the cells to heat up. A lot. Targeted cells and their neighbors can reach 65° Celsius (149° Fahrenheit) in just 20 seconds. This kills cancer cells. The down side: It kills healthy ones, too. Mittelstein’s team wanted to try something different.

Another Caltech lab had studied effects of low-intensity ultrasound on cancer cells. These cells differ from healthy ones. They have a bigger nucleus. They’re softer, too. This other Caltech team created computer models of cancer cells. These models suggested that low-intensity ultrasound might kill those cells. The process, Mittelstein explains, is “similar to how a trained singer can shatter a wine glass by singing a specific note.”

Explainer: What is a computer model?

This idea hadn’t been tested, however. So his team set out to do that.

First, they mixed cancer cells with healthy blood cells and immune cells. The cells were all suspended in a liquid. Then the scientists directed short pulses of low-intensity ultrasound at this suspension.

Ultrasound waves travel much faster and occur at a higher frequency than sounds we can hear.

The team tested different ultrasound frequencies (ranging from 300,000 to 650,000 hertz). They also tested different pulse durations (from 2 to 40 milliseconds). One minute of 500,000 hertz ultrasound, delivered in 20-millisecond bursts, killed nearly every cancer cell. It didn’t hurt the blood cells. It also left more than eight in every 10 immune cells unharmed. Mittelstein rates it a huge success.

A role for microbubbles

The treatment caused super-small microbubbles — likely tiny bubbles of air present in the fluid — to merge. The ultrasound waves caused these bigger bubbles to oscillate (move back and forth). The oscillation caused these microbubbles to grow, then violently collapse. To kill cancer cells, Mittlestein reports, “microbubble oscillation was necessary — but not sufficient.” Microbubbles oscillated in both healthy and cancer cells. “But only the cancer cells,” he notes, “were vulnerable to certain frequencies of ultrasound.”

More damage occurred when the ultrasound waves bounced back to hit the cancer cells more than once.

The initial ultrasound waves are known as traveling waves. They move out from the machine that produces them. But when those waves hit a surface of some type, they can reflect back — into the oncoming traveling waves. The colliding waves combine to form a special pattern known as “a standing wave,” Mittelstein notes. And this wave has some “special stationary spots called ‘nodes,’” he explains. At these, the pressure remains constant. Some other stationary spots, called “anti-nodes,” also develop. In them, he says, “the pressure goes up and down at twice the amplitude [height] of the traveling wave.” In the end, bubbles in the standing wave oscillate more than do those in a normal wave. And that extra oscillation proved essential to killing cancer cells. The team suspects the standing wave brings microbubbles closer together. That then boosts the ultrasound energy deposited on the cells, Mittelstein says. Not all cells respond equally to this standing wave. Which do will depend on their physical properties. Here, only cancer cells were harmed.

High-intensity ultrasound (left, depicted as red) kills all cells. In contrast, low-intensity ultrasound (depicted as blue), targets only cancer cells (depicted in red), leaving healthy ones (green) intact.David Mittelstein/Caltech

In his experiment, Mittelstein used a reflector to bounce the sound waves back into the suspension to create that standing wave. Bouncing ultrasound against bone might provide the same type of boosted impact, he suspects.

The team published its findings January 7 in Applied Physics Letters.

This study is exciting, says Timothy Meakem. He was not involved with the study. He does, however, know about ultrasound’s value in medicine. He works at Focused Ultrasound Foundation in Charlottesville, Va., as its chief medical officer. If the effect seen in these cells also occurs in people, he says, it would let doctors target cancer cells in ways not currently possible.

However, he cautions, this technique is not ready for use in patients. This is just the first step in the process of developing a new treatment. But if the next stages go well, it “might be a huge benefit to patients.”

Mittelstein is already moving ahead. His team’s next experiments will go beyond targeting cells in a liquid. They will focus on mounds of cells, which model a cancerous tumor. If they get similar cell killing in treated tumors, he says, “we think this therapy could make a significant impact in cancer therapy.”

Power Words

More About Power Words

amplitude: A measure of the height of a recurring wave in some signal, water or beam of radiation. In sound, wave amplitude corresponds with intensity — loudness or softness.

cancer: Any of more than 100 different diseases, each characterized by the rapid, uncontrolled growth of abnormal cells. The development and growth of cancers, also known as malignancies, can lead to tumors, pain and death.

cell: The smallest structural and functional unit of an organism. Typically too small to see with the unaided eye, it consists of a watery fluid surrounded by a membrane or wall. Depending on their size, animals are made of anywhere from thousands to trillions of cells.

chemical: A substance formed from two or more atoms that unite (bond) in a fixed proportion and structure. For example, water is a chemical made when two hydrogen atoms bond to one oxygen atom. Its chemical formula is H2O. Chemical also can be an adjective to describe properties of materials that are the result of various reactions between different compounds. computer model: A program that runs on a computer that creates a model, or simulation, of a real-world feature, phenomenon or event.

development: (in engineering) The growth or change of something from an idea to a prototype. engineer: A person who uses science to solve problems. As a verb, to engineer means to design a device, material or process that will solve some problem or unmet need.

focus: (in physics) The point at which rays (of light or heat for example) converge sometimes with the aid of a lens. frequency: The number of times some periodic phenomenon occurs within a specified time interval. (In physics) The number of wavelengths that occurs over a particular interval of time.

hertz: The frequency with which something (such as a wavelength) occurs, measured in the number of times the cycle repeats per second of time.

immune: (adj.) Having to do with the immunity. (v.) Able to ward off a particular infection. Alternatively, this term can be used to mean an organism shows no impacts from exposure to a particular poison or process. More generally, the term may signal that something cannot be hurt by a particular drug, disease or chemical.

millisecond: A thousandth of a second.

nucleus: Plural is nuclei. (in biology) A dense structure present in many cells. Typically, a single rounded structure encased within a membrane, the nucleus contains the genetic information.

oscillate: (n. oscillation) To swing back and forth with a steady, uninterrupted rhythm.

physics: The scientific study of the nature and properties of matter and energy. Classical physics is an explanation of the nature and properties of matter and energy that relies on descriptions such as Newton’s laws of motion. A scientist who works in such areas is known as a physicist.

pressure: Force applied uniformly over a surface, measured as force per unit of area.

radiation: (in physics) One of the three major ways that energy is transferred. In radiation, electromagnetic waves carry energy from one place to another. Radiation can transfer energy across empty space.

sound wave: A wave that transmits sound. Sound waves have alternating swaths of high and low pressure.

suspension: (in chemistry) A mixture in which particles are dispersed throughout the bulk of a fluid.

therapy: (adj. therapeutic) Treatment intended to relieve or heal a disorder.

tissue: Made of cells, it is any of the distinct types of materials that make up animals, plants or fungi. Cells within a tissue work as a unit to perform a particular function in living organisms. Different organs of the human body, for instance, often are made from many different types of tissues.

toxic: Poisonous or able to harm or kill cells, tissues or whole organisms. The measure of risk posed by such a poison is its toxicity. tumor: A mass of cells characterized by atypical and often uncontrolled growth. Benign tumors will not spread; they just grow and cause problems if they press against or tighten around healthy tissue. Malignant tumors will ultimately shed cells that can seed the body with new tumors. Malignant tumors are also known as cancers.

ultrasound: (adj. ultrasonic) Sounds at frequencies above the range that can be detected by the human ear. Also the name given to a medical procedure that uses ultrasound to “see” within the body.

unique: Something that is unlike anything else; the only one of its kind.

vibrate: To rhythmically shake or to move continuously and rapidly back and forth.

wave: A disturbance or variation that travels through space and matter in a regular, oscillating fashion