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Neuromuscular diseases like amyotrophic lateral sclerosis (ALS) and muscular dystrophy often involve a progressive loss of muscle function, but tracking the health of muscles over time is not always easy or precise. The best way to diagnose and evaluate muscle degeneration involves an uncomfortable needle test; both this test and other approaches like questionnaires are subjective and not easy to reproduce over multiple sessions.

A new device, under development by Seward Rutkove, a neurologist and scientist at Harvard Medical School, and his colleagues at MIT could provide a painless, noninvasive, and quantitative alternative. The prototype handheld probe, similar to an ultrasound probe, measures electrical impedance in the muscle, which changes depending on the health of the tissue.

The approach, also known as electric impedance myography (EIM), is a modification of the basic technology used in body composition devices to measure the percentage of fat or muscle in the body. A high-frequency electric current is applied to the skin through a set of noninvasive electrodes, while another set of skin electrodes records the resulting voltages from the tissue. The properties of the current change depend on the composition and microscopic structure of the underlying tissue.

Muscles are made of long bundled fibers oriented in the same direction. An electrical current passes more easily when it travels parallel to the fibers; when it passes across the fibers, it encounters more cell membranes, which cause a greater delay or phase shift in the current. Rutkove’s group at Beth Israel Deaconess Medical Center has found that this phase shift varies depending on the health of the muscle, since diseased muscle has fewer cell membranes. In addition, energy is lost as the current flows through muscle, and more so when flowing across the fibers. Rutkove’s group has found that looking at both phase shift and energy loss can provide unique information on the health of the muscle, since diseased muscles have fewer muscle fibers, smaller cell membranes, and abnormal amounts of fat and water in the muscle, all of which impact these measurements.

Rutkove’s group initially made muscle measurements using off-the-shelf body composition devices modified to perform EIM. But the process required stick-on electrodes placed at several positions along a muscle, and a single body part might require multiple rounds placing the electrodes at various angles. The handheld probe, developed in collaboration with Joel Dawson’s electrical-engineering lab at MIT, makes it possible to take the measurements quickly without a need for electrodes.

Dawson says that the main technical challenge in developing the device was to find a way to deliver electric currents at varying angles without requiring complex machinery. “We came up with the idea of having a lot of little pixel probes and connecting them together,” he says. The head of the device contains two rings of small electrodes: one to send current, and one to measure voltage. These individual electrodes can be electrically connected in different combinations to act as single larger electrodes, or can be isolated individually to give a finer resolution. This allows the researchers to program the specific angles that they want to measure. The device is connected to a computer that calculates impedance measurements and displays the results graphically.

Rutkove is currently testing EIM in patients with ALS and in children with spinal muscular atrophy. He says that the biggest challenge for making EIM useful is knowing how to interpret the data. His work has shown that neuromuscular diseases can have unique EIM “signatures” that can be used to diagnose and treat the disease, but it’s an ongoing research effort “to find the right signature or impedance profile that tells you it’s one type of disease versus another.” The technique must also be tested in enough patients to understand the normal range of individual variability.

“The idea of having a tool that is noninvasive and painless to assess muscle function is very attractive,” says Michael Benatar, a neurologist at Emory University, who is testing the device in patients. Currently, the best test for muscle function is electromyography (EMG), which involves placing a needle into the muscle and having the patient contract the muscle. Benatar has been testing the EIM method in patients with ALS to see if the technique could be used for early detection of disease. “We’re hoping we might be able to detect abnormalities with EIM that aren’t apparent clinically or with conventional techniques,” he says. But he adds that EIM is not ready to be used more widely in the clinic until it’s clear how to interpret the results.

Rutkove hopes that in the meantime, EIM will prove useful as a research tool. His group is also conducting studies on animals with neuromuscular diseases to understand in more detail how EIM readings relate to the underlying tissue changes with disease.

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Credit: Brittany Sauser
Video by Brittany Sauser

Tagged: Biomedicine, muscle, ALS

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