Optical-acoustic imaging helps treat spinal muscular atrophy

Spinal muscular atrophy (SMA) is a serious disease in which a genetic mutation causes degeneration of certain nerves responsible for transmitting signals to muscles. This leads to muscle wasting and many patients die painful deaths due to this rare disease. Genetic treatments became available only a few years ago.

Now a team led by Emmanuel Nedoshill, Ferdinand Knieling and Adrian Regensburger from the translational pediatrics working group at the Department of Pediatrics and Adolescent Medicine at the University Hospital Erlangen has developed a complex procedure that shows promising results when used in combination with these treatments: short laser pulses create sound waves, which then provide images of muscle tissue.

They published an article about their results in the magazine Med.

"This method is similar to ultrasound scans, which have been used for a long time," explains Nedoshill. "In just a few minutes, a scan taken outside the body can provide an image of the muscles inside the body."

One of the main advantages of this optical-acoustic imaging technique is that even young children usually cooperate without much effort, since it is a non-invasive procedure that does not require swallowing or injection of a contrast agent. This not only simplifies the work of the medical team, but also improves the environment for children and their parents during their hospital stay.

The situation is usually incredibly stressful for those affected. The disease is caused by just a small change in the genome in terms of a protein called "SNM", but the absence of this protein leads to the degeneration of certain nerves responsible for transmitting signals to muscle cells. The affected muscles atrophy. It can be very difficult for ordinary people to hear about the consequences and the different ways the disease progresses.

One category is “walkers,” who are still able to take a few steps on their own. The situation for those who are sedentary is much worse. Without assistance, they can only sit, but cannot stand up on their own. The worst situation is for the “non-sedentary”, who cannot even sit. If the muscles needed for swallowing or breathing are affected, the disease can be fatal.

Fortunately, only 1 in approximately 10,000 newborns has the SNM genetic mutation. However, the suffering of those affected is so great that any improvement in available treatments is a significant breakthrough, as is the case with a treatment known as "optoacoustic imaging" (OAI), researched at the Department of Pediatrics and Adolescent Medicine at the University Hospital Erlangen.

These treatments, which became available just a few years ago, have led to significant breakthroughs in the treatment of this disease, which was previously virtually incurable. Noticeable improvements were achieved even in the most severe cases, called "non-sedentary".

Until now, however, the only way to track this success was through grueling motor tests that could last several days. The very nature of these tests could also compromise their objectivity. Some people may exert more effort than others, leading to better results in some children than others. Children's moods can also change from day to day, which affects test scores.

The OAI procedure with short laser pulses using near-infrared light can greatly improve the objectivity of these observations. These light pulses heat the affected tissue, which then emits sound waves that provide important information about various structures in the patient's body. Tissue, for example, is composed of collagen proteins, which return a different spectrum of sound waves compared to muscle or fat tissue.

Source: Med (2024). DOI: 10.1016/j.medj.2024.02.010

"In muscle, we can identify the hemoglobin spectrum in red blood cells, which is responsible for transporting oxygen to the body and removing carbon dioxide," Nedoshill explains. The more muscle cells there are and the more active they are, the more oxygen they need to do their job.

If a researcher at the University Hospital Erlangen sees a lot of hemoglobin, he knows that this means significant muscle mass. On the other hand, if muscle atrophies and is replaced by connective tissue, 3D images show how the disease progresses and leads to an increase in collagen, documenting muscle atrophy.

This provides doctors like Nedoshill with a tool that is as fast and easy to use as an ultrasound scan, and provides dramatic images of how muscle and connective tissue come and go.

Studies conducted in Erlangen based on hemoglobin tracking showed that children with SMA have significantly less muscle tissue than healthy controls. However, after receiving life-saving genetic therapy, hemoglobin concentration increases, atrophied muscles begin to recover, and ultrasound signals soon begin to resemble those from healthy organisms.

Thanks to research at the Department of Pediatrics and Adolescent Medicine in Erlangen, a relatively simple tool is now available to monitor the progress of muscle wasting and the success of treatment.