What is Focused Ultrasound and How can it be used to treat Brain Disorders?

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We are continuously surrounded by an array of sound waves; some we can hear and many we cannot. But what is a sound wave? Essentially, sound waves are a type of energy that is released when an object, such as a guitar string, vibrates. The vibration travels through the air and eventually reaches your eardrum, allowing you to hear the sound of the guitar. The human ear can discern sounds within the frequency range of 20 to 20,000 Hertz (number of wave cycles occurring per second).

Scientists have figured out how to harness sound waves with different frequencies for medical purposes, such as ultrasound imaging.

The Sound Waves Beyond Human Hearing

Ultrasound waves are a type of sound wave with a frequency of over 20,000 Hertz, unable to be heard by humans. Because sound waves are a form of energy, scientists discovered that aiming these high-frequency sound waves onto a specific area of the body could actually burn tissue. Known as focused ultrasound (FUS), this technique uses an acoustic lens to focus 1000s of ultrasound beams onto one precise location within the body. As the sound waves converge, they heat up the tissue area, killing the targeted cells. The concept is similar to how you can use a magnifying glass to concentrate the sun’s rays to burn a hole in a leaf.

Focused Ultrasound (FUS): A Revolution in Non-invasive Surgery

Perhaps one of the most revolutionary applications of high-intensity FUS is its use in “knife-free” brain surgery. By leveraging this ultrasound technology, surgeons can now perform intricate brain procedures without ever using a scalpel or physically opening up the patient’s skull. During these procedures, the patient is lying inside a magnetic resonance imaging (MRI) machine so that the surgeon can see where to target the ultrasound in real-time.

After years of refinement, high-intensity FUS is now approved to treat tremors in movement disorders like essential tremor and Parkinson’s disease. People with these conditions often experience uncontrollable shaking in their arms and hands, making it difficult to do everyday activities like holding a cup or writing. The cause of this shaking is believed to be due to abnormal activity in a central brain structure called the thalamus, which relays sensory and motor information. Burning small lesions in the thalamus with FUS, can eliminate this abnormal activity and reduce tremor symptoms in patients.

High-intensity FUS can also be used to burn and kill brain tumours, however, this has not yet been approved by the FDA since there are still some limitations to the procedure.

Focused Ultrasound (FUS): Unblocking Brain Disorder Treatments

If you take a medication by mouth or by IV injection it will enter your bloodstream and eventually reach the target organ. However, if the target organ you are trying to treat is the brain, the situation is more complicated as most therapeutics cannot access the brain from general circulation because of the blood-brain barrier (BBB). The BBB has blocked progress in developing therapeutics for many brain disorders, including Alzheimer’s disease, where many drugs trialed have been too large to readily pass through the BBB. Therefore, researchers are exploring how FUS can be used to briefly open up the blood-brain barrier to enhance the penetration of therapeutic drugs into the brain. To do this, they are employing FUS at a much lower intensity, intentionally avoiding any tissue destruction.

What is the Blood-Brain Barrier and Why Would We Want to Open it?

The blood-brain barrier (BBB) is a protective barrier that acts as a filter between the brain and the blood, allowing only certain molecules in and out. While the brain is abundantly supplied with blood vessels, the lining of these vessels differs from those found in other parts of the body. In other areas of the body, molecules are relatively free to flow between the blood and tissue because of gaps between the cells that make up the vessel lining. However, this is not the case in the brain because of the BBB. The BBB is comprised of tightly interlocked cells lining the brain blood vessels. These cells are so tightly packed, there’s almost no room for anything to pass through aside from very small molecules, fat-soluble molecules and some gases (i.e. caffeine, nicotine, oxygen). This high selectivity prevents harmful pathogens like viruses from getting into the brain but also makes it very difficult to deliver therapeutics to treat brain disorders.

Opening up the brain with sound and bubbles

To overcome the challenge created by the blood-brain barrier, researchers are harnessing the power of FUS to breach the BBB temporarily in target brain regions. The key lies in creating spaces between the cells of the BBB to allow for the larger drug molecules to pass through from the blood vessels into the brain space. To achieve this, scientists have combined tiny bubbles with focused ultrasound. These microscopic bubbles (microbubbles), smaller than red blood cells, are injected into the patient’s bloodstream through an IV. Once in circulation, the low-intensity ultrasound waves are applied to the target area and make the microbubbles compress and expand causing them to vibrate. These vibrations loosen the gaps between the cells that make up the BBB, selectively disrupting the barrier’s permeability only in the targeted area.

FUS combined with microbubbles has now been shown to successfully open the BBB in people with Parkinson’s disease, Alzheimer’s disease and some cancers in clinical trials. When these research patients were given therapeutic drugs along with the ultrasound, more of the therapeutic reached the target brain area and symptoms improved. Crucially, the BBB opening is not permanent and it re-closes on its own within 24 hours after the procedure.

The future sounds bright with FUS

The ability to deliver therapeutics to brain cells noninvasively could open up a whole host of compounds that were once thought to be ineffective in the brain. Using FUS at different frequencies and intensities has the potential to transform treatment for many neurological conditions like Parkinson’s disease, as well as psychiatric conditions such as addiction and depression. Moreover, the potential to destroy a tumour deep within the brain or to deliver chemotherapy directly to a brain tumour would further revolutionize brain cancer treatments.

As this technology develops further and its applications rapidly expand, it would be worth keeping an eye on focused ultrasound. You can check out the latest report on the current progress of all of the FUS applications worldwide here.