Eureka Staff

Gray Matters: Functional Ultrasound in CNS Research (Video)

Ultrasounds are often associated with smoky images of fetuses. Functional ultrasound imaging looks quite different. Eureka's live coverage of Neuroscience 2018. 

Finding effective drugs for neurodegenerative disorders has been a Sisyphean struggle. Drug development is notoriously difficult, but none more so than for diseases of the CNS, which according to one study take 20 percent longer to develop and about 19 months longer on average than other medications to win US Food and Drug Administration approval. 

One of the key challenges in finding CNS drugs that work is that the neurodegenerative process itself is not amenable to direct observation and thus cannot be monitored by clinical trials. For this reason, surrogate biomarkers are required for use as outcome parameters. Pharmacological MRI or simply phMRI is one way to study the effect of drugs on the brain activity. phMRI of the central nervous system addresses the increasing demands in the biopharmaceutical industry for new methods that can accurately predict, as early as possible, whether novel CNS agents will be effective and safe. Imaging of physiological and molecular-level function can provide a more direct measure of a drug mechanism of action, enabling more predictive measures of drug activity. 

But the tool has limitations. The machines are big, use complex methodologies and come with hefty price tags. Their resolution is also not particularly sensitive. An alternative to this is functional ultrasound imaging (fUI), a state-of-the-art method for measuring brain responses to drugs. Because the new tool receives better brain signals in relation to noise, it offers greater spatio-temporal resolution. It's also cheaper and portable.

Functional ultrasound imaging is based on ultra high sensitivity Doppler imaging of plane wave acquisitions and was  pioneered by the Langevin Institute in Paris, France. In preclinical studies, fUI has been used in both sleeping and waking rodents. In sleeping mice and rats, ultrasound images are obtained non-invasively, through the skull and the skin and without using contrast agents, which are common in other techniques because they improve the visibility of tissues and fluids. For mice that are awake, a small plate is inserted on the skull of the mouse and images of brain function are obtained while the animals are freely moving.

At the Society for Neuroscience meeting in San Diego, Charles River presented several applications of fUI in preclinical drug development, including vascular imaging in a stroke model and a neuropathic pain model induced by chemotherapy. .

"I wouldn't characterize functional ultrasound as an alternative model to phMRI, it's more like a complementary model," says Artem Shatillo, Head of Imaging at Charles River's CNS Discovery site in Finland. "Its advantages are higher specificity, higher spatial resolution and it is also much more applicable in mouse models. Pharmacological MRI is extremely hard to do in larger animals, even in rats, and in mouse models it becomes really, really demanding. Functional ultrasound is made to fix that.". 

You can learn more about these new inhibitors by watching Gray Matters, which is highlighting hot topics at this year's SfN meeting. Look for our next installment of Gray Matters about some exciting work in Parkinson's disease..