Functional ultrasound (fUS) is an advanced neuroimaging technique that allows scientists to observe brain activity. It achieves this by precisely detecting changes in blood flow within the brain. This non-invasive method provides insights into how the brain functions, as these hemodynamic shifts are closely linked to neural activity.
Principles of Functional Ultrasound
Functional ultrasound operates on the principle of neurovascular coupling, which describes the close relationship between neuronal activity and changes in cerebral blood flow. When neurons become active, they require more oxygen and nutrients, leading to an increase in blood supply to that specific brain region. fUS uses ultrasonic waves to detect these changes in blood volume and flow.
The technique employs ultrafast Doppler imaging, transmitting high-frequency plane-wave ultrasound pulses. These pulses are emitted at a fast rate, often around 20 kHz, allowing for rapid data acquisition. Echoes from moving red blood cells within the cerebral vasculature are captured. After filtering out signals from stationary tissues, the remaining higher-frequency signal indicates blood movement.
The mean intensity of this blood signal is known as the “Power Doppler” value, which is directly proportional to the relative cerebral blood volume (rCBV). By combining many responses from these fast pulses into a single image, fUS significantly improves its signal-to-noise ratio and sensitivity. This allows for the detection of slow blood flows, as low as 1 mm/s, which are associated with neuronal activation in small arterioles.
Applications in Brain Imaging
Functional ultrasound is used in neuroscience research for studying brain circuits and mapping neural activity, particularly in animal models like rodents and non-human primates. It allows researchers to visualize brain activation during stimulus-based tasks or to observe spontaneous activity in resting conditions. For instance, fUS has explored whisker-evoked cortical and thalamic responses in awake rats, providing detailed brain activation maps.
The technology also shows potential for human applications, including intraoperative brain mapping during surgery. During awake brain surgeries for tumor resections, fUS has successfully mapped hemodynamics-based functional brain activity as patients perform language, motor, and sensory tasks. Its portability and safety make it suitable for monitoring brain function in neonates at the bedside, offering dynamic and high-resolution imaging without needing to move the infant.
Researchers are also applying fUS to study drug-induced hemodynamic responses and to characterize animal models of neurological and neurodegenerative diseases. This includes pharmaco-fUS for acute pharmacological challenges, and resting-state fUS to identify altered neurotransmitter systems or changes in functional connectivity. Imaging intrinsic brain connectivity by detecting correlations in blood flow between different areas shows promise for diagnosing brain disorders.
Comparison to Other Neuroimaging Techniques
Functional ultrasound offers advantages when compared to established brain imaging methods like functional Magnetic Resonance Imaging (fMRI) and Electroencephalography (EEG). fUS provides superior spatial and temporal resolution compared to fMRI, with five times the sampling rate and three times the spatial resolution. While fMRI detects changes in blood-oxygen-level-dependent (BOLD) signals, fUS directly measures cerebral blood volume, offering a more sensitive, direct view of hemodynamic changes.
EEG, known for its millisecond-level temporal resolution in detecting electrical activity, has a limited ability to pinpoint the exact location of brain activity due to its low spatial resolution. In contrast, fUS provides more spatial information, including details on global blood flow and structures deep within the brain. Its portability and lower cost also stand out against expensive, large fMRI scanners, which require subjects to remain completely still.
Despite its advantages, fUS currently has limitations, such as requiring a cranial window in some preclinical research to overcome skull attenuation. Methods using microbubble contrast agents are being explored to enable non-invasive transcranial imaging. Compared to fMRI, fUS may also have a more restricted penetration depth in larger brains without such enhancements.
Emerging Uses and Future Potential
Research continues to expand functional ultrasound’s capabilities, aiming to overcome current limitations and broaden its clinical reach. Advancements in transducer design and signal processing are leading to higher image resolution and improved tissue characterization. The integration of artificial intelligence (AI) and machine learning (ML) algorithms is expected to automate image analysis, enhance diagnostic accuracy, and enable faster interpretation of fUS data.
Future clinical applications include diagnosing neurological disorders more precisely and guiding therapies. Its potential for personalized medicine and targeted treatments is being explored, leveraging its ability to provide detailed, real-time insights into brain activity. The development of more compact, wireless, and even wearable ultrasound devices could make fUS more widely accessible for continuous patient monitoring and point-of-care imaging.