Functional Ultrasound Neuroimaging

“Not your momma’s ultrasound”

Introduction to fUS

Functional Ultrasound (fUS) Neuroimaging is an innovative technique that uses Doppler imaging and plane-wave ultrasound to measure changes in cerebral blood volume, providing an indirect measure of neuronal activity. It offers high sensitivity and spatial resolution at high frame rates, allowing for detailed imaging of brain function. This technique was first introduced by Macé et al. in 2011 (Nature Methods) and has been primarily used in animal studies with species such as rats and monkeys. While less common in human studies, fUS is noted for its superior sensitivity compared to BOLD fMRI in detecting subtle hemodynamic changes.

Types of Data

• Pharmaco-fUS: Assesses hemodynamic responses to pharmacological agents, aiding in drug development and testing.
• Stimulation-fUS: Observes brain responses to specific stimuli, such as sensory or electrical stimulation.
• Resting State-fUS: Studies intrinsic brain activity patterns during rest, providing insights into functional connectivity networks​​.

Equipment/Tech

fUS systems typically include a specialized ultrasound probe and high-performance ultrasound scanners capable of ultrafast imaging. Recent advancements have enabled four-dimensional (4D) fUS, which offers volumetric recordings of cerebral blood volume changes across the entire brain with high temporal resolution. This setup includes a 2D matrix array transducer and multiplane-wave transmission, allowing for high-frequency imaging of brain activities such as functional connectivity and transient events like seizures​​.

Clinical Applications

fUS has significant potential in clinical settings, including intraoperative brain mapping and neonatal brain monitoring. It provides high-resolution, real-time imaging without the need for contrast agents. For example, 4D fUS has been used to study sensory-evoked responses and track epileptiform events, demonstrating its capability to monitor dynamic brain processes​​.

Safety and Precautions

As a non-invasive method, fUS is generally considered safe. However, precautions should be taken to prevent tissue heating or cavitation, especially during high-intensity imaging sessions. The use of appropriate settings and parameters ensures safe application in both research and clinical environments.

Techniques and Modalities

fUS can be combined with other neuroimaging modalities, such as EEG and optogenetics, to provide a comprehensive understanding of brain function. This technique is particularly useful for studying awake and freely moving animals, offering insights into naturalistic behaviors and brain activity. Quantitative hemodynamic measurements, such as cerebral blood flow (CBF), cerebral blood volume (CBV), and red blood cell velocity (RBCv), are possible, providing a deeper understanding of neurovascular coupling and its implications for neurological diseases.

What does fUS work well with?

fUS data can be effectively integrated with other imaging techniques, such as fMRI, EEG, and calcium imaging, to offer complementary insights into brain function and dynamics.

Practical Guide and Tutorials

Numerous resources, including practical guides and tutorials, are available for those interested in fUS. These materials cover essential aspects such as equipment setup, data acquisition, and analysis techniques, making them valuable for both new and experienced users.

• Read, Process, and View Ultrasound Data
• Using FAST on Ultrasound data in python
• Machine Learning for Medical Ultrasound: Status, Methods, and Future Opportunities
• Hough-CNN: Deep learning for segmentation of deep brain regions in MRI and ultrasound

Reference Papers:

• Macé et al., Nature Methods (2011)
• Deffieux et al., Current Opinion in Neurobiology (2018)
• Brunner et al., Frontiers in Neuroscience (2022)
• Rabut et al., Nature Methods (2019)
• Montaldo et al., Annual Review of Neuroscience (2022)