Functional ultrasound imaging
[1] Optics-based methods generally provide the highest spatial and temporal resolutions; however, due to scattering, they are limited to measuring regions close to the surface.
fMRI and PET, which measure the blood-oxygen level dependent (BOLD) signal, were the only techniques capable of imaging brain activation in depth.
In fact, in-depth imaging of cerebral hemodynamic responses by fMRI, being noninvasive, paved the way for major discoveries in neurosciences in the early stage, and is applicable on humans.
However, conventional power Doppler imaging lacks sensitivity to detect small arterioles/venules and thus is unable to provide local neurofunctional information through neurovascular coupling.
As a result, coherent adding of several echo waves leads to cancellation of out-of-phase waveforms, narrowing the point spread function (PSF), and thus increasing spatial resolution.
[2] The sensitivity was recently further improved using multiple plane wave transmissions[9] and advanced spatiotemporal clutter filters for better discrimination between low blood flow and tissue motion.
[10] This signal boost enables the sensitivity required to map subtle blood variations in small arterioles (down to 1mm/s) related to neuronal activity.
By applying an external stimulus such as a sensory, auditory or visual stimulation, it is then possible to construct a map of brain activation from the ultrasensitive Doppler movie.
Functional ultrasound (fUS) measures indirectly cerebral blood volume which provides an effect size close to 20% and as such is quite more sensitive than fMRI whose BOLD response is typically only a few percents.
fUS has been shown to have a spatial resolution on the order of 100 μm at 15 MHz in ferrets[11] and is sensitive enough to perform single trial detection in awake primates.
Commercial scanners with specialized hardware and software[13] are enabling fUS to rapidly expand behind ultrasound research labs to the neuroscience community.
To counterbalance the intrinsically poor sensitivity of matrix elements, they devised a 3D multiplane-wave scheme with 3D spatiotemporal encoding of transmit signals using Hadamard coefficients.
[6] fUS can be applied for chronic studies in animal models through a thinned-skull[18] or smaller cranial window or directly through the skull in mice.
[22] Seed-based maps, independent component analysis of resting states modes or functional connectivity matrix between atlas-based regions of interests can be constructed with high resolution.
For adults, this method can be used during neurosurgery to guide the surgeon through the vasculature and to monitor the patient's brain function prior to tumor resection[26][27]
