What is functional ultrasound (fUS)?
A new modality for fast, sensitive, high-resolution brain imaging
Functional ultrasound, abbreviated ‘fUS’ by analogy to functional MRI (fMRI), is a method for brain imaging that generates information on blood volumes with unprecedented detail. Unlike regular ultrasound, it uses plane-wave ultrasound to provide high sensitivity and high spatial resolution at the same time as a high image framerate.
How does functional ultrasound work?
The concept of functional ultrasound was presented in a high-profile paper co-authored by our founder, Mickael Tanter (Macé et al., Nature Methods, 2011). Because fUS uses a succession of ultrasound ‘plane waves’, rather than a beam focused on a point, echoes are received from an entire 2D plane in one go. This improves on conventional ultrasound imaging by avoiding the need to acquire data from small volumes sequentially.
But the success of fUS also depends crucially on the rate at which those plane-wave pulses can be generated. Because we employ ultrasound technology capable of generating pulses at about 20 kHz, a large number of responses can be combined into one image. This improves the signal-to-noise ratio and so vastly increases sensitivity.
Every ultrasound pulse transmitted gives rise to an echo (backscatter) from the bodily tissues. After subtracting unwanted low-frequency ‘quasi-static’ echoes, we are left with the higher-frequency signal due to the moving red blood cells alone. The mean intensity of this signal is known as the ‘Power Doppler’ value, which is proportional to the number of red blood cells in a unit volume, and hence to the cerebral blood volume (CBV).
The fact that brain activity is closely synchronized with the dilation of the blood vessels supplying the neurons involved (the neurovascular coupling) means that the CBV measured by fUS can be used as a surrogate for neuronal activity. Therefore, with a bit of behind-the-scenes number-crunching, the complex datasets generated from an fUS scan can be converted into easy-to-understand images (and videos) showing patterns of brain activation – as they happen.
Better than BOLD-based fMRI
Functional magnetic resonance imaging (fMRI) using the blood-oxygen-level-dependent (BOLD) response is the ‘gold standard’ for deep brain imaging in humans. But its restricted spatial and temporal resolution makes it of limited use when looking at small animals in preclinical settings (especially mice). Also, the small responses generated by BOLD mean that you need to take an average of many experiments to get an acceptable signal-to-noise ratio.
Functional ultrasound using Iconeus One provides an alternative approach, by offering:
- High spatial resolution (down to 100 µm)
- High temporal resolution (as low as 100 ms)
- High sensitivity (about 100× that of conventional ultrasound systems).
The result is performance that’s as good as, or better than, the best fMRI systems – even minor blood vessels in small mammalian brains can be imaged with a single scan. Not only that, but the size of the probes allows animals to be imaged while they’re awake and moving, which is impossible with fMRI.
Complementary to other techniques
In contrast to fMRI and the strong magnetic fields it requires, fUS has little (or zero) impact on tissues or equipment. It’s therefore straightforward to combine with other modalities such as electro-encephalography (EEG), multi-electrode arrays, positron emission tomography (PET), optical imaging, or optogenetics.
This means you can easily obtain a detailed understanding of brain vasculature and blood flows at the same time as carrying out electrophysiology, metabolism, optogenetics, guided injections and more… and so gain better research insights.
Keep up to date with new fUS research
Functional ultrasound is a new technology that’s constantly evolving: we’re always busy coming up with new hardware and software advances, and of course the range of applications is growing as more researchers join our fUS community.
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