Functional Ultrasound (fUS) Imaging: a new neuroimaging modality for neuroscience

In the last twenty years, the progressive introduction of plane or diverging ultrasonic wave transmissions rather than line by line scanning focused beams broke the resolution limits of ultrasound imaging. By using such large field of view transmissions, the frame rate reaches the theoretical limit of physics dictated by the ultrasound speed and an ultrasonic map can be provided typically in tens of micro-seconds (several thousands of frames per second). Interestingly, this leap in frame rate is not only a technological breakthrough but it permits the advent of completely new ultrasound imaging modes, including shear wave elastography, electromechanical wave imaging, ultrafast Doppler, ultrafast contrast imaging, and even functional ultrasound imaging (fUS imaging) of brain activity  introducing Ultrasound as an emerging full-fledged neuroimaging modality. At ultrafast frame rates, it becomes possible to track in real time the transient vibrations – known as shear waves – propagating through organs. Such "human body seismology" provides quantitative maps of local tissue stiffness whose added value for diagnosis has been recently demonstrated in many fields of radiology (breast, prostate and liver cancer, cardiovascular imaging, ...). For blood flow imaging, ultrafast Doppler permits high-precision characterization of complex vascular and cardiac flows. It also gives ultrasound the ability to detect very subtle blood flow in very small vessels. In the brain, such ultrasensitive Doppler paves the way for fUltrasound or fUS (functional ultrasound) imaging of brain activity with unprecedented spatial and temporal resolution compared to fMRI. It provides the first modality for imaging of the whole brain activity working on awake and freely moving animals with unprecedented resolutions and was also translated recently to clinics.

Finally, we recently demonstrated that it can be combined with 3 µm diameter microbubbles injections in order to provide a first in vivo and non-invasive imaging modality at microscopic scales deep into organs combined with contrast agents by localizing the position of millions of microbubbles at ultrafast frame rates. This ultrasound localization microscopy technique solves for the first time the problem of in vivo imaging at microscopic scale the whole brain vasculature. Beyond fundamental neuroscience or stroke diagnosis, it will certainly provide new insights in the understanding of tumor angiogenesis, for example combined with PET/CT imaging.

Bio
Mickael Tanter is a research professor of the French National Institute for Health and Medical Research (Inserm) and distinguished professor of ESPCI Paris. He is heading the laboratory “Physics for Medicine” and deputy director of Langevin Institute (CNRS) at ESPCI, Paris, France. He is also the director of the first INSERM Technology Research Accelerator created in 2016 and dedicated to Biomedical Ultrasound. Mickael Tanter is a world-renowned expert in biomedical ultrasound and wave physics. He authored more than 300 peer-reviewed papers and book chapters and is the recipient of 45 international patents. In the last 20 years, he co-invented several major innovations in Biomedical Ultrasound: Transient Elastography, Ultrafast Ultrasound and Shear Wave Elastography, functional Ultrasound (fUS) imaging of brain activity and Superresolution Ultrasound based on Ultrasound Localization Microscopy. He received many national and international distinctions (among them the Honored Lecture of the Radiology Society of North America in 2012, the Grand Prize of Medicine and Medical Research of Paris city in 2011, the Grand Prize of Fondation de la Recherche Médicale in 2016 and the Carl Hellmuth Hertz Prize of IEEE Ultrasonics, Ferroelectrics and Frequency Control society in 2017, and recently the highest distinction of the European Society in Molecular Imaging ESMI). M. Tanter is also the co-founder of several MedTech companies in Biomedical Ultrasound (Supersonic Imagine, CardiaWave, Iconeus).