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© Angela Erhard
For the first time ever, a team of scientists and clinicians led by the EU-funded researcher Mickael Tanter has managed to record the brain activity of a premature new-born baby during resting and during an epileptic seizure. Using a non-invasive ultrasound technology, this world premiere is a real game changer for researchers and the medical profession, offering a massive range of applications in neuroimaging and beyond. It is published today in Science Translational Medicine.
High-resolution, high-speed, safe and portable, this revolutionary ultrasound technology for neuroimaging was developed by the leading physicist Prof. Tanter and his interdisciplinary team at the Ecole Supérieure de Physique et de Chimie Industrielles de la ville de Paris (ESPCI Paris) and at the Institut national de la santé et de la recherche médicale (INSERM U979 "Wave Physics for Medicine") in Paris, with the support of the European Research Council (ERC).
The technique is non-invasive and can be used in bedside conditions, in stark contrast with current tools, including the Functional Magnetic Resonance Imaging (fMRI), the Positron Emission Tomography (PET) and the Computed Tomography (CT). Despite their high level of performance, the latter can be big, noisy, time-consuming, expensive and very disrupting for patients.
Tanter's novel technique is based on sonography, a method that relies on the generation of images by the bouncing of ultrasound waves. Commonly used by doctors - for instance during pregnancy - it had never been applied to neuroscience before as traditional ultrasound only allowed to image the blood flow in large blood vessels. To see the subtle neuronal activity of the smaller vessels of the brain, where the blood flow is less intense, an increased imaging sensitivity was indispensable. It has been achieved by Prof. Tanter’s team by combining ultrafast imaging rates and dedicated processing algorithms. The recording of the cerebral activity of premature new-borns reported today is the result of a fruitful collaboration between the researcher and his colleague, Prof. Olivier Baud, paediatrician and responsible for the department of neonatology of Robert Debré paediatric hospital in Paris. It sets an unprecedented achievement, marking the entrance of ultrasound in the world of clinical neurosciences.
From traditional sound waves to sophisticated brain functional imaging
Mickael Tanter's first attempt to boost ultrasound technology was back in 1999. With his team, he pioneered ultrafast ultrasound imaging based on plane wave transmission, instead of the usual sequential focused beams transmissions. At the time, through a complex algorithm, their state-of-the-art ultrasound scanner could already produce more than 10,000 ultrasonic images per second (fps), compared to the usual 50 fps of conventional ultrasound techniques.
"The machine was as big as a closet and we needed 45 minutes to process all the data collected. Even if we had manged to perform ultrafast ultrasound imaging, in the end, due to the technology state-of-the-art back of the 2000’s, the process was much slower than the one of the conventional Doppler method. We had to wait until computer's had evolved sufficiently, in 2008, to build a real time machine", explains Prof. Tanter.
This original development was nevertheless key, as it made possible to map, for the first time, the small and deep blood vessels of the brain with fast-speed, 50 times more sensitive, high resolution ultrasound. It also allowed to measure new and different parameters with direct clinical applications:
"With this ultrafast imaging, we could see the mechanical vibrations of the body, like those produced by the heartbeat and the breathing. By focusing the fast-speed ultrasound beam on a specific organ, we were also able to create a vibration and "palpate", in a non-invasive way, a specific part inside the body, like a doctor would do with his hands if he could reach internal organs. This "seismology" of the human body is key for diagnosis. We can now, for instance, measure the stiffness of a lesion, identify its benign or malignant nature, and spot cancerous tissues", adds Mickael Tanter.
End use applications for clinicians and researchers
Prof. Tanter has now taken his research a step forward by developing a Functional Ultrasound (fUS) technique with massive computational power for the processing of fast ultrasound images, which can reveal the functional connectivity of the brain. This includes interactions and full sequences never observed before, such as epilepsy seizure propagation.
Contrary to the fMRI, the functional ultrasound is light, portable, cheap, can be used in mobile animals and during surgery, thus offering tremendous clinical applications and new paths for fundamental research.
Video of a rat brain in 3D obtained by ultrafast Doppler tomography (related to publication Demené et al., 4D microvascular imaging based on Ultrafast Doppler tomography, NeuroImage, 2016).
"With this technique we have observed the brains of preterm babies through the fontanel and can identify the underlying mechanisms for some pathological conditions or neurological disorders, such as neonatal seizures and haemorrhages", points out the EU-funded researcher grantee. Functional ultrasound imaging can likewise be used in adults, both in neurosurgery and for transcranial imaging, as new adaptive focusing techniques can overcome the strong aberrations induced by the skull bone on ultrasonic wavefronts.
Coronal section of the cerebral vascular network, obtained in a non-invasive manner by ultrafast ultrasound Doppler imaging in a premature neonate. Credits: Inserm U979 "Physics of Waves for Medicine", Institut Langevin Waves and Images
In the near future, the resolution of fUS imaging could be further boosted thanks to a super-resolution ultrasound recently developed by the same research team. The whole functional activity of the brain could then be imaged at microscopic scales: a new world for neuroscience.
"All this is the result of human interactions", says Prof. Tanter, referring to his interdisciplinary team of physicists, neurobiologists, electrophysiologists, neurosurgeons and medical doctors in paediatric neonatality. "It is thanks to all of them that it has been possible to find new answers. Possibilities are endless: increasing image resolution even further, exploring alternatives to contrast methods currently used in fMRI ".