Ultrafast ultrasound localization microscopy for deep in vivo super-resolution vascular imaging.

Nature, 527,499–502 (November 2015)

Physicists of our team “Wave physics for medicine” (Inserm Unit 979) led by Mickaël Tanter has recently demonstrated the use of microbubbles for imaging the vascular network at a microscopic scale deep inside tissue, a work in collaboration with Dr. Zsolt Lenkei and Dr. Sophie Pezet from the Laboratory of Brain Plasticity at ESPCI.

These results are of high importance as they solve for the first time the great challenge of non invasive microscopic imaging at several cm depths into organs. Such microscopic microvascular imaging paves the way towards super resolution functional brain imaging by the fusimagine team in the future.

Our paper presents a new imaging technique called Ultrafast Ultrasound Localization Microscopy (UULM) that enables microvascular imaging at a microscopic scale. Non-invasive imaging deep into organs at microscopic scales remains an open quest in biomedical imaging.

Here we demonstrate in vivo that ultrasound imaging at ultrafast frame rates (more than 500 frames per second) provides an analogue to optical localization microscopy by capturing the transient signal decorrelation of contrast agents—inert gas microbubbles. Ultrafast ultrasound localization microscopy allowed both non-invasive sub-wavelength structural imaging and haemodynamic quantification of rodent cerebral microvessels more than ten millimetres below the tissue surface, leading to transcranial whole-brain imaging within short acquisition times (tens of seconds). After intravenous injection, single echoes from individual microbubbles were detected through ultrafast imaging. Their localization, not limited by diffraction, was accumulated over 75,000 images, yielding 1,000,000 events per coronal plane and statistically independent pixels of ten micrometres in size.

“ Our results pave the way for deep non-invasive microscopy in animals and humans using ultrasound. We anticipate that ultrafast ultrasound localization microscopy may become an invaluable tool for the fundamental understanding and diagnostics of various disease processes that modify the microvascular blood flow, such as cancer, stroke and arteriosclerosis. ” explains Claudia Errico, the first Author of this research work and PHD student at the Langevin Institute – Wave Physics for Medicine.

For more information, see:

Ultrafast ultrasound localization microscopy for deep in vivo super-resolution vascular imaging. Claudia Errico, Juliette Pierre, Sophie Pezet, Yann Desailly, Zolt Lenkei, Olivier Couture & Mickaël Tanter, Nature 2015.

http://www.nature.com/nature/journal/v527/n7579/abs/nature16066.html

See also the press release from ESPCI and Inserm :

https://www.espci.fr/en/news/2015/biomedical-imaging-with-microscopic-resolution-the