Changes in cerebral blood flow are associated with stroke, aneurysms, vascular cognitive impairment, neurodegenerative diseases and other pathologies. Brain angiograms, typically performed via computed tomography or magnetic resonance imaging, are limited to millimetre-scale resolution and are insensitive to blood-flow dynamics. Here we show that ultrafast ultrasound localization microscopy of intravenously injected microbubbles enables transcranial imaging of deep vasculature in the adult human brain at microscopic resolution and the quantification of haemodynamic parameters. Adaptive speckle tracking to correct for micrometric brain-motion artefacts and ultrasonic-wave aberrations induced during transcranial propagation allowed us to map the vascular network of tangled arteries to functionally characterize blood-flow dynamics at a resolution of up to 25 μm and to detect blood vortices in a small deep-seated aneurysm in a patient. Ultrafast ultrasound localization microscopy may facilitate the understanding of brain haemodynamics and of how vascular abnormalities in the brain are related to neurological pathologies.
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Data examples are available from the repository with the identifier https://zenodo.org/record/4048550#.X6GPlVBCdPY. All raw and analysed data used in this study are available on request.
Data samples and MATLAB codes regarding the most important steps of the processing routine are available from the Zenodo repository at https://zenodo.org/record/4048550#.X6GPlVBCdPY. Codes for the loading and management of data are available on request.
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This work was supported by a research grant from the European Research Council (ERC) under the European Union’s Seventh Framework Program (FP7/2007–2013)/ERC Advanced grant agreement no. 339244-FUSIMAGINE (M.T.), by the Swiss National Foundation (Fond National Suisse) grant no. CR3213_150654 (F.P.) and the Fondation Bettencourt–Schueller. We thank L. Puke for her help with patient recruitment. We thank the NVIDIA Corporation for their support through the NVIDIA GPU Grant program and the donation of a Titan Xp GPU used for this research.
M.P. and M.T. are co-founders and shareholders of the Iconeus company commercializing ultrasound neuroimaging scanners. M.T. is co-inventor of the patent WO2012080614A1 on the ultrasound localization microscopy method filed on 16 December 2010 and licenced to the Iconeus company. All other authors declare no competing interests.
Peer review information Nature Biomedical Engineering thanks James Greenleaf and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary figures and video captions.
Principles and implementation of t-ULM.
Comparison of t-ULM and CT scan angiography.
Transcranial ULM of a 63-year-old patient.
Transcranial ULM of a 79-year-old patient.
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Demené, C., Robin, J., Dizeux, A. et al. Transcranial ultrafast ultrasound localization microscopy of brain vasculature in patients. Nat Biomed Eng 5, 219–228 (2021). https://doi.org/10.1038/s41551-021-00697-x