Acoustic biomolecules enhance hemodynamic functional ultrasound imaging of neural activity
Abstract
Hemodynamic functional ultrasound imaging (fUS) of neural activity provides a unique combination of spatial coverage, spatiotemporal resolution and compatibility with freely moving animals. However, deep and transcranial monitoring of brain activity and the imaging of dynamics in slow-flowing blood vessels remains challenging. To enhance fUS capabilities, we introduce biomolecular hemodynamic enhancers based on gas vesicles (GVs), genetically encodable ultrasound contrast agents derived from buoyant photosynthetic microorganisms. We show that intravenously infused GVs enhance ultrafast Doppler ultrasound contrast and visually-evoked hemodynamic contrast in transcranial fUS of the mouse brain. This hemodynamic contrast enhancement is smoother than that provided by conventional microbubbles, allowing GVs to more reliably amplify neuroimaging signals.
Additional Information
© 2019 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Received 19 August 2019, Revised 19 November 2019, Accepted 13 December 2019, Available online 15 December 2019. We thank Di Wu and Thomas Deffieux for helpful discussions. DM is supported by a Human Frontiers Science Program Cross-Disciplinary Postdoctoral Fellowship (Award No. LT000637/2016). This research was funded by the National Institutes of Health (grant U01NS099724 to MGS). Related research in the Shapiro laboratory is also supported by the Heritage Medical Research Institute, Burroughs Wellcome Career Award at the Scientific Interface, the Pew Scholarship in the Biomedical Sciences and the Packard Fellowship for Science and Engineering. Author contributions: David Maresca: Conceptualization, Methodology, Software, Validation, Formal Analysis, Investigation, Resources, Data Curation, Visualization, Project Administration, Writing – Original Draft, Funding Acquisition. Thomas Payen: Methodology, Software, Formal Analysis, Investigation, Resources, Data Curation, Writing – Original Draft. Audrey Lee-Gosselin: Methodology, Investigation, Project Administration. Bill Ling: Methodology, Investigation. Dina Malounda: Resources. Charlie Demené: Conceptualization, Methodology, Software, Investigation, Writing – Review and Editing. Mickaël Tanter: Conceptualization, Funding Acquisition, Writing – Review and Editing, Supervision. Mikhail G. Shapiro: Conceptualization, Formal Analysis, Funding Acquisition, Writing – Review and Editing, Supervision. Declaration of competing interest: MT is a co-founder and shareholder of Iconeus, a company commercializing ultrasound neuroimaging scanners. Other authors declare no competing financial interests.Attached Files
Published - 1-s2.0-S1053811919310584-main.pdf
Submitted - 734939.full.pdf
Supplemental Material - 1-s2.0-S1053811919310584-mmc1.pdf
Supplemental Material - 1-s2.0-S1053811919310584-mmc2.xml
Files
Additional details
- PMCID
- PMC6955150
- Eprint ID
- 97914
- Resolver ID
- CaltechAUTHORS:20190815-094537072
- LT000637/2016
- Human Frontier Science Program
- U01NS099724
- NIH
- Heritage Medical Research Institute
- Burroughs Wellcome Fund
- Pew Charitable Trust
- David and Lucile Packard Foundation
- Created
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2019-08-15Created from EPrint's datestamp field
- Updated
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2023-06-01Created from EPrint's last_modified field
- Caltech groups
- Heritage Medical Research Institute