Understanding the neurovascular unit at multiple scales: Advantages and limitations of multi-photon and functional ultrasound imaging

Alan Urban, Lior Golgher, Clément Brunner, Amos Gdalyahu, Hagai Har-Gil, David Kain, Gabriel Montaldo, Laura Sironi, Pablo Blinder*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

36 Scopus citations


Developing efficient brain imaging technologies by combining a high spatiotemporal resolution and a large penetration depth is a key step for better understanding the neurovascular interface that emerges as a main pathway to neurodegeneration in many pathologies such as dementia. This review focuses on the advances in two complementary techniques: multi-photon laser scanning microscopy (MPLSM) and functional ultrasound imaging (fUSi). MPLSM has become the gold standard for in vivo imaging of cellular dynamics and morphology, together with cerebral blood flow. fUSi is an innovative imaging modality based on Doppler ultrasound, capable of recording vascular brain activity over large scales (i.e., tens of cubic millimeters) at unprecedented spatial and temporal resolution for such volumes (up to 10 μm pixel size at 10 kHz). By merging these two technologies, researchers may have access to a more detailed view of the various processes taking place at the neurovascular interface. MPLSM and fUSi are also good candidates for addressing the major challenge of real-time delivery, monitoring, and in vivo evaluation of drugs in neuronal tissue.

Original languageAmerican English
Pages (from-to)73-100
Number of pages28
JournalAdvanced Drug Delivery Reviews
StatePublished - 15 Sep 2017
Externally publishedYes

Bibliographical note

Funding Information:
This research was supported by a grant from the Leducq Foundation – Protect Stroke 15CVD02 . PB would like to acknowledge support from the European Research Council grant ERC-2014-STG_639416 , the Marie Curie grant CIG-2013 (#project 618251), and Israeli Science Foundation grant 1019/15 . AU would like to acknowledge support from the core research grant from Neuro-Electronics Research Flanders (NERF) funded by IMEC, VIB, and KU LEUVEN.

Publisher Copyright:
© 2017 Elsevier B.V.


  • Brain vasculature
  • Calcium imaging
  • Cerebral blood volume
  • Doppler
  • Functional brain imaging
  • Functional ultrasound imaging
  • Multi- and two-photon imaging
  • Neurovascular coupling


Dive into the research topics of 'Understanding the neurovascular unit at multiple scales: Advantages and limitations of multi-photon and functional ultrasound imaging'. Together they form a unique fingerprint.

Cite this