Evidence of cerebral hypoperfusion consecutive to ultrasound-mediated blood-brain barrier opening in rats
Wafae Labriji, Julien Clauzel, Jean-Louis Mestas, Maxime Lafond, Cyril Lafon, Anne-Sophie Salabert , Lydiane Hirschler, Jan M. Warnking, Emmanuel L. Barbier, Isabelle Loubinoux, Franck Desmoulin
Abstract
Purpose
This work aims to explore the effect of Blood Brain Barrier (BBB) opening using ultrasound combined with microbubbles injection on cerebral blood flow in rats.
Methods
Two groups of n = 5 rats were included in this study. The first group was used to investigate the impact of BBB opening on the Arterial Spin Labeling (ASL) signal, in particular on the arterial transit time (ATT). The second group was used to analyze the spatiotemporal evolution of the change in cerebral blood flow (CBF) over time following BBB opening and validate these results using DSC-MRI.
Results
Using pCASL, a decrease in CBF of up to 29.6 ± 15.1% was observed in the target hemisphere, associated with an increase in arterial transit time. The latter was estimated to be 533±121ms in the BBB opening impacted regions against 409±93ms in the contralateral hemisphere. The spatio-temporal analysis of CBF maps indicated a nonlocal hypoperfusion. DSC-MRI measurements were consistent with the obtained results.
Conclusion
This study provided strong evidence that BBB opening using microbubble intravenous injection induces a transient hypoperfusion. A spatiotemporal analysis of the hypoperfusion changes allows to establish some points of similarity with the cortical spreading depression phenomenon.