A local difference in blood-brain barrier permeability in the caudate putamen and thalamus of a rat brain induced by focused ultrasound

Abstract

A blood-brain barrier (BBB) opening induced by focused ultrasound (FUS) has been widely studied as an effective way of treating brain diseases. We investigate the effect of ultrasound's incidence angle at caudate putamen (Cp) and thalamus (Th) of the rat brain by inducing the same power of focused ultrasound that corresponds to the acoustic pressure of 0.65 MPa in free field. The BBB permeability (K-trans) was quantitatively evaluated with dynamic contrast-enhanced magnetic resonance imaging. The group averaged (n=11) maximum K-trans at Cp (0.021 +/- 0.012 min(-1)) was 1.39 times smaller than the K-trans of Th (0.029 +/- 0.01 min(-1)) with p=0.00343. The group averaged (n=6) ultrasound's incidence angles measured using the computed tomography image of rat skulls were compared with the maximum K-trans and showed a negatively linear relation R-2=0.7972). The maximum acoustic pressure computed from the acoustic simulation showed higher average acoustic pressures at Th (0.37 +/- 0.02 MPa) compared to pressures at Cp (0.32 +/- 0.01 MPa) with p=0.138x10(-11). More red blood cell were observed at the Th region compared to the Cp region in the tissue staining. These results indicate that localized characteristics of the sonication target within the subject should be considered for safer and more efficient BBB disruption induced by FUS.