C-mode passive cavitation images for predicting large volume FUS-mediated drug delivery outcome

Passive cavitation detection has been commonly used to monitor focused ultrasound (FUS)-mediated blood-brain barrier disruption (FUS-BBBD). Previous research by our team has shown the feasibility to correlate passive cavitation imaging (PCI) with drug delivery outcome via FUS-BBBD at a single target. This study proposed to perform c-mode PCI for predicting the spatial distribution of aPD-L1 delivered by FUSBBBD. A single-element FUS transducer was used to perform sonication iteratively in a 3×3 grid at the whole brainstem of wild-type mice. PCI were acquired using an ultrasound imaging probe co-aligned with the FUS transducer. Reconstruction was performed to obtain c-mode PCI for the whole sonicated area in the plane normal to the PCI imaging plane (axial plane of FUS transducer). Fluorescence-labeled aPD-L1 was intravenously injected after FUS sonication and the delivery outcome was quantified using ex vivo fluorescence imaging. A high correlation (R2 = 0.79) was obtained between the fluorescence intensity and the cavitation dosage calculated from the c-mode PCI. No significant difference was found between 3dB area of the fluroescence images (6.93 ± 2.24mm2) and the 3 dB area of the c-mode PCI images (7.20 ± 0.74mm2). This study demonstrated that the c-mode PCI had the potential to predict drug delivery outcome by large volume FUS-BBBD.