Numerical Optimisation of Photoacoustic Imaging of Mouse Brain Vasculature in Transcranial Ultrasound Applications

OBJECTIVE: Focused ultrasound (FUS) combined with microbubbles can locally and transiently open the blood-brain barrier (BBB), allowing enhanced drug delivery into the brain. During treatment, monitoring techniques are required to identify BBB disruption and downstream effects. Photoacoustic imaging (PAI), as a high contrast and high spatial resolution imaging modality, provides the capability to visualize dynamic processes during therapy, without interfering with the therapeutic acoustic field. The objective of this study was to evaluate transcranial light propagation in the mouse brain and define the optimal characteristics of a preclinical PAI monitoring system. METHODS: We performed 3D Monte Carlo simulations to evaluate transcranial light propagation in the mouse brain. After determining the optimal optical parameters and acquiring optical fluence in the mouse brain, we conducted photoacoustic (PA) reconstruction to obtain PAI of the cerebral blood vessels. RESULTS: We numerically determined the optimal near-infrared (NIR) wavelength range (890-1030 nm) and incident angle range (12°-63°) for long-axis lateral illumination, as well as the wavelength range (890-1030 nm) and incident angle range (10°-50°) for standard dark-field illumination, to optimize PAI during therapeutic ultrasound exposure. The resulting PAI had a signal-to-noise ratio of up to 28.1 dB. Furthermore, resolution analysis using vessel-mimicking phantoms demonstrated lateral and axial resolutions of approximately 160 μm and 100 μm, respectively, highlighting the system's capability to detect fine vessel-mimicking structures during BBB-opening monitoring. CONCLUSION: Our findings indicate that a wavelength of 980 nm with an incidence angle of 25° under standard dark-field illumination is an ideal commercially available option for preclinical implementation of transcranial PAI in mouse models.