Transcranial photoacoustic imaging shows promise for non-invasive evaluation of brain injury and blood-brain barrier disruption (BBB-D). Our study used neonatal rats with immature cerebral blood vessels, making them more susceptible to brain injury. Neuroinflammation was induced using lipopolysaccharide (LPS), leading to BBB-D. We employed a small-animal photoacoustic imaging system that integrated a wavelength-tunable laser (680-970 nm) and a high-frequency ultrasound transducer to obtain transcranial ultrasound and photoacoustic (PA) images. BBB-D was visualized by the migration and accumulation of indocyanine green (ICG) J-aggregate nanoprobes in the brain, resulting in enhanced PA signal. Following LPS injection, a two-fold increase in PA signal intensity was observed at 2 hours, peaking at a four-fold increase at 4 hours. The enhanced PA signal persisted up to 24 hours and remained within 30% of the baseline at 48 hours. These findings have significant implications for early detection of BBB-D using transcranial photoacoustic imaging, made possible by the use of neonatal rats with thin skulls and photoacoustic contrast agents with distinct spectral signatures in vivo.
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