Transcranial photoacoustic imaging of indocyanine green J-aggregates reveals cerebral signal changes in lipopolysaccharide-induced systemic inflammation.

BACKGROUND

Systemic inflammation associated with surgery, infections, and trauma can damage organs, including the brain, and contribute to stroke and cognitive decline. Rapid assessment of inflammation-associated cerebrovascular changes remains difficult with existing neuroimaging modalities, particularly in settings requiring repeated or rapid measurements. Contrast-enhanced photoacoustic (PA) imaging may provide a research approach for monitoring cerebral vasculature.

OBJECTIVE

This pilot study investigated intracranial changes in dynamic PA signals of a novel photoacoustic imaging (PAI) tracer, non-encapsulated indocyanine green J-aggregates (J-aggs), in a model of lipopolysaccharide (LPS)-induced inflammation. This work is a pilot study to assess the potential of J-aggs for detecting systemic inflammation related changes in brain PAI signals.

METHODS

Systemic inflammation was induced in Sprague-Dawley rats with intraperitoneal (IP) LPS (3 mg/kg, n = 6) while sham rats received equal volume IP saline injections (n = 5). Transcranial PAI was performed before IP injections, 2-hours, and 4-hours after IP injections. Within the cerebral region of interest, P90 was defined as the mean PA signal intensity of voxels above the 90th-percentile intensity threshold, corresponding to the upper 10% of pixel values; group×time interactions were assessed using a linear mixed-effects model.

RESULTS

Intravenous J-aggs produced sustained PAI enhancement in sham rat brains (ΔP90(%) ~70% at 4-hours) whereas LPS-treated rats showed attenuated and more variable enhancement (ΔP90(%) ~30% at 4 h; group×time p = 0.0262). Reduced cerebral PA signal in LPS-treated rats may reflect altered J-aggs circulation or cerebral delivery, inflammation-related changes in cerebral blood volume, oxygenation, perfusion, or a combination of these factors.

CONCLUSION

Because imaging was performed at a single wavelength of 890 nm, P90 represents a composite photoacoustic signal arising from J-aggs and endogenous hemoglobin; therefore, the attenuated response in LPS-treated rats may reflect altered J-aggs circulation or cerebral delivery, inflammation-related changes in cerebral blood volume or oxygenation, or a combination of these mechanisms.