Cocaine-induced abnormal cerebral hemodynamic responses to forepaw stimulation assessed by integrated multi-wavelength spectroimaging and laser speckle contrast imaging

Simultaneous imaging of cerebral hemodynamic changes in response to functional activation during drug intoxication provides a valuable strategy to assess cocaine-induced neurovascular dysfunction. However, this requires tools with sufficient spatiotemporal resolution and an adequate signal to noise ratio (SNR). Though several technologies have been developed to address this demand during functional brain activation, their spatiotemporal resolution has been compromised to preserve SNR. In this study, we combine spatiotemporal-domain laser speckle contrast analysis and image correlation techniques to integrate the multi-wavelength spectroimaging and laser speckle contrast imaging (MW-LSCI). Experimental results show that optimized spatiotemporal resolution with enhanced SNR were achieved that enabled simultaneous measurement of multiple hemodynamic responses (i.e., ΔHbO₂, ΔHbR, ΔHBT, and ΔCBF) during cocaine administration. Specifically, cocaine-induced functional cerebral hemodynamic changes were accessed by measuring the activation responses to forepaw electrical stimulation at different times after cocaine administration. With an improved spatiotemporal resolution and SNR, the system was able to differentiate the heterogeneity of cocaine's effects on the cerebral vasculature and on tissue metabolism, demonstrating the unique capability of MW-LSCI for various brain functional and pharmacological studies.