Time-resolved laser speckle contrast imaging (TR-LSCI) of cerebral blood flow response to intracranial pressure elevation

Significance: Cerebral autoregulation (CA) reflects the dynamic coupling among cerebral blood flow (CBF), intracranial pressure (ICP), and arterial blood pressure (ABP); its failure contributes to secondary brain injury. Existing bedside methods rely on indirect or spatially limited CBF surrogates and cannot resolve microvascular flow dynamics across space, depth, and time. Aim: To develop, optimize, and apply a scalable, noncontact time-resolved laser speckle contrast imaging (TR-LSCI) platform for depth-sensitive, high-speed, wide-field CBF imaging during controlled ICP perturbations. Approach: ) to detect diffuse photons at varying path lengths, enabling depth-resolved microvascular CBF imaging. Noise-corrected diffuse speckle analysis was implemented to reduce bias at gates with low signal-to-noise ratio and depth sensitivity was assessed across multiple time gates. Benchtop and mobile TR-LSCI systems were applied in adult rats and a neonatal piglet with synchronized invasive ICP and ABP measurements. Results: TR-LSCI captured spatially heterogeneous, pulsatile CBF dynamics at up to 52 Hz over large cortical fields of view, with heart rate estimates statistically equivalent to those from ICP and ABP. Consistent CBF trends across gates support robust physiological interpretation despite depth-dependent differences in absolute magnitude. Multivariable analysis identified reproducible, phase-dependent CA transitions encompassing preserved autoregulation, ABP-driven compensation, and ICP-constrained CBF suppression; notably, CBF alone exhibited distinct phase signatures. Conclusion: TR-LSCI enables dynamic, physiology-informed neurovascular monitoring and supports future bedside CA assessment.