Noninvasive diffuse optical monitoring of cerebral blood flow and oxygenation responses to intermittent hypoxia in neonatal rats

Significance: Intermittent hypoxia (IH) is common in preterm neonates and can cause hypoxic–ischemic brain injury. Simultaneous monitoring of cerebral blood flow (CBF) and oxygenation is essential to detect oxygen delivery-extraction mismatches and guide intervention. Aim: We aimed to adapt and test an innovative diffuse speckle contrast flow oximetry (DSCFO) system for continuous monitoring of cerebral hemodynamics during IH in neonatal rats, a model approximating human neonates. Approach: Two compact laser diodes and a miniature CMOS camera were integrated into a fiber-free probe for continuous monitoring of changes in relative CBF (rCBF) and oxy- and deoxy-hemoglobin concentrations (Δ[HbO₂] and Δ[Hb]) in 8-day-old neonatal rats. Sham rats (n=6) underwent 10 min of normoxia, whereas IH rats (n=8) experienced 10 cycles of sequential 2-min hypoxia (8% O₂) and 2-min hyperoxia (100% O₂). Results: Sham rats maintained stable cerebral hemodynamics under normoxia, whereas IH rats exhibited pronounced periodic fluctuations during IH. Hypoxic episodes caused instantaneous decreases in rCBF and Δ[HbO₂] and increases in Δ[Hb], whereas hyperoxic episodes reversed these effects, reducing hypoxic stress. However, the pronounced cerebral hemodynamic fluctuations during IH may still contribute to brain injury. Conclusions: We demonstrate an affordable, noninvasive, wearable, fiber-free DSCFO system for continuous monitoring of rCBF, Δ[HbO₂], and Δ[Hb] during IH in neonatal rats. The system captured hypoxia-induced cerebral deoxygenation and hyperoxia-driven recovery, revealing episode-dependent protective and disruptive mechanisms. Future work will correlate DSCFO findings with neurological and histological outcomes to guide IH interventions in large neonatal animal models and human infants.