Abstract Body: Subarachnoid hemorrhage (SAH) is an uncommon stroke type that disproportionately contributes to stroke mortality and morbidity rates. A common complication of SAH is cerebral vasospasm, an abnormal narrowing of the cerebral blood vessels that typically develops between days 3 and 21 after the initial hemorrhage. Although the exact cause of vasospasm is not fully understood, it is known that this maladaptive response can precipitate delayed cerebral ischemia (DCI). Intrathecal (IT) administration of the calcium channel blocker nicardipine has been shown to be a promising treatment for vasospasm that reduces the incidence of delayed cerebral ischemia following SAH. In this study, we used a novel, non-invasive optical tool known as diffuse correlation spectroscopy (DCS) to determine the microvascular cerebral blood flow response to IT nicardipine over the first three days of treatment in a cohort of 41 non-traumatic, medium-to-high grade SAH patients (age: 49.6 ± 10.4 years (mean ± standard error), 73% female). For each dose, regional cerebral blood flow in the frontal cortex was continuously monitored for 90 min post-administration. We found cerebral blood flow increased significantly in response to nicardipine on all 3 days of treatment (Figure 1a, all p<0.001). However, the magnitude of this increase was blunted by day 3, indicating a progression towards a steady state. This result aligns with our previously published pharmacokinetic model for this intervention. Additionally, we observed that the cerebral blood flow response was significantly associated with radiographical DCI occurrence within six weeks of the initial hemorrhage (Fig 1 b-d). Patients who developed DCI on average had a blunted cerebral blood flow response to treatment. This difference in response between outcome groups was evident throughout all three days of monitoring. Collectively, these findings suggest that DCS could serve as a valuable biomarker for monitoring cerebral hemodynamic responses to therapeutic interventions in SAH and may aid in refining clinical decisions to reduce secondary stroke risk.