Ultrasound harmonic imaging of perfusion after ultrasound contrast agent (UCA) bolus injection (BHI) can detect cerebral perfusion deficits. In a pilot study, we evaluated the ability of time-intensity curve (TIC) measurements to differentiate between normal and hypoperfused brain areas in acute ischemic stroke. Ten patients with symptoms of acute middle cerebral artery infarction were investigated (SONOS 5500, Harmonic Imaging 1.6/3.8 MHz, diencephalic plane, 10 cm investigation depth, SonoVue 2.4 mL bolus). Peak signal increase (PSI), time-to-peak intensity (TPI) and area under the curve (AUC) were calculated for 60 regions-of-interest (ROIs) in each patient. Reference methods: Perfusion- and diffusion-weighted MRI (PWI/DWI) within 4 h before/after BHI (PWI threshold: 4 s). Receiver operating characteristics (ROC) analysis defined cut-off values for each TIC variable to distinguish between normal and affected brain areas as defined by PWI/DWI. In five patients, PWI showed a perfusion delay >4 s; seven patients had a DWI lesion. In three patients, both PWI and DWI findings showed pathology; one patient had a normal MRI of the insonation plane. Cut-off values for PWI delay: PSI: 5.53% (sensitivity .98, specificity .89); TPI: 4.04 s (sensitivity .74, specificity .69) and AUC: .63 (sensitivity .94, specificity .58). Referred to the mean value in unaffected brain areas the relative thresholds were 17.6%, 109.5% and 16.1%, respectively. Regarding DWI, only for PSI, a significant cut-off value was defined: 10.86%, sensitivity .84, specificity .60 (34.6% of mean). In conclusion, these thresholds distinguish between normal and affected brain areas in acute ischemic stroke.