Clinical and biomedical researchers interested in cerebral hemodynamics and the application of novel MRI techniques in this context in clinical populations.Arterial Spin Labeling (ASL) MRI is a non-invasive MR technique that circumvents the need for PET-or-SPECT based evaluations of tissue viability, and allows us to assess perfusion in relation to stroke risk in Sickle Cell Disease (SCD). SCD is a hereditary form of anemia leading to red blood cell damage and neurovascular tissue insults. Local deficits in perfusion lead to silent infarcts as a result of impaired cerebrovascular reserve (CVR). Our aim was to gain understanding of cerebral hemodynamics in SCD using a perfusion MRI approach by utilizing ASL MRI. We investigated the acute CBF response to an administration of acetazolamide (ACZ) ‒ a potent vasodilator ‒in order to probe CVR in patients with SCD who were in a steady-disease state. We hypothesized that patients would have a limited CVR in response to ACZ due to pre-existing increased vasodilation and elevated resting CBF¹.21 SCD patients (aged 34±12 years) with HbSS or HbSß⁰-thalassaemia genotypes, and 4 age- and ethnicity-matched healthy controls (aged 34±16years) were scanned with pseudo continuous ASL (pCASL) before and 15 minutes after an intravenous administration 16mg/kg ACZ on a 3.0Tesla Philips Ingenia system (Philips Healthcare, Best, the Netherlands) with a 32-channel head coil and body coil transmission. Parameters were: 2D gradient-echo single-shot EPI read-out, FOV 240x240x133mm, resolution 3x3x7mm, 19 axial slices, with background suppression, TR/TE4400/14ms,flip angle 90°, PLD 1800, labeling duration 1800, SENSE 2.5 in AP direction, 35 dynamic scans, acquisition time 5 mins. T1 of blood was measured in the sagittal sinus with a separate Look-locker MR sequence. This provided group-specific mean values for T1blood that were subsequently used for the quantification of CBF (1800 ms for patients and 1650 ms for controls). ASL data were processed in an in-house developed SPM12-based processing pipeline in which ASL label-control pairs were subtracted to obtain perfusion-weighted images, aligned, motion-corrected, and registered to MNI standard space on T2-weighted segmentations. CBF was quantified using a single-compartment flow model². Wilcoxon rank-sum tests were performed to compare groups on CBF at baseline, and CVR, as shown in table 1. CBF was compared in the middle and anterior vascular flow territories. ASL CVR=(CBF_post–CBF_pre)/CBF_post*100%, where CBF_pre is baseline and CBF_post is post-acetazolamide CBF. Pearson’s correlation was performed between baseline CBF and CVR. P<0.05 was considered statistically significant and group results are shown with standard deviations.CBF was not significantly higher in patients (mean 33 ± 10 mL/100g/min) compared to controls (mean 23 ± 3 mL/100g/min) at baseline (p=0.06) but was significantly correlated with Hct (Pearson’s R=0.73, p<0.001). Furthermore, CBF was significantly related to the magnitude of CVR in response to ACZ administration. Mean CVR in patients (29 ± 12%) was significantly higher (p=0.01) than in controls (47 ± 5%) (figure 1). CVR was greater in all vascular territory regions in controls (mean CVR=41%) compared to patients (mean CVR=29%). Figure 1 shows the inverse linear relationship between CBF at baseline and the CVR in response to acetazolamide (y=-0.66*x+53.9, R² 0.25, p=0.02).The finding that patients had no higher CBF at baseline is contradictory to previous studies³. This could be explained by the small sample size of n=4 in controls or by a better quantification due to incorporation of measured blood T1. The CVR response to acetazolamide was robust and can be appreciated on single subject images. The finding that hematocrit correlated with CBF confirms previous findings in which perfusion increases may compensate for anemia in order to allow stable blood flow to the brain to provide sufficient oxygen. The relatively low CVR in SCD patients is in line with literature suggesting that maximum vasodilation has been reached in SCD. Since this can already by observed in SCD patients in a steady-state of their disease course, it is very imaginable that the CVR will become exhausted during times of increased metabolic demand. The results show that CVR has the potential of becoming a cerebrovascular biomarker for treatment selection for patients.In conclusion, we found that ASL-based CBF measurements with ACZ showed robust CVR results indicating the cerebral hemodynamics of some patients may be impaired.