Abstract A097: Cerebral capillary blood transit time in sickle cell anemia

Background: The overall goal of this work is to apply novel MRI methods of vascular kinetics to test how anemia influences cerebral capillary transit times, with the ultimate goal of improving stroke risk assessments in patients with sickle cell anemia (SCA). More specifically, SCA patients have an increased risk of silent cerebral infarcts and stroke, yet patients often lack traditional stroke risk factors and imaging methods sensitive to ischemic risk are incomplete. Increased cerebral blood flow (CBF) occurs in SCA to compensate for decreased arterial oxygen content, which can lead to rapid capillary transit and reduced time for tissue oxygen delivery, an effect that manifests as dural sinus hyperintensity on arterial spin labeling (ASL) MRI. Here, we quantify blood transit times and shunted venous blood volume in control and SCA participants to test the hypothesis that quantitative arterio-venous transit time is reduced in SCA and warrants further investigation as a biomarker of ischemic risk. Methods: Adults with SCA and age- and race-matched healthy controls provided informed consent and were prospectively scanned using 3-Tesla MRI with a standard anatomical and angiography protocol supplemented with pulsed ASL MRI with 16 post-labeling times (200-3200 ms), which enabled quantification of arterial, tissue, and venous blood arrival times as well as venous shunted blood volume non-invasively in vivo (Figure 1A-C). Each variable was compared between cohorts and related to hemoglobin level with regression within SCA patients (significance: p<0.05). Results: 50 SCA and 25 healthy age-matched controls were enrolled (Table 1). Shunted blood volume was increased (p<0.001; Figure 2A) and venous arrival time shortened (p=0.019; Figure 2B) in SCA. While arterio-tissue transit was not significantly different (p=0.19), tissue-venous transit (p=0.039) and arterio-venous transit (p=0.026) differed (Figure 2C). A significant relationship was found between arterio-tissue transit (p=0.03; rho=0.31) as well as shunted blood volume (p=0.003; rho=-0.42) and hemoglobin. Conclusion: We found a significantly shorter venous arrival time and greater shunted blood volume in SCA relative to healthy participants, which may indicate reduced capacity to offload oxygen to brain parenchyma and may provide a new biomarker of infarct risk. Ongoing work is focused on surveillance imaging in patients with SCA to understand how blood transit times may portend to infarct development.