Cerebral Oxygen Supply and Demand in Sickle Cell Disease: Evidence of Local Ischemia Despite Global Hyperemia

Stroke, fundamentally caused by a mismatch in cerebral oxygen delivery and utilization, is a common and devastating complication of sickle cell disease in both low- and high-income countries. Clinically, elevated middle cerebral artery velocity measured with transcranial doppler remains the most widely used biomarker of stroke risk in patients with sickle cell disease. Despite its historical success, stroke risk determined using transcranial doppler is based on data that is over 30 years old, has a large false positive rate (80%) and is ineffective at determining risk for silent stroke. Currently, several novel therapeutics and noninvasive imaging technologies are being developed for use in sickle cell disease and stand ready to once again revolutionize stroke management and outcomes in patients with sickle cell disease. A comprehensive understanding of the balance between cerebral oxygen delivery and utilization in sickle cell disease is therefore crucial for guiding the application of these therapies to minimize stroke in this population. 
The goal of this research topic is to review and present recent findings related to oxygen delivery and utilization in sickle cell disease. In quest of this goal, we invite submissions that shed light on the basic mechanistic, methodological and clinical aspects of cerebral oxygen supply and demand physiology in sickle cell disease.  These include manuscripts that:synthesize recent data and physiological conclusions related to cerebral oxygen supply and demand matching in sickle cell diseasedescribe normal brain physiology and/or adaptive ischemic physiologydetermine stroke risk and/or predict clinical outcomes in sickle cell diseasepresent techniques to measure and analyze oxygen delivery and utilization (e.g. local, whole brain, regional, peripheral, spatial variation, etc.)compare cerebral oxygen delivery and utilization in sickle cell disease to other known disease models and organ systemsmodel cerebral oxygen delivery and utilization in sickle cell disease on the cellular, tissue and/or systems levelhighlight differences between clinical and research biomarkers in regard to feasibility, utility and physiological conclusions in sickle cell diseaserelate hematological and imaging biomarkers that may inform clinical decision makingshow the effect of emerging and commonly prescribed medications in sickle cell disease on physiology and imaging biomarkers
Reviews, original research, and small-scale studies are welcome. Manuscripts based on animal, pediatric and adult human studies are welcome.
Topic Editor Dr. Melanie Fields is a consultant for Global Blood Therapeutics (South San Francisco, CA, USA) and is an equity holder in Proclara Biosciences (Cambridge, MA, USA). Topic Editor Dr. Lena Vaclavu is partly funded by Philips Healthcare. All other Topic Editors declare no competing interests with regards to the Research Topic subject.