Cerebral perfusion in sickle cell disease patients assessed by ultrasound with microbubble contrast compared to Single Photon Emission Computed Tomography (SPECT)

• Grant number: 16/21112-0
• Support Opportunities: Regular Research Grants
• Duration: April 01, 2017 - July 31, 2021
• Field of knowledge: Health Sciences - Medicine - Medical Radiology
• Principal Investigator: José Claudio Meneghetti
• Grantee: José Claudio Meneghetti
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Renato Davino Chiovatto

Abstract

Introduction:Sickle cell disease (SCD) is the most common hereditary blood disease in the world and monogenic hereditary disease most common in Brazil, occurring predominantly among African descent.The cause of the disease is a mutation on the beta hemoglobin globin gene causing an abnormal hemoglobin called S hemoglobin (HbS). This mutation leads to physical-chemical modification of the hemoglobin molecule. In certain situations, these molecules can undergo polymerization with sickling of red blood cells, causing shortening of the average life of red blood cells, oclusion phenomena and episodes of pain and organ damage. (1,2)The distribution of S gene in Brazil is quite heterogeneous, and the prevalence of heterozygotes for hemoglobiona S (Hb S) higher in the North and Northeast regions (6% to 10%), while in South and Southeast prevalence is lower (2 % to 3%). (2-4) According to the National Neonatal Screening Program, 3,500 SCD children born per year in Brazil and 200,000 with sickle cell trait, it is estimated that 7.2 million people are carriers of the sickle cell trait (HbAS) (1,2,4) .SCD is a chronic inflammatory disease associated with clinically controlled acute episodes. Advances achieved through studies STOP I and II (Stroke Prevention Trial in Sickle Cell Anemia I, 1998, II, 2005) enabled the identification and treatment of children with increased risk of stroke (stroke), determining early onset of red blood cell transfusions one of the conditions that are currently the main causes of death in adolescents and young adult (4-6)The current prevalence order of the major complications of the central nervous system (CNS) in SCD patients include silent cerebral infarcts (39% up to 18 years), headache (both acute and chronic: 36% in children), stroke ischemic (1% in children with SCD with effective screening and prophylaxis, but 11% in children with SCD without screening) and hemorrhagic stroke in children and adults (3% and 10%, respectively). (7)Single photon emission computed tomography (SPECT) is the gold standard for evaluation of cerebral perfusion. Consists in a functional neuroimaging technique that allows non-invasive assessment of physiological and pathophysiological state of the brain. Ethyl cysteinate dimer 99m technetium (99mTc-ECD) is a lipophilic compound that crosses the blood-brain barrier. Upon entering the neuronal cell, it is converted into a hydrophilic form and remain trapped inside the cell. The distribution of label in the brain is proportional to the size of the regional cerebral blood flow. However, 99mTc-ECD is an infusion agent which requires a metabolic process termed desertification inside the cell, thus demonstrating indirect evidence of cellular metabolism. (8)Ultrasound contrast is gaining acceptance worldwide as a complement to conventional ultrasound. Consists in a soluble capsule which surrounds a gas sulfur based compound (sulfur hexafluoride) with lower dimensions of an erythrocyte (7-10 uM). Performed by intravenous injection, expanded the horizon of ultrasound by providing a technique with excellent sensitivity stages of arterial enhancement and dynamic real-time. For the first time, the blood flow in microcirculation demonstration or infusion levels are available for ultrasound. Furthermore, the microbubbles are exclusively intravascular, allow ultrasound is used to monitor changes in blood flow in tumors or inflammatory regions. Its performance is safe, without any requirement of ionizing radiation and no nephrotoxicity, making it an attractive option in many clinical areas and certainly for children. (9-11)In recent years, great progress has been made in cerebral perfusion imaging using brain ultrasound. Different approaches have been evaluated and shown to be capable of early detection of cerebral perfusion deficits in stroke patients. (11,12)This technological leap was possible because of the physical properties of the microbubbles that have a non-linear (AU)