Quantifying the Cerebral Hemometabolic Response to Blood Transfusion in Pediatric Sickle Cell Disease With Diffuse Optical Spectroscopies

• Type of Material: Article
• Authors: Seung Lee, Emory University; Rowan O Brothers, Georgia Institute of Technology; Katherine B Turrentine, Georgia Institute of Technology; Ayesha Quadri, Georgia Institute of Technology; Eashani Sathialingam, Georgia Institute of Technology; Kyle R Cowdrick, Georgia Institute of Technology; Scott Gillespie, Emory University; Shasha Bai, Emory University; Adam Goldman-Yassen, Emory University; Clinton Joiner, Emory University; Robert Brown, Emory University; Erin Buckley, Emory University
• Language: English
• Date: 2022-07-01
• Publisher: FRONTIERS MEDIA SA
• Publication Version: Final Published Version
• Copyright Statement: © 2022 Lee, Brothers, Turrentine, Quadri, Sathialingam, Cowdrick, Gillespie, Bai, Goldman-Yassen, Joiner, Brown and Buckley.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fneur.2022.869117
• Title of Journal or Parent Work: FRONTIERS IN NEUROLOGY
• Volume: 13
• Start Page: 869117
• End Page: 869117
• Grant/Funding Information: This project was supported by National Institute of Health R01HL152322 (EB), R21HL138062 (EB), F31HL154703 (ES), and American Heart Association 19POST34380337 (SYL).; This work was supported by the National Science Foundation Graduate Research Fellowship Program under Grant No. 1937971 (ROB).
• Keywords: Neurosciences & Neurology; Science & Technology; CHILDREN; METABOLISM; sickle cell disease (SCD); blood transfusion; THERAPY; frequency-domain near-infrared spectroscopy; ADULTS; diffuse correlation spectroscopy (DCS); INFARCTS; Neurosciences; OXYGEN EXTRACTION FRACTION; RISK; Life Sciences & Biomedicine; PREVENTION; near-infrared spectroscopy; cerebral hemometabolics; cerebral blood flow; STROKE; cerebral oxygen extraction fraction; Clinical Neurology; FLOW
• Research Categories: Health Sciences, Oncology; Biology, Biostatistics; Engineering, Biomedical

Abstract

Red blood cell transfusions are common in patients with sickle cell disease who are at increased risk of stroke. Unfortunately, transfusion thresholds needed to sufficiently dilute sickle red blood cells and adequately restore oxygen delivery to the brain are not well defined. Previous work has shown that transfusion is associated with a reduction in oxygen extraction fraction and cerebral blood flow, both of which are abnormally increased in sickle patients. These reductions are thought to alleviate hemometabolic stress by improving the brain's ability to respond to increased metabolic demand, thereby reducing susceptibility to ischemic injury. Monitoring the cerebral hemometabolic response to transfusion may enable individualized management of transfusion thresholds. Diffuse optical spectroscopies may present a low-cost, non-invasive means to monitor this response. In this study, children with SCD undergoing chronic transfusion therapy were recruited. Diffuse optical spectroscopies (namely, diffuse correlation spectroscopy combined with frequency domain near-infrared spectroscopy) were used to quantify oxygen extraction fraction (OEF), cerebral blood volume (CBV), an index of cerebral blood flow (CBFi), and an index of cerebral oxygen metabolism (CMRO2i) in the frontal cortex immediately before and after transfusion. A subset of patients receiving regular monthly transfusions were measured during a subsequent transfusion. Data was captured from 35 transfusions in 23 patients. Transfusion increased median blood hemoglobin levels (Hb) from 9.1 to 11.7 g/dL (p < 0.001) and decreased median sickle hemoglobin (HbS) from 30.9 to 21.7% (p < 0.001). Transfusion decreased OEF by median 5.9% (p < 0.001), CBFi by median 21.2% (p = 0.020), and CBV by median 18.2% (p < 0.001). CMRO2i did not statistically change from pre-transfusion levels (p > 0.05). Multivariable analysis revealed varying degrees of associations between outcomes (i.e., OEF, CBFi, CBV, and CMRO2i), Hb, and demographics. OEF, CBFi, and CBV were all negatively associated with Hb, while CMRO2i was only associated with age. These results demonstrate that diffuse optical spectroscopies are sensitive to the expected decreases of oxygen extraction, blood flow, and blood volume after transfusion. Diffuse optical spectroscopies may be a promising bedside tool for real-time monitoring and goal-directed therapy to reduce stroke risk for sickle cell disease.