MRI detection of brain abnormality in sickle cell disease

Abstract

Introduction: Over the past decades, neuroimaging studies have clarified that a significant proportion of patients with sickle cell disease (SCD) have functionally significant brain abnormalities. Clinically, structural magnetic resonance imaging (MRI) sequences (T2, FLAIR, diffusion-weighted imaging) have been used by radiologists to diagnose chronic and acute cerebral infarction (both overt and clinically silent), while magnetic resonance angiography and venography have been used to diagnose arteriopathy and venous thrombosis. In research settings, imaging scientists are increasingly applying quantitative techniques to shine further light on underlying mechanisms. Areas covered: From a June 2020 PubMed search of 'magnetic' or 'MRI' and 'sickle' over the previous 5 years, we selected manuscripts on T1-based morphometric analysis, diffusion tensor imaging, arterial spin labeling, T2-oximetry, quantitative susceptibility, and connectivity. Expert Opinion: Quantitative MRI techniques are identifying structural and hemodynamic biomarkers associated with risk of neurological and neurocognitive complications. A growing body of evidence suggests that these biomarkers are sensitive to change with treatments, such as blood transfusion and hydroxyurea, indicating that they may hold promise as endpoints in future randomized clinical trials of novel approaches including hemoglobin F upregulation, reduction of polymerization, and gene therapy. With further validation, such techniques may eventually also improve neurological and neurocognitive risk stratification in this vulnerable population.

Brain Oxygen Extraction and Metabolism in Pediatric Patients With Sickle Cell Disease: Comparison of Four Calibration Models

“…This also leads to hemolysis and decreased hemoglobin, thus decreased arterial oxygen content, resulting in an elevated cerebral blood flow (CBF) in order to compensate for the oxygen demand of the brain (Herold et al, 1986;Hurlet-Jensen et al, 1994a;Li et al, 2020). SCD has been associated with a number of brain physiological disorders, including increased cerebral vasculopathy, reduced cerebrovascular reactivity, and increased risk of overt stroke or silent cerebral infarction (SCI) (Pauling et al, 1949;Hurlet-Jensen et al, 1994b;Miller et al, 2001;Prengler et al, 2002;Switzer et al, 2006;Leung et al, 2016;Juttukonda et al, 2017;Bush et al, 2018a;Jordan and DeBaun, 2018;Václavů et al, 2019;Jacob et al, 2020;Kirkham and Lagunju, 2021;Stotesbury et al, 2021). An increased risk of neurodevelopmental disorders in pediatric SCD patients was also reported (Berkelhammer et al, 2007;Lance et al, 2015Lance et al, , 2021.…”

Epidemiology of Stroke in Sickle Cell Disease

“…Even in infancy ICA/MCA velocities are higher than control but those in the Conditional range are rare and Abnormal velocities have not so far been documented [ 74 , 75 ], so there are no data as yet on the range predicting stroke risk in this age group; most screening programmes start at age 2 years and stroke secondary to other mechanisms, e.g., embolus through a patent foramen ovale [ 76 ], may be important in those younger than this [ 6 , 7 ]. The prevalence of abnormal TCD in preschool and school-age children was 8% in the original Augusta cohort in the USA in the 1990s [ 73 ] and was 6% in the East London neonatally screened cohort in the UK [ 62 ].…”

“…In Tanzanian studies of children with TAMMV outside [ 86 ] and within [ 87 ] the normal range on TCD screening, 43% and 27% respectively had SCI. Of note, prevalence estimates may vary not only with age but also with scanner magnet strength and voxel size [ 7 ]. The high prevalence of silent infarcts on MRI in children with SCD compared with children with non-sickle stroke [ 192 ] probably at least in part reflects the chronicity of the vascular compromise in this population.…”

“…However, MRI studies at higher field strength have been less likely to find an association between cognitive function and SCI [ 182 , 198 , 199 ]. Quantitative MRI may clarify some of these issues [ 7 ] as well as providing information of clinical use in addition to an experienced radiologist’s reading of the conventional MRI study.…”

“…Earlier studies used definitions which were not necessarily standardised [ 4 ] and, although more recent studies have included neuroimaging, as well as using the World Health Organisation definition of stroke, there is little evidence of neurological or neuroradiological over-reading or of the inclusion/exclusion criteria applied. In fact, there is a wide differential of focal and generalised vascular and non-vascular pathologies [ 5 , 6 ], often distinguished using acute MR techniques [ 7 ], with important management implications.…”