Detecting white matter injury in sickle cell disease using voxel-based morphometry

2006 ◽  
Vol 59 (4) ◽  
pp. 662-672 ◽  
Author(s):  
Torsten Baldeweg ◽  
Alexandra M. Hogan ◽  
Dawn E. Saunders ◽  
Paul Telfer ◽  
David G. Gadian ◽  
...  
Keyword(s):  
White Matter ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
White Matter Injury ◽  
Voxel Based Morphometry ◽  
Cell Disease

scholarly journals Volume of white matter hyperintensities is an independent predictor of intelligence quotient and processing speed in children with sickle cell disease

2014 ◽  
Vol 168 (4) ◽  
pp. 553-556 ◽  
Author(s):  
Veronica van der Land ◽  
Channa T. Hijmans ◽  
Marieke de Ruiter ◽  
Henri J. M. M. Mutsaerts ◽  
Marjon H. Cnossen ◽  
...  
Keyword(s):  
White Matter ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Processing Speed ◽  
Intelligence Quotient ◽  
White Matter Hyperintensities ◽  
Independent Predictor ◽  
Cell Disease

scholarly journals Reduced Cerebrovascular Reserve Capacity in Adults with Sickle Cell Disease

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 972-972
Author(s):  
Lena Vaclavu ◽  
Lena Vaclavu ◽  
Henri JMM Mutsaerts ◽  
Esben Thade Petersen ◽  
Ed T VanBavel ◽  
...  
Keyword(s):  
White Matter ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Stroke Risk ◽  
Adult Patients ◽  
Healthy Controls ◽  
Cell Disease ◽  
Cerebrovascular Reserve ◽  
Cerebral Vasodilation ◽  
O2 Delivery

Abstract Introduction: Sickle Cell Disease (SCD) is frequently complicated by stroke. Although transcranial Doppler effectively identifies children at risk for stroke, adult patients do not benefit from this test. In SCD, chronic hemolytic anemia leads to cerebral vasodilation, elevated cerebral blood flow (CBF) and subsequently, impaired cerebrovascular reserve (CVR) capacity. CVR represents the maximum increase in CBF in response to metabolic stressors. CVR mapping is a promising imaging biomarker for stroke risk assessment, potentially identifying patients with preclinical hemodynamic impairment. Our laboratory performs CVR mapping by measuring CBF prior to and following maximum cerebral vasodilation with acetazolamide (ACZ). The primary aim of this study was to quantitatively assess CVR in adult patients with SCD compared to healthy controls. Methods: Adult SCD patients (HbSS/HbSβ0) were recruited for this IRB-approved study with ACZ-induced vasodilation and venous blood sampling. Patients with a history of clinically overt stroke were excluded. Controls were selected from patients' friends and family members without SCD and matched on age, sex, and race. The following MRI images were acquired at 3T (Philips Healthcare, Best, NL): time of flight MRA for visualization of major cerebral vessels, T2 FLAIR for manual segmentation of white matter hyperintensities (WMHs), and pseudo-continuous arterial spin labeling (ASL) for CBF assessment. CBF was measured at baseline and 10min post ACZ (16mg/kg intravenous infusion over 3min). MRI images were processed with the ExploreASL toolbox, to obtain registered maps of quantified CBF and CVR (% change in CBF). We measured T1blood in each subject to improve quantification accuracy as these values can differ in SCD. Group comparisons were performed using non-parametric two-sample tests. Correlations were characterized by Spearman's rho (ρ). P<0.05 was considered significant. Median values with interquartile range (IQR) are reported for non-normally distributed variables, otherwise mean and standard deviation are reported. Results: 30 patients with SCD (mean age 33±12y,19M) and 11 controls (mean age 37±15y, 6M) were included in this cross-sectional controlled cohort study. Mean hemoglobin levels in patients with SCD were 8.8±1.4 g/dL and in healthy controls were 13.7±1.3 g/dL. Patients with SCD had higher baseline CBF compared to healthy controls (median 73(IQR:25) vs 42(IQR:6) mL/100g/min, p<0.001, F1a). CBF was inversely related to hemoglobin (ρ=-0.84, p<0.001, F1b). ACZ elicited an increase in CBF(p<0.001) which was similar in magnitude in both groups (patients 29±16, controls 35±11, mL/100g/min, F1c), resulting in a lower mean CVR in patients compared to controls (41±24% vs 81±27%, p<0.001, F1d). Baseline CBF predicted CVR (ρ=-0.68, p<0.001, F1e). WMHs were present in both groups, and WMH volume correlated with age (ρ = 0.54, p<0.001). There were no statistical associations between WMH volume and CVR (ρ = -0.15, p=0.4) or CBF(ρ = 0.02, p=0.9), however, two patients with the largest WMH volume (>6 mL) had the lowest CVR (<20%). Discussion: This study shows that regional CVR can be measured using ASL-MRI with ACZ challenge. ACZ was well-tolerated and elicited a robust cerebrovasodilatory response in both groups. However, the relative increase in oxygen delivery (CVR) was much lower in SCD patients, which suggests that patients with SCD have nearly maximal cerebrovascular dilation at baseline. Our data suggest that chronic vasodilation due to anaemia has let to outward remodelling of vessels in adult patients, permitting a larger vascular bed to compensate their anemia. Our premise is that resting O2 delivery is normal in SCD patients; we showed that increasing CBF overcomes severe anemia. However, high resting CBF limits the brain's ability to recruit additional O2 under times of stress. SCD patients have many transient interruptions in O2 delivery including aplastic crisis, splenic sequestration and sleep apnea, as well as metabolic stressors such as fever, sickle cell crisis, infection, and seizure. While baseline CBF predicted global CVR, ASL provides information regarding regional O2 delivery that may offer insight into distribution of ischemic white matter damage. Further study is needed to determine the impact of blood transfusions and hydroxyurea on CVR and whether there is a critical CVR threshold that predicts stroke risk. Disclosures No relevant conflicts of interest to declare.

White Matter Integrity and Core Cognitive Function in Children Diagnosed With Sickle Cell Disease

2011 ◽  
Vol 33 (3) ◽  
pp. 163-171 ◽  
Author(s):  
Nadia Scantlebury ◽  
Donald Mabbott ◽  
Laura Janzen ◽  
Conrad Rockel ◽  
Elysa Widjaja ◽  
...  
Keyword(s):  
Cognitive Function ◽  
White Matter ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
White Matter Integrity ◽  
Cell Disease

scholarly journals Risk factor analysis of cerebral white matter hyperintensities in children with sickle cell disease

2015 ◽  
Vol 172 (2) ◽  
pp. 274-284 ◽  
Author(s):  
Veronica van der Land ◽  
Henri J. M. M. Mutsaerts ◽  
Marc Engelen ◽  
Harriët Heijboer ◽  
Mark Roest ◽  
...  
Keyword(s):  
Factor Analysis ◽  
Risk Factor ◽  
White Matter ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
White Matter Hyperintensities ◽  
Risk Factor Analysis ◽  
Cerebral White Matter ◽  
Cell Disease

scholarly journals Regional oxygen extraction predicts border zone vulnerability to stroke in sickle cell disease

Neurology ◽  
2018 ◽  
Vol 90 (13) ◽  
pp. e1134-e1142 ◽  
Author(s):  
Melanie E. Fields ◽  
Kristin P. Guilliams ◽  
Dustin K. Ragan ◽  
Michael M. Binkley ◽  
Cihat Eldeniz ◽  
...  
Keyword(s):  
White Matter ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Border Zone ◽  
Oxygen Extraction Fraction ◽  
Oxygen Extraction ◽  
Cell Disease ◽  
Oxygen Utilization ◽  
Deep White Matter ◽  
Regional Vulnerability

ObjectiveTo determine mechanisms underlying regional vulnerability to infarction in sickle cell disease (SCD) by measuring voxel-wise cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen utilization (CMRO2) in children with SCD.MethodsParticipants underwent brain MRIs to measure voxel-based CBF, OEF, and CMRO2. An infarct heat map was created from an independent pediatric SCD cohort with silent infarcts and compared to prospectively obtained OEF maps.ResultsFifty-six participants, 36 children with SCD and 20 controls, completed the study evaluation. Whole-brain CBF (99.2 vs 66.3 mL/100 g/min, p < 0.001), OEF (42.7% vs 28.8%, p < 0.001), and CMRO2 (3.7 vs 2.5 mL/100 g/min, p < 0.001) were higher in the SCD cohort compared to controls. A region of peak OEF was identified in the deep white matter in the SCD cohort, delineated by a ratio map of average SCD to control OEF voxels. CMRO2 in this region, which encompassed the CBF nadir, was low relative to all white matter (p < 0.001). Furthermore, this peak OEF region colocalized with regions of greatest infarct density derived from an independent SCD cohort.ConclusionsElevated OEF in the deep white matter identifies a signature of metabolically stressed brain tissue at increased stroke risk in pediatric patients with SCD. We propose that border zone physiology, exacerbated by chronic anemic hypoxia, explains the high risk in this region.

scholarly journals Hemoglobin and mean platelet volume predicts diffuse T1-MRI white matter volume decrease in sickle cell disease patients

2017 ◽  
Vol 15 ◽  
pp. 239-246 ◽  
Author(s):  
Soyoung Choi ◽  
Adam M. Bush ◽  
Matthew T. Borzage ◽  
Anand A. Joshi ◽  
William J. Mack ◽  
...  
Keyword(s):  
White Matter ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Mean Platelet Volume ◽  
White Matter Volume ◽  
Cell Disease ◽  
Platelet Volume ◽  
Matter Volume ◽  
Volume Decrease

scholarly journals Study of montelukast in children with sickle cell disease (SMILES): a study protocol for a randomised controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Anna M. Hood ◽  
Hanne Stotesbury ◽  
Melanie Kölbel ◽  
Michelle DeHaan ◽  
Michelle Downes ◽  
...  
Keyword(s):  
Cognitive Function ◽  
White Matter ◽  
Sickle Cell Disease ◽  
Young Children ◽  
Sickle Cell ◽  
Processing Speed ◽  
Post Treatment ◽  
Cell Disease ◽  
Double Blind ◽  
Randomised Controlled

Abstract Background Young children with sickle cell anaemia (SCA) often have slowed processing speed associated with reduced brain white matter integrity, low oxygen saturation, and sleep-disordered breathing (SDB), related in part to enlarged adenoids and tonsils. Common treatments for SDB include adenotonsillectomy and nocturnal continuous positive airway pressure (CPAP), but adenotonsillectomy is an invasive surgical procedure, and CPAP is rarely well-tolerated. Further, there is no current consensus on the ability of these treatments to improve cognitive function. Several double-blind, randomised controlled trials (RCTs) have demonstrated the efficacy of montelukast, a safe, well-tolerated anti-inflammatory agent, as a treatment for airway obstruction and reducing adenoid size for children who do not have SCA. However, we do not yet know whether montelukast reduces adenoid size and improves cognition function in young children with SCA. Methods The Study of Montelukast In Children with Sickle Cell Disease (SMILES) is a 12-week multicentre, double-blind, RCT. SMILES aims to recruit 200 paediatric patients with SCA and SDB aged 3–7.99 years to assess the extent to which montelukast can improve cognitive function (i.e. processing speed) and sleep and reduce adenoidal size and white matter damage compared to placebo. Patients will be randomised to either montelukast or placebo for 12 weeks. The primary objective of the SMILES trial is to assess the effect of montelukast on processing speed in young children with SCA. At baseline and post-treatment, we will administer a cognitive evaluation; caregivers will complete questionnaires (e.g. sleep, pain) and measures of demographics. Laboratory values will be obtained from medical records collected as part of standard care. If a family agrees, patients will undergo brain MRIs for adenoid size and other structural and haemodynamic quantitative measures at baseline and post-treatment, and we will obtain overnight oximetry. Discussion Findings from this study will increase our understanding of whether montelukast is an effective treatment for young children with SCA. Using cognitive testing and MRI, the SMILES trial hopes to gain critical knowledge to help develop targeted interventions to improve the outcomes of young children with SCA. Trial registration ClinicalTrials.govNCT04351698. Registered on April 17, 2020. European Clinical Trials Database (EudraCT No. 2017-004539-36). Registered on May 19, 2020

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