Sickle cell anaemia is a monogenetic disorder with a high incidence of stroke. While stroke screening procedures exist for children with sickle cell anaemia, no accepted screening procedures exist for assessing stroke risk in adults. The purpose of this study is to use novel magnetic resonance imaging methods to evaluate physiological relationships between oxygen extraction fraction, cerebral blood flow, and clinical markers of cerebrovascular impairment in adults with sickle cell anaemia. The specific goal is to determine to what extent elevated oxygen extraction fraction may be uniquely present in patients with higher levels of clinical impairment and therefore may represent a candidate biomarker of stroke risk. Neurological evaluation, structural imaging, and the non-invasive T2-relaxation-under-spin-tagging magnetic resonance imaging method were applied in sickle cell anaemia (n = 34) and healthy race-matched control (n = 11) volunteers without sickle cell trait to assess whole-brain oxygen extraction fraction, cerebral blood flow, degree of vasculopathy, severity of anaemia, and presence of prior infarct; findings were interpreted in the context of physiological models. Cerebral blood flow and oxygen extraction fraction were elevated (P < 0.05) in participants with sickle cell anaemia (n = 27) not receiving monthly blood transfusions (interquartile range cerebral blood flow = 46.2-56.8 ml/100 g/min; oxygen extraction fraction = 0.39-0.50) relative to controls (interquartile range cerebral blood flow = 40.8-46.3 ml/100 g/min; oxygen extraction fraction = 0.33-0.38). Oxygen extraction fraction (P < 0.0001) but not cerebral blood flow was increased in participants with higher levels of clinical impairment. These data provide support for T2-relaxation-under-spin-tagging being able to quickly and non-invasively detect elevated oxygen extraction fraction in individuals with sickle cell anaemia with higher levels of clinical impairment. Our results support the premise that magnetic resonance imaging-based assessment of elevated oxygen extraction fraction might be a viable screening tool for evaluating stroke risk in adults with sickle cell anaemia.

Silent cerebral infarcts (SCIs) are the most commonly recognized cause of neurologic injury in patients with sickle cell anemia (SCA), identified in $20% of children. In children with SCA, SCIs are associated with an average 5 full-scale IQ point decrement, 1 poor academic performance, 2 and future overt strokes. 3 Recently, Bernaudin et al 4 reported that in children with SCA, the cumulative risk for SCI was 19.2% by age 8 years, 32.4% by age 14 years, and 39.1% by age 18 years. Very little is known about the prevalence of SCI in adults with SCA. We tested the hypothesis that the prevalence of SCI was significantly .39% in patients .18 years old with SCA.Due to the high age-dependent prevalence of SCI in children and adolescents with SCA, associated deficits in neuropsychometric performance, 5 the association of SCI with future overt stroke, 5 and the impact of these associated morbidities on health care outcomes in adults with SCA, including adherence to complex instructions associated with management of chronic illness, we elected to obtain, as part of routine clinical practice, magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) scans of the brain in adults with SCA. If SCI or cerebral vasculopathy is found via neuroimaging, we refer these adults for cognitive testing, neurology consultation, or both. We completed a retrospective chart review of adults with SCA (hemoglobin SS or hemoglobin S b zero [Sb 0 ] thalassemia) followed in the comprehensive sickle cell disease clinic, with surveillance MRI and MRA of the brain performed as part of standard-of-care assessment for SCI from 2011 to 2013. The cerebral MRIs and MRAs were rereviewed by 2 board-certified neuroradiologists for the purpose of this study. Consensus findings were recorded including presence of cerebral infarcts ($3 mm on T2-weighted images in 2 imaging planes), 6 intracerebral hemorrhage, aneurysms, 7,8 and cerebral vasculopathy 9,10 according to prior established criteria for MRI and MRA. If no neurologic concerns were reported in the medical record and the neurologic examination was normal, infarcts were judged to be silent. STATA version 13 (StataCorporation, College Station, TX) was used for all analyses. Patient characteristics were described by median and interquartile range (IQR) for continuous measures and by number and percent for categorical measures. A 2-sided P # .05 was considered statistically significant. This study was approved by the Vanderbilt University Institutional Review Board as a retrospective cohort analysis.The study population included 121 adults with SCA (hemoglobin SS or Sb 0 thalassemia) out of ;200 individuals with sickle cell disease that were followed in the clinic. Of these 121 individuals, 69 unselected adults underwent neuroimaging with brain MRI. Nine adults with SCA and overt strokes were excluded. The final study population included 60 adults with SCA and neuroimaging. Of note, a total of 52 individuals were excluded because they did not have neuroimaging, primarily because of failure...

Background and Purpose-Pediatric acute stroke teams are a new phenomenon. We sought to characterize the final diagnoses of children with brain attacks in the emergency department where the pediatric acute stroke protocol was activated and to describe the time to neurological evaluation and neuroimaging. Methods-Clinical and demographic information was obtained from a quality improvement database and medical records for consecutive patients (age, ≤20 years) presenting to a single institution's pediatric emergency department where the acute stroke protocol was activated between April 2011 and October 2014. Stroke protocol activation means that a neurology resident evaluates the child within 15 minutes, and urgent magnetic resonance imaging is available. Results-There were 124 stroke alerts (age, 11.2±5.2 years; 63 boys/61 girls); 30 were confirmed strokes and 2 children had a transient ischemic attack. Forty-six of 124 (37%) cases were healthy children without any significant medical history. Nonstroke neurological emergencies were found in 17 children (14%); the majority were meningitis/encephalitis (n=5) or intracranial neoplasm (n=4). Other common final diagnoses were complex migraine (17%) and seizure (15%). All children except 1 had urgent neuroimaging. Magnetic resonance imaging was the first study in 76%. The median time from emergency department arrival to magnetic resonance imaging was 94 minutes (interquartile range, 49-151 minutes); the median time to computed tomography was 59 minutes (interquartile range, 40-112 minutes). Conclusions-Of pediatric brain attacks, 24% were stroke, 2% were transient ischemic attack, and 14% were other neurological emergencies. Together, 40% had a stroke or other neurological emergency, underscoring the need for prompt evaluation and management of children with brain attacks.

Sickle cell anemia (SCA) is a genetic disorder resulting in reduced oxygen carrying capacity and elevated stroke risk. Pseudo-continuous arterial spin labeling (pCASL) measures of cerebral blood flow (CBF) may have relevance for stroke risk assessment, however the effects of elevated flow velocity and reduced bolus arrival time (BAT) on CBF quantification in SCA patients have not been thoroughly characterized, and pCASL model parameters used in healthy adults are often applied to patients with SCA. Here, cervical arterial flow velocities and pCASL labeling efficiencies were computed in adults with SCA (n=19) and age- and race-matched controls without sickle trait (n=7) using pCASL in sequence with phase contrast MR angiography (MRA). A subgroup of controls (n=7) and patients (n=8) also underwent multi-postlabeling-delay pCASL for BAT assessment. Mean flow velocities were elevated in SCA adults (velocity=28.3±4.1 cm/s) compared to controls (velocity=24.5±3.8 cm/s) and mean pCASL labeling efficiency (α) was reduced in SCA adults (α=0.72) relative to controls (α=0.91). In patients, mean whole-brain CBF from phase contrast MRA was 91.8±18.1ml/100g/min, while mean pCASL CBF when assuming a constant labeling efficiency of 0.86 was 75.2±17.3 ml/100g/min (p<0.01), resulting in a mean absolute quantification error of 23% when a labeling efficiency appropriate for controls was assumed. This difference cannot be accounted for by BAT (whole-brain BAT; control=1.13±0.06s; SCA=1.02±0.09s) or tissue T1 variation. In conclusion, BAT variation influences pCASL quantification less than elevated cervical arterial velocity and labeling efficiency variation in SCA adults; thus, a lower labeling efficiency (α=0.72) or subject-specific labeling efficiency should be incorporated for SCA patients.

Moyamoya is a bilateral, complex cerebrovascular condition characterized by progressive non-atherosclerotic intracranial stenosis and collateral vessel formation. Moyamoya treatment focuses on restoring cerebral blood flow (CBF) through surgical revascularization, however stratifying patients for revascularization requires abilities to quantify how well parenchyma is compensating for arterial steno-occlusion. Globally elevated oxygen extraction fraction (OEF) secondary to CBF reduction may serve as a biomarker for tissue health in moyamoya patients, as suggested in patients with sickle cell anemia (SCA) and reduced oxygen carrying capacity. Here, OEF was measured (TRUST-MRI) to test the hypothesis that OEF is globally elevated in patients with moyamoya (n = 18) and SCA (n = 18) relative to age-matched controls (n = 43). Mechanisms underlying the hypothesized OEF increases were evaluated by performing sequential CBF-weighted, cerebrovascular reactivity (CVR)-weighted, and structural MRI. Patients were stratified by treatment and non-parametric tests applied to compare study variables (significance: two-sided P < 0.05). OEF was significantly elevated in moyamoya participants (interquartile range = 0.38-0.45) compared to controls (interquartile range = 0.29-0.38), similar to participants with SCA (interquartile range = 0.37-0.45). CBF was inversely correlated with OEF in moyamoya participants. Elevated OEF was only weakly related to reductions in CVR, consistent with basal CBF level, rather than vascular reserve capacity, being most closely associated with OEF.