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ABSTRACT: We sought to test the hypothesis that deficits in grey matter volume are characteristic of psychotic youth with early-onset schizophrenia-spectrum disorders (EOSS) but not of psychotic youth with early-onset mood disorders (EOMD).
We used magnetic resonance imaging to examine brain volume in 24 psychotic youth (13 male, 11 female) with EOSS (n = 12) or EOMD (n = 12) and 17 healthy controls (10 male, 7 female). We measured the volume of grey and white matter using an automated segmentation program.
After adjustment for age and intracranial volume, whole brain volume was lower in the EOSS patients than in the healthy controls (p = 0.001) and EOMD patients (p = 0.002). The EOSS patients had a deficit in grey matter volume (p = 0.005), especially in the frontal (p = 0.003) and parietal (p = 0.006) lobes, with no significant differences in white matter volume.
The main limitations of our study were its small sample size and the inclusion of patients with depression and mania in the affective group.
Adolescents with EOSS have grey matter deficits compared with healthy controls and psychotic adolescents with EOMD. Our results suggest that grey matter deficits are not generally associated with psychosis but may be specifically associated with schizophrenia. Larger studies with consistent methods are needed to reconcile the contradictory findings among imaging studies involving psychotic youth.
Journal of psychiatry & neuroscience: JPN 07/2010; 35(4):229-36. · 5.34 Impact Factor
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PEDIATRICS 08/2007; 120(1):232-4; author reply 234-5. · 4.47 Impact Factor
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ABSTRACT: The precision [coefficient of variation or CV (%) = 100SD/X] of single-voxel point resolved spectroscopic data was characterized bilaterally, in anterior cingulate and in hippocampus, at 4.0 T in a healthy subject. Data acquisition was replicated 10 times after voxel repositioning and readjusting higher order shims. Precision measurements show that the scan-to-scan precision is better in anterior cingulate than in hippocampus, with an average CV of 9.2% (for total NAA, tCho and Cr) in anterior cingulate and 13.9% in hippocampus. Variability measurements made by the same method in 24 healthy subjects and in 29 schizophrenia patients showed that there is substantial biological variability in metabolite levels, even in healthy subjects. Simple calculations suggest that more than 200 subjects would be needed to detect a 5% difference in NAA between patients and controls.
NMR in Biomedicine 07/2006; 19(4):484-91. · 3.21 Impact Factor
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ABSTRACT: Studies of people with schizophrenia assessed using magnetic resonance imaging (MRI) usually include patients with first-episode and chronic disease, yet brain abnormalities may be limited to those with chronic schizophrenia.
To determine whether patients with a first episode of schizophrenia have characteristic brain abnormalities.
Systematic review and meta-analysis of 66 papers comparing brain volume in patients with a first psychotic episode with volume in healthy controls.
A total of 52 cross-sectional studies included 1424 patients with a first psychotic episode; 16 longitudinal studies included 465 such patients. Meta-analysis suggests that whole brain and hippocampal volume are reduced (both P<0.0001) and that ventricular volume is increased (P<0.0001) in these patients relative to healthy controls.
Average volumetric changes are close to the limit of detection by MRI methods. It remains to be determined whether schizophrenia is a neurodegenerative process that begins at about the time of symptom onset, or whether it is better characterised as a neurodevelopmental process that produces abnormal brain volumes at an early age.
The British Journal of Psychiatry 06/2006; 188:510-8. · 6.62 Impact Factor
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ABSTRACT: A systematic review of the literature identified 64 published English-language papers that used proton (1H) magnetic resonance spectroscopy to measure N-acetylaspartate (NAA) concurrently in healthy controls and in patients with a diagnosis of schizophrenia (SZ). A total of 1209 controls and 1256 patients have been evaluated, with 88% of studies carried out at 1.5 T field strength, and 77% of studies focused on patients with chronic SZ. There is consistent evidence that NAA is reduced in a broad range of tissues in the SZ brain. Broad consensus (> or =10 studies) is emerging that NAA levels are reduced > or =5% in hippocampus and in both cortical gray matter (GM) and white matter (WM) of the frontal lobe. There is no evidence to support a hypothesis that relative NAA levels are reduced to a different degree in frontal lobe GM and WM, nor is there robust evidence of a difference in NAA levels between patients with first-episode and chronic SZ. Study reliability may be a problem, as most studies appear to be underpowered. With simple assumptions about the inherent difference in NAA levels between patients and controls, it can be calculated that a minimum sample size of approximately 39 patients and 39 controls is required for acceptable statistical power. Only three of 64 studies included enough subjects to have 80% power to detect a 10% NAA reduction in patients, and no studies were adequately powered to detect a 5% NAA reduction with 80% power.
Neuropsychopharmacology 11/2005; 30(11):1949-62. · 7.99 Impact Factor
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ABSTRACT: After the resection of brain tumors in pediatric patients, it can be difficult to differentiate recurrent tumor from treatment effects. Although late-delayed reactions are thought to be permanent, in this study the authors sought to characterize transient brain lesions (TBLs) in the late-delayed period that completely resolved without imaging or neurological sequelae.
In a retrospective review of an institutional neuroimaging brain tumor database, 11 patients were identified who met the imaging criteria (transient T2-weighted hyperintense enhancing lesions outside of the tumor bed, which occurred after radiation and/or chemotherapy) and had undergone three-dimensional dosimetry; their radiographic, clinical, and radiation-dosimetry results were analyzed. In the 11 patients who had been treated with multiple protocols 17 loci of abnormality, including 43 discrete, asymptomatic TBLs, were detected. The median TBL diameter was 1 cm or smaller, without mass effect or necrosis, and occurred 10 months after radiation therapy, 11 months after chemotherapy, resolved by 3 months, and occurred within the high-dose radiation treatment volume (median 55.8 Gy). The findings from extended follow up revealed the development of additional permanent complications of radiation therapy within the radiation port in five of the 11 patients.
A benign form of treatment-induced brain injury in children, TBLs should be treated using short-interval follow up. When these lesions are identified as a result of their characteristic imaging features, location, and temporal course, TBLs may be clearly distinguished from recurrent tumor or radiation necrosis and do not require biopsy. Further studies are needed to determine whether patients with TBLs are at an increased risk of developing more severe treatment-related brain injury.
Journal of Neurosurgery 04/2005; 102(2 Suppl):179-86. · 2.96 Impact Factor
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ABSTRACT: Despite the large body of data available about somatic growth delay in patients with sickle cell disease (SCD), virtually nothing is known about the effect of the disease on volumetric growth of the brain. This study was designed to test a hypothesis that children with SCD have a disease-related delay in brain volumetric growth compared with healthy children.
A cross-sectional study design was used to evaluate 83 children with SCD and 43 age-similar healthy children, including 27 patient siblings. Brain volume was measured by segmenting and classifying MR imaging data, by using at least three separate image sets (T1-, T2-, and proton density-weighted MR images). A linear model was used to compare the various brain volumes with the covariates of group (patient versus control) and age, with age treated as a continuous variable.
With age controlled for, no significant difference was noted in total brain volume between patients and control subjects at age 9.5 years. However, patients showed a deficit specifically in gray matter volume (P=.005), without significant differences in white matter or ventricular volume. The deficit in patient gray matter was greater in central gray matter (P <.005) than in cortical gray matter (P <.02). In healthy control subjects, gray matter volume decreased significantly with age (P <.005), probably due to myelination of white matter tracts. In patients with SCD, gray matter volume did not change with age.
Volumetric growth of brain gray matter may be delayed in children with SCD, suggesting that there may be neurodevelopmental consequences of this disease.
American Journal of Neuroradiology 03/2005; 26(3):455-62. · 2.93 Impact Factor
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ABSTRACT: The most abundant metabolite visible by proton magnetic resonance spectroscopy (MRS) in human brain is N-acetylaspartate (NAA), which is often used as a marker of viable neurons. NAA is anecdotally reported to be elevated in children with sickle cell disease (SCD), even though patients can have brain injury or atrophy. We measured NAA levels rigorously in SCD patients to test the hypothesis that NAA is elevated in this patient population.
We evaluated 26 children with SCD and 25 age-similar healthy control subjects using a double spin-echo MRS technique to interrogate a 16 cc volume of interest in the basal ganglia. We acquired MRS spectra with an echo time (TE) of 30 ms to evaluate lipids, and with TE = 144 to show abundant metabolites against a flat baseline. We characterized metabolite relaxation properties and measured the water peak as an internal standard, to calculate the absolute quantity of metabolites.
The ratio of NAA:Choline was significantly elevated in basal ganglia of patients at both echo times (P <.016), and the absolute quantity of NAA was also elevated, with [NAA] 7-12% higher in patients than in control subjects. The measured increase in [NAA] cannot be explained by metabolite relaxation properties or by differences in tissue water content.
Brain NAA is greater in children with SCD than in healthy control subjects and appears not to be a reliable marker of viable neurons in SCD patients.
American Journal of Neuroradiology 03/2005; 26(3):463-8. · 2.93 Impact Factor
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ABSTRACT: We tested a hypothesis that children with sickle cell disease who are completely normal by magnetic resonance imaging can still be cognitively impaired, as predicted by a model of diffuse brain injury. Fifty-four patients with hemoglobin SS (average age 10.9 years +/- 2.9 years SD) were examined with the Wechsler Intelligence Scale for Children-III (WISC-III) and were randomly matched by age, race, and gender with healthy children from the Wechsler normative database. Patients were also imaged at 1.5 Tesla with standard imaging sequences. Among 30 patients who were normal by magnetic resonance imaging, there were substantial deficits in Wechsler Full-Scale IQ, Verbal IQ, and Performance IQ (all P < .01) compared with African-American controls. The patient Wechsler Full-Scale IQ was 12.9 points lower than that of controls and decreased as a function of age (probability = .014). The findings suggest that there is diffuse brain injury in patients and that patient deficits increase with age.
Journal of Child Neurology 02/2005; 20(2):102-7. · 1.75 Impact Factor
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ABSTRACT: We test a hypothesis that proton T(1) is accurately measured independent of the physics inherent to the method. We used two well-validated but quite different imaging methods to measure T(1) in phantoms and in humans; an echo-planar imaging T-one measurement (EPITOME) method, and a segmented k-space acquisition precise and accurate inversion recovery (TurboPAIR) method. Agreement between the methods was generally excellent; the square of the correlation coefficient (r(2)) in phantoms was 0.9996. The r(2) in brain tissue of volunteers was 0.79 overall, and 0.85 if cortical gray matter and corpus callosum were excluded. Nevertheless, small but significant differences were observed between methods in vivo and T(1) measurements were sensitive to tissue type, although measurements could be made comparable. The major difference between the methods is that EPITOME takes 97 s to image 15 slices at low resolution, while TurboPAIR takes 240 s to image one slice at high resolution.
Magnetic Resonance Imaging 05/2004; 22(3):291-8. · 1.99 Impact Factor
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ABSTRACT: Measurement of tissue spin lattice relaxation time (T(1)) has been used to characterize brain development in healthy children. Here we report the first study of brain T(1) in young children with sickle cell disease (SCD). The T(1) in 10 tissue samples was measured by established techniques; 46 SCD patients under the age of 4 years were compared to 267 controls, including 55 well children under the age of 4 years. A model was developed to predict the relationship between age and brain T(1) in controls, then we compared patient T(1) to healthy normal T(1). Most white matter and gray matter tissues in infant patients (<2 years old), had T(1) values significantly higher than normal. For example, 15.0% of patient caudate T(1) values were above the upper bound of the 95% confidence interval for controls, but only 2.5% of normal values are expected to be this high (p = 0.0003). Among infant patients, brain T(1) was significantly higher than normal in every tissue (p < 0.01) except cortical gray matter. However, patient T(1) values declined rapidly to values lower than normal by about age 4. Our findings imply that patients follow an abnormal developmental trajectory beginning early in infancy.
Magnetic Resonance Imaging 04/2004; 22(3):299-306. · 1.99 Impact Factor
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ABSTRACT: Our objective was to evaluate the relationship between brain injury by magnetic resonance imaging (MRI) and vasculopathy by magnetic resonance angiography (MRA) in children with hemoglobin SS, the most serious form of sickle cell disease. We reviewed imaging for all 146 SS patients imaged at St. Jude Children's Research Hospital since 1993. Standard MRI criteria were used to identify cystic infarction, leukoencephalopathy, encephalomalacia, or atrophy. Standard MRA criteria were used to identify arterial tortuousity (limited vasculopathy), and stenosis or occlusion (extensive vasculopathy). At an average age of 10 years, the estimated prevalence of infarction, ischemic damage, or atrophy in SS patients was 46%, and of vasculopathy was 64%. Only 28% of patients were normal by both modalities, and patients abnormal by MRA often were abnormal by MRI (p < 0.00001). Patients with cystic infarction had limited vasculopathy, whereas patients with encephalomalacia had stenosis or occlusion (p < 0.0001). Large arteries were affected in 31% of brain injury patients, whereas small arteries are inferred to be abnormal in up to 69% of patients with brain injury. The degree of vasculopathy is closely related to the degree of brain injury, implying that vasculopathy is prodromal to most forms of brain injury in hemoglobin SS.
Annals of Neurology 11/2003; 54(5):564-72. · 11.09 Impact Factor
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ABSTRACT: Our objective was to evaluate the relationship between brain injury by magnetic resonance imaging (MRI) and vasculopathy by magnetic resonance angiography (MRA) in children with hemoglobin SS, the most serious form of sickle cell disease. We reviewed imaging for all 146 SS patients imaged at St. Jude Children's Research Hospital since 1993. Standard MRI criteria were used to identify cystic infarction, leukoencephalopathy, encephalomalacia, or atrophy. Standard MRA criteria were used to identify arterial tortuousity (limited vasculopathy), and stenosis or occlusion (extensive vasculopathy). At an average age of 10 years, the estimated prevalence of infarction, ischemic damage, or atrophy in SS patients was 46%, and of vasculopathy was 64%. Only 28% of patients were normal by both modalities, and patients abnormal by MRA often were abnormal by MRI (p < 0.00001). Patients with cystic infarction had limited vasculopathy, whereas patients with encephalomalacia had stenosis or occlusion (p < 0.0001). Large arteries were affected in 31% of brain injury patients, whereas small arteries are inferred to be abnormal in up to 69% of patients with brain injury. The degree of vasculopathy is closely related to the degree of brain injury, implying that vasculopathy is prodromal to most forms of brain injury in hemoglobin SS.
Annals of Neurology 10/2003; 54(5):564 - 572. · 11.09 Impact Factor
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ABSTRACT: To determine whether sickle cell trait (hemoglobin AS) is associated with abnormalities in the brain of asymptomatic children.
Magnetic resonance (MR) imaging and MR angiography were performed prospectively in 26 siblings (eight girls, 18 boys; mean age, 10.5 years) of patients with sickle cell disease. Two neuroradiologists, blinded as to whether a child had hemoglobin AS or AA, reviewed images obtained in siblings. With MR imaging, lacunae, loss of white matter volume, encephalomalacia, or leukoencephalopathy was identified. With MR angiography, arterial stenosis, occlusion, or tortuosity was identified. Images with definite or possible abnormalities were mixed with randomly selected images and were referred to a third neuroradiologist for a completely blinded review. In cases in which all neuroradiologists concurred, a score was assigned that indicated the sibling had an abnormality. MR angiographic findings were assigned a score for tortuosity with a new quantitative scale.
Among 26 siblings screened, 21 children had sickle cell trait. Among these 21 children, two had mild abnormalities at MR imaging (sample prevalence rate, 10% [95% CI: 1%, 29%]), and four had arterial tortuosity (sample prevalence rate, 19% [95% CI: 5%, 42%]). When children with sickle cell trait were compared with 31 control subjects without the trait, arterial tortuosity was significantly more common in children with sickle cell trait (P =.014). Among children with sickle cell trait, percentage of hemoglobin S was significantly greater in children who had tortuosity than percentage of hemoglobin S in children who had normal blood vessels at MR angiography (P <.03).
Findings suggest that greater percentage of hemoglobin S is associated with mild vasculopathy. This vasculopathy may explain some of the excess risk of stroke among African Americans.
Radiology 08/2003; 228(1):208-15. · 5.73 Impact Factor
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ABSTRACT: To determine prevalence of imaging abnormalities in the brain of children with sickle cell disease (SCD) and to identify clinical and methodological factors that influence prevalence estimate.
Magnetic resonance (MR) imaging and MR angiographic findings for 185 patients with SCD examined at St Jude Children's Research Hospital since 1993 were reviewed. At least two readers independently reviewed images. Standard MR imaging criteria were used to identify lacunae, loss of white matter volume, encephalomalacia, or leukoencephalopathy. Patients were assigned grades to indicate limited or extensive abnormalities. Standard MR angiographic criteria were used to identify arterial tortuosity (limited vasculopathy) and stenosis or occlusion (extensive vasculopathy). Findings were evaluated as a function of patient clinical status (including stroke) and diagnosis. Recent methods (T1- and T2-weighted MR imaging plus fluid-attenuated inversion recovery [FLAIR] at 3-mm section thickness) were compared with older methods (T1- and T2-weighted MR imaging without FLAIR at 5-mm section thickness).
At mean age of 10 years, overall prevalence of infarction, ischemia, or atrophy in patients with SCD was 44% (82 of 185), and prevalence of vasculopathy was 55% (102 of 185), without evidence of a significant referral bias. Twenty-six of 27 patients with clinical stroke had abnormal findings at imaging, but even if patients with stroke were excluded, 35% (56 of 158) had a "silent infarction" (MR imaging-visible injury without clinical stroke), and 49% (78 of 158) had abnormal findings at MR angiography. Patients with clinically severe disease had more abnormalities at MR imaging (P <.001) and MR angiography (P <.004) than did patients with milder disease. Severe vasculopathy was more prevalent in patients with hemoglobin SS than in those with hemoglobin SC (P <.001). Recent imaging methods showed more abnormalities than did older methods (P <.01). With newer methods, 43% (29 of 67) of patients had extensive abnormalities, whereas with older methods, 28% (33 of 116) had extensive abnormalities.
Prevalence of ischemic brain injury in pediatric patients with SCD is substantially higher than was previously reported, in part because of improvements in imaging methods.
Radiology 07/2003; 228(1):216-25. · 5.73 Impact Factor
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ABSTRACT: Children with hemoglobin SS sickle cell disease are known to suffer cognitive impairment if they have silent infarct, but recent evidence suggests that patients with hemoglobin SS sickle cell disease may be impaired even if they are free of infarction. We test a hypothesis that cognitive impairment in children with hemoglobin SS sickle cell disease is associated with low hematocrit and MR imaging abnormalities.
A cohort of 49 patients was examined, all of whom had hemoglobin SS sickle cell disease but no history of clinical stroke. The Wechsler scales, which are standardized and age-adjusted, were used to assess cognitive function. Patients also underwent MR imaging examination of the brain, and hematocrit was measured in a subset of 45 patients. MR images were evaluated by at least two readers, and abnormal imaging findings were evaluated by at least three readers. Any lesion was sufficient to be classified as abnormal, with lesions defined to include lacunar infarction, encephalomalacia, or leukoencephalopathy. Hematocrit data were used if obtained within 3 months of psychometric testing and if there were no confounding events in the patients' charts. Wechsler test scores were then evaluated in relation to imaging findings and hematocrit values.
Patients with imaging abnormalities had more cognitive impairment than did patients with normal imaging findings in verbal intelligence quotient (P <.02) and verbal comprehension (P <.01). Patients with low hematocrit had cognitive impairment shown by many performance measures, including full-scale intelligence quotient (P <.006), verbal comprehension (P <.006), and freedom from distractibility (P <.02). Multivariate analysis showed that MR imaging and hematocrit were independent predictors of full-scale intelligence quotient.
Focal brain injury, revealed by MR imaging, is associated with cognitive impairment, but our data suggest that diffuse brain injury may also contribute to impairment. These findings show that impairment is multifactorial and suggest that chronic brain hypoxia is part of the pathophysiology of sickle cell disease.
American Journal of Neuroradiology 03/2003; 24(3):382-9. · 2.93 Impact Factor
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ABSTRACT: The goal of this study was to characterize the expected range of variation in T1 (spin-lattice relaxation time) of brain tissue in vivo, as a function of age, and to use these maturational norms to study children with sickle cell disease (SCD). A well-validated method (TurboPAIR) was used to measure T1 in 10 tissues in a study group of 200 healthy subjects (ages 4.5 to 79.3; 101 male and 99 female), in a transverse slice at the level of the basal ganglia. Brain T1 was significantly related to age in every tissue characterized (p < 0.001), including the splenium (p < 0.01). Quantitative MRI suggests that brain T1 continues to change throughout the lifespan of healthy subjects free of neurologic complaints. Age-related changes follow a different schedule in each tissue, and age is a stronger determinant of T1 in gray matter than in white matter. Analysis of 141 patients with SCD shows that patients have lower T1 than normal, in both the caudate and the cortex (p < 0.001).
Magnetic Resonance Imaging 01/2003; 21(1):9-15. · 1.99 Impact Factor
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ABSTRACT: Young children with sickle cell disease are at risk of brain damage, including stroke. We tested the hypothesis that such patients are also at risk of cognitive impairment. We characterized the cognitive ability of kindergarten children to minimize the effect of disease-related school absence. The Memphis City Schools use the Developing Skills Checklist, a teacher-administered test given in the classroom, to assess kindergarten-appropriate skills. Data were obtained for 34 patients, who were matched to controls by gender, race, date of birth, school, and approximate income. Two controls were selected for each patient, and paired t-tests were used to compare patient's scores to composite control scores. Patients scored lower than controls in auditory discrimination (P < .01), and there was a trend (P < .10) toward lower patient scores in language. Deficits cannot be attributed to school absence and may predict academic problems for patients with sickle cell disease.
Journal of Child Neurology 02/2002; 17(2):111-6. · 1.75 Impact Factor
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ABSTRACT: To determine whether children with sickle cell disease (SCD), but without clinical evidence of cerebrovascular disease, have vasculopathy shown by quantitative magnetic resonance angiography (MRA).
In a retrospective review of MRA films, we compared 47 SCD patients with 49 control patients. Time-of-flight three-dimensional T1-weighted gradient-echo images were reconstructed, by maximum-intensity projection, to show the basilar artery in coronal view, and basilar volume was calculated from measurements made on films. Basilar volume was correlated with hematocrit and with results of cognitive testing.
Mean basilar artery volume was 74% larger in SCD patients than in controls (P<.001). If the upper limit of normal is defined as mean adult volume +2 SD (< or =427 mm(3)), 2% (1 of 43) of controls but 37% (17 of 46) of SCD patients exceed this value (chi(2)=19.0; P<.001). Basilar volume correlated inversely with hematocrit (r=-.60; P<.0001), with full-scale IQ (r=-.62; P<.005), and with freedom from distractability (r=-.61; P<.006) in SCD patients. Analysis of basilar artery tissue from a 5-year-old SCD patient showed that basilar dilatation can be associated with pathological changes typical of hypertension.
Approximately 37% of a heterogenous group of pediatric SCD patients had ectasia of the basilar artery. Quantitative MRA is sensitive to subtle vasculopathy that can go undetected in the qualitative analysis more commonly done. Data suggest that there is a substantial elevation of arteriolar blood volume in pediatric SCD patients, and that such patients may share disease features in common with adult hypertension.
Journal of Stroke and Cerebrovascular Diseases 7(1):32-43.
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ABSTRACT: To determine if children with sickle cell disease (SCD) and basilar artery ectasia show evidence of general arterial ectasia.
A novel method was used to analyze the base images normally used to reconstruct a magnetic resonance angiogram (MRA). A signal intensity threshold was set empirically to exclude pixels from subcutaneous fat, then base images for each patient were evaluated for the number and relative size of vessel profiles. Data from three SCD patients, imaged before and after transfusion, were analyzed to determine sensitivity of the method to blood flow. We then compared 11 SCD patients with basilar ectasia to 11 age-matched SCD patients with a normal basilar, after excluding patients with clinical stroke.
Before transfusion, patients have an apparent blood volume 48% higher than after (P<.001). Transfusion reduces apparent blood volume because flow rate is reduced by transfusion and MRA is flow-sensitive. But apparent blood volume was not significantly lower in any individual vessel size class, suggesting that fast flow simply increases vessel conspicuity. Patients with basilar ectasia have an apparent blood volume 62% higher than normal (P<.001). Although this could be due to faster blood flow, apparent blood volume was higher specifically in vessels > or =2 mm in diameter (P<.001), suggesting that small arteries can become generally ectatic in patients with basilar ectasia.
Basilar ectasia is associated with an increased blood flow rate, generalized arterial ectasia, or both phenomena. This suggests that basilar volume measurements may supplement blood flow velocity measurements as an indicator of stroke risk.
Journal of Stroke and Cerebrovascular Diseases 7(5):330-8.
