2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease

The recommendations listed in this document are, whenever possible, evidence based. An extensive evidence review was conducted as the document was compiled through December 2008. Repeated literature searches were performed by the guideline development staff and writing committee members as new issues were considered. New clinical trials published in peer-reviewed journals and articles through December 2011 were also reviewed and incorporated when relevant. Furthermore, because of the extended development time period for this guideline, peer review comments indicated that the sections focused on imaging technologies required additional updating, which occurred during 2011. Therefore, the evidence review for the imaging sections includes published literature through December 2011

Silent cerebral infarcts in very young children with sickle cell anaemia are associated with a higher risk of stroke

Silent cerebral infarctions (SCI) are the most common neurological injury in children with sickle cell anaemia (SCA), but their incidence/prognosis in early childhood has not been well described. We report clinical, neuroradiological, psychometric and academic follow-up over an average period of 14 years in 37 children with SCA who had magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) of the brain between ages 7 and 48 months. Ten patients (27%) younger than age 5 years (Group I) had SCI, as did 12 (32%) older than 5 years (Group II). Fifteen (41%) had no lesions (Group III). Overt stroke or transient ischaemic attack occurred in 5/9 (56%) in Group I. Most Group I patients had progressive MRI abnormalities, concurrent stenosis, decreased cognitive ability, attention/executive function deficits and hindered academic attainment. The proportions of subjects in Group I with subsequent neurological events (P ≤ 0·006), progressive ischaemia (P ≤ 0·001) and vascular stenosis (P ≤ 0·006) were greater than in Groups II and III. Thus, SCI in young children with SCA may predict overt central nervous system events, progressive MRI abnormalities, stenosis, cognitive dysfunction and poor academic performance. Children younger than 5 years may benefit from MRI/MRA testing and should be considered for aggressive intervention when SCI are detected

The impact of preparation and support procedures for children with sickle cell disease undergoing MRI

Background: Children with sickle cell disease (SCD) often undergo MRI studies to assess brain injury or to quantify hepatic iron. MRI requires the child to lie motionless for 30- 60 min, thus sedation/anesthesia might be used to facilitate successful completion of exams, but this poses additional risks for SCD patients. To improve children\u27s ability to cope with MRI examinations and avoid sedation, our institution established preparation and support procedures (PSP). Objective To investigate the impact of PSP in reducing the need for sedation during MRI exams among children with SCD. Materials and methods: Data on successful completion of MRI testing were compared among 5- to 12-year-olds who underwent brain MRI or liver R2*MRI with or without receiving PSP. Results: Seventy-one children with SCD (median age 9.85 years, range 5.57-12.99 years) underwent a brain MRI (n=60) or liver R2*MRI (n=11). Children who received PSP were more likely to complete an interpretable MRI exam than those who did not (30 of 33; 91% vs. 27 of 38; 71%, unadjusted OR=4.1 (P=0.04) and OR=8.5 (p \u3c 0.01) when adjusting for age. Conclusion: PSP can help young children with SCD complete clinically interpretable, nonsedated MRI exams, avoiding the risks of sedation/anesthesia. © Springer-Verlag 2012

Hemodynamic responses to visual stimulation in children with sickle cell anemia

Blood oxygenation level-dependent (BOLD) and cerebral blood flow (CBF)-based functional magnetic resonance imaging (fMRI) were used to measure primary visual cortex responses to photic stimulation in 23 children (12. 4 ± 0. 7 years old) with sickle cell anemia (SCA) and 21 clinical controls (11 ± 1. 0 years old). The objectives were to investigate the effect of SCA on detection of brain activation with fMRI and to explore the relationship between fMRI responses and global cognitive function. The BOLD responses were diminished in children with SCA. Clinical indicators of disease severity were greatest in patients without detectable visual cortex activation, but blood hemoglobin concentration and resting CBF were not predictive of BOLD signal amplitude in the SCA patients. Unexpectedly, the BOLD signal amplitude was positively associated (rs ≥ 0. 8, p ≤ 0. 05) with Wechsler Abbreviated Scale of Intelligence scores, suggesting that fMRI may help clarify medical, hemodynamic, and neural factors that mediate adverse effects of SCA on neurocognitive function. © 2011 Springer Science+Business Media, LLC

Spatiotemporal Patterns of Tumor Occurrence in Children with Intraocular Retinoblastoma - Fig 6

<p>The tumor centroid distribution rendered in the azimuthal-equidistant projection by (A) tumor area quartiles and (B) mutation type. C) Scatter plot of tumor centroid eccentricity vs. tumor area. The range of each tumor area quartile is indicated on the x-axis. The black curve shows the approximate maximum eccentricity for a tumor of a given size (see text). Plotting symbol color indicates age at diagnosis quartile (magenta, yellow, blue, green) and shape indicates mutation type and disease laterality.</p

Hydroxycarbamide treatment and brain MRI/MRA findings in children with sickle cell anaemia

Silent cerebral infarction (SCI) is the most common neurological abnormality among children with sickle cell anaemia (SCA). The effect of hydroxycarbamide (also termed hydroxyurea) on the development and progression of SCI is unclear. We evaluated brain magnetic resonance imaging/angiography (MRI/MRA) in children with SCA receiving long-term hydroxycarbamide therapy. Fifty participants (median 9·4 years, range 1·1–17·3) enrolled in the Hydroxyurea Study of Long-Term Effects (HUSTLE; NCT00305175) underwent brain MRI/MRA and laboratory evaluations before hydroxycarbamide initiation and after 3 and 6 years of treatment to maximum tolerated dose. SCI and vascular stenosis were evaluated. At baseline, 3 and 6 years, SCI were present in 19/50 (38%), 20/49 (41%), and 7/17 (41%), respectively. At 3 years, one child developed a SCI lesion, and another progressed (single lesion to multiple). Lower haemoglobin (Hb) (80 g/l vs. 86 g/l, P = 0·049), fetal Hb (5·0% vs. 10·4%, P \u3c 0·001) and oxygen saturation (97% vs. 98%, P = 0·027) before hydroxycarbamide initiation were associated with SCI. No patients had vascular stenosis identified on MRA, transient ischaemic attack or stroke. Our data indicate that children receiving hydroxycarbamide over a 3- to 6-year period have a low rate of new or worsening cerebrovascular disease. Further studies are needed to confirm that hydroxycarbamide can prevent the onset and progression of SCI

Arterial spin-labeled perfusion combined with segmentation techniques to evaluate cerebral blood flow in white and gray matter of children with sickle cell anemia

Background. Changes in cerebral perfusion are an important feature of the pathophysiology of sickle cell anemia (SCA); cerebrovascular ischemia occurs frequently and leads to neurocognitive deficits, silent infarcts, and overt stroke. Non-invasive MRI methods to measure cerebral blood flow (CBF) by arterial spin labeling (ASL) afford new opportunities to characterize disease- and therapy-induced changes in cerebral hemodynamics in patients with SCA. Recent studies have documented elevated gray matter (GM) CBF in untreated children with SCA, but no measurements of white matter (WM) CBF have been reported. Procedures. Pulsed ASL with automated brain image segmentation- classification techniques were used to determine the CBF in GM, WM, and abnormal white matter (ABWM) of 21 children with SCA, 18 of whom were receiving hydroxyurea therapy. Results. GM and WM CBF were highly associated (R 2 = 0.76, P \u3c 0.0001) and the GM to WM CBF ratio was 1.6 (95% confidence interval: 1.43-1.83). Global GM CBF in our treated cohort was 87 ± 24 mL/min/100 g, a value lower than previously reported in untreated patients with SCA. CBF was elevated in normal appearing WM (43 ± 14 mL/min/100 g) but decreased in ABWM (6 ± 12 mL/min/100 g), compared to published normal pediatric controls. Hemispheric asymmetry in CBF was noted in most patients. Conclusions. These perfusion measurements suggest that hydroxyurea may normalize GM CBF in children with SCA, but altered perfusion in WM may persist. This novel combined approach for CBF quantification will facilitate prospective studies of cerebral vasculopathy in SCA, particularly regarding the effects of treatments such as hydroxyurea. © 2008 Wiley-Liss, Inc

Comparing segmented ASL perfusion of vascular territories using manual versus semiautomated techniques in children with sickle cell anemia

Purpose: Elevated cerebral blood flow (CBF) in sickle cell anemia (SCA) is an adaptive pathophysiologic response associated with decreased vascular reserve and increased risk for ischemia. We compared manual (M) and semiautomated (SA) vascular territory delineation to facilitate standardized evaluation of CBF in children with SCA. Materials and Methods: ASL perfusion values from 21 children were compared for gray matter and white matter (WM) in vascular territories defined by M and SA delineation. SA delineated CBF was compared with clinical and hematologic variables acquired within 4 weeks of the MRI. Results: CBF measurements from M (MCA 82 left, 79 right) and SA (MCA 81 left, 81 right) delineated territories were highly correlated (R = 0.99, P \u3c 0.0001). Bland-Altman plots had close-fitting limits of agreement of -1.8 to -3.5 lower limit and 0 to 1.8 upper limit. SA vascular territory delineation was comparable to the expert delineation with a kappa index of 0.62-0.85 and was considerably faster. Median territorial CBF values did not differ by gender or age. WM perfusion in the posterior cerebral artery territories was positively correlated with degree of hemolysis (R = 0.58, P = 0.01 left, 0.73, P \u3c 0.001 right) and negatively correlated with hemoglobin (R = -0.48; P = 0.03 left; -0.47; P = 0.04 right) and hemoglobin F (R = -0.42; P = .09 left; -0.47; P = 0.049 right). Conclusion: We established the validity of the SA method, which in our experience was much faster than the M method for delineation of vascular territories. Associations between CBF and hematologic variables may demonstrate pathophysiologic changes that contribute to clinical variation in CBF