Accurate Learning with Few Atlases (ALFA): an algorithm for MRI neonatal brain extraction and comparison with 11 publicly available methods.

Accurate whole-brain segmentation, or brain extraction, of magnetic resonance imaging (MRI) is a critical first step in most neuroimage analysis pipelines. The majority of brain extraction algorithms have been developed and evaluated for adult data and their validity for neonatal brain extraction, which presents age-specific challenges for this task, has not been established. We developed a novel method for brain extraction of multi-modal neonatal brain MR images, named ALFA (Accurate Learning with Few Atlases). The method uses a new sparsity-based atlas selection strategy that requires a very limited number of atlases 'uniformly' distributed in the low-dimensional data space, combined with a machine learning based label fusion technique. The performance of the method for brain extraction from multi-modal data of 50 newborns is evaluated and compared with results obtained using eleven publicly available brain extraction methods. ALFA outperformed the eleven compared methods providing robust and accurate brain extraction results across different modalities. As ALFA can learn from partially labelled datasets, it can be used to segment large-scale datasets efficiently. ALFA could also be applied to other imaging modalities and other stages across the life course.

Epigenomic profiling of preterm infants reveals DNA methylation differences at sites associated with neural function.

DNA methylation (DNAm) plays a determining role in neural cell fate and provides a molecular link between early-life stress and neuropsychiatric disease. Preterm birth is a profound environmental stressor that is closely associated with alterations in connectivity of neural systems and long-term neuropsychiatric impairment. The aims of this study were to examine the relationship between preterm birth and DNAm, and to investigate factors that contribute to variance in DNAm. DNA was collected from preterm infants (birth<33 weeks gestation) and healthy controls (birth>37 weeks), and a genome-wide analysis of DNAm was performed; diffusion magnetic resonance imaging (dMRI) data were acquired from the preterm group. The major fasciculi were segmented, and fractional anisotropy, mean diffusivity and tract shape were calculated. Principal components (PC) analysis was used to investigate the contribution of MRI features and clinical variables to variance in DNAm. Differential methylation was found within 25 gene bodies and 58 promoters of protein-coding genes in preterm infants compared with controls; 10 of these have neural functions. Differences detected in the array were validated with pyrosequencing. Ninety-five percent of the variance in DNAm in preterm infants was explained by 23 PCs; corticospinal tract shape associated with 6th PC, and gender and early nutritional exposure associated with the 7th PC. Preterm birth is associated with alterations in the methylome at sites that influence neural development and function. Differential methylation analysis has identified several promising candidate genes for understanding the genetic/epigenetic basis of preterm brain injury.

Imaging paediatric blunt abdominal trauma in the emergency department: ultrasound versus computed tomography.

OBJECTIVE: To determine whether an abdominal ultrasound scan performed by paediatric radiologists is effective in the diagnosis of abdominal injuries in children. METHOD: A retrospective cohort study was undertaken of all children who presented with blunt abdominal trauma to a paediatric teaching hospital (RHSC) over a 5-year period between 1 January 2001 and 31 December 2005. Hospital notes and radiology computer systems were interrogated and data were collected and analysed. RESULTS: Of the 80 children with blunt abdominal trauma, 56 (70%) had abdominal imaging and 23 (30%) had no imaging. Of the 56 imaged, 48 (86%) had an USS of which 25 (52%) were positive (16 demonstrated solid organ injury, 8 free fluid and 1 suspected bladder rupture); 3 of these went on to have a CT scan. 23 had a normal USS; 2 of these children went on to have a CT scan because of a high index of suspicion for small bowel perforation due to their mechanism of injury and clinical signs. Both of these CT scans were normal. Eight children (14%) had a CT scan as the primary investigation, 6 of which (75%) were positive (5 demonstrated liver lacerations and 1 free fluid with no obvious source). All these abnormalities were demonstrated on follow-up USS. 23 children had no abdominal imaging and once their symptoms and signs had settled they were safely discharged home. CONCLUSION: Abdominal USS performed by paediatric radiologists is an accurate method of assessing abdominal injuries. However, CT scanning can assess certain abnormalities such as pancreatic or duodenal injuries and small amounts of free intraperitoneal air more accurately. The importance of serial clinical examination must not be overlooked.

The rate of skeletal maturation in the Scottish population: a comparison across 25 years (1980-2005).

BACKGROUND: A retrospective, cross-sectional study was performed to compare the rates of skeletal maturation in Scottish populations 25 years apart (1980-2005). METHODS: Two cohorts of sequentially radiographs were identified from patients at a Scottish pediatric hospital in 1980 and 2005. All radiographs were performed after trauma. The bone age was measured according to the Carpal scoring system of the Tanner-Whitehouse 2 method. RESULTS: One hundred four and 103 radiographs were included from 1980 and 2005, respectively. The radiographs from 2005 showed the children to have achieved older bone ages for given chronological ages than in 1980 (P < 0.0001). CONCLUSIONS: The findings have an important implication for the management of children with limb-length discrepancy. Children may not have the growth potential anticipated by chronological age; this will affect the timing of surgery and medical treatment of abnormalities of puberty and stature.

Incidental radiological diagnosis of rickets.

Rickets fortunately remains rare in the United Kingdom, although its actual incidence is currently undetermined.1 Many still consider it to be a disease of poverty prevalent during the Victorian era. However, a number of recent articles have highlighted concern among British health professionals about the number of cases still being diagnosed in this country. These cases have nearly all involved non-Caucasian children who are considered to be at high risk due to skin colour, prolonged breast feeding, and low maternal vitamin D levels. Their presentations are variable ranging from failure to thrive, bone deformities, seizures, and even stridor. The diagnosis is usually made in babies and toddlers.We present a series of patients attending our accident and emergency (A&E) department, over a five month period, where the diagnosis of rickets was primarily a radiological diagnosis.

Can we abolish skull x rays for head injury?

OBJECTIVES: To assess the effect of a change in skull x ray policy on the rate of admission, use of computed tomography (CT), radiation dose per head injury, and detection of intracranial injuries; and to compare the characteristics of patients with normal and abnormal head CT. DESIGN: Retrospective cohort study. SETTING: UK paediatric teaching hospital emergency department. PATIENTS: 1535 patients aged between 1 and 14 years with a head injury presenting to the emergency department between 1 August 1998 and 31 July 1999 (control period), and 1867 presenting between 1 August 2002 and 31 July 2003 (first year of new skull x ray policy). INTERVENTION: Hospital notes and computer systems were analysed and data were collected on all patients presenting with a head injury. RESULTS: The abolition of skull x rays in children aged over 1 year prevented about 400 normal skull x rays being undertaken in period 2. The percentage of children undergoing CT rose from 1.0% to 2.1% with no change in the positive CT pick up rate (25.6% v 25.0%). There was no significant change in admission rate (10.9% v 10.1%), and a slight decrease in the radiation dose per head injury (0.042 mSv compared to 0.045 mSv). CONCLUSIONS: Skull x rays can be abandoned in children aged 1 to 14 without a significant increase in admission rate, radiation dose per head injury, or missed intracranial injury. The mechanism and history of the injury and a reduced Glasgow coma scale are probably the most important indicators of significant head injury in children.

Imaging infants with head injury: effect of a change in policy.

OBJECTIVE: Head injury is one of the commoner injuries presenting to the emergency department (ED). Infants are hard to assess clinically and emphasis has been placed on radiological examination. Skull radiographs, however, are not a reliable indicator of intracranial injury. As a result of this the policy in this ED was revised so that skull radiographs were only to be performed in those infants less than 1 year with visible evidence of head injury or a suspicious history for non-accidental injury. METHODS: Retrospective cohort study of all infants less than 1 year who presented with head trauma to the ED of a paediatric teaching hospital between 1 August 1998 and 31 July 1999, and between 1 August 2002 and 31 July 2003. Hospital notes and radiology computer systems were examined and data were collected and analysed. RESULTS: 181 infants aged less than 1 year presenting to the ED in 1998/9 and 190 infants in 2002/3. Altogether 140 (77.3%) infants had a skull radiograph in 1998/9, five (3.6%) identified skull fractures. During 2002/3, 56 (29.5%) infants had a radiograph, a reduction of 47.5%, of which three (5.4%) had skull fractures. All fractures had reported haematomas to their scalp. The change in policy decreased the total radiation dose to the population by 9.4 mSv. No significant injuries were missed as a result of the change in policy. INTERPRETATION: In infants under 1 year, unless non-accidental injury is suspected, it is suggested that skull radiographs should only be performed when there are visible signs of a head injury.

Fracture of the sternum in children.

OBJECTIVE: Sternal fracture is poorly characterised in children. The purpose of this study was to gain insight into the mechanism, radiological characteristics, and accompanying injuries of sternal fracture in children. METHODS: The study was retrospective. The records of all children who underwent plain radiography of the sternum, or computed tomography of the thorax after trauma, over a 40 month period in our paediatric hospital were reviewed for evidence of sternal fracture. RESULTS: 12 of 33 children identified had radiological evidence of sternal fracture. The age range of children with fractures was 5 to 12 years. Eleven children had fracture of the anterior cortex of the first or second sternebra of the body of the sternum. One child had fracture through the manubriosternal joint with posterior displacement of the body. Seven fractures resulted from direct blows to the anterior chest, five fractures resulted from hyperflexion injury of the thoracic spine. None were the result of motor vehicle crash. All fractures were isolated injuries. CONCLUSIONS: Sternal fracture is uncommon in children. Injury may result from direct or indirect violence. The child's sternum is commonly fractured by more minor blunt trauma than generally recognised in the literature. All patients with sternal fracture after indirect violence should have careful examination of the spine. Patients with undisplaced anterior cortical fracture without other injury may be safely discharged from the emergency department.

Emmetropisation following preterm birth.

BACKGROUND/AIMS: Even in the absence of retinopathy of prematurity (ROP), premature birth signals increased risk for abnormal refractive development. The present study examined the relation between clinical risk factors and refractive development among preterm infants without ROP. METHODS: Cycloplegic refraction was measured at birth, term, 6, 12, and 48 months corrected age in a cohort of 59 preterm infants. Detailed perinatal history and cranial ultrasound data were collected. 40 full term (plus or minus 2 weeks) subjects were tested at birth, 6, and 12 months old. RESULTS: Myopia and anisometropia were associated with prematurity (p<0.05). More variation in astigmatic axis was found among preterm infants (p<0.05) and a trend for more astigmatism (p<0.1). Emmetropisation occurred in the preterm infants so that at term age they did not differ from the fullterm group in astigmatism or anisometropia. However, preterm infants remained more myopic (less hyperopic) than the fullterm group at term (p<0.05) and those infants born <1500 g remained more anisometropic than their peers until 6 months (p<0.05). Infants with abnormal cranial ultrasound were at risk for higher hyperopia (p<0.05). Other clinical risk factors were not associated with differences in refractive development. At 4 years of age 19% of the preterm group had clinically significant refractive errors. CONCLUSION: Preterm infants without ROP had high rates of refractive error. The early emmetropisation process differed from that of the fullterm group but neither clinical risk factors nor measures of early refractive error were predictive of refractive outcome at 4 years.

Management of simple renal cysts in children.

Simple renal cysts are uncommon in children and their presentation and management has changed with increasing use of ultrasound scans. The aim of this study was to review our experience and highlight some peculiarities in diagnosis and management of these cases. Eight cases were diagnosed and two symptomatic cases underwent aspiration under ultrasound guidance; one case recurred and required re-aspiration. Differentiation of simple renal cysts from other cystic lesions of the kidney, aspiration of symptomatic cysts and the importance of long-term follow-up are discussed.

A novel acropectoral syndrome maps to chromosome 7q36.

F syndrome (acropectorovertebral syndrome) is a dominantly inherited skeletal dysplasia affecting the hands, feet, sternum, and lumbosacral spine, which has previously been described in only two families. Here we report a six generation Turkish family with a related but distinct dominantly inherited acropectoral syndrome. All 22 affected subjects have soft tissue syndactyly of all fingers and all toes and 14 also have preaxial polydactyly of the hands and/or feet. In addition, 14 have a prominent upper sternum and/or a blind ending, inverted U shaped sinus in the anterior chest wall. Linkage studies and haplotype analysis carried out in 16 affected and nine unaffected members of this family showed that the underlying locus maps to a 6.4 cM interval on chromosome 7q36, between EN2 and D7S2423, a region to which a locus for preaxial polydactyly and triphalangeal thumb-polysyndactyly has previously been mapped. Our findings expand the range of phenotypes associated with this locus to include total soft tissue syndactyly and sternal deformity, and suggest that F syndrome may be another manifestation of the same genetic entity. In mice, ectopic expression of the gene Sonic hedgehog (Shh) in limb buds and lateral plate mesoderm during development causes preaxial polydactyly and sternal defects respectively, suggesting that misregulation of SHH may underlie the unusual combination of abnormalities in this family. A recently proposed candidate gene for 7q36 linked preaxial polydactyly is LMBR1, encoding a novel transmembrane receptor which may be an upstream regulator of SHH.

Renal venous thrombosis with calcification and preservation of renal function.

Two neonates were found on US to have branching linear calcification in the renal parenchyma, right sided in one and bilateral in the other. CT confirmed the presence of branching calcification in the kidneys and demonstrated calcified thrombus in the inferior vena cava in both babies. Antenatal detection of adrenal haemorrhage in one baby and presence of calcification at the age of 3 days in the other indicate that thrombosis probably occurred before birth. The kidneys remained normal in size, and uptake of 99mTc-labelled dimercaptosuccinic acid (99mTc-DMSA) was normal on follow-up examination. The presence of branching calcification and normal renal size probably indicates good prognosis for renal function in neonates in whom renal venous thrombosis is found and may indicate prenatal thrombosis.

Treatment of oesophageal strictures in children: a comparison of fluoroscopically guided balloon dilatation with surgical bouginage.

PURPOSE: To compare the technical feasibility and procedural complications of fluoroscopically guided balloon dilatation with conventional surgical bouginage for the treatment of oesophageal strictures in children. MATERIALS AND METHODS: A retrospective analysis of 125 balloon dilatations in 37 children with oesophageal strictures of varying aetiology. Twenty-four of the 37 children also underwent 88 procedures of surgical bouginage and comparison was made between the methods. RESULTS: Fluoroscopic balloon dilatation had fewer technical failures (0/125 vs. 4/88, P<0.02) and fewer iatrogenic perforations (2/125 vs. 5/88 P = 0.1) than surgical bouginage. CONCLUSION: Fluoroscopically guided balloon dilatation is safer and has fewer technical failures than surgical bouginage and should be considered the first line of treatment for oesophageal strictures in children.

Survey of intussusception reduction in England, Scotland and Wales: how and why we could do better.

Britton, I. and Wilkinson, A. G. (2000). Clinical Radiology55, 984-985.

Children of renal transplant recipient mothers.

OBJECTIVE: To assess the current physical status and developmental outcome of children born to mothers following renal transplantation. METHODOLOGY: A cross-sectional prevalence survey of 48 children born to 34 women transplanted at a single centre from 1971 to 1992 was performed. Data on maternal renal disease, immunosuppression, pregnancy, delivery and child development were collected using hospital records and parental questionnaire. Children underwent physical examination, urinalysis and urinary tract ultrasound examination (US). RESULTS: Maternal renal failure was due to reflux nephropathy/chronic pyelonephritis (16), chronic glomerulonephritis (eight) and other causes (10). All mothers received prednisolone immunosuppression, as sole therapy (one), as part of triple therapy (one). Sixteen (47%) received azathioprine/prednisolone and 16 (47%) cyclosporin/prednisolone. Twenty-three girls and 25 boys aged 9 months to 18 years were studied (median age 5.2 years); 27/48 (56%) were born prematurely, 21/48 (44%) with birthweight (BW) < 2500 g 21/48 (44%) were small for gestation (BW < 10th centile). General health and physical assessment were unremarkable in 45/48 (94%) and 41/43 (95%), respectively. Development was considered normal in 47/48 (98%). Four of 40 (10%) had urinary tract abnormalities on US. CONCLUSIONS: Despite a high incidence of preterm delivery, low birth weight, intrauterine growth retardation and urinary tract abnormalities, the overall outcome for children of renal transplant recipient mothers is good.

Ultrasound features of intussusception predicting outcome of air enema.

OBJECTIVE: To examine features identified on US which predict success or failure of air-enema reduction of intussusception. MATERIALS AND METHODS: A retrospective study of 117 consecutive episodes of intussusception, presenting for US over a 6-year period. The specific features examined were: free fluid within the peritoneum, small-bowel obstruction, colonic wall thickness, and fluid trapped between the colon and the intussusceptum. RESULTS: The overall reduction rate, irrespective of US features, over the 6-year period was 72 %. Reduction rates were significantly higher with the absence of free fluid, trapped fluid, or small-bowel obstruction (93 %). The presence of trapped fluid predicted an unfavourable outcome, with a significantly lower success rate (25 %). Colonic wall thickness did not predict outcome; in successful reductions, mean wall thickness was 7.2 mm and in failed reductions 7.6 mm. CONCLUSIONS: Where free fluid, small-bowel obstruction, and trapped fluid are absent, almost 100 % success with air-enema reduction should be achievable. Where trapped fluid is present, air enema should be performed cautiously to avoid perforation caused by overvigorous attempts at pneumatic reduction of an incarcerated intussusception.