Susceptibility artifact correction for sub-millimeter fMRI using inverse phase encoding registration and T1 weighted regularization.

BACKGROUND: Functional magnetic resonance imaging (fMRI) enables non-invasive examination of both the structure and the function of the human brain. The prevalence of high spatial-resolution (sub-millimeter) fMRI has triggered new research on the intra-cortex, such as cortical columns and cortical layers. At present, echo-planar imaging (EPI) is used exclusively to acquire fMRI data; however, susceptibility artifacts are unavoidable. These distortions are especially severe in high spatial-resolution images and can lead to misrepresentation of brain function in fMRI experiments. NEW METHOD: This paper presents a new method for correcting susceptibility artifacts by combining a T1-weighted (T1w) image and inverse phase-encoding (PE) based registration. The latter uses two EPI images acquired using identical sequences but with inverse-PE directions. In the proposed method, the T1w image is used to regularize the registration, and to select the regularization parameters automatically. The motivation is that the T1w image is considered to reflect the anatomical structure of the brain. RESULTS: Our proposed method is evaluated on two sub-millimeter EPI-fMRI datasets, acquired using 3T and 7T scanners. Experiments show that the proposed method provides improved corrections that are well-aligned to the T1w image. COMPARISON WITH EXISTING METHODS: The proposed method provides more robust and sharper corrections and runs faster compared with two other state-of-the-art inverse-PE based correction methods, i.e. HySCO and TOPUP. CONCLUSIONS: The proposed correction method used the T1w image as a reference in the inverse-PE registration. Results show its promising performance. Our proposed method is timely, as sub-millimeter fMRI has become increasingly popular.

Vascular effects on the BOLD response and the retinotopic mapping of hV4.

Despite general acceptance that the retinotopic organisation of human V4 (hV4) takes the form of a single, uninterrupted ventral hemifield, measured retinotopic maps of this visual area are often incomplete. Here, we test hypotheses that artefact from draining veins close to hV4 cause inverted BOLD responses that may serve to obscure a portion of the lower visual quarterfield-including the lower vertical meridian-in some hemispheres. We further test whether correcting such responses can restore the 'missing' retinotopic coverage in hV4. Subjects (N = 10) viewed bowtie, ring, drifting bar and full field flash stimuli. Functional EPIs were acquired over approximately 1.5h and analysed to reveal retinotopic maps of early visual cortex, including hV4. Normalised mean maps (which show the average EPI signal amplitude) were constructed by voxel-wise averaging of the EPI time course and used to locate venous eclipses, which can be identified by a decrease in the EPI signal caused by deoxygenated blood. Inverted responses are shown to cluster in these regions and correcting these responses improves maps of hV4 in some hemispheres, including restoring a complete hemifield map in one. A leftwards bias was found whereby 6/10 left hemisphere hV4 maps were incomplete, while this was the case in only 1/10 right hemisphere maps. Incomplete hV4 maps did not correspond with venous artefact in every instance, with incomplete maps being present in the absence of a venous eclipse and complete maps coexisting with a proximate venous eclipse. We also show that mean maps of upper surfaces (near the boundary between cortical grey matter and CSF) provide highly detailed maps of veins on the cortical surface. Results suggest that venous eclipses and inverted voxels can explain some incomplete hV4 maps, but cannot explain the remainder nor the leftwards bias in hV4 coverage reported here.

Discordance in neonatal risk factors and early childhood outcomes of very low birth weight (<1.5 kg) twins.

OBJECTIVE: To examine the rates of discordance in neonatal risk factors and neurodevelopmental outcomes within very low birth weight twin pairs and the factors associated with discordant outcomes. STUDY DESIGN: Rates of neonatal risk factors and neurodevelopmental outcomes, and discordance in outcomes were examined for 88 very low birth weight twin pairs born between 1990 and 2005 and followed through 20 months' corrected age. RESULT: Discordance rates ranged from 17 to 42% for neonatal risk factors and from 18 to 31% for neurodevelopmental outcomes. In regression analysis, affected co-twins were significantly more likely to have had an abnormal cerebral ultrasound than their unaffected co-twins in pairs discordant for cerebral palsy (odds ratio (OR): 13.00, 95% confidence interval (CI): 2.22 to 76.03)) and in pairs discordant for neurodevelopmental impairment (OR: 4.00, 95% CI: 1.13 to 14.18). Outcomes and discordance in outcomes were similar for monochorionic and dichorionic pairs. CONCLUSION: Despite shared genetics and risk factors, twins may have discordant outcomes. Information on discordant neonatal and neurodevelopmental outcomes is important for counseling families of twins.

The Childhood Adenotonsillectomy Trial (CHAT): rationale, design, and challenges of a randomized controlled trial evaluating a standard surgical procedure in a pediatric population.

Each year, over 500,000 adenotonsillectomies (AT), mostly for the treatment of pediatric obstructive sleep apnea (OSA) are performed in the US in children under 15 years of age. No definitive study, however, has been yet conducted that has rigorously evaluated the effectiveness of AT for not only improving sleep disordered breathing, but also for improving clinically relevant outcomes, such as neurocognitive function, behavior, and quality of life. The Childhood Adenotonsillectomy Trial (CHAT) was designed to assess neuropsychological and health outcomes in children randomized to receive early AT (eAT) as compared to Watchful Waiting with Supportive Care (WWSC). Important secondary goals of the study are to evaluate outcomes in subgroups defined by obesity and race. This paper addresses key elements in the design and implementation of a controlled trial for a widely used "standard practice" surgical intervention in a pediatric population, that include establishment of standardized data collection procedures across sites for a wide variety of data types, establishment of equipoise, and approaches for minimizing unblinding of selected key personnel. The study framework that was established should provide a useful template for other pediatric controlled studies or other studies that evaluate surgical interventions.

Further evidence of pleiotropy influencing speech and language: analysis of the DYX8 region.

BACKGROUND/AIMS: Genetic studies have raised the possibility of common bases for cognitive linguistic disorders such as speech sound disorder (SSD), reading disorder (RD) and language impairment (LI). Thus, some of the same genes may jointly influence cognitive components within and between these three disorders. We examined the plausibility of this theory in a sample of families ascertained on the basis of a child with SSD. METHODS: Using the method of generalized estimating equations to solve a bivariate family predictive model we obtained measures of comorbidity and familial aggregation of SSD and LI. We then used two methods of multipoint model-free linkage analysis to evaluate SSD and LI psychometric test measures over a region previously implicated in linkage studies of RD, DYX8 region, 1p34-p36. RESULTS: Bivariate phenotypic analyses show evidence of comorbidity and within family aggregation and coaggregation of SSD and LI. In addition, two regions on chromosome 1 show suggestive evidence of linkage. The first region was previously reported in dyslexia studies. Our maximum linkage signal in this region measured articulation (p = 0.0009) in SSD sibling pairs. The second region is characterized by processes involved in language production, with the maximum linkage signal measuring listening comprehension (p = 0.0019) using all sibling pairs. CONCLUSION: We conclude that the DYX8 region could bear genes controlling pleiotropic effects on SSD, LI and RD.

Clinical outcomes of neonatal meningitis in very-low birth-weight infants.

We sought to describe the clinical presentation and consequences of meningitis among 64 very-low-birth-weight (VLBW <1.5 kg) infants who had 67 culture-proven episodes of meningitis over an 18-year period, 1977 through 1995. Demographic and neonatal descriptors of meningitis and later outcomes were retrospectively examined and neurodevelopmental outcomes of 39 of 45 (87%) meningitis survivors were compared to those of nonmeningitis survivors followed up to 20 months corrected age. Causes of meningitis included coagulase-negative Staphylococcus in 43% of episodes, other gram-positive bacteria in 19%, gram-negative bacteria in 17%, and Candida species in 20% of episodes. Spinal fluid abnormalities were sparse, regardless of etiologic organism. Of 38 nonbloody spinal fluid taps (<1,000 erythrocytes/mm3), 6 had >30 leukocytes/mm3, 5 protein >150 mg/dL%, and 6 glucose <30 mg/dL (1.67 mmol/L). Only 10 infants (26%) had 1 or more of these spinal fluid abnormalities. Meningitis survivors had a higher rate of major neurologic abnormality (41% vs 11%, p<0.001) and subnormal (<70) Mental Development Index (38% vs 14%, p<0.001) than nonmeningitis survivors. Impairment rates did not differ by etiologic organism. The effect of meningitis on neurologic outcome persisted even after controlling for birth weight, intraventricular hemorrhage, chronic lung disease, and social risk factors (odds ratio 2.27 [95% CI 1.02, 5.05]). We conclude that despite a sparsity of abnormal spinal fluid findings, culture-proven neonatal meningitis among VLBW infants has a detrimental effect on neurologic outcome, which persists even after controlling for other risk factors.

Bidirectional child-family influences on outcomes of traumatic brain injury in children.

Child behavior problems, injury-related family burden, and parent psychological distress were assessed longitudinally over the first year post injury in 40 children with severe traumatic brain injury (TBI), 52 with moderate TBI, and 55 with orthopedic injuries not involving brain insult. Parents rated children's preinjury behavior soon after injury. Postinjury child behavior and family outcomes were assessed at 6- and 12-month follow-ups. Findings from path analysis revealed both direct and indirect effects of TBI on child behavior and family outcomes, as well as cross-lagged child-family associations. Higher parent distress at 6 months predicted more child behavior problems at 12 months, controlling for earlier behavior problems; and more behavior problems at 6 months predicted poorer family outcomes at 12 months, controlling for earlier family outcomes. Support for bidirectional influences is tentative given that limited sample size precluded use of structural equation modeling. The findings nevertheless provide impetus for considering the influences of person-environment interactions on outcomes of TBI.

Constipation in very-low-birth-weight children at 10 to 14 years of age.

BACKGROUND: The authors documented that very-low-birth-weight children (less than 750-g) when compared with 750-to 1,499-g birth-weight and normal-birth-weight-matched controls have higher than normal rates of neurosensory and cognitive impairments at school age. In this population, the authors found a higher rate of constipation than expected among 19 of 59 (32%) less-than-750-g-birth-weight children. The authors therefore wanted to evaluate in greater detail the problem of constipation and associated toileting problems in this population. METHODS: Nineteen less-than-750-g-birth-weight children with constipation were matched to the next less than 750-g-birth-weight child of comparable age, sex, and race who did not have constipation. A telephone questionnaire was administered to 15 of 19 parents of the less-than-750-g-birth-weight children who had constipation. RESULTS: The 15 children with constipation had significantly higher rates of neurosensory impairment (7 [47%] vs. 1 [7%]) and lower mean WISC III IQ scores (72 +/- 22 vs. 89 +/- 13) when compared with birth-weight-matched controls without constipation (P < 0.05). The constipated children also had significantly higher rates of associated toileting problems, including encopresis (8[53%] vs. 1 [7%])and stool withholding (9 [60%] vs. 2 [13%]; P < 0.05). CONCLUSION: The higher incidence of constipation among less-than-750-g-birth-weight children is associated with neurodevelopment impairment. Awareness of this problem and preventive intervention to ensure regular stools could possibly decrease the high rate of constipation and associated toileting problems.

The relationship of caregiver coping to family outcomes during the initial year following pediatric traumatic injury.

This study identified coping strategies associated with caregiver outcomes following pediatric injury and examined injury type as a moderator of coping efficacy. Families of 103 children with traumatic brain injury (TBI) and 71 children with orthopedic injuries were followed prospectively during the initial year postinjury. The groups had comparable preinjury characteristics and hospitalization experiences but differed on neurological insult. In hierarchical regression analyses, acceptance was associated with lower burden and denial was associated with greater distress in both groups. Active coping resulted in higher distress following TBI but not orthopedic injuries. Conversely, the use of humor was related to diminishing distress following TBI but unrelated to distress following orthopedic injuries. Results are discussed in terms of the implications for intervention following TBI.

Child and family functioning 6 and 12 months after a serious pediatric fracture.

BACKGROUND: Previous findings indicate that pediatric fractures can have adverse consequences for child adjustment and family functioning immediately after injury. However, longer term effects of the fractures are unknown. The purposes of the present prospective study were to examine the child and family outcomes of pediatric traumatic fractures at 6 months and 1 year after injury, and to identify injury and treatment factors associated with these outcomes. METHODS: We evaluated 57 children 6 to 12 years of age with traumatic fractures requiring hospitalization. Using standardized measures and parent interview, we obtained measures of pre- and postinjury child and family functioning. RESULTS: Although outcomes were primarily positive at 1 year after injury, child functional limitations and family stress were observed up to 6 months after injury. Lower extremity fractures had a more negative impact on families across all three assessment points. Children with fracture interventions that involved prolonged immobilization had more functional limitations at 6 months than children who were ambulatory. Family burden was higher at 1 month for the immobilized children, but not at later follow-up. CONCLUSION: Some children and families experience adverse effects during the year after a serious pediatric fracture, especially if sustained in a lower extremity. Fracture stabilization that allows for greater ambulation may offer some benefits related to functional outcomes and family impact.

Long-term family outcomes for children with very low birth weights.

OBJECTIVE: To examine long-term outcomes in families of children with very low birth weights (<1500 g) in relation to the extent of low birth weight and neonatal medical risk. DESIGN: Concurrent/cohort prospective study. SETTING: Regional follow-up program. PARTICIPANTS: Families of 60 children of school age with birth weights less than 750 g, 55 with birth weights between 750 and 1499 g, and 49 normal birth weight full-term controls. MAIN OUTCOME MEASURES: Parent ratings of psychological distress, family function, and child-related stress. RESULTS: Families with children with birth weights less than 750 g experienced greater stress than did families of controls (born at full term), and families who were sociodemographically advantaged experienced greater stress than did those who were disadvantaged. Higher neonatal medical risk also predicted a more negative impact on the family, but only in advantaged families. Regression analyses suggested that adverse family outcomes were mediated by ongoing problems in child functioning. CONCLUSIONS: Families of children with birth weights less than 750 g experience more long-term adversity than families of full-term children. Family sequelae are also present for children with very low birth weight at high neonatal medical risk. Ongoing child health and behavior problems may be the major source of these sequelae, and sociodemographic status is an important consideration in identifying family adversity. Although many families appear unaffected, results support the need to monitor family outcomes and develop interventions for both the child and family.

School-age consequences of birth weight less than 750 g: a review and update.

Recent advances in perinatal care have led to the survival of increasing numbers of children born at the lower limits of viability. Children with very low birth weight (LBW; less than 1,500 g, 3 lb 5 oz) have been studied extensively. Findings document poorer outcomes relative to normal birth weight term-born controls in neurologic and health status, cognitive-neuropsychological skills, school performance, academic achievement, and behavior. This report reviews current knowledge regarding LBW children, with special emphasis on outcomes for children with birth weight less than 750 g (1 lb 10 oz). Results from an ongoing longitudinal study suggest a gradient of sequelae, with poorer outcomes in less than 750 g birth weight children compared to both 750 g to 1,499 g birth weight children and term-born controls. Children with less than 750 g birth weight fail to catch up with their peers over time and may even be at risk for age-related increases in sequelae. Outcomes are highly variable but related to neonatal medical complications of prematurity and social risk factors. Further research is needed to understand the etiology and neuropathological basis of sequelae, the long-term developmental implications of LBW, and treatment needs.

Longitudinal outcomes of Haemophilus influenzae meningitis in school-age children.

The purpose of this study was to investigate long-term outcomes of Haemophilus influenzae Type b meningitis in a cohort of school-age survivors. Findings from an initial assessment at mean age 10 years revealed neuropsychological, achievement, and behavioral sequelae in the children with neurologic complications during the acute-phase illness (H. Taylor, C. Schatschneider, & D. Rich, 1992). Here, the cohort was reassessed 1 and 2 years after the initial evaluation to investigate age-related influences on disease sequelae. After excluding children with hearing loss, the sample was divided into 2 groups: an affected group of 39 children with acute-phase neurologic complications and an unaffected group of 73 children without these complications. Growth-curve modeling showed poorer outcomes at the final assessment and less rapid improvement at follow-up for the affected group. Later age at assessment and later age at illness were associated with larger group differences in some outcomes. Results suggest that children with diffuse early brain insults are at risk for later-emerging sequelae.

Functional limitations and special health care needs of 10- to 14-year-old children weighing less than 750 grams at birth.

OBJECTIVE: To examine the health status, functioning, and special health care needs of children 10 to 14 years old weighing <750 g at birth. METHODS: We compared outcomes of a regional cohort of 59 children born from 1982 through 1986 weighing <750 g at birth (mean: 665 g; gestational age: 26 weeks) to matched groups of 54 children weighing 750 to 1499 g at birth and 49 children born at term. Assessments of limitations in functioning, compensatory dependence and needs for services above routine, at a mean age of 11 years, were based on responses to maternal questionnaires. Rates of these outcomes were compared between groups using logistic regression analyses that controlled for gender and social risk. RESULTS: Children weighing <750 g at birth had significantly higher rates of functional limitations, greater compensatory dependence, and need for services above routine than the other 2 groups. Compared with children born at term, the odds ratio for mental or emotional delay was 4.7 (95% confidence interval [CI]: 2.0-11.0), for restrictions in activity, 5.1 (CI: 1.6-16.3) and for blindness or difficulty seeing 3.9 (CI:1.3-11.4). With the exception of 3% of children who were severely impaired, the only compensatory aid that differentiated the children weighing <750 g at birth from the children born at term was the greater need for glasses (odds ratio [OR]: 2.8 [CI: 1.3-6.3]). Increased services above routine included special education (OR: 5.0 [CI: 2.1-11.7]), counseling (OR: 4.8 [CI: 1.0-23.1]) and special arrangements in school (OR: 9.5 [C.I. 2.1-43. 6]). CONCLUSION: Parents and educators need to be informed of the potential for disability and special health care needs of children weighing <750 g at birth.

Academic outcomes in children with histories of speech sound disorders.

Tests of phonology, semantics, and syntax were administered to 52 preschool children (19 girls and 33 boys, age 4-6 years) with moderate to severe speech sound disorders. The children's performance on these tests was used to predict language, reading, and spelling abilities at school age (age 8-11 years). Language impairment at school age was related to poor performance on preschool tests of syntax and nonsense word repetition, while reading impairment was predicted by poor performance in all preschool test domains (phonology, semantics, and syntax). In contrast, spelling impairment was predicted by deficits in preschool tests of phonological processing as measured by the Word Discrimination subtest of the Test of Language Development - Primary 2. Family history for speech and language disorders did not predict language, reading, or spelling impairment at school age. However, family history for reading disorders was a good predictor of school-age spelling difficulties.

Middle-school-age outcomes in children with very low birthweight.

Most previous studies of children with birthweight <750 g have focused on early childhood sequelae. To evaluate later outcomes, a regional sample of 60 <750-g birthweight children was compared at middle school age (M = 11 years) to 55 children with birthweight 750-1,499 g and 49 term controls. The groups were matched on age, gender, and demographic variables at the time of an early-school-age assessment (mean age 7 years). The <750-g birthweight group fared less well at middle school age than the term group on measures of cognitive function, achievement, behavior, and academic performance. In many instances, outcomes were less favorable for the <750-g children than for the 750 to 1,499-g group. Children in the <750-g group who were free of neurosensory disorders and global cognitive impairment performed more poorly on several tests than their term counterparts. Group differences in this subsample on tests of motor skills, math, and the ability to copy and recall a complex drawing remained significant even after controlling for IQ. Disparities between the <750-g and term groups increased with age for some measures. Despite favorable outcomes for many children in the <750-g group, this population is at risk for long-term developmental problems.

Follow-up of children with early expressive phonology disorders.

Fifty-two children identified at age 4 to 6 years as demonstrating a moderate to severe expressive phonology disorder were followed to the third and fourth grades. Children were classified into two groups based on the presence of an early phonology disorder in isolation (P) or the presence of a phonology disorder with other language problems (PL). At follow-up, articulation measures failed to differentiate the groups; however, the PL group performed more poorly than the P group on measures of phoneme awareness, language, reading decoding, reading comprehension, and spelling. The P group demonstrated poor spelling skills relative to their reading and language abilities, suggesting residual spelling weaknesses in these children. The PL group reported more nuclear family members with speech-language disorders and with reading disorders than the P group. Findings support previous research linking early language disorders with later reading difficulties.

Utility of kindergarten teacher judgments in identifying early learning problems.

Most existing research on early identification of learning difficulties has examined the validity of methods for predicting future academic problems. The present study focused instead on the sensitivity of kindergarten teachers to learning problems in their students and on the continuity of teacher-identified problems over time. To identify early learning problems, kindergarten teachers in a suburban school district rated student progress toward six academic objectives as satisfactory or unsatisfactory. Twenty percent of the district's 303 kindergarten children received unsatisfactory ratings in at least one area. Thirty-eight of these children (identified group) were matched to 34 children with satisfactory ratings in all areas (nonidentified group). Results of testing conducted during kindergarten revealed poorer academic achievement in identified children than in nonidentified children. Children from the identified group also performed more poorly than children from the nonidentified group on tests of phonological processing and working memory/executive function and were rated by teachers as having more behavior and attention problems and lower social competence. Follow-up of the sample to first grade documented continued learning problems in the identified group. These findings support the use of teacher judgements in early detection of learning problems and argue against reliance on discrepancy criteria.