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Biomedical subjects

Terrie E Inder

Publications and source records attributed to Terrie E Inder.

At least 19 recordsLinked to original sources
PubMed2006

Perinatal risk factors altering regional brain structure in the preterm infant.

Neuroanatomical structure appears to be altered in preterm infants, but there has been little insight into the major perinatal risk factors associated with regional cerebral structural alterations. MR images were taken to quantitatively compare regional brain tissue volumes between term and preterm infants and to investigate associations between perinatal risk factors and regional neuroanatomical alterations in a large cohort of preterm infants. In a large prospective longitudinal cohort study of 202 preterm and 36 term infants, MR scans at term equivalent were undertaken for volumetric estimates of cortical and deep nuclear grey matter, unmyelinated and myelinated white matter (WM) and CSF within 8 parcellated regions for each hemisphere of the brain. Perinatal correlates analysed in relation to regional brain structure included gender, gestational age, intrauterine growth restriction, bronchopulmonary dysplasia, white matter injury (WMI) and intraventricular haemorrhage. Results revealed region-specific reductions in brain volumes in preterm infants compared with term controls in the parieto-occipital (preterm mean difference: -8.1%; 95% CI = -13.8--2.3%), sensorimotor (-11.6%; -18.2--5.0%), orbitofrontal (-30.6%; -49.8--11.3%) and premotor (-7.6%; -14.2--0.9%) regions. Within the sensorimotor and orbitofrontal regions cortical grey matter and unmyelinated WM were most clearly reduced in preterm infants, whereas deep nuclear grey matter was reduced mainly within the parieto-occipital and subgenual regions. CSF (ventricular and extracerebral) was doubled in volume within the superior regions in preterm infants compared with term controls. Cerebral WMI and intrauterine growth restriction were both associated with a more posterior reduction in brain volumes, whereas bronchopulmonary dysplasia was associated with a more global reduction across all regions. In contrast degree of immaturity was not related to regional brain structure among preterm infants. In summary, preterm birth is associated with regional cerebral tissue reductions, with the adverse pattern varying between risk factors. These findings add to our understanding of the potential pathways leading to altered brain structure and outcome in the preterm infant.

Brain↗
PubMed2006

Neonatal MRI to predict neurodevelopmental outcomes in preterm infants.

BACKGROUND: Very preterm infants are at high risk for adverse neurodevelopmental outcomes. Magnetic resonance imaging (MRI) has been proposed as a means of predicting neurodevelopmental outcomes in this population. METHODS: We studied 167 very preterm infants (gestational age at birth, 30 weeks or less) to assess the associations between qualitatively defined white-matter and gray-matter abnormalities on MRI at term equivalent (gestational age of 40 weeks) and the risks of severe cognitive delay, severe psychomotor delay, cerebral palsy, and neurosensory (hearing or visual) impairment at 2 years of age (corrected for prematurity). RESULTS: At two years of age, 17 percent of infants had severe cognitive delay, 10 percent had severe psychomotor delay, 10 percent had cerebral palsy, and 11 percent had neurosensory impairment. Moderate-to-severe cerebral white-matter abnormalities present in 21 percent of infants at term equivalent were predictive of the following adverse outcomes at two years of age: cognitive delay (odds ratio, 3.6; 95 percent confidence interval, 1.5 to 8.7), motor delay (odds ratio, 10.3; 95 percent confidence interval, 3.5 to 30.8), cerebral palsy (odds ratio, 9.6; 95 percent confidence interval, 3.2 to 28.3), and neurosensory impairment (odds ratio, 4.2; 95 percent confidence interval, 1.6 to 11.3). Gray-matter abnormalities (present in 49 percent of infants) were also associated, but less strongly, with cognitive delay, motor delay, and cerebral palsy. Moderate-to-severe white-matter abnormalities on MRI were significant predictors of severe motor delay and cerebral palsy after adjustment for other measures during the neonatal period, including findings on cranial ultrasonography. CONCLUSIONS: Abnormal findings on MRI at term equivalent in very preterm infants strongly predict adverse neurodevelopmental outcomes at two years of age. These findings suggest a role for MRI at term equivalent in risk stratification for these infants.

Brain↗
PubMed2006

Reduction in cerebellar volumes in preterm infants: relationship to white matter injury and neurodevelopment at two years of age.

A substantial number of prematurely born infants will experience later neurodevelopmental challenges. Abnormal development of the cerebellum may be related to some of the impairments exhibited by preterm children. To test the hypothesis that cerebellar development is structurally impaired in preterm infants and associated with adverse outcomes, we studied 83 preterm infants and 13 term controls using volumetric magnetic resonance imaging techniques to obtain cerebellar volumes (CV) at term corrected and subsequent neurodevelopmental assessment at 2 y of age. The preterm group had smaller mean CV at term compared with the term control infants [mean (SD) CV, 22.0 (5.0) versus 23.5 (5.0) cc; mean difference (95% confidence interval), 1.5 (-1.5, 4.4)] although this did not reach statistical significance. Within the preterm group, there was evidence of a reduction in CV related to the presence of white matter injury (WMI) after adjusting for intracranial volume (ICV) [WMI grade 1 versus grade 2: mean (SD) CV, 23.6 (5.0) versus 21.6 (4.5); p = 0.01; WMI grade 1 versus grade 3 and 4: 23.6 (5.0) versus 20.8 (5.6); p = 0.07]. Within the preterm infants, there was no apparent relationship between CV at term and gestational age at birth after adjusting for ICV. At 2 y of age, CV showed a weak correlation with cognitive and motor development, although this was principally mediated by WMI. In conclusion, we found no evidence for a primary impairment in cerebellar development in relation to prematurity, although there was evidence for a secondary effect of cerebral WMI on cerebellar development independent of immaturity.

Aging↗
PubMed2006

Seizure detection algorithm for neonates based on wave-sequence analysis.

OBJECTIVE: The description and evaluation of the performance of a new real-time seizure detection algorithm in the newborn infant. METHODS: The algorithm includes parallel fragmentation of EEG signal into waves; wave-feature extraction and averaging; elementary, preliminary and final detection. The algorithm detects EEG waves with heightened regularity, using wave intervals, amplitudes and shapes. The performance of the algorithm was assessed with the use of event-based and liberal and conservative time-based approaches and compared with the performance of Gotman's and Liu's algorithms. RESULTS: The algorithm was assessed on multi-channel EEG records of 55 neonates including 17 with seizures. The algorithm showed sensitivities ranging 83-95% with positive predictive values (PPV) 48-77%. There were 2.0 false positive detections per hour. In comparison, Gotman's algorithm (with 30s gap-closing procedure) displayed sensitivities of 45-88% and PPV 29-56%; with 7.4 false positives per hour and Liu's algorithm displayed sensitivities of 96-99%, and PPV 10-25%; with 15.7 false positives per hour. CONCLUSIONS: The wave-sequence analysis based algorithm displayed higher sensitivity, higher PPV and a substantially lower level of false positives than two previously published algorithms. SIGNIFICANCE: The proposed algorithm provides a basis for major improvements in neonatal seizure detection and monitoring.

Algorithms↗
PubMed2006

Modeling water diffusion anisotropy within fixed newborn primate brain using Bayesian probability theory.

An active area of research involves optimally modeling brain diffusion MRI data for various applications. In this study Bayesian analysis procedures were used to evaluate three models applied to phase-sensitive diffusion MRI data obtained from formalin-fixed perinatal primate brain tissue: conventional diffusion tensor imaging (DTI), a cumulant expansion, and a family of modified DTI expressions. In the latter two cases the optimum expression was selected from the model family for each voxel in the image. The ability of each model to represent the data was evaluated by comparing the magnitude of the residuals to the thermal noise. Consistent with previous findings from other laboratories, the DTI model poorly represented the experimental data. In contrast, the cumulant expansion and modified DTI expressions were both capable of modeling the data to within the noise using six to eight adjustable parameters per voxel. In these cases the model selection results provided a valuable form of image contrast. The successful modeling procedures differ from the conventional DTI model in that they allow the MRI signal to decay to a positive offset. Intuitively, the positive offset can be thought of as spins that are sufficiently restricted to appear immobile over the sampled range of b-values.

Animals↗
PubMed2006

Neonatal hypoglycemia and occipital cerebral injury.

Occipital brain injury associated with neonatal hypoglycemia can result in long-term disability, epilepsy, and visual impairment. The etiology of this pattern of injury is unclear; however, transient hyperinsulinism may be an independent risk factor. Magnetic resonance brain imaging can delineate the extent of brain injury and guide follow-up.

Brain Diseases, Metabolic↗
PubMed2006

Health service utilisation of a regional cohort of very preterm infants over the first 2 years of life.

AIM: Very preterm infants represent major consumers of health services following neonatal discharge. We examined the health service utilisation of a regional cohort of very preterm infants over the first 2 years of life, including the association with neurodevelopmental outcome. METHODS: A regionally based 2-year cohort of 100 very preterm infants along with a comparison sample of 104 full term control infants matched for sex, time and place of birth were recruited. Perinatal and social background factors that predispose very preterm infants to increased risk of subsequent general practitioner (GP) and hospital service use were identified. At 2 years, all children underwent a neurodevelopmental assessment, Bayley Scales of Infant Development (BSID-II). Details of children's medical contacts obtained by parent interview were cross-checked against GP and hospital records/databases. RESULTS: Very preterm infants had a similar number of GP visits to term infants but more outpatient hospital visits. Fifty-three (55%) very preterm infants were admitted to hospital on 131 occasions compared with 26 (26%) term infants on 37 occasions (p<0.001). The main reason for hospitalisation in the preterm cohort was respiratory disorder. The frequency of hospital admissions was significantly related to birthweight (P=0.01), gestational age (P<0.001) and the number of people living in the family household (P=0.02). No associations were found between hospital admission and neurodevelopment at 2 years. CONCLUSION: Very preterm infants had higher rates of hospital admissions and visits than term infants unrelated to neurodevelopmental outcome at 2 years of age. These findings highlight that very preterm birth is associated with ongoing health morbidity.

Age Distribution↗
PubMed2006

Reduced occipital regional volumes at term predict impaired visual function in early childhood in very low birth weight infants.

PURPOSE: Premature infants are at increased risk of impaired visual performance related to both cortical and subcortical pathways for oculomotor control. The hypothesis for the current study was that preterm infants with impaired saccades, smooth pursuit, and binocular eye alignment at age 2 years would have smaller occipital brain volumes at term equivalent, as measured by volumetric magnetic resonance (MR) techniques, than would preterm infants without such abnormalities. METHODS: Study participants consisted of 68 infants from a representative regional cohort of 100 preterm infants born between 23 and 33 weeks' gestation. At term equivalent, all infants underwent MR imaging, and the images were coregistered, tissue segmented into five cerebral tissue subtypes, and further subdivided into eight regions for each hemisphere. At 2 years corrected, all infants completed a comprehensive orthoptic evaluation performed by a single examiner. RESULTS: Twenty-four (35%) of the 68 infants had abnormal oculomotor control at 2 years, including abnormalities in saccadic movements (n = 7), smooth pursuit (n = 14), or strabismus (n = 9, four with esotropia and five with exotropia). When compared with preterm infants without visuomotor impairment, these infants had significantly smaller inferior occipital region brain tissue volumes bilaterally (n = 24 vs. n = 44; total tissue, mean +/- SD, left, 37.9 +/- 7.4 cm(3) vs. 43.7 +/- 7.4 cm(3); mean difference [95% CI] -5.7 [-9.4 to -2.0] cm(3), P = 0.003; right, 36.8 +/- 7.1 cm(3) vs. 41.4 +/- 6.2 cm(3), mean difference -4.6 [-7.9 to -1.3] cm(3), P = 0.007). This difference remained significant after adjusting for intracranial volume (ICV; left, mean difference -3.5 [-6.7 to -0.2] cm(3), P = 0.04; right, mean difference -2.4 [-5.2 to -0.4] cm(3), P = 0.09). Within this region, the cortical gray matter volume was the most significantly reduced (left, 20.4 +/- 6.2 cm(3) vs. 25.4 +/- 5.6 cm(3), mean difference -3.1 [-5.7 to -0.5] cm(3), P = 0.02; right 21.0 +/- 5.4 cm(3) vs. 24.9 +/- 5.0 cm(3), mean difference -2.2 [-4.4 to 0.0] cm(3), P = 0.05, ICV adjusted). Abnormalities in saccadic eye movements accounted for the largest effect on inferior occipital regional brain volumes (left side, P = 0.02). CONCLUSIONS: Volumetric MR imaging techniques demonstrated an overall reduction in the inferior occipital regional brain volumes in preterm infants at term corrected who later exhibit impaired oculomotor function control. These findings assist in understanding the neuroanatomic correlates of later visual difficulties experienced by infants born prematurely.

Child, Preschool↗
PubMed2006

Detection of wallerian degeneration in a newborn by diffusion magnetic resonance imaging (MRI).

We present the case of an infant with hypoxic-ischemic encephalopathy in whom wallerian degeneration is demonstrated in white-matter fiber tracts by diffusion magnetic resonance imaging (MRI). MRI was undertaken on days 2 and 9 and then at 9 months of age. On day 2, conventional MRI was normal, but diffusion MRI showed bioccipital abnormalities. On day 9, diffusion MRI showed marked abnormalities in the deep white matter of the occipital regions (left > right), corpus callosum, left posterior limb of the internal capsule, and left cerebral peduncle. Water apparent diffusion coefficient values showed a significant reduction in the left occipital white matter and corpus callosum between days 2 and 9 while demonstrating the expected pseudonormalization in cortical gray matter. Images at 9 months showed left occipital porencephaly and atrophy of the left cerebral peduncle, with the infant displaying right hemiplegia at 18 months of age. In this case, the time course of diffusion changes differed between white and gray matter, with diffusion MRI showing delayed wallerian degeneration of the cerebral white matter. This case characterizes this degeneration with clinical and follow-up MRI at 9 months of age.

Asphyxia Neonatorum↗
PubMed2006

Use of 2-channel bedside electroencephalogram monitoring in term-born encephalopathic infants related to cerebral injury defined by magnetic resonance imaging.

OBJECTIVE: Single-channel amplitude-integrated electroencephalography has been shown to be predictive of neurodevelopmental outcome in term infants with hypoxic-ischemic encephalopathy. We describe the relationship of quantifiable electroencephalogram (EEG) measures, obtained using a 2-channel digital bedside EEG monitor from term newborn infants with encephalopathy and/or seizures, to cerebral injury defined qualitatively by MRI. METHODS: Median values of minimum, mean, and maximum EEG amplitude were obtained from term-born encephalopathic infants during a 2-hour seizure-free period obtained within 72 hours of admission. Infants underwent MRI with images qualitatively scored for abnormalities of cortex, white matter, deep nuclear gray matter, and posterior limb of the internal capsule. Eighty-six infants had EEG measures related to qualitative MRI outcomes. RESULTS: The most common diagnosis was hypoxic ischemic encephalopathy (n = 40). For all infants there was a negative relationship between EEG amplitude measures and MRI abnormality scores assessed on a scale from 4 to 15, with a higher score indicating more abnormalities. This relationship was strongest for the minimum amplitude measures in both hemispheres; that is, for every unit increase in score there was a mean drop of 0.41 microV for the left cerebral hemisphere, with 35% of variance explained. This relationship persisted on sub-group analyses for infants with hypoxic-ischemic encephalopathy, infants with other diagnoses and infants monitored after the first 24 hours of life. Using an MRI abnormality score cutoff of 8 or worse for cerebral injury in infants with hypoxic-ischemic encephalopathy, a minimum amplitude of 4 microV showed a higher specificity (80%: left hemisphere), whereas a minimum amplitude of 6 muV showed a higher sensitivity (92%: left hemisphere). CONCLUSIONS: Bedside EEG measures in term-born encephalopathic infants are related to the severity of cerebral injury as defined by qualitative MRI. A minimum amplitude of <4 microV appears useful in predicting outcome.

Cerebral Cortex↗
PubMed2006

Regional brain development in serial magnetic resonance imaging of low-risk preterm infants.

OBJECTIVE: MRI studies have shown that preterm infants with brain injury have altered brain tissue volumes. Investigation of preterm infants without brain injury offers the opportunity to define the influence of early birth on brain development and provide normative data to assess effects of adverse conditions on the preterm brain. In this study, we investigated serial MRI of low-risk preterm infants with the aim to identify regions of altered brain development. METHODS: Twenty-three preterm infants appropriate for gestational age without magnetic resonance-visible brain injury underwent MRI twice at 32 and at 42 weeks' postmenstrual age. Fifteen term infants were scanned 2 weeks after birth. Brain tissue classification and parcellation were conducted to allow comparison of regional brain tissue volumes. Longitudinal brain growth was assessed from preterm infants' serial scans. RESULTS: At 42 weeks' postmenstrual age, gray matter volumes were not different between preterm and term infants. Myelinated white matter was decreased, as were unmyelinated white matter volumes in the region including the central gyri. The gray matter proportion of the brain parenchyma constituted 30% and 37% at 32 and 42 weeks' postmenstrual age, respectively. CONCLUSIONS: This MRI study of preterm infants appropriate for gestational age and without brain injury establishes the influence of early birth on brain development. No decreased cortical gray matter volumes were found, which is in contrast to findings in preterm infants with brain injury. Moderately decreased white matter volumes suggest an adverse influence of early birth on white matter development. We identified a sharp increase in cortical gray matter volume in preterm infants' serial data, which may correspond to a critical period for cortical development.

Brain↗
PubMed2006

Detection of impaired growth of the corpus callosum in premature infants.

OBJECTIVE: There is an urgent need for a bedside method to assess the effectiveness of neonatal therapies designed to improve cerebral development in very low birth-weight infants. The aim of this study was to assess the impact of preterm birth on the serial growth of the corpus callosum and how soon it could be detected after birth with cranial ultrasound. METHODS: We recruited 61 very low birth-weight infants admitted to a single regional level III NICU from 1998 to 2000. Study infants had 2 cranial sonograms > or = 7 days apart in the first 2 weeks of life and further sonograms at 6 weeks and at term equivalent. At each time point, the length of the corpus callosum and cerebellar vermis was measured on midline sagittal images, with growth rates calculated in millimeters per day. We compared growth of corpus callosum and cerebellar vermis in individuals, between birth age groups, and with corrected gestational age. We used antenatal growth rate of the corpus callosum of 0.2 to 0.27 mm/day as a reference. Relationships between corpus callosum growth rates and neurodevelopmental outcome at 2 years of age (corrected) were also examined. RESULTS: Growth of the corpus callosum was normal in most infants during the first 2 weeks of life but slowed after this (0.21 mm/day from 0-2 weeks vs 0.11 mm/day for weeks 2-6). Slowing of corpus callosum growth below expected reference range was consistently detectable by age 6 weeks for 96% of infants born between 23 and 33 weeks' gestation. Although some improvement in growth rate was observed for 15% of infants after 6 weeks, this was confined to infants born after 28 weeks. Vermis length correlated strongly with corpus callosum length. By 2 years of age, serious motor delay and cerebral palsy were associated with poorer growth of the length of the corpus callosum between 2 and 6 weeks after birth. CONCLUSIONS: The effect of preterm birth on growth of the corpus callosum is detectable by 6 weeks after delivery in preterm infants born at gestations of 23 to 33 weeks. Reduced growth of the corpus callosum in weeks 2 to 6, places these infants at elevated risks of later psychomotor delay and cerebral palsy.

Cerebral Palsy↗
PubMed2006

Alterations in neurobehavior at term reflect differing perinatal exposures in very preterm infants.

OBJECTIVES: Preterm infants have higher rates of cognitive and behavioral difficulties at school age than their term-born peers. We hypothesized that neurobehavior at term would be different in very preterm infants compared with term infants and that perinatal exposures would be associated with these alterations in neurobehavior. PATIENTS AND METHODS: Two standardized neurobehavioral evaluations were completed on 207 infants at term equivalent, including 168 very preterm infants (<1250 g or <30 weeks' gestation) and 39 term control infants. The assessments used were the Neonatal Intensive Care Unit Network Neurobehavioral Scale and the revised Hammersmith Neonatal Neurologic Examination. The relationship of perinatal variables to preterm infant neurobehavioral scores for both evaluations was examined. RESULTS: Compared with term-born infants, preterm infant neurobehavior was significantly altered for the Hammersmith Neonatal Neurologic Examination total score and all of the subtotals. Similarly, preterm infants displayed altered neurobehavior for the majority of the Neonatal Intensive Care Unit Network Neurobehavioral Scale summary scores. Complete perinatal data were available for 157 of 168 very preterm infants. The perinatal variables most strongly associated with altered preterm infant neurobehavior on multivariate regression analysis included the total number of days of assisted ventilation, intraventricular hemorrhage, and necrotizing enterocolitis. Positive perinatal influences on neurobehavioral performance at term on multivariate analysis included maternal antenatal steroids, female gender, and infants receiving breast milk at discharge home. CONCLUSIONS: Preterm infants at term equivalent showed alterations in motor behavior and higher cortically integrated functions. The pattern of abnormality in neurobehavior differed in relation to perinatal exposures. Neurobehavioral examination at term equivalent age is useful in evaluating the impact of neonatal intensive care.

Female↗
PubMed2005

Object working memory deficits predicted by early brain injury and development in the preterm infant.

Children born preterm and of very low birth weight are at increased risk of learning difficulties and educational under-achievement. However, little is known about the specific neuropsychological problems facing these children or their neurological basis. Using prospective longitudinal data from a regional cohort of 92 preterm and 103 full-term children, this study examined relations between term MRI measures of cerebral injury and structural brain development and children's subsequent performance on an object working memory task at the age of 2 years. Results revealed clear between-group differences, with preterm children having greater difficulty encoding new information in working memory than term control children. Within the preterm group, task performance at the age of 2 years was related to both qualitative MRI measures of white matter (WM) injury and quantitative measures of total and regional brain volumes assessed at term equivalent. Bilateral reductions in total tissue volumes (%region) of the following cerebral regions were specifically related to subsequent working memory performance: dorsolateral prefrontal cortex, sensorimotor, parietooccipital and premotor. Associations between total cerebral tissue volumes at term (adjusted and unadjusted for intracranial volume) persisted even after the effects of WM injury were taken into account. This suggests that early disturbance in cerebral development may have an independent adverse impact on later working memory function in the preterm infant. These findings add to our understanding of the neuropathological pathways associated with later executive dysfunction in the very preterm infant.

Brain↗
PubMed2005

Diffusion MR imaging characteristics of the developing primate brain.

Diffusion-based magnetic resonance imaging holds the potential to non-invasively demonstrate cellular-scale structural properties of brain. This method was applied to fixed baboon brains ranging from 90 to 185 days gestational age to characterize the changes in diffusion properties associated with brain development. Within each image voxel, a probability-theory-based approach was employed to choose, from a group of analytic equations, the one that best expressed water displacements. The resulting expressions contain eight or fewer adjustable parameters, indicating that relatively simple expressions are sufficient to obtain a complete description of the diffusion MRI signal in developing brain. The measured diffusion parameters changed systematically with gestational age, reflecting the rich underlying microstructural changes that take place during this developmental period. These changes closely parallel those of live, developing human brain. The information obtained from this primate model of cerebral microstructure is directly applicable to studies of human development.

Algorithms↗