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Biomedical subjects

Petra S Huppi

Publications and source records attributed to Petra S Huppi.

8 recordsLinked to original sources

Functional MRI of the newborn.

In order to provide accurate prognosis and developmental intervention to newborns, new methods of assessing cerebral functions are needed. The non-invasive technique of functional magnetic resonance imaging (fMRI) can be considered as the leading technique for functional exploration of the infant's brain. Several studies have previously applied fMRI in both healthy and diseased newborns with different sensory and cognitive tasks. In this chapter, the methodological issues that are proper to the use of fMRI in the newborn are detailed. In addition, an overview of the major findings of previous fMRI studies is provided, with a focus on notable differences from those in adult subjects. More specifically, the functional responses and the localization of cortical activations in healthy and diseased newborns are discussed. We expect a rapid expansion of this field and the establishment of fMRI as a valid clinical diagnostic tool in the newborn.

Brain↗

Visual recovery after perinatal stroke evidenced by functional and diffusion MRI: case report.

BACKGROUND: After perinatal brain injury, clinico-anatomic correlations of functional deficits and brain plasticity remain difficult to evaluate clinically in the young infant. Thus, new non-invasive methods capable of early functional diagnosis are needed in young infants. CASE PRESENTATION: The visual system recovery in an infant with perinatal stroke is assessed by combining diffusion tensor imaging (DTI) and event-related functional MRI (ER-fMRI). All experiments were done at 1.5T. A first DTI experiment was performed at 12 months of age. At 20 months of age, a second DTI experiment was performed and combined with an ER-fMRI experiment with visual stimuli (2 Hz visual flash). At 20 months of age, ER-fMRI showed significant negative activation in the visual cortex of the injured left hemisphere that was not previously observed in the same infant. DTI maps suggest recovery of the optic radiation in the vicinity of the lesion. Optic radiations in the injured hemisphere are more prominent in DTI at 20 months of age than in DTI at 12 months of age. CONCLUSION: Our data indicate that functional cortical recovery is supported by structural modifications that concern major pathways of the visual system. These neuroimaging findings might contribute to elaborate a pertinent strategy in terms of diagnosis and rehabilitation.

Asphyxia Neonatorum↗

Late gestation cerebellar growth is rapid and impeded by premature birth.

OBJECTIVE: Cognitive impairments and academic failure are commonly reported in survivors of preterm birth. Recent studies suggest an important role for the cerebellum in the development of cognitive and social functions. The objective of this study was to examine the impact of prematurity itself, as well as prematurity-related brain injuries, on early postnatal cerebellar growth with quantitative MRI. METHODS: Advanced 3-dimensional volumetric MRI was performed and cerebellar volumes were obtained by manual outlining in preterm (<37 weeks) and healthy term-born infants. Intracranial and total brain volumes were also calculated. RESULTS: A total of 169 preterm and 20 healthy full-term infants were studied; 145 had preterm MRI (pMRI), 75 had term MRI (tMRI), and 51 underwent both pMRI and tMRI. From 28 weeks' postconceptional age to term, mean cerebellar volume (177%) in preterm infants increased at a much faster rate than did mean intracranial (110%) or mean brain (107%) volumes. Smaller cerebellar volume was significantly related to lower gestational age at birth and to intracranial and total brain volumes. Mean cerebellar volume of preterm infants at tMRI was significantly smaller than the volumes of term-born infants. Cerebellar growth impairment was correlated strongly with associated brain injuries, even in the absence of direct cerebellar injury. CONCLUSIONS: Our data suggest that the growth of the immature cerebellum is particularly rapid during late gestation. However, this accelerated growth seems to be impeded by premature birth and associated brain injury. The long-term neurodevelopmental disabilities seen in survivors of premature birth may be attributable in part to impaired cerebellar development.

Analysis of Variance↗

Structural and functional brain development after hydrocortisone treatment for neonatal chronic lung disease.

OBJECTIVE: There is much concern about potential neurodevelopmental impairment after neonatal corticosteroid treatment for chronic lung disease. Dexamethasone is the corticosteroid most often used in this clinical setting, and it has been shown to impair cortical growth among preterm infants. This study evaluated long-term effects of prematurity itself and of neonatal hydrocortisone treatment on structural and functional brain development using three-dimensional MRI with advanced image-processing and neurocognitive assessments. METHODS: Sixty children born preterm, including 25 children treated with hydrocortisone and 35 children not treated with hydrocortisone, and 21 children born at term were evaluated, at a mean age of 8 years, with quantitative MRI and neurocognitive assessments (Wechsler Intelligence Scales for Children-Revised [WISC-R]). Automatic image segmentation was used to determine the tissue volumes of cerebral gray matter, white matter, and cerebrospinal fluid. In addition, the volume of the hippocampus was determined manually. WISC-R scores were recorded as mean intelligence scores at evaluation. Neonatal hydrocortisone treatment for chronic lung disease consisted of a starting dose of 5 mg/kg per day tapered over a minimum of 3 weeks. RESULTS: Cerebral gray matter volume was reduced among preterm children (regardless of hydrocortisone treatment), compared with children born at term (preterm: 649 +/- 4.4 mL; term: 666 +/- 7.3 mL). Birth weight was shown to correlate with gray matter volume at 8 years of age in the preterm group (r = 0.421). Cerebrospinal fluid volume was increased among children born preterm, compared with children born at term (preterm: 228 +/- 4.9 mL; term: 206 +/- 8.2 mL). Total hippocampal volume tended to be lower among children born preterm, with a more pronounced reduction of hippocampal volume among boys (preterm: 6.1 +/- 0.13 mL; term: 6.56 +/- 0.2 mL). The WISC-R score was lower for children born preterm, compared with children born at term (preterm: 99.4 +/- 12.4; term: 109.6 +/- 8.8). Children treated with neonatal hydrocortisone had very similar volumes of gray matter (preterm with hydrocortisone: 650 +/- 7.0 mL; preterm without hydrocortisone: 640 +/- 5.6 mL), white matter (preterm with hydrocortisone: 503 +/- 6.1 mL; preterm without hydrocortisone: 510 +/- 4.9 mL), and cerebrospinal fluid (preterm with hydrocortisone: 227 +/- 7.4 mL; preterm without hydrocortisone: 224 +/- 6.0 mL), compared with untreated infants. The hippocampal volumes were similar in the 2 groups (preterm with hydrocortisone: 5.92 +/- 0.15 mL; preterm without hydrocortisone: 5.81 +/- 0.12 mL). The WISC-R score assessments were within the normal range for both groups, with no difference between the groups (preterm with hydrocortisone: 100.8 +/- 13; preterm without hydrocortisone: 98.6 +/- 12.3). CONCLUSIONS: Prematurity is associated with mild brain structural differences that persist at 8 years of age, with associated lower scores in neurocognitive assessments. The data suggest that perinatal hydrocortisone given at the described dosage has no long-term effects on either neurostructural brain development or neurocognitive outcomes.

Anti-Inflammatory Agents↗

Impaired trophic interactions between the cerebellum and the cerebrum among preterm infants.

BACKGROUND: Advanced neuroimaging techniques have brought increasing recognition of cerebellar injury among premature infants. The developmental relationship between early brain injury and effects on the cerebrum and cerebellum remains unclear. OBJECTIVES: To examine whether cerebral parenchymal brain lesions among preterm infants are associated with subsequent decreases in cerebellar volume and, conversely, whether primary cerebellar injury is associated with decreased cerebral brain volumes, with advanced, 3-dimensional, volumetric MRI at term gestational age equivalent. METHODS: Total cerebellar volumes and cerebellar gray and myelinated white matter volumes were determined through manual outlining for 74 preterm infants with unilateral periventricular hemorrhagic infarction (14 infants), bilateral diffuse periventricular leukomalacia (20 infants), cerebellar hemorrhage (10 infants), or normal term gestational age equivalent MRI findings (30 infants). Total brain and right/left cerebral and cerebellar hemispheric volumes were calculated. RESULTS: Unilateral cerebral brain injury was associated with significantly decreased volume of the contralateral cerebellar hemisphere. Conversely, unilateral primary cerebellar injury was associated with a contralateral decrease in supratentorial brain volume. Cerebellar gray matter and myelinated white matter volumes were reduced significantly not only among preterm infants with primary cerebellar hemorrhage but also among infants with cerebral parenchymal brain injury. CONCLUSIONS: These data suggest strongly that both reduction in contralateral cerebellar volume with unilateral cerebral parenchymal injury and reduction in total cerebellar volume with bilateral cerebral lesions are related to trophic transsynaptic effects. Early-life cerebellar injury may contribute importantly to the high rates of cognitive, behavioral, and motor deficits reported for premature infants.

Cerebellum↗

Early alteration of structural and functional brain development in premature infants born with intrauterine growth restriction.

Placental insufficiency with fetal intrauterine growth restriction (IUGR) is an important cause of perinatal mortality and morbidity and is subsequently associated with significant neurodevelopmental impairment in cognitive function, attention capacity, and school performance. The underlying biologic cause for this association is unclear. Twenty-eight preterm infants (gestational age 32.5 +/- 1.9 wk) were studied by early and term magnetic resonance imaging (MRI). An advanced quantitative volumetric three-dimensional MRI technique was used to measure brain tissue volumes in 14 premature infants with placental insufficiency, defined by abnormal antenatal Doppler measurements and mean birth weights <10(th) percentile (1246 +/- 299 g) (IUGR) and in 14 preterm infants matched for gestational age with normal mean birth weights 1843 +/- 246 g (control). Functional outcome was measured at term in all infants by a specialized assessment scale of preterm infant behavior. Premature infants with IUGR had a significant reduction in intracranial volume (mean +/- SD: 253.7 +/- 29.9 versus 300.5 +/- 43.5 mL, p < 0.01) and in cerebral cortical gray matter (mean +/- SD: 77.2 +/- 16.3 versus 106.8 +/- 24.6 mL, p < 0.01) when measured within the first 2 wk of life compared with control premature infants. These findings persisted at term with intracranial volume (mean +/- SD: 429.3 +/- 47.9 versus 475.9 +/- 53.4 mL, p < 0.05) and cerebral cortical gray matter (mean +/- SD: 149.3 +/- 29.2 versus 189 +/- 34.2 mL, p < 0.01). Behavioral assessment at term showed a significantly less mature score in the subsystem of attention-interaction availability in IUGR infants (p < 0.01). Cerebral cortical gray matter volume at term correlated with attention-interaction capacity measured at term (r = 0.45, p < 0.05). These results suggest that placental insufficiency with IUGR have specific structural and functional consequences on cerebral cortical brain development. These findings may provide insight into the structural-functional correlate for the developmental deficits associated with IUGR.

Brain↗

Combination of event-related fMRI and diffusion tensor imaging in an infant with perinatal stroke.

Focal ischemic brain injury, or stroke, is an important cause of later handicap in children. Early assessment of structure-function relationships after such injury will provide insight into clinico-anatomic correlation and potentially guide early intervention strategies. We used combined functional MRI (fMRI) with diffusion tensor imaging (DTI) in a 3-month-old infant to explore the structure-function relationship after unilateral perinatal stroke that involved the visual pathways. With visual stimuli, fMRI showed a negative BOLD activation in the visual cortex of the intact right hemisphere, principally in the anterior part, and no activation in the injured hemisphere. The functional activation in the intact hemisphere correlated clearly with the fiber tract of the optic radiation visualized with DTI. DTI confirmed the absence of the optic radiation in the damaged left hemisphere. In addition, event-related fMRI (ER-fMRI) experiments were performed to define the characteristics of the BOLD response. The shape is that of an inverted gamma function (similar to a negative mirror image of the known positive adult BOLD response). The maximum decrease was reached at 5-7 s with signal changes of -1.7 +/- 0.4%.Thus, this report describes for the first time the combined use of DTI and event-related fMRI in an infant and provides insight into the localization of the fMRI visual response in the young infant and the characteristics of the BOLD response.

Asphyxia Neonatorum↗

Early experience alters brain function and structure.

OBJECTIVE: To investigate the effects of early experience on brain function and structure. METHODS: A randomized clinical trial tested the neurodevelopmental effectiveness of the Newborn Individualized Developmental Care and Assessment Program (NIDCAP). Thirty preterm infants, 28 to 33 weeks' gestational age (GA) at birth and free of known developmental risk factors, participated in the trial. NIDCAP was initiated within 72 hours of intensive care unit admission and continued to the age of 2 weeks, corrected for prematurity. Control (14) and experimental (16) infants were assessed at 2 weeks' and 9 months' corrected age on health status, growth, and neurobehavior, and at 2 weeks' corrected age additionally on electroencephalogram spectral coherence, magnetic resonance diffusion tensor imaging, and measurements of transverse relaxation time. RESULTS: The groups were medically and demographically comparable before as well as after the treatment. However, the experimental group showed significantly better neurobehavioral functioning, increased coherence between frontal and a broad spectrum of mainly occipital brain regions, and higher relative anisotropy in left internal capsule, with a trend for right internal capsule and frontal white matter. Transverse relaxation time showed no difference. Behavioral function was improved also at 9 months' corrected age. The relationship among the 3 neurodevelopmental domains was significant. The results indicated consistently better function and more mature fiber structure for experimental infants compared with their controls. CONCLUSIONS: This is the first in vivo evidence of enhanced brain function and structure due to the NIDCAP. The study demonstrates that quality of experience before term may influence brain development significantly.

Brain↗