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P S Hüppi

Publications and source records attributed to P S Hüppi.

15 recordsLinked to original sources

Early assessment of brain maturation by MR imaging segmentation in neonates and premature infants.

PURPOSE: We evaluated the impact of premature extrauterine life on brain maturation. PATIENTS AND METHODS: Twelve neonates underwent MR imaging at 40 (39.64 +/- 0.98) weeks (full term). Fifteen premature infants underwent 2 MR imaging examinations, after birth (preterm at birth) and at 40 weeks (41.03 +/- 1.33) (preterm at term). A 3D MR imaging technique was used to measure brain volumes compared with intracranial volume: total brain volume, cortical gray matter, myelinated white matter, unmyelinated white matter, basal ganglia (BG), and CSF. RESULTS: The average absolute volume of intracranial volume (269.8 mL +/- 36.5), total brain volume (246.5 +/- 32.3), cortical gray matter (85.53 mL +/- 22.23), unmyelinated white matter (142.4 mL +/-14.98), and myelinated white matter (6.099 mL +/-1.82) for preterm at birth was significantly lower compared with that for the preterm at term: the average global volume of intracranial volume (431.7 +/- 69.98), total brain volume (391 +/- 66,1), cortical gray matter (179 mL +/- 41.54), unmyelinated white matter (185.3 mL +/- 30.8), and myelinated white matter (10.66 mL +/- 3.05). It was also lower compared with that of full-term infants: intracranial volume (427.4 mL +/- 53.84), total brain volume (394 +/- 49.22), cortical gray matter (181.4 +/- 29.27), unmyelinated white matter (183.4 +/- 27.37), and myelinated white matter (10.72 +/- 4.63). The relative volume of cortical gray matter (30.62 +/- 5.13) and of unmyelinated white matter (53.15 +/- 4.8) for preterm at birth was significantly different compared with the relative volume of cortical gray matter (41.05 +/- 5.44) and of unmyelinated white matter (43.22 +/- 5.11) for the preterm at term. Premature infants had similar brain tissue volumes at 40 weeks to full-term infants. CONCLUSION: MR segmentation techniques demonstrate that cortical neonatal maturation in moderately premature infants at term and term-born infants was similar.

Brain↗

Brain metabolite composition during early human brain development as measured by quantitative in vivo 1H magnetic resonance spectroscopy.

Biochemical maturation of the brain can be studied noninvasively by (1)H magnetic resonance spectroscopy (MRS) in human infants. Detailed time courses of cerebral tissue contents are known for the most abundant metabolites only, and whether or not premature birth affects biochemical maturation of the brain is disputed. Hence, the last trimester of gestation was observed in infants born prematurely, and their cerebral metabolite contents at birth and at expected term were compared with those of fullterm infants. Successful quantitative short-TE (1)H MRS was performed in three cerebral locations in 21 infants in 28 sessions (gestational age 32-43 weeks). The spectra were analyzed with linear combination model fitting, considerably extending the range of observable metabolites to include acetate, alanine, aspartate, cholines, creatines, gamma-aminobutyrate, glucose, glutamine, glutamate, glutathione, glycine, lactate, myo-inositol, macromolecular contributions, N-acetylaspartate, N-acetylaspartylglutamate, o-phosphoethanolamine, scyllo-inositol, taurine, and threonine. Significant effects of age and location were found for many metabolites, including the previously observed neuronal maturation reflected by an increase in N-acetylaspartate. Absolute brain metabolite content in premature infants at term was not considerably different from that in fullterm infants, indicating that prematurity did not affect biochemical brain maturation substantially in the studied population, which did not include infants of extremely low birthweight.

Aspartic Acid↗

Advanced magnetic resonance imaging techniques in perinatal brain injury.

Despite marked improvements in perinatal practice, perinatal brain injury remains one of the most common complications causing chronic handicapping conditions. Experimental advances have elucidated many of the cellular and vascular mechanisms of perinatal brain damage showing a correlation between the nature of the injury and the maturation of the brain. New diagnostic tools, such as quantitative three-dimensional magnetic resonance (MR) imaging, diffusion-weighted MR imaging and proton MR spectroscopy, are presented in this review article that allow to assess brain development, detect early brain injury and monitor effects of perinatal brain injury on subsequent brain development and brain plasticity. These techniques will guide future therapeutic interventions aimed at minimizing irreversible perinatal brain injury.

Animals↗

Microstructural brain development after perinatal cerebral white matter injury assessed by diffusion tensor magnetic resonance imaging.

OBJECTIVE: Brain injury in premature infants is characterized predominantly by perinatally acquired lesions in the cerebral white matter (WM). The impact of such injury on the subsequent development of cerebral WM is not clear. This study uses diffusion tensor magnetic resonance imaging (MRI) to evaluate the effects of cerebral WM injury on subsequent microstructural brain development in different WM areas of the brain. METHODS: Twenty premature infants (gestational age: 29.1 +/- 1.9 weeks) were studied by conventional MRI within the first 3 weeks of life and again at term, with the addition at the latter time of diffusion tensor MRI. Ten of the preterm infants had cerebral WM injury identified by the early MRI and were matched with 10 premature infants of similar gestational age and neonatal course but with normal neonatal MRI scans. Diffusion tensor MRI at term was acquired in coronal and axial planes and used to determine the apparent diffusion coefficient, a measure of overall restriction to water diffusion, and the relative anisotropy (RA), a measure of preferred directionality of diffusion, in central WM, anterior frontal WM, occipital WM, temporal WM, and the posterior limb of the internal capsule. Diffusion vector maps were generated from the diffusion tensor analysis to define the microstructural architecture of the cerebral WM regions. RESULTS: At term, the diffusion tensor MRI revealed no difference in apparent diffusion coefficient among preterm infants with or without perinatal WM lesions. By contrast, RA, the measure of preferred directionality of diffusion and thereby dependent on development of axonal fibers and oligodendroglia, was 25% lower in central WM, the principal site of the original WM injury. However, RA was unaffected in relatively uninjured WM areas, such as temporal, anterior frontal, and occipital regions. Notably, RA values in the internal capsule, which contains fibers that descend from the injured cerebral WM, were 20% lower in the infants with WM injury versus those without. Diffusion vector maps showed striking alterations in the size, orientation, and organization of fiber tracts in central WM and in those descending to the internal capsule. CONCLUSIONS: Perinatal cerebral WM injury seems to have major deleterious effects on subsequent development of fiber tracts both in the cerebral WM and more distally. The ultimate impact of brain injury in the newborn should be considered as a function not only of tissue destruction, but also of impaired subsequent brain development.

Humans↗

MR imaging and spectroscopy of brain development.

MR imaging provides an invaluable tool for the study of brain development in vivo. Current MR imaging techniques allow noninvasive methodologies, without ionizing radiation, that provide a diversity of information on structure, metabolism, and function of the developing brain. This article focuses on the application of conventional and advanced MR imaging techniques, including quantitative morphometric MR imaging, diffusion-weighted, functional MR, and MR spectroscopic imaging to the study of early human brain development.

Brain↗

Quantitative magnetic resonance imaging of brain development in premature and mature newborns.

Definition in the living premature infant of the anatomical and temporal characteristics of development of critical brain structures is crucial for insight into the time of greatest vulnerability of such brain structures. We used three-dimensional magnetic resonance imaging (3D MRI) and image-processing algorithms to quantitate total brain volume and total volumes of cerebral gray matter (GM), unmyelinated white matter (WM), myelinated WM, and cerebrospinal fluid (CSF) in 78 premature and mature newborns (postconceptional age, 29-41 weeks). Total brain tissue volume was shown to increase linearly at a rate of 22 ml/wk. Total GM showed a linear increase in relative intracranial volume of approximately 1.4% or 15 ml in absolute volume per week. The pronounced increase in total GM reflected primarily a fourfold increase in cortical GM. Unmyelinated WM was found to be the most prominent brain tissue class in the preterm infant younger than 36 weeks of postconceptional age. Although minimal myelinated WM was present in the preterm infant at 29 weeks, between 35 and 41 weeks an abrupt fivefold increase in absolute volume of myelinated WM was documented. Extracerebral and intraventricular CSF was readily quantitated by this technique and found to change minimally. The application of 3D MRI and tissue segmentation to the study of human infant brain from 29 to 41 weeks of postconceptional age has provided new insights into cerebral cortical development and myelination and has for the first time provided means of quantitative assessment in vivo of early human brain development.

Body Composition↗

Microstructural development of human newborn cerebral white matter assessed in vivo by diffusion tensor magnetic resonance imaging.

Alterations of the architecture of cerebral white matter in the developing human brain can affect cortical development and result in functional disabilities. A line scan diffusion-weighted magnetic resonance imaging (MRI) sequence with diffusion tensor analysis was applied to measure the apparent diffusion coefficient, to calculate relative anisotropy, and to delineate three-dimensional fiber architecture in cerebral white matter in preterm (n = 17) and full-term infants (n = 7). To assess effects of prematurity on cerebral white matter development, early gestation preterm infants (n = 10) were studied a second time at term. In the central white matter the mean apparent diffusion coefficient at 28 wk was high, 1.8 microm2/ms, and decreased toward term to 1.2 microm2/ms. In the posterior limb of the internal capsule, the mean apparent diffusion coefficients at both times were similar (1.2 versus 1.1 microm2/ms). Relative anisotropy was higher the closer birth was to term with greater absolute values in the internal capsule than in the central white matter. Preterm infants at term showed higher mean diffusion coefficients in the central white matter (1.4 +/- 0.24 versus 1.15 +/- 0.09 microm2/ms, p = 0.016) and lower relative anisotropy in both areas compared with full-term infants (white matter, 10.9 +/- 0.6 versus 22.9 +/- 3.0%, p = 0.001; internal capsule, 24.0 +/- 4.44 versus 33.1 +/- 0.6% p = 0.006). Nonmyelinated fibers in the corpus callosum were visible by diffusion tensor MRI as early as 28 wk; full-term and preterm infants at term showed marked differences in white matter fiber organization. The data indicate that quantitative assessment of water diffusion by diffusion tensor MRI provides insight into microstructural development in cerebral white matter in living infants.

Anisotropy↗

Magnetic resonance techniques in the evaluation of the newborn brain.

MR imaging provides unequaled sensitivity as compared with US or CT scanning for evaluating developmental changes and pathologic processes in the newborn brain. Myelination can be assessed qualitatively and quantitatively using newer 3D-MR imaging methods. MR imaging provides a much clearer delineation of many developmental disorders, including anomalies of migration and organization, as well as a variety of metabolic disorders and congenital infections. Neonatal intracranial hemorrhage is detected in all its locations by MR imaging. The timing of the hemorrhage is a unique feature of MR imaging. Venous thrombosis also can be identified by MR imaging and confirmed with MR angiography. HIE is the major cause of potentially preventable or reversible brain injury that results in considerable long-term neurologic morbidity. Early detection is crucial for interventions aimed at preventing or reversing ongoing injury. DWI can show early changes at the cellular level that are not detectable by any other imaging modality. MR spectroscopy has further opened the possibility of studying the metabolic mechanisms that define the pathophysiologic events taking place in neonatal brain injury. Both 31P-MR spectroscopy, as a marker of the acute changes in energy metabolism, and 1H-MR spectroscopy, with the measurement of lactate and the excitotoxic aminoacids glutamate and glutamine, have enabled us to study the early and late effects of insults to the newborn brain in a noninvasive fashion. Studies performed to determine the predictive value of MR spectroscopy for later neurodevelopmental outcome after HIE have shown promising results but need further evaluation on larger patient samples. The potential use of these methods in the evaluation of early neuroprotective treatment regimens in the newborn remains to be determined.

Brain↗

Structural and neurobehavioral delay in postnatal brain development of preterm infants.

Postnatal brain development of healthy prematurely born infants was assessed to study possible influence of premature birth and early extrauterine environment on structural, biochemical, and functional brain development. Myelination and differentiation of gray and white matter were studied by in vivo magnetic resonance (MR) imaging (MRI), changes in cerebral metabolism by 1HMR spectroscopy (MRS), and changes in early human neurobehavior by the assessment of preterm infant's behavior (APIB). The stage of intrauterine and extrauterine brain development in prematurely born infants at term was compared with the stage of mainly intrauterine brain development in a group of full-term infants. Eighteen preterm infants unremarkable with respect to neurologic and medical status were studied at approximately 2 wk of postnatal age [gestational age (GA) 1: 32.5 +/- 1.2 wk] and again at term (GA 2: 40.0 +/- 1.1 wk). For comparison a group of 13 full-term born infants (GA T: 40.6 +/- 2.1 wk) were studied by MR and six by APIB. When GA 2 to GA 1 was compared, significant maturational changes were found with MRI in gray and white matter and myelination, with 1H MRS in the concentration of N-acetylaspartate and with all scores of APIB. In preterm infants at term (GA 2) compared with full-term infants (GA T) significantly less gray and white matter differentiation and myelination was observed as well as significantly poorer performance in four neurobehavioral parameters (autonomic reactivity, motoric reactivity, state organization, attentional availability). We conclude that MRI and 1H MRS can be used to study postnatal brain development in preterm infants. Structural and biochemical maturation is accompanied by functional maturation as shown with the neurobehavior assessment. Preterm infants at term compared with full-term infants show a structural as well as a functional delay in brain development assessed at 40 wk of postconceptional age.

Age Factors↗

Regional metabolic assessment of human brain during development by proton magnetic resonance spectroscopy in vivo and by high-performance liquid chromatography/gas chromatography in autopsy tissue.

To study the course of regional metabolite concentrations during early brain development, we measured in vivo metabolites [N-acetyl-aspartate (NAA), choline-containing compounds, and myoinositol (M-Ino)] in the precentral area of the cerebrum by short echo-time single volume proton magnetic resonance spectroscopy and compared in vivo established spectroscopic data with classic chromatographic data (HPLC) on age-corresponding autopsy tissue in different regions of the brain. In autopsy tissue, regional (frontal lobe, precentral area, basal ganglia, thalamus) and age-dependent differences of the concentration of creatine, NAA, and M-Ino were determined. In vivo measurement of NAA by proton magnetic resonance spectroscopy shows a significant increase of NAA by increasing postconceptional age. M-Ino shows a weak correlation and a nonsignificant decrease with increasing postconceptional age. Choline shows no age-dependent changes. Creatine concentrations measured by HPLC in different regions of the developing brain at autopsy showed an age-dependent increase that was identical for the left and right side and similar for the precentral area and frontal lobe and more pronounced for the basal ganglia and thalamus. Comparison of the results obtained by the two methods shows agreement for the age-dependent changes and the absolute concentration of M-Ino. NAA determined in autopsy tissue by HPLC is significantly lower than that measured in vivo by proton magnetic resonance spectroscopy. A comparison of the concentrations measured by HPLC in frontal lobe, basal ganglia, and thalamus with the results obtained from the precentral area showed significant regional differences in all measured metabolites. These results define important age-dependent changes detected with both methods and further indicate limitations of both methods that have to be considered when presenting absolute concentration values.

Age Factors↗

Magnetic resonance in preterm and term newborns: 1H-spectroscopy in developing human brain.

Localized proton magnetic resonance spectra were recorded from human cerebellum in vivo with a 1.5-T magnet. The spectra from healthy adults and preterm and term babies showed resonances from N-acetylaspartate, creatine and phosphocreatine, choline-containing compounds such as phosphocholine and glycerophosphocholine, taurine, and inositol. The age-dependent changes of in vivo molar concentrations of N-acetylaspartate, choline, taurine, and inositol were estimated in preterm babies, babies at term, and adults. The range of postconceptional age in the studied babies was 31 to 45 wk. Taking the biochemically measured creatine concentrations in age-corresponding autopsy material as an internal standard, the in vivo concentrations of the other metabolites were calculated from the proton spectra. N-acetylaspartate showed an increase from 1.9 mM in preterm babies to 3.1 mM in term babies and to 6.5 mM in adult brain. Taurine was noted to increase from 1.1 mM in preterm infants to 2.3 mM in term infants and did not decrease significantly in adult brain. Choline and inositol concentrations did not change significantly throughout the studied age groups. These new data on in vivo, localized 1H-spectroscopy show that it is a sensitive method for studying early metabolic brain development in humans.

Adult↗

Diffusion tensor imaging of normal and injured developing human brain - a technical review.

The application of diffusion tensor imaging (DTI) to the evaluation of developing brain remains an area of active investigation. This review focuses on the changes in DTI parameters which accompany both brain maturation and injury. The two primary pieces of information available from DTI studies-water apparent diffusion coefficient and diffusion anisotropy measures-change dramatically during development, reflecting underlying changes in tissue water content and cytoarchitecture. DTI parameters also change in response to brain injury. In this context, not only does DTI offer the possibility of detecting injury earlier than conventional imaging methods, but also appears more sensitive to disruption of white matter than any other imaging method. DTI offers unique insight into brain injury and maturation, and does so in a fashion that can be readily applied in a clinical setting.

Adolescent↗