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1.
Neuroimage ; 206: 116310, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31669303

RESUMO

Recent advances in image reconstruction techniques have enabled high resolution MRI studies of fetal brain development in human subjects. Rhesus macaques (Macaca mulatta) are valuable animal models for use in studies of fetal brain development due to the similarities between this species and humans in brain development and anatomy. There is a need to develop fetal brain templates for the rhesus macaque to facilitate the characterization of the normal brain growth trajectory and departures from this trajectory in rhesus models of neurodevelopmental disorders. Here we have developed unbiased population-based anatomical T2-weighted, fractional anisotropy (FA) and apparent diffusion coefficient (ADC) templates for fetal brain from MR images scanned at 3 time points over the second and third trimesters of the 168 day gestational term. Specifically, atlas images are constructed for brains at gestational ages of 85 days (G85, N = 18, 9 females), 110 days (G110, N = 10, 7 females) and 135 days (G135, N = 16, 7 females). We utilized this atlas to perform segmentation of fetal brain MR images and fetal brain volumetric and microstructure analysis. The T2-weighted template images facilitated characterization of the growth within six fetal brain regions. The template images of diffusion tensor indices provided information related to the maturation of white matter tracts. These growth trajectories are referenced to human studies of fetal brain development. Similarities in the temporal and regional patterns of brain growth over the corresponding periods of central nervous system development are identified between the two species. Atlas images are available online as a reference for registration, reconstruction, segmentation, and for longitudinal analysis of early fetal brain growth over this unique time window.

2.
Top Magn Reson Imaging ; 28(5): 265-273, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31592993

RESUMO

The white matter structure of the human brain undergoes critical developmental milestones in utero, which we can observe noninvasively using diffusion-weighted magnetic resonance imaging. In order to understand this fascinating developmental process, we must establish the variability inherent in such a challenging imaging environment and how measurable quantities can be transformed into meaningful connectomes. We review techniques for reconstructing and studying the brain connectome and explore promising opportunities for in utero studies that could lead to more accurate measurement of structural properties and allow for more refined and insightful analyses of the fetal brain. Opportunities for more sophisticated analyses of the properties of the brain and its dynamic changes have emerged in recent years, based on the development of iterative techniques to reconstruct motion-corrupted diffusion-weighted data. Although reconstruction quality is greatly improved, the treatment of fundamental quantities like edge strength requires careful treatment because of the specific challenges of imaging in utero. There are intriguing challenges to overcome, from those in analysis due to both imaging limitations and the significant changes in structural connectivity, to further image processing to address the specific properties of the target anatomy and quantification into a developmental connectome.


Assuntos
Encéfalo/embriologia , Conectoma/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Encéfalo/anatomia & histologia , Humanos , Processamento de Imagem Assistida por Computador
3.
Artigo em Inglês | MEDLINE | ID: mdl-31395540

RESUMO

Reconstruction of white matter connectivity in the fetal brain from in utero diffusion-weighted MRI faces many challenges, including subject motion, small anatomical scale, and limited image resolution and signal. These issues are compounded by the need to track significant changes in structural connectivity throughout development. We present an automated method for improved reliability and completeness of tract extraction across a wide range of gestational ages, based on the geometry of coherent patterns in streamline tractography, and apply it to the reconstruction of the corpus callosum. This method, focused specifically at addressing the challenges of fetal brain imaging, avoids depending on a tractography atlas and handles variations in size, shape, and tissue properties of developing brains, both between subjects and across ages. Although tractography from in utero MRI generally suffers from a significant number of misleading and missing pathways, we demonstrate the feasibility of extracting the coherent bundle of the corpus callosum while avoiding inappropriate diversions into other tracts.

4.
Pediatr Res ; 85(3): 299-304, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30635642

RESUMO

BACKGROUND: To assess whether postnatal plasma cholesterol levels are associated with microstructural and macrostructural regional brain development in preterm newborns. METHODS: Sixty preterm newborns (born 24-32 weeks gestational age) were assessed using MRI studies soon after birth and again at term-equivalent age. Blood samples were obtained within 7 days of each MRI scan to analyze for plasma cholesterol and lathosterol (a marker of endogenous cholesterol synthesis) levels. Outcomes were assessed at 3 years using the Bayley Scales of Infant Development, Third Edition. RESULTS: Early plasma lathosterol levels were associated with increased axial and radial diffusivities and increased volume of the subcortical white matter. Early plasma cholesterol levels were associated with increased volume of the cerebellum. Early plasma lathosterol levels were associated with a 2-point decrease in motor scores at 3 years. CONCLUSIONS: Higher early endogenous cholesterol synthesis is associated with worse microstructural measures and larger volumes in the subcortical white matter that may signify regional edema and worse motor outcomes. Higher early cholesterol is associated with improved cerebellar volumes. Further work is needed to better understand how the balance of cholesterol supply and endogenous synthesis impacts preterm brain development, especially if these may be modifiable factors to improve outcomes.

5.
Nat Med ; 24(3): 368-374, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29400709

RESUMO

Zika virus (ZIKV) is a flavivirus with teratogenic effects on fetal brain, but the spectrum of ZIKV-induced brain injury is unknown, particularly when ultrasound imaging is normal. In a pregnant pigtail macaque (Macaca nemestrina) model of ZIKV infection, we demonstrate that ZIKV-induced injury to fetal brain is substantial, even in the absence of microcephaly, and may be challenging to detect in a clinical setting. A common and subtle injury pattern was identified, including (i) periventricular T2-hyperintense foci and loss of fetal noncortical brain volume, (ii) injury to the ependymal epithelium with underlying gliosis and (iii) loss of late fetal neuronal progenitor cells in the subventricular zone (temporal cortex) and subgranular zone (dentate gyrus, hippocampus) with dysmorphic granule neuron patterning. Attenuation of fetal neurogenic output demonstrates potentially considerable teratogenic effects of congenital ZIKV infection even without microcephaly. Our findings suggest that all children exposed to ZIKV in utero should receive long-term monitoring for neurocognitive deficits, regardless of head size at birth.


Assuntos
Feto/virologia , Complicações Infecciosas na Gravidez/fisiopatologia , Infecção por Zika virus/virologia , Zika virus/patogenicidade , Animais , Modelos Animais de Doenças , Feminino , Feto/fisiopatologia , Humanos , Macaca nemestrina/virologia , Microcefalia/diagnóstico por imagem , Microcefalia/fisiopatologia , Microcefalia/virologia , Neurogênese/genética , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico por imagem , Complicações Infecciosas na Gravidez/virologia , Zika virus/genética , Infecção por Zika virus/genética , Infecção por Zika virus/fisiopatologia
6.
Reprod Sci ; 25(1): 64-73, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28330415

RESUMO

The placenta is a vital organ necessary for healthy fetal development. Placental insufficiency creates an in utero environment where the fetus is at risk of insufficient oxygen or nutrient exchange. This is primarily caused by impairment of either maternal or fetal circulation or vascular thrombosis such as placental infarction. As a result of placental dysfunction, affected fetuses may be growth restricted, neurologically impaired, and at risk of increased morbidity and mortality. In a cohort of 4 pregnant Rhesus macaques, we describe antenatal detection of naturally occurring intrauterine growth restriction (IUGR) and aberrant fetal neurodevelopment in 1 animal. Abnormal growth parameters were detected by Doppler ultrasound, and vascular insufficiency in the intervillous space was characterized by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Furthermore, placental oxygen reserve was shown to be reduced compared to control animals by measurements of placental water T2*. To characterize the effects of IUGR on fetal brain development, T2 and diffusion anisotropy images of the fetal brain were acquired in utero. Reduced brain volume and cerebral cortical surface area were apparent macroscopically. Microstructural abnormalities within the developing white matter and cerebral cortex were also observed through analysis of water diffusion anisotropy. After delivery by cesarean section, pathological examination confirmed placental insufficiency with hypoxia. These findings exemplify how DCE-MRI and T2*-based measurements of blood oxygenation within the placenta can provide noninvasive imaging methods for assessing in vivo placental health to potentially identify pregnancies affected by placental insufficiency and abnormal fetal neurodevelopment prior to the onset of fetal and neonatal distress.


Assuntos
Retardo do Crescimento Fetal/diagnóstico por imagem , Imagem por Ressonância Magnética , Placenta/diagnóstico por imagem , Insuficiência Placentária/diagnóstico por imagem , Animais , Feminino , Macaca mulatta , Circulação Placentária/fisiologia , Gravidez
7.
Pediatr Res ; 83(1-1): 93-101, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28915231

RESUMO

BackgroundHuman studies investigating the link between postnatal polyunsaturated fatty acids and preterm brain growth are limited, despite emerging evidence of potential effects on outcomes.MethodsSixty preterm neonates <32 weeks gestational age with magnetic resonance imaging (MRI) scanning at near-birth and near-term age were assessed for brain tissue volumes, including cortical gray matter, white matter, deep gray matter, cerebellum, brainstem, and ventricular cerebrospinal fluid. Red blood cell fatty acid content was evaluated within 1 week of each MRI scan. Neurodevelopmental outcome at 30-36 months corrected age was assessed.ResultsAdjusting for potential confounders, higher near-birth docosahexaenoic acid levels are associated with larger cortical gray matter, deep gray matter, and brainstem volumes and higher near-term levels with larger deep gray matter, cerebellar, and brainstem volumes at near-term age; lower near-birth linoleic acid levels are correlated with larger white matter volume at near-term age. By 30-36 months corrected age, larger cortical and deep gray matter, cerebellar, and brainstem volumes by term age are associated with improved language scores and larger cerebellar and brainstem volumes with improved motor scores.ConclusionSpecific polyunsaturated fatty acid levels have differential and time-dependent associations with brain region growth. Larger brain volumes are associated with improved outcomes at preschool age.


Assuntos
Encéfalo/anatomia & histologia , Encéfalo/diagnóstico por imagem , Sistema Nervoso Central/crescimento & desenvolvimento , Ácidos Graxos Insaturados/química , Recém-Nascido Prematuro/crescimento & desenvolvimento , Encéfalo/crescimento & desenvolvimento , Desenvolvimento Infantil/fisiologia , Pré-Escolar , Estudos de Coortes , Ácidos Docosa-Hexaenoicos/sangue , Eritrócitos/metabolismo , Ácidos Graxos/sangue , Idade Gestacional , Humanos , Processamento de Imagem Assistida por Computador , Imagem Tridimensional , Lactente , Recém-Nascido , Imagem por Ressonância Magnética , Transtornos do Neurodesenvolvimento , Resultado do Tratamento
8.
PLoS One ; 12(8): e0180866, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28846692

RESUMO

Accurately describing the anatomy of individual brains enables interlaboratory communication of functional and developmental studies and is crucial for possible surgical interventions. The human parietal lobe participates in multimodal sensory integration including language processing and also contains the primary somatosensory area. We describe detailed protocols to subdivide the parietal lobe, analyze morphological and volumetric characteristics, and create probabilistic atlases in MNI152 stereotaxic space. The parietal lobe was manually delineated on 3D T1 MR images of 30 healthy subjects and divided into four regions: supramarginal gyrus (SMG), angular gyrus (AG), superior parietal lobe (supPL) and postcentral gyrus (postCG). There was the expected correlation of male gender with larger brain and intracranial volume. We examined a wide range of anatomical features of the gyri and the sulci separating them. At least a rudimentary primary intermediate sulcus of Jensen (PISJ) separating SMG and AG was identified in nearly all (59/60) hemispheres. Presence of additional gyri in SMG and AG was related to sulcal features and volumetric characteristics. The parietal lobe was slightly (2%) larger on the left, driven by leftward asymmetries of the postCG and SMG. Intersubject variability was highest for SMG and AG, and lowest for postCG. Overall the morphological characteristics tended to be symmetrical, and volumes also tended to covary between hemispheres. This may reflect developmental as well as maturation factors. To assess the accuracy with which the labels can be used to segment newly acquired (unlabelled) T1-weighted brain images, we applied multi-atlas label propagation software (MAPER) in a leave-one-out experiment and compared the resulting automatic labels with the manually prepared ones. The results showed strong agreement (mean Jaccard index 0.69, corresponding to a mean Dice index of 0.82, average mean volume error of 0.6%). Stereotaxic probabilistic atlases of each subregion were obtained. They illustrate the physiological brain torque, with structures in the right hemisphere positioned more anteriorly than in the left, and right/left positional differences of up to 10 mm. They also allow an assessment of sulcal variability, e.g. low variability for parietooccipital fissure and cingulate sulcus. Illustrated protocols, individual label sets, probabilistic atlases, and a maximum-probability atlas which takes into account surrounding structures are available for free download under academic licences.


Assuntos
Lobo Parietal/anatomia & histologia , Adulto , Mapeamento Encefálico/métodos , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Lobo Parietal/diagnóstico por imagem , Adulto Jovem
9.
Hum Brain Mapp ; 38(9): 4322-4336, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28608653

RESUMO

Preterm birth is associated with brain injury and altered cognitive development. However, the consequences of extrauterine development are not clearly distinguished from perinatal brain injury. Therefore, we characterized cortical growth patterns from 30 to 46 postmenstrual weeks (PMW) in 27 preterm neonates (25-32 PMW at birth) without detectable brain injury on magnetic resonance imaging. We introduce surface-based morphometric descriptors that quantify radial (thickness) and tangential (area) change rates. Within a tensor-based morphometry framework, we use a temporally weighted formulation of regression to simultaneously model local age-related changes in cortical gray matter (GM) and underlying white matter (WM) mapped onto the cortical surface. The spatiotemporal pattern of GM and WM development corresponded to the expected gyrification time course of primary sulcal deepening and branching. In primary gyri, surface area and thickness rates were below average along sulcal pits and above average on gyral banks and crests in both GM and WM. Above average surface area rates in GM corresponded to emergence of secondary and tertiary folds. These findings map the development of neonatal cortical morphometry in the context of extrauterine brain development using a novel approach. Future studies may compare this developmental trajectory to preterm populations with brain injury. Hum Brain Mapp 38:4322-4336, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
Encéfalo/crescimento & desenvolvimento , Substância Cinzenta/crescimento & desenvolvimento , Recém-Nascido Prematuro/crescimento & desenvolvimento , Substância Branca/crescimento & desenvolvimento , Encéfalo/diagnóstico por imagem , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Imagem Tridimensional/métodos , Recém-Nascido , Imagem por Ressonância Magnética/métodos , Masculino , Tamanho do Órgão , Estudos Prospectivos , Substância Branca/diagnóstico por imagem
10.
J Neurosci ; 37(8): 1971-1983, 2017 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-28069920

RESUMO

Altered macroscopic anatomical characteristics of the cerebral cortex have been identified in individuals affected by various neurodevelopmental disorders. However, the cellular developmental mechanisms that give rise to these abnormalities are not understood. Previously, advances in image reconstruction of diffusion magnetic resonance imaging (MRI) have made possible high-resolution in utero measurements of water diffusion anisotropy in the fetal brain. Here, diffusion anisotropy within the developing fetal cerebral cortex is longitudinally characterized in the rhesus macaque, focusing on gestation day (G85) through G135 of the 165 d term. Additionally, for subsets of animals characterized at G90 and G135, immunohistochemical staining was performed, and 3D structure tensor analyses were used to identify the cellular processes that most closely parallel changes in water diffusion anisotropy with cerebral cortical maturation. Strong correlations were found between maturation of dendritic arbors on the cellular level and the loss of diffusion anisotropy with cortical development. In turn, diffusion anisotropy changes were strongly associated both regionally and temporally with cortical folding. Notably, the regional and temporal dependence of diffusion anisotropy and folding were distinct from the patterns observed for cerebral cortical surface area expansion. These findings strengthen the link proposed in previous studies between cellular-level changes in dendrite morphology and noninvasive diffusion MRI measurements of the developing cerebral cortex and support the possibility that, in gyroencephalic species, structural differentiation within the cortex is coupled to the formation of gyri and sulci.SIGNIFICANCE STATEMENT Abnormal brain morphology has been found in populations with neurodevelopmental disorders. However, the mechanisms linking cellular level and macroscopic maturation are poorly understood, even in normal brains. This study contributes new understanding to this subject using serial in utero MRI measurements of rhesus macaque fetuses, from which macroscopic and cellular information can be derived. We found that morphological differentiation of dendrites was strongly associated both regionally and temporally with folding of the cerebral cortex. Interestingly, parallel associations were not observed with cortical surface area expansion. These findings support the possibility that perturbed morphological differentiation of cells within the cortex may underlie abnormal macroscopic characteristics of individuals affected by neurodevelopmental disorders.


Assuntos
Córtex Cerebral/citologia , Córtex Cerebral/embriologia , Embrião de Mamíferos/citologia , Fatores Etários , Animais , Anisotropia , Mapeamento Encefálico , Córtex Cerebral/diagnóstico por imagem , Imagem de Tensor de Difusão , Embrião de Mamíferos/diagnóstico por imagem , Desenvolvimento Embrionário/fisiologia , Feminino , Idade Gestacional , Processamento de Imagem Assistida por Computador , Macaca mulatta , Imagem por Ressonância Magnética , Masculino , Proteínas Associadas aos Microtúbulos/metabolismo , Vias Neurais/embriologia , Vias Neurais/fisiologia , Organogênese , Gravidez , Estatística como Assunto , Vimentina/metabolismo
11.
Magn Reson Med ; 78(3): 909-916, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-27699879

RESUMO

PURPOSE: Maximization of the blood oxygen level-dependent (BOLD) functional MRI (fMRI) contrast requires the echo time of the MR sequence to match the T2* value of the tissue of interest, which is expected to be higher in the fetal brain compared with the brain of a child or an adult. METHODS: T2* values of the cortical plate/cortical gray matter tissue in utero in healthy fetuses from mid-gestation onward (20-36 gestational weeks) were measured using 3D T2* maps calculated from 2D dual-echo T2*-weighted data corrected for between-slice motion and reconstructed in 1.0 mm3 isotropic resolution from a sequence of multiple time points, together with 1.0 mm3 isotropic resolution T2-weighted structural data. RESULTS: Mean T2* relaxation times of the cortical tissue were about twice as high as those reported previously in adults. In a supporting experiment applying single seed analysis, default mode and auditory networks appeared better localized and less noisy while using an echo time of 100 ms versus 43 ms. The results of the previous study reporting a trend for T2* values to decrease with fetal age were reproduced and extended to include cortical tissues and subjects in earlier gestation (20-26 gestational weeks). CONCLUSION: The first measurement of T2* values in fetal cortical tissues suggested the appropriate echo time range for fetal BOLD fMRI protocol optimization to be 130-190 ms. Magn Reson Med 78:909-916, 2017. © 2016 International Society for Magnetic Resonance in Medicine.


Assuntos
Encéfalo/diagnóstico por imagem , Feto/diagnóstico por imagem , Imagem Tridimensional/métodos , Imagem por Ressonância Magnética/métodos , Diagnóstico Pré-Natal/métodos , Adulto , Feminino , Humanos , Masculino , Gravidez
12.
Nat Med ; 22(11): 1256-1259, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27618651

RESUMO

We describe the development of fetal brain lesions after Zika virus (ZIKV) inoculation in a pregnant pigtail macaque. Periventricular lesions developed within 10 d and evolved asymmetrically in the occipital-parietal lobes. Fetal autopsy revealed ZIKV in the brain and significant cerebral white matter hypoplasia, periventricular white matter gliosis, and axonal and ependymal injury. Our observation of ZIKV-associated fetal brain lesions in a nonhuman primate provides a model for therapeutic evaluation.


Assuntos
Encéfalo/diagnóstico por imagem , Feto/diagnóstico por imagem , Complicações Infecciosas na Gravidez/diagnóstico por imagem , Infecção por Zika virus/diagnóstico por imagem , Animais , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/virologia , Colina/metabolismo , Creatina/metabolismo , Ecoencefalografia , Feminino , Feto/metabolismo , Feto/patologia , Feto/virologia , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Inositol/metabolismo , Macaca nemestrina , Imagem por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Gravidez , Complicações Infecciosas na Gravidez/metabolismo , Complicações Infecciosas na Gravidez/patologia , RNA Viral/metabolismo , Ultrassonografia Pré-Natal , Zika virus/genética , Infecção por Zika virus/metabolismo , Infecção por Zika virus/patologia
13.
Hum Brain Mapp ; 37(11): 4158-4178, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27510837

RESUMO

Recently, there has been considerable interest, especially for in utero imaging, in the detection of functional connectivity in subjects whose motion cannot be controlled while in the MRI scanner. These cases require two advances over current studies: (1) multiecho acquisitions and (2) post processing and reconstruction that can deal with significant between slice motion during multislice protocols to allow for the ability to detect temporal correlations introduced by spatial scattering of slices into account. This article focuses on the estimation of a spatially and temporally regular time series from motion scattered slices of multiecho fMRI datasets using a full four-dimensional (4D) iterative image reconstruction framework. The framework which includes quantitative MRI methods for artifact correction is evaluated using adult studies with and without motion to both refine parameter settings and evaluate the analysis pipeline. ICA analysis is then applied to the 4D image reconstruction of both adult and in utero fetal studies where resting state activity is perturbed by motion. Results indicate quantitative improvements in reconstruction quality when compared to the conventional 3D reconstruction approach (using simulated adult data) and demonstrate the ability to detect the default mode network in moving adults and fetuses with single-subject and group analysis. Hum Brain Mapp 37:4158-4178, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Imagem Tridimensional/métodos , Imagem por Ressonância Magnética/métodos , Diagnóstico Pré-Natal , Adulto , Algoritmos , Encéfalo/embriologia , Simulação por Computador , Feminino , Humanos , Modelos Lineares , Masculino , Modelos Neurológicos , Movimento (Física) , Vias Neurais/diagnóstico por imagem , Vias Neurais/embriologia , Vias Neurais/fisiologia , Gravidez , Terceiro Trimestre da Gravidez , Descanso
14.
J Pediatr ; 172: 81-87.e2, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26763312

RESUMO

OBJECTIVE: To examine the relationship between morphine exposure and growth of the cerebellum and cerebrum in very preterm neonates from early in life to term-equivalent age, as well as to examine morphine exposure and brain volumes in relation to neurodevelopmental outcomes at 18 months corrected age (CA). STUDY DESIGN: A prospective cohort of 136 very preterm neonates (24-32 weeks gestational age) was serially scanned with magnetic resonance imaging near birth and at term-equivalent age for volumetric measurements of the cerebellum and cerebrum. Motor outcomes were assessed with the Peabody Developmental Motor Scales, Second Edition and cognitive outcomes with the Bayley Scales of Infant and Toddler Development, Third Edition at 18 months CA. Generalized least squares models and linear regression models were used to assess relationships between morphine exposure, brain volumes, and neurodevelopmental outcomes. RESULTS: A 10-fold increase in morphine exposure was associated with a 5.5% decrease in cerebellar volume, after adjustment for multiple clinical confounders and total brain volume (P = .04). When infants exposed to glucocorticoids were excluded, the association of morphine was more pronounced, with an 8.1% decrease in cerebellar volume. Morphine exposure was not associated with cerebral volume (P = .30). Greater morphine exposure also predicted poorer motor (P < .001) and cognitive outcomes (P = .006) at 18 months CA, an association mediated, in part, by slower brain growth. CONCLUSIONS: Morphine exposure in very preterm neonates is independently associated with impaired cerebellar growth in the neonatal period and poorer neurodevelopmental outcomes in early childhood. Alternatives to better manage pain in preterm neonates that optimize brain development and functional outcomes are urgently needed.


Assuntos
Analgésicos Opioides/efeitos adversos , Cerebelo/anormalidades , Cerebelo/efeitos dos fármacos , Cérebro/crescimento & desenvolvimento , Deficiências do Desenvolvimento/induzido quimicamente , Morfina/efeitos adversos , Malformações do Sistema Nervoso/induzido quimicamente , Cerebelo/crescimento & desenvolvimento , Cérebro/efeitos dos fármacos , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro/crescimento & desenvolvimento , Imagem por Ressonância Magnética , Masculino , Estudos Prospectivos
15.
Neuroimage ; 127: 387-408, 2016 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-26702777

RESUMO

Accurate automated tissue segmentation of premature neonatal magnetic resonance images is a crucial task for quantification of brain injury and its impact on early postnatal growth and later cognitive development. In such studies it is common for scans to be acquired shortly after birth or later during the hospital stay and therefore occur at arbitrary gestational ages during a period of rapid developmental change. It is important to be able to segment any of these scans with comparable accuracy. Previous work on brain tissue segmentation in premature neonates has focused on segmentation at specific ages. Here we look at solving the more general problem using adaptations of age specific atlas based methods and evaluate this using a unique manually traced database of high resolution images spanning 20 gestational weeks of development. We examine the complimentary strengths of age specific atlas-based Expectation-Maximization approaches and patch-based methods for this problem and explore the development of two new hybrid techniques, patch-based augmentation of Expectation-Maximization with weighted fusion and a spatial variability constrained patch search. The former approach seeks to combine the advantages of both atlas- and patch-based methods by learning from the performance of the two techniques across the brain anatomy at different developmental ages, while the latter technique aims to use anatomical variability maps learnt from atlas training data to locally constrain the patch-based search range. The proposed approaches were evaluated using leave-one-out cross-validation. Compared with the conventional age specific atlas-based segmentation and direct patch based segmentation, both new approaches demonstrate improved accuracy in the automated labeling of cortical gray matter, white matter, ventricles and sulcal cortical-spinal fluid regions, while maintaining comparable results in deep gray matter.


Assuntos
Encéfalo/anatomia & histologia , Processamento de Imagem Assistida por Computador/métodos , Recém-Nascido Prematuro , Imagem por Ressonância Magnética/métodos , Neuroimagem/métodos , Algoritmos , Feminino , Humanos , Recém-Nascido , Masculino
16.
Front Neuroanat ; 9: 147, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26635541

RESUMO

Distinct populations of progenitor and postmitotic neural and glial cells are stratified in the fetal primate brain across developmentally transient tissue zones between the ventricular and pial surfaces. These zones were originally identified by light microscopy. However, it has subsequently been shown that various forms of magnetic resonance image (MRI) contrast can be used to distinguish layers of developing neural tissue in ex vivo, as well as in vivo (including in utero) conditions. Here we compare mid-gestation rhesus macaque tissue zones identified using histological techniques to ex vivo as well as in utero MRI performed on the same brains. These data are compared to mid-gestation fetal human brain MRI results, obtained in utero. We observe strong similarity between MRI contrast in vivo and post mortem, which facilitates interpretation of in utero images based on the histological characterization performed here. Additionally, we observe differential correspondence between the various forms of ex vivo MRI contrast and microscopy data, with maps of the water apparent diffusion coefficient providing the closest match to histologically-identified lamina of the nonhuman primate brain. Examination of histology and post mortem MRI helps to provide a better understanding of cytoarchitectrual characteristics that give rise to in utero MRI contrast.

17.
Semin Perinatol ; 39(2): 105-12, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25813665

RESUMO

Magnetic resonance imaging of the human fetal brain has been a clinical tool for many years and provides valuable additional information to compliment more common ultrasound studies. Advances in both MRI acquisition and post processing over the last 10 years have enabled full 3D imaging and the accurate combination of data acquired in different head positions to create improved geometric integrity, tissue contrast, and resolution. This research is now motivating the development of new quantitative MRI-based techniques for clinical imaging that can more accurately characterize brain development and detect abnormalities. In this article, we will review some of the key areas that are driving changes in our understanding of fetal brain growth using quantitative measures derived from in utero MRI and the possible directions for its increased use in improving the evaluation of pregnancies and the accurate characterization of abnormal brain growth.


Assuntos
Encefalopatias/diagnóstico , Mapeamento Encefálico/instrumentação , Encéfalo/patologia , Imagem por Ressonância Magnética , Encéfalo/anatomia & histologia , Encéfalo/embriologia , Encefalopatias/embriologia , Encefalopatias/patologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética/instrumentação , Imagem por Ressonância Magnética/métodos , Gravidez , Diagnóstico Pré-Natal , Reprodutibilidade dos Testes , Razão Sinal-Ruído
18.
Int J Dev Neurosci ; 32: 3-10, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23831076

RESUMO

Recent advances in medical imaging are beginning to allow us to quantify brain tissue maturation in the growing human brain prior to normal term age, and are beginning to shed new light on early human brain growth. These advances compliment the work already done in cellular level imaging in animal and post mortem studies of brain development. The opportunities for collaborative research that bridges the gap between macroscopic and microscopic windows on the developing brain are significant. The aim of this paper is to provide a review of the current research into MR imaging of the living fetal brain with the aim of motivating improved interfaces between the two fields. The review begins with a description of faster MRI techniques that are capable of freezing motion of the fetal head during the acquisition of a slice, and how these have been combined with advanced post-processing algorithms to build 3D images from motion scattered slices. Such rich data has motivated the development of techniques to automatically label developing tissue zones within MRI data allowing their quantification in 3D and 4D within the normally growing fetal brain. These methods have provided the basis for later work that has created the first maps of tissue growth rate and cortical folding in normally developing brains in-utero. These measurements provide valuable findings that compliment those derived from post-mortem anatomy, and additionally allow for the possibility of larger population studies of the influence of maternal environmental and genes on early brain development.


Assuntos
Encéfalo/anatomia & histologia , Encéfalo/embriologia , Imagem por Ressonância Magnética , Fatores Etários , Feto/anatomia & histologia , Feto/embriologia , Humanos , Processamento de Imagem Assistida por Computador , Modelos Anatômicos , Diagnóstico Pré-Natal
19.
IEEE Trans Med Imaging ; 33(2): 272-89, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24108711

RESUMO

This paper presents an approach to 3-D diffusion tensor image (DTI) reconstruction from multi-slice diffusion weighted (DW) magnetic resonance imaging acquisitions of the moving fetal brain. Motion scatters the slice measurements in the spatial and spherical diffusion domain with respect to the underlying anatomy. Previous image registration techniques have been described to estimate the between slice fetal head motion, allowing the reconstruction of 3D a diffusion estimate on a regular grid using interpolation. We propose Approach to Unified Diffusion Sensitive Slice Alignment and Reconstruction (AUDiSSAR) that explicitly formulates a process for diffusion direction sensitive DW-slice-to-DTI-volume alignment. This also incorporates image resolution modeling to iteratively deconvolve the effects of the imaging point spread function using the multiple views provided by thick slices acquired in different anatomical planes. The algorithm is implemented using a multi-resolution iterative scheme and multiple real and synthetic data are used to evaluate the performance of the technique. An accuracy experiment using synthetically created motion data of an adult head and an experiment using synthetic motion added to sedated fetal monkey dataset show a significant improvement in motion-trajectory estimation compared to current state-of-the-art approaches. The performance of the method is then evaluated on challenging but clinically typical in utero fetal scans of four different human cases, showing improved rendition of cortical anatomy and extraction of white matter tracts. While the experimental work focuses on DTI reconstruction (second-order tensor model), the proposed reconstruction framework can employ any 5-D diffusion volume model that can be represented by the spatial parameterizations of an orientation distribution function.


Assuntos
Encéfalo/anatomia & histologia , Imagem de Tensor de Difusão/métodos , Feto/anatomia & histologia , Imagem Tridimensional/métodos , Diagnóstico Pré-Natal/métodos , Algoritmos , Feminino , Humanos , Gravidez
20.
Med Image Anal ; 18(2): 285-300, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24317121

RESUMO

This paper presents a method for intensity inhomogeniety removal in fMRI studies of a moving subject. In such studies, subtle changes in signal as the subject moves in the presence of a bias field can be a significant confound for BOLD signal analysis. The proposed method avoids the need for a specific tissue model or assumptions about tissue homogeneity by making use of the multiple views of the underlying bias field provided by the subject's motion. A parametric bias field model is assumed and a regression model is used to estimate the basis function weights of this model. Quantitative evaluation of the effects of motion and noise in motion estimates are performed using simulated data. Results demonstrate the strength and robustness of the new method compared to the state of the art 4D nonparametric bias estimator (N4ITK). We also qualitatively demonstrate the impact of the method on resting state neuroimage analysis of a moving adult brain with simulated motion and bias fields, as well as on in vivo moving fetal fMRI.


Assuntos
Mapeamento Encefálico/métodos , Encéfalo/crescimento & desenvolvimento , Processamento de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Adulto , Algoritmos , Artefatos , Encéfalo/embriologia , Simulação por Computador , Feminino , Humanos , Gravidez , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
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