-
[show abstract]
[hide abstract]
ABSTRACT: Cortical maturation was studied in 65 infants between 27 and 46 wk postconception using structural and diffusion magnetic resonance imaging. Alterations in neural structure and complexity were inferred from changes in mean diffusivity and fractional anisotropy, analyzed by sampling regions of interest and also by a unique whole-cortex mapping approach. Mean diffusivity was higher in gyri than sulci and in frontal compared with occipital lobes, decreasing consistently throughout the study period. Fractional anisotropy declined until 38 wk, with initial values and rates of change higher in gyri, frontal and temporal poles, and parietal cortex; and lower in sulcal, perirolandic, and medial occipital cortex. Neuroanatomical studies and experimental diffusion-anatomic correlations strongly suggested the interpretation that cellular and synaptic complexity and density increased steadily throughout the period, whereas elongation and branching of dendrites orthogonal to cortical columns was later and faster in higher-order association cortex, proceeding rapidly before becoming undetectable after 38 wk. The rate of microstructural maturation correlated locally with cortical growth, and predicted higher neurodevelopmental test scores at 2 y of age. Cortical microstructural development was reduced in a dose-dependent fashion by longer premature exposure to the extrauterine environment, and preterm infants at term-corrected age possessed less mature cortex than term-born infants. The results are compatible with predictions of the tension theory of cortical growth and show that rapidly developing cortical microstructure is vulnerable to the effects of premature birth, suggesting a mechanism for the adverse effects of preterm delivery on cognitive function.
Proceedings of the National Academy of Sciences 05/2013; · 9.68 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Fetal magnetic resonance imaging (MRI) is now routinely used to further investigate cerebellar malformations detected with ultrasound. However, the lack of 2D and 3D biometrics in the current literature hinders the detailed characterisation and classification of cerebellar anomalies. The main objectives of this fetal neuroimaging study were to provide normal posterior fossa growth trajectories during the second and third trimesters of pregnancy via semi-automatic segmentation of reconstructed fetal brain MR images and to assess common cerebellar malformations in comparison with the reference data. Using a 1.5-T MRI scanner, 143 MR images were obtained from 79 normal control and 53 fetuses with posterior fossa abnormalities that were grouped according to the severity of diagnosis on visual MRI inspections. All quantifications were performed on volumetric datasets, and supplemental outcome information was collected from the surviving infants. Normal growth trajectories of total brain, cerebellar, vermis, pons and fourth ventricle volumes showed significant correlations with 2D measurements and increased in second-order polynomial trends across gestation (Pearson r, p < 0.05). Comparison of normal controls to five abnormal cerebellum subgroups depicted significant alterations in volumes that could not be detected exclusively with 2D analysis (MANCOVA, p < 0.05). There were 15 terminations of pregnancy, 8 neonatal deaths, and a spectrum of genetic and neurodevelopmental outcomes in the assessed 24 children with cerebellar abnormalities. The given posterior fossa biometrics enhance the delineation of normal and abnormal cerebellar phenotypes on fetal MRI and confirm the advantages of utilizing advanced neuroimaging tools in clinical fetal research.
The Cerebellum 04/2013; · 3.21 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We studied methods for the automatic segmentation of neonatal and developing brain images into 50 anatomical regions, utilizing a new set of manually segmented magnetic resonance (MR) images from 5 term-born and 15 preterm infants imaged at term corrected age called ALBERTs. Two methods were compared: individual registrations with label propagation and fusion; and template based registration with propagation of a maximum probability neonatal ALBERT (MPNA). In both cases we evaluated the performance of different neonatal atlases and MPNA, and the approaches were compared with the manual segmentations by means of the Dice overlap coefficient. Dice values, averaged across regions, were 0.81±0.02 using label propagation and fusion for the preterm population, and 0.81±0.02 using the single registration of a MPNA for the term population. Segmentations of 36 further unsegmented target images of developing brains yielded visibly high-quality results. This registration approach allows the rapid construction of automatically labeled age-specific brain atlases for neonates and the developing brain.
PLoS ONE 01/2013; 8(4):e59990. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We propose a method for the reconstruction of volumetric fetal MRI from 2D slices, comprising super-resolution reconstruction of the volume interleaved with slice-to-volume registration to correct for the motion. The method incorporates novel intensity matching of acquired 2D slices and robust statistics which completely excludes identified misregistered or corrupted voxels and slices. The reconstruction method is applied to motion-corrupted data simulated from MRI of a preterm neonate, as well as 10 clinically acquired thick-slice fetal MRI scans and three scan-sequence optimized thin-slice fetal datasets. The proposed method produced high quality reconstruction results from all the datasets to which it was applied. Quantitative analysis performed on simulated and clinical data shows that both intensity matching and robust statistics result in statistically significant improvement of super-resolution reconstruction. The proposed novel EM-based robust statistics also improves the reconstruction when compared to previously proposed Huber robust statistics. The best results are obtained when thin-slice data and the correct approximation of the point spread function is used. This paper addresses the need for a comprehensive reconstruction algorithm of 3D fetal MRI, so far lacking in the scientific literature.
Medical image analysis 08/2012; · 3.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Premature birth is a major and growing problem. Investigations into neuroanatomical correlates and consequences of preterm birth are hampered by complex neonatal brain anatomy and unavailability of atlases and protocols covering the whole brain. We developed delineation protocols for the manual segmentation of cerebral magnetic resonance (MR) images from newborn infants into 50 regions with comprehensive coverage of the brain. We then segmented MR scans from 15 infants born preterm at median 29, range 26-35, weeks postmenstrual age and scanned at term-corrected age, and five term-born infants born at median 41, range 39-45, weeks postmenstrual age. Total and regional brain volumes were estimated in each infant, and regional volumes expressed as a fraction of total brain volume. Total brain volumes were higher with greater age at birth and at time of scan, but once corrected for age at scan there was no difference between preterm and term infants. Fractional age-corrected regional volumes were bigger unilaterally in terms in middle and inferior temporal gyri, anterior temporal lobe, fusiform gyrus and posterior cingulate gyrus. Fractional age-corrected regional volumes were larger in preterms bilaterally in hippocampus, amygdala, thalamus and lateral ventricles, left superior temporal gyrus and right caudate nucleus. These differences were not significant after correcting for multiple hypothesis testing, but suggest subtle differences between preterms and term-borns accessible to regional analysis. Detailed illustrated protocols are made available in the Appendix.
NeuroImage 06/2012; 62(3):1499-509. · 5.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To examine the spectrum of isolated white matter (WM)/cortical injury and its relation to outcomes in infants with hypoxic-ischemic encephalopathy (HIE) and normal appearing basal ganglia and thalami.
From 1992-2007, 84 term infants with HIE and normal basal ganglia and thalami on neonatal magnetic resonance imaging were studied; WM/cortical lesions were classified by site and severity. Neurodevelopmental outcomes and head growth were documented at a median age of 2 years.
The WM was normal or mildly abnormal in 33.5%, moderate in 40.5%, and severely abnormal in 26% of infants. Cortical involvement was not seen or was only mild in 75.5%, moderate in 13%, and severe in 12% of infants. WM and cortical injury severity were highly correlated (Spearman ρ = 0.74; P < .001). Infants with severe WM injury had more severe neonatal courses and a higher incidence of hypoglycemia. No infant died. Five infants (6%) developed cerebral palsy but all could walk independently. Cognitive, visual, language, behavioral, and seizure problems were highly prevalent and correlated significantly with the severity of WM injury and poor postnatal head growth.
Infants with HIE and selective WM/cortical injury have a low prevalence of cerebral palsy but have a wide range of other problems, which occur more often with severe WM/cortical lesions.
The Journal of pediatrics 06/2012; 161(5):799-807. · 4.02 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Basal ganglia and thalamic (BGT) injury is common after acute perinatal hypoxia-ischaemia. Cerebral palsy is the most obvious consequence of BGT injury affecting 70-75% of survivors and is predictable from neonatal magnetic resonance imaging (MRI). However there is no equivalent predictive data for other specific outcomes. Feeding and communication impairments are also common in children following hypoxic-ischaemic encephalopathy (HIE) and BGT injury.
To describe, in infants with HIE and BGT injury, the prevalence of feeding and communication impairments; and to evaluate the accuracy of early MRI for predicting these outcomes.
175 term infants with HIE and BGT injury were studied. Brain lesions were classified by site and severity from the MRI scans. Motor, feeding and communication impairments were documented at 2 years.
Feeding and communication impairments occurred in 65% and 82% of 126 survivors respectively and related strongly to the severity of motor impairment. Forty-one children had a gastrostomy or long-term nasogastric tube. Injury severity in all brain regions was significantly associated with feeding and communication impairment on univariate analysis. On logistic regression analysis BGT (OR 10.9) and mesencephalic lesions (OR 3.7) were independently associated with feeding impairment; BGT (OR 10.5) and pontine lesions (OR 3.8) were associated with gastrostomy; the severity of BGT lesions (OR 20.1) was related to the severity of communication impairment.
Feeding and communication impairment are very common in children with BGT and brainstem injury of neonatal origin and can be well predicted from early MRI scans.
European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 05/2012; 16(6):688-96. · 2.01 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Medical imaging has shown that, during early development, the brain undergoes more changes in size, shape and appearance than at any other time in life. A better understanding of brain development requires a spatio-temporal atlas that characterizes the dynamic changes during this period. In this paper we present an approach for constructing a 4D atlas of the developing brain, between 28 and 44 weeks post-menstrual age at time of scan, using T1 and T2 weighted MR images from 204 premature neonates. The method used for the creation of the average 4D atlas utilizes non-rigid registration between all pairs of images to eliminate bias in the atlas toward any of the original images. In addition, kernel regression is used to produce age-dependent anatomical templates. A novelty in our approach is the use of a time-varying kernel width, to overcome the variations in the distribution of subjects at different ages. This leads to an atlas that retains a consistent level of detail at every time-point. Comparisons between the resulting atlas and atlases constructed using affine and non-rigid registration are presented. The resulting 4D atlas has greater anatomic definition than currently available 4D atlases created using various affine and non-rigid registration approaches, an important factor in improving registrations between the atlas and individual subjects. Also, the resulting 4D atlas can serve as a good representative of the population of interest as it reflects both global and local changes. The atlas is publicly available at www.brain-development.org.
NeuroImage 02/2012; 59(3):2255-65. · 5.89 Impact Factor
-
Elise Roze,
Polly A Harris,
Gareth Ball,
Leire Zubiaurre Elorza,
Rodrigo M Braga,
Joanna M Allsop,
Nazakat Merchant,
Emma Porter,
Tomoki Arichi,
A David Edwards, Mary A Rutherford,
Frances M Cowan,
Serena J Counsell
[show abstract]
[hide abstract]
ABSTRACT: Our aims were to (1) assess the corticospinal tracts (CSTs) in infants with focal injury and healthy term controls using probabilistic tractography and (2) to correlate the conventional magnetic resonance imaging (MRI) and tractography findings in infants with focal injury with their later motor function.
We studied 20 infants with focal lesions and 23 controls using MRI and diffusion tensor imaging. Tract volume, fractional anisotropy (FA), apparent diffusion coefficient (ADC) values, axial diffusivity and radial diffusivity (RD) of the CSTs were determined. Asymmetry indices (AIs) were calculated by comparing ipsilateral to contralateral CSTs. Motor outcome was assessed using a standardized neurological examination.
Conventional MRI was able to predict normal motor development (n = 9) or hemiplegia (n = 6). In children who developed a mild motor asymmetry (n = 5), conventional MRI predicted a hemiplegia in two and normal motor development in three infants. The AIs for tract volume, FA, ADC and RD showed a significant difference between controls and infants who developed a hemiplegia, and RD also showed a significant difference in AI between controls and infants who developed a mild asymmetry.
Conventional MRI was able to predict subsequent normal motor development or hemiplegia following focal injury in newborn infants. Measures of RD obtained from diffusion tractography may offer additional information for predicting a subsequent asymmetry in motor function.
Neuroradiology 10/2011; 54(5):507-16. · 2.82 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Magnetic Resonance Imaging (MRI) has become an established technique in fetal medicine, providing complementary information to ultrasound in studies of the brain. MRI can provide detailed structural information irrespective of the position of the fetal head or maternal habitus. Proton Magnetic Resonance Spectroscopy ((1)HMRS) is based on the same physical principles as MRI but data are collected as a spectrum, allowing the biochemical and metabolic status of in vivo tissue to be studied in a non-invasive manner. (1)HMRS has been used to assess metabolic function in the neonatal brain but fetal studies have been limited, primarily due to fetal motion. This review will assess the technique and findings from fetal studies to date.
European journal of obstetrics, gynecology, and reproductive biology 09/2011; 158(1):3-8. · 1.97 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to investigate alterations in brain metabolism in fetuses with intrauterine growth restriction (IUGR) and evidence of cerebral redistribution of blood flow.
Biometry and Doppler assessment of blood flow was assessed with ultrasound in 28 fetuses with IUGR and cerebral redistribution and in 41 appropriately grown control subjects. Proton magnetic resonance spectroscopy of the fetal brain was then performed to determine the presence of choline (Cho), creatine (Cr), N-acetylaspartate (NAA), and lactate and to generate ratios for NAA:Cho, NAA:Cr, and Cho:Cr.
Sixty-five percent of spectra were interpretable: N-acetylaspartate, choline, and creatine peaks were identified in all these spectra; lactate was present in 5 IUGR fetuses and in 3 appropriately grown fetuses. NAA:Cr and NAA:Cho ratios were significantly lower in IUGR fetuses with cerebral redistribution.
Cerebral redistribution is associated with altered brain metabolism that is evidenced by a reduction in NAA:Cho and NAA:Cr ratios.
American journal of obstetrics and gynecology 06/2011; 205(5):483.e1-8. · 3.28 Impact Factor
-
Laura Bassi,
Andrew Chew,
Nazakat Merchant,
Gareth Ball,
Luca Ramenghi,
James Boardman,
Joanna M Allsop,
Valentina Doria,
Tomoki Arichi,
Fabio Mosca,
A David Edwards,
Frances M Cowan, Mary A Rutherford,
Serena J Counsell
[show abstract]
[hide abstract]
ABSTRACT: Our aim was to compare white matter (WM) microstructure in preterm infants with and without punctate WM lesions on MRI using tract-based spatial statistics (TBSS) and probabilistic tractography. We studied 23 preterm infants with punctate lesions, median GA at birth 30 (25-35) wk, and 23 GA- and sex-matched preterm controls. TBSS and tractography were performed to assess differences in fractional anisotropy (FA) between the two groups at term equivalent age. The impact of lesion load was assessed by performing linear regression analysis of the number of lesions on term MRI versus FA in the corticospinal tracts in the punctate lesions group. FA values were significantly lower in the posterior limb of the internal capsule, cerebral peduncles, decussation of the superior cerebellar peduncles, superior cerebellar peduncles, and pontine crossing tract in the punctate lesions group. There was a significant negative correlation between lesion load at term and FA in the corticospinal tracts (p = 0.03, adjusted r² = 0.467). In conclusion, punctate lesions are associated with altered microstructure in the WM fibers of the corticospinal tract at term equivalent age.
Pediatric Research 03/2011; 69(6):561-6. · 2.70 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To correlate the site and severity of brain lesions seen on magnetic resonance imaging (MRI) with the quality of general movements in term infants with hypoxic-ischemic encephalopathy (HIE) and compare the prognostic value of general movements and MRI for motor outcome.
Early brain MRI scans in 34 term infants with HIE not treated with hypothermia were reviewed and scored for site of injury and lesion pattern by an experienced neuroradiologist. General movement quality and trajectories at 1 and 3 postnatal months were evaluated. Motor outcome was assessed at 24 months.
MRI scores for the basal ganglia and thalami, posterior limb of the internal capsule, white matter, and cortex and lesion patterns were correlated with 1-month and 3-month general movements and general movement trajectories; central gray matter scores were correlated most strongly with cramped-synchronized general movements and abnormal motor outcome. MRI scores were 100% sensitive and 72.2% specific for motor outcome, and cramped-synchronized general movements were 100% specific and 68.7% sensitive for motor outcome.
In term infants with HIE, the site and severity of brain lesions seen on early MRI are highly correlated with general movements. Central gray matter damage leads to cramped-synchronized general movements and poor motor outcome. Early MRI scans and general movements are complementary tools for predicting motor outcome.
The Journal of pediatrics 01/2011; 158(6):904-11. · 4.02 Impact Factor
-
IEEE Trans. Med. Imaging. 01/2011; 30:2072-2086.
-
[show abstract]
[hide abstract]
ABSTRACT: Central grey matter damage following perinatal hypoxia-ischaemia frequently leads to death or motor abnormality often with deficits in other developmental domains. Predicting these different outcomes is difficult yet very important for early management, planning and providing for needs on discharge and later and not least for parents to know how their children will be affected. The best single predictor of the pattern of outcomes for an individual infant is an early MRI scan. We present a guide for predicting outcome at 2 years in different developmental domains based on the severity of injury seen in the basal ganglia and thalami (BGT) on neonatal MRI.
Early human development 11/2010; 86(11):675-82. · 2.12 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Preterm birth is associated with altered white matter microstructure, defined by metrics derived from diffusion tensor imaging (DTI). Tract-based spatial statistics (TBSS) is a useful tool for investigating developing white matter using DTI, but standard TBSS protocols have limitations for neonatal studies. We describe an optimised TBSS protocol for neonatal DTI data, in which registration errors are reduced. As chronic lung disease (CLD) is an independent risk factor for abnormal white matter development, we investigate the effect of this condition on white matter anisotropy and diffusivity using the optimised protocol in a proof of principle experiment. DTI data were acquired from 93 preterm infants (48 male) with a median gestational age at birth of 28(+5) (23(+4)-35(+2))weeks at a median postmenstrual age at scan of 41(+4) (38(+1)-46(+6))weeks. Nineteen infants developed CLD, defined as requiring supplemental oxygen at 36weeks postmenstrual age. TBSS was modified to include an initial low degrees-of-freedom linear registration step and a second registration to a population-average FA map. The additional registration steps reduced global misalignment between neonatal fractional anisotropy (FA) maps. Infants with CLD had significantly increased radial diffusivity (RD) and significantly reduced FA within the centrum semiovale, corpus callosum and inferior longitudinal fasciculus (p<0.05) compared to their peers, controlling for degree of prematurity and age at scan. The optimised TBSS protocol improved reliability for neonatal DTI analysis. These data suggest that potentially modifiable respiratory morbidity is associated with widespread altered white matter microstructure in preterm infants at term-equivalent age.
NeuroImage 10/2010; 53(1):94-102. · 5.89 Impact Factor
-
Maria Kuklisova-Murgasova,
Paul Aljabar,
Latha Srinivasan,
Serena J Counsell,
Valentina Doria,
Ahmed Serag,
Ioannis S Gousias,
James P Boardman, Mary A Rutherford,
A David Edwards,
Joseph V Hajnal,
Daniel Rueckert
[show abstract]
[hide abstract]
ABSTRACT: Probabilistic atlases are widely used in the neuroscience community as a tool for providing a standard space for comparison of subjects and as tissue priors used to enhance the intensity-based classification of brain MRI. Most efforts so far have focused on static brain atlases either for adult or pediatric cohorts. In contrast to the adult brain the rapid growth of the neonatal brain requires an age-specific spatial probabilistic atlas to provide suitable anatomical and structural information. In this paper we describe a 4D probabilistic atlas that allows dynamic generation of prior tissue probability maps for any chosen stage of neonatal brain development between 29 and 44 gestational weeks. The atlas is created from the segmentations of 142 neonatal subjects at different ages using a kernel-based regression method and provides prior tissue probability maps for six structures - cortex, white matter, subcortical grey matter, brainstem, cerebellum and cerebro-spinal fluid. The atlas is publicly available at www.brain-development.org.
NeuroImage 10/2010; 54(4):2750-63. · 5.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To prospectively evaluate the clinical effectiveness of snapshot inversion recovery (SNAPIR), which is a dedicated optimized inversion-recovery-prepared single-shot fast spin-echo T1-weighted sequence, in the delineation of normal fetal brain anatomy compared with that of the currently used T1-weighted gradient-echo protocol, which often yields images of poor quality due to motion artifacts and inadequate contrast.
This study was approved by the hospital research ethics committee, and informed written consent was obtained from all patients. Forty-one fetuses were examined at 19-37 weeks gestation (mean, 29 weeks gestation) by using both the standard T1-weighted protocol and the optimized T1-weighted SNAPIR protocol with a 1.5-T imager. Two independent blinded observers performed qualitative analysis, evaluating overall diagnostic quality, detailed anatomic delineation, and severity of motion artifacts. Quantitative analysis comprised calculation of contrast ratios (CRs) for the cortical gray matter, subplate, white matter, and cerebrospinal fluid. The Wilcoxon signed rank test was used to compare image rating scores, the paired t test was used to compare CRs, and κ statistics were used to test interobserver agreement.
Both overall diagnostic quality (P < .001) and detailed anatomic delineation (P < .001) were enhanced with SNAPIR compared with the standard T1-weighted acquisition. Also, motion artifacts were less severe (P = .008) and less extensive (P < .001) with SNAPIR. Corresponding CRs were increased with SNAPIR in seven of eight examined regions.
SNAPIR is a promising robust alternative to the current T1-weighted acquisitions; its role in the detection of disease requires further study.
Radiology 10/2010; 258(1):229-35. · 5.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Periventricular leucomalacia (PVL) and parenchymal venous infarction complicating germinal matrix/intraventricular haemorrhage have long been recognised as the two significant white matter diseases responsible for the majority of cases of cerebral palsy in survivors of preterm birth. However, more recent studies using magnetic resonance imaging to assess the preterm brain have documented two new appearances, adding to the spectrum of white matter disease of prematurity: punctate white matter lesions, and diffuse excessive high signal intensity (DEHSI). These appear to be more common than PVL but less significant in terms of their impact on individual neurodevelopment. They may, however, be associated with later cognitive and behavioural disorders known to be common following preterm birth. It remains unclear whether PVL, punctate lesions, and DEHSI represent a continuum of disorders occurring as a result of a similar injurious process to the developing white matter. This review discusses the role of MR imaging in investigating these three disorders in terms of aetiology, pathology, and outcome.
Neuroradiology 06/2010; 52(6):505-21. · 2.82 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Magnetic resonance imaging (MRI) is noninvasive and nonionizing and offers excellent soft-tissue contrast and good spatial resolution, providing anatomical detail that cannot be obtained by any other imaging modality. In this review, we discuss the imaging findings in perinatal arterial stroke, hypoxic ischemic encephalopathy, metabolic abnormalities, and infection. Conventional imaging can detect patterns of injury that relate to the etiology and timing of an insult and provide valuable information about prognosis. In many cases, diffusion-weighted imaging provides additional information to conventional MRI, and we recommend its use in all clinical MRI investigations. We also consider the utility of tools such as functional MRI, diffusion tensor imaging, and diffusion tractography in the neonatal population.
Seminars in perinatology 02/2010; 34(1):67-78. · 2.33 Impact Factor
