Central gray matter damage, the hallmark of term acute perinatal hypoxia-ischemia, frequently leads to severe cerebral palsy and sometimes death. The precision with which these outcomes can be ...determined from neonatal imaging has not been fully explored. We evaluated the accuracy of early brain MRI for predicting death, the presence and severity of motor impairment, and ability to walk at 2 years in term infants with hypoxic-ischemic encephalopathy (HIE) and basal ganglia-thalamic (BGT) lesions.
From 1993 to 2007, 175 term infants with evidence of perinatal asphyxia, HIE, and BGT injury seen on early MRI scans were studied. BGT, white matter, posterior limb of the internal capsule (PLIC), and cortex and brainstem abnormality were classified by severity. Motor impairment was staged using the Gross Motor Function Classification System.
The severity of BGT lesions was strongly associated with the severity of motor impairment (Spearman rank correlation 0.77; p < 0.001). The association between white matter, cortical, and brainstem injury and motor impairment was less strong and only BGT injury correlated significantly in a logistic regression model. The predictive accuracy of severe BGT lesions for severe motor impairment was 0.89 (95% confidence interval 0.83-0.96). Abnormal PLIC signal intensity predicted the inability to walk independently by 2 years (sensitivity 0.92, specificity 0.77, positive predictive value 0.88, negative predictive value 0.85). Brainstem injury was the only factor with an independent association with death.
We have shown that in term newborns with HIE and BGT injury, early MRI can be used to predict death and specific motor outcomes.
Campylobacter jejuni, from the delta-epsilon group of proteobacteria,
is a microaerophilic, Gram-negative, flagellate, spiral bacterium-properties
it shares with the related gastric pathogen ...Helicobacter pylori. It
is the leading cause of bacterial food-borne diarrhoeal disease throughout
the world. In addition, infection with C. jejuni is
the most frequent antecedent to a form of neuromuscular paralysis known as
Guillain-Barré syndrome. Here we report the genome
sequence of C. jejuni NCTC11168. C. jejuni has a circular chromosome
of 1,641,481 base pairs (30.6% G+C) which is predicted to encode 1,654 proteins
and 54 stable RNA species. The genome is unusual in that there are virtually
no insertion sequences or phage-associated sequences and very few repeat sequences.
One of the most striking findings in the genome was the presence of hypervariable
sequences. These short homopolymeric runs of nucleotides were commonly found
in genes encoding the biosynthesis or modification of surface structures,
or in closely linked genes of unknown function. The apparently high rate of
variation of these homopolymeric tracts may be important in the survival strategy
of C. jejuni.
We automatically quantify patterns of normal cortical folding in the developing fetus from in utero MR images (N=80) over a wide gestational age (GA) range (21.7 to 38.9weeks). This work on data from ...healthy subjects represents a first step towards characterising abnormal folding that may be related to pathology, facilitating earlier diagnosis and intervention. The cortical boundary was delineated by automatically segmenting the brain MR image into a number of key structures. This utilised a spatio-temporal atlas as tissue priors in an expectation–maximization approach with second order Markov random field (MRF) regularization to improve the accuracy of the cortical boundary estimate. An implicit high resolution surface was then used to compute cortical folding measures. We validated the automated segmentations with manual delineations and the average surface discrepancy was of the order of 1mm. Eight curvature-based folding measures were computed for each fetal cortex and used to give summary shape descriptors. These were strongly correlated with GA (R2=0.99) confirming the close link between neurological development and cortical convolution. This allowed an age-dependent non-linear model to be accurately fitted to the folding measures. The model supports visual observations that, after a slow initial start, cortical folding increases rapidly between 25 and 30weeks and subsequently slows near birth. The model allows the accurate prediction of fetal age from an observed folding measure with a smaller error where growth is fastest. We also analysed regional patterns in folding by parcellating each fetal cortex using a nine-region anatomical atlas and found that Gompertz models fitted the change in lobar regions. Regional differences in growth rate were detected, with the parietal and posterior temporal lobes exhibiting the fastest growth, while the cingulate, frontal and medial temporal lobes developed more slowly.
•We automatically quantify cortical folding in 80 normal foetuses (22–38weeks GA).•Eight curvature-based cortical folding measures were evaluated for each foetus.•Folding measures were better correlated with GA than volume and GA.•A Gompertz function accurately models the increase in folding measures with GA.•This model allows an accurate prediction of GA from folding measures.
Fetal and neonatal MR imaging is increasingly used as a complementary diagnostic tool to sonography. MR imaging is an ideal technique for imaging fetuses and neonates because of the absence of ...ionizing radiation, the superior contrast of soft tissues compared with sonography, the availability of different contrast options, and the increased FOV. Motion in the normally mobile fetus and the unsettled, sleeping, or sedated neonate during a long acquisition will decrease image quality in the form of motion artifacts, hamper image interpretation, and often necessitate a repeat MR imaging to establish a diagnosis. This article reviews current techniques of motion compensation in fetal and neonatal MR imaging, including the following: 1) motion-prevention strategies (such as adequate patient preparation, patient coaching, and sedation, when required), 2) motion-artifacts minimization methods (such as fast imaging protocols, data undersampling, and motion-resistant sequences), and 3) motion-detection/correction schemes (such as navigators and self-navigated sequences, external motion-tracking devices, and postprocessing approaches) and their application in fetal and neonatal brain MR imaging. Additionally some background on the repertoire of motion of the fetal and neonatal patient and the resulting artifacts will be presented, as well as insights into future developments and emerging techniques of motion compensation.
Motion correction is a key element for imaging the fetal brain in-utero using Magnetic Resonance Imaging (MRI). Maternal breathing can introduce motion, but a larger effect is frequently due to fetal ...movement within the womb. Consequently, imaging is frequently performed slice-by-slice using single shot techniques, which are then combined into volumetric images using slice-to-volume reconstruction methods (SVR). For successful SVR, a key preprocessing step is to isolate fetal brain tissues from maternal anatomy before correcting for the motion of the fetal head. This has hitherto been a manual or semi-automatic procedure. We propose an automatic method to localize and segment the brain of the fetus when the image data is acquired as stacks of 2D slices with anatomy misaligned due to fetal motion. We combine this segmentation process with a robust motion correction method, enabling the segmentation to be refined as the reconstruction proceeds. The fetal brain localization process uses Maximally Stable Extremal Regions (MSER), which are classified using a Bag-of-Words model with Scale-Invariant Feature Transform (SIFT) features. The segmentation process is a patch-based propagation of the MSER regions selected during detection, combined with a Conditional Random Field (CRF). The gestational age (GA) is used to incorporate prior knowledge about the size and volume of the fetal brain into the detection and segmentation process. The method was tested in a ten-fold cross-validation experiment on 66 datasets of healthy fetuses whose GA ranged from 22 to 39weeks. In 85% of the tested cases, our proposed method produced a motion corrected volume of a relevant quality for clinical diagnosis, thus removing the need for manually delineating the contours of the brain before motion correction. Our method automatically generated as a side-product a segmentation of the reconstructed fetal brain with a mean Dice score of 93%, which can be used for further processing.
•We automatically segment fetal brain tissues for a fully automated motion correction.•Prior knowledge of the size of the brain is used in the segmentation process.•The initial segmentation is refined throughout motion correction.•In 85% of the cases tested, the results were found suitable for medical diagnosis.
ACT: the Artemis comparison tool Carver, Tim J.; Rutherford, Kim M.; Berriman, Matthew ...
Bioinformatics,
08/2005, Letnik:
21, Številka:
16
Journal Article
Recenzirano
Odprti dostop
The Artemis Comparison Tool (ACT) allows an interactive visualisation of comparisons between complete genome sequences and associated annotations. The comparison data can be generated with several ...different programs; BLASTN, TBLASTX or Mummer comparisons between genomic DNA sequences, or orthologue tables generated by reciprocal FASTA comparison between protein sets. It is possible to identify regions of similarity, insertions and rearrangements at any level from the whole genome to base-pair differences. ACT uses Artemis components to display the sequences and so inherits powerful searching and analysis tools. ACT is part of the Artemis distribution and is similarly open source, written in Java and can run on any Java enabled platform, including UNIX, Macintosh and Windows. Availability: ACT is freely available (under a GPL licence) for download from the Sanger Institute web site, http://www.sanger.ac.uk Contact: artemis@sanger.ac.uk
Survivors of preterm birth have a high incidence of neurodevelopmental impairment which is not explained by currently understood brain abnormalities. The aim of this study was to test the hypothesis ...that the neurodevelopmental abilities of 2-year-old children who were born preterm and who had no evidence of focal abnormality on conventional MR imaging were consistently linearly related to specific local changes in white matter microstructure. We studied 33 children, born at a median (range) gestational age of 28+5 (24+4–32+1) weeks. The children were recruited as infants from the Neonatal Intensive Care Unit at Queen Charlotte's and Hammersmith Hospital in the early neonatal period and imaged at a median corrected age of 25.5 (24–27) months. The children underwent diffusion tensor imaging to measure fractional anisotropy (FA) as a measure of tissue microstructure, and neurodevelopmental assessment using the Griffiths Mental Development Scales giving an overall developmental quotient (DQ) and sub-quotients scores for motor, personal–social, hearing–language, eye–hand coordination and performance scales at 2 years corrected age. Tract-based spatial statistics with linear regression analysis of voxel-wise cross-subject statistics were used to assess the relationship between FA and DQ/sub-quotient scores and results confirmed by reduced major axis regression of regions with significant correlations. We found that DQ was linearly related to FA values in parts of the corpus callosum; performance sub-scores to FA values in the corpus callosum and right cingulum; and eye–hand coordination sub-scores to FA values in the cingulum, fornix, anterior commissure, corpus callosum and right uncinate fasciculus. This study shows that specific neurodevelopmental impairments in infants born preterm are precisely related to microstructural abnormalities in particular regions of cerebral white matter which are consistent between individuals. FA may aid prognostication and provide a biomarker for therapeutic or mechanistic studies of preterm brain injury.
Diffuse white matter injury is common in preterm infants and is a candidate substrate for later cognitive impairment. This injury pattern is associated with morphological changes in deep grey nuclei, ...the localization of which is uncertain. We test the hypotheses that diffuse white matter injury is associated with discrete focal tissue loss, and that this image phenotype is associated with impairment at 2
years.
We acquired magnetic resonance images from 80 preterm infants at term equivalent (mean gestational age 29
+
6
weeks) and 20 control infants (mean GA 39
+
2
weeks). Diffuse white matter injury was defined by abnormal apparent diffusion coefficient values in one or more white matter region (frontal, central or posterior white matter at the level of the centrum semiovale), and morphological difference between groups was calculated from 3D images using deformation based morphometry. Neurodevelopmental assessments were obtained from preterm infants at a mean chronological age of 27.5
months, and from controls at a mean age of 31.1
months.
We identified a common image phenotype in 66 of 80 preterm infants at term equivalent comprising: diffuse white matter injury; and tissue volume reduction in the dorsomedial nucleus of the thalamus, the globus pallidus, periventricular white matter, the corona radiata and within the central region of the centrum semiovale (
t
=
4.42
p
<
0.001 false discovery rate corrected). The abnormal image phenotype is associated with reduced median developmental quotient (DQ) at 2
years (DQ
=
92) compared with control infants (DQ
=
112),
p
<
0.001.
These findings indicate that specific neural systems are susceptible to maldevelopment after preterm birth, and suggest that neonatal image phenotype may serve as a useful biomarker for studying mechanisms of injury and the effect of putative therapeutic interventions.
DNA-damaging agents are among the most frequently used anticancer drugs. However, they provide only modest benefit in most cancers. This may be attributed to a genome maintenance network, the DNA ...damage response (DDR), that recognizes and repairs damaged DNA. ATR is a major regulator of the DDR and an attractive anticancer target. Herein, we describe the discovery of a series of aminopyrazines with potent and selective ATR inhibition. Compound 45 inhibits ATR with a K i of 6 nM, shows >600-fold selectivity over related kinases ATM or DNA-PK, and blocks ATR signaling in cells with an IC50 of 0.42 μM. Using this compound, we show that ATR inhibition markedly enhances death induced by DNA-damaging agents in certain cancers but not normal cells. This differential response between cancer and normal cells highlights the great potential for ATR inhibition as a novel mechanism to dramatically increase the efficacy of many established drugs and ionizing radiation.
Streptomyces coelicolor is a representative of the group of soil-dwelling, filamentous bacteria responsible for producing most natural antibiotics used in human and veterinary medicine. Here we ...report the 8,667,507 base pair linear chromosome of this organism, containing the largest number of genes so far discovered in a bacterium. The 7,825 predicted genes include more than 20 clusters coding for known or predicted secondary metabolites. The genome contains an unprecedented proportion of regulatory genes, predominantly those likely to be involved in responses to external stimuli and stresses, and many duplicated gene sets that may represent 'tissue-specific' isoforms operating in different phases of colonial development, a unique situation for a bacterium. An ancient synteny was revealed between the central 'core' of the chromosome and the whole chromosome of pathogens Mycobacterium tuberculosis and Corynebacterium diphtheriae. The genome sequence will greatly increase our understanding of microbial life in the soil as well as aiding the generation of new drug candidates by genetic engineering.
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