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A New Methodology of Viewing Extra-Axial Fluid and Cortical Abnormalities in Children with Autism via Transcranial Ultrasonography.

ABSTRACT: BACKGROUND:Autism spectrum disorders (ASDs) are developmental conditions of uncertain etiology which have now affected more than 1% of the school-age population of children in many developed nations. Transcranial ultrasonography (TUS) via the temporal bone appeared to be a potential window of investigation to determine the presence of both cortical abnormalities and increased extra-axial fluid (EAF). METHODS:TUS was accomplished using a linear probe (10-5?MHz). Parents volunteered ASD subjects (N?=?23; males 18, females 5) for evaluations (mean?=?7.46?years?±?3.97?years), and 15 neurotypical siblings were also examined (mean?=?7.15?years?±?4.49?years). Childhood Autism Rating Scale (CARS2(®)) scores were obtained and the ASD score mean was 48.08?+?6.79 (Severe). RESULTS:Comparisons of the extra-axial spaces indicated increases in the ASD subjects. For EAF we scored based on the gyral summit distances between the arachnoid membrane and the cortical pia layer (subarachnoid space): (1) <0.05?cm, (2) 0.05-0.07?cm, (3) 0.08-0.10?cm, (4) >0.10?cm. All of the neurotypical siblings scored 1, whereas the ASD mean score was 3.41?±?0.67. We also defined cortical dysplasia as the following: hypoechoic lesions within the substance of the cortex, or disturbed layering within the gray matter. For cortical dysplasia we scored: (1) none observed, (2) rare hypoechogenic lesions and/or mildly atypical cortical layering patterns, (3) more common, but separated areas of cortical hypoechogenic lesions, (4) very common or confluent areas of cortical hypoechogenicity. Again all of the neurotypical siblings scored 1, while the ASD subjects' mean score was 2.79?±?0.93. CONCLUSION:TUS may be a useful screening technique for children at potential risk of ASDs which, if confirmed with repeated studies and high resolution MRI, provides rapid, non-invasive qualification of EAF, and cortical lesions.

SUBMITTER: Bradstreet JJ

PROVIDER: S-EPMC3892177 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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A New Methodology of Viewing Extra-Axial Fluid and Cortical Abnormalities in Children with Autism via Transcranial Ultrasonography.

Bradstreet James Jeffrey JJ Pacini Stefania S Ruggiero Marco M

Frontiers in human neuroscience 20140115

<h4>Background</h4>Autism spectrum disorders (ASDs) are developmental conditions of uncertain etiology which have now affected more than 1% of the school-age population of children in many developed nations. Transcranial ultrasonography (TUS) via the temporal bone appeared to be a potential window of investigation to determine the presence of both cortical abnormalities and increased extra-axial fluid (EAF).<h4>Methods</h4>TUS was accomplished using a linear probe (10-5 MHz). Parents volunteered ...[more]

PMID: 24459462

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Project description:BACKGROUND:We previously showed, in two separate cohorts, that high-risk infants who were later diagnosed with autism spectrum disorder had abnormally high extra-axial cerebrospinal fluid (CSF) volume from age 6-24 months. The presence of increased extra-axial CSF volume preceded the onset of behavioural symptoms of autism and was predictive of a later diagnosis of autism spectrum disorder. In this study, we aimed to establish whether increased extra-axial CSF volume is found in a large, independent sample of children diagnosed with autism spectrum disorder, whether extra-axial CSF remains abnormally increased beyond infancy, and whether it is present in both normal-risk and high-risk children with autism. METHODS:In this case-control MRI study, children with autism spectrum disorder or with typical development aged 2-4 years were recruited from the community to the UC Davis MIND Institute Autism Phenome Project, based in Sacramento, CA, USA. The autism spectrum disorder group comprised children with autism spectrum disorder who were either normal risk (ie, from simplex families) or high risk (ie, from multiplex families). Measurements of extra-axial CSF volume, brain volume, head circumference, sleep problems, and familial risk status were derived from MRI and behavioural assessments. We applied a previously validated machine learning algorithm based on extra-axial CSF volume, brain volume, age, and sex to the current dataset. FINDINGS:Between July 20, 2007, and Dec 13, 2012, 159 children with autism spectrum disorder (132 male, 27 female) and 77 with typical development (49 male, 28 female) underwent MRI scans. The autism spectrum disorder group had an average of 15·1% more extra-axial CSF than controls after accounting for differences in brain volume, weight, age, and sex (least-squares mean 116·74 cm3 [SE 3·33] in autism group vs 101·40 cm3 [3·93] in typical development group; p=0·007; Cohen's d = 0·39). Subgroups of normal-risk (n=132) and high-risk (n=27) children with autism spectrum disorder had nearly identical extra-axial CSF volumes (p=0·78), and both subgroups had significantly greater volumes than controls. Both extra-axial CSF volume (p=0·004) and brain volume (p<0·0001) uniquely contributed to enlarged head circumference in the autism spectrum disorder group (p=0·04). Increased extra-axial CSF volume was associated with greater sleep disturbances (p=0·03) and lower non-verbal ability (p=0·04). The machine learning algorithm correctly predicted autism spectrum disorder diagnosis with a positive predictive value of 83% (95% CI 76·2-88·3). INTERPRETATION:Increased extra-axial CSF volume is a reliable brain anomaly that has now been found in three independent cohorts, comprising both high-risk and normal-risk children with autism spectrum disorder. Increased extra-axial CSF volume is detectable using conventional structural MRI scans from infancy through to age 3 years. These results suggest that increased extra-axial CSF volume could be an early stratification biomarker of a biologically based subtype of autism that might share a common underlying pathophysiology. FUNDING:US National Institutes of Health.

Project description:ImportanceThe prevalence of autism spectrum disorder (ASD) has been increasing rapidly, with current estimates of 1 in 68 children affected. Simultaneously, use of prenatal ultrasonography has increased substantially, with limited investigation into its safety and effects on brain development. Animal studies have demonstrated that prenatal ultrasonography can adversely affect neuronal migration.ObjectiveTo quantify prenatal ultrasound exposure by the frequency, timing, duration, and strength of ultrasonographic scans in children with later ASD, developmental delay, and typical development.Design, setting, and participantsThis case-control study included 107 patients with ASD, 104 control individuals with developmental delay, and 209 controls with typical development. Participants were identified from medical records based on prenatal care and delivery at Boston Medical Center, a diverse, academic, safety-net medical center, from July 1, 2006, through December 31, 2014, with a gestational age at birth of at least 37 weeks. Data were analyzed from May 1, 2015, through November 30, 2017.ExposuresUltrasonographic exposure was quantified by the number and timing of scans, duration of exposure, mean strength (depth, frame rate, mechanical index, and thermal index), and time of Doppler and 3- and 4-dimensional imaging.Main outcomes and measuresAmong participants with ASD and controls with developmental delay and typical development, ultrasound exposure was quantified and compared per trimester and for the entire pregnancy, with adjustment for infant sex, gestational age at birth, and maternal age.ResultsA total of 420 participants were included in the study (328 boys [78.1%] and 92 girls [21.9%]; mean age as of January 1, 2016, 6.6 years; 95% CI, 6.5-6.8 years). The ASD group received a mean of 5.9 scans (95% CI, 5.2-6.6), which was not significantly different from the 6.1 scans (95% CI, 5.4-6.8) in the developmental delay group or the 6.3 scans (95% CI, 5.8-6.8) in the typical development group. Compared with the typical development group, the ASD group had shorter duration of ultrasound exposure during the first (290.4 seconds [95% CI, 212.8-368.0 seconds] vs 406.4 seconds [95% CI, 349.5-463.3 seconds]) and second (1687.6 seconds [95% CI, 1493.8-1881.4 seconds] vs 2011.0 seconds [95% CI, 1868.9-2153.1 seconds]) trimesters but no difference in the number of scans. The ASD group had greater mean depth of ultrasonographic penetration than the developmental delay group in the first trimester (12.5 cm [95% CI, 12.0-13.0 cm] vs 11.6 cm [95% CI, 11.1-12.1 cm]). The ASD group had greater mean depth than the typical development group during the first (12.5 cm [95% CI, 12.0-13.0 cm] vs 11.6 cm [95% CI, 11.3-12.0 cm]) and the second (12.9 cm [95% CI, 12.6-13.3 cm] vs 12.5 cm [95% CI, 12.2-12.7 cm]) trimesters.Conclusions and relevanceThis study found significantly greater mean depth of ultrasonographic penetration in the ASD group compared with the developmental delay group in the first trimester and compared with the typical development group in the first and second trimesters. Further research is needed to determine whether other variables of ultrasound exposure also have adverse effects on the developing fetus.

Project description:BackgroundDuctal lesions are an important, often overlooked, and poorly understood issue in breast imaging, which have a risk of underlying malignancy ranging from 5 to 23%. Ultrasonography (US), which has largely replaced galactography or ductography, has become an important imaging method to assess patients with ductal lesions. However, it is difficult to distinguish benign from malignant ductal abnormalities only by ultrasonography, most of which are recommended to be at least in subcategory 4A; these require biopsy according to the ACR BI-RADS®atlas 5th Edition-breast ultrasound. Contrast-enhanced ultrasound (CEUS) has been shown to be valuable for differentiating benign from malignant tumors, but its value is unclear in breast ductal lesions. Therefore, the purposes of this study were to explore the characteristics of malignant ductal abnormalities on US and CEUS imaging and the diagnostic value of CEUS in breast ductal abnormalities.MethodsOverall, 82 patients with 82 suspicious ductal lesions were recruited for this prospective study. They were divided into benign and malignant groups according to the pathological results. Morphologic features and quantitative parameters of US and CEUS were analyzed by comparison and multivariate logistic regression to determine the independent risk factors. The diagnostic performance was assessed by receiver operating characteristic (ROC) curve analysis.ResultsShape, margin, inner echo, size, microcalcification and blood flow classification on US, wash-in time, enhancement intensity, enhancement mode, enhancement scope, blood perfusion defects, peripheral high enhancement and boundary on CEUS were identified as features correlated with malignant ductal lesions. However, multivariate logistic regression showed that only microcalcification (OR = 8.96, P = 0.047) and enhancement scope (enlarged, OR = 27.42, P = 0.018) were independent risk factors for predicting malignant ductal lesions. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy and area under the ROC curve of microcalcifications combined with an enlarged enhancement scope were 0.895, 0.886, 0.872, 0.907, 0.890, and 0.92, respectively.ConclusionsMicrocalcification and enlarged enhancement scope are independent factors for predicting malignant ductal lesions. The combined diagnosis can greatly improve the diagnostic performance, indicating that CEUS can be useful in the differentiation of benign and malignant lesions to formulate more appropriate management for ductal lesions.

Project description:The neurophysiology of face processing has been studied extensively in the context of social impairments associated with autism spectrum disorder (ASD), but the existing studies have concentrated mainly on univariate analyses of responses to upright faces, and, less frequently, inverted faces. The small number of existing studies on neurophysiological responses to inverted face in ASD have used univariate approaches, with divergent results. Here, we used a data-driven, classification-based, multivariate machine learning decoding approach to investigate the temporal and spatial properties of the neurophysiological evoked response for upright and inverted faces, relative to the neurophysiological evoked response for houses, a neutral stimulus. 21 (2 females) ASD and 29 (4 females) TD participants ages 7 to 19 took part in this study. Group level classification accuracies were obtained for each condition, using first the temporal domain of the evoked responses, and then the spatial distribution of the evoked responses on the cortical surface, each separately. We found that classification of responses to inverted neutral faces vs. houses was less accurate in ASD compared to TD, in both the temporal and spatial domains. In contrast, there were no group differences in the classification of evoked responses to upright neutral faces relative to houses. Using the classification in the temporal domain, lower decoding accuracies in ASD were found around 120 ms and 170 ms, corresponding the known components of the evoked responses to faces. Using the classification in the spatial domain, lower decoding accuracies in ASD were found in the right superior marginal gyrus (SMG), intra-parietal sulcus (IPS) and posterior superior temporal sulcus (pSTS), but not in core face processing areas. Importantly, individual classification accuracies from both the temporal and spatial classifiers correlated with ASD severity, confirming the relevance of the results to the ASD phenotype.

Dataset Information

A New Methodology of Viewing Extra-Axial Fluid and Cortical Abnormalities in Children with Autism via Transcranial Ultrasonography.

Publications

A New Methodology of Viewing Extra-Axial Fluid and Cortical Abnormalities in Children with Autism via Transcranial Ultrasonography.

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