Joshua S Shimony

Washington University in St. Louis, San Luis, Missouri, United States

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Publications (92)394.42 Total impact

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    ABSTRACT: While histological studies and conventional magnetic resonance imaging (MRI) investigations have elucidated the trajectory of structural changes in the developing brain, less is known regarding early functional cerebral development. Recent investigations have demonstrated that resting-state functional connectivity MRI (fcMRI) can identify networks of functional cerebral connections in infants. However, technical and logistical challenges frequently limit the ability to perform MRI scans early or repeatedly in neonates, particularly in those at greatest risk for adverse neurodevelopmental outcomes. High-density diffuse optical tomography (HD-DOT), a portable imaging modality, potentially enables early continuous and quantitative monitoring of brain function in infants. We introduce an HD-DOT imaging system that combines advancements in cap design, ergonomics, and data analysis methods to allow bedside mapping of functional brain development in infants. In a cohort of healthy, full-term neonates scanned within the first days of life, HD-DOT results demonstrate strong congruence with those obtained using co-registered, subject-matched fcMRI and reflect patterns of typical brain development. These findings represent a transformative advance in functional neuroimaging in infants, and introduce HD-DOT as a powerful and practical method for quantitative mapping of early functional brain development in normal and high-risk neonates. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
    Cerebral cortex (New York, N.Y. : 1991). 01/2015;
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    ABSTRACT: Inflammation and infection within the central nervous system is initiated during primary HIV infection (PHI), but the association of these processes with the integrity of brain white matter during PHI is unknown. We used diffusion tensor imaging (DTI) in this prospective cross-sectional neuroimaging study to determine the extent of white matter involvement in early HIV infection. Antiretroviral-naive PHI (defined as <1 year after infection, n = 62), chronic HIV infection (CHI, n = 16), and HIV-uninfected (HIV-, n = 19) participants had DTI, laboratory, and neuropsychometric performance assessments. DTI metrics were examined using region of interest and whole brain voxelwise analyses. Linear mixed-effects models assessed correlations between DTI measures and laboratory and neuropsychometric performance values. PHI participants were assessed at a median 4.1 months after estimated infection, and had median CD4 cell count of 573 cells/μl, and HIV-1 RNA viral load of 4.5 log10 copies/ml in plasma and 2.6 log10 copies/ml in cerebrospinal fluid (CSF). DTI metrics in PHI individuals were similar to HIV- participants and correlated with disruptions in the blood-brain barrier (indicated by CSF/plasma albumin ratio and CSF protein). CHI participants had significant loss of white matter integrity that correlated with biomarkers of infection and inflammation (blood viral load, CD4 T-cell count, and neopterin, and CSF white blood cell). Within the PHI group, DTI metrics inversely correlated with increasing days since infection. In individuals assessed during PHI, group DTI measures suggested relative preservation of white matter microstructural integrity, but were associated with disruption of the blood-brain barrier and estimated duration of infection.
    AIDS (London, England) 12/2014; · 6.56 Impact Factor
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    ABSTRACT: In this study, we retrospectively examined the microstructural white matter integrity of children with early- and continuously-treated PKU (N = 36) in relation to multiple indices of phenylalanine (Phe) control over the lifetime. White matter integrity was assessed using mean diffusivity (MD) from diffusion tensor imaging (DTI). Eight lifetime indices of Phe control were computed to reflect average Phe (mean, index of dietary control), variability in Phe (standard deviation, standard error of estimate, % spikes), change in Phe with age (slope), and prolonged exposure to Phe (mean exposure, standard deviation exposure). Of these indices, mean Phe, mean exposure, and standard deviation exposure were the most powerful predictors of widespread microstructural white matter integrity compromise. Findings from the two previously unexamined exposure indices reflected the accumulative effects of elevations and variability in Phe. Given that prolonged exposure to elevated and variable Phe was particularly detrimental to white matter integrity, Phe should be carefully monitored and controlled throughout childhood, without liberalization of Phe control as children with PKU age.
    Molecular Genetics and Metabolism 11/2014; · 2.83 Impact Factor
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    ABSTRACT: Premature birth is associated with high rates of motor and cognitive disability. Investigations have described resting-state functional magnetic resonance imaging (rs-fMRI) correlates of prematurity in older children, but comparable data in the neonatal period remain scarce. We studied 25 term-born control infants within the first week of life and 25 very preterm infants (born at gestational ages ranging from 23 to 29 weeks) without evident structural injury at term equivalent postmenstrual age. Conventional resting-state network (RSN) mapping revealed only modest differences between the term and prematurely born infants, in accordance with previous work. However, clear group differences were observed in quantitative analyses based on correlation and covariance matrices representing the functional MRI time series extracted from 31 regions of interest in 7 RSNs. In addition, the maximum likelihood dimensionality estimates of the group-averaged covariance matrices in the term and preterm infants were 5 and 3, respectively, indicating that prematurity leads to a reduction in the complexity of rs-fMRI covariance structure. These findings highlight the importance of quantitative analyses of rs-fMRI data and suggest a more sensitive method for delineating the effects of preterm birth in infants without evident structural injury.
    Cerebral Cortex 10/2014; · 8.31 Impact Factor
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    ABSTRACT: Resting-state functional MR imaging (rsfMR imaging) measures spontaneous fluctuations in the blood oxygen level-dependent (BOLD) signal and can be used to elucidate the brain's functional organization. It is used to simultaneously assess multiple distributed resting-state networks. Unlike task-based functional MR imaging, rsfMR imaging does not require task performance. This article presents a brief introduction of rsfMR imaging processing methods followed by a detailed discussion on the use of rsfMR imaging in presurgical planning. Example cases are provided to highlight the strengths and limitations of the technique. Copyright © 2014 Elsevier Inc. All rights reserved.
    Neuroimaging Clinics of North America 09/2014; · 1.29 Impact Factor
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    ABSTRACT: RATIONALE AND OBJECTIVES To compare quantitative imaging parameter measures from diffusion- and perfusion-weighted imaging magnetic resonance imaging (MRI) sequences in subjects with brain tumors that have been processed with different software platforms. MATERIALS AND METHODS Scans from 20 subjects with primary brain tumors were selected from the Comprehensive Neuro-oncology Data Repository at Washington University School of Medicine (WUSM) and the Swedish Neuroscience Institute. MR images were coregistered, and each subject's data set was processed by three software packages: 1) vendor-specific scanner software, 2) research software developed at WUSM, and 3) a commercially available, Food and Drug Administration–approved, processing platform (Nordic Ice). Regions of interest (ROIs) were chosen within the brain tumor and normal nontumor tissue. The results obtained using these methods were compared. RESULTS For diffusion parameters, including mean diffusivity and fractional anisotropy, concordance was high when comparing different processing methods. For perfusion-imaging parameters, a significant variance in cerebral blood volume, cerebral blood flow, and mean transit time (MTT) values was seen when comparing the same raw data processed using different software platforms. Correlation was better with larger ROIs (radii ≥ 5 mm). Greatest variance was observed in MTT. CONCLUSIONS Diffusion parameter values were consistent across different software processing platforms. Perfusion parameter values were more variable and were influenced by the software used. Variation in the MTT was especially large suggesting that MTT estimation may be unreliable in tumor tissues using current MRI perfusion methods.
    Academic Radiology 08/2014; · 2.08 Impact Factor
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    ABSTRACT: Objective:Determine the association of prenatal and neonatal infections with neurodevelopmental outcomes in very preterm infants.Study Design:Secondary retrospective analysis of 155 very preterm infants at a single tertiary referral center. General linear or logistic regression models were used to evaluate the association with hospital factors; brain injury, growth and development; and neurobehavioral outcome.Result:Necrotizing enterocolitis with sepsis was associated with reduced transcerebellar diameter (38.3 vs 48.4 mm, P<0.001) and increased left ventricular diameter (12.0 vs 8.0 mm, P=0.005). Sepsis alone was associated with higher diffusivity in the left frontal lobe (1.85 vs 1.68 × 10(-3) mm(2) s(-1), P=0.001) and right cingulum bundle (1.52 vs 1.45 × 10(-)(3) mm(2) s(-1), P=0.002). Neurobehavioral outcomes were worse in children exposed to maternal genitourinary infection (cognitive composite: β=-8.8, P=0.001; receptive language score: β=-2.7, P<0.001; language composite: β=-14.9, P<0.001) or histological chorioamnionitis (language composite: β=-8.6, P=0.006), but not neonatal infection.Conclusion:Neonatal infection was associated with changes in brain structure but not with neurobehavioral outcomes, whereas the opposite pattern was observed for maternal genitourinary tract infection. These findings emphasize the potential importance of infections during pregnancy on the neurodevelopmental outcomes of preterm infants.Journal of Perinatology advance online publication, 17 July 2014; doi:10.1038/jp.2014.79.
    Journal of perinatology: official journal of the California Perinatal Association 07/2014; · 1.59 Impact Factor
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    ABSTRACT: Objective: Language acquisition was assumed to proceed normally in children with unilateral hearing loss (UHL) since they have one functioning ear. However, children with UHL score poorly on speech-language tests and have higher rates of educational problems compared to normal hearing (NH) peers. Diffusion tensor imaging (DTI) is an imaging modality used to measure microstructural integrity of brain white matter. The purpose of this pilot study was to investigate differences in fractional anisotropy (FA) and mean diffusivity (MD) in hearing- and non-hearing-related structures in the brain between children with UHL and their NH siblings. Study Design: Prospective observational cohort. Setting: Academic medical center. Subjects and Methods: Sixty one children were recruited, tested and imaged. Twenty nine children with severe-to-profound UHL were compared to 20 siblings with NH using IQ and oral language testing, and MRI with DTI. Twelve children had inadequate MRI data. Parents provided demographic data and indicated whether children had a need for an individualized educational program (IEP) or speech therapy (ST). DTI parameters were measured in auditory and non-auditory regions of interest (ROIs). Between-group comparisons were evaluated with non-parametric tests. Results: Lower FA of left lateral lemniscus was observed for children with UHL compared to their NH siblings, as well as trends toward differences in other auditory and non-auditory regions. Correlation analyses showed associations between several DTI parameters and outcomes in children with UHL. Regression analyses revealed relationships between educational outcome variables and several DTI parameters, which may provide clinically useful information for guidance of speech therapy. Discussion/Conclusion: Our data suggests that white matter microstructural patterns in several brain regions are preserved despite unilateral rather than bilateral auditory input which contrasts with findings in patients with bilateral hearing loss.
    Frontiers in Systems Neuroscience 05/2014; 8:87.
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    ABSTRACT: The phenotype of recurrent ∼600 kb microdeletion and microduplication on proximal 16p11.2 is characterized by a spectrum of neurodevelopmental impairments including developmental delay and intellectual disability, epilepsy, autism and psychiatric disorders which are all subject to incomplete penetrance and variable expressivity. A variety of brain MRI abnormalities were reported in patients with 16p11.2 rearrangements, but no systematic correlation has been studied among patients with similar brain anomalies, their neurodevelopmental and clinical phenotypes. We present three patients with the proximal 16p11.2 microduplication exhibiting significant developmental delay, anxiety disorder and other variable clinical features. Our patients have abnormal brain MRI findings of cerebral T2 hyperintense foci (3/3) and ventriculomegaly (2/3). The neuroradiological or neurological findings in two cases prompted an extensive diagnostic work-up. One patient has exhibited neurological regression and progressive vision impairment and was diagnosed with juvenile neuronal ceroid-lipofuscinosis. We compare the clinical course and phenotype of these patients in regard to the clinical significance of the cerebral lesions and the need for MRI surveillance. We conclude that in all three patients the lesions were not progressive, did not show any sign of malignant transformation and could not be correlated to specific clinical features. We discuss potential etiologic mechanisms that may include overexpression of genes within the duplicated region involved in control of cell proliferation and complex molecular mechanisms such as the MAPK/ERK pathway. Systematic studies in larger cohorts are needed to confirm our observation and to establish the prevalence and clinical significance of these neuroanatomical abnormalities in patients with 16p11.2 duplications. © 2014 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 05/2014; · 2.30 Impact Factor
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    ABSTRACT: In this work, we present a subject-matched comparison between fcDOT and fcMRI maps obtained in a cohort of full-term neonates. Our results demonstrate the potential of functional connectivity DOT as a bedside monitor of brain function.
    Biomedical Optics; 04/2014
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    ABSTRACT: Background:Moderate-severe white matter abnormality (WMA) in the newborn has been shown to produce persistent disruptions in cerebral connectivity, but does not universally result in neurodevelopmental disability in very preterm (VPT) children. The aims of this hypothesis driven study were to apply diffusion imaging to: 1) examine whether bilateral WMA detected in VPT children in the newborn period can predict microstructural organization at age 7; 2) compare corticospinal tract (CST) and corpus callosum (CC) measures in VPT children at age 7 with neonatal WMA with normal versus impaired motor functioning.Methods:Diffusion parameters of the CST and CC were compared between VPT 7-year-olds with (n=20) and without (n=42) bilateral WMA detected in the newborn period. For those with WMA, diffusion parameters were further examined.Results:Microstructural organization of CST and CC tracts at age 7 years were altered in VPT children with moderate-severe WMA detected at term equivalent age compared to those without injury. Furthermore, diffusion parameters differed in the CC for children with WMA categorized by motor outcome (N=8).Conclusions:WMA on conventional MRI at term equivalent age is associated with altered microstructural organization of the CST and CC at 7 years of age.Pediatric Research (2014); doi:10.1038/pr.2014.45.
    Pediatric Research 04/2014; · 2.84 Impact Factor
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    ABSTRACT: Intragenic copy number variations involving the calmodulin-binding transcription activator 1 (CAMTA1) gene have recently been reported in four unrelated families with intellectual disability (ID), ataxia, behavioral- and cerebellar abnormalities.We report a detailed phenotypic and molecular characterization of three individuals with novel intragenic CAMTA1 deletions from two unrelated families and compare the findings to those of previously reported patients.Our patients had deletions of exons 6-11 and presented with ID, developmental delay (DD), attention deficit hyperactivity disorder (ADHD) and constipation. Two individuals from one family had also unsteady gait. Consistent phenotypes associated with CAMTA1 intragenic rearrangements include ID, speech problems and some dysmorphic features whereas neurobehavioral abnormalities are variable. We did not observe obvious phenotypic differences between patients with in-frame and those with frameshift rearrangements.There is increased evidence that CAMTA1 has a role in brain and cerebellar function. CAMTA1 should be added to the growing list of genes associated with ID/DD, especially when behavioral problems, cerebellar signs, and/or dysmorphism are also present.
    Clinical Genetics 04/2014; · 3.65 Impact Factor
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    ABSTRACT: Object Chiari malformation Type I (CM-I) is a developmental abnormality often associated with a spinal syrinx. Patients with syringomyelia are known to have an increased risk of scoliosis, yet the influence of specific radiographically demonstrated features on the prevalence of scoliosis remains unclear. The primary objective of the present study was to investigate the relationship of maximum syrinx diameter and tonsillar descent to the presence of scoliosis in patients with CM-I-associated syringomyelia. A secondary objective was to explore the role of craniovertebral junction (CVJ) characteristics as additional risk factors for scoliosis. Methods The authors conducted a retrospective review of pediatric patients evaluated for CM-I with syringomyelia at a single institution in the period from 2000 to 2012. Syrinx morphology and CVJ parameters were evaluated with MRI, whereas the presence of scoliosis was determined using standard radiographic criteria. Multiple logistic regression was used to analyze radiological features that were independently associated with scoliosis. Results Ninety-two patients with CM-I and syringomyelia were identified. The mean age was 10.5 ± 5 years. Thirty-five (38%) of 92 patients had spine deformity; 23 (66%) of these 35 patients were referred primarily for deformity, and 12 (34%) were diagnosed with deformity during workup for other symptoms. Multiple regression analysis revealed maximum syrinx diameter > 6 mm (OR 12.1, 95% CI 3.63-40.57, p < 0.001) and moderate (5-12 mm) rather than severe (> 12 mm) tonsillar herniation (OR 7.64, 95% CI 2.3-25.31, p = 0.001) as significant predictors of spine deformity when controlling for age, sex, and syrinx location. Conclusions The current study further elucidates the association between CM-I and spinal deformity by defining specific radiographic characteristics associated with the presence of scoliosis. Specifically, patients presenting with larger maximum syrinx diameters (> 6 mm) have an increased risk of scoliosis.
    Journal of Neurosurgery Pediatrics 02/2014; · 1.63 Impact Factor
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    ABSTRACT: Background Functional imaging and lesion studies have associated willed behavior with anterior cingulate cortex (ACC). Abulia is a syndrome characterized by apathy and deficiency of motivated behavior. Abulia is most frequently associated with ACC damage, but also occurs following damage to subcortical nuclei (striatum, globus pallidus, thalamic nuclei). We present resting state functional connectivity MRI (fcMRI) data from an individual who suffered a stroke leading to abulia. We hypothesized that, although structural imaging revealed no damage to the patient’s ACC, fcMRI would uncover aberrant function in this region and in the relevant cortical networks. Methods Resting state correlations in the patient’s gray matter were compared to those of age-matched controls. Using a novel method to identify abnormal patterns of functional connectivity in single subjects, we identified areas and networks with aberrant connectivity. Results Networks associated with memory (default mode network) and executive function (cingulo-opercular network) were abnormal. The patient’s anterior cingulate was among the areas showing aberrant functional connectivity. In a rescan 3 years later, deficits remained stable and fcMRI findings were replicated. Conclusions These findings suggest that the aberrant functional connectivity mapping approach described may be useful for linking stroke symptoms to disrupted network connectivity.
    NeuroImage: Clinical. 01/2014;
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    ABSTRACT: CONCLUSION The TIP has enabled streamlined integration of research-based image processing tools into clinical workflows, allowing both clinical use and bidirectional feedback between clinicians and research scientists. The TIP is open source and can be downloaded from the XNAT Marketplace website. BACKGROUND Quantitative imaging processing tools developed in research settings have the potential to enhance clinical diagnostic practice. Conversely, feedback from clinical use could be used to researchers to continue to improve algorithms and functionality. However, integrating these tools into clinical workflows is often a difficult and time consuming process. We have developed a customized version of the XNAT imaging informatics platform to overcome these obstacles. This system is referred to as the Translational Imaging Platform (TIP). EVALUATION The TIP includes a user interface to retrieve specific patient imaging studies from a selected PACS system using standard DICOM query/retrieve services. Selected patients can be selected and automatically imported to the TIP repository. Once in TIP, the study can be processed with automated image processing pipelines. The TIP uses XNAT's pipeline engine service to configure and exeucte these pipelines. The pipelines are designed to produce addtional DICOM series that may include derived images and/or structured reports. This generated content can be reviewed by qualified personnel and then sent to the PACS for clinical use. DISCUSSION The TIP has been deployed at the Washington University School of Medicine and is jointly managed by BJC Hospital inforamtion technology department and the Mallinckrodt Institute of Radiology Division of Radiological Sciences. The initial pipeline within the TIP generates a series of brain network maps from resting state functional MRI data (rfMRI). These maps are used by neuroradiology and neurosurgery teams to develop surgical navigation plans. An additional pipeline is in development to generate quantitative brain region volumetry reports for use in Alzheimer's Disease diagnosis.
    Radiological Society of North America 2013 Scientific Assembly and Annual Meeting; 12/2013
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    ABSTRACT: CONCLUSION Our findings indicate that the reliability of automated processing of multi-center clinical imaging studies would be improved by secure image-based methods for determining head orientation and tight control over clinical study acquisition protocols, including file naming conventions. These measures offer the potential to significantly improve large scale, clinical imaging research studies. BACKGROUND Processing pipelines for large neuroimaging clinical research projects must be reliable. This is challenging in multi-site studies because inconsistent acquisition protocols cannot be entirely avoided. We report our experience with the pipeline developed to automatically preprocess and co-register multispectral MRI data acquired by the Comprehensive Neuro-oncology Data Repository (CONDR) project, and analyze the most common reasons of automatic processing failures. EVALUATION A typical CONDR MR study contains several T1-, T2- and susceptibility-weighted images plus dynamic susceptibility contrast (DSC) perfusion and diffusion sensitized sequences. Our CONDR processing pipeline includes detection of available DICOM scans, identification of known scan types, generation of perfusion and diffusion maps and spatial co-registration of all image data to a pre-selected atlas. Although this preprocessing is intended to be fully automatic, variable patient anatomy (brain distortion consequent to mass lesions) and inconsistent sequence settings may result in a processing failure. We evaluated the most common reasons for pre-processing failure in over 60 tumor studies acquired in two different institutions. DISCUSSION Diffusion processing failures were most often attributable to incorrectly detected scan orientation because of missing DICOM metadata. Image registration failures were most commonly attributable to pathologic anatomical distortions and highly anisotropic voxels (i.e., thick slices with high in-plane resolution). A minority of studies failed processing because the required scans were either absent or not detected because of naming inconsistencies.
    Radiological Society of North America 2013 Scientific Assembly and Annual Meeting; 12/2013
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    ABSTRACT: PURPOSE To quantify and compare the cerebral oxygen extraction fraction (OEF) measurement in the normal brain and brain tumors using 15O positron emission tomography (PET) and oxygen sensitive magnetic resonance (MR)1,2 imaging. METHOD AND MATERIALS 30 participants (20 with brain tumors) were recruited. MRI included standard clinical sequences plus OEF-MR1; a two-dimensional multi-echo gradient spin echo sequence. Concurrent with the MR acquisition, subjects with brain tumors underwent PET scanning, which included 2 sets of 3 scans with serial inhalation of air with 40-75 mCi radiolabeled carbon monoxide (C15O), 40-75 mCi radiolabeled oxygen (15O2), and injection of 25-50 mCi radiolabeled water (H215O). MR and PET data were post-processed off line and registered to the anatomic T1 pre-and post-contrast images. Regions of interest were drawn based upon contrast-enhancing tumor areas, contra-lateral normal white matter (NWM), and normal gray matter (NGM) Ratios of OEF (rOEF) were obtained for lesions compared to normal tissue. RESULTS There is very good correlation between two OEF-PET measurements for tumor (R2=0.90 with slope of 0.82), and for rOEF (R2=0.93 and slope of 1.14). The OEF values of NWM are not significantly different between the OEF-PETmeasurements. OEF-MR and OEF-PET correlates well when subjects with SWI abnormalities (blood cloth, hemorrhage, calcification) are excluded (R=0.73). CONCLUSION Both MR and [15O] PET can measure OEF in brain tumors and in peritumoral edema. Variable OEF measurements for tumor and edema may be implication for tumor grade and prognosis. BOLD MR fails in regions with signal loss on SWI or T2*. Both techniques have tremendous potential and may offer new insight into the underlying physiology of brain tumors and their response to therapy without requiring radiation or injected contrast. References: 1 An and Lin (2000), "Quantitative measurements of cerebral blood oxygen saturation using magnetic resonance imaging." J. Cereb. Blood, Flow Metab 2 He and Yablonskiy (2007), "Quantitative BOLD: mapping of human cerebral deoxygenated blood volume and oxygen extraction fraction: default state." Magn Reson Med. CLINICAL RELEVANCE/APPLICATION Both MR and [15O] PET can measure OEF in brain tumors and in peritumoral edema and have potential to predict treatment response. BOLD MR fails in regions with signal loss on SWI or T2*.
    Radiological Society of North America 2013 Scientific Assembly and Annual Meeting; 12/2013
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    ABSTRACT: Recent findings associated with resting-state cortical networks have provided insight into the brain's organizational structure. In addition to their neuroscientific implications, the networks identified by resting-state functional magnetic resonance imaging (rs-fMRI) may prove useful for clinical brain mapping. To demonstrate that a data-driven approach to analyze resting-state networks (RSNs) is useful in identifying regions classically understood to be eloquent cortex as well as other functional networks. This study included 6 patients undergoing surgical treatment for intractable epilepsy and 7 patients undergoing tumor resection. rs-fMRI data were obtained before surgery and 7 canonical RSNs were identified by an artificial neural network algorithm. Of these 7, the motor and language networks were then compared with electrocortical stimulation (ECS) as the gold standard in the epilepsy patients. The sensitivity and specificity for identifying these eloquent sites were calculated at varying thresholds, which yielded receiver-operating characteristic (ROC) curves and their associated area under the curve (AUC). RSNs were plotted in the tumor patients to observe RSN distortions in altered anatomy. The algorithm robustly identified all networks in all patients, including those with distorted anatomy. When all ECS-positive sites were considered for motor and language, rs-fMRI had AUCs of 0.80 and 0.64, respectively. When the ECS-positive sites were analyzed pairwise, rs-fMRI had AUCs of 0.89 and 0.76 for motor and language, respectively. A data-driven approach to rs-fMRI may be a new and efficient method for preoperative localization of numerous functional brain regions. AUC, area under the curveBA, Brodmann areaBOLD, blood oxygen level dependentECS, electrocortical stimulationfMRI, functional magnetic resonance imagingICA, independent component analysisMLP, multilayer perceptronMP-RAGE, magnetization-prepared rapid gradient echoROC, receiver-operating characteristicrs-fMRI, resting-state functional magnetic resonance imagingRSN, resting-state network.
    Neurosurgery 12/2013; 73(6):969-983. · 3.03 Impact Factor
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    ABSTRACT: Advanced imaging methods have the potential to serve as quantitative biomarkers in neuro-oncology research. However, a lack of standardization of image acquisition, processing, and analysis limits their application in clinical research. Standardization of these methods and an organized archival platform are required to better validate and apply these markers in research settings and ultimately in clinical practice. The primary objective of the Comprehensive Neuro-oncology Data Repository (CONDR) is to develop a dataset for assessing and validating advanced imaging methods in patients diagnosed with brain tumors. As a secondary objective, informatics resources will be developed to facilitate the integrated collection, processing, and analysis of imaging, tissue, and clinical data in multi-center clinical trials. Finally, CONDR data and informatics resources will be shared with the research community for further analysis. CONDR will enroll 200 patients diagnosed with primary brain tumors. Clinical, imaging, and tissue-based data are obtained from patients serially, beginning with diagnosis and continuing over the course of their treatment. The CONDR imaging protocol includes structural and functional sequences, including diffusion- and perfusion-weighted imaging. All data are managed within an XNAT-based informatics platform. Imaging markers are assessed by correlating image and spatially-aligned pathological markers and a variety of clinical markers. CONDR will generate data for developing and validating imaging markers of primary brain tumors, including multi-spectral and probabilistic maps. CONDR implements a novel, open research model that will provide the research community with both open access data and open source informatics resources.
    Neurosurgery 10/2013; · 3.03 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE:Hydrocephalus is a severe pathologic condition in which WM damage is a major factor associated with poor outcomes. The goal of the study was to investigate tract-based WM connectivity and DTI measurements in children with hydrocephalus by using the probabilistic diffusion tractography method.MATERIALS AND METHODS:Twelve children with hydrocephalus and 16 age-matched controls were included in the study. Probabilistic diffusion tractography was conducted to generate tract-based connectivity distribution and DTI measures for the genu of the corpus callosum and the connectivity index. Tract-based summary measurements, including the connectivity index and DTI measures (fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity), were calculated and compared between the 2 study groups.RESULTS:Tract-based summary measurement showed a higher percentage of voxels with lower normalized connectivity index values in the WM tracts in children with hydrocephalus. In the genu of the corpus callosum, the left midsegment of the corticospinal tract, and the right midsegment of the corticospinal tract, the normalized connectivity index value in children with hydrocephalus was found to be significantly lower (P < .05, corrected). The tract-based DTI measures showed that the children with hydrocephalus had significantly higher mean diffusivity, axial diffusivity, and radial diffusivity in the genu of the corpus callosum, left midsegment of the corticospinal tract, and right midsegment of corticospinal tract and lower fractional anisotropy in the genu of the corpus callosum (P < .05, corrected).CONCLUSIONS:The analysis of WM connectivity showed that the probabilistic diffusion tractography method is a sensitive tool to detect the decreased continuity in WM tracts that are under the direct influence of mechanical distortion and increased intracranial pressure in hydrocephalus. This voxel-based connectivity method can provide quantitative information complementary to the standard DTI summary measures.
    American Journal of Neuroradiology 09/2013; · 3.17 Impact Factor

Publication Stats

4k Citations
394.42 Total Impact Points

Institutions

  • 1999–2014
    • Washington University in St. Louis
      • • Department of Neurology
      • • Department of Pediatrics
      • • Department of Neurosurgery
      San Luis, Missouri, United States
  • 2012
    • Université de Reims Champagne-Ardenne
      Rheims, Champagne-Ardenne, France
  • 2009
    • University of Kentucky
      • Department of Neurology
      Lexington, KY, United States