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Grant, P.

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Grant, P.
Author's Publications: search.filters.isAuthorOfPublication.ba420e51-bcfa-4a4f-9fd2-84621c998e8d

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Now showing 1 - 10 of 13
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    Editorial on emerging neuroimaging tools for studying normal and abnormal human brain development
    (Frontiers Media S.A., 2015) Papadelis, Christos; Grant, P.; Okada, Yoshio; Preissl, Hubert
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    Biallelic Mutations In Human DCC Cause Developmental Split Brain Syndrome
    (2017) Jamuar, Saumya; Schmitz-Abe, Klaus; D’Gama, Alissa M.; Drottar, Marie; Chan, Wai-Man; Peeva, Maya; Servattalab, Sarah; Lam, Anh-Thu N.; Delgado, Mauricio R.; Clegg, Nancy J.; Al Zayed, Zayed; Dogar, Mohammad Asif; Alorainy, Ibrahim A.; Jamea, Abdullah Abu; Abu-Amero, Khaled; Griebel, May; Ward, Wendy; Lein, Ed S.; Markianos, Kyriacos; Barkovich, A. James; Robson, Caroline; Grant, P.; Bosley, Thomas M.; Engle, Elizabeth; Walsh, Christopher; Yu, Timothy W.
    Motor, sensory, and integrative activities of the brain are coordinated by a series of midline-bridging neuronal commissures whose development is tightly regulated. Here we report a novel human syndrome in which these commissures are widely disrupted, causing clinical manifestations of horizontal gaze palsy, scoliosis, and intellectual disability. Affected individuals were found to possess biallelic loss-of-function mutations in the axon guidance receptor Deleted in Colorectal Carcinoma (DCC), a gene previously implicated in congenital mirror movements when mutated in the heterozygous state, but whose biallelic loss-of-function human phenotype has not been reported. Structural MRI and diffusion tractography demonstrated broad disorganization of white matter tracts throughout the human CNS including loss of all commissural tracts at multiple levels of the neuraxis. Combined with data from animal models, these findings show that DCC is a master regulator of midline crossing and development of white matter projections throughout the human CNS.
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    Two uniqueTUBB3mutations cause both CFEOM3 and malformations of cortical development
    (Wiley, 2015) Whitman, Mary; Andrews, Caroline; Chan, Wai-Man; Tischfield, Max A.; Stasheff, Steven F.; Brancati, Francesco; Ortiz-Gonzalez, Xilma; Nuovo, Sara; Garaci, Francesco; MacKinnon, Sarah E.; Hunter, David; Grant, P.; Engle, Elizabeth
    One set of missense mutations in the neuron specific beta tubulin isotype 3 (TUBB3) has been reported to cause malformations of cortical development (MCD), while a second set has been reported to cause isolated or syndromic Congenital Fibrosis of the Extraocular Muscles type 3 (CFEOM3). Because TUBB3 mutations reported to cause CFEOM had not been associated with cortical malformations, while mutations reported to cause MCD had not been associated with CFEOM or other forms of paralytic strabismus, it was hypothesized that each set of mutations might alter microtubule function differently. Here, however, we report two novel de novo heterozygous TUBB3 amino acid substitutions, G71R and G98S, in four patients with both MCD and syndromic CFEOM3. These patients present with moderately severe CFEOM3, nystagmus, torticollis, and developmental delay, and have intellectual and social disabilities. Neuroimaging reveals defective cortical gyration, as well as hypoplasia or agenesis of the corpus callosum and anterior commissure, malformations of hippocampi, thalami, basal ganglia and cerebella, and brainstem and cranial nerve hypoplasia. These new TUBB3 substitutions meld the two previously distinct TUBB3-associated phenotypes, and implicate similar microtubule dysfunction underlying both.
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    Non-invasive Assessment of Cerebral Blood Flow and Oxygen Metabolism in Neonates during Hypothermic Cardiopulmonary Bypass: Feasibility and Clinical Implications
    (Nature Publishing Group, 2017) Ferradal, Silvina L.; Yuki, Koichi; Vyas, Rutvi; Ha, Christopher G.; Yi, Francesca; Stopp, Christian; Wypij, David; Cheng, Henry; Newburger, Jane; Kaza, Aditya; Franceschini, Maria; Kussman, Barry; Grant, P.
    The neonatal brain is extremely vulnerable to injury during periods of hypoxia and/or ischemia. Risk of brain injury is increased during neonatal cardiac surgery, where pre-existing hemodynamic instability and metabolic abnormalities are combined with long periods of low cerebral blood flow and/or circulatory arrest. Our understanding of events associated with cerebral hypoxia-ischemia during cardiopulmonary bypass (CPB) remains limited, largely due to inadequate tools to quantify cerebral oxygen delivery and consumption non-invasively and in real-time. This pilot study aims to evaluate cerebral blood flow (CBF) and oxygen metabolism (CMRO2) intraoperatively in neonates by combining two novel non-invasive optical techniques: frequency-domain near-infrared spectroscopy (FD-NIRS) and diffuse correlation spectroscopy (DCS). CBF and CMRO2 were quantified before, during and after deep hypothermic cardiopulmonary bypass (CPB) in nine neonates. Our results show significantly decreased CBF and CMRO2 during hypothermic CPB. More interestingly, a change of coupling between both variables is observed during deep hypothermic CPB in all subjects. Our results are consistent with previous studies using invasive techniques, supporting the concept of FD-NIRS/DCS as a promising technology to monitor cerebral physiology in neonates providing the potential for individual optimization of surgical management.
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    Pediatric neuroimaging in early childhood and infancy: challenges and practical guidelines
    (Wiley-Blackwell, 2012) Raschle, Nora; Zuk, Jennifer; Ortiz-Mantilla, Silvia; Sliva, Danielle D.; Franceschi, Angela; Grant, P.; Benasich, April A.; Gaab, Nadine
    Structural and functional magnetic resonance imaging (fMRI) has been used increasingly to investigate typical and atypical brain development. However, in contrast to studies in school-aged children and adults, MRI research in young pediatric age groups is less common. Practical and technical challenges occur when imaging infants and children, which presents clinicians and research teams with a unique set of problems. These include procedural difficulties (e.g., participant anxiety or movement restrictions), technical obstacles (e.g., availability of child-appropriate equipment or pediatric MR head coils), and the challenge of choosing the most appropriate analysis methods for pediatric imaging data. Here, we summarize and review pediatric imaging and analysis tools and present neuroimaging protocols for young nonsedated children and infants, including guidelines and procedures that have been successfully implemented in research protocols across several research sites.
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    Reduced cerebral blood flow and oxygen metabolism in extremely preterm neonates with low-grade germinal matrix- intraventricular hemorrhage
    (Nature Publishing Group, 2016) Lin, Pei-Yi; Hagan, Katherine; Fenoglio, Angela; Grant, P.; Franceschini, Maria Angela
    Low-grade germinal matrix-intraventricular hemorrhage (GM-IVH) is the most common complication in extremely premature neonates. The occurrence of GM-IVH is highly associated with hemodynamic instability in the premature brain, yet the long-term impact of low-grade GM-IVH on cerebral blood flow and neuronal health have not been fully investigated. We used an innovative combination of frequency-domain near infrared spectroscopy and diffuse correlation spectroscopy (FDNIRS-DCS) to measure cerebral oxygen saturation (SO2) and an index of cerebral blood flow (CBFi) at the infant’s bedside and compute an index of cerebral oxygen metabolism (CMRO2i). We enrolled twenty extremely low gestational age (ELGA) neonates (seven with low-grade GM-IVH) and monitored them weekly until they reached full-term equivalent age. During their hospital stay, we observed consistently lower CBFi and CMRO2i in ELGA neonates with low-grade GM-IVH compared to neonates without hemorrhages. Furthermore, lower CBFi and CMRO2i in the former group persists even after the resolution of the hemorrhage. In contrast, SO2 does not differ between groups. Thus, CBFi and CMRO2i may have better sensitivity than SO2 in detecting GM-IVH-related effects on infant brain development. FDNIRS-DCS methods may have clinical benefit for monitoring the evolution of GM-IVH, evaluating treatment response, and potentially predicting neurodevelopmental outcome.
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    Failure to Identify the Left Arcuate Fasciculus at Diffusion Tractography Is a Specific Marker of Language Dysfunction in Pediatric Patients with Polymicrogyria
    (Hindawi Publishing Corporation, 2015) Paldino, Michael J.; Hedges, Kara; Gaab, Nadine; Galaburda, Albert; Grant, P.
    Background:. Polymicrogyric cortex demonstrates interindividual variation with regard to both extent of dyslamination and functional capacity. Given the relationship between laminar structure and white matter fibers, we sought to define the relationship between polymicrogyria (PMG), intrahemispheric association pathways, and network function. Methods:. Each arcuate fasciculus (AF) was categorized as present or absent. Language was characterized by a pediatric neurologist. The presence of dysplastic cortex in the expected anatomic locations of Broca's (BA) and Wernicke's areas (WA) was evaluated by two pediatric neuroradiologists blinded to DTI and language data. Results:. 16 PMG patients and 16 age/gender-matched controls were included. All normative controls had an identifiable left AF. 6/7 PMG patients with dysplastic cortex within BA and/or WA had no left AF; PMG patients without involvement of these regions had a lower frequency of absence of the left AF (p < 0.006). All patients without a left AF had some degree of language impairment. PMG patients without a left AF had a significantly greater frequency of language impairment compared to those PMG patients with a left AF (p < 0.003). Conclusion:. In patients with PMG (1) the presence of dysplastic cortex within WA and/or BA is associated with absence of the left AF and (2) absence of the left AF is associated with language impairment.
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    Maximum Entropy Estimation of Glutamate and Glutamine in MR Spectroscopic Imaging
    (Springer Science + Business Media, 2014) Rathi, Yogesh; Ning, Lipeng; Michailovich, Oleg; Liao, Huijun; Gagoski, Borjan; Grant, P.; Shenton, Martha; Stern, Robert; Westin, Carl-Fredrik; Lin, Alexander
    Magnetic resonance spectroscopic imaging (MRSI) is often used to estimate the concentration of several brain metabolites. Abnormalities in these concentrations can indicate specific pathology, which can be quite useful in understanding the disease mechanism underlying those changes. Due to higher concentration, metabolites such as N-acetylaspartate (NAA), Creatine (Cr) and Choline (Cho) can be readily estimated using standard Fourier transform techniques. However, metabolites such as Glutamate (Glu) and Glutamine (Gln) occur in significantly lower concentrations and their resonance peaks are very close to each other making it di!cult to accurately estimate their concentrations (separately). In this work, we propose to use the theory of ‘Spectral Zooming’ or high-resolution spectral analysis to separate the Glutamate and Glutamine peaks and accurately estimate their concentrations. The method works by estimating a unique power spectral density, which corresponds to the maximum entropy solution of a zero-mean stationary Gaussian process. We demonstrate our estimation technique on several physical phantom data sets as well as on invivo brain spectroscopic imaging data. The proposed technique is quite general and can be used to estimate the concentration of any other metabolite of interest.
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    Reliable Identification of Deep Sulcal Pits: The Effects of Scan Session, Scanner, and Surface Extraction Tool
    (Public Library of Science, 2013) Im, Kiho; Lee, Jong-Min; Jeon, Seun; Kim, Jong-Heon; Seo, Sang Won; Na, Duk L.; Grant, P.
    Sulcal pit analysis has been providing novel insights into brain function and development. The purpose of this study was to evaluate the reliability of sulcal pit extraction with respect to the effects of scan session, scanner, and surface extraction tool. Five subjects were scanned 4 times at 3 MRI centers and other 5 subjects were scanned 3 times at 2 MRI centers, including 1 test-retest session. Sulcal pits were extracted on the white matter surfaces reconstructed with both Montreal Neurological Institute and Freesurfer pipelines. We estimated similarity of the presence of sulcal pits having a maximum value of 1 and their spatial difference within the same subject. The tests showed high similarity of the sulcal pit presence and low spatial difference. The similarity was more than 0.90 and the spatial difference was less than 1.7 mm in most cases according to different scan sessions or scanners, and more than 0.85 and about 2.0 mm across surface extraction tools. The reliability of sulcal pit extraction was more affected by the image processing-related factors than the scan session or scanner factors. Moreover, the similarity of sulcal pit distribution appeared to be largely influenced by the presence or absence of the sulcal pits on the shallow and small folds. We suggest that our sulcal pit extraction from MRI is highly reliable and could be useful for clinical applications as an imaging biomarker.
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    Transient and Persistent Pain Induced Connectivity Alterations in Pediatric Complex Regional Pain Syndrome
    (Public Library of Science, 2013) Linnman, Clas; Becerra, Lino; Lebel, Alyssa; Berde, Charles; Grant, P.; Borsook, David
    Evaluation of pain-induced changes in functional connectivity was performed in pediatric complex regional pain syndrome (CRPS) patients. High field functional magnetic resonance imaging was done in the symptomatic painful state and at follow up in the asymptomatic pain free/recovered state. Two types of connectivity alterations were defined: (1) Transient increases in functional connectivity that identified regions with increased cold-induced functional connectivity in the affected limb vs. unaffected limb in the CRPS state, but with normalized connectivity patterns in the recovered state; and (2) Persistent increases in functional connectivity that identified regions with increased cold-induced functional connectivity in the affected limb as compared to the unaffected limb that persisted also in the recovered state (recovered affected limb versus recovered unaffected limb). The data support the notion that even after symptomatic recovery, alterations in brain systems persist, particularly in amygdala and basal ganglia systems. Connectivity analysis may provide a measure of temporal normalization of different circuits/regions when evaluating therapeutic interventions for this condition. The results add emphasis to the importance of early recognition and management in improving outcome of pediatric CRPS.