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    Ellen Grant

    About 30% of children with drug-resistant epilepsy (DRE) continue to have seizures after epilepsy surgery. Since epilepsy is increasingly conceptualized as a network disorder, understanding how brain regions interact may be critical for... more
    About 30% of children with drug-resistant epilepsy (DRE) continue to have seizures after epilepsy surgery. Since epilepsy is increasingly conceptualized as a network disorder, understanding how brain regions interact may be critical for planning re-operation in these patients. We aimed to estimate functional brain connectivity using scalp EEG and its evolution over time in patients who had repeated surgery (RS-group, n = 9) and patients who had one successful surgery (seizure-free, SF-group, n = 12). We analyzed EEGs without epileptiform activity at varying time points (before and after each surgery). We estimated functional connectivity between cortical regions and their relative centrality within the network. We compared the pre- and post-surgical centrality of all the non-resected (untouched) regions (far or adjacent to resection) for each group (using the Wilcoxon signed rank test). In alpha, theta, and beta frequency bands, the post-surgical centrality of the untouched cortical...
    MRI studies have consistently demonstrated disproportionately smaller corpus callosa in individuals with a history of prenatal alcohol exposure but have not previously examined the feasibility of detecting this effect in infants. Tissue... more
    MRI studies have consistently demonstrated disproportionately smaller corpus callosa in individuals with a history of prenatal alcohol exposure but have not previously examined the feasibility of detecting this effect in infants. Tissue segmentation of the newborn brain is challenging because analysis techniques developed for the adult brain are not directly transferable, and segmentation for cerebral morphometry is difficult in neonates, due to the latter's incomplete myelination. This study is the first to use volumetric structural MRI to investigate prenatal alcohol exposure effects in newborns using manual tracing and to examine the cross-sectional area of the corpus callosum (CC). 43 nonsedated infants born to 32 Cape Coloured heavy drinkers and 11 controls recruited prospectively during pregnancy were scanned using a custom-designed birdcage coil for infants, which increases signal-to-noise ratio almost two-fold compared to the standard head coil. Alcohol use was ascertain...
    Tuberous sclerosis complex (TSC) is characterized by benign hamartomas in multiple organs including the brain and its clinical phenotypes may be associated with abnormal neural connections. We aimed to provide the first detailed findings... more
    Tuberous sclerosis complex (TSC) is characterized by benign hamartomas in multiple organs including the brain and its clinical phenotypes may be associated with abnormal neural connections. We aimed to provide the first detailed findings on disrupted structural brain networks in TSC patients. Structural whole-brain connectivity maps were constructed using structural and diffusion MRI in 20 TSC (age range: 3-24 years) and 20 typically developing (TD; 3-23 years) subjects. We assessed global (short- and long-association and interhemispheric fibers) and regional white matter connectivity, and performed graph theoretical analysis using gyral pattern- and atlas-based node parcellations. Significantly higher mean diffusivity (MD) was shown in TSC patients than in TD controls throughout the whole brain and positively correlated with tuber load severity. A significant increase in MD was mainly influenced by an increase in radial diffusivity. Furthermore, interhemispheric connectivity was pa...
    To determine the role of surface-coil MR imaging in evaluating medically refractory neocortical partial epilepsy. A prospective study of 25 patients with medically refractory neocortical partial epilepsy was performed. Head- and... more
    To determine the role of surface-coil MR imaging in evaluating medically refractory neocortical partial epilepsy. A prospective study of 25 patients with medically refractory neocortical partial epilepsy was performed. Head- and surface-coil images were reviewed by two neuroradiologists to determine the clarity with which cortical lesions were depicted. The ability of imaging, combined with surface electroencephalography (EEG), to locate the suspected epileptogenic zone was evaluated. Compared with head-coil studies, surface-coil studies showed four more lesions, caused the most probable diagnosis to be altered in five patients, and better defined the lesions in four patients. Of 11 patients with lobar EEG abnormalities, imaging showed focal cortical abnormalities within the same or adjacent lobe in five and multifocal abnormalities in two. Of six patients with EEG abnormalities restricted to two adjacent lobes, imaging showed focal cortical abnormalities in one of these lobes in fi...
    Little is known about the emergence of structural asymmetry of white matter tracts during early brain development. We examined whether and when asymmetry in diffusion parameters of limbic and association white matter pathways emerged in... more
    Little is known about the emergence of structural asymmetry of white matter tracts during early brain development. We examined whether and when asymmetry in diffusion parameters of limbic and association white matter pathways emerged in humans in 23 brains ranging from 15 gestational weeks (GW) up to 3 years of age (11 ex vivo and 12 in vivo cases) using high-angular resolution diffusion imaging tractography. Age-related development of laterality was not observed in a limbic connectional pathway (cingulum bundle or fornix). Among the studied cortico-cortical association pathways (inferior longitudinal fasciculus [ILF], inferior fronto-occipital fasciculus, and arcuate fasciculus), only the ILF showed development of age-related laterality emerging as early as the second trimester. Comparisons of ages older and younger than 40 GW revealed a leftward asymmetry in the cingulum bundle volume and a rightward asymmetry in apparent diffusion coefficient and leftward asymmetry in fractional ...
    Background and Purpose— We report on the use of line scan diffusion magnetic resonance imaging in the evaluation of spinal cord infarctions. Methods— Data on 19 patients with clinical findings consistent with spinal cord infarctions and... more
    Background and Purpose— We report on the use of line scan diffusion magnetic resonance imaging in the evaluation of spinal cord infarctions. Methods— Data on 19 patients with clinical findings consistent with spinal cord infarctions and abnormal findings on line scan diffusion imaging were reviewed. The Apparent Diffusion Coefficient (ADC) measurements for the normal spinal cord and for the areas of abnormality were calculated from trace ADC maps. Results— Restricted diffusion was found in all 19 patients. Absolute ADC values in the ischemic area ranged between 395.4 and 575.8×10 −6 mm 2 /s, with ADC ratios ranging between 39.4% and 57.4%. Conclusions— Line scan diffusion imaging is technically feasible and appears to be a reliable method to diagnose spinal cord infarction in the acute setting.
    In patients presenting with cerebral ischemic injury, the outcome of injured brain tissue quantified as decreased apparent diffusion coefficient (ADC) may depend on associated alterations in cerebral blood perfusion (CBP). This study... more
    In patients presenting with cerebral ischemic injury, the outcome of injured brain tissue quantified as decreased apparent diffusion coefficient (ADC) may depend on associated alterations in cerebral blood perfusion (CBP). This study proposes a non-biased method to quantify associations between ADC and CBP in newborns with global or focal cerebral ischemia. The study population consisted of nine neonates (age: 0 to 3 days) presenting with clinical and imaging evidence of ischemia (seven with global hypoxic ischemia, and two with focal arterial ischemic stroke) with decreased ADC. Six newborns without diffusion abnormalities on magnetic resonance (MR) imaging served as a comparative cohort (age: 0 days to 4 weeks). All patients underwent MR imaging including diffusion weighted imaging (DWI) to determine ADC and axial arterial spin labeling (ASL) to determine CBP. An algorithm was developed that uses the B0 volume from the DWI raw data as a reference, co-registers the ADC and ASL-CBP data to the B0, generates mask filters, and finally performs a statistical analysis to automatically select regions of interest (ROIs) with ADC or ASL-CBP values that deviate significantly from the rest of the brain. If ROIs are identified in this analysis, the algorithm then evaluates correlation based on ROI location and volume. A significant correlation was found between decreased ADC and elevated ASL-CBP with regions of elevated ASL-CBP typically larger than the corresponding ADC abnormality. The association between decreased diffusivity and increased ASL-CBP suggests that, for this cohort, cerebral ischemia is associated with hyperperfusion.
    With the increasing interest in treatments for neonatal brain injury, bedside methods for detecting and assessing injury status and evolution are needed. We aimed to determine whether cerebral tissue oxygenation (StO2), cerebral blood... more
    With the increasing interest in treatments for neonatal brain injury, bedside methods for detecting and assessing injury status and evolution are needed. We aimed to determine whether cerebral tissue oxygenation (StO2), cerebral blood volume (CBV), and estimates of relative cerebral oxygen consumption (rCMRO2) determined by bedside frequency-domain near-infrared spectroscopy (FD-NIRS) have the potential to distinguish neonates with brain injury from those with non-brain issues and healthy controls. We recruited 43 neonates ≤15 days old and >33 weeks gestational age (GA): 14 with imaging evidence of brain injury, 29 without suspicion of brain injury (4 unstable, 6 stable, and 19 healthy). A multivariate analysis of variance with Newman–Keuls post hoc comparisons confirmed group similarity for GA and age at measurement. StO2 was significantly higher in brain injured compared with unstable neonates, but not statistically different from stable or healthy neonates. Brain-injured neona...
    ABSTRACT Purpose: Uncertainty in the location of the distal dose edge is one of the main concerns about proton therapy. It leads to cautious treatment plans that partially neutralize the dosimetric advantage of protons. Vertebral bone... more
    ABSTRACT Purpose: Uncertainty in the location of the distal dose edge is one of the main concerns about proton therapy. It leads to cautious treatment plans that partially neutralize the dosimetric advantage of protons. Vertebral bone marrow responds to radiation with fatty replacement that is visible on post‐treatment MRI. This presents a unique opportunity to visualize radiation effects in vivo. We have developed a method that uses spine MRI changes to precisely localize the distal dose edge in spinal proton radiation patients. Method and Materials: We carefully registered treatment planning CT scans and follow‐up T1‐weighted MRI scans from 10 proton spinal radiation patients. A radiation dose‐MRI signal intensity curve was created using the lateral beam penumbra in the sacrum. This curve was then used to quantitatively examine possible systematic or spatially varying proton range errors. Results: In the lateral penumbra there was a gradual increase in signal intensity with higher dose throughout the full dose range of 0–37.5 Gy. In the distal dose fall‐off region, the beam appeared to penetrate farther than planned in the central part of the vertebral bodies. The mean overshoot in five patients was 2.71 mm (95% confidence interval 1.13–4.28 mm). These errors are probably not clinically significant with current treatment planning procedures. Conclusion: We have demonstrated in vivo proton range verification based on post‐treatment spine MRI changes. Our analysis indicates that if range errors occur in spine treatments, their magnitude is at most a few millimeters in the majority of patients. It may be possible to extend our technique to MRI sequences that show early bone marrow changes. It could then be used for adaptive modification of spine radiation plans in order to reduce radiation dose to bone marrow and other normal tissues.
    Cortical tubers are very common in tuberous sclerosis complex (TSC) and widely vary in size, appearance and location. The relationship between tuber features and clinical phenotype is unclear. The aim of the study is to propose a... more
    Cortical tubers are very common in tuberous sclerosis complex (TSC) and widely vary in size, appearance and location. The relationship between tuber features and clinical phenotype is unclear. The aim of the study is to propose a classification of tuber types ...
    ABSTRACT Purpose: Uncertainty in the location of the distal dose edge is one of the main concerns about proton therapy. It leads to cautious treatment plans that partially neutralize the dosimetric advantage of protons. Vertebral bone... more
    ABSTRACT Purpose: Uncertainty in the location of the distal dose edge is one of the main concerns about proton therapy. It leads to cautious treatment plans that partially neutralize the dosimetric advantage of protons. Vertebral bone marrow responds to radiation with fatty replacement that is visible on post‐treatment MRI. This presents a unique opportunity to visualize radiation effects in vivo. We have developed a method that uses spine MRI changes to precisely localize the distal dose edge in spinal proton radiation patients. Method and Materials: We carefully registered treatment planning CT scans and follow‐up T1‐weighted MRI scans from 10 proton spinal radiation patients. A radiation dose‐MRI signal intensity curve was created using the lateral beam penumbra in the sacrum. This curve was then used to quantitatively examine possible systematic or spatially varying proton range errors. Results: In the lateral penumbra there was a gradual increase in signal intensity with higher dose throughout the full dose range of 0–37.5 Gy. In the distal dose fall‐off region, the beam appeared to penetrate farther than planned in the central part of the vertebral bodies. The mean overshoot in five patients was 2.71 mm (95% confidence interval 1.13–4.28 mm). These errors are probably not clinically significant with current treatment planning procedures. Conclusion: We have demonstrated in vivo proton range verification based on post‐treatment spine MRI changes. Our analysis indicates that if range errors occur in spine treatments, their magnitude is at most a few millimeters in the majority of patients. It may be possible to extend our technique to MRI sequences that show early bone marrow changes. It could then be used for adaptive modification of spine radiation plans in order to reduce radiation dose to bone marrow and other normal tissues.