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Biomedical subjects

P Ellen Grant

Publications and source records attributed to P Ellen Grant.

At least 19 recordsLinked to original sources
PubMed2006

Detailed semiautomated MRI based morphometry of the neonatal brain: preliminary results.

In the neonate, regional growth trajectories provide information about the coordinated development of cerebral substructures and help identify regional vulnerability by identifying times of faster growth. Segmentation of magnetic resonance images (MRI) has provided detailed information for the myelinated brain but few reports of regional neonatal brain growth exist. We report the method and preliminary results of detailed semiautomated segmentation of 12 normative neonatal brains (gestational age 31.1-42.6 weeks at time of MRI) using volumetric T1-weighted images. Accuracy was confirmed by expert review of every segmented image. In 5 brains, repeat segmentation resulted in intraclass correlation coefficients >0.9 (except for the right amygdala) and an average percent voxel overlap of 90.0%. Artifacts or image quality limited the number of regions segmented in 9/12 data sets and 1/12 was excluded from volumetric analysis due to ventriculomegaly. Brains were segmented into cerebral exterior (N = 8), cerebral lobes (N = 5), lateral ventricles (N = 8), cerebral cortex (N = 6), white matter (N = 6), corpus callosum (N = 7), deep central gray (N = 8), hippocampi (N = 8), amygdalae (N = 8), cerebellar hemispheres (N = 8), vermis (N = 8), midbrain (N = 8), pons (N = 8) and medulla (N = 8). Linear growth (P < 0.05) was identified in all regions except the cerebral white matter, medulla and ventricles. Striking differences in regional growth rates were noted. These preliminary results are consistent with the heterochronous nature of cerebral development and provide initial estimates of regional brain growth and therefore regional vulnerability in the perinatal time period.

Algorithms↗
PubMed2006

Acute injury to the immature brain with hypoxia with or without hypoperfusion.

Hypoxia with or without hypoperfusion is a common mechanism of injury in the immature brain and can result in normal or minimally abnormal imaging studies in the first 12 hours. Often, injury progresses over time suggesting a central role for delayed cell death pathways. An awareness of the patterns of injury associated with different mechanisms of injury and the central role of delayed cell death pathways in injury evolution is important for the radiologist to understand the significance and potential outcome of these injuries.

Journal Article↗
PubMed2006

Diffusion-weighted MR imaging: pediatric clinical applications.

We have summarized the diffusion-weighed imaging (DWI) findings in a number of different cerebral disorders. In many cases, DWI with the accompanying apparent diffusion coefficient (ADC) map provides additional useful information to the standard imaging sequences. Pathophysiologic mechanisms resulting in baseline normal ADC values and changes with disease processes are not well understood; therefore, caution should be used when prognosticating the outcome of regions with abnormal ADCs. DWI should be used as an adjunct to routine imaging and interpreted in the context of the routine imaging findings and clinical scenario. As our understanding of ADC mechanisms increases and we begin to incorporate information about tissue organization from diffusion tensor imaging or diffusion spectrum imaging, the role of these methods in clinical diagnosis should continue to increase.

Brain Diseases↗
PubMed2006

Acute injury to the immature brain with hypoxia with or without hypoperfusion.

This article reviews the imaging features and evolution of immature brain injury caused by hypoxia with or without hypoperfusion in the neonate and young child. Clinical presentations and available literature on mechanisms and clinical outcomes are discussed. In many of these cases, diffusion-weighted imaging does not show the full extent of the injury but detects a pattern of injury that is important in guiding clinical care. Awareness of the delayed cell death mechanisms is essential to understand diffusion-weighted imaging sensitivity and evolution and to provide the most accurate clinical interpretation, especially in cases of hypoxia with or without hypoperfusion.

Age Factors↗
PubMed2006

Proton magnetic resonance spectroscopy and diffusion-weighted imaging in isolated sulfite oxidase deficiency.

Isolated sulfite oxidase deficiency is a rare autosomal recessive disorder of the newborn that can be mistaken for neonatal asphyxia. Diffusion-weighted imaging of the brain demonstrates widespread diffusion restriction, and proton magnetic resonance spectroscopy shows an elevated lactate level, a decrease in the ratio of N-acetylaspartate to creatine, and a rise in the ratio of choline to creatine. This precedes severe cystic encephalomalacia and suggests that the energy failure associated with neuronal dysfunction and myelin disintegration occurs early in isolated sulfite oxidase deficiency.

Amino Acid Metabolism, Inborn Errors↗
PubMed2005

Pediatric stroke: the child is not merely a small adult.

Arterial ischemic stroke and sinovenous thrombosis are a significant yet under-recognized causes of mortality and morbidity in the pediatric population. With increasingly complex etiologies yet urgency for rapid diagnosis and treatment, pediatric stroke teams likely will become the standard of care. A common terminology must be developed to avoid confusing types of acute cerebral insults--such as focal arterial ischemic stroke and global hypoxia and ischemia--that have different causes and pathophysiologic mechanisms of injury. Increased awareness of unique pediatric stroke subtypes, their clinical presentation, and their imaging findings will facilitate early identification and development of optimal treatment strategies.

Adolescent↗
PubMed2005

Imaging the developing epileptic brain.

Accurate identification of cortical malformations in children with epilepsy can be crucial for successful clinical management. Although standard head-coil magnetic resonance imaging (MRI) at 1.5 tesla (T) can be used to view the macrostructure of the brain, phased array technology at both 1.5 and 3T significantly improves signal-to-noise ratio (SNR). As a result, spatial resolution and contrast can be optimized to increase visual detection of subtle macrostructural changes that occur with small epileptogenic lesions. In addition, these improvements in SNR allow more accurate quantitative analysis of brain macrostructure and more accurate assessment of brain microstructure using newer sophisticated imaging techniques. For example, phased array imaging enables more accurate diffusion tensor imaging (DTI), and 3T imaging, when combined with phased array technology, enables more informative diffusion spectroscopic imaging (DSI). Recent technological improvements therefore result in improved lesion detection and enable assessment of cerebral growth trajectories and associated longitudinal changes in tissue microstructural organization that occur in association with various types of epilepsy. This article presents a brief comparison of imaging techniques currently in use, both clinically and experimentally, to diagnose, treat, and increase our understanding of the neuropathology of epilepsy in the developing brain.

Adult↗
PubMed2005

Structural brain magnetic resonance imaging of limbic and thalamic volumes in pediatric bipolar disorder.

BACKGROUND: Youths with bipolar disorder are ideal for studying illness pathophysiology given their early presentation, lack of extended treatment, and high genetic loading. Adult bipolar disorder MRI studies have focused increasingly on limbic structures and the thalamus because of their role in mood and cognition. On the basis of adult studies, the authors hypothesized a priori that youths with bipolar disorder would have amygdalar, hippocampal, and thalamic volume abnormalities. METHOD: Forty-three youths 6-16 years of age with DSM-IV bipolar disorder (23 male, 20 female) and 20 healthy comparison subjects (12 male, eight female) similar in age and sex underwent structured and clinical interviews, neurological examination, and cognitive testing. Differences in limbic and thalamic brain volumes, on the logarithmic scale, were tested using a two-way (diagnosis and sex) univariate analysis of variance, with total cerebral volume and age controlled. RESULTS: The subjects with bipolar disorder had smaller hippocampal volumes. Further analysis revealed that this effect was driven predominantly by the female bipolar disorder subjects. In addition, both male and female youths with bipolar disorder had significantly smaller cerebral volumes. No significant hemispheric effects were seen. CONCLUSIONS: These findings support the hypothesis that the limbic system, in particular the hippocampus, may be involved in the pathophysiology of pediatric bipolar disorder. While this report may represent the largest MRI study of pediatric bipolar disorder to date, more work is needed to confirm these findings and to determine if they are unique to pediatric bipolar disorder.

Adolescent↗
PubMed2005

Dynamic statistical parametric mapping for analyzing the magnetoencephalographic epileptiform activity in patients with epilepsy.

Our current purpose is to evaluate the applicability of dynamic statistical parametric mapping, a novel method for localizing epileptiform activity recorded with magnetoencephalography in patients with epilepsy. We report four pediatric patients with focal epilepsies. Magnetoencephalographic data were collected with a 306-channel whole-head helmet-shaped sensor array. We calculated equivalent current dipoles and dynamic statistical parametric mapping movies of the interictal epileptiform discharges that were based in the minimum-L2 norm estimate, minimizing the square sum of the dipole element amplitudes. The dynamic statistical parametric mapping analysis of interictal epileptiform discharges can demonstrate the rapid change and propagation of interical epileptiform discharges. According to these findings, specific epileptogenic lesion-focal cortical dysplasia could be found and patients could be operated on successfully. The presurgical analysis of interictal epileptiform discharges using dynamic statistical parametric mapping seems to be promising in patients with a possible underlying focal cortical dysplasia and might help to guide the placement of invasive electrodes.

Adolescent↗
PubMed2005

Isolated sulfite oxidase deficiency: a case report with a novel mutation and review of the literature.

Isolated sulfite oxidase deficiency is a rare but devastating neurologic disease that usually presents in early infancy with seizures and alterations in muscle tone. Only 21 cases have been reported in the literature. We report a case of a newborn infant boy with isolated sulfite oxidase deficiency who presented with generalized seizures on his fourth day of life. Plasma total homocysteine was not detectable. Urinary sulfite, thiosulfate, and S-sulfocysteine levels were elevated. The patient began a low-methionine and low-cysteine diet and was treated with thiamine and dextromethorphan. However, he became increasingly microcephalic and was severely developmentally delayed. Mutation analysis of the sulfite oxidase gene revealed that the patient was homozygous for a novel 4-base pair deletion, and both of his parents were found to be heterozygous carriers of the same deletion. We reviewed the clinical, biochemical, neuroradiologic, and neuropathologic features in all published cases of isolated sulfite oxidase deficiency. Seizures or abnormal movements were prominent features in all cases. Developmental delays were reported in 17 cases. Ectopia lentis was detected in 9 cases. Clinical improvement with dietary therapy was seen in only 2 patients, both of whom presented after the age of 6 months and had relatively mild developmental delays. Plasma or urinary S-sulfocysteine levels were elevated in all cases. Urinary sulfite was detected in all except 1 case. Cerebral atrophy and cystic encephalomalacia were observed with neuroradiologic imaging and were noted in all 3 postmortem reports of isolated sulfite oxidase deficiency. The main alternative in the differential diagnosis of isolated sulfite oxidase deficiency is molybdenum cofactor deficiency.

Amino Acid Metabolism, Inborn Errors↗
PubMed2004

Multimodal longitudinal imaging of focal status epilepticus.

BACKGROUND: Little is understood about the evolution of structural and functional brain changes during the course of uncontrolled focal status epilepticus in humans. METHODS: We serially evaluated and treated a nine-year-old girl with refractory focal status epilepticus. Long-term EEG monitoring, MRI, MRA, SPECT, intraoperative visualization of affected cortex, and neuropathological examination of a biopsy specimen were conducted over a three year time span. Imaging changes were correlated with simultaneous treatment and EEG findings. RESULTS: The EEG monitoring showed almost continuous spike discharges emanating initially from the right frontocentral area. These EEG abnormalities were intermittently suppressed by treatment with anesthetics. Over time, additional brain areas developed epileptiform EEG abnormalities. Serial MRI studies demonstrated an evolution of changes from normal, through increased regional T2 signal to generalized atrophy. An MRA demonstrated dilatation of the middle cerebral artery stem on the right compared to the left with a broad distribution of flow-related enhancement. An 18FDG-PET scan showed a dramatically abnormal metabolic profile in the same right frontocentral areas, which modulated in response to treatment during the course of the illness. A right frontotemporal craniotomy revealed a markedly hyperemic cortical focus including vascular shunting. A sample of resected cortex showed severe gliosis and neuronal death. CONCLUSIONS: The co-registration of structural and functional imaging and its correlation with operative and pathological findings in this case illustrates the relentless progression of regional and generalized abnormalities in intractable focal status epilepticus that were only transiently modified by exhaustive therapeutic interventions. Increased flow through large vessels appeared to be shunted and did not translate into increased microvascular perfusion.

Atrophy↗
PubMed2004

Structural MR imaging.

Phased-array imaging at 1.5 and 3 T significantly improves image quality compared with that in routine 1.5-T head coil studies. These improvements significantly increase lesion detection in patients with focal epilepsy. Semiautomated image-analysis techniques have the potential to improve lesion detection, assess lesion burden more accurately, characterize cortical abnormalities, and determine the location and extent of associated cortical and deep gray nuclei involvement. With increasing interest in understanding the role white matter plays in epileptogenesis and seizure propagation, diffusion tensor imaging may yield useful information about changes in white matter organization. Our current multimodality imaging combines these structural imaging advances with coregistered neurophysiological information obtained with magnetoencephalography and with simultaneous EEG recordings. Our initial experience suggests that multimodality imaging will improve our ability to detect and define the extent of epileptogenic lesions.

Adult↗
PubMed2004

Evolution of water diffusion and anisotropy in hyperacute stroke: significant correlation between fractional anisotropy and T2.

BACKGROUND AND PURPOSE: We hypothesized that, in acute cerebral ischemic stroke, anisotropic diffusion increases if T2 signal intensity is not substantially elevated and decreases once T2 hyperintensity becomes apparent. Our purpose was to correlate fractional anisotropy (FA) measurements with the clinical time of stroke onset, apparent diffusion coefficients (ADC), and T2 signal intensity. METHODS: Tensor diffusion-weighted images (DWIs) of 25 patients were obtained within 12 hours of symptom onset. Trace DWIs, ADCs, FAs, and echo-planar T2-weighted images (T2WI) were generated. Stroke and contralateral normal volumes of interest (VOIs) were outlined on DWIs and projected onto the inherently coregistered ADC map, FA map, and echo-planar T2WI. Mean signal intensity of the ischemic and contralateral normal VOIs were compared for relatives change in ADC, FA, and signal intensity on T2WIs. RESULTS: A significant negative correlation was observed between FA and T2 signal-intensity change (r = -0.61, P =.00009). A trend of correlation between FA signal intensity and time of onset were found (r = -0.438, P =.025). No significant correlation was found between ADC and FA values (r = -0.302, P =.134). The mean ADC reduction in the ipsilateral ischemic volume was 31% +/- 11 compared with the contralateral normal side. CONCLUSION: Change in FA is inversely correlated with T2 signal intensity and, to a lesser extent, the time of onset, but it is not well correlated with ADC values in the acute stage.

Acute Disease↗