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Search Results: 1 - 10 of 219326 matches for " John G Csernansky "
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Neurodegeneration in Schizophrenia: Evidence from In Vivo Neuroimaging Studies
John G. Csernansky
The Scientific World Journal , 2007, DOI: 10.1100/tsw.2007.47
Improving the long term outcome of schizophrenia
Csernansky John
Annals of General Psychiatry , 2006, DOI: 10.1186/1744-859x-5-s1-s28
Neuroanatomical markers of early Alzheimer's disease
Csernansky John
Annals of General Psychiatry , 2006, DOI: 10.1186/1744-859x-5-s1-s33
Large deformation diffeomorphic metric mapping registration of reconstructed 3D histological section images and in vivo MR images
Can Ceritoglu,Lei Wang,Lynn D. Selemon,John G. Csernansky,Michael I. Miller,J. Tilak Ratnanather
Frontiers in Human Neuroscience , 2010, DOI: 10.3389/fnhum.2010.00043
Abstract: Our current understanding of neuroanatomical abnormalities in neuropsychiatric diseases is based largely on magnetic resonance imaging (MRI) and post mortem histological analyses of the brain. Further advances in elucidating altered brain structure in these human conditions might emerge from combining MRI and histological methods. We propose a multistage method for registering 3D volumes reconstructed from histological sections to corresponding in vivo MRI volumes from the same subjects: (1) manual segmentation of white matter (WM), gray matter (GM) and cerebrospinal fluid (CSF) compartments in histological sections, (2) alignment of consecutive histological sections using 2D rigid transformation to construct a 3D histological image volume from the aligned sections, (3) registration of reconstructed 3D histological volumes to the corresponding 3D MRI volumes using 3D affine transformation, (4) intensity normalization of images via histogram matching, and (5) registration of the volumes via intensity based large deformation diffeomorphic metric (LDDMM) image matching algorithm. Here we demonstrate the utility of our method in the transfer of cytoarchitectonic information from histological sections to identify regions of interest in MRI scans of nine adult macaque brains for morphometric analyses. LDDMM improved the accuracy of the registration via decreased distances between GM/CSF surfaces after LDDMM (0.39 ± 0.13 mm) compared to distances after affine registration (0.76 ± 0.41 mm). Similarly, WM/GM distances decreased to 0.28 ± 0.16 mm after LDDMM compared to 0.54 ± 0.39 mm after affine registration. The multistage registration method may find broad application for mapping histologically based information, for example, receptor distributions, gene expression, onto MRI volumes.
A Longitudinal Analysis of Regional Brain Volumes in Macaques Exposed to X-Irradiation in Early Gestation
Kristina Aldridge, Lei Wang, Michael P. Harms, Amanda J. Moffitt, Kimberly K. Cole, John G. Csernansky, Lynn D. Selemon
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0043109
Abstract: Background Early gestation represents a period of vulnerability to environmental insult that has been associated with adult psychiatric disease. However, little is known about how prenatal perturbation translates into adult brain dysfunction. Here, we use a longitudinal study design to examine the effects of disruption of early gestational neurogenesis on brain volume in the non-human primate. Methods and Principal Findings Five Rhesus macaques were exposed to x-irradiation in early gestation (E30–E41), and four control monkeys were sham-irradiated at comparable ages. Whole brain magnetic resonance imaging was performed at 6 months, 12 months, and 3 and 5 years of age. Volumes of whole cerebrum, cortical gray matter, caudate, putamen, and thalamus were estimated using semi-automated segmentation methods and high dimensional brain mapping. Volume reductions spanning all ages were observed in irradiated monkeys in the putamen (15–24%, p = 0.01) and in cortical gray matter (6–15%, p = 0.01). Upon covarying for whole cerebral volume, group differences were reduced to trend levels (putamen: p = 0.07; cortical gray matter: p = 0.08). No group-by-age effects were significant. Conclusions Due to the small number of observations, the conclusions drawn from this study must be viewed as tentative. Early gestational irradiation may result in non-uniform reduction of gray matter, mainly affecting the putamen and cerebral cortex. This may be relevant to understanding how early prenatal environmental insult could lead to brain morphological differences in neurodevelopmental diseases.
Relationships among neurocognition, symptoms and functioning in patients with schizophrenia: a path-analytic approach for associations at baseline and following 24 weeks of antipsychotic drug therapy
Ilya A Lipkovich, Walter Deberdt, John G Csernansky, Bernard Sabbe, Richard SE Keefe, Sara Kollack-Walker
BMC Psychiatry , 2009, DOI: 10.1186/1471-244x-9-44
Abstract: Data were obtained from a clinical trial assessing the cognitive effects of selected antipsychotic drugs in patients with schizophrenia. Patients were randomly assigned to 24 weeks of treatment with olanzapine (n = 159), risperidone (n = 158), or haloperidol (n = 97). Psychosocial functioning was assessed with the Heinrichs-Carpenter Quality of Life Scale [QLS], cognition with a standard battery of neurocognitive tests; and psychiatric symptoms with the Positive and Negative Syndrome Scale [PANSS]. A path-analytic approach was used to evaluate the effects of changes in cognitive functioning on subdomains of quality of life, and to determine whether such effects were direct or mediated via changes in psychiatric symptoms.At baseline, processing speed affected functioning mainly indirectly via negative symptoms. Positive symptoms also affected functioning at baseline although independent of cognition. At 24 weeks, changes in processing speed affected changes in functioning both directly and indirectly via PANSS negative subscale scores. Positive symptoms no longer contributed to the path-analytic models. Although a consistent relationship was observed between processing speed and the 3 functional domains, variation existed as to whether the paths were direct and/or indirect. Working memory and verbal memory did not significantly contribute to any of the path-analytic models studied.Processing speed demonstrated direct and indirect effects via negative symptoms on three domains of functioning as measured by the QLS at baseline and following 24 weeks of antipsychotic treatment.Neurocognitive impairment has been found to be strongly correlated with deficits in psychosocial and occupational functioning in patients with schizophrenia [1,2]. These earlier reviews of the literature (including a meta-analysis) were focused on identifying specific neurocognitive deficits that restrict the functioning of schizophrenia patients, as opposed to the use of more global measures of n
Analysis of Metric Distances and Volumes of Hippocampi Indicates Different Morphometric Changes over Time in Dementia of Alzheimer Type and Nondemented Subjects
Elvan Ceyhan,Can Ceritoglu,M. Faisal Beg,Lei Wang,John C. Morris,John G. Csernansky,Michael I. Miller,John Tilak Ratnanather
Statistics , 2008,
Abstract: In this article, we analyze the morphometry of hippocampus in subjects with very mild dementia of Alzheimer's type (DAT) and nondemented controls and how it changes over a two-year period. Morphometric differences with respect to a template hippocampus were measured by the metric distance obtained from the Large Deformation Diffeomorphic Metric Mapping (LDDMM) algorithm which was previously used to calculate dense one-to-one correspondence vector fields between the shapes. LDDMM assigns metric distances on the space of anatomical images thereby allowing for the direct comparison and quantization of morphometric changes. We use various statistical methods to compare the metric distances in a cross-sectional and longitudinal manner. At baseline, the metric distances for demented subjects are found not to be significantly different from those for nondemented subjects. At follow-up, the metric distances for demented subjects were significantly larger compared to nondemented subjects. The metric distances for demented subjects increased significantly from baseline to follow-up but not for nondemented subjects. We also use the metric distances in logistic regression for diagnostic discrimination of subjects. We compare metric distances with the volumes and obtain similar results. In classification, the model that uses volume, metric distance, and volume loss over time together performs better in detecting DAT. Thus, metric distances with respect to a template computed via LDDMM can be a powerful tool in detecting differences in shape in cross-sectional as well as longitudinal studies.
MRI Shows More Severe Hippocampal Atrophy and Shape Deformation in Hippocampal Sclerosis Than in Alzheimer's Disease
C. Zarow,L. Wang,H. C. Chui,M. W. Weiner,J. G. Csernansky
International Journal of Alzheimer's Disease , 2011, DOI: 10.4061/2011/483972
Abstract: While hippocampal atrophy is a key feature of both hippocampal sclerosis (HS) and Alzheimer's disease (AD), the pathology underlying this finding differs in these two conditions. In AD, atrophy is due primarily to loss of neurons and neuronal volume as a result of neurofibrillary tangle formation. While the etiology of HS is unknown, neuron loss in the hippocampus is severe to complete. We compared hippocampal volume and deformations from premortem MRI in 43 neuropathologically diagnosed cases of HS, AD, and normal controls (NC) selected from a longitudinal study of subcortical ischemic vascular disease (IVD Program Project). HS cases ( ) showed loss of neurons throughout the rostral-caudal extent of the hippocampus in one or both hemispheres. AD cases ( ) met NIA-Reagan criteria for high likelihood of AD. Normal control cases ( ) were cognitively intact and showed no significant AD or hippocampal pathology. The mean hippocampal volumes were significantly lower in HS versus AD groups ( ). Mean shape deformations in the CA1 and subiculum differed significantly between HS versus AD, HS versus NC, and AD versus NC ( ). Additional study is needed to determine whether these differences will be meaningful for clinical diagnosis of individual cases. 1. Introduction Hippocampal sclerosis (HS) is a highly prevalent pathologic lesion, found in approximately 15% of elderly dementia cases in autopsy series [1]. It is a common cause of memory loss in late life, but is rarely diagnosed before autopsy. HS is characterized by selective neuronal loss with gliosis in the absence of cystic cavitation, involving the CA1 sector of the hippocampus and often extending into the subiculum. A sharp demarcation is often noted histologically between affected and adjacent normal hippocampal subfields. HS can affect one or both hemispheres and can be focal or widespread in its rostral-caudal extent [2]. HS is often accompanied by other types of pathology, but may occur as a relatively isolated finding [1]. The pathogenesis of HS is not well understood, and ischemia/hypoxia, neurodegeneration, or a combination of these nonmutually exclusive processes has been postulated. A clinical diagnosis of HS is rarely made in late life. Most HS cases are discovered at autopsy and were diagnosed clinically as AD. The typical hallmarks of HS seen in early adulthood (namely, partial complex seizures and T-2 hyperintensity in the hippocampus) are absent in late-onset HS [3–5]. While hippocampal atrophy is the sine qua non of AD, it is also observed in HS. Late-life HS is associated with hippocampal
Diabetes mortality and environmental heavy metals in North Carolina counties: An ecological study  [PDF]
John G. Spangler
Journal of Diabetes Mellitus (JDM) , 2012, DOI: 10.4236/jdm.2012.24057
Abstract: Introduction: Arsenic, beryllium, cadmium and nickel have been associated with the prevalence of diabetes mellitus in populations exposed to these elements. However, diabetes mortality has not been evaluated. This ecological study correlated airborne concentrations of these metals with diabetes mortality in North Carolina counties. Methods: County level data were extracted from the 2000 US Census, the 1999 US Environmental Protection Agency National Air Toxins Assessment, and 2001-2005 diabetes mortality rates by county from the North Carolina State Center for Health Statistics. Multivariable linear regression correlated airborne concentrations of each element with diabetes mellitus mortality rates in all 100 North Carolina counties controlling for county-level characteristics. Airborne concentrations were logarithmically transformed to normalize their distribution. Results: The lowest air concentrations detected were beryllium and cadmium, with nickel showing the highest concentration. Logarithmic concentrations spanned from 3.74 to 4.02 orders of magnitude. County-level diabetes mortality rates were negatively associated with median county income, but positively associated with county-level air concentrations of arsenic, beryllium, cadmium and nickel. Conclusions: These results support diabetes mortality effects of air pollution, and agree with other studies correlating arsenic, beryllium, cadmium and nickel with diabetes prevalence. Policy implications include regulating point source air pollution.
The myocardial microcirculation: A key target for salvaging ischemic myocardium?  [PDF]
John G. Kingma
World Journal of Cardiovascular Diseases (WJCD) , 2013, DOI: 10.4236/wjcd.2013.35A002
Abstract: Clinical management of patients with acute myocardial infarction for the most part involves re-opening of an infarct-related coronary vessel by the use of clot-busting pharmacologic treatment or percutaneous coronary interventions. While blood flow in the epicardial coronary vessel is restored downstream, effects remain largely unexplored; progressive injury at the microvessel level has significant repercussions on restoration of cardiocyte viability and the ventricular blood flow and contractile function relationship. This review focuses on the cardiac microcirculation and the fact that it should be a principle target of future studies to permit improvement of clinical outcomes in patients presenting with evolving myocardial infarction.

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