The Experts below are selected from a list of 30012 Experts worldwide ranked by ideXlab platform

Allan G Johnson - One of the best experts on this subject based on the ideXlab platform.

  • qualitative and quantitative neuropathology approaches using Magnetic Resonance Microscopy diffusion tensor imaging and stereology in a hexachlorophene model of myelinopathy in sprague dawley rats
    Toxicologic Pathology, 2020
    Co-Authors: Robert C Sills, Allan G Johnson, Robert J Anderson, Crystal L Johnson, Michael Staup, Danielle L Brown, Sheba R Churchill, David M Kurtz, Jesse D Cushman, Suramya Waidyanatha
    Abstract:

    It is well established that hexachlorophene, which is used as an antibacterial agent, causes intramyelinic edema in humans and animal models. The hexachlorophene myelinopathy model, in which male Sprague-Dawley rats received 25 to 30 mg/kg hexachlorophene by gavage for up to 5 days, provided an opportunity to compare traditional neuropathology evaluations with Magnetic Resonance Microscopy (MRM) findings. In addition, stereology assessments of 3 neuroanatomical sites were compared to quantitative measurements of similar structures by MRM. There were positive correlations between hematoxylin and eosin and luxol fast blue stains and MRM for identifying intramyelinic edema in the cingulum of corpus callosum, optic chiasm, anterior commissure (aca), lateral olfactory tracts, pyramidal tracts (py), and white matter tracts in the cerebellum. Stereology assessments were focused on the aca, longitudinal fasciculus of the pons, and py and demonstrated differences between control and treated rats, as was observed using MRM. The added value of MRM assessments was the ability to acquire qualitative 3-dimensional (3-D) images and obtain quantitative measurements of intramyelinic edema in 26 neuroanatomical sites in the intact brain. Also, diffusion tensor imaging (fractional anisotropy [FA]) indicated that there were changes in the cytoarchitecture of the white matter as detected by decreases in the FA in the treated compared to the control rats. This study demonstrates creative strategies that are possible using qualitative and quantitative assessments of potential white matter neurotoxicants in nonclinical toxicity studies. Our results lead us to the conclusion that volumetric analysis by MRM and stereology adds significant value to the standard 2-D microscopic evaluations.

  • Magnetic Resonance Microscopy based analyses of the neuroanatomical effects of gestational day 9 ethanol exposure in mice
    Neurotoxicology and Teratology, 2013
    Co-Authors: Scott E Parnell, Allan G Johnson, Shonagh K Olearymoore, Deborah B Dehart, Martin Styner, Hunter T Holloway, Beatriz Paniaqua, Ipek Oguz, Francois Budin, Kathleen K Sulik
    Abstract:

    Abstract Animal model-based studies have shown that ethanol exposure during early gestation induces developmental stage-specific abnormalities of the face and brain. The exposure time-dependent variability in ethanol's teratogenic outcomes is expected to contribute significantly to the wide spectrum of effects observed in humans with fetal alcohol spectrum disorder (FASD). The work presented here employs a mouse FASD model and Magnetic Resonance Microscopy (MRM; high resolution Magnetic Resonance imaging) in studies designed to further our understanding of the developmental stage-specific defects of the brain that are induced by ethanol. At neurulation stages, i.e. at the beginning of gestational day (GD) 9 and again 4 hours later, time-mated C57Bl/6J dams were intraperitoneally administered 2.9 g/kg ethanol or vehicle. Ethanol-exposed fetuses were collected on GD 17, processed for MRM analysis, and results compared to comparably staged controls. Linear and volume measurements as well as shape changes for numerous individual brain regions were determined. GD 9 ethanol exposure resulted in significantly increased septal region width, reduction of cerebellar volume, and enlargement of all of the ventricles. Additionally, the results of shape analyses showed that many areas of the ethanol-exposed brains including the cerebral cortex, hippocampus and right striatum were significantly misshapen. These data demonstrate that ethanol can induce dysmorphology that may not be obvious based on volumetric analyses alone, highlight the asymmetric aspects of ethanol-induced defects, and add to our understanding of ethanol’s developmental stage-dependent neuroteratogenesis.

  • Magnetic Resonance Microscopy based analyses of the brains of normal and ethanol exposed fetal mice
    Birth Defects Research Part A-clinical and Molecular Teratology, 2010
    Co-Authors: Shonagh K Olearymoore, Allan G Johnson, Scott E Parnell, Elizabeth A Godin, Deborah B Dehart, Jacob J Ament, Amber A Khan, Martin Styner, Kathleen K Sulik
    Abstract:

    Background The application of Magnetic Resonance Microscopy (MRM) to the study of normal and abnormal prenatal mouse development has facilitated discovery of dysmorphology following prenatal ethanol insult. The current analyses extend this work, providing a regional brain volume-based description of normal brain growth and illustrating the consequences of gestational day (GD) 10 ethanol exposure in the fetal mouse.

  • contrast enhanced in vivo Magnetic Resonance Microscopy of the mouse brain enabled by noninvasive opening of the blood brain barrier with ultrasound
    Magnetic Resonance in Medicine, 2010
    Co-Authors: Gabriel P Howles, Kristin F Bing, Stephen J Rosenzweig, Kathryn R Nightingale, Allan G Johnson
    Abstract:

    The use of contrast agents for neuroimaging is limited by the blood-brain barrier (BBB), which restricts entry into the brain. To administer imaging agents to the brain of rats, intracarotid infusions of hypertonic mannitol have been used to open the BBB. However, this technically challenging approach is invasive, opens only a limited region of the BBB, and is difficult to extend to mice. In this work, the BBB was opened in mice, using unfocused ultrasound combined with an injection of microbubbles. This technique has several notable features: it (a) can be performed transcranially in mice; (b) takes only 3 min and uses only commercially available components; (c) opens the BBB throughout the brain; (d) causes no observed histologic damage or changes in behavior (with peak-negative acoustic pressures of 0.36 MPa); and (e) allows recovery of the BBB within 4 h. Using this technique, Gadopentetate Dimeglumine (Gd-DTPA) was administered to the mouse brain parenchyma, thereby shortening T(1) and enabling the acquisition of high-resolution (52 × 52 × 100 micrometers(3)) images in 51 min in vivo. By enabling the administration of both existing anatomic contrast agents and the newer molecular/sensing contrast agents, this technique may be useful for the study of mouse models of neurologic function and pathology with MRI.

  • Magnetic Resonance Microscopy defines ethanol induced brain abnormalities in prenatal mice effects of acute insult on gestational day 7
    Alcoholism: Clinical and Experimental Research, 2010
    Co-Authors: Elizabeth A Godin, Allan G Johnson, Shonagh K Olearymoore, Scott E Parnell, Deborah B Dehart, Jacob J Ament, Amber A Khan, Martin Styner, Brice W Johnson, Kathleen K Sulik
    Abstract:

    Background:  This Magnetic Resonance Microscopy (MRM)-based report is the second in a series designed to illustrate the spectrum of craniofacial and central nervous system (CNS) dysmorphia resulting from single- and multiple-day maternal ethanol treatment. The study described in this report examined the consequences of ethanol exposure on gestational day (GD) 7 in mice, a time in development when gastrulation and neural plate development begins; corresponding to the mid- to late third week postfertilization in humans. Acute GD 7 ethanol exposure in mice has previously been shown to result in CNS defects consistent with holoprosencephaly (HPE) and craniofacial anomalies typical of those in Fetal Alcohol Syndrome (FAS). MRM has facilitated further definition of the range of GD 7 ethanol-induced defects. Methods:  C57Bl/6J female mice were intraperitoneally (i.p.) administered vehicle or 2 injections of 2.9 g/kg ethanol on day 7 of pregnancy. Stage-matched control and ethanol-exposed GD 17 fetuses selected for imaging were immersion fixed in a Bouins/Prohance solution. MRM was conducted at either 7.0 Tesla (T) or 9.4 T. Resulting 29 μm isotropic spatial resolution scans were segmented and reconstructed to provide 3D images. Linear and volumetric brain measures, as well as morphological features, were compared for control and ethanol-exposed fetuses. Following MRM, selected specimens were processed for routine histology and light microscopic examination. Results:  Gestational day 7 ethanol exposure resulted in a spectrum of median facial and forebrain deficiencies, as expected. This range of abnormalities falls within the HPE spectrum; a spectrum for which facial dysmorphology is consistent with and typically is predictive of that of the forebrain. In addition, other defects including median facial cleft, cleft palate, micrognathia, pituitary agenesis, and third ventricular dilatation were identified. MRM analyses also revealed cerebral cortical dysplasia/heterotopias resulting from this acute, early insult and facilitated a subsequent focused histological investigation of these defects. Conclusions:  Individual MRM scans and 3D reconstructions of fetal mouse brains have facilitated demonstration of a broad range of GD 7 ethanol-induced morphological abnormality. These results, including the discovery of cerebral cortical heterotopias, elucidate the teratogenic potential of ethanol insult during the third week of human prenatal development.

Helene Benveniste - One of the best experts on this subject based on the ideXlab platform.

  • in vivo 3d digital atlas database of the adult c57bl 6j mouse brain by Magnetic Resonance Microscopy
    Frontiers in Neuroanatomy, 2008
    Co-Authors: David Smith, Stephen J Blackband, Patrick R Hof, Helene Benveniste, Bernd Foerster, Scott Hamilton
    Abstract:

    In this study, a 3D digital atlas of the live mouse brain based on Magnetic Resonance Microscopy (MRM) is presented. C57BL/6J adult mouse brains were imaged in vivo on a 9.4 Tesla MR instrument at an isotropic spatial resolution of 100 μm. With sufficient signal-to-noise (SNR) and contrast-to-noise ratio (CNR), 20 brain regions were identified. Several atlases were constructed including 12 individual brain atlases, an average atlas, a probabilistic atlas and average geometrical deformation maps. We also investigated the feasibility of using lower spatial resolution images to improve time efficiency for future morphological phenotyping. All of the new in vivo data were compared to previous published in vitro C57BL/6J mouse brain atlases and the morphological differences were characterized. Our analyses revealed significant volumetric as well as unexpected geometrical differences between the in vivo and in vitro brain groups which in some instances were predictable (e.g. collapsed and smaller ventricles in vitro but not in other instances. Based on these findings we conclude that although in vitro datasets, compared to in vivo images, offer higher spatial resolutions, superior SNR and CNR, leading to improved image segmentation, in vivo atlases are likely to be an overall better geometric match for in vivo studies, which are necessary for longitudinal examinations of the same animals and for functional brain activation studies. Thus the new in vivo mouse brain atlas dataset presented here is a valuable complement to the current mouse brain atlas collection and will be accessible to the neuroscience community on our public domain mouse brain atlas website.

  • a three dimensional digital atlas database of the adult c57bl 6j mouse brain by Magnetic Resonance Microscopy
    Neuroscience, 2005
    Co-Authors: Patrick R Hof, Stephen J Blackband, Samuel C Grant, Robert D Bennett, L A Slatest, Michael Mcguigan, Helene Benveniste
    Abstract:

    A comprehensive three-dimensional digital atlas database of the C57BL/6J mouse brain was developed based on Magnetic Resonance Microscopy images acquired on a 17.6-T superconducting magnet. By using both manual tracing and an atlas-based semi-automatic segmentation approach, T2-weighted Magnetic Resonance Microscopy images of 10 adult male formalin-fixed, excised C57BL/6J mouse brains were segmented into 20 anatomical structures. These structures included the neocortex, hippocampus, amygdala, olfactory bulbs, basal forebrain and septum, caudate-putamen, globus pallidus, thalamus, hypothalamus, central gray, superior colliculi, inferior colliculi, the rest of midbrain, cerebellum, brainstem, corpus callosum/external capsule, internal capsule, anterior commissure, fimbria, and ventricles. The segmentation data were formatted and stored into a database containing three different atlas types: 10 single-specimen brain atlases, an average brain atlas and a probabilistic atlas. Additionally, quantitative group information, such as variations in structural volume, surface area, Magnetic Resonance Microscopy image intensity and local geometry, were computed and stored as an integral part of the database. The database augments ongoing efforts with other high priority strains as defined by the Mouse Phenome Database focused on providing a quantitative framework for accurate mapping of functional, genetic and protein expression patterns acquired by a myriad of technologies and imaging modalities.

  • Magnetic Resonance Microscopy of the c57bl mouse brain
    NeuroImage, 2000
    Co-Authors: Helene Benveniste, Katie Kim, Lin Zhang, Allan G Johnson
    Abstract:

    With the rapid progression in gene technologies, transgenic, targeted, and chemically induced mutations in mice are continually created. The major goal of these studies is to understand and characterize the effects of genotype on anatomy, physiology, and behavior and ultimately the role of genotype in development of disease. The demand for imaging techniques with high spatial resolution potential is rising because such imaging tools would expedite anatomical phenotyping in the genetically altered mice. Magnetic Resonance Microscopy (MRM) is a noninvasive, inherently three-dimensional (3D) imaging technique capable of visualizing several anatomical structures in the small mouse. The 3D nature of MRM also allows for interpretation of complex spatial relationships between substructures, which is important when phenotyping anatomically. The goal of this paper is to systematically describe three major brain regions in the C57BL/6J mouse at microanatomical spatial resolution ranges using in vitro MRM. We explore different MR contrast parameters, voxel sizes, and signal-to-noise ratios to best characterize C57BL/6J mouse brain microstructure by MRM. Further, we compare all MRM images with Nissl-stained brain sections. Major findings were as follows: T2* MR images visualized several gross anatomical regions in the mouse brain but not, for example, subregions within the hippocampus. Diffusion proton stains on the other hand were superior to T2* MR images and delineated many subregions within the hippocampus proper. Finally, contrast enhancement facilitated visualization of hippocampal anatomy on the T2* MR images. The results of this study are part of an ongoing initiative at our Center focused on creating a complete C57BL/6J mouse anatomical 3D image database by MRM.

  • detection of neuritic plaques in alzheimer s disease by Magnetic Resonance Microscopy
    Proceedings of the National Academy of Sciences of the United States of America, 1999
    Co-Authors: Helene Benveniste, Gillian Einstein, K R Kim, Christine M Hulette, G A Johnson
    Abstract:

    Magnetic Resonance Microscopy (MRM) theoretically provides the spatial resolution and signal-to-noise ratio needed to resolve neuritic plaques, the neuropathological hallmark of Alzheimer’s disease (AD). Two previously unexplored MR contrast parameters, T2* and diffusion, are tested for plaque-specific contrast to noise. Autopsy specimens from nondemented controls (n = 3) and patients with AD (n = 5) were used. Three-dimensional T2* and diffusion MR images with voxel sizes ranging from 3 × 10−3 mm3 to 5.9 × 10−5 mm3 were acquired. After imaging, specimens were cut and stained with a microwave king silver stain to demonstrate neuritic plaques. From controls, the alveus, fimbria, pyramidal cell layer, hippocampal sulcus, and granule cell layer were detected by either T2* or diffusion contrast. These structures were used as landmarks when correlating MRMs with histological sections. At a voxel resolution of 5.9 × 10−5 mm3, neuritic plaques could be detected by T2*. The neuritic plaques emerged as black, spherical elements on T2* MRMs and could be distinguished from vessels only in cross-section when presented in three dimension. Here we provide MR images of neuritic plaques in vitro. The MRM results reported provide a new direction for applying this technology in vivo. Clearly, the ability to detect and follow the early progression of amyloid-positive brain lesions will greatly aid and simplify the many possibilities to intervene pharmacologically in AD.

  • histology by Magnetic Resonance Microscopy
    Magnetic Resonance Quarterly, 1993
    Co-Authors: G A Johnson, Helene Benveniste, Robert R Maronpot, Laurence W Hedlund, R D Black, Bradley R Smith
    Abstract:

    Abstract Magnetic Resonance Microscopy (MRM) has advanced from a technical challenge to a practical tool in a wide range of basic sciences. This article focuses on the use of MRM as a tool for histological studies. The technical challenges of limited signal to noise have been overcome by improved radio-frequency (rf) coil design and 3DFT encoding with large arrays. Resolution limits imposed by motion in in vivo studies have been overcome by improved physiologic monitoring and control and projection encoding. Integration of technologies now permits routine studies in vivo down to 50 microns. MRM has also been applied to in vitro studies of fixed tissues where absence of motion allows studies down to 10 microns. The nondestructive nature of the technique allows repeated studies of the same sample, retrospective studies through any arbitrary plane, registered studies using different contrast mechanisms, and examination of valuable specimens. The many and unique proton contrasts provided by MRM, i.e., T1, T2, and diffusion weighting, permit direct examination of the state of water in tissues, something not possible with other microscopic techniques. Finally, the inherent three-dimensional nature of MRM allows acquisition of perfectly registered isotropic 3D arrays that, when displayed with appropriate visualization tools, provide new perspectives to histologic examination. The technology of MRM continues to develop rapidly. New pulse sequences are reducing acquisition times. New computer architectures allow larger arrays. A new class of superconducting rf probe has increased the signal to noise ratio by 10 times. These developments promise routine use of MRM in histology studies with resolution to 1 micron in the near future.

Kathleen K Sulik - One of the best experts on this subject based on the ideXlab platform.

  • dysmorphogenic effects of first trimester equivalent ethanol exposure in mice a Magnetic Resonance Microscopy based study
    Alcoholism: Clinical and Experimental Research, 2014
    Co-Authors: Scott E Parnell, Martin Styner, Hunter T Holloway, Lorinda K Baker, Kathleen K Sulik
    Abstract:

    Background The first trimester of human development and the equivalent developmental period in animal models is a time when teratogenic ethanol (EtOH) exposure induces the major structural birth defects that fall within fetal alcohol spectrum disorder (FASD). Previous FASD research employing an acute high dose maternal intraperitoneal EtOH treatment paradigm has identified sensitive periods for a number of these defects. Extending this work, this investigation utilized high resolution Magnetic Resonance Microscopy (MRM)-based analyses to examine the dysmorphology resulting from maternal dietary EtOH intake occurring during selected first trimester-equivalent time periods. Methods Female C57Bl/6J mice were acclimated to a liquid 4.8% EtOH (v/v)-containing diet, then bred while on standard chow. Dams were again provided the EtOH-containing liquid diet for a period that extended either from the beginning of gestational day (GD) 7 to the end of GD 11 or from the beginning of GD 12 to the end of GD 16. On GD 17, a subset of fetuses was selected for MRM-based analyses. Group comparisons were made for litter characteristics and gross dysmorphology, as well as whole and regional brain volumes. Results EtOH-induced stage of exposure-dependent structural brain abnormalities were observed. The GD 7 to 11 EtOH-exposed group presented with a significant decrease in cerebellar volume and an increase in septal volume, while GD 12 to 16 EtOH treatment resulted in a reduction in right hippocampal volume accompanied by enlarged pituitaries. Additionally, the GD 12 to 16 EtOH exposure caused a high incidence of edema/fetal hydrops. Conclusions These results illustrate the teratogenic impact of maternal dietary EtOH intake occurring at time periods approximately equivalent to weeks 3 through 6 (GD 7 to 11 in mice) and weeks 7 through 12 (GD 12 to 16 in mice) of human gestation, further documenting EtOH's stage of exposure-dependent neuroteratogenic end points and highlighting the vulnerability of selected brain regions during the first trimester. Additionally they suggest that clinical attention should be paid to fetal hydrops as a likely component of FASD.

  • Magnetic Resonance Microscopy based analyses of the neuroanatomical effects of gestational day 9 ethanol exposure in mice
    Neurotoxicology and Teratology, 2013
    Co-Authors: Scott E Parnell, Allan G Johnson, Shonagh K Olearymoore, Deborah B Dehart, Martin Styner, Hunter T Holloway, Beatriz Paniaqua, Ipek Oguz, Francois Budin, Kathleen K Sulik
    Abstract:

    Abstract Animal model-based studies have shown that ethanol exposure during early gestation induces developmental stage-specific abnormalities of the face and brain. The exposure time-dependent variability in ethanol's teratogenic outcomes is expected to contribute significantly to the wide spectrum of effects observed in humans with fetal alcohol spectrum disorder (FASD). The work presented here employs a mouse FASD model and Magnetic Resonance Microscopy (MRM; high resolution Magnetic Resonance imaging) in studies designed to further our understanding of the developmental stage-specific defects of the brain that are induced by ethanol. At neurulation stages, i.e. at the beginning of gestational day (GD) 9 and again 4 hours later, time-mated C57Bl/6J dams were intraperitoneally administered 2.9 g/kg ethanol or vehicle. Ethanol-exposed fetuses were collected on GD 17, processed for MRM analysis, and results compared to comparably staged controls. Linear and volume measurements as well as shape changes for numerous individual brain regions were determined. GD 9 ethanol exposure resulted in significantly increased septal region width, reduction of cerebellar volume, and enlargement of all of the ventricles. Additionally, the results of shape analyses showed that many areas of the ethanol-exposed brains including the cerebral cortex, hippocampus and right striatum were significantly misshapen. These data demonstrate that ethanol can induce dysmorphology that may not be obvious based on volumetric analyses alone, highlight the asymmetric aspects of ethanol-induced defects, and add to our understanding of ethanol’s developmental stage-dependent neuroteratogenesis.

  • Magnetic Resonance based imaging in animal models of fetal alcohol spectrum disorder
    Neuropsychology Review, 2011
    Co-Authors: Shonagh K Olearymoore, Scott E Parnell, Robert J Lipinski, Kathleen K Sulik
    Abstract:

    Magnetic Resonance imaging (MRI) techniques, such as Magnetic Resonance Microscopy (MRM), diffusion tensor imaging (DTI), and Magnetic Resonance spectroscopy (MRS), have recently been applied to the study of both normal and abnormal structure and neurochemistry in small animals. Herein, findings from studies in which these methods have been used for the examination of animal models of Fetal Alcohol Spectrum Disorder (FASD) are discussed. Emphasis is placed on results of imaging studies in fetal and postnatal mice that have highlighted the developmental stage dependency of prenatal ethanol exposure-induced CNS defects. Consideration is also given to the promise of methodological advances to allow in vivo studies of aberrant brain and behavior relationships in model animals and to the translational nature of this work.

  • Magnetic Resonance Microscopy based analyses of the brains of normal and ethanol exposed fetal mice
    Birth Defects Research Part A-clinical and Molecular Teratology, 2010
    Co-Authors: Shonagh K Olearymoore, Allan G Johnson, Scott E Parnell, Elizabeth A Godin, Deborah B Dehart, Jacob J Ament, Amber A Khan, Martin Styner, Kathleen K Sulik
    Abstract:

    Background The application of Magnetic Resonance Microscopy (MRM) to the study of normal and abnormal prenatal mouse development has facilitated discovery of dysmorphology following prenatal ethanol insult. The current analyses extend this work, providing a regional brain volume-based description of normal brain growth and illustrating the consequences of gestational day (GD) 10 ethanol exposure in the fetal mouse.

  • Magnetic Resonance Microscopy defines ethanol induced brain abnormalities in prenatal mice effects of acute insult on gestational day 7
    Alcoholism: Clinical and Experimental Research, 2010
    Co-Authors: Elizabeth A Godin, Allan G Johnson, Shonagh K Olearymoore, Scott E Parnell, Deborah B Dehart, Jacob J Ament, Amber A Khan, Martin Styner, Brice W Johnson, Kathleen K Sulik
    Abstract:

    Background:  This Magnetic Resonance Microscopy (MRM)-based report is the second in a series designed to illustrate the spectrum of craniofacial and central nervous system (CNS) dysmorphia resulting from single- and multiple-day maternal ethanol treatment. The study described in this report examined the consequences of ethanol exposure on gestational day (GD) 7 in mice, a time in development when gastrulation and neural plate development begins; corresponding to the mid- to late third week postfertilization in humans. Acute GD 7 ethanol exposure in mice has previously been shown to result in CNS defects consistent with holoprosencephaly (HPE) and craniofacial anomalies typical of those in Fetal Alcohol Syndrome (FAS). MRM has facilitated further definition of the range of GD 7 ethanol-induced defects. Methods:  C57Bl/6J female mice were intraperitoneally (i.p.) administered vehicle or 2 injections of 2.9 g/kg ethanol on day 7 of pregnancy. Stage-matched control and ethanol-exposed GD 17 fetuses selected for imaging were immersion fixed in a Bouins/Prohance solution. MRM was conducted at either 7.0 Tesla (T) or 9.4 T. Resulting 29 μm isotropic spatial resolution scans were segmented and reconstructed to provide 3D images. Linear and volumetric brain measures, as well as morphological features, were compared for control and ethanol-exposed fetuses. Following MRM, selected specimens were processed for routine histology and light microscopic examination. Results:  Gestational day 7 ethanol exposure resulted in a spectrum of median facial and forebrain deficiencies, as expected. This range of abnormalities falls within the HPE spectrum; a spectrum for which facial dysmorphology is consistent with and typically is predictive of that of the forebrain. In addition, other defects including median facial cleft, cleft palate, micrognathia, pituitary agenesis, and third ventricular dilatation were identified. MRM analyses also revealed cerebral cortical dysplasia/heterotopias resulting from this acute, early insult and facilitated a subsequent focused histological investigation of these defects. Conclusions:  Individual MRM scans and 3D reconstructions of fetal mouse brains have facilitated demonstration of a broad range of GD 7 ethanol-induced morphological abnormality. These results, including the discovery of cerebral cortical heterotopias, elucidate the teratogenic potential of ethanol insult during the third week of human prenatal development.

Stephen J Blackband - One of the best experts on this subject based on the ideXlab platform.

  • Magnetic Resonance Microscopy mrm of single mammalian myofibers and myonuclei
    Scientific Reports, 2017
    Co-Authors: Choong H Lee, Niclas E Bengtsson, Stephen M Chrzanowski, Jeremy J Flint, Glenn A Walter, Stephen J Blackband
    Abstract:

    Recently, the first Magnetic Resonance Microscopy (MRM) images at the cellular level in isolated mammalian brain tissues were obtained using microsurface coils. These methods can elucidate the cellular origins of MR signals and describe how these signals change over the course of disease progression and therapy. In this work, we explore the capability of these microimaging techniques to visualize mouse muscle fibers and their nuclei. Isolated myofibers expressing lacZ were imaged with and without a stain for β-galactosidase activity (S-Gal + ferric ammonium citrate) that produces both optical and MR contrast. We found that MRM can be used to image single myofibers with 6-μm resolution. The ability to image single myofibers will serve as a valuable tool to study MR properties attributed to healthy and myopathic cells. The ability to image nuclei tagged with MR/Optical gene markers may also find wide use in cell lineage MRI studies.

  • a microperfusion and in bore oxygenator system designed for Magnetic Resonance Microscopy studies on living tissue explants
    Scientific Reports, 2015
    Co-Authors: Jeremy J Flint, Stephen J Blackband, Brian Benjamin Hansen, Kannan Menon, John R Forder
    Abstract:

    Spectrometers now offer the field strengths necessary to visualize mammalian cells but were not designed to accommodate imaging of live tissues. As such, spectrometers pose significant challenges--the most evident of which are spatial limitations--to conducting experiments in living tissue. This limitation becomes problematic upon trying to employ commercial perfusion equipment which is bulky and--being designed almost exclusively for light Microscopy or electrophysiology studies--seldom includes MR-compatibility as a design criterion. To overcome problems exclusive to ultra-high Magnetic field environments with limited spatial access, we have designed microperfusion and in-bore oxygenation systems capable of interfacing with Bruker's series of micro surface-coils. These devices are designed for supporting cellular resolution imaging in MR studies of excised, living tissue. The combined system allows for precise control of both dissolved gas and pH levels in the perfusate thus demonstrating applicability for a wide range of tissue types. Its compactness, linear architecture, and MR-compatible material content are key design features intended to provide a versatile hardware interface compatible with any NMR spectrometer. Such attributes will ensure the microperfusion rig's continued utility as it may be used with a multitude of contemporary NMR systems in addition to those which are currently in development.

  • investigation of the subcellular architecture of l7 neurons of aplysia californica using Magnetic Resonance Microscopy mrm at 7 8 microns
    Scientific Reports, 2015
    Co-Authors: Choong H Lee, Jeremy J Flint, Brian Benjamin Hansen, Stephen J Blackband
    Abstract:

    Magnetic Resonance Microscopy (MRM) is a non-invasive diagnostic tool which is well-suited to directly resolve cellular structures in ex vivo and in vitro tissues without use of exogenous contrast agents. Recent advances in its capability to visualize mammalian cellular structure in intact tissues have reinvigorated analytical interest in aquatic cell models whose previous findings warrant up-to-date validation of subcellular components. Even if the sensitivity of MRM is less than other microscopic technologies, its strength lies in that it relies on the same image contrast mechanisms as clinical MRI which make it a unique tool for improving our ability to interpret human diagnostic imaging through high resolution studies of well-controlled biological model systems. Here, we investigate the subcellular MR signal characteristics of isolated cells of Aplysia californica at an in-plane resolution of 7.8 μm. In addition, direct correlation and positive identification of subcellular architecture in the cells is achieved through well-established histology. We hope this methodology will serve as the groundwork for studying pathophysiological changes through perturbation studies and allow for development of disease-specific cellular modeling tools. Such an approach promises to reveal the MR contrast changes underlying cellular mechanisms in various human diseases, for example in ischemic stroke.

  • Magnetic Resonance Microscopy of human and porcine neurons and cellular processes
    NeuroImage, 2012
    Co-Authors: Jeremy J Flint, Brian Benjamin Hansen, Choongheon Lee, Michael Fey, Michael A King, Peter Vestergaardpoulsen, Sharon Portnoy, Franck Vincent, Greg J Stanisz, Stephen J Blackband
    Abstract:

    Abstract With its unparalleled ability to safely generate high-contrast images of soft tissues, Magnetic Resonance imaging (MRI) has remained at the forefront of diagnostic clinical medicine. Unfortunately due to resolution limitations, clinical scans are most useful for detecting macroscopic structural changes associated with a small number of pathologies. Moreover, due to a longstanding inability to directly observe Magnetic Resonance (MR) signal behavior at the cellular level, such information is poorly characterized and generally must be inferred. With the advent of the MR microscope in 1986 came the ability to measure MR signal properties of theretofore unobservable tissue structures. Recently, further improvements in hardware technology have made possible the ability to visualize mammalian cellular structure. In the current study, we expand upon previous work by imaging the neuronal cell bodies and processes of human and porcine α-motor neurons. Complimentary imaging studies are conducted in pig tissue in order to demonstrate qualitative similarities to human samples. Also, apparent diffusion coefficient (ADC) maps were generated inside porcine α-motor neuron cell bodies and portions of their largest processes (mean = 1.7 ± 0.5 μm2/ms based on 53 pixels) as well as in areas containing a mixture of extracellular space, microvasculature, and neuropil (0.59 ± 0.37 μm2/ms based on 33 pixels). Three-dimensional reconstruction of MR images containing α-motor neurons shows the spatial arrangement of neuronal projections between adjacent cells. Such advancements in imaging portend the ability to construct accurate models of MR signal behavior based on direct observation and measurement of the components which comprise functional tissues. These tools would not only be useful for improving our interpretation of macroscopic MRI performed in the clinic, but they could potentially be used to develop new methods of differential diagnosis to aid in the early detection of a multitude of neuropathologies.

  • Magnetic Resonance Microscopy of mammalian neurons
    NeuroImage, 2009
    Co-Authors: Jeremy J Flint, Brian Benjamin Hansen, Choongheon Lee, Michael Fey, Daniel Schmidig, Jonathan D Bui, Michael A King, Peter Vestergaardpoulsen, Stephen J Blackband
    Abstract:

    Abstract Magnetic Resonance imaging (MRI) is now a leading diagnostic technique. As technology has improved, so has the spatial resolution achievable. In 1986 MR Microscopy (MRM) was demonstrated with resolutions in the tens of micrometers, and is now an established subset of MRI with broad utility in biological and non-biological applications. To date, only large cells from plants or aquatic animals have been imaged with MRM limiting its applicability. Using newly developed microsurface coils and an improved slice preparation technique for correlative histology, we report here for the first time direct visualization of single neurons in the mammalian central nervous system (CNS) using native MR signal at a resolution of 4–8 μm. Thus MRM has matured into a viable complementary cellular imaging technique in mammalian tissues.

Scott E Parnell - One of the best experts on this subject based on the ideXlab platform.

  • dysmorphogenic effects of first trimester equivalent ethanol exposure in mice a Magnetic Resonance Microscopy based study
    Alcoholism: Clinical and Experimental Research, 2014
    Co-Authors: Scott E Parnell, Martin Styner, Hunter T Holloway, Lorinda K Baker, Kathleen K Sulik
    Abstract:

    Background The first trimester of human development and the equivalent developmental period in animal models is a time when teratogenic ethanol (EtOH) exposure induces the major structural birth defects that fall within fetal alcohol spectrum disorder (FASD). Previous FASD research employing an acute high dose maternal intraperitoneal EtOH treatment paradigm has identified sensitive periods for a number of these defects. Extending this work, this investigation utilized high resolution Magnetic Resonance Microscopy (MRM)-based analyses to examine the dysmorphology resulting from maternal dietary EtOH intake occurring during selected first trimester-equivalent time periods. Methods Female C57Bl/6J mice were acclimated to a liquid 4.8% EtOH (v/v)-containing diet, then bred while on standard chow. Dams were again provided the EtOH-containing liquid diet for a period that extended either from the beginning of gestational day (GD) 7 to the end of GD 11 or from the beginning of GD 12 to the end of GD 16. On GD 17, a subset of fetuses was selected for MRM-based analyses. Group comparisons were made for litter characteristics and gross dysmorphology, as well as whole and regional brain volumes. Results EtOH-induced stage of exposure-dependent structural brain abnormalities were observed. The GD 7 to 11 EtOH-exposed group presented with a significant decrease in cerebellar volume and an increase in septal volume, while GD 12 to 16 EtOH treatment resulted in a reduction in right hippocampal volume accompanied by enlarged pituitaries. Additionally, the GD 12 to 16 EtOH exposure caused a high incidence of edema/fetal hydrops. Conclusions These results illustrate the teratogenic impact of maternal dietary EtOH intake occurring at time periods approximately equivalent to weeks 3 through 6 (GD 7 to 11 in mice) and weeks 7 through 12 (GD 12 to 16 in mice) of human gestation, further documenting EtOH's stage of exposure-dependent neuroteratogenic end points and highlighting the vulnerability of selected brain regions during the first trimester. Additionally they suggest that clinical attention should be paid to fetal hydrops as a likely component of FASD.

  • Magnetic Resonance Microscopy based analyses of the neuroanatomical effects of gestational day 9 ethanol exposure in mice
    Neurotoxicology and Teratology, 2013
    Co-Authors: Scott E Parnell, Allan G Johnson, Shonagh K Olearymoore, Deborah B Dehart, Martin Styner, Hunter T Holloway, Beatriz Paniaqua, Ipek Oguz, Francois Budin, Kathleen K Sulik
    Abstract:

    Abstract Animal model-based studies have shown that ethanol exposure during early gestation induces developmental stage-specific abnormalities of the face and brain. The exposure time-dependent variability in ethanol's teratogenic outcomes is expected to contribute significantly to the wide spectrum of effects observed in humans with fetal alcohol spectrum disorder (FASD). The work presented here employs a mouse FASD model and Magnetic Resonance Microscopy (MRM; high resolution Magnetic Resonance imaging) in studies designed to further our understanding of the developmental stage-specific defects of the brain that are induced by ethanol. At neurulation stages, i.e. at the beginning of gestational day (GD) 9 and again 4 hours later, time-mated C57Bl/6J dams were intraperitoneally administered 2.9 g/kg ethanol or vehicle. Ethanol-exposed fetuses were collected on GD 17, processed for MRM analysis, and results compared to comparably staged controls. Linear and volume measurements as well as shape changes for numerous individual brain regions were determined. GD 9 ethanol exposure resulted in significantly increased septal region width, reduction of cerebellar volume, and enlargement of all of the ventricles. Additionally, the results of shape analyses showed that many areas of the ethanol-exposed brains including the cerebral cortex, hippocampus and right striatum were significantly misshapen. These data demonstrate that ethanol can induce dysmorphology that may not be obvious based on volumetric analyses alone, highlight the asymmetric aspects of ethanol-induced defects, and add to our understanding of ethanol’s developmental stage-dependent neuroteratogenesis.

  • Magnetic Resonance based imaging in animal models of fetal alcohol spectrum disorder
    Neuropsychology Review, 2011
    Co-Authors: Shonagh K Olearymoore, Scott E Parnell, Robert J Lipinski, Kathleen K Sulik
    Abstract:

    Magnetic Resonance imaging (MRI) techniques, such as Magnetic Resonance Microscopy (MRM), diffusion tensor imaging (DTI), and Magnetic Resonance spectroscopy (MRS), have recently been applied to the study of both normal and abnormal structure and neurochemistry in small animals. Herein, findings from studies in which these methods have been used for the examination of animal models of Fetal Alcohol Spectrum Disorder (FASD) are discussed. Emphasis is placed on results of imaging studies in fetal and postnatal mice that have highlighted the developmental stage dependency of prenatal ethanol exposure-induced CNS defects. Consideration is also given to the promise of methodological advances to allow in vivo studies of aberrant brain and behavior relationships in model animals and to the translational nature of this work.

  • Magnetic Resonance Microscopy based analyses of the brains of normal and ethanol exposed fetal mice
    Birth Defects Research Part A-clinical and Molecular Teratology, 2010
    Co-Authors: Shonagh K Olearymoore, Allan G Johnson, Scott E Parnell, Elizabeth A Godin, Deborah B Dehart, Jacob J Ament, Amber A Khan, Martin Styner, Kathleen K Sulik
    Abstract:

    Background The application of Magnetic Resonance Microscopy (MRM) to the study of normal and abnormal prenatal mouse development has facilitated discovery of dysmorphology following prenatal ethanol insult. The current analyses extend this work, providing a regional brain volume-based description of normal brain growth and illustrating the consequences of gestational day (GD) 10 ethanol exposure in the fetal mouse.

  • Magnetic Resonance Microscopy defines ethanol induced brain abnormalities in prenatal mice effects of acute insult on gestational day 7
    Alcoholism: Clinical and Experimental Research, 2010
    Co-Authors: Elizabeth A Godin, Allan G Johnson, Shonagh K Olearymoore, Scott E Parnell, Deborah B Dehart, Jacob J Ament, Amber A Khan, Martin Styner, Brice W Johnson, Kathleen K Sulik
    Abstract:

    Background:  This Magnetic Resonance Microscopy (MRM)-based report is the second in a series designed to illustrate the spectrum of craniofacial and central nervous system (CNS) dysmorphia resulting from single- and multiple-day maternal ethanol treatment. The study described in this report examined the consequences of ethanol exposure on gestational day (GD) 7 in mice, a time in development when gastrulation and neural plate development begins; corresponding to the mid- to late third week postfertilization in humans. Acute GD 7 ethanol exposure in mice has previously been shown to result in CNS defects consistent with holoprosencephaly (HPE) and craniofacial anomalies typical of those in Fetal Alcohol Syndrome (FAS). MRM has facilitated further definition of the range of GD 7 ethanol-induced defects. Methods:  C57Bl/6J female mice were intraperitoneally (i.p.) administered vehicle or 2 injections of 2.9 g/kg ethanol on day 7 of pregnancy. Stage-matched control and ethanol-exposed GD 17 fetuses selected for imaging were immersion fixed in a Bouins/Prohance solution. MRM was conducted at either 7.0 Tesla (T) or 9.4 T. Resulting 29 μm isotropic spatial resolution scans were segmented and reconstructed to provide 3D images. Linear and volumetric brain measures, as well as morphological features, were compared for control and ethanol-exposed fetuses. Following MRM, selected specimens were processed for routine histology and light microscopic examination. Results:  Gestational day 7 ethanol exposure resulted in a spectrum of median facial and forebrain deficiencies, as expected. This range of abnormalities falls within the HPE spectrum; a spectrum for which facial dysmorphology is consistent with and typically is predictive of that of the forebrain. In addition, other defects including median facial cleft, cleft palate, micrognathia, pituitary agenesis, and third ventricular dilatation were identified. MRM analyses also revealed cerebral cortical dysplasia/heterotopias resulting from this acute, early insult and facilitated a subsequent focused histological investigation of these defects. Conclusions:  Individual MRM scans and 3D reconstructions of fetal mouse brains have facilitated demonstration of a broad range of GD 7 ethanol-induced morphological abnormality. These results, including the discovery of cerebral cortical heterotopias, elucidate the teratogenic potential of ethanol insult during the third week of human prenatal development.