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Core Facilities
Bionutrition Research
This core provides comprehensive assessment of the research patient’s nutritional status to aid in research protocols. The core has a BodPod® to perform body composition measurements by air-displacement plethysmography and recently acquired a MedGraphic Combined Pulmonary Exercise and Critical Care Management Testing system to expand core services into resting energy expenditure and exercise testing.
Contact Information:
Catherine J. Klein, PhD, RD, CNSD
Director, Bionutrition Research Program
General Clinical Research Center, 3rd Floor
Children's National Medical Center
111 Michigan Avenue, N.W.
Washington D.C., 20010
Phone Office: 202-476-2910
Phone GCRC: 202-476-2922
Fax: 202-476-6636
CKlein@cnmc.org
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Biostatistics and Informatics
This core provides state-of-the-art support to investigators in the planning, implementation, and analysis of studies requiring quantitative methodologies and data management. Services include consultation on appropriate study design and data acquisition and analysis, evaluation of the comparative feasibility and validity of alternative study designs, calculation of sample size for statistical precision, and training on study design and biostatistics.
Contact Information:
Robert J. McCarter, Jr., ScD
Director
Center for Clinical and Community Research
Children's Research Institute
Children's National Medical Center
111 Michigan Avenue, NW
Washington, DC 20010
202-476-3856
eward@cnmc.org
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Cellular Neuroimaging
The Cellular Imaging Core has one 2000 square foot facility at the Center for Neuroscience Research at Children's with equipment dedicated to time-lapse multiphoton microscopy, confocal microscopy, calcium imaging, electrophysiology, and the production and maintenance of primary, organotypic slice, and cell line cultures. A second 2000 square foot facility at the George Washington University Center for Microscopy and Image Analysis has equipment and support for electron microscopy, confocal imaging and image analysis.
The Children's facility is under the direction of Tarik F. Haydar, PhD. Major equipment in the facility include an LSM510 Meta NLO multiphoton/confocal microscope for time-lapse investigation in living brain tissue, a stereo fluorescence LUMAR microscope system and a newly acquired Zeiss Apotome grid microscope for optical sectioning and live imaging. In addition, several other calcium imaging, stereo dissecting and patch clamping systems are also housed within the Children's facility.
Contact Information:
Tarik F. Haydar, PhD
Children’s Research Institute
Center for Neuroscience Research
Children's National Medical Center
111 Michigan Avenue, NW
Washington, DC 20010
202-476-2389
202-476-4988 fax
thaydar@cnmcresearch.org
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Fluorescence Activated Cell Sorter (FACS)
This facility houses state-of-the-art fluorescence activated cell-sorting instrumentation and is part of the Hematopoetic Stem Cell Laboratory. The core is available to CRI investigators for analysis of cell surface and intra-cellular molecule expression, cell viability, cell cycle analysis, DNA ploidy, and cell sorting. In addition, the laboratory quantifies hematopoietic stem cells from clinical specimens and stem cell components for the stem cell transplantation program at Children's. The involvement of David Leitenberg, MD, PhD, has increased collaboration with the George Washington University FACS facility, by routine exchange of personnel and sample analysis.
The Flow core Facility has a newely acquired Cytopeia Influx cell sorter. The modular design of the influx allow for customization for specific research demands where applications require configurations that are different from those available on current off-the-shelf machines. The instrument is under full digital contril, operating at high-speed with unparalleled sensitivity and unprecedented attention to cleanliness, safety, and functionality. Modern electronics and dectors can easily analyze cells at speeds greater than 200,000 events per second. The physics of drop formation and the statistics of disturbing cells among the droplets limit the actual sort rates to about 50,000 cells per second. This combination of speed and reliable separation allows scientists to seek cut rate events (occurring less 0.0001% of the time) and isolate them for further study. The versatile design supports clean room sorting, using patented disposable nozzles. It has the capability for three lasers, 16 detector configuration.
Also within the center, a quantitative real time (RT-PCR) capability exists as part of the laboratory effort of Brian R. Rood, MD, and includes the Bio-Rad IQ iCycler, qRT-PCR which is available to CRI investigators for the quantitation of gene expression with support for assay design and data interpretation. And, currently an HPLC core facility is under development.
Contact Information:
Stephan Ladisch, MD
Chair for External Affairs, Department of Pediatrics
Children's Research Institute
Center for Cancer and Immunology Research
Children's National Medical Center
111 Michigan Avenue, NW
Washington, DC 20010
202-476-3898
202-476-3929 fax
sladisch@cnmc.org
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Functional Neuroimaging Core
Advances in human brain imaging techniques are rapidly improving our understanding of motor, perceptual and cognitive function in health and disease. Applications of functional brain imaging and related imaging techniques now allow identification of regionally specific neural abnormalities in learning disabilities (Eden -, Functional MRI studies of the pathophysiology of dyslexia in adults; Zeffiro - Early detection of developmental dyslexia with functional brain imaging), ADHD (Chandan Vaidya, PhD - Integrating brain imaging and genetic analysis of ADHD), autism (William Davis Gaillard, MD / Lauren Kenworthy, PhD / Zeffiro – Studies to Advance Autism Research and Training) and inborn errors of metabolism (Mark L. Batshaw, MD - Genotype – Phenotype testing in urea cycle disorders). Finally, these techniques can be used to determine changes over time in specific cortical functions in chronic neurological disorders in children, such as partial epilepsy (Dr. Gaillard - Plasticity of language networks in childhood epilepsy).
The purpose of the Neuroimaging Core is to provide expertise and support to Mental Retardation and Developmental Disablities Research (MRDDRC) investigators in the areas of experimental design, data acquisition, data analysis, and data management for experiments utilizing structural, functional and metabolic brain imaging techniques. The Core provides support for studies employing: (a) structural MRI, (b) diffusion MRI (c) magnetic resonance spectroscopy (MRS), (d) functional MRI (fMRI), (e) near infrared spectroscopy (NIRS) and electrophysiology. This support includes consultation and training for new investigators in issues pertaining to experimental methods and MRI compatible task construction.
The overall objective of the Neuroimaging Core is to provide center investigators with both consultation pertaining to structural and functional neuroimaging experimental design and access to the specialized imaging acquisition and analysis techniques that are needed to study brain structure and function. The equipment provided, as well as the expertise and sophisticated methods supported in this Core are not feasible to acquire or develop in the laboratories of individual investigators and so organization of these services as a core facility realizes significant cost savings.
The core services are as follows:
- To provide consultation in identifying efficient and effective imaging protocols to investigate experimental questions in specific clinical populations. For each study design, the use of spectroscopy, diffusion imaging, structural brain imaging, and functional brain imaging will be explored
- To provide consultation in processing and data analysis of structural and functional MRI scans in studies designed to detect structural or regional cortical activation alterations
- To provide access to and training in the use of 1.5 and 3.0T MRI systems for structural, functional and metabolic imaging
- To provide access to and training in the use of near infra-red spectroscopy systems
- To provide access to and training in the use of a high-density electrophysiology systems
- To support investigators in developing and utilizing a broad spectrum of functional imaging tasks (paradigms) focusing on early visual processing, memory, language, executive function, visuospatial skills and sensorimotor coordination
- To implement and support techniques to desensitize anxious research subjects to the staff, settings, equipment and procedures associated with neuroimaging
- To provide a supportive and encouraging training environment for new investigators entering the neuroimaging field
The Neuroimaging Core provides sophisticated imaging research methods support to ongoing MRDDRC protocols and will help develop or validate new methods to support these protocols. Despite the sophisticated methodological advances that have taken place in molecular genetics, our rate of scientific advancement for understanding complex behavioral disorders is limited by our ability to reliably and precisely define the underlying neural systems. The overall goal of this core is to provide state-of-the art neurophysiological assessment services to researchers, utilizing reliable and valid measures of brain structure and function.
Many studies that could potentially benefit from utilization of neuroimaging outcome measures have not included such assessments due to issues related to cost-constraints within research project budgets and/or access to personnel skilled in the performance of these techniques. The primary goal of the Neuroimaging Core is to improve this situation by providing uniform access to appropriate neuroimaging techniques and to improve the overall quality of research conducted through the MRDDRC by providing assessment services, consultation, and training.
The specific goals of the Neuroimaging Core are to:
- Provide consultation to MRDDRC investigators pertaining to the selection of appropriate behavioral tasks for studying particular aspects of regional functional neural specialization
- Provide consultation to MRDDRC investigators regarding selection of imaging methods appropriate to assessing various aspects of brain structure, function or metabolism
The specific goals of the Neuroimaging Core in collaboration with the neuropsychological Evaluation Core are:
- Provide investigators with consultation concerning the optimal psychometric characterization of their study populations through behavioral assessments that might be used as covariates in brain imaging experiments. This and the next 3 objectives are done in collaboration with the Neuropsychological Evaluation Core.
- Assist in the development and validation of the measures used in psychometric assessment for this purpose
- Facilitate the selection of optimal behavioral assessment and imaging tools and instruments to test specific hypotheses
- Provide consultation regarding the establishment of appropriate timing and sequencing of behavioral and physiological assessments in order to minimize bias or practice effects and to detect developmental trajectories and changes related to interventions
- Develop and maintain a library of standardized and validated tasks appropriate for functional imaging studies of children, adolescents, and adults
- Help in performing imaging assessments of children, adolescents and adults
- Assist in manuscript preparation for studies involving imaging
- Assist in the monitoring of outcomes (efficacy, safety) in clinical trials utilizing imaging measures
Neuroimaging Core staff will be available to meet with MRDDRC investigators to explain the scope and availability of Core services and explain how these services can enhance their clinical research. The staff also provides both lectures on available services as well as hands-on training.
Staff
Thomas Zeffiro, MD, PhD - Core Director, Associate Professor Neurology, Georgetown University
Dr. Zeffiro has experience in the design and execution of functional neuroimaging experiments utilizing PET, MRI and optical imaging technology to study motor control and cognitive processing. His role is to assist in the design of the behavioral paradigms used in the imaging experiments, design and implement data analysis procedures, supervise data analysis procedures and aid in the development of new fMRI data analysis and visualization tools as required for the proposed experiments.
Louis-Gilbert Vézina, MD - Professor of Radiology and Pediatrics Children's
Director of Neuroradiology in the Department of Diagnostic Imaging and Radiology at CNMC
Louis-Gilbert Vézina, MD provides pediatric neuroradiologic and medical expertise for conducting clinical imaging protocols.
William Davis Gaillard, MD – Professor of Neurology and Pediatrics Children's
Dr. Gaillard has extensive expertise in pediatric functional neuroimaging with PET, SPECT, structural and functional MRI. He provides expertise in designing and conducting studies for young and cognitively impaired children.
John VanMeter, PhD – Assistant Professor of Neurology Georgetown University
Dr. VanMeter is a Computer Scientist, is the 3T MRI system manager, and has developed many specialized software tools for the application of functional and anatomical data analysis. He is principally responsible for supporting the daily operations of the 3T MRI system as well as developing and maintaining image analysis procedures for all users of the core.
Andrei Medvedev, PhD – Assistant Professor of Neurology Georgetown University
Dr. Medvedev is a neurophysiologist and is the manager for both the near infrared spectroscopy (NIRS) and EEG systems. He has an extensive background in signal and image processing. He has the primary responsibility for assisting in the development of advanced signal processing methods and for supporting protocols involving combination of electrophysiological and NIRS imaging techniques.
Stanley Fricke, PhD – Assistant Professor of Neuroscience Georgetown University
Dr. Fricke is an MRI Physicist with extensive background in animal and human spectroscopy. He has the responsibility for the development of techniques for acquisition and quantitative analysis of magnetic resonance spectroscopy (MRS) data, including quality assurance monitoring.
Resources
The imaging facilities of the core are located in Neuroradiology at Children's and the Center for Functional and Molecular Imaging (GU). The imaging center at Georgetown University is connected to Children's by a secure network allowing DICOM transfer of research imaging studies from the central image archive at CFMI.
1.5T Magnetic Resonance Imaging Facility (Children's)
Neuroradiology at CNMC provides two 1.5 T GE Twinspeed whole body imaging systems with the ability to support clinical research including structural imaging, diffusion imaging, echo-planar imaging (EPI), perfusion imaging with contrast agents, magnetic resonance angiography (MRA), and spectroscopy (MRS).
3.0T Magnetic Resonance Imaging Facility (Georgetown University)
The Siemens Trio is a 3T whole body imaging system with the ability to support both basic and clinical research including echo-planar imaging (EPI), diffusion tensor imaging, perfusion imaging with contrast agents or pulsed arterial spin labeling, second order shimming, magnetic resonance angiography (MRA), CINE and spectroscopy (MRS).
Near Infra-Red Spectroscopy (NIRS) Facility (Georgetown University)
CFMI has two NIRS systems that are now available to support functional brain imaging studies. NIRS is the most recent version of a family of techniques that utilize interactions between light in the near-infrared part of the spectrum and blood components to allow non-invasive measurements of brain activity related to language, communication and sensorimotor integration.
EEG/ERP Facility (Georgetown University)
Electrical Geodesics is a high-density EEG system for averaged event-related potentials (ERPs) can that be examined with both topographic waveform plots and surface electrical field animations. The addition of electrophysiology to the other imaging modalities available to Core users will allow experiments combining the superior temporal resolving capabilities ERP approaches with the sensitivity and superior spatial resolving properties of functional MRI. The integration of these two methods allows investigation of research questions probing modulations in the spatiotemporal character of brain activity.
Computational Support (Georgetown University & Children's)
For Core users includes a 40 processor LINUX computational cluster with 10 Terabytes of storage. Workstations include 10 imaging workstations (two at Children's and eight at Georgetown University) and a LINUX file server digital tape backup for data archiving. This data analysis system will be available to support collaborative projects among users of the Core.
MRI Simulators (Georgetown University & Children's)
There are two mock scanners. One system at Children's and another at Georgetown University This system is used to acclimate participants to physical aspects of the MRI environment prior to their participation in actual experimental sessions. Contact Information:
Tarik F. Haydar, PhD
Children's Research Institute
Center for Neuroscience Research
Children's National Medical Center
111 Michigan Avenue, NW
Washington, DC 20010
202-476-4996
202-476-4988 fax
thaydar@cnmcresearch.org
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GIS/Geospatial Analysis
Our Geographic Information Systems (GIS) Lab is a function of the Center for Health Services and Community Research. The lab's mission is to provide GIS and spatial analysis support to projects that promote the health and wellbeing of children, particularly those living in disadvantaged circumstances. We have developed unique methods for measuring geospatial accessibility of healthcare providers, as well as health promotion/disease prevention opportunities. Our projects have addressed problems in the fields of primary care access, ED services, asthma morbidity, obesity prevention, mental health services, exposure to violence, and the spatial epidemiology of lead poisoning. Our services include geocoding of addresses, mapping of census and administrative data, and quantitative spatial analysis for exploratory research or hypothesis testing.
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Microarray Center -Public Expression Profiling Resource (PEPR)
PEPR is an experiment in web-database access to large multi-dimensinal data sets using a standardized experimental platform.
The primary goal of PEPR is to determine if the larger scientific community can be given simple, intuitive, and user-friendly web-based access to large microarray data sets.
Contact Information:
PEPR Portal
http://pepr.cnmcresearch.org
Eric P. Hoffman, PhD
Director
Research Center for Genetic Medicine
Children's Research Institute
Children's National Medical Center
111 Michigan Avenue, NW
Washington, DC 20010
202-476-6014 fax
pepr@cnmcresearch.org
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Molecular Genetics/Proteomics Core
The Proteomics Core was recently funded through a supplement from The National Institute of Child Health and Human Development (NICHD), and provides both small molecule and large molecule mass spectrometry. The large molecule core is run by Genetic Medicine, and includes ABI TOF/TOF, Finnigan LTQ ion trap with nanospray source, and robotics and chromatog-raphy separations units.
Since its inception, the MS Core has expanded significantly its repertoire of services using a large number of mass-spectrometry devices including GC-MS, LC-MS, and MS/MS. In 2003 Steve Soldin, MD was awarded a competitive industrial grant that included an API-4000 instrument that has approximately 10-fold greater sensitivity than the API-3000. This system allows to measure analytes that are present in very low concentrations (e.g. aldosterone, estradiol, estrone, 2-OH estrone, 16-OH estrone,25 hydroxy and 1:25 dihydroxy Vitamin D and free T4, free T3). The combined Core contains 10 mass spectrometers including 2 tandem mass spectrometers that provide state of the art analytical chemistry. We also have acquired the Immulite/ DPC immunoassay system that allows for analysis of greater than 60 analytes, including cotinine,IGF-1, IGFBP-3, and IL-6 among others. This will be used to provide Mental Retardation Developmental Disablities Research Center (MRDDRC) investigators with a larger menu of analytes that can be measured in-house, and we can also provide testing to other cores across the country.
The function of the Mass Spectrometry Core is to provide for the rapidly growing need of sophisticated biochemical analyses by MRDDRC projects. The core provides quantitation of analytes and drug metabolites using isotope dilution tandem mass spectrometry and stable isotope studies. The laboratory is also a primary analytical training site available to graduate students and medical trainees. The following mass spectrometry services are provided:
- Experimental design and implementation (selection of technique)
- Method development (extraction, separation, detection, quantification)
- Method validation and quality control
- Synthesis of stable isotopes
- Sample processing
- Data collection and interpretation
The overall objective of the Molecular Genetics Core is to provide investigators with basic and advanced molecular biology, molecular genetics, and genetic counseling tools to enhance their clinical research protocols. The Core offers automated sequencing, SNP discovery, SNP genotyping, expression profiling using microarrays, genetic counseling consultations for IRB and consent forms utilizing DNA or tissue, sample storage and referral, and new high throughput proteomic profiling methodologies (TOF/TOF and electrospray ion trap). The Genetics Core also has considerable resident expertise in public dissemination of data, and will provide interfaces for MRDDRC investigators for the Public Expression Profiling Resource (PEPR) Oracle web database dissemination of microarray data, and sample tracking developed by the Center (in collaboration with data analysis core). In addition to providing direct research support to MRDDRC investigators, the core provides training in state-of-the-art molecular methods for young investigators, medical students, residents and fellows. The range of services is outlined below:
mRNA Expression profiling
- Assistance with experimental design and implementation
- Processing of Affymetrix GeneChips
- Interpretation of data, and verification/validation
- Data dissemination
DNA Sequence And Mutation Analyses
- Molecular diagnosis, mutation detection
- SNP association studies
- Automated sequence analysis
- DHPLC testing for localization of changes and genotyping
- TTGE mutation detection system
- TGCE mutation Reveal system
mRNA Quantitative Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) and PC R
- LiCor IR2 quantification
- TaqMan quantification
- Laser capture microdissection (Arcturus, Leica)
Genetic Counseling
- Study design and implementation
- IRB/GAC and consent form assistance for genetics studies
- Patient confidentiality consultation
Contact Information:
Eric P. Hoffman, PhD
Director
Research Center for Genetic Medicine
Children's Research Institute
Children's National Medical Center
111 Michigan Avenue, NW
Washington, DC 20010
202-476-6029
202-476-6014 fax
ehoffman@cnmcresearch.org
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Neuropsychology
Pediatric Clinical Research Scholar Program (PCRC), Behavioral Phenotyping Core
This core, directed by Gerard A. Gioia, PhD, is part of the General Clinical Research Center (GCRC) and provides state-of-the art consultation and neuropsychological assessment services to researchers utilizing reliable and valid measures of behavior, cognition, and social and environmental factors.
Contact Information:
Gerard A. Gioia, PhD
Children's Research Institute
Children's National Medical Center
111 Michigan Avenue, NW
Washington, DC 20010
(202) 745-8860
ggioia@cnmc.org
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