IDDRC: Neuroimaging Core

Staff Director William Davis Gaillard, MD, Director 202-476-2120 Faculty Maria Acosta, MD Madison M. Berl, PhD William Davis Gaillard, MD Adre DuPlessis, MD Mary Donofrio, MD Andrea Gropman, MD Lauren Krivitzky, PhD Catherine Limperopoulos, PhD An Massaro, MD Chandan Vaidya, PhD L. Gilbert Vezina, MD Ben Yerys, PhD Georgetown University Hospital Faculty Guinevere Eden, PhD Andrei Medvedev, PhD Josef Rauschecker, PhD DSc Maximillian Riesenhuber, PhD John VanMeter, PhD

A variety of techniques including structural MRI, functional MRI (fMRI), diffusion tensor imaging (DTI), and MR spectroscopy are used to explore the neural substrates and correlates of different childhood diseases and developmental disorders. By mapping the key structural pathways and functional networks, researchers are able to increase their understanding of the brain basis for the cognitive, social, emotional, and behavioral problems associated with developmental disorders and childhood diseases. This research leads to important developments in diagnosis, disease progression, management, and intervention.

Current studies are investigating the impact of a range of acquired or developmental disorders including:

• Reorganization of language networks in children with epilepsy
• Working memory impairments in children with epilepsy
• Evaluation of neurobiology of cognitive deficits in carriers and late onset males with ornithine transcarbamylase deficiency
• Effect of DAT genotypes on brain structure and executive function
• Face processing and remediation in autism
• Top-down and bottom-up organization of executive functions in autism
• Functional anatomy of flexibility in autism informed by serotonin gene polymorphisms
• Effect of dyslexia remediation on functional organization of reading networks
• Structural and functional consequences of fetal and neonatal brain injury
• Structural and functional consequences of traumatic brain injury and its recovery
• Effect of novel neurofibromatosis treatments on executive functions

• Identifying efficient and effective imaging protocols to investigate experimental questions in specific clinical populations
• Processing and data analysis of structural and functional MRI scans in studies designed to detect structural or regional cortical activation alterations
• Optimal psychometric characterization of study populations through behavioral assessments that might be used as covariates in brain imaging experiments*
• 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*

• Selecting, implementing, and interpreting the statistical plan in conjunction with the Biostatistics and Informatics core
• Preparing manuscripts for studies involving imaging
• Monitoring of outcomes (efficacy, safety) in clinical trials utilizing imaging measures
• Developing and utilizing functional imaging tasks (“paradigms”) focusing on visual, auditory, and sensorimotor processing, memory, language, executive function, and visuospatial skills
• Development and validation of measures used in psychometric assessment*
• Selection of optimal behavioral assessment and imaging tools and instruments to test specific hypotheses*

• Access to the 3.0T MRI systems for structural, functional, and metabolic imaging and corresponding training
• Techniques to desensitize anxious research subjects to the staff, settings, equipment and procedures associated with neuroimaging assessments of children, adolescents, and adults

Equipment

• Advantage GE 1.5 MRI
• Advantage GE 3TMRI with audio and visual stimulus presentation, behavioral response recording and mock scanners.
• 3T Siemans Trio MRI (EPI BOLD, ASL, PEPSI MRS) with audio and visual stimulus presentation, behavioral response recording, eye tracking, cardiac monitoring, and mock scanners
• Linux workstations with multiple software packages including Matlab, SPM, AFNI, FSL, MEDEX and SPSS statistical packages for image analysis as well as data storage and backup

• Data is used for regional, whole brain, and voxel-based morphometric analysis for both gray and white matter; co-registration of functional and DTI data; and volume correction

• Primarily employing EPI BOLD (arterial spin labeling is also available) sequences are used for functional anatomic and brain mapping investigations
• Bank of fMRI paradigms for language, executive function, sensory-motor, visual, auditory, and reading
• Personnel skilled in paradigm design and implementation

• Resting state connectivity analysis

• Investigates white matter macro and microstructure integrity in normal development and disease
• Examines diffusibility and anisotropy in white matter tracts
  • Tracks and maps the white matter tracts that connect cortical regions and cognitive networks and are used to inform fMRI and functional connectivity studies
• Up to 512 directions can be routinely acquired, and different analysis approaches are employed

• Biochemical/metabolic investigation of gray and white matter and other systems
• Such methods may be used to examine conventional energetics, but may also be used to probe biochemical perturbations and consequences of inborn errors of metabolism
• Multivoxel/multislice capacity is available (PEPSI sequence) with increasing resolution

Lee PS*, Yerys BE*, Della Rosa A, Foss-Feig J, Barnes KA, James JD, VanMeter JW, Vaidya CJ, Gaillard WD, Kenworthy LE. Functional connectivity of the inferior frontal cortex changes with age in children with autism spectrum disorders: A fcMRI study of response inhibition. Cereb Cortex, 2009;19:1787-94, [Epub 2008 Dec 9].

Mbwana J, Berl MM, Ritzl EK, Rosenberger LR, Mayo J, Weinstein SL, Conry JA, Pearl PL, Ritter FF, Shamin S, Moore EN, Sato S, Vezina LG, Theodore WH, Gaillard WD. Limitations to Plasticity of Language Network Reorganization in Localization Related Epilepsy. Brain, 2009;132(pt 2):347-356.

Yerys BE, Jankowski KF, Snook D, Rosenberger LR, Barnes KA, Berl MM, VanMeter JW, Vaidya CJ, Gaillard WD. The fMRI success rate of children and adolescents with autism spectrum disorders, epilepsy, attention deficit/hyperactivity disorder, and typical development. Human Brain Map, 2009;30:3426-35.

Gropman AL, Fricke ST, Seltzer RR, Hailu A, Adeyemo A, Sawyer A, van Meter J, Gaillard WD, McCarter R, Tuchman M, Batshaw M; Urea Cycle Disorders Consortium (2008). 1H MRS identifies symptomatic and asymptomatic subjects with partial ornithine transcarbamylase deficiency. Mol Genet Metab, 95(1-2):21-30

Jiang X, Bradley E, Rini RA, Zeffiro T, Vanmeter J, Riesenhuber M. Categorization training results in shape- and category-selective human neural plasticity. Neuron, 2007 Mar 15;53(6):891-903.PMID: 17359923