Introduction to the Radiology Research Division

The Radiology Research Division comprises a program of multimodal, multidisciplinary research, housed in CSH1 (MRI), CSH0 (MEG) and Roberts 5th Floor (Clinical coordination). The primary focus of the group is pediatric developmental neuroscience, with specific clinical application to autism spectrum disorder (ASD), intellectual disability (ID), related genetic syndromes and mild traumatic brain injury. To understand brain structure and function pathology, the group also undertakes large N imaging studies of “typical” controls to understand typical brain development in infants, children and adolescents. The main tools employed to image the brain are structural, microstructural and functional MRI, edited MRS, and magnetoencephalography (MEG) and electroencephalography (EEG). In addition to the above, comprehensive tailored neuropsychological and clinical batteries are administered to all participants. Close interface with the clinical section of Neuroradiology (Director Prof. G. Zuccoli) is established to facilitate clinical translation. Across the group there is considerable expertise encompassing MRI physics, electrophysiology, spectroscopy, imaging science, computational modeling, engineering, statistics, as well as in clinical psychology and neuropsychological assessment.

Timothy P.L. Roberts, PhD is Professor of Radiology and vice-chair of research in the Department of Radiology at The Children’s Hospital of Philadelphia and directs the Lurie Family Foundations' MEG Imaging Center. He also holds the Oberkircher Family Chair in Pediatric Radiology at CHOP. With a PhD in MRI Physics (Cambridge University, 1988-1991), he has 30 years’ experience in medical imaging and has published in excess of 300 manuscripts primarily in the area of physiological and functional imaging, including perfusion, permeability and diffusion MRI. He has 25 years accumulated expertise in magnetoencephalography (MEG), and has published over 100 MEG articles, primarily on auditory processes in control and patient populations, especially ASD. Additionally, with Dr. Edgar and partners at Tristan Technologies, Dr. Roberts co-designed the Artemis 123™ infant/young child MEG scanner, installed at CHOP. He has successfully conducted multicenter multimodal imaging studies in the recent past (e.g. Simons Foundation SVIP 16p11.2 Study). He is a distinguished investigator of the Academy of Radiology Research and an Associate Editor of Frontiers in Integrative Neuroscience.

J. Chris Edgar, PhD is Associate Professor of Radiology. Dr. Edgar is a Clinical Neuropsychologist with over 25 years’ experience in clinical brain imaging research (infants, children and adults). Over the last 25 years he has published studies examining brain structure and function in psychiatric and neurodevelopmental disorders, with a primary focus on schizophrenia and autism spectrum disorder. He is co-designer with Dr. Roberts of the Artemis 123™ infant MEG device. His recent research focuses on (1) understanding the maturation of brain structure and function in children with autism spectrum disorder as well as in typically developing infants, and (2) the use of normative databases to identify neural pathology in adolescents with mild traumatic brain injury.

Hao Huang, PhD is Research Associate Professor of Radiology and an authority on neonatal and infant MRI acquisition and analysis. He is on the editorial board of Neuroimage, a top neuroimaging journal. He has about 20 years of research experience on 1) delineating structural, physiological and functional brain development and 2) identifying clinical biomarkers by 3) developing, optimizing and utilizing advanced preclinical and clinical MR imaging and analysis techniques. He has been continuously funded by NIH grants (as the PI) and published more than 80 journal papers.

William C Gaetz, PhD is Research Assistant Professor of Radiology (promotion pending) and an authority on electrophysiological studies of motor development. Dr Gaetz has over 20 years of experience with MEG and EEG and has pioneered several advances in spectrotemporal analysis and source localization for components of the sensorimotor system responses in research and clinical settings, especially epilepsy.

Jeffrey Berman, PhD is a Research Assistant Professor of Radiology and a Senior Scientist in the Department of Radiology at CHOP. Dr. Berman is an expert in bioengineering and neuroimaging with significant experience in the application of dMR tractography of white matter in youth with neurodevelopmental disorders, including ASD and NF1. Additionally, Dr. Berman has significant expertise in assessing normal white matter development in typically developing children. Dr. Berman has contributed to studies identifying associations between brain structure and function using MEG.

Dah-Jyuu (DJ) Wang, PhD is a Research Assistant Professor of Radiology and an MR physicist with over 30 years of experience and special expertise in MR spectroscopy as well as multinuclear imaging. Dr. Wang is especially interested in developing MRI and MRS biomarkers for monitoring progression and treatment responses in pediatric diseases. He is experienced in applying imaging techniques, such as  CrCEST (Creatine Chemical Exchange Saturation Transfer), Dixon, T2 mapping, as well as proton and heteronuclear MRS techniques in clinical and research applications.

Luke Bloy, PhD is a CHOP Senior Research Scientist and an authority on image data analysis, with special focus on structural and microstructural MRI as well as technical aspects of MEG, including motion compensation, registration and advanced source modeling.

Yuhan Chen, PhD is a CHOP Research Scientist with 10 years’ experience using magnetoencephalography (MEG) and structural MRI to study cognitive processing (e.g., social cognition and auditory processing) as well as resting state activity in neurodevelopmental and psychiatric patient populations. She recently received a K01 award to obtain additional training in multimodal and clinical imaging research, with a primary focus on research involving infants and children.

Lisa Blaskey PhD is a Clinical Neuropsychologist at the Lurie Family Foundations MEG Imaging Center. Over the last ten years, Dr. Blaskey has performed clinical and neuropsychological assessments for a variety of clinical imaging studies involving typically developing children as well as children with disorders such as autism, specifically language impaired, and 16p11.2 duplication/deletion. In addition, Dr. Blaskey assesses children presenting with a wide variety of symptoms for her clinical practice (including children with head trauma as well as developmental disabilities).

Emily Kuschner PhD is an Assistant Professor of Psychology in Psychiatry and a Clinical Psychologist with expertise is assessment and diagnosis of autism spectrum disorder (ASD). She has special focus on eating disorders as a part of the ASD phenotype. Dr. Kuschner is also the lead developer of the MEG-PLAN approach – a comprehensive strategic and behavioral approach to encouraging participation of low-functioning and infant populations in MEG studies.

Jillian Lebus, MA is a psychometrician with expertise in assessment and treatment of infants and children, especially focused on ASD.

Mina Kim, PhD NCSP is a nationally certified school psychologist. She has experience administering developmental and psychological assessments to infants and school-age children, in addition to providing applied behavior analysis (ABA) therapy to children with ASD. Dr. Kim provides support and consultation for the implementation of applied behavioral methods to encourage participation of young and impaired children in imaging studies, with resultant increase in data yield.

Additionally, the group currently has 3 post-doctoral fellows (Heather Green, PhD, Junko Matsuzaki, PhD, Joni Saby, PhD) and 1 graduate student actively engaged in imaging research as well as a staff programming scientist (Song Liu) and a well-assembled and trained team of research assistants, coordinators and experienced MRI and MEG technologists.

2. Major hardware resources

The group’s activities center on multimodal imaging and electrophysiology of infants and children during typical development and in the setting of developmental disorders. To achieve the related goals, the Radiology Research Division houses advanced MRI and MEG hardware, listed below and dedicated to research:

3T Siemens Prisma MRI (“MR4”), equipped with connectome gradients and 20-, 32- and 64-channel RF head coils as well as 16-channel neonatal head coil, fMRI and multinuclear capabilities. Our master research agreement with Siemens allows for close collaboration with developers of WIPs and C2P pulse sequences.

3T Siemens Trio MRI (“MR5”) – ideally located adjacent to research Prisma MR4. Pending “Fit” upgrade to Prisma level to accommodate anticipated needs in evening/infant scanning.

Waiting room, infant “night-time” preparation room

PST Mock MRI Scanner (adjacent to MR4/MR5 suite)

MEG (CTF) – a 275 channel biomagnetometer equipped with a 64-channel EEG system for simultaneous MEG and EEG

2nd MEG CTF (to be installed 2019), specifications similar to MEG-1

Artemis 123 (Tristan Technologies) dedicated infant MEG – a custom designed 123-channel infant MEG system with a helmet sized appropriately for infants and young children 0-36months.

A set of 8 pre-wired 60-channel EEG caps of varying size from infants to adults.

A full array of stimulus presentation and response recording systems (including MEG-compatible driving simulator, fiber-optic response buttons for MRI and MEG as well as auditory, visual, somatosensory and gustatory delivery systems, along with Eprime, Presentation and PsychoPy presentation software).

The imaging facility has direct connection to the high performance computing cluster (HPC) and isilon storage area network (SAN), supported by CHOP IS and locally administered by Dr Bloy. Most Windows and Linux software applications are available on a CHOP virtual machine (VM) again locally administered by Dr Bloy, giving all local and VPN-linked users access to the vast majority of required processing software, in a secure manner, with CHOP IS data archiving.

3. Recent and Current Grants

Current and notable recent grants with group PI’s are listed to introduce the areas of direct focus of the group. Many of the group members are valued co-investigators on collaborators’ grants (not listed) as well as faculty on related CHOP/Penn training grants (e.g. for Roberts: three T32’s led by Robinson M, Cohen Y and Gur R).

CURRENT

NIH R01-DC008871-10 (Roberts)                                                       2007-2019      

Electrophysiological Signatures of Language Impairment in Autism Spectrum Disorder

Goal: To explore electrophysiological characteristics of ASD via MEG/MRS/HARDI studies of auditory processing in high-functioning school-aged children with ASD.

NIH U54-HD086984 (Yudkoff / Roberts, PI Research Project and Director, Neuroimaging and Neurocircuitry Core)     2015-2020

Intellectual and Developmental Disabilities Research Center

Goal: to support research that seeks to identify the causes and to develop potential treatments for school-aged children with intellectual and/or developmental disabilities. Research project focuses on MEG in Non-verbal children with ASD.

NIH R21-MH109158 (Roberts)                                                           2016-2019

Structural and functional characteristics of XYY – Relationship to ASD

Goal: to compare the imaging phenotype of boys with 47,XYY syndrome +/- ASD diagnosis

NIH R21-NS106135 (Roberts, Hocking, MPI)                                     2018-2020

Neurophysiological and neuroanatomical processes related to autism spectrum disorder in neurofibromatosis type 1

Goal: to compare the imaging/MEG phenotype of children with NF1 +/- ASD diagnosis

NIH R01-MH107506 (Edgar)                                                               2015-2020

A longitudinal study of brain development in children with ASD

Goal: To characterize the emergence and development of brain rhythms and evoked responses using a longitudinal design (over 3yrs) in school-aged children.

NIH R01-HD093776 (Edgar)                                                               2018-2023

Brain structure and function in infants

Goal: To examine changes in brain function (MEG) and structure (MRI) as well as function-structure associations in typically developing infants via a longitudinal design.

NIH R01-MH092535 (Huang)                                                                    2016-2021

Structural Development of Human Infant Brain (competitive renewal)

The goal is to establish next-generation diffusion MRI atlases (quantitative UPenn-CHOP infant brain atlases) and to harness a more advanced cortical microstructural measurement by delineating its 4D spatiotemporal frameworks as well as uncovering its relationship to brain function and behavior during infancy (0-2 years).

NIH R21-MH110869 (Berman)                                                           2017-2019                  

Phase-Amplitude Coupling and Dysfunction in ASD

This project examines spatial patterns of phase amplitude coupling (PAC) in children with ASD. Deficiencies in PAC are hypothesized to correlate with diffusion MR measures of white matter integrity and behavioral phenotype.

NIH K01-MH108822 (Chen, mentor: Roberts)                                   2015-2020

Development of infant brain MEG responses to social stimuli: comparison to ASD

Goal: To identify age-appropriate social neural endophenotypes in typical developing infants and young children as well as young children with ASD via infant MEG and eye-tracking, with this information leveraged to identify age-specific abnormalities in the neural processes associated with face processing impairments in young children with ASD.

NIH K01-MH108762 (Bloy, mentor: Roberts)                                    2016–2020
MEG Imaging Techniques for Low-Functioning Pediatric Populations                  

Project goals are to develop MEG analysis methodologies, specifically motion correction, head modeling and real-time analysis, to better support electrophysiology studies focused on low-functioning populations.

4500-9282661220-02 (Edgar & Master (Imaging projects PIs))         2017-2021

Pennsylvania Tobacco Grant

Integrative Science to Advance Pediatric Concussion Diagnosis and Treatment

Goal: This multicomponent study evaluates sports head injury in children, including wearable head-impact sensor field work, rodent models, and brain imaging. The brain imaging component involves the use of normative MEG databases to identify neural pathology at the individual level in adolescents with mild traumatic brain injury and to track changes in neural brain activity across recovery.

RECENT (OF NOTE)

Simons Foundation (Roberts)                                                                        2011-2015

Simons Variation in Individuals Project (SVIP)

Goal: Structural and functional brain abnormalities are identified by comprehensive sMRI, DTI, fMRI and MEG in 16p11.2 del/dup children and adults.

US Department of Defense CDMRP AR140197        (Roberts)         2015-2018

Neural correlates of the Y chromosome in autism: XYY Syndrome as Genetic Model

Project goals are to evaluate the structural and functional determinants of autism in boys with 47,XYY compared to idiopathic ASD.

Clinical Research Associates / Simons Foundation  #412802 (Roberts) 2015-2018

MEG/MRS Dose Response Study of STX209 in ASD

This pilot study investigates the response of MEG/MRI and MRS candidate biomarkers to acute administration of a GABA-B agonist in adolescents with ASD

NIH R01HD073258 (Embick / Roberts, Sub-contract PI)                    2012-2018 (renewal in preparation)

Magnetoencephalographic studies of lexical processing and abstraction in autism

Goal: to define MEG signatures of linguistic processes in ASD and to manipulate word stimulus acoustic properties to enhance brain responses.