Imaging Genomics Research Affinity Group (IG-RAG)

Background

Imaging genomics is an emerging research area that involves the multidimensional integration of large and complex datasets including radiology, pathology, genomics, clinical and laboratory data.  By definition, imaging genomics is a highly multidisciplinary field that requires close collaboration among clinicians, laboratory researchers, and data scientists.  This systems-level approach generates novel insights into multiscale biological processes, offering quantitative biomarkers for patient diagnosis, prognosis, and treatment response.  Furthermore, translational laboratory investigations can help reveal underlying mechanisms of disease and provide opportunities for development and testing of next-generation therapies. 

The Imaging Genomics Research Affinity Group (IG-RAG) fosters interdisciplinary collaborations and provides support to investigators who are interested in translational omics research, big data analytics, and precision medicine.  Through research and educational meetings, visiting lectures, and seed grant funding, we are elevating the profile of imaging genomics across a wide variety of clinical specialties and research centers at Nationwide Children’s Hospital, The Ohio State University, and beyond.  Our group is well aligned with existing hospital strengths, core accelerators, and strategic priorities in radiology, neuroscience, genomics and gene therapy, and population health.

Mission

To facilitate cutting-edge interdisciplinary research in imaging genomics by establishing university collaborations and developing content expertise in quantitative advanced imaging, multi-omics, and translational data analytics.  The IG-RAG will promote team science across Nationwide Children’s Hospital and Research Institute, leverage key research collaborations with The Ohio State University, and provide educational and research opportunities for physicians and scientists-in-training.  In addition, the IG-RAG will advise on strategic external partnerships that help establish the reputation of NCH as a leader in the field.

Goals

  1. Engage faculty interest and networking in novel interdisciplinary areas, promoting multicenter and multidepartmental collaborations, and establishing NCH as a leader in imaging genomics.
  2. Build core NCH resources for study design, data analysis, grant/manuscript writing, and mentorship in imaging genomics.
  3. Institute standardized approaches to imaging genomics including study design, imaging protocols, genomic testing, structured reporting, data analysis and synthesis, and biomarker development.
  4. Create multicenter imaging genomics registry for orphan and rare diseases.

Research Areas

Research studies within the IG-RAG will include ongoing funded projects, as well as new pilot projects supported by seed grants.  We have defined the following key priority areas, which represent cutting-edge and impactful areas in the field, as well as integrating investigators from multiple research areas and clinical departments.
Orphan and Rare Diseases

I-ROAR

I-ROAR (Imaging Registry for Orphan and Rare Diseases) is the recipient of an American College of Radiology Innovation Fund Grant (Drs. Krishnamurthy and Ho, Radiology).  This is a multi-institutional imaging registry, research engine, and academic resource that plans to centralize and standardize imaging and genomics data for advancement of practice, education, and research in patients with rare diseases.  We are starting with Batten disease (Dr. de los Reyes, Neurology) and will subsequently expand to other disorders including mucopolysaccharidosis (Dr. Flanigan, Gene Therapy, Dr. McBride, Genetic and Genomic Medicine), Krabbe disease (Dr. Bradbury, Gene Therapy), vascular anomalies (Dr. Lillis, Radiology, Dr. Ibrahim, Plastic Surgery, Dr. Cottrell, IGM), and neuromuscular disorders (Dr. Mendell, Gene Therapy).

Rare Diseases Program

The Rare Diseases Program (Drs. White, Wilson, Koboldt, and Chaudhari, IGM, Dr. McBride, Genetic and Genomic Medicine) enrolls patients with undiagnosed diseases for next-generation research sequencing, including whole-genome sequencing and transcriptomics.  Expert case reviews are conducted quarterly.

Additional potential funding mechanisms include patient foundations and the NIH Rare Diseases Clinical Research Network and Undiagnosed Diseases Network.

Advanced Neuroimaging Core

The Advanced Neuroimaging Core (Dr. Ho, Radiology) supports advanced neuroimage acquisition, quantitative analysis, and clinical trials with a focus on biomarker discovery and validation.  This core resource is available to all investigators and is currently utilized for collaborative projects with the Center for Gene Therapy and Institute for Genomic Medicine.

Genetics Post-Clinic Conference

The Genetics Post-Clinic Conference (Drs. Bartholomew and McBride, Genetic and Genomic Medicine) is a weekly clinical working conference, in which clinical phenotypes are correlated with genetic testing results.  Often, a radiologist is invited to discuss imaging findings.

Artificial Intelligence

Medical Data Mining

A collaborative big data analytics project is in progress, which will utilize Epic data mining technologies and natural language processing approaches (Dr. Rust, RISI), to be integrated with genomic data (Dr. Chaudhari, IGM), and radiology reports (Dr. Ho, Radiology). The objective is to develop Epic software toolboxes in Epic that can synthesize clinical, imaging, and genomic data to develop a risk score for genetic disease and establish a threshold for recommended genetic testing. This toolbox will assist in both clinical and research applications, and can be deployed/tested in other hospitals that utilize the Epic environment.

Radiology Deep Learning

The Advanced Neuroimaging Core (Dr. Ho, Radiology) is building local experience in deep learning for medical imaging through local collaborations (Dr. Bambach, RISI). In addition, we plan to recruit a postdoctoral fellow who will focus on high-dimensional feature extraction and convolutional neural networks for neuroimage analysis, to be correlated with genomic and clinomic datasets (tumor, epilepsy, hearing loss). Finally, we are evaluating potential industry partnerships (Icometrix, SOPHiA, Face2Gene) to augment content expertise and resource development in imaging genomics.

Laboratory Genomics

Neonatal Abstinence Syndrome

The Neonatal Research Network (Drs. Maitre and Benninger, Neonatology) has obtained funding from the Cardinal Health Foundation to prospectively characterize infants with neonatal abstinence syndrome using multimodal imaging, functional electroencephalography, and longitudinal neurodevelopmental features in comparison with a matched cohort of typically developing infants. Genomic and transcriptomic profiles from blood and saliva samples will be correlated with results from in vitro organoid models to better evaluate the mechanisms of NAS (Dr. Hester, IGM). MRI protocols will evaluate advanced imaging biomarkers from perfusion, structural and functional connectivity (Dr. Ho, Radiology).

Epilepsy and Overgrowth Syndromes

  • Brain organoid models of tuberous sclerosis have been developed (Dr. Hester, IGM), which provide insight into the mechanisms of mTOR pathway disorders. This work has implications for various diseases (vascular anomalies, overgrowth syndromes) and potential treatments (off-label use of mTOR inhibitors).
  • IGM has established a research program to enroll complex epilepsy patients (Drs. Ostendorf and Patel, Neurology, Dr. Pindrik, Neurosurgery).  Tissue samples are sent for enhanced whole exome sequencing and RNA sequencing. A REDCap database is maintained with relevant patient demographics, laboratory values, EEG data, and genomic results.  Patients are discussed in multidisciplinary epilepsy conference to achieve a diagnostic consensus.
  • The Hemangioma and Vascular Anomalies Clinic (Dr. Khansa, Plastic Surgery, Dr. Witman, Dermatology, Dr. Lillis, Radiology, Dr. Cottrell, IGM) has high patient referral volumes and monthly multidisciplinary conferences. Treatment of vascular anomalies is complex, multistaged, and in most cases palliative rather than curative.  Targeted therapies based on genomic data could change the paradigm for management, and the clinic provides opportunity for tissue biobanking with deep sequencing. 
  • A small animal imaging unit could be helpful for imaging correlation of in vitro organoids (Dr. Hester, IGM), ex vivo specimens (Dr. Pierson, Pathology), and in vivo imaging (Dr. Ho, Radiology).

Translational Neuro-Oncology Laboratory

  • A mouse model has been developed for low- to high-grade glioma transformation based on the tumor immune microenvironment (Dr. Rajappa, IGM). Translated to human patients, this work could guide the development of imaging biomarkers of glioma grade, as well as precision medicine approaches using immunotherapy.
  • IGM has established a research program to enroll complex brain tumor patients (Dr. Leonard, Neurosurgery, Dr. Finlay, Neuro-Oncology, Dr. Cottrell, IGM). Tissue samples are sent for enhanced whole exome sequencing, RNA sequencing, and methylation profiling.  A REDCap database is maintained with relevant patient demographics, laboratory values, histologic and genomic results.  Patients are discussed in multidisciplinary neuro-oncology conference to achieve a diagnostic consensus.
  • A small animal imaging program could be helpful for imaging correlation of animal models (Dr. Rajappa, IGM), ex vivo specimens (Dr. Pierson, Pathology), and in vivo imaging (Dr. Ho, Radiology).

Faculty

Faculty Lead

  • Mai-Lan Ho, MD
    Associate Professor of Radiology, The Ohio State University
    Director of Research, Department of Radiology, Nationwide Children’s Hospital
    Director, Advanced Neuroimaging Core, Nationwide Children’s Hospital
    Faculty Lead, Imaging Genomics Research Affinity Group, Nationwide Children’s Hospital
    Secretary, Association for Staff and Faculty Women, The Ohio State University
    Chair, Asian Pacific American Network, Nationwide Children’s Hospital

Program Manager

  • Amanda Heater

Steering Committee

 
Nationwide Children's Clinical Departments

Radiology

Genetic and Genomic Medicine

Neurology

Neuro-Oncology

Neurosurgery

Otolaryngology

Plastic Surgery

Cardiology

Hematology & Oncology

Dermatology

Pathology

Nationwide Children's Research Centers

The Steve and Cindy Rasmussen Institute for Genomic Medicine

  • Rick Wilson, PhD
  • Elaine Mardis, PhD
  • Peter White, PhD
  • Catherine Cottrell, MD
  • Dan Koboldt, MS
  • Bimal Chaudhari, MD
  • Prajwal Rajappa, MD
  • Mark Hester, PhD
  • Tracy Bedrosian, PhD

Battelle Center for Mathematical Medicine

Center for Gene Therapy

Research Information Solutions & Innovations Department 

OSU Collaborators
  • Raghu Majirachu, PhD (Translational Data Analytics Institute)
  • Michael Knopp, MD, PhD (Wright Center of Innovation in Biomedical Imaging) 
  • Arnab Chakravarti, MD (Radiation Oncology)
  • Shuman He, MD, PhD (Audiology)
  • Yasushi Kisanuki, MD (Neurology)
  • Krzysztof Bankiewicz, MD (Neurosurgery)
  • Jose Otero, MD, PhD (Pathology)