Imaging Genomics Research Affinity Group (IG-RAG)

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.

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.

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).

Radiology

• Raj Krishnamurthy, MD
• Mai-Lan Ho, MD
• Brent Adler, MD
• Eric Diaz, MD
• Anna Lillis, MD

Genetic and Genomic Medicine

• Dennis Bartholomew, MD
• Kim McBride, MD
• Nicholas Abreu, MD

Neurology

• Anne Connolly, MD
• Anup Patel, MD
• Adam Ostendorf, MD
• Margie Ream, MD, PhD
• Chang-Yong Tsao, MD
• Emily de los Reyes, MD
• Monica Islam, MD

Neuro-Oncology

• Maryam Fouladi, MD, MSc, FRCPC
• Rachid Drissi, PhD
• Mohamed AbdelBaki, MD

Neurosurgery

• Jeff Leonard, MD
• Jonathan Pindrik, MD

Otolaryngology

• Prashant Malhotra, MD

Plastic Surgery

• Ibrahim Khansa, MD

Cardiology

• Kan Hor, MD
• Linda Cripe, MD

Hematology & Oncology

• Timothy Cripe, MD
• Dean Lee, MD

Dermatology

• Patricia Witman, MD

Pathology

• Chris Pierson, MD

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

• Veronica Vieland, PhD
• Jayajit Das, PhD
• David Greenberg, PhD
• Paola Malerba, PhD
• William Stewart, PhD
• William Ray, PhD
• Christopher Bartlett, PhD

Center for Gene Therapy

• Kevin Flanigan, MD
• Allison Bradbury, MD
• Megan Waldrop, MD
• Linda Lowes, MD
• Jerry Mendell, MD

Research Information Solutions & Innovations Department 

• Simon Lin, MD, MBA
• Steve Rust, PhD
• Sven Bambach, PhD

• 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)