NeuroImage (Aug 2024)
Identifying novel data-driven subgroups in congenital heart disease using multi-modal measures of brain structure
- Marlee M. Vandewouw,
- Ami Norris-Brilliant,
- Anum Rahman,
- Stephania Assimopoulos,
- Sarah U. Morton,
- Azadeh Kushki,
- Sean Cunningham,
- Eileen King,
- Elizabeth Goldmuntz,
- Thomas A. Miller,
- Nina H. Thomas,
- Heather R. Adams,
- John Cleveland,
- James F. Cnota,
- P Ellen Grant,
- Caren S. Goldberg,
- Hao Huang,
- Jennifer S. Li,
- Patrick McQuillen,
- George A. Porter,
- Amy E. Roberts,
- Mark W. Russell,
- Christine E. Seidman,
- Madalina E. Tivarus,
- Wendy K. Chung,
- Donald J. Hagler,
- Jane W. Newburger,
- Ashok Panigrahy,
- Jason P Lerch,
- Bruce D. Gelb,
- Evdokia Anagnostou
Affiliations
- Marlee M. Vandewouw
- Autism Research Centre, Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Corresponding author at: Autism Research Centre, Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada.
- Ami Norris-Brilliant
- Department of Psychiatry, Icahn School of Medicine, Mount Sinai, New York, USA
- Anum Rahman
- Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON, Canada; Translational Medicine, The Hospital for Sick Children, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
- Stephania Assimopoulos
- Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
- Sarah U. Morton
- Division of Newborn Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA; Fetal Neonatal Neuroimaging and Developmental Science Center, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Department of Genetics, Harvard Medical School, Boston, MA, USA
- Azadeh Kushki
- Autism Research Centre, Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada
- Sean Cunningham
- Department of Pediatrics, Division of General Pediatrics, University of Utah, Salt Lake City, UT, USA
- Eileen King
- Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA; Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Centre, Cincinnati, OH, USA
- Elizabeth Goldmuntz
- Division of Cardiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Thomas A. Miller
- Department of Pediatrics, Maine Medical Center, Portland, ME, USA
- Nina H. Thomas
- Department of Child and Adolescent Psychiatry and Behavioral Sciences and Center for Human Phenomic Science, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA
- Heather R. Adams
- Departments of Neurology and Pediatrics, University of Rochester Medical Center, Rochester, NY, USA
- John Cleveland
- Departments of Surgery and Pediatrics, Keck School of Medicine, University of Southern California, LA, USA
- James F. Cnota
- Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA; Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
- P Ellen Grant
- Division of Newborn Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA; Fetal Neonatal Neuroimaging and Developmental Science Center, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Department of Radiology, Boston Children's Hospital, Boston, MA, USA; Department of Radiology, Harvard Medical School, Boston, MA, USA
- Caren S. Goldberg
- Department of Pediatrics, C.S. Mott Children's Hospital, University of Michigan, Ann Arbor, MI, USA
- Hao Huang
- Department of Radiology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Jennifer S. Li
- Department of Pediatrics, Duke University Medical Center, Durham, NC, USA
- Patrick McQuillen
- Departments of Pediatrics and Neurology, University of California San Francisco, San Francisco, CA, USA
- George A. Porter
- Departments of Neurology and Pediatrics, University of Rochester Medical Center, Rochester, NY, USA
- Amy E. Roberts
- Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Department of Cardiology, Boston Children's Hospital, Boston, MA USA; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA
- Mark W. Russell
- Department of Pediatrics, C.S. Mott Children's Hospital, University of Michigan, Ann Arbor, MI, USA
- Christine E. Seidman
- Department of Genetics, Harvard Medical School, Boston, MA, USA; Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA
- Madalina E. Tivarus
- Department of Imaging Sciences and Department of Neuroscience, University of Rochester Medical Center, Rochester, NY, USA
- Wendy K. Chung
- Departments of Pediatrics and Medicine, Columbia University, New York, NY, USA
- Donald J. Hagler
- Center for Multimodal Imaging and Genetics, University of California San Diego, USA; Department of Radiology, School of Medicine, University of California San Diego, USA; Departments of Cognitive Science and Neuroscience, University of California San Diego, USA
- Jane W. Newburger
- Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Department of Cardiology, Boston Children's Hospital, Boston, MA USA
- Ashok Panigrahy
- Department of Pediatric Radiology, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA USA
- Jason P Lerch
- Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada; Program in Neurosciences & Mental Health, The Hospital for Sick Children, Toronto, ON, Canada; Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
- Bruce D. Gelb
- Mindich Child Health and Development Institute and Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY USA
- Evdokia Anagnostou
- Autism Research Centre, Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada; Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Journal volume & issue
-
Vol. 297
p. 120721
Abstract
Individuals with congenital heart disease (CHD) have an increased risk of neurodevelopmental impairments. Given the hypothesized complexity linking genomics, atypical brain structure, cardiac diagnoses and their management, and neurodevelopmental outcomes, unsupervised methods may provide unique insight into neurodevelopmental variability in CHD. Using data from the Pediatric Cardiac Genomics Consortium Brain and Genes study, we identified data-driven subgroups of individuals with CHD from measures of brain structure. Using structural magnetic resonance imaging (MRI; N = 93; cortical thickness, cortical volume, and subcortical volume), we identified subgroups that differed primarily on cardiac anatomic lesion and language ability. In contrast, using diffusion MRI (N = 88; white matter connectivity strength), we identified subgroups that were characterized by differences in associations with rare genetic variants and visual-motor function. This work provides insight into the differential impacts of cardiac lesions and genomic variation on brain growth and architecture in patients with CHD, with potentially distinct effects on neurodevelopmental outcomes.
