Single Ventricle Reconstruction III: Brain Connectome and Neurodevelopmental Outcomes: Design, Recruitment, and Technical Challenges of a Multicenter, Observational Neuroimaging Study
Vanessa Schmithorst,
Rafael Ceschin,
Vincent Lee,
Julia Wallace,
Aurelia Sahel,
Thomas L. Chenevert,
Hemant Parmar,
Jeffrey I. Berman,
Arastoo Vossough,
Deqiang Qiu,
Nadja Kadom,
Patricia Ellen Grant,
Borjan Gagoski,
Peter S. LaViolette,
Mohit Maheshwari,
Lynn A. Sleeper,
David C. Bellinger,
Dawn Ilardi,
Sharon O’Neil,
Thomas A. Miller,
Jon Detterich,
Kevin D. Hill,
Andrew M. Atz,
Marc E. Richmond,
James Cnota,
William T. Mahle,
Nancy S. Ghanayem,
J. William Gaynor,
Caren S. Goldberg,
Jane W. Newburger,
Ashok Panigrahy
Affiliations
Vanessa Schmithorst
Department of Radiology, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Avenue, Floor 2, Pittsburgh, PA 15224, USA
Rafael Ceschin
Department of Radiology, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Avenue, Floor 2, Pittsburgh, PA 15224, USA
Vincent Lee
Department of Radiology, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Avenue, Floor 2, Pittsburgh, PA 15224, USA
Julia Wallace
Department of Radiology, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Avenue, Floor 2, Pittsburgh, PA 15224, USA
Aurelia Sahel
Department of Radiology, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Avenue, Floor 2, Pittsburgh, PA 15224, USA
Thomas L. Chenevert
Michigan Medicine Department of Radiology, University of Michigan, 1500 E Medical Center Dr., Ann Arbor, MI 48109, USA
Hemant Parmar
Michigan Medicine Department of Radiology, University of Michigan, 1500 E Medical Center Dr., Ann Arbor, MI 48109, USA
Jeffrey I. Berman
Department of Radiology, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd., Philadelphia, PA 19104, USA
Arastoo Vossough
Department of Radiology, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd., Philadelphia, PA 19104, USA
Deqiang Qiu
Department of Radiology and Imaging Sciences, Children’s Healthcare of Atlanta, Emory University, 1364 Clifton Rd, Atlanta, GA 30322, USA
Nadja Kadom
Department of Radiology and Imaging Sciences, Children’s Healthcare of Atlanta, Emory University, 1364 Clifton Rd, Atlanta, GA 30322, USA
Patricia Ellen Grant
Children’s Hospital Boston, Fetal-Neonatal Neuroimaging and Developmental Science Center (FNNDSC), 300 Longwood Avenue, Boston, MA 02115, USA
Borjan Gagoski
Department of Radiology, Children’s Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA
Peter S. LaViolette
Department of Radiology, Medical College of Wisconsin, 9200 W Wisconsin Avenue, Milwaukee, WI 53226, USA
Mohit Maheshwari
Department of Radiology, Medical College of Wisconsin, 9200 W Wisconsin Avenue, Milwaukee, WI 53226, USA
Lynn A. Sleeper
Department of Cardiology, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115, USA
David C. Bellinger
Cardiac Neurodevelopmental Program, Department of Neurology, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115, USA
Dawn Ilardi
Department of Neuropsychology, Children’s Healthcare of Atlanta, 1400 Tullie Road NE, Atlanta, GA 30329, USA
Sharon O’Neil
Children’s Hospital Los Angeles, Neuropsychology Core of the Saban Research Institute, 4661 Sunset Blvd., Los Angeles, CA 90027, USA
Thomas A. Miller
Division of Pediatric Cardiology, Department of Pediatrics, University of Utah School of Medicine, 30 N 1900 E, Salt Lake City, UT 84132, USA
Jon Detterich
Division of Pediatric Cardiology, Children’s Hospital Los Angeles, 4650 Sunset Blvd., Los Angeles, CA 90027, USA
Kevin D. Hill
Division of Pediatric Cardiology, Department of Pediatrics, Duke University School of Medicine, 7506 Hospital North, DUMC Box 3090, Durham, NC 27710, USA
Andrew M. Atz
Division of Pediatric Cardiology, Medical University of South Carolina, 96 Jonathan Lucas St. Ste. 601, MSC 617, Charleston, SC 29425, USA
Marc E. Richmond
Program for Pediatric Cardiomyopathy, Heart Failure, and Transplantation, New York-Presbyterian Morgan Stanley Children’s Hospital, 3959 Broadway MSCH North, 2nd Floor, New York, NY 10032, USA
Division of Pediatric Cardiology, Children’s Healthcare of Atlanta, 1400 Tullie Rd NE Suite 630, Atlanta, GA 30329, USA
Nancy S. Ghanayem
Section of Pediatric Critical Care, Department of Pediatrics, Comer Children’s Hospital, University of Chicago Medicine, 5721 S. Maryland Avenue, Chicago, IL 60637, USA
J. William Gaynor
Heart Failure and Transplant Program, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd., Philadelphia, PA 19104, USA
Caren S. Goldberg
Department of Pediatrics, Division of Cardiology, C.S. Mott Children’s Hospital, 1540 E Hospital Dr #4204, Ann Arbor, MI 48109, USA
Jane W. Newburger
Department of Cardiology, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115, USA
Ashok Panigrahy
Department of Radiology, UPMC Children’s Hospital of Pittsburgh, 4401 Penn Avenue, Floor 2, Pittsburgh, PA 15224, USA
Patients with hypoplastic left heart syndrome who have been palliated with the Fontan procedure are at risk for adverse neurodevelopmental outcomes, lower quality of life, and reduced employability. We describe the methods (including quality assurance and quality control protocols) and challenges of a multi-center observational ancillary study, SVRIII (Single Ventricle Reconstruction Trial) Brain Connectome. Our original goal was to obtain advanced neuroimaging (Diffusion Tensor Imaging and Resting-BOLD) in 140 SVR III participants and 100 healthy controls for brain connectome analyses. Linear regression and mediation statistical methods will be used to analyze associations of brain connectome measures with neurocognitive measures and clinical risk factors. Initial recruitment challenges occurred that were related to difficulties with: (1) coordinating brain MRI for participants already undergoing extensive testing in the parent study, and (2) recruiting healthy control subjects. The COVID-19 pandemic negatively affected enrollment late in the study. Enrollment challenges were addressed by: (1) adding additional study sites, (2) increasing the frequency of meetings with site coordinators, and (3) developing additional healthy control recruitment strategies, including using research registries and advertising the study to community-based groups. Technical challenges that emerged early in the study were related to the acquisition, harmonization, and transfer of neuroimages. These hurdles were successfully overcome with protocol modifications and frequent site visits that involved human and synthetic phantoms.
