Single Ventricle Reconstruction III: Brain Connectome and Neurodevelopmental Outcomes: Design, Recruitment, and Technical Challenges of a Multicenter, Observational Neuroimaging Study

• Type of Material: Article
• Authors: Vanessa Schmithorst, University of Pennsylvania; Rafael Ceschin, University of Pennsylvania; Vincent Lee, University of Pennsylvania; Julia Wallace, University of Pennsylvania; Aurelia Sahel, University of Pennsylvania; Dawn Ilardi, Emory University; Nadja Kadom, Emory University; William Mahle, Emory University; Deqiang Qiu, Emory University
• Language: English
• Date: 2023-04-30
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2023 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/diagnostics13091604
• Title of Journal or Parent Work: DIAGNOSTICS
• Volume: 13
• Issue: 9
• Grant/Funding Information: This work was supported by grants from the National Heart, Lung, and Blood Institute (HL135680, HL135685, HL135683, HL135689, HL135691, HL135646, HL135665, HL135678, HL135682, and HL135666). AP was supported by the Department of Defense (W81XWH-16-1-0613), the National Heart, Lung and Blood Institute (R01 HL152740-1, R01 HL128818-05), National Library of Medicine (5T15LM007059-320), a Society for Pediatric Radiology Multi-Institutional Pilot Award and Additional Ventures.
• Keywords: Life Sciences & Biomedicine; Science & Technology; hypoplastic left heart syndrome; General & Internal Medicine; CIRCULATORY ARREST; D-TRANSPOSITION; multi-center neuroimaging; FUNCTIONAL CONNECTIVITY; DIFFUSION MRI; harmonization; TEST-RETEST; CONGENITAL HEART-DISEASE; GREAT-ARTERIES; QUALITY-OF-LIFE; brain connectome; NETWORK; Medicine, General & Internal; phantoms; CHILDREN
• Research Categories: Biology, Neuroscience; Health Sciences, Radiology

Abstract

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.