Integrating neuroimaging biomarkers into the multicentre, high-dose erythropoietin for asphyxia and encephalopathy (HEAL) trial: rationale, protocol and harmonisation. Issue 4 (22nd April 2021)

• Record Type: Journal Article
• Authors: Wisnowski, Jessica L; Bluml, Stefan; Panigrahy, Ashok; Mathur, Amit M; Berman, Jeffrey; Chen, Ping-Sun Keven; Dix, James; Flynn, Trevor; Fricke, Stanley; Friedman, Seth D; Head, Hayden W; Ho, Chang Y; Kline-Fath, Beth; Oveson, Michael; Patterson, Richard; Pruthi, Sumit; Rollins, Nancy; Ramos, Yanerys M; Rampton, John; Rusin, Jerome; Shaw, Dennis W; Smith, Mark; Tkach, Jean; Vasanawala, Shreyas; Vossough, Arastoo; Whitehead, Matthew T; Xu, Duan; Yeom, Kristen; Comstock, Bryan; Heagerty, Patrick J; Juul, Sandra E; Wu, Yvonne W; McKinstry, Robert C;
• Other Names: author non-byline.; Ahmed Kaashif author non-byline.; Beserga Mariana author non-byline.; Bendel-Stenzel Ellen author non-byline.; Chalak Lina author non-byline.; Chang Taeun author non-byline.; Flibotte John author non-byline.; Gonzalez Fernando author non-byline.; Lampland Andrea author non-byline.; Maitre Nathalie author non-byline.; Mathur Amit M. author non-byline.; Mayock Dennis author non-byline.; Mietzsch Ulrike author non-byline.; Poindexter Brenda author non-byline.; Rao Rakesh author non-byline.; Riley David author non-byline.; Sokol Gregory M. author non-byline.; Meurs Krisa Van author non-byline.; Weitkamp Hendrik author non-byline.; Wu Tai-Wei author non-byline.; Yanowitz Toby author non-byline.
• Is Part Of: BMJ open. Volume 11:Issue 4(2021)
• Publication Date: 2021-04-22
• Subjects: neonatal intensive & critical care -- neonatology -- neurological injury -- neuroradiology -- developmental neurology & neurodisability -- paediatric radiology; Medicine -- Research -- Periodicals; 610.72
• DOI: 10.1136/bmjopen-2020-043852
• Languages: English
• ISSNs: 2044-6055

Abstract

Abstract : Introduction: MRI and MR spectroscopy (MRS) provide early biomarkers of brain injury and treatment response in neonates with hypoxic-ischaemic encephalopathy). Still, there are challenges to incorporating neuroimaging biomarkers into multisite randomised controlled trials. In this paper, we provide the rationale for incorporating MRI and MRS biomarkers into the multisite, phase III high-dose erythropoietin for asphyxia and encephalopathy (HEAL) Trial, the MRI/S protocol and describe the strategies used for harmonisation across multiple MRI platforms. Methods and analysis: Neonates with moderate or severe encephalopathy enrolled in the multisite HEAL trial undergo MRI and MRS between 96 and 144 hours of age using standardised neuroimaging protocols. MRI and MRS data are processed centrally and used to determine a brain injury score and quantitative measures of lactate and n-acetylaspartate. Harmonisation is achieved through standardisation—thereby reducing intrasite and intersite variance, real-time quality assurance monitoring and phantom scans. Ethics and dissemination: IRB approval was obtained at each participating site and written consent obtained from parents prior to participation in HEAL. Additional oversight is provided by an National Institutes of Health-appointed data safety monitoring board and medical monitor. Trial registration number: NCT02811263; Pre-result .