BMJ Open (Apr 2021)
Integrating neuroimaging biomarkers into the multicentre, high-dose erythropoietin for asphyxia and encephalopathy (HEAL) trial: rationale, protocol and harmonisation
- ,
- Taeun Chang,
- Brenda Poindexter,
- Gregory M. Sokol,
- Ashok Panigrahy,
- Stefan Bluml,
- Patrick J Heagerty,
- Mark Smith,
- Jessica L Wisnowski,
- Amit M Mathur,
- Jeffrey Berman,
- Ping-Sun Keven Chen,
- James Dix,
- Trevor Flynn,
- Stanley Fricke,
- Seth D Friedman,
- Hayden W Head,
- Chang Y Ho,
- Beth Kline-Fath,
- Michael Oveson,
- Richard Patterson,
- Sumit Pruthi,
- Nancy Rollins,
- Yanerys M Ramos,
- John Rampton,
- Jerome Rusin,
- Dennis W Shaw,
- Jean Tkach,
- Shreyas Vasanawala,
- Arastoo Vossough,
- Matthew T Whitehead,
- Duan Xu,
- Kristen Yeom,
- Bryan Comstock,
- Sandra E Juul,
- Yvonne W Wu,
- Robert C McKinstry,
- Kaashif Ahmed,
- Mariana Beserga,
- Ellen Bendel-Stenzel,
- Lina Chalak,
- John Flibotte,
- Fernando Gonzalez,
- Andrea Lampland,
- Nathalie Maitre,
- Amit M. Mathur,
- Dennis Mayock,
- Ulrike Mietzsch,
- Rakesh Rao,
- David Riley,
- Krisa Van Meurs,
- Hendrik Weitkamp,
- Tai-Wei Wu,
- Toby Yanowitz
Affiliations
- 4Association of British Neurologists
- Taeun Chang
- Brenda Poindexter
- Gregory M. Sokol
- Ashok Panigrahy
- Radiology, Children`s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
- Stefan Bluml
- Radiology, USC Keck School of Medicine, Los Angeles, California, USA
- Patrick J Heagerty
- Department of Biostatistics, University of Washington, Seattle, Washington, USA
- Mark Smith
- KHP Cardiovascular & Respiratory Partnership, Guy`s and St Thomas` NHS Foundation Trust, London, UK
- Jessica L Wisnowski
- Radiology, Children’s Hospital of Los Angeles, Los Angeles, California, USA
- Amit M Mathur
- Pediatrics, Division of Neonatal-Perinatal Medicine, SSM Health Cardinal Glennon Childrens Hospital, Saint Louis, Missouri, USA
- Jeffrey Berman
- Radiology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
- Ping-Sun Keven Chen
- Radiology, Children’s Hospital of San Antonio, San Antonio, Texas, USA
- James Dix
- Radiology, Methodist Children’s Hospital, San Antonio, Texas, USA
- Trevor Flynn
- Radiology, University of California San Francisco, San Francisco, California, USA
- Stanley Fricke
- Radiology, Georgetown University Medical Center, Washington, District of Columbia, USA
- Seth D Friedman
- Radiology, Seattle Children’s Hospital, Seattle, Washington, USA
- Hayden W Head
- Radiology, Cook Children’s Medical Center, Fort Worth, Texas, USA
- Chang Y Ho
- Radiology, Indiana University School of Medicine, Indianapolis, Indiana, USA
- Beth Kline-Fath
- Radiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
- Michael Oveson
- Radiology, Primary Children’s Hospital, Salt Lake City, Utah, USA
- Richard Patterson
- Radiology, Children’s Hospitals and Clinics of Minnesota, Minneapolis, Minnesota, USA
- Sumit Pruthi
- Radiology, Vanderbilt University, Nashville, Tennessee, USA
- Nancy Rollins
- Radiology, University of Texas Southwestern Medical School, Dallas, Texas, USA
- Yanerys M Ramos
- Radiology, Children’s Hospitals and Clinics of Minnesota, Minneapolis, Minnesota, USA
- John Rampton
- Radiology, Primary Children’s Hospital, Salt Lake City, Utah, USA
- Jerome Rusin
- Radiology, Nationwide Children’s Hospital, Columbus, Ohio, USA
- Dennis W Shaw
- Radiology, Seattle Children’s Hospital, Seattle, Washington, USA
- Jean Tkach
- Radiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
- Shreyas Vasanawala
- Radiology, Stanford University, Stanford, California, USA
- Arastoo Vossough
- Radiology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
- Matthew T Whitehead
- Radiology, Children’s National Medical Center, Washington, District of Columbia, USA
- Duan Xu
- Radiology, University of California San Francisco, San Francisco, California, USA
- Kristen Yeom
- Radiology, Stanford University, Stanford, California, USA
- Bryan Comstock
- Biostatistics, University of Washington, Seattle, Washington, USA
- Sandra E Juul
- 18 University of Washington, Seattle, Washington, USA
- Yvonne W Wu
- Neurology, University of California San Francisco, San Francisco, California, USA
- Robert C McKinstry
- Radiology, St. Louis Children’s Hospital and Washington University, Saint Louis, Missouri, USA
- Kaashif Ahmed
- Mariana Beserga
- Ellen Bendel-Stenzel
- Lina Chalak
- John Flibotte
- Department of Pediatrics, The Children`s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
- Fernando Gonzalez
- Andrea Lampland
- Nathalie Maitre
- 1 Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA
- Amit M. Mathur
- Dennis Mayock
- Ulrike Mietzsch
- Rakesh Rao
- David Riley
- Krisa Van Meurs
- Hendrik Weitkamp
- Tai-Wei Wu
- 1 Fetal and Neonatal Institute, Division of Neonatology, Children`s Hospital Los Angeles, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
- Toby Yanowitz
- DOI
- https://doi.org/10.1136/bmjopen-2020-043852
- Journal volume & issue
-
Vol. 11,
no. 4
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.
