. 2024 Dec:70:101452.

doi: 10.1016/j.dcn.2024.101452. Epub 2024 Sep 21.

Quantifying brain development in the HEALthy Brain and Child Development (HBCD) Study: The magnetic resonance imaging and spectroscopy protocol

Douglas C Dean 3rd¹, M Dylan Tisdall², Jessica L Wisnowski³, Eric Feczko⁴, Borjan Gagoski⁵, Andrew L Alexander⁶, Richard A E Edden⁷, Wei Gao⁸, Timothy J Hendrickson⁹, Brittany R Howell¹⁰, Hao Huang¹¹, Kathryn L Humphreys¹², Tracy Riggins¹³, Chad M Sylvester¹⁴, Kimberly B Weldon¹⁵, Essa Yacoub¹⁶, Banu Ahtam¹⁷, Natacha Beck¹⁸, Suchandrima Banerjee¹⁹, Sergiy Boroday¹⁸, Arvind Caprihan²⁰, Bryan Caron¹⁸, Samuel Carpenter²¹, Yulin Chang²², Ai Wern Chung¹⁷, Matthew Cieslak²³, William T Clarke²⁴, Anders Dale²⁵, Samir Das¹⁸, Christopher W Davies-Jenkins⁷, Alexander J Dufford²⁶, Alan C Evans¹⁸, Laetitia Fesselier¹⁸, Sandeep K Ganji²⁷, Guillaume Gilbert²⁸, Alice M Graham²¹, Aaron T Gudmundson⁷, Maren Macgregor-Hannah²⁹, Michael P Harms³⁰, Tom Hilbert³¹, Steve C N Hui³², M Okan Irfanoglu³³, Steven Kecskemeti³⁴, Tobias Kober³¹, Joshua M Kuperman³⁵, Bidhan Lamichhane³⁶, Bennett A Landman³⁷, Xavier Lecour-Bourcher¹⁸, Erik G Lee⁹, Xu Li⁷, Leigh MacIntyre³⁸, Cecile Madjar¹⁸, Mary Kate Manhard³⁹, Andrew R Mayer²⁰, Kahini Mehta²³, Lucille A Moore¹⁵, Saipavitra Murali-Manohar⁷, Cristian Navarro⁴⁰, Mary Beth Nebel⁴¹, Sharlene D Newman⁴², Allen T Newton⁴³, Ralph Noeske⁴⁴, Elizabeth S Norton⁴⁵, Georg Oeltzschner⁷, Regis Ongaro-Carcy¹⁸, Xiawei Ou⁴⁶, Minhui Ouyang¹¹, Todd B Parrish⁴⁷, James J Pekar⁷, Thomas Pengo²⁹, Carlo Pierpaoli³³, Russell A Poldrack⁴⁸, Vidya Rajagopalan³, Dan W Rettmann⁴⁹, Pierre Rioux¹⁸, Jens T Rosenberg⁵⁰, Taylor Salo²³, Theodore D Satterthwaite²³, Lisa S Scott⁵¹, Eunkyung Shin⁵², Gizeaddis Simegn⁷, W Kyle Simmons⁵³, Yulu Song⁷, Barry J Tikalsky¹⁵, Jean Tkach³⁹, Peter C M van Zijl⁷, Jennifer Vannest⁵⁴, Maarten Versluis²⁷, Yansong Zhao⁵⁵, Helge J Zöllner⁷, Damien A Fair⁵⁶, Christopher D Smyser⁵⁷, Jed T Elison⁵⁸; HBCD MRI Working Group

Affiliations

¹ Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA; Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, USA; Waisman Center, University of Wisconsin-Madison, Madison, WI, USA. Electronic address: deaniii@wisc.edu.
² Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
³ Department of Pediatrics, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA; Department of Radiology, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
⁴ Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA; Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, USA.
⁵ Department of Radiology, Harvard Medical School, Boston, MA, USA; Fetal-Neonatal Neuroimaging & Developmental Science Center, Boston Children's Hospital, Boston, MA, USA.
⁶ Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, USA; Waisman Center, University of Wisconsin-Madison, Madison, WI, USA; Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA.
⁷ Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA.
⁸ Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Biomedical Sciences and Imaging, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁹ Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, USA; Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN, USA; Bioinformatics and Computational Biology Program, University of Minnesota, Minneapolis, MN, USA.
¹⁰ Fralin Biomedical Research Institute at VTC, Virginia Tech, Roanoke, VA, USA; Department of Human Development and Family Science, Virginia Tech, Blacksburg, VA, USA.
¹¹ Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
¹² Department of Psychology and Human Development, Vanderbilt University, Nashville, TN, USA.
¹³ Department of Psychology, University of Maryland, College Park, MD, USA.
¹⁴ Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, USA; Department of Radiology, Washington University in St. Louis, St. Louis, MO, USA; Taylor Family Institute for Innovative Psychiatric Research, Washington University in St. Louis, St. Louis, MO, USA.
¹⁵ Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, USA.
¹⁶ Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, USA.
¹⁷ Fetal-Neonatal Neuroimaging & Developmental Science Center, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
¹⁸ McGill Centre for Integrative Neuroscience, McGill University, Montréal, Québec, Canada; Montréal Neurological Institute-Hospital, Montréal, Québec, Canada; McConnell Brain Imaging Centre, McGill University, Montréal, Québec, Canada.
¹⁹ GE HealthCare, Menlo Park, CA, USA.
²⁰ The Mind Research Network, Albuquerque, NM, USA.
²¹ Department of Psychiatry, Oregon Health & Science University, Portland, OR, USA.
²² Siemens Medical Solutions USA Inc, PA, USA.
²³ Penn Lifespan Informatics and Neuroimaging Center (PennLINC), Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
²⁴ Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
²⁵ Department of Radiology, University of California San Diego, La Jolla, CA, USA; Multimodal Imaging Laboratory, University of California San Diego, La Jolla, CA, USA; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA; Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
²⁶ Department of Psychiatry and Center for Mental Health Innovation, Oregon Health & Science University, Portland, OR, USA.
²⁷ MR Clinical Science, Philips Healthcare, Best, the Netherlands.
²⁸ MR Clinical Science, Philips Healthcare, Mississauga, Ontario, Canada.
²⁹ Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, USA; Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN, USA.
³⁰ Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, USA.
³¹ Advanced Clinical Imaging Technology, Siemens Healthineers International AG, Lausanne, Switzerland,; Department of Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland,; LTS5, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
³² Developing Brain Institute, Children's National Hospital, Washington, DC, USA; Department of Radiology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA; Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
³³ Quantitative Medical Imaging Laboratory, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA.
³⁴ Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
³⁵ Department of Radiology, University of California San Diego, La Jolla, CA, USA.
³⁶ Center for Health Sciences, Oklahoma State University, Tulsa, OK, USA.
³⁷ Department of Electrical and Computer Engineering, Vanderbilt University, Nashville, TN, USA.
³⁸ McGill Centre for Integrative Neuroscience, McGill University, Montréal, Québec, Canada; Montréal Neurological Institute-Hospital, Montréal, Québec, Canada; Lasso Informatics, Canada.
³⁹ Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
⁴⁰ Center for Neurodevelopmental and Imaging Research, Kennedy Krieger Institute, Baltimore, MD, USA.
⁴¹ Center for Neurodevelopmental and Imaging Research, Kennedy Krieger Institute, Baltimore, MD, USA; Department of Neurology, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
⁴² Alabama Life Research Institute, University of Alabama, Tuscaloosa, AL, USA; Department of Psychology, University of Alabama, Tuscaloosa, AL, USA.
⁴³ Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, USA; Monroe Carell Jr. Children's Hospital at Vandebrilt, Vanderbilt University Medical Center, Nashville, TN, USA.
⁴⁴ GE HealthCare, Munich, Germany.
⁴⁵ Department of Communication Sciences and Disorders, School of Communication, Northwestern University, Evanston, IL, USA; Department of Medical Social Sciences, Feinberg School of Medicine, Chicago, IL, USA.
⁴⁶ Department of Radiology, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Arkansas Children's Research Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
⁴⁷ Department of Radiology, Feinberg School of Medicine, Chicago, IL, USA; Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.
⁴⁸ Department of Psychology, Stanford University, Stanford, CA, USA.
⁴⁹ GE HealthCare, Rochester, MN, USA.
⁵⁰ Advanced Magnetic Resonance Imaging and Spectroscopy Facility, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
⁵¹ Department of Psychology, University of Florida, Gainesville, FL, USA.
⁵² Department of Psychology, Pennsylvania State University, University Park, PA, USA.
⁵³ Department of Pharmacology and Physiology, Oklahoma State University Center for Health Sciences, Tulsa, OK, USA; OSU Biomedical Imaging Center, Oklahoma State University Center for Health Sciences, Tulsa, OK, USA.
⁵⁴ Department of Communication Sciences and Disorders, University of Cincinnati, Cincinnati, OH, USA; Communication Sciences Research Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
⁵⁵ MR Clinical Science, Philips Healthcare, Cleveland, OH, USA.
⁵⁶ Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA; Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, USA; Institute of Child Development, University of Minnesota, Minneapolis, MN, USA. Electronic address: faird@umn.edu.
⁵⁷ Department of Neurology, Washington University in St. Louis, St. Louis, MO, USA; Department of Pediatrics, Washington University in St. Louis, St. Louis, MO, USA; Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO, USA. Electronic address: smyserc@wustl.edu.
⁵⁸ Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA; Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, USA; Institute of Child Development, University of Minnesota, Minneapolis, MN, USA. Electronic address: jtelison@umn.edu.

PMID: 39341120
PMCID: PMC11466640
DOI: 10.1016/j.dcn.2024.101452

Quantifying brain development in the HEALthy Brain and Child Development (HBCD) Study: The magnetic resonance imaging and spectroscopy protocol

Douglas C Dean 3rd et al. Dev Cogn Neurosci. 2024 Dec.

. 2024 Dec:70:101452.

doi: 10.1016/j.dcn.2024.101452. Epub 2024 Sep 21.

Authors

Affiliations

¹ Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA; Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, USA; Waisman Center, University of Wisconsin-Madison, Madison, WI, USA. Electronic address: deaniii@wisc.edu.
² Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
³ Department of Pediatrics, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA; Department of Radiology, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
⁴ Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA; Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, USA.
⁵ Department of Radiology, Harvard Medical School, Boston, MA, USA; Fetal-Neonatal Neuroimaging & Developmental Science Center, Boston Children's Hospital, Boston, MA, USA.
⁶ Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, USA; Waisman Center, University of Wisconsin-Madison, Madison, WI, USA; Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA.
⁷ Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA.
⁸ Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Biomedical Sciences and Imaging, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁹ Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, USA; Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN, USA; Bioinformatics and Computational Biology Program, University of Minnesota, Minneapolis, MN, USA.
¹⁰ Fralin Biomedical Research Institute at VTC, Virginia Tech, Roanoke, VA, USA; Department of Human Development and Family Science, Virginia Tech, Blacksburg, VA, USA.
¹¹ Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
¹² Department of Psychology and Human Development, Vanderbilt University, Nashville, TN, USA.
¹³ Department of Psychology, University of Maryland, College Park, MD, USA.
¹⁴ Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, USA; Department of Radiology, Washington University in St. Louis, St. Louis, MO, USA; Taylor Family Institute for Innovative Psychiatric Research, Washington University in St. Louis, St. Louis, MO, USA.
¹⁵ Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, USA.
¹⁶ Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, USA.
¹⁷ Fetal-Neonatal Neuroimaging & Developmental Science Center, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
¹⁸ McGill Centre for Integrative Neuroscience, McGill University, Montréal, Québec, Canada; Montréal Neurological Institute-Hospital, Montréal, Québec, Canada; McConnell Brain Imaging Centre, McGill University, Montréal, Québec, Canada.
¹⁹ GE HealthCare, Menlo Park, CA, USA.
²⁰ The Mind Research Network, Albuquerque, NM, USA.
²¹ Department of Psychiatry, Oregon Health & Science University, Portland, OR, USA.
²² Siemens Medical Solutions USA Inc, PA, USA.
²³ Penn Lifespan Informatics and Neuroimaging Center (PennLINC), Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
²⁴ Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
²⁵ Department of Radiology, University of California San Diego, La Jolla, CA, USA; Multimodal Imaging Laboratory, University of California San Diego, La Jolla, CA, USA; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA; Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
²⁶ Department of Psychiatry and Center for Mental Health Innovation, Oregon Health & Science University, Portland, OR, USA.
²⁷ MR Clinical Science, Philips Healthcare, Best, the Netherlands.
²⁸ MR Clinical Science, Philips Healthcare, Mississauga, Ontario, Canada.
²⁹ Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, USA; Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN, USA.
³⁰ Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, USA.
³¹ Advanced Clinical Imaging Technology, Siemens Healthineers International AG, Lausanne, Switzerland,; Department of Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland,; LTS5, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
³² Developing Brain Institute, Children's National Hospital, Washington, DC, USA; Department of Radiology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA; Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
³³ Quantitative Medical Imaging Laboratory, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA.
³⁴ Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.
³⁵ Department of Radiology, University of California San Diego, La Jolla, CA, USA.
³⁶ Center for Health Sciences, Oklahoma State University, Tulsa, OK, USA.
³⁷ Department of Electrical and Computer Engineering, Vanderbilt University, Nashville, TN, USA.
³⁸ McGill Centre for Integrative Neuroscience, McGill University, Montréal, Québec, Canada; Montréal Neurological Institute-Hospital, Montréal, Québec, Canada; Lasso Informatics, Canada.
³⁹ Department of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
⁴⁰ Center for Neurodevelopmental and Imaging Research, Kennedy Krieger Institute, Baltimore, MD, USA.
⁴¹ Center for Neurodevelopmental and Imaging Research, Kennedy Krieger Institute, Baltimore, MD, USA; Department of Neurology, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
⁴² Alabama Life Research Institute, University of Alabama, Tuscaloosa, AL, USA; Department of Psychology, University of Alabama, Tuscaloosa, AL, USA.
⁴³ Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, USA; Monroe Carell Jr. Children's Hospital at Vandebrilt, Vanderbilt University Medical Center, Nashville, TN, USA.
⁴⁴ GE HealthCare, Munich, Germany.
⁴⁵ Department of Communication Sciences and Disorders, School of Communication, Northwestern University, Evanston, IL, USA; Department of Medical Social Sciences, Feinberg School of Medicine, Chicago, IL, USA.
⁴⁶ Department of Radiology, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Arkansas Children's Research Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
⁴⁷ Department of Radiology, Feinberg School of Medicine, Chicago, IL, USA; Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA.
⁴⁸ Department of Psychology, Stanford University, Stanford, CA, USA.
⁴⁹ GE HealthCare, Rochester, MN, USA.
⁵⁰ Advanced Magnetic Resonance Imaging and Spectroscopy Facility, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
⁵¹ Department of Psychology, University of Florida, Gainesville, FL, USA.
⁵² Department of Psychology, Pennsylvania State University, University Park, PA, USA.
⁵³ Department of Pharmacology and Physiology, Oklahoma State University Center for Health Sciences, Tulsa, OK, USA; OSU Biomedical Imaging Center, Oklahoma State University Center for Health Sciences, Tulsa, OK, USA.
⁵⁴ Department of Communication Sciences and Disorders, University of Cincinnati, Cincinnati, OH, USA; Communication Sciences Research Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
⁵⁵ MR Clinical Science, Philips Healthcare, Cleveland, OH, USA.
⁵⁶ Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA; Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, USA; Institute of Child Development, University of Minnesota, Minneapolis, MN, USA. Electronic address: faird@umn.edu.
⁵⁷ Department of Neurology, Washington University in St. Louis, St. Louis, MO, USA; Department of Pediatrics, Washington University in St. Louis, St. Louis, MO, USA; Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, MO, USA. Electronic address: smyserc@wustl.edu.
⁵⁸ Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA; Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, USA; Institute of Child Development, University of Minnesota, Minneapolis, MN, USA. Electronic address: jtelison@umn.edu.

PMID: 39341120
PMCID: PMC11466640
DOI: 10.1016/j.dcn.2024.101452

Abstract

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The acquisition of multimodal magnetic resonance-based brain development data is central to the study's core protocol. However, application of Magnetic Resonance Imaging (MRI) methods in this population is complicated by technical challenges and difficulties of imaging in early life. Overcoming these challenges requires an innovative and harmonized approach, combining age-appropriate acquisition protocols together with specialized pediatric neuroimaging strategies. The HBCD MRI Working Group aimed to establish a core acquisition protocol for all 27 HBCD Study recruitment sites to measure brain structure, function, microstructure, and metabolites. Acquisition parameters of individual modalities have been matched across MRI scanner platforms for harmonized acquisitions and state-of-the-art technologies are employed to enable faster and motion-robust imaging. Here, we provide an overview of the HBCD MRI protocol, including decisions of individual modalities and preliminary data. The result will be an unparalleled resource for examining early neurodevelopment which enables the larger scientific community to assess normative trajectories from birth through childhood and to examine the genetic, biological, and environmental factors that help shape the developing brain.

Keywords: Development; HBCD; Infant; MRI; MRS; Protocol.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Tobias Kober and Tom Hilbert are employees of Siemens Healthineers International AG, Switzerland. Yulin Chang is an employee of Siemens Medical Solutions USA Inc. Dan Rettmann and Ralph Noeske are employed by GE HealthCare. Guillaume Gilbert, Yansong Zhao, Sandeep Ganji, and Maarten Versluis are employed by Philips Healthcare. Carina Lucena, Lucky Heisler-Roman, and Dhruman Goradia are employed by PrimeNeuro Inc. Under a license agreement between Philips and the Johns Hopkins University, Dr. van Zijl and the University are entitled to fees related to an imaging device used in the study discussed for publication. Dr. van Zijl also is a paid lecturer for Philips and receives research support from Philips. This arrangement has been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. Damien Fair is a patent holder on the Framwise Integrated Real-Time Motion Monitoring (FIRMM) software. He is also a co-founder of Turing Medical Technologies, Inc. The nature of this financial interest and the design of the study have been reviewed by two committees at the University of Minnesota. They have put in place a plan to help ensure that this research is not affected by the financial interest. All other authors report no biomedical financial interests or potential conflicts of interest.

Figures

**Fig. 1**
Visit schedule for the HBCD protocol. Of note, MRI scans will be collected at each in person assessment visit (visits 2, 3, 4, and 6). Of note, procedures for Visit 4 and beyond are only current as of the time of this manuscript submission and may change during piloting.

**Fig. 2**
: Pilot data, acquired in a 5 week old participant, showing two alternative T2-weighted protocols evaluated during optimization on the Siemens platform. The vendor-matched protocol harmonized TR, TE, and echo train length (ETL) across all vendors. However, due to variations in how each vendor implements variable-flip-angle turbo spin echo, we could achieve equivalent or superior image contrast in shorter time with vendor-specific choices of TR, TE, and ETL.

**Fig. 3**
: Pilot data, acquired in a 5 month old participant, showing four acceleration factors that were evaluated for T1-weighted protocols during the optimization on the Siemens platform (either GRAPPA or Compressed SENSE, with total scan duration noted). The region outlined by the red dashed box is zoomed for each volume to highlight the effects of acceleration on fine features. Comparing GRAPPA 6:35 to CS 6:15, we can see that compressed sensing of equivalent scan time preserves fine high-contrast structures with less noise than GRAPPA. However, at CS 2:45 the high degree of acceleration leads to a subtle blurring of fine features. Our final protocol set 4 minutes as the target T1-weighted structural scan duration across all three vendors.

**Fig. 4**
(A) A depiction of the HBCD fMRI acquisition protocol. There are two resting state (rs) fMRI acquisitions lasting 7.5 min each. Each rs-fMRI run is preceded by a pair of single shot spin-echo (SE) EPI images with matched bandwidth to the resting state data. One image in the pair of spin-echo images is acquired with reversed polarity phase encoding gradients, allowing for the pair to be used in a blip-up-blip-down (BUBD) distortion correction algorithm. (B) All HBCD fMRI data are monitored in real time at the point of acquisition for motion using FIRMM. If motion is severe enough to prevent further analysis, the pair of SE-BUBD images and a 7.5 min resting state acquisition can be repeated until sufficient data have been acquired. (C) Spin-echo data pairs can be used to estimate the static field as well as the corrections necessary to account for image distortion. Spin echo images are used for this purpose to obtain better estimates in regions of significant inhomogeneity. The calculated corrections are then applied to the gradient echo resting state images, resulting in the distortion corrected rs-fMRI data.

**Fig. 5**
: Axial slices of unprocessed diffusion-weighted images from an HBCD acquisition. Slices acquired with AP and PA phase encoding directions are shown in the left and right columns, respectively. Gradient strengths in b (s/mm²) are shown per row with the number of images collected at the b value in parenthesis. The AP and PA images shown at b>0 are not the same gradient direction, as the gradient directions are split across the phase encoding directions.

**Fig. 6**
: Representative axial, sagittal, and coronal slices of quantitative T1 and T2 maps acquired in age-matched (3–4 weeks) infants across the three major MRI vendors. Histograms of quantitative T1 and T2 relaxation times of these infants highlight good inter-vendor agreement.

**Fig. 7**
: MRS data acquisition is localized to a single voxel (30×23×23 mm³) in the bilateral thalamus as shown in the top panel above. The thalamus is reciprocally interconnected with nearly the entire cerebral cortex and the GABAergic neurons of the thalamus are involved in the generation of normal and abnormal synchronized activity across the various thalamocortical networks. The MRS WG selected the thalamus as the region of interest from which glutamate, GABA and other relevant metabolites would be measured with the goal of determining how differences in the trajectory of thalamic GABA levels related to the trajectory of thalamocortical connectivity and cognitive-behavioral development across the first decade of life. Shown below are averaged spectra (solid lines) and standard deviation (shaded region) across participants acquired during the pilot phase of HBCD on each MRI vendor platform. Note that the pilot GE data were acquired using an older HERMES sequence as the GE ISTHMUS implementation had not yet been finalized at the time.

**Fig. 8**
: Schematic representations of hypothetical infant MRI scan sessions. These are example sequences of events that can occur during infant MRI scan sessions. Note the variation in total session duration (2–5+ hrs, with older infants often taking longer to acquire data), times infants are awake and asleep, and amount of usable data acquired. Scan sessions can be short due to time or staff restrictions (Case A), or because the infant falls asleep quickly and stays asleep for the duration of data acquisition (Case B – ideal situation). Infants may wake shortly after data acquisition begins (Case C), or after some data are acquired (Case E), may stay asleep for all data collection after taking a long time to fall asleep (Case F), or may never go to sleep leading to the family or imaging center policy ending the scan without any data being acquired (Case D). Some children will wiggle throughout a scan session (Case G), or a team may rush getting a sleeping infant into the scanner (Case H), when waiting for them to fall into a deeper sleep in the scanner would have been better (Case I). Others may need to be removed from the scanner and comforted multiple times in order to collect adequate data (Cases J and L). Some extended scan sessions will result in adequate data collection (Case K), while others will seem like anything and everything that can go wrong does (Case L), sometimes with data acquired and other times without. The key is to remain positive and to adapt to each family.

**Fig. 9**
: Summary of the fully automated MRS data processing workflow. The workflow includes automated data transfer and ingestion, integrates derivatives from the HBCD MRI analysis, performs the MRS analysis, and generates quantitative results and summary reports.

**Fig. 10**
: High-level schematic of the CBRAIN user interface, data management and processing components for HBCD study.

See this image and copyright information in PMC

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Quantifying brain development in the HEALthy Brain and Child Development (HBCD) Study: The magnetic resonance imaging and spectroscopy protocol

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Quantifying brain development in the HEALthy Brain and Child Development (HBCD) Study: The magnetic resonance imaging and spectroscopy protocol

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