. 2017 Jan;27(1):3-11.

doi: 10.1002/hipo.22671. Epub 2016 Nov 15.

A harmonized segmentation protocol for hippocampal and parahippocampal subregions: Why do we need one and what are the key goals?

Laura E M Wisse^#¹, Ana M Daugherty^#², Rosanna K Olsen³, David Berron⁴, Valerie A Carr^{5

6}, Craig E L Stark⁷, Robert S C Amaral^{8

9

10}, Katrin Amunts^{11

12

13}, Jean C Augustinack¹⁴, Andrew R Bender¹⁵, Jeffrey D Bernstein¹⁶, Marina Boccardi¹⁷, Martina Bocchetta¹⁸, Alison Burggren¹⁹, M Mallar Chakravarty^{8

9}, Marie Chupin²⁰, Arne Ekstrom^{21

22}, Robin de Flores²³, Ricardo Insausti²⁴, Prabesh Kanel²⁵, Olga Kedo¹¹, Kristen M Kennedy²⁶, Geoffrey A Kerchner¹⁶, Karen F LaRocque⁵, Xiuwen Liu²⁵, Anne Maass²⁷, Nicolai Malykhin^{28

29

30}, Susanne G Mueller^{31

32}, Noa Ofen^{33

34}, Daniela J Palombo³⁵, Mansi B Parekh³⁶, John B Pluta¹, Jens C Pruessner^{37

38}, Naftali Raz^{33

34}, Karen M Rodrigue²⁶, Dorothee Schoemaker^{37

38}, Andrea T Shafer^{33

34}, Trevor A Steve³⁹, Nanthia Suthana^{19

40}, Lei Wang⁴¹, Julie L Winterburn^{8

9}, Michael A Yassa^{7

42}, Paul A Yushkevich¹, Renaud la Joie²³; Hippocampal Subfields Group

Affiliations

¹ Penn Image Computing and Science Laboratory, Department of Radiology, University of Pennsylvania, Philadelphia, USA.
² Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, Champaign, USA.
³ Rotman Research Institute, Baycrest Health Sciences, Toronto, Ontario, Canada.
⁴ Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University, Magdeburg, Germany.
⁵ Department of Psychology, Stanford University, Palo Alto, USA.
⁶ Department of Psychology, San Jose State University, San Jose, USA.
⁷ Department of Neurobiology and Behavior, University of California Irvine, Irvine, USA.
⁸ Cerebral Imaging Centre, Douglas Mental Health University Institute, McGill University, Montreal, Canada.
⁹ Departments of Psychiatry and Biological and Biomedical Engineering, McGill University, Montreal, Canada.
¹⁰ Integrated Program in Neuroscience, McGill University, Montreal, Canada.
¹¹ Institute of Neuroscience and Medicine, INM-1, Research Center Jülich, Jülich, Germany.
¹² JARA-BRAIN, Jülich-Aachen Research Alliance, Jülich, Germany.
¹³ C. and O. Vogt Institute for Brain Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
¹⁴ AA Martinos Center for Biomedical Imaging, Department of Radiology, Harvard Medical School, Massachusetts General Hospital, Boston, USA.
¹⁵ Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany.
¹⁶ Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, USA.
¹⁷ LANVIE Laboratory of Neuroimaging of Aging, University of Geneva, Geneva, Switzerland.
¹⁸ Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
¹⁹ Department of Psychiatry and Biobehavioural Sciences, University of California Los Angeles, Los Angeles, USA.
²⁰ INSERM, CNRS, UMR-S975, Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France.
²¹ Center for Neuroscience, University of California Davis, Davis, USA.
²² Department of Psychology, University of California Davis, Davis, USA.
²³ INSERM U1077, Université de Caen Normandie, UMR-S1077, Ecole Pratique des Hautes Etudes, Centre Hospitalier Universitaire de Caen, Caen, France.
²⁴ Human Neuroanatomy Laboratory and C.R.I.B., School of Medicine, University of Castilla-La Mancha, Albacete, Spain.
²⁵ Department of Computer Science, Florida State University, Tallahassee, USA.
²⁶ Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, USA.
²⁷ School of Public Health and Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, USA.
²⁸ Department of Biomedical Engineering, University of Alberta, Edmonton, Canada.
²⁹ The Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Canada.
³⁰ Department of Psychiatry, University of Alberta, Edmonton, Canada.
³¹ Department of Radiology, University of California, San Francisco, USA.
³² Center for Imaging of Neurodegenerative Diseases, San Francisco VA Medical Center, San Francisco, USA.
³³ Psychology Department, Wayne State University, Detroit, USA.
³⁴ Institute of Gerontology, Wayne State University, Detroit, USA.
³⁵ VA Boston Healthcare System, Boston, USA.
³⁶ Department of Radiology, Stanford University, Palo Alto, USA.
³⁷ McGill Centre for Studies in Aging, Faculty of Medicine, McGill University, Montreal, Canada.
³⁸ Department of Psychology, McGill University, Montreal, Canada.
³⁹ Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Canada.
⁴⁰ Department of Neurosurgery, University of California Los Angeles, Los Angeles, USA.
⁴¹ Northwestern University Feinberg School of Medicine, Chicago, USA.
⁴² Department of Neurology, University of California Irvine, Irvine, USA.

^# Contributed equally.

PMID: 27862600
PMCID: PMC5167633
DOI: 10.1002/hipo.22671

A harmonized segmentation protocol for hippocampal and parahippocampal subregions: Why do we need one and what are the key goals?

Laura E M Wisse et al. Hippocampus. 2017 Jan.

. 2017 Jan;27(1):3-11.

doi: 10.1002/hipo.22671. Epub 2016 Nov 15.

Authors

Affiliations

¹ Penn Image Computing and Science Laboratory, Department of Radiology, University of Pennsylvania, Philadelphia, USA.
² Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, Champaign, USA.
³ Rotman Research Institute, Baycrest Health Sciences, Toronto, Ontario, Canada.
⁴ Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University, Magdeburg, Germany.
⁵ Department of Psychology, Stanford University, Palo Alto, USA.
⁶ Department of Psychology, San Jose State University, San Jose, USA.
⁷ Department of Neurobiology and Behavior, University of California Irvine, Irvine, USA.
⁸ Cerebral Imaging Centre, Douglas Mental Health University Institute, McGill University, Montreal, Canada.
⁹ Departments of Psychiatry and Biological and Biomedical Engineering, McGill University, Montreal, Canada.
¹⁰ Integrated Program in Neuroscience, McGill University, Montreal, Canada.
¹¹ Institute of Neuroscience and Medicine, INM-1, Research Center Jülich, Jülich, Germany.
¹² JARA-BRAIN, Jülich-Aachen Research Alliance, Jülich, Germany.
¹³ C. and O. Vogt Institute for Brain Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
¹⁴ AA Martinos Center for Biomedical Imaging, Department of Radiology, Harvard Medical School, Massachusetts General Hospital, Boston, USA.
¹⁵ Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany.
¹⁶ Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, USA.
¹⁷ LANVIE Laboratory of Neuroimaging of Aging, University of Geneva, Geneva, Switzerland.
¹⁸ Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.
¹⁹ Department of Psychiatry and Biobehavioural Sciences, University of California Los Angeles, Los Angeles, USA.
²⁰ INSERM, CNRS, UMR-S975, Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France.
²¹ Center for Neuroscience, University of California Davis, Davis, USA.
²² Department of Psychology, University of California Davis, Davis, USA.
²³ INSERM U1077, Université de Caen Normandie, UMR-S1077, Ecole Pratique des Hautes Etudes, Centre Hospitalier Universitaire de Caen, Caen, France.
²⁴ Human Neuroanatomy Laboratory and C.R.I.B., School of Medicine, University of Castilla-La Mancha, Albacete, Spain.
²⁵ Department of Computer Science, Florida State University, Tallahassee, USA.
²⁶ Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, USA.
²⁷ School of Public Health and Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, USA.
²⁸ Department of Biomedical Engineering, University of Alberta, Edmonton, Canada.
²⁹ The Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Canada.
³⁰ Department of Psychiatry, University of Alberta, Edmonton, Canada.
³¹ Department of Radiology, University of California, San Francisco, USA.
³² Center for Imaging of Neurodegenerative Diseases, San Francisco VA Medical Center, San Francisco, USA.
³³ Psychology Department, Wayne State University, Detroit, USA.
³⁴ Institute of Gerontology, Wayne State University, Detroit, USA.
³⁵ VA Boston Healthcare System, Boston, USA.
³⁶ Department of Radiology, Stanford University, Palo Alto, USA.
³⁷ McGill Centre for Studies in Aging, Faculty of Medicine, McGill University, Montreal, Canada.
³⁸ Department of Psychology, McGill University, Montreal, Canada.
³⁹ Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Canada.
⁴⁰ Department of Neurosurgery, University of California Los Angeles, Los Angeles, USA.
⁴¹ Northwestern University Feinberg School of Medicine, Chicago, USA.
⁴² Department of Neurology, University of California Irvine, Irvine, USA.

^# Contributed equally.

PMID: 27862600
PMCID: PMC5167633
DOI: 10.1002/hipo.22671

Abstract

The advent of high-resolution magnetic resonance imaging (MRI) has enabled in vivo research in a variety of populations and diseases on the structure and function of hippocampal subfields and subdivisions of the parahippocampal gyrus. Because of the many extant and highly discrepant segmentation protocols, comparing results across studies is difficult. To overcome this barrier, the Hippocampal Subfields Group was formed as an international collaboration with the aim of developing a harmonized protocol for manual segmentation of hippocampal and parahippocampal subregions on high-resolution MRI. In this commentary we discuss the goals for this protocol and the associated key challenges involved in its development. These include differences among existing anatomical reference materials, striking the right balance between reliability of measurements and anatomical validity, and the development of a versatile protocol that can be adopted for the study of populations varying in age and health. The commentary outlines these key challenges, as well as the proposed solution of each, with concrete examples from our working plan. Finally, with two examples, we illustrate how the harmonized protocol, once completed, is expected to impact the field by producing measurements that are quantitatively comparable across labs and by facilitating the synthesis of findings across different studies. © 2016 Wiley Periodicals, Inc.

Keywords: MRI; harmonization; hippocampus; parahippocampal gyrus; segmentation.

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Figures

**Figure 1**
Comparison of 21 segmentation protocols in a coronal section in the hippocampal body of one subject. Figure from Yushkevich et al, NeuroImage, 2016; reprinted with permission from Elsevier. Alv=Alveus; CA=Cornu ammonis; CSF=Cerebrospinal fluid; DG=Dentate gyrus; DG:H=Dentate gyrus Hilar region; Fim=Fimbria; GCL=Granular cell layer; H=Hippocampus; Para=Parasubiculum; PHC=Parahippocampal cortex; Pre=Presubiculum; Sub=Subiculum; SP=Stratum pyramidale; SRLM=Stratum Radiatum Lacunosum Moleculare

**Figure 2**
Overview of the concrete steps involved in the harmonization project. In Step 1 in a set of three tissue samples, the boundaries on histology will be annotated by three anatomists. In Step 2 the boundaries on MRI will be derived based on the anatomical reference set in Step 1. The se boundaries are divided into two sets: the outer boundaries with surrounding structures and the boundaries between the subfields. Note for Step 2 that for both protocols an initial reliability test will be performed and the protocols will be shared with the Boundary Working Group (BWG). In case the reliability criteria are not met or in case of considerable critique, the protocol will be adjusted. This will be an iterative process. In Step 3 feedback will be elicited from the larger Hippocampal Subfields Group (HSG). In Step 4 a formal reliability analysis will be performed by six raters from different labs.

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A harmonized segmentation protocol for hippocampal and parahippocampal subregions: Why do we need one and what are the key goals?

Affiliations

A harmonized segmentation protocol for hippocampal and parahippocampal subregions: Why do we need one and what are the key goals?

Authors

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Abstract

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