Performance of semi-automated hippocampal subfield segmentation methods across ages in a pediatric sample

ABSTRACT Episodic memory function has been shown to depend critically on the hippocampus. This region is made up of a number of subfields, which differ in both cytoarchitectural features and functional roles in the mature brain. Recent neuroimaging work in children and adolescents has suggested that these regions may undergo different developmental trajectories—a fact that has important implications for how we think about learning and memory processes in these populations. Despite the growing research interest in hippocampal structure and function at the subfield level in healthy young adults, comparatively fewer studies have been carried out looking at subfield development. One barrier to studying these questions has been that manual segmentation of hippocampal subfields—considered by many to be the best available approach for defining these regions—is laborious and can be infeasible for large cross‐sectional or longitudinal studies of cognitive development. Moreover, manual segmentation requires some subjectivity and is not impervious to bias or error. In a developmental sample of individuals spanning 6–30 years, we assessed the degree to which two semi‐automated segmentation approaches—one approach based on Automated Segmentation of Hippocampal Subfields (ASHS) and another utilizing Advanced Normalization Tools (ANTs)—approximated manual subfield delineation on each individual by a single expert rater. Our main question was whether performance varied as a function of age group. Across several quantitative metrics, we found negligible differences in subfield validity across the child, adolescent, and adult age groups, suggesting that these methods can be reliably applied to developmental studies. We conclude that ASHS outperforms ANTs overall and is thus preferable for analyses carried out in individual subject space. However, we underscore that ANTs is also acceptable and may be well‐suited for analyses requiring normalization to a single group template (e.g., voxelwise analyses across a wide age range). Previous work has supported the use of such methods in healthy young adults, as well as several special populations such as older adults and those suffering from mild cognitive impairment. Our results extend these previous findings to show that ASHS and ANTs can also be used in pediatric populations as young as six.

[1]  Anders M. Dale,et al.  An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest , 2006, NeuroImage.

[2]  Arthur F. Kramer,et al.  A neuroimaging investigation of the association between aerobic fitness, hippocampal volume, and memory performance in preadolescent children , 2010, Brain Research.

[3]  M. Mallar Chakravarty,et al.  Hippocampus and amygdala volumes from magnetic resonance images in children: Assessing accuracy of FreeSurfer and FSL against manual segmentation , 2016, NeuroImage.

[4]  Hugo J. Kuijf,et al.  Subfields of the hippocampal formation at 7T MRI: In vivo volumetric assessment , 2012, NeuroImage.

[5]  Andrew J. Saykin,et al.  Neural organization of material-specific memory functions in temporal lobe epilepsy patients as assessed by the intracarotid amobarbital test. , 1995 .

[6]  Ricardo Insausti,et al.  Automated segmentation of the human hippocampus along its longitudinal axis , 2016, Human brain mapping.

[7]  J. Fleiss,et al.  Intraclass correlations: uses in assessing rater reliability. , 1979, Psychological bulletin.

[8]  H. Eichenbaum,et al.  Evolution of declarative memory , 2006, Hippocampus.

[9]  Nora S Newcombe,et al.  The ontogeny of relational memory and pattern separation. , 2018, Developmental science.

[10]  Tracy Riggins,et al.  Developmental Differences in Relations Between Episodic Memory and Hippocampal Subregion Volume During Early Childhood. , 2015, Child development.

[11]  Ana M. Daugherty,et al.  Optimization and validation of automated hippocampal subfield segmentation across the lifespan , 2018, Human brain mapping.

[12]  Tracy Riggins,et al.  Protracted hippocampal development is associated with age-related improvements in memory during early childhood , 2018, NeuroImage.

[13]  M. Mallar Chakravarty,et al.  Quantitative comparison of 21 protocols for labeling hippocampal subfields and parahippocampal subregions in in vivo MRI: Towards a harmonized segmentation protocol , 2015, NeuroImage.

[14]  E. Gasparetto,et al.  Evaluation of hippocampal volume based on MR imaging in patients with bipolar affective disorder applying manual and automatic segmentation techniques , 2011, Journal of magnetic resonance imaging : JMRI.

[15]  N. Schuff,et al.  Measurement of hippocampal subfields and age-related changes with high resolution MRI at 4T , 2007, Neurobiology of Aging.

[16]  Stine K. Krogsrud,et al.  Development of hippocampal subfield volumes from 4 to 22 years , 2014, Human brain mapping.

[17]  Krzysztof J. Gorgolewski,et al.  A Practical Guide for Improving Transparency and Reproducibility in Neuroimaging Research , 2016, bioRxiv.

[18]  Simona Ghetti,et al.  Structural development of the hippocampus and episodic memory: developmental differences along the anterior/posterior axis. , 2014, Cerebral cortex.

[19]  John O. Willis,et al.  Wechsler Abbreviated Scale of Intelligence , 2014 .

[20]  H. Duvernoy,et al.  The Human Hippocampus: Functional Anatomy, Vascularization and Serial Sections with MRI , 1997 .

[21]  Abraham Z. Snyder,et al.  The Feasibility of a Common Stereotactic Space for Children and Adults in fMRI Studies of Development , 2002, NeuroImage.

[22]  Michael Weiner,et al.  Nearly automatic segmentation of hippocampal subfields in in vivo focal T2-weighted MRI , 2010, NeuroImage.

[23]  S. Petersen,et al.  Hemispheric Specialization in Human Dorsal Frontal Cortex and Medial Temporal Lobe for Verbal and Nonverbal Memory Encoding , 1998, Neuron.

[24]  Brigitte Landeau,et al.  MICROBLEEDS RELATED WITH BRAIN STRUCTURAL CHANGES AND CSF BIOMARKERS IN ALZHEIMER'S DISEASE , 2014, Alzheimer's & Dementia.

[25]  Nikolaus Weiskopf,et al.  Multi-voxel pattern analysis in human hippocampal subfields , 2012, Front. Hum. Neurosci..

[26]  Jon Pipitone,et al.  Automatic segmentation of the hippocampus for preterm neonates from early-in-life to term-equivalent age , 2015, NeuroImage: Clinical.

[27]  Dagmar Zeithamova,et al.  Flexible Memories: Differential Roles for Medial Temporal Lobe and Prefrontal Cortex in Cross-Episode Binding , 2010, The Journal of Neuroscience.

[28]  Kiralee M. Hayashi,et al.  Dynamic mapping of normal human hippocampal development , 2006, Hippocampus.

[29]  Tracy Riggins,et al.  It's All in the Details: Relations Between Young Children's Developing Pattern Separation Abilities and Hippocampal Subfield Volumes. , 2018, Cerebral cortex.

[30]  Sabine Peters,et al.  Longitudinal development of hippocampal subregions from childhood to adulthood , 2017, Developmental Cognitive Neuroscience.

[31]  Pierre Lavenex,et al.  Building hippocampal circuits to learn and remember: Insights into the development of human memory , 2013, Behavioural Brain Research.

[32]  H. Gundersen,et al.  Unbiased stereological estimation of the number of neurons in the human hippocampus , 1990, The Journal of comparative neurology.

[33]  Valerie A. Carr,et al.  Imaging the Human Medial Temporal Lobe with High-Resolution fMRI , 2010, Neuron.

[34]  Marlene Behrmann,et al.  The joint development of hemispheric lateralization for words and faces. , 2012, Journal of experimental psychology. General.

[35]  F Andermann,et al.  Anatomic basis of amygdaloid and hippocampal volume measurement by magnetic resonance imaging , 1992, Neurology.

[36]  Andrew R. Bender,et al.  Age differences in hippocampal subfield volumes from childhood to late adulthood , 2016, Hippocampus.

[37]  Rebecca L. Gómez,et al.  The extended trajectory of hippocampal development: Implications for early memory development and disorder , 2015, Developmental Cognitive Neuroscience.

[38]  Morris Moscovitch,et al.  A Hippocampal Marker of Recollection Memory Ability among Healthy Young Adults: Contributions of Posterior and Anterior Segments , 2011, Neuron.

[39]  D. Schacter,et al.  Hippocampal contributions to the episodic simulation of specific and general future events , 2011, Hippocampus.

[40]  M. Mallar Chakravarty,et al.  Multi-atlas segmentation of the whole hippocampus and subfields using multiple automatically generated templates , 2014, NeuroImage.

[41]  Michael Davis,et al.  The amygdala , 2000, Current Biology.

[42]  Nicholas B. Turk-Browne,et al.  Hippocampal Structure Predicts Statistical Learning and Associative Inference Abilities during Development , 2017, Journal of Cognitive Neuroscience.

[43]  Margaret L. Schlichting,et al.  CA1 subfield contributions to memory integration and inference , 2014, Hippocampus.

[44]  Marlene Behrmann,et al.  A vision of graded hemispheric specialization , 2015, Annals of the New York Academy of Sciences.

[45]  P. Yushkevich,et al.  Automated volumetry and regional thickness analysis of hippocampal subfields and medial temporal cortical structures in mild cognitive impairment , 2015, Human brain mapping.

[46]  Anders M. Dale,et al.  Regional Hippocampal Volumes and Development Predict Learning and Memory , 2014, Developmental Neuroscience.

[47]  Cheryl L. Dahle,et al.  Regional brain changes in aging healthy adults: general trends, individual differences and modifiers. , 2005, Cerebral cortex.

[48]  L. R. Dice Measures of the Amount of Ecologic Association Between Species , 1945 .

[49]  T. Achenbach Manual for the child behavior checklist/4-18 and 1991 profile , 1991 .

[50]  Michael L. Mack,et al.  Decisions about the past are guided by reinstatement of specific memories in the hippocampus and perirhinal cortex , 2016, NeuroImage.

[51]  Daniel Rueckert,et al.  Automatic segmentation of brain MRIs of 2-year-olds into 83 regions of interest , 2008, NeuroImage.

[52]  D. Altman,et al.  Agreement Between Methods of Measurement with Multiple Observations Per Individual , 2007, Journal of biopharmaceutical statistics.

[53]  Ana M. Daugherty,et al.  Hippocampal CA3-dentate gyrus volume uniquely linked to improvement in associative memory from childhood to adulthood , 2017, NeuroImage.

[54]  S. Heckers,et al.  Anterior and posterior hippocampal volumes in schizophrenia , 2005, Schizophrenia Research.

[55]  E. Darcy Burgund,et al.  Comparison of functional activation foci in children and adults using a common stereotactic space , 2003, NeuroImage.

[56]  Alex Martin,et al.  Modulation of human medial temporal lobe activity by form, meaning, and experience , 1997, Hippocampus.

[57]  Ulman Lindenberger,et al.  Hippocampal maturity promotes memory distinctiveness in childhood and adolescence , 2017, Proceedings of the National Academy of Sciences.

[58]  Brian A. Nosek,et al.  Power failure: why small sample size undermines the reliability of neuroscience , 2013, Nature Reviews Neuroscience.

[59]  Arno Klein,et al.  A reproducible evaluation of ANTs similarity metric performance in brain image registration , 2011, NeuroImage.

[60]  Alexander Hammers,et al.  Evaluation of atlas-based segmentation of hippocampi in healthy humans. , 2009, Magnetic resonance imaging.

[61]  Mark W. Woolrich,et al.  Advances in functional and structural MR image analysis and implementation as FSL , 2004, NeuroImage.

[62]  Denis Dooley,et al.  Atlas of the Human Brain. , 1971 .

[63]  G. Pell,et al.  Hippocampal volume assessment in temporal lobe epilepsy: How good is automated segmentation? , 2009, Epilepsia.

[64]  M. Yücel,et al.  Mapping subcortical brain maturation during adolescence: evidence of hemisphere- and sex-specific longitudinal changes. , 2013, Developmental science.

[65]  John S. Allen,et al.  Normal neuroanatomical variation in the human brain: an MRI-volumetric study. , 2002, American journal of physical anthropology.

[66]  Martin H. Teicher,et al.  The neurobiological consequences of early stress and childhood maltreatment , 2003, Neuroscience & Biobehavioral Reviews.

[67]  Brian Levine,et al.  Volumetric Analysis of Medial Temporal Lobe Subregions in Developmental Amnesia using High-Resolution Magnetic Resonance Imaging , 2013, Hippocampus.

[68]  D. Amaral,et al.  The Amygdala Is Enlarged in Children But Not Adolescents with Autism; the Hippocampus Is Enlarged at All Ages , 2004, The Journal of Neuroscience.

[69]  Min-Ying Su,et al.  Developmental changes in hippocampal shape among preadolescent children , 2013, International Journal of Developmental Neuroscience.

[70]  Arne D. Ekstrom,et al.  Volume of hippocampal subfields and episodic memory in childhood and adolescence , 2014, NeuroImage.

[71]  J. Desmond,et al.  Material-specific lateralization in the medial temporal lobe and prefrontal cortex during memory encoding. , 2001, Brain : a journal of neurology.

[72]  Geert Jan Biessels,et al.  A Critical Appraisal of the Hippocampal Subfield Segmentation Package in FreeSurfer , 2014, Front. Aging Neurosci..