Estimation of reference curves for brain atrophy and analysis of robustness to machine effects
Abstract
Abstract Neurodegenerative diseases like Alzheimer’s are difficult to diagnose due to brain complexity and imaging variability. However, volumetric analysis tools, using reference curves, help detect abnormal brain atrophy and support diagnosis and monitoring. This study evaluates the robustness of three segmentation algorithms, AssemblyNet, FastSurfer and FreeSurfer, in constructing brain volume reference curves and detecting hippocampal atrophy. Using data from 3,730 cognitively normal subjects, we built reference curves and assessed robustness to magnetic field strength (1.5T vs. 3T) using four error metrics (sMAPE, sMSPE, wMAPE, sMdAPE) with bootstrap validation. We evaluated classification performance using hippocampal atrophy rates and HAVAs scores (Hippocampal-Amygdalo-Ventricular Atrophy scores). AssemblyNet shows the lowest errors across all robustness metrics. In contrast, FastSurfer and FreeSurfer exhibit greater deviations, indicating higher sensitivity to field strength variability. AssemblyNet provides consistent hippocampal atrophy rates across all reference models, despite slightly lower sensitivity, while FastSurfer and FreeSurfer display greater variability. Specificity ranges from 0.87 to 0.91 for AssemblyNet, compared to 0.76-0.93 for FastSurfer and 0.86-0.93 for FreeSurfer. Using the HAVAs score, all methods detect high atrophy rates in Alzheimer’s patients. FastSurfer achieves the highest sensitivity (0.98), while AssemblyNet reaches the best specificity (0.95) and the highest balanced accuracy (0.91). This study underscores the importance of algorithm choice for reliable brain volumetric analysis in heterogeneous imaging environments. Among the methods tested, AssemblyNet stands out as both sensitive to Alzheimer’s-related atrophy and robust to acquisition variability, making it a strong candidate when analyzing hippocampal volumes in large, multi-site datasets.
Article Details
Authors (322)
Elodie Piot
Félix Renard
Arnaud Attyé
Alexandre Krainik
Michael W. Weiner
Paul Aisen
Ronald Petersen
Clifford R. Jack
William Jagust
John Q. Trojanowki
Arthur W. Toga
Laurel Beckett
Robert C. Green
Andrew J. Saykin
John Morris
Leslie M. Shaw
Zaven Khachaturian
Greg Sorensen
Maria Carrillo
Lew Kuller
Marc Raichle
Steven Paul
Peter Davies
Howard Fillit
Franz Hefti
Davie Holtzman
M. Marcel Mesulam
William Potter
Peter Snyder
Tom Montine
Ronald G. Thomas
Michael Donohue
Sarah Walter
Tamie Sather
Gus Jiminez
Archana B. Balasubramanian
Jennifer Mason
Iris Sim
Danielle Harvey
Matthew Bernstein
Nick Fox
Paul Thompson
Norbert Schuff
Charles DeCarli
Bret Borowski
Jeff Gunter
Matt Senjem
Prashanthi Vemuri
David Jones
Kejal Kantarci
Chad Ward
Robert A. Koeppe
Norm Foster
Eric M. Reiman
Kewei Chen
Chet Mathis
Susan Landau
Nigel J. Cairns
Erin Householder
Lisa Taylor-Reinwald
Virginia Lee
Magdalena Korecka
Michal Figurski
Karen Crawford
Scott Neu
Tatiana M. Foroud
Steven Potkin
Li Shen
Kelley Faber
Sungeun Kim
Lean Tha
Richard Frank
John Hsiao
Jeffrey Kaye
Joseph Quinn
Lisa Silbert
Betty Lind
Raina Carter
Sara Dolen
Beau Ances
Maria Carroll
Mary L. Creech
Erin Franklin
Mark A. Mintun
Stacy Schneider
Angela Oliver
Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis
Lon S. Schneider
Sonia Pawluczyk
Mauricio Beccera
Liberty Teodoro
Bryan M. Spann
James Brewer
Helen Vanderswag
Daniel Marson
Randall Griffith
David Clark
David Geldmacher
John Brockington
Erik Roberson
Marissa Natelson Love
Judith L. Heidebrink
Joanne L. Lord
Sara S. Mason
Colleen S. Albers
Kris Johnson
Hillel Grossman
Effie Mitsis
Raj C. Shah
Leyla deToledo-Morrell
Rachelle S. Doody
Javier Villanueva-Meyer
Munir Chowdhury
Susan Rountree
Mimi Dang
Ranjan Duara
Daniel Varon
Maria T. Greig
Peggy Roberts
Yaakov Stern
Lawrence S. Honig
Karen L. Bell
Marilyn Albert
Chiadi Onyike
Daniel D’Agostino
Stephanie Kielb
James E. Galvin
Brittany Cerbone
Christina A. Michel
Dana M. Pogorelec
Henry Rusinek
Mony J. de Leon
Lidia Glodzik
Susan De Santi
Kyle Womack
Dana Mathews
Mary Quiceno
P. Murali Doraiswamy
Jeffrey R. Petrella
Salvador Borges-Neto
Terence Z. Wong
Edward Coleman
Allan I. Levey
James J. Lah
Janet S. Cella
Jeffrey M. Burns
Russell H. Swerdlow
William M. Brooks
Steven E. Arnold
Department of Neurology, Massachusetts General Hospital
Jason H. Karlawish
David Wolk
Christopher M. Clark
Liana Apostolova
Kathleen Tingus
Ellen Woo
Daniel H. S. Silverman
Po H. Lu
George Bartzokis
Charles D. Smith
Greg Jicha
Peter Hardy
partha sinha
Elizabeth Oates
Gary Conrad
Neill R. Graff-Radford
Francine Parfitt
Tracy Kendall
Heather Johnson
School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester
Oscar L. Lopez
MaryAnn Oakley
Donna M. Simpson
Martin R. Farlow
Ann Marie Hake
Brandy R. Matthews
Jared R. Brosch
Scott Herring
Cynthia Hunt
Anton P. Porsteinsson
Bonnie S. Goldstein
Kim Martin
Kelly M. Makino
M. Saleem Ismail
Connie Brand
Ruth A. Mulnard
Gaby Thai
Catherine Mc-Adams-Ortiz
Christopher H. van Dyck
Richard E. Carson
Department of Radiology and Biomedical Imaging, Yale School of Medicine
Martha G. MacAvoy
Pradeep Varma
Howard Chertkow
Howard Bergman
Chris Hosein
Sandra Black
Bojana Stefanovic
Curtis Caldwell
Ging-Yuek Robin Hsiung
Howard Feldman
Benita Mudge
Michele Assaly
Elizabeth Finger
Stephen Pasternack
Irina Rachisky
Dick Trost
Andrew Kertesz
Charles Bernick
Donna Munic
Kristine Lipowski
Masandra Weintraub
Borna Bonakdarpour
Diana Kerwin
Chuang-Kuo Wu
Nancy Johnson
Carl Sadowsky
Teresa Villena
Raymond Scott Turner
Kathleen Johnson
Brigid Reynolds
Reisa A. Sperling
Keith A. Johnson
Gad Marshall
Jerome Yesavage
Joy L. Taylor
Barton Lane
Allyson Rosen
Jared Tinklenberg
Marwan N. Sabbagh
Christine M. Belden
Sandra A. Jacobson
Sherye A. Sirrel
Neil Kowall
Ronald Killiany
Andrew E. Budson
Alexander Norbash
Patricia Lynn Johnson
Thomas O. Obisesan
Saba Wolday
Joanne Allard
Alan Lerner
Paula Ogrocki
Curtis Tatsuoka
Parianne Fatica
Evan Fletcher
Pauline Maillard
John Olichney
Owen Carmichael
Smita Kittur
Michael Borrie
T.-Y. Lee
Rob Bartha
Sterling Johnson
Sanjay Asthana
Cynthia M. Carlsson
Adrian Preda
Dana Nguyen
Pierre Tariot
Anna Burke
Nadira Trncic
Adam Fleisher
Stephanie Reeder
Vernice Bates
Horacio Capote
Michelle Rainka
Douglas W. Scharre
Maria Kataki
Anahita Adeli
Earl A. Zimmerman
Dzintra Celmins
Alice D. Brown
Godfrey D. Pearlson
Karen Blank
Karen Anderson
Laura A. Flashman
Marc Seltzer
Mary L. Hynes
Robert B. Santulli
Kaycee M. Sink
Leslie Gordineer
Jeff D. Williamson
Pradeep Garg
Franklin Watkins
Brian R. Ott
Henry Querfurth
Geoffrey Tremont
Stephen Salloway
Paul Malloy
Stephen Correia
Howard J. Rosen
David Perry
Jacobo Mintzer
Kenneth Spicer
David Bachman
Elizabether Finger
Stephen Pasternak
Irina Rachinsky
John Rogers
Dick Drost
Nunzio Pomara
Raymundo Hernando
Antero Sarrael
Susan K. Schultz
Laura L. Boles Ponto
Hyungsub Shim
Karen Ekstam Smith
Norman Relkin
Gloria Chaing
Michael Lin
Lisa Ravdin
Amanda Smith
Balebail Ashok Raj
Kristin Fargher
Howard Rosen
Bradford C. Dickerson
Kimoko Domoto-Reilly
David Knopman
Bradley F. Boeve
Adam L. Boxer
John Kornak
Bruce L. Miller
William W. Seeley
Maria-Luisa Gorno-Tempini
Scott McGinnis
Maria Luisa Mandelli