Learning-based inference of longitudinal image changes: Applications in embryo development, wound healing, and aging brain

Longitudinal imaging data are routinely acquired for health studies and patient monitoring. A central goal in longitudinal studies is tracking relevant change over time. Traditional methods remove nuisance variation with custom pipelines to focus on significant changes. In this work, we present a machine learning-based method that automatically ignores irrelevant changes and extracts the time-varying signal of interest. Our method, called Learning-based Inference of Longitudinal imAge Changes (LILAC), performs a pairwise comparison of longitudinal images in order to make a temporal difference prediction. LILAC employs a convolutional Siamese architecture to extract feature pairs, followed by subtraction and a bias-free fully connected layer to learn meaningful temporal image differences. We first showcase LILAC's ability to capture key longitudinal changes by simply training it to predict the temporal ordering of images. In our experiments, temporal ordering accuracy exceeded 0.98, and predicted time differences were strongly correlated with actual changes in relevant variables (Pearson Correlation Coefficient <i>r</i> = 0.911 with embryo phase change, and r = 0.875 with time interval in wound healing). Next, we trained LILAC to explicitly predict specific targets, such as the change in clinical scores in patients with mild cognitive impairment. LILAC models achieved over a 40% reduction in root mean square error compared to baseline methods. Our empirical results demonstrate that LILAC effectively localizes and quantifies relevant individual-level changes in longitudinal imaging data, offering valuable insights for studying temporal mechanisms or guiding clinical decisions.

Authors

Institutions

Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2025-02-20
DOI
https://doi.org/10.1073/pnas.2411492122
Citations
5
Primary Topic
Machine Learning in Healthcare
Type
article
Field-Weighted Citation Impact
12.40

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Learning-based inference of longitudinal image changes: Applications in embryo development, wound healing, and aging brain

Arjun V. Masurkar, Evan Fletcher, Alyssa Miller, Melanie Chadwick et al.
5 citations
Proceedings of the National Academy of Sciences
Machine Learning in Healthcare
12.40
article

Learning-based inference of longitudinal image changes: Applications in embryo development, wound healing, and aging brain

Arjun V. Masurkar, Evan Fletcher, Alyssa Miller, Melanie Chadwick, Val J. Lowe, Michaela Johnson, Emily A. Largent, Loreece Haddad, Rebecca C. Taylor, Aaron Jacobson, Steven Tam, Laura Ashe, Debbie Campbell, Stephen Salloway, James Webster, Pierre N. Tariot, Laura Donnelly, John Rogers, James Ruszkiewicz, Matthew R. Jones, Winnie Kwang, Lawrence S. Honig, Jason Weller, Steven Lenio, Clifford R. Jack, Mike Nguyen, Alireza Atri, Payam Mahboubi, Warren Barker, Justin M. Long, Magdalena Korecka, Diego Mejia, Kevin Epperson, Robert B. Santulli, Terry Camarro, Beverly Meacham, Martha A. Combs, Michael Asbach, Abigail O’Connell, Catherine E. Munro, Alexander Knaack, Juliet Fockler, Duygu Tosun, Ruchi Aggarwal, Donna Munic, Amanda C. Glueck, Elizabeth Shaffer, Crystal Flynn Longmire, Faye Sheppard, Michaël Schumacher, Princess Carter, Ilya M. Nasrallah, Maria Scanlan, Richard J. Perrin, Robert A. Swarm, Jillian Turner, Judith Neugroschl, Robert Bartha, Anna Middleton, Nasrin Ghesani, Sudha S. Seshadri, Lucas Quinlan, Christina Rosario, Jason Karlawish, Kirsten Evans, Courtney Dawson, Lisa Thomas, Andrea Kippels, Y. Wan, Suzan Lowe, Karen A. Nolan, Nina Silverberg, Arthur W. Toga, Laili Soleimani, Teresa Villena, Laura Barlow, Alex Groves, Gilberto Perez, Anna G. Mattle, Stephanie S. O’Malley, Maria Gallegos, Jeffrey P. Burns, Nadira Trncic, Emma Cooper, Harold Matthew Cooper, Cesar Chirinos, Sophia I. Thomopoulos, Anaztasia Ulysse, Aparna Bhan, Kelly A. Durbin, Francisco Rivera, Shannon L. Risacher, Karen Dagerman, Parianne Fatica, Nick C. Fox, Michael Holt, Lisa Rankin, Diana Ferman, Neda Jahanshad, Paula Villela Nunes, Maria Corona, Andrew Ellison, Victor Sotelo, Brendan Kelley, Ridiane Denis, Allison Perrin, Trung Dung Nguyen, William T. Hu, Karen Crawford, Carl Sadowsky, Emmeline Lin, Sara L. Manning, Michelle Rainka, Raj C. Shah, Judith L. Heidebrink, Carol Cline, Sarah Berman, Ellen Kim, Meghan Mitchell, Allan I. Levey, Miriam T. Ashford, William Harrison, Chadwick M. Hales, Arthur Williams, Jaimie Ziolkowski, Andrea Fidell, Erin Westerhold, Marissa Natelson-Love, Ronald Bailey, Kylee York, John Q. Trojanowki, Ricardo Salazar, Kayla Nichols, Mert R. Sabuncu, Wendy Baker, Jelena Pejić, Andrew J. Saykin, Emily McKinley, Steven M. Smith, Michael S. Rafii, Dzintra Celmins, Lisa L. Barnes, Erin Franklin, Marie Bernard, Victoria Sanborn, Kenneth Spicer, Alison Pietras, Katherine Britt, Madeline Paczynski, Sanna McKinzie, Steven Chao, Joseph C. Masdeu, Elaine Most, Vijay K. Ramanan, Gillian Gabriel, Joe Strong, Sonia Pawluczyk, Courtney Williams, Cecily Jenkins, Allison Ardolino, Arvin Forghanian-Arani, Michael Donohue, Tom Montine, James Bateman, Yaakov Stern, Erin Drake, MaryAnn Oakley, Ronald Killiany, Jeanine May, Laura Goins, Yuliana Cabrera, Anton P. Porsteinsson, Kristin Harkins, Liana G. Apostolova, Eric Steinberg, Heather Russell, Martin Ayres, Allison Lapins, Katie D. Vo, Gregory M. Pontone, Bradley Wallace, Alexander O. Frolov, Christopher Scott, Costin Tanase, Arun Ramamurthy, Madison DeCapo, Minal Vasanawala, Amy R. Saklad, Lorena Monserratt, Dick Trost, Nunzio Pomara, Stephanie Rossi Chen, Caitie Hedberg, I. P. Grant, Ljubica Zotovic, Michael D. Weiner, Roberta Calzavara, Charles DeCarli, Sunnie Kenowsky, Ryan S. O’Dell, Brandon Anderson, Soumya Bouchachi, Qingyu Zhao, Julia Waszak, Ian G. Malone, Jeffrey Kaye, Liberty Teodoro, Perminder Singh Sachdev, Jeremy Pizzola, Leila Parand, Rebecca Logan, Angelica Forero, Óscar López, A. Williams, Sylvia S. White, Bela Ajtai, Prashanthi Vemuri, Thao Rodriguez, Jonathan Jackson, Jennifer Johns, Charles Bernick, Olivia Schultz, Sheila Ogwang, Kevin Hopkins, Valory Pavlik, Joanna Gonzalez, Howard Bergman, Bruce L. Miller, I.D. Young, Diana Truran Sacrey, Audrey Ruan, Joel P. Felmlee, Hugo Botha, Zoë Potter, Sandhitsu R. Das, Kaci Lacy, Romina A. Romero, Marjan Farshadi, Samantha Sullivan, Magdalena Brylska, Tatiana Foroud, Robin Bonomi, Mark Choe, Heejong Kim, Chelsea Reichert Plaska, Stephanie Santiago, Virginia Rogers, Batuhan K. Karaman, Martin G. Pomper, Robert Koeppe, Michael Shannon, Fatima Amtashar, Karen Gagnon, Maria Kataki, Lauren Garcia, Traci Aladeen, Dylan Wint, Glen Nyborg, Matthew L. Senjem, Laszlo Mechtler, Haley Bernhardt, Gustavo Jimenez‐Maggiora, Kathleen Johnson, Daniel L. Schwartz, Caileigh Zimmerman, Lauren Mariotti, Jennifer Bray, Carolyn English, R Zawislak, Wisam Elmalik, Nancy Kowalski, Michael Callan, Jeff D. Williamson, Gil Dan Rabinovici, Jeffrey Bishop, Taylor Clanton, PAUL A. NEWHOUSE, Bret Borowski, Crystal Duncan, Derek Flenniken, Colleen S. Albers, Karen Blank, Abey Thomas, Zaven Kachaturian, Danielle Goldfarb, Mike O’Connor, Susan P. Good, Kathy King, Amy M. Perkins, Shaundra Hall, Marina Reade, Victor L. Villemagne, Hillel Grossman, Rawan Tarawneh, David S. Knopman, Kaori Kubo Germano, Laurel Beckett, Amanda Jiménez, Alexandra Groome, Joshua D. Grill, Paul A. Yushkevich, Christopher G. Schwarz, Janet Taylor, Molly Goddard, Brigid Reynolds, Cyrus A. Raji, Chengshi Jin, Angelica Garcia, David Bissig, Olusegun Adegoke, Amanda Smith, Martha R. Forloines, Hannah McCoubrey, Ging‐Yuek Robin Hsiung, Michael L. Alosco, Akiva Mintz, Giuseppe Esposito, Kimberly S. Blanchard, Elaheh Salardini, Kelly McCann, Amy Thomas, Natalie Martinez, Grace Nelson, Saurabh Sharma, Meagan Yong, Rachel L. Henson, Gregory Scott Day, Phyllis Vaughn, David Geldmacher, Cynthia Stover, Sarah Walter, Stephen Correia, Jennifer Rowell, Gad Marshall, Erin Murphy, Siddharth Khasnavis, Virginia M.‐Y. Lee, Bradley F. Boeve, Abhay Moghekar, Leonie Farrington, Chris Hosein, Michael Borrie, Emily Little, Jennifer Wong, Rema Raman, Brian J. Lopresti, Ycar Devis, Emily Clark, Michelle N. McDonnell, William Z. Potter, Amy Rangel, Kelly Nudelman, Javed Ali Khan, Pamela Friedman, Veronika Solomon, Paula Ogrocki, Luter Liu, Martin R. Farlow, Sanjeev Vaishnavi, Neil Buckholtz, Howard J. Rosen, Jennifer C. Frascino, Julia Boudreau, Doris Chen, Thomas O. Obisesan, Connie Mayo, Mara Acevedo, Raymundo Hernando, K. E. Savage, Thomas C. Hawk, Nicole L. Johnson, James J. Pekar, Michael Erkkinen, Héctor Alfredo Baptista González, Eliezer Masliah, Regan Buckler, Jordan P. Harp, Robert W. Reid, Elizeva Phillips, Anthony Kaplan, Alan Q. Wang, Dorothy Ross, Talia M. Nir, Mang Yu, Ruby Endre, Jared R. Brosch, Charles Windon, Maria T. Greig‐Custo, Jaila Coleman, Cat Conti, Scott Herring, Jessica Morales, Evan T. Schulze, Terence Z. Wong, Sochenda Stephens, Denise Reyes, Richard Frank, Della Carter, Vanessa Guzmán, Megan C. King, Floyd Jones, Lindsey Hergesheimer, Rachel L. Nosheny, Andrew Kertesz, Martin Sadowski, Heather Rose, Sandra Talavera, Anne Arthur, Kathryn Turner, Jeffrey R. Petrella, Richard H. Le, Guy H. Harris, T-Y Lee, Ben Wagner, Adam P. Mecca, Roderick McColl, Hongzheng Zhang, Robert A. Koeppe, Adrienne Kormos, A. Raja, Joseph Boonsiri, Ryan Townley, Ashton Ellison, Ranjan Duara, Yingli Lu, Mario Masellis, Carolyn Liebsack, Alka Khera, Susan Landau, Peter J. Snyder, Alexandra Dahlgren, Pauline Wu, Donna Masterman, Abigail Mathewson, Lisa C. Silbert, Kwangsik Nho, Samantha Fikru, Zaven S. Khachaturian, Raymond Scott Turner, Howard Chertkow, Calvin Reyes, Maryam Beigi, Wendy A. Stewart, Abby Brown, Gary Cornell, Olga Brawman‐Mintzer, Paul Malloy, Trevor J. Hall, Cynthia M. Carlsson, Hartford Hosp, Hamid Reza Okhravi, Parichita Choudhury, Anish Kapadia, Sarah Jefferson, John R. Morris, Adam J. Fleisher, Jesse Mez, Kelly Wallace, Hannah Craft, Gladiliz Rivera-Delpin, Hannatu Amaza, Mariana Palou, Amy Boegel, Michael Glass, Emma Brennan, Helena Colvee, Jane Mwicigi, Ina Hoti, Anthony Daley, Alisa Adhikari, Sarah Malakauskas, Douglas W. Scharre, A. K. Sood, Rebecca Hunt, Andrés Soto, Jessica Lam, Michelle L. Hernandez, Mária Tóth, Robert Bryant, Steven MacDonald, Ming-Kai Chen, Walter Martínez, Karen Anderson, Trần Ngọc Anh, Hitesh Patel, Jennifer Ryan, Yanan Shang, Jennifer Davis, Claire M. Erickson, Stephanie Smith, Ozioma C. Okonkwo, Samantha Rogers, Mary Nguyen, Richard King, Justin Robison, Naomi Saito, David Jones, Lon S. Schneider, Haonan Tong, Amber Khan, Taeho Jo, Sarah Ash, Benjamin Lam, Marwan N. Sabbagh, Elizabeth J. Robinson, Brendan Lynch, Jan Clark, Edgardo Rivera, Leslie Shaw, Deb Thompson, Ashley Ko, Sanjay Asthana, Andrew Stone, Laurie Ryan, Vernice Bates, Kelsey King, Carolyn Ward, Marı́a C. Carrillo, Kelley Faber, Paul Thompson, Madiha Fairooz, Connie Kreuger, Kerry Crawley, Jonathan Cordona, Lisa Schoolcraft, Zach Bonacorsi, Xiomara Mendoza Apuango, Amelia Troutman, Erin Yurko, Josalen Gondrez, Sheryl Detling, Barbara Rodzon, Tolulope Alo, David Mossa, Emilie Geesey, Emily Petrocca, Jade Uffelman, Denece Forenback, Ann Arlene Malia, Caitlin Chiado, Cary Zik, Russell Kurvach, Beatriz Vides, Kathryn Moorlach, Virginia Boatwright, Inara Jooma, Jessica Swiniarski, Terra Burney, Ala Abusalim, Ercilia Moncayo, Heather Polson, Isabell Mwaura, Patricia Wiesenauer, Danielle Raynes-Goldfinger, Kimberly Nelsen, Kimberly Sacaza, Yanis Cavrel, Nathaniel Houghtaling, Katie Seidenberg, Ifreke Udodong, Katherine Stapleton, Allison Emborsky, Delaney Fragale, Heather Macnamara, Tatiana Jimenez-Knight, Todd Peehler, Violet Wenner, Heather Bauerle, Michael Reposa, Joseph Di Benedetto, Sarah Bohlman, Lena Moretz, Kerstin Doyon, Marie Amoyaw, Terry Fogerty, Skieff Acothley, Lora Gallagher, Elizabeth Trejo, Yair Avila, Nichol Ferng, Barbara Hackenmiller, Heather Klemp, Jasmina Kusuran, Sarah Munie, Stacey Winterton, Bryan Smelser, Gregory Ikner, Haley Hendrix, Genesis Burgos-Rivera, Maria Cereijo, Morris Wishnia, Corey Demsky, Jeffrey Maneval, Bethanie Gamble, Elizabeth Cheatham, Morgan Yazell, Linda Fenice, Paige C Tacey, Sarah Bowser, Xanthia Saganis, Brigit Lieb, Elizabeth McCorkle, Stefka Lyron, Tara Villinger, A’llana Marolt, Deborah Aloszka, Kandise Chrestensen, Mary Imhansiemhonehi, Kassandra Mejia, William Korst, Paul Eigenberger, Stephen Smilowitz, Susan DeStefano, Vanessa Clayton, Aaliyah Korkoyah, Hadley Hustead, Roxxanne Polleys, Debbie Intorcia, Jennifer Olgin, Serena Lowery, Alexa Puleio, Omobolanle Ayo, Mona Lauture, Melissa Hamski, Queennie Majorie S Kahulugan, Richard Isip, Trinity Weisensel, Phillip Hunter Ledford, Ijeoma Mba, Emily Roglaski, John Moore-Weiss, Leonard Matoush, Dariya Malyarenko, Jennifer Horenkamp, Kara Wever, Renee LaBarge, Gina Garcia-Camilo, Victoria Rufo, Veronica Briglall, Bridget Holvey, Ivan Mares, Melanie Tallakson, Jahmila Al-Amin, Sarah Basadre, Heather Dooly, Katelynn Kreszyn, Brittney Luong, Carol Gunnoud, Zhala Taghi-Zada, Kailey Basham, Leena Lukose, Aferdita Haviari, Nicole DaSilva, Sonia Olgin, Donna Veronelli, Shaniya Parkins, Matt Glittenberg, Debra Ordor, Hafsanoor Vanya, Daryn Slazyk, Joseph Hirtreiter, Susan Henkle, Joseph Bottoms, Daniel Arcuri, Teresa Kalowsky, Vita Pomara, Rebecca Devine, William Jagust, Marianne Sanders, James J. Lah, Sarab Singh, Mauro Veras Acosta, Cyndy Toso, Scott Wisniewski, Eben S. Schwartz, Sterling C. Johnson, Mary Sano, James B. Brewer, N. J. Cairns, Michael W. Weiner, Carole Ho, Li Shen, Kristin Oleary, Brandi Barger, Loren Brown Ashley, Jessica Mallory, P. V. Reyes, Kristi Ayers, S.R. Vincent, Paul Aisen, Neill R. Graff‐Radford, Maushami Gurung, Serena Cepeda, Sarah Binder, Audrie Swain, Triana Rudd, Aubree Saunders, Maurylette Gui, Robin Bean, Adam Diaz, Immaculata Okonkwo, Stacy Pot, Steven Presto, Yaneicy Gonazalez Rojas, Joanne Lim, Scott Neu, B Marti, Susan Molchan, Caroline Smith, Adaora Nwosu, Lynn Nguyen, Jacob Faircloth, Nathiel Pacini, Arlene Richards, J Knaack, Cammie Hellegers, Alexandria Montero, Maya Farchi, Anton Thomas, Sheryl Lynch, Skylar Wilson, Traci Day, Jesse Stanhope, Meghan Donahue, Lauren Jennings, Isabella Levesque, Sandra Calderon, Fabiola Magana, Erin Fransen, Katlynn Patterson, Tuba Ahmed, Ezequiel Zamora, Allison Acree, Campbell Long, Lesley Rao, Alicia Jessup, M. Sinn, Charles J. Duffy, Freda Crawford, Godfrey D. Pearlson, Leon J. Thal, Edward B. Lee, J M Falletta, S. Warren, Esmeralda Morales, Rebecca Long, Ronald Petersen, Cynthia Muñoz, Esteban Figueroa, Ellen Hartman, Robert Hernandez, Stephanie Reeder, Scott McGinnis, Kimberly Jackson, Bennett Myers, Cindy Parry, Richard J. Perrin, Rachel Rovere, Nicole Barcelos, Olga James, Rima Kaddurah-Daouk, Tera Clay, Carlota Conant, Socorro Trujillo, Tascha Helland, Jessica Nath, Cierra McCurry, Kelly Larkin, TaNisha Wilson, Tanya Harte, Charna Bates, Lindsey Booth Robbins, J. Plenge, Michelle Villar, Alayne Nieto, Prabin Mandal, Asa Widman, Stephen D’Ambrosio, Tiffani Fox, Tracey Moore, Sallie Carpentier, Samira Yeboah, Ella Wright, Kayley Lawrence, Chelsea Mendonca, E.A. Singh, Jennifer Ramirez, Kirsten Glennon, Tuan Luu, Jessica Harkins, Isabella Hoang, Ariana Moss, Talia Hamm, Adeyinka Ajayi, Chris Figueroa, Mikell White, Morgan Blackburn, Jenny Echevarria, Micah Ellis Slaughter, Lindsey Gillen, Kelly Clark, Daniel Bandy, Mai Seng Thao, Dana Mathews, P. Murali Doraiswamy, Amanda Brennan, Horacio Capote, J. A. Mahaffey, Latasha Chapman, Jennifer Salazar, Jasmine Stewart, Jonathan Graff-Radford, Christopher van Dyck, Lisa Taylor‐Reinwald, Catherine Mc-Adams-Ortiz, Chad Ward, Mauricio Becerra, Patricia O’Donnell, Chi Kim, Sandra Black, Oshoze Kadiri, Melanie J. Miller, Linda Watts, Jessica Magnuson, Aimee Pierce, Jeff Gunter, Wendy Qiu, Eugene Yau, Michele Assaly, G. Devereux, Katherin Martin, Sonia Garrison, Antonio Gama, Nicole Robert, Maria Chaudhary, Regan Brooks, Abbey Arnold, Julia Greeson, Nicole Gagliano, Kirsten Hendrickson, Christine Dittrich, Tatianne Martinez, Anjana Mandal, Milagros Rangel, Patricia Place, Maribel Nunez, Matalin Miller, Sari Pham, Casie Lyons, Mary Locke, Rachael Penn, Katherine Berner, Mercedes Madison, Nicole Mathis, Phyllis Switzer, Sylvia Grant, Caitlin Webb, Mayer Joshua Hasbani, Maria Samira Gutierrez, Kedir Adem Hussen, Brittani Evans, Candy Monarrez, Michele Gutierrez, Alyssa Ton, Kyliah Hughes, Alicia Leader, E. R. C. Walker, Bevan Hoover, Ava Stipanovich, Kejal Kantarci, Alexis DeMarco, Leslie M. Shaw, Tahlee Marian, Jacobo Mintzer, R.M. Silver, Chuang-Kuo Wu, Gaby Thai, Debra Silberberg Kovac, Meghan Riddle, M. G. McMillan, Nadeen Elayan, Randall Barker, Blake Vogler, Amber Watkins, Kimberly Martin, Neetha Basheer, Amy Browning, Lorena Macias, Elisa Hidalgo, Caila Ryan, Margaret Bassett, Sydni Jenee Hill, Seth A. Gale, Marilyn Albert
article en
5 citations

Abstract

Longitudinal imaging data are routinely acquired for health studies and patient monitoring. A central goal in longitudinal studies is tracking relevant change over time. Traditional methods remove nuisance variation with custom pipelines to focus on significant changes. In this work, we present a machine learning-based method that automatically ignores irrelevant changes and extracts the time-varying signal of interest. Our method, called Learning-based Inference of Longitudinal imAge Changes (LILAC), performs a pairwise comparison of longitudinal images in order to make a temporal difference prediction. LILAC employs a convolutional Siamese architecture to extract feature pairs, followed by subtraction and a bias-free fully connected layer to learn meaningful temporal image differences. We first showcase LILAC's ability to capture key longitudinal changes by simply training it to predict the temporal ordering of images. In our experiments, temporal ordering accuracy exceeded 0.98, and predicted time differences were strongly correlated with actual changes in relevant variables (Pearson Correlation Coefficient <i>r</i> = 0.911 with embryo phase change, and r = 0.875 with time interval in wound healing). Next, we trained LILAC to explicitly predict specific targets, such as the change in clinical scores in patients with mild cognitive impairment. LILAC models achieved over a 40% reduction in root mean square error compared to baseline methods. Our empirical results demonstrate that LILAC effectively localizes and quantifies relevant individual-level changes in longitudinal imaging data, offering valuable insights for studying temporal mechanisms or guiding clinical decisions.

Proceedings of the National Academy of SciencesVol. 122(8)
Cornell University (US), Institute of Behavioral Sciences (JP), Stanford Medicine (US), Artificial Intelligence in Medicine (Canada) (CA), Stanford University (US)
National Institute on Aging, National Cancer Institute, Division of Information and Intelligent Systems
Openalex Percentile: Top 2%
Machine Learning in Healthcare
12.40
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.