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It has not yet been peer reviewed by a journal.

The National Library of Medicine is running a pilot to include preprints that result from research funded by NIH in PMC and PubMed.

[Preprint]. 2025 Jun 17:2025.06.16.657725.

doi: 10.1101/2025.06.16.657725.

Image-Based Meta- and Mega-Analysis (IBMMA): A Unified Framework for Large-Scale, Multi-Site, Neuroimaging Data Analysis

Nick Steele^{1

2}, Rajendra A Morey^{1

2}, Ahmed Hussain^{1

2}, Courtney Russell^{1

2}, Benjamin Suarez-Jimenez³, Elena Pozzi^{4

5}, Hadis Jameei⁴, Lianne Schmaal^{4

5}, Ilya M Veer⁶, Lea Waller⁷, Neda Jahanshad⁸, Sophia I Thomopoulos⁸, Lauren E Salminen⁸, Miranda Olff^{9

10}, Jessie L Frijling^{11

9}, Dick J Veltman^{9

12}, Saskia B J Koch^{9

13}, Laura Nawijn⁹, Mirjam van Zuiden^{9

14}, Li Wang^{15

16}, Ye Zhu^{15

16}, Gen Li^{15

16}, Dan J Stein¹⁷, Jonathan Ipser¹⁷, Yuval Neria^{18

19}, Xi Zhu^{18

19}, Orren Ravid¹⁹, Sigal Zilcha-Mano²⁰, Amit Lazarov²¹, Ashley A Huggins²², Jennifer S Stevens²³, Kerry Ressler^{24

25}, Tanja Jovanovic^{26

23}, Sanne J H van Rooij²³, Negar Fani²³, Sven C Mueller²⁷, Anna R Hudson²⁷, Judith K Daniels²⁸, Anika Sierk²⁹, Antje Manthey²⁹, Henrik Walter²⁹, Nic J A van der Wee^{30

31}, Steven J A van der Werff^{30

31}, Robert R J M Vermeiren³², Christian Schmahl^{33

34}, Julia I Herzog^{33

34}, Ivan Rektor³⁵, Pavel Říha^{36

35}, Milissa L Kaufman^{25

37}, Lauren A M Lebois^{25

24}, Justin T Baker^{25

38}, Isabelle M Rosso^{25

39}, Elizabeth A Olson^{25

39}, Anthony King⁴⁰, Israel Liberzon⁴¹, Michael Angstadt⁴⁰, Nicholas D Davenport^{42

43}, Seth G Disner^{42

43}, Scott R Sponheim⁴², Thomas Straube⁴⁴, David Hofmann⁴⁴, Guangming Lu⁴⁵, Rongfeng Qi⁴⁶, Xin Wang⁴⁷, Austin Kunch⁴⁷, Hong Xie⁴⁷, Yann Quidé^{48

49}, Wissam El-Hage⁵⁰, Shmuel Lissek⁵¹, Hannah Berg⁵¹, Steven E Bruce⁵², Josh Cisler⁵³, Marisa Ross⁵⁴, Ryan J Herringa⁵⁵, Daniel W Grupe⁵⁶, Jack B Nitschke⁵⁷, Richard J Davidson^{56

57

58}, Christine Larson⁵⁹, Terri A deRoon-Cassini^{60

61}, Carissa W Tomas^{62

61}, Jacklynn M Fitzgerald⁶³, Jeremy Elman^{64

65}, Matthew Panizzon⁶⁴, Carol E Franz^{66

67}, Michael J Lyons⁶⁸, William S Kremen^{66

67

69}, Brandee Feola⁷⁰, Jennifer U Blackford⁷¹, Bunmi O Olatunji⁷², Geoffrey May^{73

74

75}, Steven M Nelson^{75

74

73

76}, Evan M Gordon⁷⁷, Chadi G Abdallah^{78

79}, Ruth Lanius^{80

81}, Maria Densmore⁸¹, Jean Théberge⁸¹, Richard W J Neufeld⁸¹, Paul M Thompson⁸, Delin Sun^{82

1

2}

Affiliations

¹ Brain Imaging and Analysis Center, Duke University, Durham, NC, USA.
² Department of Veteran Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Center, Durham, NC, USA.
³ Department of Neuroscience, University of Rochester Medical Center, Rochester, NY, USA.
⁴ Centre for Youth Mental Health, The University of Melbourne, Parkville, Australia.
⁵ Orygen, Parkville, Australia.
⁶ Department of Developmental Psychology, University of Amsterdam, Amsterdam, The Netherlands.
⁷ Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Psychiatry and Neurosciences CCM, Berlin, Germany.
⁸ Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA, USA.
⁹ Amsterdam UMC University of Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands.
¹⁰ ARQ National Psychotrauma Centre, Diemen, The Netherlands.
¹¹ De Viersprong mental health specialist in personality disorders, family and behavior, Amsterdam, The Netherlands.
¹² Amsterdam UMC Vrije Universiteit, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands.
¹³ Donders Institute for Brain, Cognition and Behavior, Centre for Cognitive Neuroimaging, Radboud University Nijmegen, Nijmegen, The Netherlands.
¹⁴ Department of Clinical Psychology, Utrecht University, Utrecht, The Netherlands.
¹⁵ Laboratory for Traumatic Stress Studies, Chinese Academy of Sciences Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.
¹⁶ Department of Psychology, University of Chinese Academy of Sciences, Beijing, China.
¹⁷ SA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
¹⁸ Department of Psychiatry, Columbia University Medical Center, New York, NY, USA.
¹⁹ New York State Psychiatric Institute, New York, NY, USA.
²⁰ University of Haifa, Haifa, Israel.
²¹ Tel-Aviv University, Tel Aviv-Yafo, Israel.
²² Department of Psychology, University of Arizona, Tucson, AZ, USA.
²³ Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
²⁴ Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, MA, USA.
²⁵ Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
²⁶ Department of Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, MI, USA.
²⁷ Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium.
²⁸ Department of Clinical Psychology, University of Groningen, Groningen, The Netherlands.
²⁹ University Medical Centre Charité, Berlin, Germany.
³⁰ Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
³¹ Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
³² Department of Child and Adolescent Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
³³ Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Germany.
³⁴ German Center for Mental Health, partner site Mannheim-Heidelberg-Ulm.
³⁵ CEITEC-Central European Institute of Technology, Multimodal and Functional Neuroimaging Research Group, Masaryk University, Brno, Czech Republic.
³⁶ First Department of Neurology, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic.
³⁷ Division of Womens Mental Health, McLean Hospital, Belmont, MA, USA.
³⁸ Institute for Technology in Psychiatry, McLean Hospital, Belmont, MA, USA.
³⁹ Center for Depression, Anxiety, and Stress Research, McLean Hospital, Harvard University, Belmont, MA, USA.
⁴⁰ Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
⁴¹ Department of Psychiatry, Texas A&M University, Bryan, TX, USA.
⁴² Minneapolis VA Health Care System, Minneapolis, MN, USA.
⁴³ Department of Psychiatry , University of Minnesota, Minneapolis, MN, USA.
⁴⁴ Institute of Medical Psychology and Systems Neuroscience, University of Mu nster, Mu nster, Germany.
⁴⁵ Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
⁴⁶ Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
⁴⁷ Department of Psychiatry, University of Toledo, Toledo, OH, USA.
⁴⁸ School of Psychology, University of New South Wales, Sydney, NSW, Australia.
⁴⁹ Neuroscience Research Australia, Randwick, NSW, Australia.
⁵⁰ Université de Tours, INSERM, Imaging Brain & Neuropsychiatry iBraiN U1253, 37032, Tours, France.
⁵¹ Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
⁵² University of Missouri-St. Louis, Department of Psychological Sciences, Center for Trauma Recovery, St. Louis, MO, USA.
⁵³ Department of Psychiatry, University of Texas at Austin, Austin, TX, USA.
⁵⁴ Northwestern Neighborhood and Network Initiative, Northwestern University Institute for Policy Research, Evanston, IL, USA.
⁵⁵ School of Medicine and Public Health, University of Wisconsin Madison, Madison, WI, USA.
⁵⁶ Center for Healthy Minds, University of Wisconsin-Madison, Madison, WI, USA.
⁵⁷ Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA.
⁵⁸ Department of Psychology, University of Wisconsin-Madison, Madison, WI, USA.
⁵⁹ Department of Psychology, University of Wisconsin- Milwaukee, Milwaukee, WI, USA.
⁶⁰ Division of Trauma and Acute Care Surgery, Department of Surgery, Medical College of Wisconsin, WI, USA.
⁶¹ Comprehensive Injury Center, Medical College of Wisconsin, WI, USA.
⁶² Department of Epidemiology, Institute of Health and Equity, Medical College of Wisconsin, WI, USA.
⁶³ Department of Psychology, Marquette University, Milwaukee, WI, USA.
⁶⁴ Department of Psychiatry, University of California San Diego, San Diego, CA, USA.
⁶⁵ Stein Institute for Research on Aging & Center for Healthy Aging, University of California San Diego, San Diego, CA, USA.
⁶⁶ Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
⁶⁷ Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, USA.
⁶⁸ Dept. of Psychological & Brain Sciences, Boston University, Boston, MA, USA.
⁶⁹ Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, LA Jolla, CA, USA.
⁷⁰ Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, TN, USA.
⁷¹ University of Nebraska Medical Center, Munroe-Meyer Institute, Omaha, NE, USA.
⁷² Department of Psychology, Vanderbilt University, TN, USA.
⁷³ Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX, USA.
⁷⁴ Department of Psychology and Neuroscience, Baylor University, Waco, TX, USA.
⁷⁵ Veterans Integrated Service Network-17 Center of Excellence for Research on Returning War Veterans, Waco, TX, USA.
⁷⁶ Department of Psychiatry and Behavioral Science, Texas A&M University Health Science Center, Bryan, TX, USA.
⁷⁷ Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
⁷⁸ Department of Psychiatry, Baylor College of Medicine, Houston, TX, USA.
⁷⁹ Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
⁸⁰ Department of Neuroscience, Western University, London, ON, Canada.
⁸¹ Department of Psychiatry, Western University, London, ON, Canada.
⁸² Department of Psychiatry and Behavioral Sciences, School of Medicine, Duke University, Durham, NC, USA.

PMID: 40667083
PMCID: PMC12262482
DOI: 10.1101/2025.06.16.657725

Image-Based Meta- and Mega-Analysis (IBMMA): A Unified Framework for Large-Scale, Multi-Site, Neuroimaging Data Analysis

Nick Steele et al. bioRxiv. 2025.

[Preprint]. 2025 Jun 17:2025.06.16.657725.

doi: 10.1101/2025.06.16.657725.

Authors

Affiliations

¹ Brain Imaging and Analysis Center, Duke University, Durham, NC, USA.
² Department of Veteran Affairs Mid-Atlantic Mental Illness Research, Education and Clinical Center, Durham, NC, USA.
³ Department of Neuroscience, University of Rochester Medical Center, Rochester, NY, USA.
⁴ Centre for Youth Mental Health, The University of Melbourne, Parkville, Australia.
⁵ Orygen, Parkville, Australia.
⁶ Department of Developmental Psychology, University of Amsterdam, Amsterdam, The Netherlands.
⁷ Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Psychiatry and Neurosciences CCM, Berlin, Germany.
⁸ Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA, USA.
⁹ Amsterdam UMC University of Amsterdam, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands.
¹⁰ ARQ National Psychotrauma Centre, Diemen, The Netherlands.
¹¹ De Viersprong mental health specialist in personality disorders, family and behavior, Amsterdam, The Netherlands.
¹² Amsterdam UMC Vrije Universiteit, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands.
¹³ Donders Institute for Brain, Cognition and Behavior, Centre for Cognitive Neuroimaging, Radboud University Nijmegen, Nijmegen, The Netherlands.
¹⁴ Department of Clinical Psychology, Utrecht University, Utrecht, The Netherlands.
¹⁵ Laboratory for Traumatic Stress Studies, Chinese Academy of Sciences Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.
¹⁶ Department of Psychology, University of Chinese Academy of Sciences, Beijing, China.
¹⁷ SA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
¹⁸ Department of Psychiatry, Columbia University Medical Center, New York, NY, USA.
¹⁹ New York State Psychiatric Institute, New York, NY, USA.
²⁰ University of Haifa, Haifa, Israel.
²¹ Tel-Aviv University, Tel Aviv-Yafo, Israel.
²² Department of Psychology, University of Arizona, Tucson, AZ, USA.
²³ Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
²⁴ Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, MA, USA.
²⁵ Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
²⁶ Department of Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, MI, USA.
²⁷ Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium.
²⁸ Department of Clinical Psychology, University of Groningen, Groningen, The Netherlands.
²⁹ University Medical Centre Charité, Berlin, Germany.
³⁰ Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
³¹ Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
³² Department of Child and Adolescent Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
³³ Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Germany.
³⁴ German Center for Mental Health, partner site Mannheim-Heidelberg-Ulm.
³⁵ CEITEC-Central European Institute of Technology, Multimodal and Functional Neuroimaging Research Group, Masaryk University, Brno, Czech Republic.
³⁶ First Department of Neurology, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic.
³⁷ Division of Womens Mental Health, McLean Hospital, Belmont, MA, USA.
³⁸ Institute for Technology in Psychiatry, McLean Hospital, Belmont, MA, USA.
³⁹ Center for Depression, Anxiety, and Stress Research, McLean Hospital, Harvard University, Belmont, MA, USA.
⁴⁰ Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
⁴¹ Department of Psychiatry, Texas A&M University, Bryan, TX, USA.
⁴² Minneapolis VA Health Care System, Minneapolis, MN, USA.
⁴³ Department of Psychiatry , University of Minnesota, Minneapolis, MN, USA.
⁴⁴ Institute of Medical Psychology and Systems Neuroscience, University of Mu nster, Mu nster, Germany.
⁴⁵ Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
⁴⁶ Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
⁴⁷ Department of Psychiatry, University of Toledo, Toledo, OH, USA.
⁴⁸ School of Psychology, University of New South Wales, Sydney, NSW, Australia.
⁴⁹ Neuroscience Research Australia, Randwick, NSW, Australia.
⁵⁰ Université de Tours, INSERM, Imaging Brain & Neuropsychiatry iBraiN U1253, 37032, Tours, France.
⁵¹ Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
⁵² University of Missouri-St. Louis, Department of Psychological Sciences, Center for Trauma Recovery, St. Louis, MO, USA.
⁵³ Department of Psychiatry, University of Texas at Austin, Austin, TX, USA.
⁵⁴ Northwestern Neighborhood and Network Initiative, Northwestern University Institute for Policy Research, Evanston, IL, USA.
⁵⁵ School of Medicine and Public Health, University of Wisconsin Madison, Madison, WI, USA.
⁵⁶ Center for Healthy Minds, University of Wisconsin-Madison, Madison, WI, USA.
⁵⁷ Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA.
⁵⁸ Department of Psychology, University of Wisconsin-Madison, Madison, WI, USA.
⁵⁹ Department of Psychology, University of Wisconsin- Milwaukee, Milwaukee, WI, USA.
⁶⁰ Division of Trauma and Acute Care Surgery, Department of Surgery, Medical College of Wisconsin, WI, USA.
⁶¹ Comprehensive Injury Center, Medical College of Wisconsin, WI, USA.
⁶² Department of Epidemiology, Institute of Health and Equity, Medical College of Wisconsin, WI, USA.
⁶³ Department of Psychology, Marquette University, Milwaukee, WI, USA.
⁶⁴ Department of Psychiatry, University of California San Diego, San Diego, CA, USA.
⁶⁵ Stein Institute for Research on Aging & Center for Healthy Aging, University of California San Diego, San Diego, CA, USA.
⁶⁶ Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
⁶⁷ Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, USA.
⁶⁸ Dept. of Psychological & Brain Sciences, Boston University, Boston, MA, USA.
⁶⁹ Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, LA Jolla, CA, USA.
⁷⁰ Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, TN, USA.
⁷¹ University of Nebraska Medical Center, Munroe-Meyer Institute, Omaha, NE, USA.
⁷² Department of Psychology, Vanderbilt University, TN, USA.
⁷³ Center for Vital Longevity, School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX, USA.
⁷⁴ Department of Psychology and Neuroscience, Baylor University, Waco, TX, USA.
⁷⁵ Veterans Integrated Service Network-17 Center of Excellence for Research on Returning War Veterans, Waco, TX, USA.
⁷⁶ Department of Psychiatry and Behavioral Science, Texas A&M University Health Science Center, Bryan, TX, USA.
⁷⁷ Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA.
⁷⁸ Department of Psychiatry, Baylor College of Medicine, Houston, TX, USA.
⁷⁹ Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
⁸⁰ Department of Neuroscience, Western University, London, ON, Canada.
⁸¹ Department of Psychiatry, Western University, London, ON, Canada.
⁸² Department of Psychiatry and Behavioral Sciences, School of Medicine, Duke University, Durham, NC, USA.

PMID: 40667083
PMCID: PMC12262482
DOI: 10.1101/2025.06.16.657725

Update in

Image-Based Meta- and Mega-Analysis (IBMMA): A Unified Framework for Large-Scale, Multi-Site, Neuroimaging Data Analysis.
Steele N, Huggins AA, Morey RA, Hussain A, Russell C, Suarez-Jimenez B, Pozzi E, Jameei H, Schmaal L, Veer IM, Waller L, Jahanshad N, Thomopoulos SI, Salminen LE, Olff M, Frijling JL, Veltman DJ, Koch SBJ, Nawijn L, van Zuiden M, Wang L, Zhu Y, Li G, Stein DJ, Ipser J, Neria Y, Zhu X, Ravid O, Zilcha-Mano S, Lazarov A, Stevens JS, Ressler K, Jovanovic T, van Rooij SJH, Fani N, Mueller SC, Hudson AR, Daniels JK, Sierk A, Manthey A, Walter H, van der Wee NJA, van der Werff SJA, Vermeiren RRJM, Schmahl C, Herzog JI, Rektor I, Říha P, Kaufman ML, Lebois LAM, Baker JT, Rosso IM, Olson EA, King A, Liberzon I, Angstadt M, Davenport ND, Disner SG, Sponheim SR, Straube T, Hofmann D, Lu G, Qi R, Wang X, Kunch A, Xie H, Quidé Y, El-Hage W, Lissek S, Berg H, Bruce SE, Cisler J, Ross M, Herringa RJ, Grupe DW, Nitschke JB, Davidson RJ, Larson C, deRoon-Cassini TA, Tomas CW, Fitzgerald JM, Elman J, Panizzon M, Franz CE, Lyons MJ, Kremen WS, Feola B, Blackford JU, Olatunji BO, May G, Nelson SM, Gordon EM, Abdallah CG, Lanius R, Densmore M, Théberge J, Neufeld RWJ, Thompson PM, Sun D. Steele N, et al. Neuroimage. 2025 Oct 23:121554. doi: 10.1016/j.neuroimage.2025.121554. Online ahead of print. Neuroimage. 2025. PMID: 41138791

Abstract

The increasing scale and complexity of neuroimaging datasets aggregated from multiple study sites present substantial analytic challenges, as existing statistical analysis tools struggle to handle missing voxel-data, suffer from limited computational speed and inefficient memory allocation, and are restricted in the types of statistical designs they are able to model. We introduce Image-Based Meta- & Mega-Analysis (IBMMA), a novel software package implemented in R and Python that provides a unified framework for analyzing diverse neuroimaging features, efficiently handles large-scale datasets through parallel processing, offers flexible statistical modeling options, and properly manages missing voxel-data commonly encountered in multi-site studies. IBMMA produced stronger effect sizes and revealed findings in brain regions that traditional software overlooked due to missing voxel-data resulting in gaps in brain coverage. IBMMA has the potential to accelerate discoveries in neuroscience and enhance the clinical utility of neuroimaging findings.

Keywords: Big Data; Mega-analysis; Meta-analysis; Neuroimaging; PTSD; Resting-state fMRI.

PubMed Disclaimer

Figures

**Figure 1.. Schematic of IBMMA Workflow.**
Neuroimaging data from multiple subjects are flattened and segmented into memory-compatible subject-by-feature matrices. Statistical models are applied in parallel across features, and the resulting outputs are extracted and reconstructed to match the original data dimensions.

**Figure 2.. Steps to Run IBMMA.**
A) IBMMA expects neuroimaging data to be organized in site-specific subdirectories. Within each subdirectory, neuroimaging files should be named starting with the subject ID followed by a naming pattern that is consistent across all files. Within the clinical data file, IBMMA expects a fID column whose elements are composed of site ID and subject ID. B) IBMMA requires the user to first input clinical and neuroimaging data file paths and model specifications in the para_path.xlsx file. C) IBMMA can be run from the command line, either locally or via a HPC, by running the ibmma.py script. D) Statistical results will be automatically generated once the script is done running and can be viewed using any neuroimaging viewer (e.g., FSLeyes, freeview, MRIcron). An HTML webpage is also generated to view results.

**Figure 3.. IBMMA Outputs.**
A) Total run time, CPU time, and maximum virtual memory usage of each processing step of IBMMA’s mega-analysis using a sample of n = 2,611. B) IBMMA generated whole-brain maps of various statistical and model fit measures. C) An automatically generated HTML webpage provided result tables and visualizations of neuroimaging findings. All tables were also saved as CSV files, and all significant voxel clusters were saved as png images.

**Figure 4.**
A) Brain maps displaying the proportion of subjects with missing data at each voxel of the brain in the ENIGMA-PTSD dataset (n = 3,193). B) The sensitivity of IBMMA at a 5% false positive rate (FPR) calculated from a simulated dataset given the observed missing rates at each voxel of the brain. C) Receiver operator characteristic (ROC) curves at different levels of subject missingness in increments of 5%. D) Performance of IBMMA, measured by area under the curve (AUC) and sensitivity at a 5% FPR, across varying levels of subject missingness.

**Figure 5.**
Seed-based functional connectivity results for the left thalamus using IBMMA, FSL, and conjunction analyses. A) IBMMA accounts for missing voxel-data by only using subjects with non-missing data for a given voxel, while FSL only analyzes voxels with complete data. Left: Number of participants with non-missing voxel-data used by IBMMA for each voxel. Right: The colored regions represent voxels that were included in the FSL analysis, while non-colored regions were excluded due to one or more participants having missing voxel-data. **B, C, D)** Significant associations found by IBMMA (left) and FSL (right). Z-statistic maps are thresholded at Z ≥ 3.1 (uncorrected). In the conjunction analysis panels (bottom), red voxels indicate regions identified as significant by both IBMMA and FSL, while purple (IBMMA only) and blue (FSL only) voxels indicate areas of disagreement between the two software. B) Significant negative associations with age. C) Significant associations with sex (female > male). D) Significant association with PTSD diagnosis (cases > controls).

See this image and copyright information in PMC

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This is a preprint.

Image-Based Meta- and Mega-Analysis (IBMMA): A Unified Framework for Large-Scale, Multi-Site, Neuroimaging Data Analysis

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Image-Based Meta- and Mega-Analysis (IBMMA): A Unified Framework for Large-Scale, Multi-Site, Neuroimaging Data Analysis

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