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.

1st Department of Neurology St Anne's University Hospital and Faculty of Medicine Masaryk University Brno Czech Republic

Amsterdam UMC University of Amsterdam Psychiatry Amsterdam Neuroscience Amsterdam The Netherlands

Amsterdam UMC Vrije Universiteit Psychiatry Amsterdam Neuroscience Amsterdam The Netherlands

ARQ National Psychotrauma Centre Diemen The Netherlands

Brain Imaging and Analysis Center Duke University Durham NC USA

CEITEC Central European Institute of Technology Multimodal and Functional Neuroimaging Research Group Masaryk University Brno Czech Republic

Center for Behavior Genetics of Aging University of California San Diego La Jolla CA USA

Center for Depression Anxiety and Stress Research McLean Hospital Harvard University Belmont MA USA

Center for Healthy Minds University of Wisconsin Madison Madison WI USA

Center for Vital Longevity School of Behavioral and Brain Sciences University of Texas at Dallas Dallas TX USA

Center of Excellence for Stress and Mental Health VA San Diego Healthcare System LA Jolla CA USA

Centre for Youth Mental Health The University of Melbourne Parkville Australia

Charité Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin Department of Psychiatry and Neurosciences CCM Berlin Germany

Comprehensive Injury Center Medical College of Wisconsin WI USA

De Viersprong mental health specialist in personality disorders family and behavior Amsterdam The Netherlands

Department of Child and Adolescent Psychiatry Leiden University Medical Center Leiden The Netherlands

Department of Clinical Psychology University of Groningen Groningen The Netherlands

Department of Clinical Psychology Utrecht University Utrecht The Netherlands

Department of Developmental Psychology University of Amsterdam Amsterdam The Netherlands

Department of Epidemiology Institute of Health and Equity Medical College of Wisconsin WI USA

Department of Experimental Clinical and Health Psychology Ghent University Ghent Belgium

Department of Medical Imaging Jinling Hospital Medical School of Nanjing University Nanjing China

Department of Neuroscience University of Rochester Medical Center Rochester NY USA

Department of Neuroscience Western University London ON Canada

Department of Psychiatry and Behavioral Neuroscience Wayne State University School of Medicine Detroit MI USA

Department of Psychiatry and Behavioral Science Texas A and M University Health Science Center Bryan TX USA

Department of Psychiatry and Behavioral Sciences Emory University School of Medicine Atlanta GA USA

Department of Psychiatry and Behavioral Sciences School of Medicine Duke University Durham NC USA

Department of Psychiatry and Behavioral Sciences Vanderbilt University Medical Center TN USA

Department of Psychiatry Baylor College of Medicine Houston TX USA

Department of Psychiatry Columbia University Medical Center New York NY USA

Department of Psychiatry Harvard Medical School Boston MA USA

Department of Psychiatry Leiden University Medical Center Leiden The Netherlands

Department of Psychiatry Texas A and M University Bryan TX USA

Department of Psychiatry University of California San Diego La Jolla CA USA

Department of Psychiatry University of California San Diego San Diego CA USA

Department of Psychiatry University of Michigan Ann Arbor MI USA

Department of Psychiatry University of Minnesota Minneapolis MN USA

Department of Psychiatry University of Texas at Austin Austin TX USA

Department of Psychiatry University of Toledo Toledo OH USA

Department of Psychiatry University of Wisconsin Madison Madison WI USA

Department of Psychiatry Western University London ON Canada

Department of Psychiatry Yale University School of Medicine New Haven CT USA

Department of Psychology and Neuroscience Baylor University Waco TX USA

Department of Psychology Marquette University Milwaukee WI USA

Department of Psychology University of Arizona Tucson AZ USA

Department of Psychology University of Chinese Academy of Sciences Beijing China

Department of Psychology University of Minnesota Minneapolis MN USA

Department of Psychology University of Wisconsin Madison Madison WI USA

Department of Psychology University of Wisconsin Milwaukee Milwaukee WI USA

Department of Psychology Vanderbilt University TN USA

Department of Psychosomatic Medicine and Psychotherapy Central Institute of Mental Health Medical Faculty Mannheim Heidelberg University Germany

Department of Radiology Washington University School of Medicine St Louis MO USA

Department of Veteran Affairs Mid Atlantic Mental Illness Research Education and Clinical Center Durham NC USA

Dept of Psychological and Brain Sciences Boston University Boston MA USA

Division of Depression and Anxiety Disorders McLean Hospital Belmont MA USA

Division of Trauma and Acute Care Surgery Department of Surgery Medical College of Wisconsin WI USA

Division of Womens Mental Health McLean Hospital Belmont MA USA

Donders Institute for Brain Cognition and Behavior Centre for Cognitive Neuroimaging Radboud University Nijmegen Nijmegen The Netherlands

German Center for Mental Health partner site Mannheim Heidelberg Ulm

Imaging Genetics Center Mark and Mary Stevens Neuroimaging and Informatics Institute Keck School of Medicine of USC Marina del Rey CA USA

Institute for Technology in Psychiatry McLean Hospital Belmont MA USA

Institute of Medical Psychology and Systems Neuroscience University of Mu nster Mu nster Germany

Laboratory for Traumatic Stress Studies Chinese Academy of Sciences Key Laboratory of Mental Health Institute of Psychology Chinese Academy of Sciences Beijing China

Leiden Institute for Brain and Cognition Leiden The Netherlands

Minneapolis VA Health Care System Minneapolis MN USA

Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing University Nanjing China

Neuroscience Research Australia Randwick NSW Australia

New York State Psychiatric Institute New York NY USA

Northwestern Neighborhood and Network Initiative Northwestern University Institute for Policy Research Evanston IL USA

Orygen Parkville Australia

SA MRC Unit on Risk and Resilience in Mental Disorders Department of Psychiatry and Neuroscience Institute University of Cape Town Cape Town South Africa

School of Medicine and Public Health University of Wisconsin Madison Madison WI USA

School of Psychology University of New South Wales Sydney NSW Australia

Stein Institute for Research on Aging and Center for Healthy Aging University of California San Diego San Diego CA USA

Tel Aviv University Tel Aviv Yafo Israel

Université de Tours INSERM Imaging Brain and Neuropsychiatry iBraiN U1253 37032 Tours France

University Medical Centre Charité Berlin Germany

University of Haifa Haifa Israel

University of Missouri St Louis Department of Psychological Sciences Center for Trauma Recovery St Louis MO USA

University of Nebraska Medical Center Munroe Meyer Institute Omaha NE USA

Veterans Integrated Service Network 17 Center of Excellence for Research on Returning War Veterans Waco TX USA

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