AI-driven framework to map the brain metabolome in three dimensions

Xin Ma; Cameron J Shedlock; Terrymar Medina; Roberto A Ribas; Harrison A Clarke; Tara R Hawkinson; Praveen K Dande; Hari K R Golamari; Lei Wu; Borhane Ec Ziani; Sara N Burke; Matthew E Merritt; Craig W Vander Kooi; Matthew S Gentry; Nirbhay N Yadav; Li Chen; Ramon C Sun

doi:10.1038/s42255-025-01242-9

AI-driven framework to map the brain metabolome in three dimensions

Nat Metab. 2025 Apr;7(4):842-853. doi: 10.1038/s42255-025-01242-9. Epub 2025 Mar 18.

Authors

Xin Ma^#^{1

2

3}, Cameron J Shedlock^#^{1

2}, Terrymar Medina^#^{1

2}, Roberto A Ribas^#^{1

2}, Harrison A Clarke^{1

2}, Tara R Hawkinson^{1

2}, Praveen K Dande^{1

2}, Hari K R Golamari^{1

2}, Lei Wu^{1

2}, Borhane Ec Ziani^{1

2}, Sara N Burke^{4

5

6}, Matthew E Merritt¹, Craig W Vander Kooi¹, Matthew S Gentry^{1

2}, Nirbhay N Yadav^{6

7}, Li Chen^{8

9}, Ramon C Sun^{10

11

12}

Affiliations

¹ Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA.
² Center for Advanced Spatial Biomolecule Research, University of Florida, Gainesville, FL, USA.
³ Department of Biostatistics, College of Public Health and Health Professions, College of Medicine, University of Florida, Gainesville, FL, USA.
⁴ Department of Neuroscience, University of Florida, Gainesville, FL, USA.
⁵ Center for Cognitive Aging and Memory Clinical Translational Research, University of Florida, Gainesville, FL, USA.
⁶ F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA.
⁷ Russell H. Morgan Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁸ Center for Advanced Spatial Biomolecule Research, University of Florida, Gainesville, FL, USA. li.chen1@ufl.edu.
⁹ Department of Biostatistics, College of Public Health and Health Professions, College of Medicine, University of Florida, Gainesville, FL, USA. li.chen1@ufl.edu.
¹⁰ Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA. ramonsun@ufl.edu.
¹¹ Center for Advanced Spatial Biomolecule Research, University of Florida, Gainesville, FL, USA. ramonsun@ufl.edu.
¹² Evelyn F. and William L. McKnight Brain Institute, University of Florida, Gainesville, FL, USA. ramonsun@ufl.edu.

^# Contributed equally.

Abstract

High-resolution spatial imaging is transforming our understanding of foundational biology. Spatial metabolomics is an emerging field that enables the dissection of the complex metabolic landscape and heterogeneity from a thin tissue section. Currently, spatial metabolism highlights the remarkable complexity in two-dimensional (2D) space and is poised to be extended into the three-dimensional (3D) world of biology. Here we introduce MetaVision3D, a pipeline driven by computer vision, a branch of artificial intelligence focusing on image workflow, for the transformation of serial 2D MALDI mass spectrometry imaging sections into a high-resolution 3D spatial metabolome. Our framework uses advanced algorithms for image registration, normalization and interpolation to enable the integration of serial 2D tissue sections, thereby generating a comprehensive 3D model of unique diverse metabolites across host tissues at submesoscale. As a proof of principle, MetaVision3D was utilized to generate the mouse brain 3D metabolome atlas of normal and diseased animals (available at https://metavision3d.rc.ufl.edu ) as an interactive online database and web server to further advance brain metabolism and related research.

MeSH terms

Algorithms
Animals
Artificial Intelligence*
Brain* / diagnostic imaging
Brain* / metabolism
Imaging, Three-Dimensional* / methods
Metabolome*
Metabolomics* / methods
Mice
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods

Abstract

MeSH terms

Grants and funding