Toward AI-driven neuroepigenetic imaging biomarker for alcohol use disorder: A proof-of-concept study

Tewodros Mulugeta Dagnew; Chieh-En J. Tseng; Chi-Hyeon Yoo; Meena M. Makary; Anna E. Goodheart; Robin Striar; Tyler N. Meyer; Anna K. Rattray; Leyi Kang; Kendall A. Wolf; Stephanie A. Fiedler; Darcy Tocci; Hannah Shapiro; Scott Provost; Eleanor Sultana; Yan Liu; Wei Ding; Ping Chen; Marek Kubicki; Shiqian Shen; Ciprian Catana; Nicole R. Zürcher; Hsiao-Ying Wey; Jacob M. Hooker; Roger D. Weiss; Changning Wang

iScience (Jul 2024)

Toward AI-driven neuroepigenetic imaging biomarker for alcohol use disorder: A proof-of-concept study

Tewodros Mulugeta Dagnew,
Chieh-En J. Tseng,
Chi-Hyeon Yoo,
Meena M. Makary,
Anna E. Goodheart,
Robin Striar,
Tyler N. Meyer,
Anna K. Rattray,
Leyi Kang,
Kendall A. Wolf,
Stephanie A. Fiedler,
Darcy Tocci,
Hannah Shapiro,
Scott Provost,
Eleanor Sultana,
Yan Liu,
Wei Ding,
Ping Chen,
Marek Kubicki,
Shiqian Shen,
Ciprian Catana,
Nicole R. Zürcher,
Hsiao-Ying Wey,
Jacob M. Hooker,
Roger D. Weiss,
Changning Wang

Affiliations

Tewodros Mulugeta Dagnew: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Chieh-En J. Tseng: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Chi-Hyeon Yoo: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Meena M. Makary: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Systems and Biomedical Engineering Department, Cairo University, Giza, Egypt
Anna E. Goodheart: Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
Robin Striar: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Tyler N. Meyer: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Anna K. Rattray: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Leyi Kang: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Kendall A. Wolf: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Stephanie A. Fiedler: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Darcy Tocci: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Hannah Shapiro: Division of Alcohol, Drugs, and Addiction, McLean Hospital, Belmont, MA, USA
Scott Provost: Division of Alcohol, Drugs, and Addiction, McLean Hospital, Belmont, MA, USA
Eleanor Sultana: Division of Alcohol, Drugs, and Addiction, McLean Hospital, Belmont, MA, USA
Yan Liu: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Wei Ding: Department of Computer Science, University of Massachusetts Boston, Boston, MA, USA
Ping Chen: Department of Engineering, University of Massachusetts Boston, Boston, MA, USA
Marek Kubicki: Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Psychiatry Neuroimaging Laboratory, Departments of Psychiatry and Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
Shiqian Shen: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Ciprian Catana: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Nicole R. Zürcher: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Hsiao-Ying Wey: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Jacob M. Hooker: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Roger D. Weiss: Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Division of Alcohol, Drugs, and Addiction, McLean Hospital, Belmont, MA, USA; Corresponding author
Changning Wang: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Corresponding author

Journal volume & issue: Vol. 27, no. 7
p. 110159

Abstract

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Summary: Alcohol use disorder (AUD) is a disorder of clinical and public health significance requiring novel and improved therapeutic solutions. Both environmental and genetic factors play a significant role in its pathophysiology. However, the underlying epigenetic molecular mechanisms that link the gene-environment interaction in AUD remain largely unknown. In this proof-of-concept study, we showed, for the first time, the neuroepigenetic biomarker capability of non-invasive imaging of class I histone deacetylase (HDAC) epigenetic enzymes in the in vivo brain for classifying AUD patients from healthy controls using a machine learning approach in the context of precision diagnosis. Eleven AUD patients and 16 age- and sex-matched healthy controls completed a simultaneous positron emission tomography-magnetic resonance (PET/MR) scan with the HDAC-binding radiotracer [11C]Martinostat. Our results showed lower HDAC expression in the anterior cingulate region in AUD. Furthermore, by applying a genetic algorithm feature selection, we identified five particular brain regions whose combined [11C]Martinostat relative standard uptake value (SUVR) features could reliably classify AUD vs. controls. We validate their promising classification reliability using a support vector machine classifier. These findings inform the potential of in vivo HDAC imaging biomarkers coupled with machine learning tools in the objective diagnosis and molecular translation of AUD that could complement the current diagnostic and statistical manual of mental disorders (DSM)-based intervention to propel precision medicine forward.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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