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
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.
