Derek B Archer1, Justin T Bricker1, Winston T Chu2, Roxana G Burciu3, Johanna L McCracken1, Song Lai4, Stephen A Coombes1, Ruogu Fang5, Angelos Barmpoutis6, Daniel M Corcos7, Ajay S Kurani8, Trina Mitchell1, Mieniecia L Black1, Ellen Herschel9, Tanya Simuni9, Todd B Parrish8, Cynthia Comella7, Tao Xie10, Klaus Seppi11, Nicolaas I Bohnen12, Martijn Ltm Müller13, Roger L Albin14, Florian Krismer11, Guangwei Du15, Mechelle M Lewis16, Xuemei Huang17, Hong Li18, Ofer Pasternak19, Nikolaus R McFarland20, Michael S Okun21, David E Vaillancourt22. 1. Laboratory for Rehabilitation Neuroscience, Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, USA. 2. Laboratory for Rehabilitation Neuroscience, Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, USA; J Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA. 3. Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE, USA. 4. Department of Radiation Oncology, University of Florida, Gainesville, FL, USA; CTSI Human Imaging Core, University of Florida, Gainesville, FL, USA. 5. J Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA. 6. J Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA; Digital Worlds Institute, University of Florida, Gainesville, FL, USA. 7. Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA. 8. Department of Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. 9. Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. 10. Department of Neurology, University of Chicago, Chicago, IL, USA. 11. Neuroimaging Research Core Facility, Department of Neurology, Medical University Innsbruck, Innsbruck, Austria. 12. Department of Radiology, University of Michigan, Ann Arbor, MI, USA; Department of Neurology, University of Michigan, Ann Arbor, MI, USA; Neurology Service and Geriatrics Research, Education, and Clinical Center, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA; Udall Center of Excellence for Parkinson's Disease Research, University of Michigan, Ann Arbor, MI, USA. 13. Department of Radiology, University of Michigan, Ann Arbor, MI, USA; Udall Center of Excellence for Parkinson's Disease Research, University of Michigan, Ann Arbor, MI, USA. 14. Department of Neurology, University of Michigan, Ann Arbor, MI, USA; Neurology Service and Geriatrics Research, Education, and Clinical Center, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA; Udall Center of Excellence for Parkinson's Disease Research, University of Michigan, Ann Arbor, MI, USA. 15. Department of Neurology, Penn State Milton S Hershey Medical Center, Hershey, PA, USA. 16. Department of Neurology, Penn State Milton S Hershey Medical Center, Hershey, PA, USA; Department of Pharmacology, Penn State Milton S Hershey Medical Center, Hershey, PA, USA. 17. Department of Neurology, Penn State Milton S Hershey Medical Center, Hershey, PA, USA; Department of Pharmacology, Penn State Milton S Hershey Medical Center, Hershey, PA, USA; Department of Neurosurgery, Penn State Milton S Hershey Medical Center, Hershey, PA, USA; Department of Radiology, Penn State Milton S Hershey Medical Center, Hershey, PA, USA; Department of Kinesiology, Penn State Milton S Hershey Medical Center, Hershey, PA, USA. 18. Department of Public Health Sciences, Medical College of South Carolina, Charleston, SC, USA. 19. Department of Psychiatry and Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 20. Fixel Institute for Neurological Disease, University of Florida, Gainesville, FL, USA; Department of Neurology, McKnight Brain Institute, University of Florida, Gainesville, FL, USA. 21. Fixel Institute for Neurological Disease, University of Florida, Gainesville, FL, USA; Department of Neurology, McKnight Brain Institute, University of Florida, Gainesville, FL, USA; Department of Neurosurgery, McKnight Brain Institute, University of Florida, Gainesville, FL, USA. 22. Laboratory for Rehabilitation Neuroscience, Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, USA; J Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA; Fixel Institute for Neurological Disease, University of Florida, Gainesville, FL, USA; Department of Neurology, McKnight Brain Institute, University of Florida, Gainesville, FL, USA. Electronic address: vcourt@ufl.edu.
Abstract
BACKGROUND: Development of valid, non-invasive biomarkers for parkinsonian syndromes is crucially needed. We aimed to assess whether non-invasive diffusion-weighted MRI can distinguish between parkinsonian syndromes using an automated imaging approach. METHODS: We did an international study at 17 MRI centres in Austria, Germany, and the USA. We used diffusion-weighted MRI from 1002 patients and the Movement Disorders Society Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) to develop and validate disease-specific machine learning comparisons using 60 template regions and tracts of interest in Montreal Neurological Institute space between Parkinson's disease and atypical parkinsonism (multiple system atrophy and progressive supranuclear palsy) and between multiple system atrophy and progressive supranuclear palsy. For each comparison, models were developed on a training and validation cohort and evaluated in an independent test cohort by quantifying the area under the curve (AUC) of receiving operating characteristic curves. The primary outcomes were free water and free-water-corrected fractional anisotropy across 60 different template regions. FINDINGS: In the test cohort for disease-specific comparisons, the diffusion-weighted MRI plus MDS-UPDRS III model (Parkinson's disease vs atypical parkinsonism had an AUC 0·962; multiple system atrophy vs progressive supranuclear palsy AUC 0·897) and diffusion-weighted MRI only model had high AUCs (Parkinson's disease vs atypical parkinsonism AUC 0·955; multiple system atrophy vs progressive supranuclear palsy AUC 0·926), whereas the MDS-UPDRS III only models had significantly lower AUCs (Parkinson's disease vs atypical parkinsonism 0·775; multiple system atrophy vs progressive supranuclear palsy 0·582). These results indicate that a non-invasive imaging approach is capable of differentiating forms of parkinsonism comparable to current gold standard methods. INTERPRETATIONS: This study provides an objective, validated, and generalisable imaging approach to distinguish different forms of parkinsonian syndromes using multisite diffusion-weighted MRI cohorts. The diffusion-weighted MRI method does not involve radioactive tracers, is completely automated, and can be collected in less than 12 min across 3T scanners worldwide. The use of this test could positively affect the clinical care of patients with Parkinson's disease and parkinsonism and reduce the number of misdiagnosed cases in clinical trials. FUNDING: National Institutes of Health and Parkinson's Foundation.
BACKGROUND: Development of valid, non-invasive biomarkers for parkinsonian syndromes is crucially needed. We aimed to assess whether non-invasive diffusion-weighted MRI can distinguish between parkinsonian syndromes using an automated imaging approach. METHODS: We did an international study at 17 MRI centres in Austria, Germany, and the USA. We used diffusion-weighted MRI from 1002 patients and the Movement Disorders Society Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) to develop and validate disease-specific machine learning comparisons using 60 template regions and tracts of interest in Montreal Neurological Institute space between Parkinson's disease and atypical parkinsonism (multiple system atrophy and progressive supranuclear palsy) and between multiple system atrophy and progressive supranuclear palsy. For each comparison, models were developed on a training and validation cohort and evaluated in an independent test cohort by quantifying the area under the curve (AUC) of receiving operating characteristic curves. The primary outcomes were free water and free-water-corrected fractional anisotropy across 60 different template regions. FINDINGS: In the test cohort for disease-specific comparisons, the diffusion-weighted MRI plus MDS-UPDRS III model (Parkinson's disease vs atypical parkinsonism had an AUC 0·962; multiple system atrophy vs progressive supranuclear palsy AUC 0·897) and diffusion-weighted MRI only model had high AUCs (Parkinson's disease vs atypical parkinsonism AUC 0·955; multiple system atrophy vs progressive supranuclear palsy AUC 0·926), whereas the MDS-UPDRS III only models had significantly lower AUCs (Parkinson's disease vs atypical parkinsonism 0·775; multiple system atrophy vs progressive supranuclear palsy 0·582). These results indicate that a non-invasive imaging approach is capable of differentiating forms of parkinsonism comparable to current gold standard methods. INTERPRETATIONS: This study provides an objective, validated, and generalisable imaging approach to distinguish different forms of parkinsonian syndromes using multisite diffusion-weighted MRI cohorts. The diffusion-weighted MRI method does not involve radioactive tracers, is completely automated, and can be collected in less than 12 min across 3T scanners worldwide. The use of this test could positively affect the clinical care of patients with Parkinson's disease and parkinsonism and reduce the number of misdiagnosed cases in clinical trials. FUNDING: National Institutes of Health and Parkinson's Foundation.
Authors: Winston Thomas Chu; Wei-En Wang; Laszlo Zaborszky; Todd Eliot Golde; Steven DeKosky; Ranjan Duara; David A Loewenstein; Malek Adjouadi; Stephen A Coombes; David E Vaillancourt Journal: Neurology Date: 2021-12-14 Impact factor: 9.910
Authors: Derek B Archer; Trina Mitchell; Roxana G Burciu; Jing Yang; Salvatore Nigro; Aldo Quattrone; Andrea Quattrone; Andreas Jeromin; Nikolaus R McFarland; Michael S Okun; David E Vaillancourt Journal: Mov Disord Date: 2020-05-01 Impact factor: 10.338