title: Multimodal imaging biomarkers in premanifest and early Huntington's disease: 30-month IMAGE-HD data.
abstract: The discovery of potential disease-modifying therapies in a neurodegenerative condition like Huntington's disease depends on the availability of sensitive biomarkers that reflect decline across disease stages and that are functionally and clinically relevant.
  
  
  
  To quantify macrostructural and microstructural changes in participants with premanifest and symptomatic Huntington's disease over 30 months, and to establish their functional and clinical relevance.
  
  
  
  Multimodal magnetic resonance imaging study measuring changes in macrostructural (volume) and microstructural (diffusivity) measures in 40 patients with premanifest Huntington's disease, 36 patients with symptomatic Huntington's disease and 36 healthy control participants over three testing sessions spanning 30 months.
  
  
  
  Relative to controls, there was greater longitudinal atrophy in participants with symptomatic Huntington's disease in whole brain, grey matter, caudate and putamen, as well as increased caudate fractional anisotropy; caudate volume loss was the only measure to differ between premanifest Huntington's disease and control groups. Changes in caudate volume and fractional anisotropy correlated with each other and neurocognitive decline; caudate volume loss also correlated with clinical and disease severity.
  
  
  
  Caudate neurodegeneration, especially atrophy, may be the most suitable candidate surrogate biomarker for consideration in the development of upcoming clinical trials.
authors.affiliation: Juan F. Domínguez D., PhD, Julie C. Stout, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia; Govinda Poudel, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia, Monash Biomedical Imaging (MBI), Monash University, Melbourne, Victoria, Australia and VLSCI Life Sciences Computation Centre, Melbourne, Victoria, Australia; Andrew Churchyard, MD, PhD, Department of Neurology, Monash Medical Centre, Clayton, Victoria, Australia; Phyllis Chua, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia; Gary F. Egan, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia and Monash Biomedical Imaging (MBI), Monash University, Melbourne, Victoria, Australia; Nellie Georgiou-Karistianis, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: Juan F Domínguez
authors.initials: JF
authors.lastname: D
authors.affiliation: Juan F. Domínguez D., PhD, Julie C. Stout, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia; Govinda Poudel, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia, Monash Biomedical Imaging (MBI), Monash University, Melbourne, Victoria, Australia and VLSCI Life Sciences Computation Centre, Melbourne, Victoria, Australia; Andrew Churchyard, MD, PhD, Department of Neurology, Monash Medical Centre, Clayton, Victoria, Australia; Phyllis Chua, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia; Gary F. Egan, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia and Monash Biomedical Imaging (MBI), Monash University, Melbourne, Victoria, Australia; Nellie Georgiou-Karistianis, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: Julie C
authors.initials: JC
authors.lastname: Stout
authors.affiliation: Juan F. Domínguez D., PhD, Julie C. Stout, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia; Govinda Poudel, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia, Monash Biomedical Imaging (MBI), Monash University, Melbourne, Victoria, Australia and VLSCI Life Sciences Computation Centre, Melbourne, Victoria, Australia; Andrew Churchyard, MD, PhD, Department of Neurology, Monash Medical Centre, Clayton, Victoria, Australia; Phyllis Chua, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia; Gary F. Egan, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia and Monash Biomedical Imaging (MBI), Monash University, Melbourne, Victoria, Australia; Nellie Georgiou-Karistianis, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: Govinda
authors.initials: G
authors.lastname: Poudel
authors.affiliation: Juan F. Domínguez D., PhD, Julie C. Stout, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia; Govinda Poudel, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia, Monash Biomedical Imaging (MBI), Monash University, Melbourne, Victoria, Australia and VLSCI Life Sciences Computation Centre, Melbourne, Victoria, Australia; Andrew Churchyard, MD, PhD, Department of Neurology, Monash Medical Centre, Clayton, Victoria, Australia; Phyllis Chua, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia; Gary F. Egan, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia and Monash Biomedical Imaging (MBI), Monash University, Melbourne, Victoria, Australia; Nellie Georgiou-Karistianis, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Churchyard
authors.affiliation: Juan F. Domínguez D., PhD, Julie C. Stout, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia; Govinda Poudel, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia, Monash Biomedical Imaging (MBI), Monash University, Melbourne, Victoria, Australia and VLSCI Life Sciences Computation Centre, Melbourne, Victoria, Australia; Andrew Churchyard, MD, PhD, Department of Neurology, Monash Medical Centre, Clayton, Victoria, Australia; Phyllis Chua, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia; Gary F. Egan, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia and Monash Biomedical Imaging (MBI), Monash University, Melbourne, Victoria, Australia; Nellie Georgiou-Karistianis, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: Phyllis
authors.initials: P
authors.lastname: Chua
authors.affiliation: Juan F. Domínguez D., PhD, Julie C. Stout, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia; Govinda Poudel, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia, Monash Biomedical Imaging (MBI), Monash University, Melbourne, Victoria, Australia and VLSCI Life Sciences Computation Centre, Melbourne, Victoria, Australia; Andrew Churchyard, MD, PhD, Department of Neurology, Monash Medical Centre, Clayton, Victoria, Australia; Phyllis Chua, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia; Gary F. Egan, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia and Monash Biomedical Imaging (MBI), Monash University, Melbourne, Victoria, Australia; Nellie Georgiou-Karistianis, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: Gary F
authors.initials: GF
authors.lastname: Egan
authors.affiliation: Juan F. Domínguez D., PhD, Julie C. Stout, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia; Govinda Poudel, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia, Monash Biomedical Imaging (MBI), Monash University, Melbourne, Victoria, Australia and VLSCI Life Sciences Computation Centre, Melbourne, Victoria, Australia; Andrew Churchyard, MD, PhD, Department of Neurology, Monash Medical Centre, Clayton, Victoria, Australia; Phyllis Chua, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia; Gary F. Egan, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia and Monash Biomedical Imaging (MBI), Monash University, Melbourne, Victoria, Australia; Nellie Georgiou-Karistianis, PhD, School of Psychological Sciences, Monash University, Clayton, Victoria, Australia nellie.georgiou-karistianis@monash.edu.
authors.forename: Nellie
authors.initials: N
authors.lastname: Georgiou-Karistianis
mesh_terms: D000328:Adult; D001284:Atrophy; D015415:Biomarkers; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D006816:Huntington Disease / Q000000981:diagnostic imaging / Q000473:pathology*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D062706:Prodromal Symptoms; D011699:Putamen / Q000000981:diagnostic imaging / Q000473:pathology
chemical_list: D015415:Biomarkers