Automated differentiation of pre-diagnosis Huntington's disease from healthy control individuals based on quadratic discriminant analysis of the basal ganglia: the IMAGE-HD study

Georgiou-Karistianis, N., Gray, M.A., Domínguez D., J.F., Dymowski, A.R., Bohanna, I., Johnston, L.A., Churchyard, A., Chua, P., Stout, J.C., and Egan, G.F. (2013) Automated differentiation of pre-diagnosis Huntington's disease from healthy control individuals based on quadratic discriminant analysis of the basal ganglia: the IMAGE-HD study. Neurobiology of Disease, 51. pp. 82-92.

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Abstract

We investigated two measures of neural integrity, T1-weighted volumetric measures and diffusion tensor imaging (DTI), and explored their combined potential to differentiate pre-diagnosis Huntington's disease (pre-HD) individuals from healthy controls. We applied quadratic discriminant analysis (QDA) to discriminate pre-HD individuals from controls and we utilised feature selection and dimension reduction to increase the robustness of the discrimination method. Thirty six symptomatic HD (symp-HD), 35 pre-HD, and 36 control individuals participated as part of the IMAGE-HD study and underwent T1-weighted MRI, and DTI using a Siemens 3 Tesla scanner. Volume and DTI measures [mean diffusivity (MD) and fractional anisotropy (FA)] were calculated for each group within five regions of interest (ROI; caudate, putamen, pallidum, accumbens and thalamus). QDA was then performed in a stepwise manner to differentiate pre-HD individuals from controls, based initially on unimodal analysis of motor or neurocognitive measures, or on volume, MD or FA measures from within the caudate, pallidum and putamen. We then tested for potential improvements to this model, by examining multi-modal MRI classifications (volume, FA and MD), and also included motor and neurocognitive measures, and additional brain regions (i.e., accumbens and thalamus). Volume, MD and FA differed across the three groups, with pre-HD characterised by significant volumetric reductions and increased FA within caudate, putamen and pallidum, relative to controls. The QDA results demonstrated that the differentiation of pre-HD from controls was highly accurate when both volumetric and diffusion data sets from basal ganglia (BG) regions were used. The highest discriminative accuracy however was achieved in a multi-modality approach and when including all available measures: motor and neurocognitive scores and multi-modal MRI measures from the BG, accumbens and thalamus. Our QDA findings provide evidence that combined multi-modal imaging measures can accurately classify individuals up to 15 years prior to onset when therapeutic intervention is likely to have maximal effects in slowing the trajectory of disease development.

Item ID: 25511
Item Type: Article (Research - C1)
ISSN: 1095-953X
Keywords: Huntington's disease, T1-weighted volume, mean diffusivity, fractional anisotropy, quadratic discriminant function analysis, magnetic resonance imaging, diffusion weighted imaging, multivariate classification, basal ganglia
Funders: CHDI Foundation, Inc., USA, National Health and Medical Research Council (NHMRC)
Date Deposited: 13 Mar 2013 05:35
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1109 Neurosciences > 110903 Central Nervous System @ 34%
11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110320 Radiology and Organ Imaging @ 33%
11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110311 Medical Genetics (excl Cancer Genetics) @ 33%
SEO Codes: 92 HEALTH > 9202 Health and Support Services > 920203 Diagnostic Methods @ 34%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920199 Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified @ 33%
97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 33%
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