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Title: Diagnosis and prognosis of Alzheimer's disease using brain morphometry and white matter connectomes

Abstract

Accurate, reliable prediction of risk for Alzheimer's disease (AD) is essential for early, disease-modifying therapeutics. Multimodal MRI, such as structural and diffusion MRI, is likely to contain complementary information of neurodegenerative processes in AD. Here we tested the utility of the multimodal MRI (T1-weighted structure and diffusion MRI), combined with high-throughput brain phenotyping—morphometry and structural connectomics—and machine learning, as a diagnostic tool for AD. We used, firstly, a clinical cohort at a dementia clinic (National Health Insurance Service-Ilsan Hospital [NHIS-IH]; N = 211; 110 AD, 64 mild cognitive impairment [MCI], and 37 cognitively normal with subjective memory complaints [SMC]) to test the diagnostic models; and, secondly, Alzheimer's Disease Neuroimaging Initiative (ADNI)-2 to test the generalizability. Our machine learning models trained on the morphometric and connectome estimates (number of features = 34,646) showed optimal classification accuracy (AD/SMC: 97% accuracy, MCI/SMC: 83% accuracy; AD/MCI: 97% accuracy) in NHIS-IH cohort, outperforming a benchmark model (FLAIR-based white matter hyperintensity volumes). In ADNI-2 data, the combined connectome and morphometry model showed similar or superior accuracies (AD/HC: 96%; MCI/HC: 70%; AD/MCI: 75% accuracy) compared with the CSF biomarker model (t-tau, p-tau, and Amyloid β, and ratios). In predicting MCI to AD progression in a smaller cohortmore » of ADNI-2 (n = 60), the morphometry model showed similar performance with 69% accuracy compared with CSF biomarker model with 70% accuracy. Our comparisons of the classifiers trained on structural MRI, diffusion MRI, FLAIR, and CSF biomarkers showed the promising utility of the white matter structural connectomes in classifying AD and MCI in addition to the widely used structural MRI-based morphometry, when combined with machine learning.« less

Authors:
ORCiD logo [1];  [2];  [2];  [3];  [4];  [5];  [6];  [7]; ORCiD logo [8]
  1. Columbia Univ., New York, NY (United States). Medical Center. Dept. of Psychiatry
  2. Stony Brook Univ., NY (United States). Dept. of Applied Mathematics
  3. Columbia Univ., New York, NY (United States). Medical Center. Dept. of Biostatistics. School of Public Health
  4. Columbia Univ., New York, NY (United States). Medical Center. Dept. of Neurology
  5. Brookhaven National Lab. (BNL), Upton, NY (United States). Computational Science Initiative
  6. National Health Insurance Service Ilsan Hospital, Goyang (Korea, Republic of). Dept. of Neurology
  7. National Health Insurance Service Ilsan Hospital, Goyang (Korea, Republic of). Dept. of Physical Medicine and Rehabilitation
  8. Columbia Univ., New York, NY (United States). Medical Center. Dept. of Psychiatry. Data Science Inst.
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL), Upton, NY (United States); Columbia Univ., New York, NY (United States); National Health Insurance Service Ilsan Hospital, Goyang (Korea, Republic of)
Sponsoring Org.:
USDOE; National Inst. of Health (NIH) (United States); National Health Insurance Ilsan Hospital Research Fund (Korea, Republic of)
OSTI Identifier:
1514489
Report Number(s):
BNL-211602-2019-JAAM
Journal ID: ISSN 2213-1582
Grant/Contract Number:  
SC0012704; K01 MH109836
Resource Type:
Accepted Manuscript
Journal Name:
NeuroImage: Clinical
Additional Journal Information:
Journal Volume: 23; Journal ID: ISSN 2213-1582
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; Alzheimer's disease; multimodal MRI; DWI; machine learning

Citation Formats

Wang, Yun, Xu, Chenxiao, Park, Ji-Hwan, Lee, Seonjoo, Stern, Yaakov, Yoo, Shinjae, Kim, Jong Hun, Kim, Hyoung Seop, and Cha, Jiook. Diagnosis and prognosis of Alzheimer's disease using brain morphometry and white matter connectomes. United States: N. p., 2019. Web. doi:10.1016/j.nicl.2019.101859.
Wang, Yun, Xu, Chenxiao, Park, Ji-Hwan, Lee, Seonjoo, Stern, Yaakov, Yoo, Shinjae, Kim, Jong Hun, Kim, Hyoung Seop, & Cha, Jiook. Diagnosis and prognosis of Alzheimer's disease using brain morphometry and white matter connectomes. United States. https://doi.org/10.1016/j.nicl.2019.101859
Wang, Yun, Xu, Chenxiao, Park, Ji-Hwan, Lee, Seonjoo, Stern, Yaakov, Yoo, Shinjae, Kim, Jong Hun, Kim, Hyoung Seop, and Cha, Jiook. Mon . "Diagnosis and prognosis of Alzheimer's disease using brain morphometry and white matter connectomes". United States. https://doi.org/10.1016/j.nicl.2019.101859. https://www.osti.gov/servlets/purl/1514489.
@article{osti_1514489,
title = {Diagnosis and prognosis of Alzheimer's disease using brain morphometry and white matter connectomes},
author = {Wang, Yun and Xu, Chenxiao and Park, Ji-Hwan and Lee, Seonjoo and Stern, Yaakov and Yoo, Shinjae and Kim, Jong Hun and Kim, Hyoung Seop and Cha, Jiook},
abstractNote = {Accurate, reliable prediction of risk for Alzheimer's disease (AD) is essential for early, disease-modifying therapeutics. Multimodal MRI, such as structural and diffusion MRI, is likely to contain complementary information of neurodegenerative processes in AD. Here we tested the utility of the multimodal MRI (T1-weighted structure and diffusion MRI), combined with high-throughput brain phenotyping—morphometry and structural connectomics—and machine learning, as a diagnostic tool for AD. We used, firstly, a clinical cohort at a dementia clinic (National Health Insurance Service-Ilsan Hospital [NHIS-IH]; N = 211; 110 AD, 64 mild cognitive impairment [MCI], and 37 cognitively normal with subjective memory complaints [SMC]) to test the diagnostic models; and, secondly, Alzheimer's Disease Neuroimaging Initiative (ADNI)-2 to test the generalizability. Our machine learning models trained on the morphometric and connectome estimates (number of features = 34,646) showed optimal classification accuracy (AD/SMC: 97% accuracy, MCI/SMC: 83% accuracy; AD/MCI: 97% accuracy) in NHIS-IH cohort, outperforming a benchmark model (FLAIR-based white matter hyperintensity volumes). In ADNI-2 data, the combined connectome and morphometry model showed similar or superior accuracies (AD/HC: 96%; MCI/HC: 70%; AD/MCI: 75% accuracy) compared with the CSF biomarker model (t-tau, p-tau, and Amyloid β, and ratios). In predicting MCI to AD progression in a smaller cohort of ADNI-2 (n = 60), the morphometry model showed similar performance with 69% accuracy compared with CSF biomarker model with 70% accuracy. Our comparisons of the classifiers trained on structural MRI, diffusion MRI, FLAIR, and CSF biomarkers showed the promising utility of the white matter structural connectomes in classifying AD and MCI in addition to the widely used structural MRI-based morphometry, when combined with machine learning.},
doi = {10.1016/j.nicl.2019.101859},
journal = {NeuroImage: Clinical},
number = ,
volume = 23,
place = {United States},
year = {Mon May 13 00:00:00 EDT 2019},
month = {Mon May 13 00:00:00 EDT 2019}
}

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Works referenced in this record:

Histological Validation of DW-MRI Tractography in Human Postmortem Tissue
journal, February 2012


CSF biomarker changes precede symptom onset of mild cognitive impairment
journal, October 2013


Integrated multimodal imaging in neurodegenerative disease
journal, October 2015


Just pretty pictures? What diffusion tractography can add in clinical neuroscience
journal, August 2006


The basis of anisotropic water diffusion in the nervous system - a technical review
journal, January 2002

  • Beaulieu, Christian
  • NMR in Biomedicine, Vol. 15, Issue 7-8
  • DOI: 10.1002/nbm.782

The Neonatal Connectome During Preterm Brain Development
journal, May 2014

  • van den Heuvel, Martijn P.; Kersbergen, Karina J.; de Reus, Marcel A.
  • Cerebral Cortex, Vol. 25, Issue 9
  • DOI: 10.1093/cercor/bhu095

Machine learning for neuroimaging with scikit-learn
journal, January 2014

  • Abraham, Alexandre; Pedregosa, Fabian; Eickenberg, Michael
  • Frontiers in Neuroinformatics, Vol. 8
  • DOI: 10.3389/fninf.2014.00014

DTI measures in crossing-fibre areas: Increased diffusion anisotropy reveals early white matter alteration in MCI and mild Alzheimer's disease
journal, April 2011


Seoul Neuropsychological Screening Battery-Dementia Version (SNSB-D): A Useful Tool for Assessing and Monitoring Cognitive Impairments in Dementia Patients
journal, January 2010


Neural Correlates of Aggression in Medication-Naive Children with ADHD: Multivariate Analysis of Morphometry and Tractography
journal, February 2015

  • Cha, Jiook; Fekete, Tomer; Siciliano, Francesco
  • Neuropsychopharmacology, Vol. 40, Issue 7
  • DOI: 10.1038/npp.2015.18

Can lumbar puncture help to identify patients with incipient Alzheimer's disease?
journal, October 2006

  • Bouwman, Femke H.; van der Flier, Wiesje M.; Scheltens, Philip
  • Nature Clinical Practice Neurology, Vol. 2, Issue 10
  • DOI: 10.1038/ncpneuro0295

Diffusion Tensor Tractography Reveals Abnormal Topological Organization in Structural Cortical Networks in Alzheimer's Disease
journal, December 2010


Denoising of diffusion MRI using random matrix theory
journal, November 2016


Disrupted structural and functional brain connectomes in mild cognitive impairment and Alzheimer’s disease
journal, April 2014


Direct estimation of the fiber orientation density function from diffusion-weighted MRI data using spherical deconvolution
journal, November 2004


White matter damage in frontotemporal dementia and Alzheimer's disease measured by diffusion MRI
journal, May 2009


Multimodal classification of Alzheimer's disease and mild cognitive impairment
journal, April 2011


A Direct Demonstration of Functional Differences between Subdivisions of Human V5/MT+
journal, November 2016

  • Strong, Samantha L.; Silson, Edward H.; Gouws, André D.
  • Cerebral Cortex, Vol. 27, Issue 1
  • DOI: 10.1093/cercor/bhw362

Inter-site and inter-scanner diffusion MRI data harmonization
journal, July 2016


Diffusion-based tractography in neurological disorders: concepts, applications, and future developments
journal, August 2008


Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade
journal, January 2010


N4ITK: Improved N3 Bias Correction
journal, June 2010

  • Tustison, Nicholas J.; Avants, Brian B.; Cook, Philip A.
  • IEEE Transactions on Medical Imaging, Vol. 29, Issue 6
  • DOI: 10.1109/tmi.2010.2046908

Mild cognitive impairment as a diagnostic entity
journal, September 2004


Clinical validity of CSF biomarkers for Alzheimer's disease: necessary indeed, but sufficient?
journal, June 2016


FreeSurfer
journal, August 2012


The Human Connectome: a Complex Network
journal, April 2012


An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest
journal, July 2006


A Validation Study of Multicenter Diffusion Tensor Imaging: Reliability of Fractional Anisotropy and Diffusivity Values
journal, December 2011

  • Fox, R. J.; Sakaie, K.; Lee, J. -C.
  • American Journal of Neuroradiology, Vol. 33, Issue 4
  • DOI: 10.3174/ajnr.a2844

The organisation of the elderly connectome
journal, July 2015


Machine learning for neuroimaging with scikit-learn
journal, January 2014

  • Abraham, Alexandre; Pedregosa, Fabian; Eickenberg, Michael
  • Frontiers in Neuroinformatics, Vol. 8
  • DOI: 10.3389/fninf.2014.00014

Absolute diffusivities define the landscape of white matter degeneration in Alzheimer's disease
journal, November 2009

  • Acosta-Cabronero, Julio; Williams, Guy B.; Pengas, George
  • Brain, Vol. 133, Issue 2
  • DOI: 10.1093/brain/awp257

Seoul Neuropsychological Screening Battery-Dementia Version (SNSB-D): A Useful Tool for Assessing and Monitoring Cognitive Impairments in Dementia Patients
journal, January 2010


An integrated approach to correction for off-resonance effects and subject movement in diffusion MR imaging
journal, January 2016


Validation of High-Resolution Tractography AgainstIn VivoTracing in the Macaque Visual Cortex
journal, March 2015

  • Azadbakht, Hojjatollah; Parkes, Laura M.; Haroon, Hamied A.
  • Cerebral Cortex, Vol. 25, Issue 11
  • DOI: 10.1093/cercor/bhu326

The basis of anisotropic water diffusion in the nervous system - a technical review
journal, January 2002

  • Beaulieu, Christian
  • NMR in Biomedicine, Vol. 15, Issue 7-8
  • DOI: 10.1002/nbm.782

Neural Correlates of Aggression in Medication-Naive Children with ADHD: Multivariate Analysis of Morphometry and Tractography
journal, February 2015

  • Cha, Jiook; Fekete, Tomer; Siciliano, Francesco
  • Neuropsychopharmacology, Vol. 40, Issue 7
  • DOI: 10.1038/npp.2015.18

Abnormal reward circuitry in anorexia nervosa: A longitudinal, multimodal MRI study
journal, October 2016

  • Cha, Jiook; Ide, Jaime S.; Bowman, F. Dubois
  • Human Brain Mapping, Vol. 37, Issue 11
  • DOI: 10.1002/hbm.23279

Disrupted structural and functional brain connectomes in mild cognitive impairment and Alzheimer’s disease
journal, April 2014


An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest
journal, July 2006


Automatic parcellation of human cortical gyri and sulci using standard anatomical nomenclature
journal, October 2010


DTI measures in crossing-fibre areas: Increased diffusion anisotropy reveals early white matter alteration in MCI and mild Alzheimer's disease
journal, April 2011


FreeSurfer
journal, August 2012


Measuring the thickness of the human cerebral cortex from magnetic resonance images
journal, September 2000

  • Fischl, B.; Dale, A. M.
  • Proceedings of the National Academy of Sciences, Vol. 97, Issue 20
  • DOI: 10.1073/pnas.200033797

Cortical Surface-Based Analysis
journal, February 1999


Harmonization of multi-site diffusion tensor imaging data
journal, November 2017


Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study
journal, March 2006


Alzheimer's Disease: The Challenge of the Second Century
journal, April 2011


Extracting and summarizing white matter hyperintensities using supervised segmentation methods in Alzheimer's disease risk and aging studies
journal, February 2014

  • Ithapu, Vamsi; Singh, Vikas; Lindner, Christopher
  • Human Brain Mapping, Vol. 35, Issue 8
  • DOI: 10.1002/hbm.22472

Just pretty pictures? What diffusion tractography can add in clinical neuroscience
journal, August 2006


Inter-site and inter-scanner diffusion MRI data harmonization
journal, July 2016


CSF biomarker changes precede symptom onset of mild cognitive impairment
journal, October 2013


APP binds DR6 to trigger axon pruning and neuron death via distinct caspases
journal, February 2009

  • Nikolaev, Anatoly; McLaughlin, Todd; O’Leary, Dennis D. M.
  • Nature, Vol. 457, Issue 7232
  • DOI: 10.1038/nature07767

CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis
journal, June 2016


Machine learning of neuroimaging for assisted diagnosis of cognitive impairment and dementia: A systematic review
journal, January 2018

  • Pellegrini, Enrico; Ballerini, Lucia; Hernandez, Maria del C. Valdes
  • Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, Vol. 10, Issue 1
  • DOI: 10.1016/j.dadm.2018.07.004

The organisation of the elderly connectome
journal, July 2015


Mild cognitive impairment as a diagnostic entity
journal, September 2004


Histological Validation of DW-MRI Tractography in Human Postmortem Tissue
journal, February 2012


Connectome imaging for mapping human brain pathways
journal, May 2017


The human connectome: a complex network
journal, January 2011


Multimodal imaging in Alzheimer's disease: validity and usefulness for early detection
journal, October 2015


Direct estimation of the fiber orientation density function from diffusion-weighted MRI data using spherical deconvolution
journal, November 2004


Comparison of diffusion tractography and tract-tracing measures of connectivity strength in rhesus macaque connectome
journal, June 2015

  • van den Heuvel, Martijn P.; de Reus, Marcel A.; Feldman Barrett, Lisa
  • Human Brain Mapping, Vol. 36, Issue 8
  • DOI: 10.1002/hbm.22828

The Neonatal Connectome During Preterm Brain Development
journal, May 2014

  • van den Heuvel, Martijn P.; Kersbergen, Karina J.; de Reus, Marcel A.
  • Cerebral Cortex, Vol. 25, Issue 9
  • DOI: 10.1093/cercor/bhu095

Assessing and tuning brain decoders: Cross-validation, caveats, and guidelines
journal, January 2017


Denoising of diffusion MRI using random matrix theory
journal, November 2016


Identification of MCI individuals using structural and functional connectivity networks
journal, February 2012


White matter damage in frontotemporal dementia and Alzheimer's disease measured by diffusion MRI
journal, May 2009


Multimodal classification of Alzheimer's disease and mild cognitive impairment
journal, April 2011


Connectome-scale assessments of structural and functional connectivity in MCI
journal, September 2013

  • Zhu, Dajiang; Li, Kaiming; Terry, Douglas P.
  • Human Brain Mapping, Vol. 35, Issue 7
  • DOI: 10.1002/hbm.22373

Figures/Tables have been extracted from DOE-funded journal article accepted manuscripts.