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Neuroimage Clin. 2018 Aug 19;20:603-610. doi: 10.1016/j.nicl.2018.08.023. eCollection 2018.

Data driven diagnostic classification in Alzheimer's disease based on different reference regions for normalization of PiB-PET images and correlation with CSF concentrations of Aβ species.

Author information

1
CiBIT, ICNAS, Institute for Biomedical Imaging in Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Portugal.
2
Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Translational Alzheimer Neurobiology, Karolinska Institutet, Stockholm, Sweden.
3
Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark.
4
Division of Clinical Neurosciences, Turku University Hospital, University of Turku, Turku, Finland.
5
Department of Neurology and Laboratory of Neurosciences, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
6
Department of Neurology, University of Ulm, Germany.
7
Neurology Department, Hospital de Sant Pau, Barcelona, Spain and Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
8
Centro Hospitalar e Universitário de Coimbra, Neurology Department, Faculty of Medicine, University of Coimbra, Portugal.
9
Turku University Hospital, Turku PET Centre, Turku, Finland.
10
Department of Nuclear Medicine, Ulm University Hospital, Ulm, Germany.
11
Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
12
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Lab, Sahlgrenska University Hospital, Mölndal, Sweden.
13
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Lab, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, United Kingdom; UK Dementia Research Institute, London, United Kingdom.
14
Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Translational Alzheimer Neurobiology, Karolinska Institutet, Stockholm, Sweden; Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
15
CiBIT, ICNAS, Institute for Biomedical Imaging in Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, Portugal. Electronic address: mcbranco@fmed.uc.pt.

Abstract

Positron emission tomography (PET) neuroimaging with the Pittsburgh Compound_B (PiB) is widely used to assess amyloid plaque burden. Standard quantification approaches normalize PiB-PET by mean cerebellar gray matter uptake. Previous studies suggested similar pons and white-matter uptake in Alzheimer's disease (AD) and healthy controls (HC), but lack exhaustive comparison of normalization across the three regions, with data-driven diagnostic classification. We aimed to compare the impact of distinct reference regions in normalization, measured by data-driven statistical analysis, and correlation with cerebrospinal fluid (CSF) amyloid β (Aβ) species concentrations. 243 individuals with clinical diagnosis of AD, HC, mild cognitive impairment (MCI) and other dementias, from the Biomarkers for Alzheimer's/Parkinson's Disease (BIOMARKAPD) initiative were included. PiB-PET images and CSF concentrations of Aβ38, Aβ40 and Aβ42 were submitted to classification using support vector machines. Voxel-wise group differences and correlations between normalized PiB-PET images and CSF Aβ concentrations were calculated. Normalization by cerebellar gray matter and pons yielded identical classification accuracy of AD (accuracy-96%, sensitivity-96%, specificity-95%), and significantly higher than Aβ concentrations (best accuracy 91%). Normalization by the white-matter showed decreased extent of statistically significant multivoxel patterns and was the only method not outperforming CSF biomarkers, suggesting statistical inferiority. Aβ38 and Aβ40 correlated negatively with PiB-PET images normalized by the white-matter, corroborating previous observations of correlations with non-AD-specific subcortical changes in white-matter. In general, when using the pons as reference region, higher voxel-wise group differences and stronger correlation with Aβ42, the Aβ42/Aβ40 or Aβ42/Aβ38 ratios were found compared to normalization based on cerebellar gray matter.

PMID:
30186764
PMCID:
PMC6120605
DOI:
10.1016/j.nicl.2018.08.023
[Indexed for MEDLINE]
Free PMC Article

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