Antemortem MRI based STructural Abnormality iNDex (STAND)-scores correlate with postmortem Braak neurofibrillary tangle stage

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Abstract

The clinical diagnosis of Alzheimer's disease (AD) does not exactly match the pathological findings at autopsy in every subject. Therefore, in-vivo imaging measures, such as Magnetic Resonance Imaging (MRI) that reflect underlying pathology, would be clinically useful independent supplementary measures of disease stage. We have developed an algorithm that extracts atrophy information from individual patient's 3D MRI scans and assigns a STructural Abnormality iNDex (STAND)-score to the scan based on the degree of atrophy in comparison to patterns extracted from a large library of clinically well characterized AD and CN (cognitively normal) subject's MRI scans. STAND-scores can be adjusted for demographics to give adjusted-STAND (aSTAND)-scores which are > 0 for subjects with brains identified as abnormal by the algorithm. Since histopathological findings are considered to represent the "ground truth", our objective was to assess the sensitivity of aSTAND-scores to pathological AD staging. This was done by comparing antemortem MRI based aSTAND-scores with postmortem grading of disease severity in 101 subjects who had both antemortem MRI and postmortem Braak neurofibrillary tangle (NFT) staging. We found a rank correlation of 0.62 (p < 0.0001) between Braak NFT stage and aSTAND-scores. The results show that optimally extracted information from MRI scans such as STAND-scores accurately capture the severity of neuronal pathology and can be used as an independent approximate surrogate marker for in-vivo pathological staging as well as for early identification of AD in individual subjects.

Original languageEnglish (US)
Pages (from-to)559-567
Number of pages9
JournalNeuroImage
Volume42
Issue number2
DOIs
StatePublished - Aug 15 2008

Fingerprint

Neurofibrillary Tangles
Magnetic Resonance Imaging
Alzheimer Disease
Atrophy
Pathology
Libraries
Autopsy
Biomarkers
Demography
Brain

Keywords

  • Alzheimer's disease
  • Amnestic mild cognitive impairment
  • Braak NFT stage
  • Magnetic resonance imaging
  • Neurofibrillary tangles

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Neurology

Cite this

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title = "Antemortem MRI based STructural Abnormality iNDex (STAND)-scores correlate with postmortem Braak neurofibrillary tangle stage",
abstract = "The clinical diagnosis of Alzheimer's disease (AD) does not exactly match the pathological findings at autopsy in every subject. Therefore, in-vivo imaging measures, such as Magnetic Resonance Imaging (MRI) that reflect underlying pathology, would be clinically useful independent supplementary measures of disease stage. We have developed an algorithm that extracts atrophy information from individual patient's 3D MRI scans and assigns a STructural Abnormality iNDex (STAND)-score to the scan based on the degree of atrophy in comparison to patterns extracted from a large library of clinically well characterized AD and CN (cognitively normal) subject's MRI scans. STAND-scores can be adjusted for demographics to give adjusted-STAND (aSTAND)-scores which are > 0 for subjects with brains identified as abnormal by the algorithm. Since histopathological findings are considered to represent the {"}ground truth{"}, our objective was to assess the sensitivity of aSTAND-scores to pathological AD staging. This was done by comparing antemortem MRI based aSTAND-scores with postmortem grading of disease severity in 101 subjects who had both antemortem MRI and postmortem Braak neurofibrillary tangle (NFT) staging. We found a rank correlation of 0.62 (p < 0.0001) between Braak NFT stage and aSTAND-scores. The results show that optimally extracted information from MRI scans such as STAND-scores accurately capture the severity of neuronal pathology and can be used as an independent approximate surrogate marker for in-vivo pathological staging as well as for early identification of AD in individual subjects.",
keywords = "Alzheimer's disease, Amnestic mild cognitive impairment, Braak NFT stage, Magnetic resonance imaging, Neurofibrillary tangles",
author = "Vemuri, {Prashanthi D} and Whitwell, {Jennifer Lynn} and Kantarci, {Kejal M} and Josephs, {Keith Anthony} and Parisi, {Joseph E} and Shiung, {Maria S.} and Knopman, {David S} and Boeve, {Bradley F} and Petersen, {Ronald Carl} and Dickson, {Dennis W} and Jack, {Clifford R Jr.}",
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AU - Vemuri, Prashanthi D

AU - Whitwell, Jennifer Lynn

AU - Kantarci, Kejal M

AU - Josephs, Keith Anthony

AU - Parisi, Joseph E

AU - Shiung, Maria S.

AU - Knopman, David S

AU - Boeve, Bradley F

AU - Petersen, Ronald Carl

AU - Dickson, Dennis W

AU - Jack, Clifford R Jr.

PY - 2008/8/15

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N2 - The clinical diagnosis of Alzheimer's disease (AD) does not exactly match the pathological findings at autopsy in every subject. Therefore, in-vivo imaging measures, such as Magnetic Resonance Imaging (MRI) that reflect underlying pathology, would be clinically useful independent supplementary measures of disease stage. We have developed an algorithm that extracts atrophy information from individual patient's 3D MRI scans and assigns a STructural Abnormality iNDex (STAND)-score to the scan based on the degree of atrophy in comparison to patterns extracted from a large library of clinically well characterized AD and CN (cognitively normal) subject's MRI scans. STAND-scores can be adjusted for demographics to give adjusted-STAND (aSTAND)-scores which are > 0 for subjects with brains identified as abnormal by the algorithm. Since histopathological findings are considered to represent the "ground truth", our objective was to assess the sensitivity of aSTAND-scores to pathological AD staging. This was done by comparing antemortem MRI based aSTAND-scores with postmortem grading of disease severity in 101 subjects who had both antemortem MRI and postmortem Braak neurofibrillary tangle (NFT) staging. We found a rank correlation of 0.62 (p < 0.0001) between Braak NFT stage and aSTAND-scores. The results show that optimally extracted information from MRI scans such as STAND-scores accurately capture the severity of neuronal pathology and can be used as an independent approximate surrogate marker for in-vivo pathological staging as well as for early identification of AD in individual subjects.

AB - The clinical diagnosis of Alzheimer's disease (AD) does not exactly match the pathological findings at autopsy in every subject. Therefore, in-vivo imaging measures, such as Magnetic Resonance Imaging (MRI) that reflect underlying pathology, would be clinically useful independent supplementary measures of disease stage. We have developed an algorithm that extracts atrophy information from individual patient's 3D MRI scans and assigns a STructural Abnormality iNDex (STAND)-score to the scan based on the degree of atrophy in comparison to patterns extracted from a large library of clinically well characterized AD and CN (cognitively normal) subject's MRI scans. STAND-scores can be adjusted for demographics to give adjusted-STAND (aSTAND)-scores which are > 0 for subjects with brains identified as abnormal by the algorithm. Since histopathological findings are considered to represent the "ground truth", our objective was to assess the sensitivity of aSTAND-scores to pathological AD staging. This was done by comparing antemortem MRI based aSTAND-scores with postmortem grading of disease severity in 101 subjects who had both antemortem MRI and postmortem Braak neurofibrillary tangle (NFT) staging. We found a rank correlation of 0.62 (p < 0.0001) between Braak NFT stage and aSTAND-scores. The results show that optimally extracted information from MRI scans such as STAND-scores accurately capture the severity of neuronal pathology and can be used as an independent approximate surrogate marker for in-vivo pathological staging as well as for early identification of AD in individual subjects.

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KW - Amnestic mild cognitive impairment

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KW - Magnetic resonance imaging

KW - Neurofibrillary tangles

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