conflict of interest disclosure amanda f. khan, msc. medical biophysics has no real or apparent...
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Conflict of Interest Disclosure Amanda F. Khan, MSc. Medical Biophysics
Has no real or apparent conflicts of interest to report.
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Alzheimer’s Disease International – March 28th, 2011
Ventricle Sub-Region Segmentation Utilizing MRI as a Structural Ventricle Sub-Region Segmentation Utilizing MRI as a Structural Biomarker of Alzheimer’s DiseaseBiomarker of Alzheimer’s Disease
Amanda F. Khan Department of Medical Biophysics
Imaging Research LaboratoriesRobarts Research Institute
The University of Western Ontario
Supervisors: Dr. Michael Borrie, Dr. Robert Bartha
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The Ventricular System
Lateral ventricles
•structures containing CSF in the midbrain
•atrophy of surrounding tissues leads to increase in CSF volume
•increase in CSF = increase in lateral ventricles (surrogate measure)
•capture this increase on MRI, sometimes years before cognitive decline can be measured
3D image adapted from: The Biodidac
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Atrophy as Captured on MRI
Images adapted from: The Alzheimer's Disease Research Center, Florida
Normal AD
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NIH: AD Biomarker Criteria
Development of Specific AD Treatment Strategies
Requires
Ventricular Enlargement as a Biomarker
1 Dx in early stages when intervention is most effective
Can detect very early brain atrophy before cognitive decline can be measured
2 Treatment efficacy can be monitored
Serial MRI can measure atrophy (or lack thereof) over time in clinical trials in a way cognitive tests cannot
Source: NIH -Ways Towards an Early Diagnosis in Alzheimer’s Disease
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Hypothesis
That sub-region ventricular volume expansion, particularly that of the temporal horns, may be a more sensitive biomarker of disease progression than total ventricular volume
Normal Elderly Control AD Patient
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Alzheimer’s Disease Neuroimaging Initiative
ADNI
• 6 year multi-site study of NEC, MCI & AD
• 55 participating sites
• imaging, clinical + cognitive measures, biological samples
MRI
• 1.5T (T1 –weighted)
• MP-RAGE pulse sequence
Source of Map: The Alzheimer’s Disease Neuroimaging Initiative
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Methods
Baseline
NEC n=26
MCI n=42
AD n=29
Month 12 Month 24
• 97 subjects total• blinded segmentation• lateral ventricle volumes
extracted with software
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Brain Ventricle Quantification (BVQ)
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Ventricle Sub-Regions
Left and Right Hemispheres
Ventricle Sub-Region
Lateral Ventricle lateral anterior (LA) lateral middle (LM)
lateral posterior (LP)
Temporal Horn anterior horn (AH)posterior horn (PH)
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Preliminary Statistical Analysis
Procedure Data Used Evaluate
Repeated-measures ANOVA
Conducted on each sub-region over the 3 time
periods
Sub-region volumelongitudinal significance
Paired t-tests Post-hoc analysis to ANOVAs
Pair-wise significance between any two time points
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Normal Elderly Controls (NEC)
Temporal Horn Sub-Region
Significant?Type of Pairwise Significance
LPH YES Baseline and M24 Superior view of lateral (shades
of red) and temporal horn (green) regions
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Mild Cognitive Impairment (MCI)
Temporal Horn Sub-Region
Significant?Type of Pairwise Significance
LAH, RAH, LPH, RPH
YES Baseline and M24 Superior view of lateral (shades
of red) and temporal horn (green) regions
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Alzheimer’s Disease (AD)
Temporal Horn Sub-Region
Significant?Type of Pairwise Significance
LAH, RAH, LPH, RPH
YES Baseline and M24 Superior view of lateral (shades
of red) and temporal horn (green) regions
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Total Ventricle vs. Horn Volume
Normal controls: NO significant temporal horn enlargement
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Calculated Sample Sizes
Measure Patient Classification Calculated n Number
Temporal Horn Only AD 284
Total Ventricle AD 226
Temporal Horn Only MCI 1547
Total Ventricle MCI 420
ADAS-cog AD 3237
ADAS-cog MCI 2066
2
22/1
2
ˆ25.0
2
powerD zzn
Equation source: The ADNI Biostatistics Core
Estimated sample size required to detect a 25% reduction in the mean annual rate of atrophy in a two-sided test with α=0.05 for a two-arm study over one year
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Summary
• NEC AD more sub-regions show significant growth in more pair-wise comparisons
• MCI & AD significant enlargement in temporal horns, NEC do not
• Temporal horn: discriminate patients based on normal age-related atrophy and AD
• Smaller sample sizes for total ventricle than horn volumes but significantly smaller for both measures compared to ADAS-cog
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Acknowledgements
Supervisors:
Dr. Robert BarthaDr. Michael Borrie
Collaborators:
Matthew SmithYun-Hee Choi
Support:
Michael MarynowskiHenry BettaVaishali Karnik
Sources of Funding and Collaboration: