Conflict of Interest Disclosure Amanda F. Khan, MSc. Medical Biophysics

Has no real or apparent conflicts of interest to report.

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

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

Atrophy as Captured on MRI

Images adapted from: The Alzheimer's Disease Research Center, Florida

Normal AD

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

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

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

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

Brain Ventricle Quantification (BVQ)

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)

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

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

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

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

Total Ventricle vs. Horn Volume

Normal controls: NO significant temporal horn enlargement

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

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

Acknowledgements

Supervisors:

Dr. Robert BarthaDr. Michael Borrie

Collaborators:

Matthew SmithYun-Hee Choi

Support:

Michael MarynowskiHenry BettaVaishali Karnik

Sources of Funding and Collaboration: