cortical gray matter segmentation on ex vivo t2w imaging

Elyse Migdal, Grace Choi, Sydney Lim, Eunice Chung, Noah Capp, Daniel Ohm, Winifred Trotman, David Irwin, David Wolk, John Detre, Paul Yushkevich, Shokufeh Sadaghiani Departments of Radiology and Neurology, University of Pennsylvania Introduction • Alzheimer’s disease neuropathological change is classically defined by tau and amyloid inclusions, but other pathologies including TDP-43 and alpha-synuclein may be present. • Cortical thickness serves as a biomarker of neurodegeneration and relates to disease progression. • Reduced cortical thickness in different brain regions correlates to different pathologies. • The purpose of this study is to determine the cortical thickness of various brain regions and assess whether they correlate with the neuropathology present. Analysis and Results • Each pathology was plotted against cortical thickness to determine which pathologies may lead to cortical thinning. • Evaluated data from 21 subjects with autopsy confirmation of Alzheimer’s Disease Methods • ITK-SNAP was used to model the cortical thickness of 18 brain regions in 35 subjects. • Cortical grey matter was manually segmented in one slice of a post-mortem T2- weighted MRI scan. • A trained classifier semi-automatically segmented the other slices, with some manual edits necessary. • A 3D patch of cortex called a “pancake” was produced by stitching together multiple layers of segmented cortex. • ParaView was used to calculate the cortical thickness of the brain regions. • The fully-segmented “pancakes” were uploaded and a sphere was inscribed in each one. • The diameter of the sphere was equivalent to the width of the pancake and therefore the cortical thickness of the brain region. The Correlation between Cortical Thickness and Neuropathologies/Age Pathologies Tau TDP -43 Neuron Loss Age Cortical Thickness of Brain Regions Angular Cortex r = -0.42 p = 0.0602 N/A r = -0.51 p = 0.0194 r = 0.33 p = 0.1441 Hippocampal Subregion CA1 r = 0.26 p = 0.3237 r = -0.35 p = 0.1858 r = -0.38 p = 0.1443 r = 0.03 p = 0.9218 Entorhinal Cortex r = -0.35 p = 0.1635 r = -0.46 p = 0.0638 r = -0.66 p = -0.0041 r = -0.06 p = 0.8119 Middle Frontal Cortex r = -0.26 p = 0.2625 r = 0.06 p = 0.8058 r = -0.23 p = 0.3158 r = -0.10 p = 0.6667 Visual Cortex r = -0.15 p = 0.5098 N/A r = 0.31 p = 0.1702 r = -0.15 p = 0.5035 Superior Temporal Cortex r = -0.27 p = 0.2529 r = 0.01 p = 0.9724 r = -0.00 p = 0.9955 r = -0.29 p = 0.2218 • As neuron loss increases, cortical thickness decreases. • As the presence of tau and TDP-43 pathologies increase, cortical thickness tends to decrease. • There does not appear to be a significant correlation between age and cortical thickness. • Future work will include a larger sample size and statistical analyses that take additional potentially confounding variables into account. • Future work may also involve using the method described to segment additional brain regions. Cortical Gray Matter Segmentation on Ex Vivo T2W Imaging and the Effect of Neurodegenerative Pathologies on Cortical Thinning Conclusions Example Graphs: Pathologies/Age vs. Cortical Thickness in the Entorhinal Cortex

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Page 1: Cortical Gray Matter Segmentation on Ex Vivo T2W Imaging

/Elyse Migdal, Grace Choi, Sydney Lim, Eunice Chung, Noah Capp, Daniel Ohm, Winifred Trotman, David Irwin, David Wolk, John Detre, Paul Yushkevich, Shokufeh Sadaghiani

Departments of Radiology and Neurology, University of Pennsylvania

Introduction• Alzheimer’s disease neuropathological change is classically defined by tau and

amyloid inclusions, but other pathologies including TDP-43 and alpha-synuclein may be present.

• Cortical thickness serves as a biomarker of neurodegeneration and relates to disease progression.

• Reduced cortical thickness in different brain regions correlates to different pathologies.• The purpose of this study is to determine the cortical thickness of various brain

regions and assess whether they correlate with the neuropathology present.

Analysis and Results• Each pathology was plotted against cortical thickness to determine which pathologies may lead to cortical thinning.• Evaluated data from 21 subjects with autopsy confirmation of Alzheimer’s Disease

Methods• ITK-SNAP was used to model the cortical thickness of 18 brain regions in 35

subjects.• Cortical grey matter was manually segmented in one slice of a post-mortem T2-

weighted MRI scan.• A trained classifier semi-automatically segmented the other slices, with some manual

edits necessary. • A 3D patch of cortex called a “pancake” was produced by stitching together multiple

layers of segmented cortex.

• ParaView was used to calculate the cortical thickness of the brain regions.

• The fully-segmented “pancakes” were uploaded and a sphere was inscribed in each one.

• The diameter of the sphere was equivalent to the width of the pancake and therefore the cortical thickness of the brain region.

The Correlation between Cortical Thickness and Neuropathologies/AgePathologies

Tau TDP-43 Neuron Loss Age

Cortical Thickness of Brain Regions

Angular Cortex r = -0.42p = 0.0602

N/A r = -0.51p = 0.0194

r = 0.33p = 0.1441

Hippocampal Subregion CA1

r = 0.26p = 0.3237

r = -0.35p = 0.1858

r = -0.38p = 0.1443

r = 0.03p = 0.9218

Entorhinal Cortex r = -0.35p = 0.1635

r = -0.46p = 0.0638

r = -0.66p = -0.0041

r = -0.06p = 0.8119

Middle Frontal Cortex r = -0.26p = 0.2625

r = 0.06p = 0.8058

r = -0.23p = 0.3158

r = -0.10p = 0.6667

Visual Cortex r = -0.15p = 0.5098

N/A r = 0.31p = 0.1702

r = -0.15p = 0.5035

Superior Temporal Cortex

r = -0.27p = 0.2529

r = 0.01p = 0.9724

r = -0.00p = 0.9955

r = -0.29p = 0.2218

• As neuron loss increases, cortical thickness decreases.• As the presence of tau and TDP-43 pathologies increase, cortical thickness tends to decrease.• There does not appear to be a significant correlation between age and cortical thickness.• Future work will include a larger sample size and statistical analyses that take additional potentially confounding

variables into account.• Future work may also involve using the method described to segment additional brain regions.

Cortical Gray Matter Segmentation on Ex Vivo T2W Imaging and the Effect of Neurodegenerative Pathologies on Cortical Thinning

Conclusions

Example Graphs:Pathologies/Age vs. Cortical Thickness in the Entorhinal Cortex

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