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Jahandar Jahanipour
Department of Electrical and Computer
Engineering
University of Houston, TX
Deep Hierarchical Profiling & Pattern Discovery:
Application to Whole Brain Rat Slices After Traumatic
Brain Injury
Advisor:
Prof. Badrinath Roysam
Introduction
Concussion: disruption in the normal
function of the brain caused by a bump,
blow, …
 Headache
 Dizziness
 Depression
Chris
Henry
John Grimsley
2
1.5 atm Fluid percussion injury multiplexed imaging technique Whole brain rat slice
~ 300,000 cells
~ 3Gb
~32,000 ×47,000 pixels
Motivation: Computational data-driven image interpretation on large datasets
GOAL:
Profile tissue alterations in a manner that
is comprehensive , quantitative and
sensitive to multiple types of changes.
Deep Feature Extraction
 Nuclear morphological features
are not able to capture
thorough molecular signature.
 Associative features are
dependent on nuclear
segmentation of object.
3
NeuN+
NeuN-
40µm
NeuN
DAPI+Histones
Conventional Cytometric Features:
Deep Features:
Nuclear segmentation of cells using DAPI +Histone channels.
Scattering network formed by wavelet-modulus
cascading.
 Deep features capture
basal cell morphology and
molecular distribution,
JOINTLY.
Can We Perform Computationally Guided
Biological Interpretation?
Can we profile heterogeneity among cells?
4
S100 GFAP
200 µm
20µm
20µm
20µm
Is there any relation between activation level of a cell to the location of the
cell from the center of the injury?
GFAPAPCRECA-1IBA-1S100NeuNDAPI
Pipeline
5
DAPI
200 µm
Feature
Extraction
Using
Scattering
Net
Clustering
algorithm
Highly multiplexed
fluorescence image
Visualize the
clusters on the
image
Cell
Detection
Using Faster
RCNN
S100
GFAP
200 µm
Profiling Heterogeneity Within Same Structure
6
Astrocyte
Classification
Biomarkers for astrocyte phenotyping
S100 GFAP GLAST
Resting Astrocytes All (+) Subset (low) Subset (+)
Reactive Astrocytes All (+) All (high) All (+)
S100 GFAP
200 µm
S100-
S100+
S100+
S100-
All cells
Classifying astrocytes
within cortex
Astrocyte can be reconstructed using S100 and GFAP biomarkers for further analysis.
Li+VPa (treatment)
Profiling Cell Status Activation
7
S100 GFAP
200 µm
20µm 20µm20µm
S100+S100-
All cells
reactive resting
highmoderate
Astrocyte
Classification
Biomarkers for astrocyte
phenotyping
S100 GFAP GLAST
Resting Astrocytes All (+)
Subset
(low)
Subset (+)
Reactive
Astrocytes
All (+) All (high) All (+)
Moderately active
astrocytes
Very active
astrocytes
Profiling of astrocytes’ activation status reveals the relation of each
cell’s location relative to the site of injury.
Distance to the injury activation
Li+VPa (treatment)
Profiling Heterogeneity Within Same Structure
8
200 µm
group 1
group 2
group 3
group 4
group 5
Oligo-glial markers
S100 APC MBP PLP
Laminar-like pattern
resembling cortical
neuronal layers using
oligo-glial biomarkers:
Identifying 5
different cell
subpopulations
organized in
cortical layer
fashion
Profiling of oligo-glial biomarkers to discriminate cortical layers.
LiVPa

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Deep Hierarchical Profiling & Pattern Discovery: Application to Whole Brain Rat Slices After Traumatic Brain Injury - by Jahandar Jahanipour

  • 1. Jahandar Jahanipour Department of Electrical and Computer Engineering University of Houston, TX Deep Hierarchical Profiling & Pattern Discovery: Application to Whole Brain Rat Slices After Traumatic Brain Injury Advisor: Prof. Badrinath Roysam
  • 2. Introduction Concussion: disruption in the normal function of the brain caused by a bump, blow, …  Headache  Dizziness  Depression Chris Henry John Grimsley 2 1.5 atm Fluid percussion injury multiplexed imaging technique Whole brain rat slice ~ 300,000 cells ~ 3Gb ~32,000 ×47,000 pixels Motivation: Computational data-driven image interpretation on large datasets GOAL: Profile tissue alterations in a manner that is comprehensive , quantitative and sensitive to multiple types of changes.
  • 3. Deep Feature Extraction  Nuclear morphological features are not able to capture thorough molecular signature.  Associative features are dependent on nuclear segmentation of object. 3 NeuN+ NeuN- 40µm NeuN DAPI+Histones Conventional Cytometric Features: Deep Features: Nuclear segmentation of cells using DAPI +Histone channels. Scattering network formed by wavelet-modulus cascading.  Deep features capture basal cell morphology and molecular distribution, JOINTLY.
  • 4. Can We Perform Computationally Guided Biological Interpretation? Can we profile heterogeneity among cells? 4 S100 GFAP 200 µm 20µm 20µm 20µm Is there any relation between activation level of a cell to the location of the cell from the center of the injury?
  • 6. Profiling Heterogeneity Within Same Structure 6 Astrocyte Classification Biomarkers for astrocyte phenotyping S100 GFAP GLAST Resting Astrocytes All (+) Subset (low) Subset (+) Reactive Astrocytes All (+) All (high) All (+) S100 GFAP 200 µm S100- S100+ S100+ S100- All cells Classifying astrocytes within cortex Astrocyte can be reconstructed using S100 and GFAP biomarkers for further analysis. Li+VPa (treatment)
  • 7. Profiling Cell Status Activation 7 S100 GFAP 200 µm 20µm 20µm20µm S100+S100- All cells reactive resting highmoderate Astrocyte Classification Biomarkers for astrocyte phenotyping S100 GFAP GLAST Resting Astrocytes All (+) Subset (low) Subset (+) Reactive Astrocytes All (+) All (high) All (+) Moderately active astrocytes Very active astrocytes Profiling of astrocytes’ activation status reveals the relation of each cell’s location relative to the site of injury. Distance to the injury activation Li+VPa (treatment)
  • 8. Profiling Heterogeneity Within Same Structure 8 200 µm group 1 group 2 group 3 group 4 group 5 Oligo-glial markers S100 APC MBP PLP Laminar-like pattern resembling cortical neuronal layers using oligo-glial biomarkers: Identifying 5 different cell subpopulations organized in cortical layer fashion Profiling of oligo-glial biomarkers to discriminate cortical layers. LiVPa