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Diagnosis of alzheimer's disease
with deep learning
2016. 7. 4
Seonho Park
2 / 42
Outline
Introduction to Machine Learning
Convolutional Neural Network
Diagnosing of Alzheimer’s disease
3 / 42
Introduction to Machine Learning
Convolutional Neural Network
Diagnosing of Alzheimer’s disease
4 / 42
Introduction to Machine Learning
x1
x2
x1
y
x1
x2
<Supervised Learning> <Unsupervised Learning>
classification regression clustering
Category of Machine Learning
문제 + 정답
문제 + 정답
문제 + 정답
데이터 + 레이블 머신러닝 학습
머신러닝 모델 정답 예측새로운 데이터
문제 + 정답
문제 + ???
분류 회귀
Cat
Computer
Lion
Pencil
Pig
레이블 없는 데이터 머신러닝 학습 군집화
5 / 42
Introduction to Machine Learning
Scikit-Learn
• Machine Learning Library in Python
• http://scikit-learn.org/
• Classification: Decision trees, SVM, NN
• Regression: GP, Ordinary LS, Ridge Regression, SVR
• Clustering: k-Means, Spectral Clustering
6 / 42
Introduction to Machine Learning
Why Deep Learning?
• Deep Learning = Deep Neural Network
• Data and Machine Learning
† http://cs229.stanford.edu/materials/CS229-DeepLearning.pdf
7 / 42
Introduction to Machine Learning
Artificial neural networks
Training = Find weights (parameters)
Inference = get output by specific input and trained weights
8 / 42
Introduction to Machine Learning
Convolutional Neural Network (CNN)
• Image Processing (Computer Vision)
9 / 42
Introduction to Machine Learning
Recurrent Neural Network (RNN)
• Time Series Data
• Natural Language Processing
• Translation, Speech Recognition, Auto Caption
• 자동번역, 음성인식, 이미지 캡션 생성 등에 활용
† Towards End-to-End Speech Recognition with Recurrent Neural Networks, Alex Graves et al (2014)
10 / 42
Introduction to Machine Learning
Why GPU?
• CuDNN: GPU-accelerated library of primitives for deep neural networks
• VRAM limitation, Double/Single/Half Precision
• Linear Algebra: CuBLAS, MAGMA
11 / 42
Introduction to Machine Learning
Frameworks
Cuda-ConvNetPylearn2
Lasagne
12 / 42
Introduction to Machine Learning
Open Sources for Deep Learning
† Comparative Study of Deep Learning Software Frameworks, Soheil Bahrampour et al (2015)
13 / 42
Introduction to Machine Learning
Pioneers
• Yann Lecun
• Geoffrey Hinton
• Yoshua Bengio
• Andrew Ng
• Jürgen Schmidhuber
14 / 42
Image Recognition Speech Recognition Auto Caption
Self Driving Car Natural Language Processing Recommendation System
Introduction to Machine Learning
Applications
15 / 42
Introduction to Machine Learning
Convolutional Neural Network
Diagnosing of Alzheimer’s disease
16 / 42
Convolutional Neural Network
Overview
• Classification
• Convolution Operation + MLP
• Architecture
• Convolutional Layer (Convolution Operator, Activation)
• Subsampling (Downsampling, Pooling)
• Fully Connected Layer
• Classifier
17 / 42
Convolutional Neural Network
LeNet5† Convolutional Operation
† Gradient Based Learning Applied to Document Recognition
, Yann LeCun et al (1998)
• Digit Recognition • Weight matrix (filter): 4D tensor
[# of feature at layer m,
# of features at layer m-1,
height, width]
18 / 42
Convolutional Neural Network
Activation function (nonlinearity)
† Systematic evaluation of CNN advances on the ImageNet, Dmytro Mishkin, et al (2016)
19 / 42
Convolutional Neural Network
Pooling Layer
• Erase Noise
• Reduce Feature Map Size (Memory Save)
† Systematic evaluation of CNN advances on the ImageNet, Dmytro Mishkin, et al (2016)
20 / 42
Convolutional Neural Network
Training
• Error(Loss) Function: Categorical Cross Entropy
• Design Variable: weights(W), bias(b)
• Backpropagation
conjunction with an optimization method
such as gradient descent
• Vanishing gradient
21 / 42
Convolutional Neural Network
Mini-Batch Method
• Computational Efficiency
• Memory Use
• Iteration & Epoch
Vanilla Gradient Descent
Stochastic Gradient Descent
• Parameter update for each training example x(i) and label y(i)
• Step size(η) is typically set to 10-3
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Convolutional Neural Network
Training (Optimization)
• Update Functions
• Second-order Method (L-BFGS) is not common in practice
• NAG is more standard
23 / 42
Convolutional Neural Network
Overfitting and Regularization
• Dropout
• Relaxation: Add Regularization Term to Loss Function
• Remove Layer (Reduce Parameters), Add Feature
† Dropout: A Simple Way to Prevent Neural Networks from Overfitting, Nitish Srivastava et al (2014)
24 / 42
Convolutional Neural Network
Local Optimum?
† Identifying and attacking the saddle point problem in high-dimensional non-convex optimization, Yann N. Dauphin et al (2014)
• Non-convex optimization problem
• deeper and more profound difficulty originates from the proliferation of saddle points, not
local minima, especially in high dimensional problems of practical interest
25 / 42
Convolutional Neural Network
Parallel Computation
• Architectural Parallel: Divide Channel
• Data Parallel: Divide Batch
26 / 42
ILSVRC
• Evaluate algorithms for object detection and image classification at large scale
• Training: 1.3M/ Test: 100k, 1000 categories
Convolutional Neural Network
27 / 42
AlexNet
• ILSVRC12 1st Place
• 15.3% error rate (2nd place achieved 26.5% error rate)
• Architecture Parallel (2GPU used)
† ImageNet Classification with Deep Convolutional Neural Networks, Alex Krizhevsky et al. (2012)
Convolutional Neural Network
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VGG Net
• DeepMind
• ILSVRC14 2nd Place
• 6.8% error rate
† VERY DEEP CONVOLUTIONAL NETWORKS FOR LARGE-SCALE IMAGE RECOGNITION, Karen Simonyan et al. (2014)
Convolutional Neural Network
29 / 42
GoogLeNet
• Google
• Inception module
• ILSVRC14 1st Place
• 6.67% error rate
† Going Deeper with Convolutions, Christian Szegedy et al. (2014)
Convolutional Neural Network
30 / 42
MSRA
• MicroSoft
• PReLU activation
• Weight initialization
• 4.94% error rate (Surpass Human Level, 5.1%)
† Delving Deep into Rectifiers: Surpassing Human-Level Performance on ImageNet Classification, Kaiming He et al. (2015)
Convolutional Neural Network
31 / 42
Inception-v3
• Google
• Inception Module Upgrade
• 50 GPUs
• 3.46% error rate
• Public Use with TensorFlow
† Going Deeper with Convolutions, Christian Szegedy et al. (2015)
Convolutional Neural Network
32 / 42
Convolutional Neural Network
Deep Neural Networks are Easily Fooled†
† Deep Neural Networks are Easily Fooled: High Confidence Predictions for Unrecognizable Images, A Nguyen et al (2014)
• It is possible to produce images totally unrecognizable to
human eyes
• interesting differences between human vision and current DNNs
• raise questions about the generality of DNN computer vision
33 / 42
Convolutional Neural Network
Neural Style
† A Neural Algorithm of Artistic Style, Leon A. Gatys et al (2014)
• Style + Contents reconstruction
• Caffe framework
• https://github.com/jcjohnson/neural-style
34 / 42
Introduction to Machine Learning
Convolutional Neural Network
Diagnosing of Alzheimer’s disease
35 / 42
Diagnosing of Alzheimer’s disease
Traditional Diagnosis of Alzheimer’s disease
• Review medical history
• Mini Mental Status Exam
• Physical Exam
• Neurological Exam
• Brain Image: Structural(MRI,CT), Functional(fMRI)
• NC(Normal Condition), MCI(Mild Cognitive Impairment), AD
• AD: Vascular/Non-Vascular
36 / 42
Diagnosing of Alzheimer’s disease
AD Patients’ MRI Features
• Temporal Lobe: Hippocampus
• Ventricle
37 / 42
Diagnosing of Alzheimer’s disease
Case Study: Machine Learning for diagnosing of AD
• PET, MRI images
• Patch Extraction
• Restrict Bolzmann Machine
• Accuracy: 92.4%(MRI), 95.35%(MRI+PET)
† Hierarchical feature representation and multimodal fusion with deep learning for AD/MCI diagnosis, Heung-Il Suk et al (2014)
38 / 42
Diagnosing of Alzheimer’s disease
Case Study: Machine Learning for diagnosing of AD
• Feature: Cortex Thickness
• FreeSurfer
• Linear discriminant analysis (LDA)
• Accuracy: Sensitivity: 82%, Specificity: 93%
† Individual subject classification for Alzheimer’s disease based on incremental learning using a
spatial frequency representation of cortical thickness data, Young-Sang Cho et al (2012)
39 / 42
Diagnosing of Alzheimer’s disease
Preprocessing
• Data Set: about 1400 of T1 MRI from SMC
• FreeSurfer: Skull Stripping: reduce size [256,256,256][190,190,190] / 67MB27MB
• Pixel Value Normalization [0,255]  [-1,1]
• Mirrored cropping
40 / 42
Diagnosing of Alzheimer’s disease
Architecture
• CNN
• Lasagne (Theano) Framework
• Inception Module, Batch Normalization
• 3D Convolution + CuDNN v3 (Github)
• 2 TITAN X GPU: Data Parallel (PyCUDA)
• Batch Size: 80
• Training Set
#Healthy Condition(HC): 761
#Alzheimer’s Disease (AD): 389
• Test Set
#Healthy Condition(HC): 105
#Alzheimer’s Disease (AD): 84
Data
41 / 42
Diagnosing of Alzheimer’s disease
Architecture
input
24*Conv11/5
MaxPool7/2
288*Conv3/2
FC120
DropOut
SoftMax
input
36*Conv16/6
MaxPool3/2
120*Conv4/1
BatchNorm
MaxPool3/2
60*Conv1/1
96*Conv3/1
12*Conv1/1
24*Conv5/124*Conv1/1
MaxPool3/1
48*Conv1/1
Concatenate
MaxPool3/2
FC150
128*Conv1/1
192*Conv3/1
32*Conv1/1
96*Conv5/164*Conv1/1
MaxPool3/1
128*Conv1/1
Concatenate
96*Conv1/1
208*Conv3/1
16*Conv1/1
48*Conv5/164*Conv1/1
MaxPool3/1
192*Conv1/1
Concatenate
SoftMax
input
60*Conv10/2
MaxPool2/2
144*Conv3/1
BatchNorm
MaxPool3/2
48*Conv1/1
72*Conv3/1
18*Conv1/1
36*Conv5/148*Conv1/1
MaxPool3/1
48*Conv1/1
Concatenate
MaxPool3/2
FC500
96*Conv1/1
208*Conv3/1
16*Conv1/1
48*Conv5/164*Conv1/1
MaxPool3/1
192*Conv1/1
Concatenate
160*Conv1/1
320*Conv3/1
32*Conv1/1
128*Conv5/1128*Conv1/1
MaxPool3/1
256*Conv1/1
Concatenate
SoftMax
280*Conv1/1
340*Conv3/1
32*Conv1/1
128*Conv5/1128*Conv1/1
MaxPool3/1
228*Conv1/1
Concatenate
AvgPool3/1
MidasNet1
MidasNet2
MidasNet3
42 / 42
Convergence History
Model Accuracy
MidasNet1 167/189 (88.4%)
MidasNet2 169/189 (89.4%)
MidasNet3 169/189 (89.4%)
0.01
0.1
1
10
0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190
Cost
Epoch
Diagnosing of Alzheimer’s disease
Result
Thank You

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Convolutional Neural Network for Alzheimer’s disease diagnosis with Neuroimaging

  • 1. 1 / 42 Diagnosis of alzheimer's disease with deep learning 2016. 7. 4 Seonho Park
  • 2. 2 / 42 Outline Introduction to Machine Learning Convolutional Neural Network Diagnosing of Alzheimer’s disease
  • 3. 3 / 42 Introduction to Machine Learning Convolutional Neural Network Diagnosing of Alzheimer’s disease
  • 4. 4 / 42 Introduction to Machine Learning x1 x2 x1 y x1 x2 <Supervised Learning> <Unsupervised Learning> classification regression clustering Category of Machine Learning 문제 + 정답 문제 + 정답 문제 + 정답 데이터 + 레이블 머신러닝 학습 머신러닝 모델 정답 예측새로운 데이터 문제 + 정답 문제 + ??? 분류 회귀 Cat Computer Lion Pencil Pig 레이블 없는 데이터 머신러닝 학습 군집화
  • 5. 5 / 42 Introduction to Machine Learning Scikit-Learn • Machine Learning Library in Python • http://scikit-learn.org/ • Classification: Decision trees, SVM, NN • Regression: GP, Ordinary LS, Ridge Regression, SVR • Clustering: k-Means, Spectral Clustering
  • 6. 6 / 42 Introduction to Machine Learning Why Deep Learning? • Deep Learning = Deep Neural Network • Data and Machine Learning † http://cs229.stanford.edu/materials/CS229-DeepLearning.pdf
  • 7. 7 / 42 Introduction to Machine Learning Artificial neural networks Training = Find weights (parameters) Inference = get output by specific input and trained weights
  • 8. 8 / 42 Introduction to Machine Learning Convolutional Neural Network (CNN) • Image Processing (Computer Vision)
  • 9. 9 / 42 Introduction to Machine Learning Recurrent Neural Network (RNN) • Time Series Data • Natural Language Processing • Translation, Speech Recognition, Auto Caption • 자동번역, 음성인식, 이미지 캡션 생성 등에 활용 † Towards End-to-End Speech Recognition with Recurrent Neural Networks, Alex Graves et al (2014)
  • 10. 10 / 42 Introduction to Machine Learning Why GPU? • CuDNN: GPU-accelerated library of primitives for deep neural networks • VRAM limitation, Double/Single/Half Precision • Linear Algebra: CuBLAS, MAGMA
  • 11. 11 / 42 Introduction to Machine Learning Frameworks Cuda-ConvNetPylearn2 Lasagne
  • 12. 12 / 42 Introduction to Machine Learning Open Sources for Deep Learning † Comparative Study of Deep Learning Software Frameworks, Soheil Bahrampour et al (2015)
  • 13. 13 / 42 Introduction to Machine Learning Pioneers • Yann Lecun • Geoffrey Hinton • Yoshua Bengio • Andrew Ng • Jürgen Schmidhuber
  • 14. 14 / 42 Image Recognition Speech Recognition Auto Caption Self Driving Car Natural Language Processing Recommendation System Introduction to Machine Learning Applications
  • 15. 15 / 42 Introduction to Machine Learning Convolutional Neural Network Diagnosing of Alzheimer’s disease
  • 16. 16 / 42 Convolutional Neural Network Overview • Classification • Convolution Operation + MLP • Architecture • Convolutional Layer (Convolution Operator, Activation) • Subsampling (Downsampling, Pooling) • Fully Connected Layer • Classifier
  • 17. 17 / 42 Convolutional Neural Network LeNet5† Convolutional Operation † Gradient Based Learning Applied to Document Recognition , Yann LeCun et al (1998) • Digit Recognition • Weight matrix (filter): 4D tensor [# of feature at layer m, # of features at layer m-1, height, width]
  • 18. 18 / 42 Convolutional Neural Network Activation function (nonlinearity) † Systematic evaluation of CNN advances on the ImageNet, Dmytro Mishkin, et al (2016)
  • 19. 19 / 42 Convolutional Neural Network Pooling Layer • Erase Noise • Reduce Feature Map Size (Memory Save) † Systematic evaluation of CNN advances on the ImageNet, Dmytro Mishkin, et al (2016)
  • 20. 20 / 42 Convolutional Neural Network Training • Error(Loss) Function: Categorical Cross Entropy • Design Variable: weights(W), bias(b) • Backpropagation conjunction with an optimization method such as gradient descent • Vanishing gradient
  • 21. 21 / 42 Convolutional Neural Network Mini-Batch Method • Computational Efficiency • Memory Use • Iteration & Epoch Vanilla Gradient Descent Stochastic Gradient Descent • Parameter update for each training example x(i) and label y(i) • Step size(η) is typically set to 10-3
  • 22. 22 / 42 Convolutional Neural Network Training (Optimization) • Update Functions • Second-order Method (L-BFGS) is not common in practice • NAG is more standard
  • 23. 23 / 42 Convolutional Neural Network Overfitting and Regularization • Dropout • Relaxation: Add Regularization Term to Loss Function • Remove Layer (Reduce Parameters), Add Feature † Dropout: A Simple Way to Prevent Neural Networks from Overfitting, Nitish Srivastava et al (2014)
  • 24. 24 / 42 Convolutional Neural Network Local Optimum? † Identifying and attacking the saddle point problem in high-dimensional non-convex optimization, Yann N. Dauphin et al (2014) • Non-convex optimization problem • deeper and more profound difficulty originates from the proliferation of saddle points, not local minima, especially in high dimensional problems of practical interest
  • 25. 25 / 42 Convolutional Neural Network Parallel Computation • Architectural Parallel: Divide Channel • Data Parallel: Divide Batch
  • 26. 26 / 42 ILSVRC • Evaluate algorithms for object detection and image classification at large scale • Training: 1.3M/ Test: 100k, 1000 categories Convolutional Neural Network
  • 27. 27 / 42 AlexNet • ILSVRC12 1st Place • 15.3% error rate (2nd place achieved 26.5% error rate) • Architecture Parallel (2GPU used) † ImageNet Classification with Deep Convolutional Neural Networks, Alex Krizhevsky et al. (2012) Convolutional Neural Network
  • 28. 28 / 42 VGG Net • DeepMind • ILSVRC14 2nd Place • 6.8% error rate † VERY DEEP CONVOLUTIONAL NETWORKS FOR LARGE-SCALE IMAGE RECOGNITION, Karen Simonyan et al. (2014) Convolutional Neural Network
  • 29. 29 / 42 GoogLeNet • Google • Inception module • ILSVRC14 1st Place • 6.67% error rate † Going Deeper with Convolutions, Christian Szegedy et al. (2014) Convolutional Neural Network
  • 30. 30 / 42 MSRA • MicroSoft • PReLU activation • Weight initialization • 4.94% error rate (Surpass Human Level, 5.1%) † Delving Deep into Rectifiers: Surpassing Human-Level Performance on ImageNet Classification, Kaiming He et al. (2015) Convolutional Neural Network
  • 31. 31 / 42 Inception-v3 • Google • Inception Module Upgrade • 50 GPUs • 3.46% error rate • Public Use with TensorFlow † Going Deeper with Convolutions, Christian Szegedy et al. (2015) Convolutional Neural Network
  • 32. 32 / 42 Convolutional Neural Network Deep Neural Networks are Easily Fooled† † Deep Neural Networks are Easily Fooled: High Confidence Predictions for Unrecognizable Images, A Nguyen et al (2014) • It is possible to produce images totally unrecognizable to human eyes • interesting differences between human vision and current DNNs • raise questions about the generality of DNN computer vision
  • 33. 33 / 42 Convolutional Neural Network Neural Style † A Neural Algorithm of Artistic Style, Leon A. Gatys et al (2014) • Style + Contents reconstruction • Caffe framework • https://github.com/jcjohnson/neural-style
  • 34. 34 / 42 Introduction to Machine Learning Convolutional Neural Network Diagnosing of Alzheimer’s disease
  • 35. 35 / 42 Diagnosing of Alzheimer’s disease Traditional Diagnosis of Alzheimer’s disease • Review medical history • Mini Mental Status Exam • Physical Exam • Neurological Exam • Brain Image: Structural(MRI,CT), Functional(fMRI) • NC(Normal Condition), MCI(Mild Cognitive Impairment), AD • AD: Vascular/Non-Vascular
  • 36. 36 / 42 Diagnosing of Alzheimer’s disease AD Patients’ MRI Features • Temporal Lobe: Hippocampus • Ventricle
  • 37. 37 / 42 Diagnosing of Alzheimer’s disease Case Study: Machine Learning for diagnosing of AD • PET, MRI images • Patch Extraction • Restrict Bolzmann Machine • Accuracy: 92.4%(MRI), 95.35%(MRI+PET) † Hierarchical feature representation and multimodal fusion with deep learning for AD/MCI diagnosis, Heung-Il Suk et al (2014)
  • 38. 38 / 42 Diagnosing of Alzheimer’s disease Case Study: Machine Learning for diagnosing of AD • Feature: Cortex Thickness • FreeSurfer • Linear discriminant analysis (LDA) • Accuracy: Sensitivity: 82%, Specificity: 93% † Individual subject classification for Alzheimer’s disease based on incremental learning using a spatial frequency representation of cortical thickness data, Young-Sang Cho et al (2012)
  • 39. 39 / 42 Diagnosing of Alzheimer’s disease Preprocessing • Data Set: about 1400 of T1 MRI from SMC • FreeSurfer: Skull Stripping: reduce size [256,256,256][190,190,190] / 67MB27MB • Pixel Value Normalization [0,255]  [-1,1] • Mirrored cropping
  • 40. 40 / 42 Diagnosing of Alzheimer’s disease Architecture • CNN • Lasagne (Theano) Framework • Inception Module, Batch Normalization • 3D Convolution + CuDNN v3 (Github) • 2 TITAN X GPU: Data Parallel (PyCUDA) • Batch Size: 80 • Training Set #Healthy Condition(HC): 761 #Alzheimer’s Disease (AD): 389 • Test Set #Healthy Condition(HC): 105 #Alzheimer’s Disease (AD): 84 Data
  • 41. 41 / 42 Diagnosing of Alzheimer’s disease Architecture input 24*Conv11/5 MaxPool7/2 288*Conv3/2 FC120 DropOut SoftMax input 36*Conv16/6 MaxPool3/2 120*Conv4/1 BatchNorm MaxPool3/2 60*Conv1/1 96*Conv3/1 12*Conv1/1 24*Conv5/124*Conv1/1 MaxPool3/1 48*Conv1/1 Concatenate MaxPool3/2 FC150 128*Conv1/1 192*Conv3/1 32*Conv1/1 96*Conv5/164*Conv1/1 MaxPool3/1 128*Conv1/1 Concatenate 96*Conv1/1 208*Conv3/1 16*Conv1/1 48*Conv5/164*Conv1/1 MaxPool3/1 192*Conv1/1 Concatenate SoftMax input 60*Conv10/2 MaxPool2/2 144*Conv3/1 BatchNorm MaxPool3/2 48*Conv1/1 72*Conv3/1 18*Conv1/1 36*Conv5/148*Conv1/1 MaxPool3/1 48*Conv1/1 Concatenate MaxPool3/2 FC500 96*Conv1/1 208*Conv3/1 16*Conv1/1 48*Conv5/164*Conv1/1 MaxPool3/1 192*Conv1/1 Concatenate 160*Conv1/1 320*Conv3/1 32*Conv1/1 128*Conv5/1128*Conv1/1 MaxPool3/1 256*Conv1/1 Concatenate SoftMax 280*Conv1/1 340*Conv3/1 32*Conv1/1 128*Conv5/1128*Conv1/1 MaxPool3/1 228*Conv1/1 Concatenate AvgPool3/1 MidasNet1 MidasNet2 MidasNet3
  • 42. 42 / 42 Convergence History Model Accuracy MidasNet1 167/189 (88.4%) MidasNet2 169/189 (89.4%) MidasNet3 169/189 (89.4%) 0.01 0.1 1 10 0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 Cost Epoch Diagnosing of Alzheimer’s disease Result