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Toward the Future of AI-Driven Medicine 葉肇元 醫師 雲象科技執行長

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Page 1: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Toward the Future of

AI-Driven Medicine

葉肇元 醫師

雲象科技執行長

Page 2: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

雲象科技

Bring state-of-the-art technology to healthcare.

Our Core

Our Mission

Our Goal

We’re a Medical Image AI company.

Empower medical imaging with A.I.

Page 3: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

A survey of deep learning in medical image analysis

Mammographic Mass Classification

Diabetic RetinopathyDetection

Breast CancerMetastasis Detection

Brain Lesion Segmentation

Airway Segmentation of Chest CT Image

Lung Nodule Detection

Bone Suppression in X-Ray Image

Skin DiseaseClassification

Prostate

Segmentation

Page 4: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Organs of interest for Medical Image AI

• Brain

• Brain tumor segmentation

• Disease classification

• Survival Prediction

• Eyes (Retina)

• DM retinopathy, cardiac risk factor

• Lungs

• Lung nodule detection

• Breast

• Breast cancer screening

• Heart

• Cardiac image analysis

• Intestine

• Polyp classification

• Prostate

• Prostate segmentation

• Bones

• Age determination

• Skins

• Disease classification

• Blood Vessels

• Blood vessel segmentation

• Blood

• Blood cell counting and classification

Page 5: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

• Authored by Google, Verily Life Sciences, and Stanford School of Medicine

• Inception-V3 Model trained on data from 236,234 patients from EyePACS , 48,101(UK Biobank), validated on data from 12,026 patients from UK Biobank, and 999 patients from EyePACS.

• Used Retinal Fundus Image to predict

• Age, gender, smoking status, BMI, systolic blood pressure, diastolic blood pressure

Poplin R, et al. Nature Biomedical Engineeringvolume 2, pages158–164(2018)

Page 6: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

MAE : Mean Absolute ErrorFor continuous risk factors (like age), the baseline value is the Mean Absolute Error of Predicting the mean value for all patients.

Page 7: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients
Page 8: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

The cost of making medical image AI not often talked about :

Time

Page 9: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Expected Timeline for a Medical Image AI Project

Required Skill Category:• Interdisciplinary Knowledge• Hospital Information System

Time(Month)

Identify Topic

Collect & Process

Data

Train & Validate ModelCollect More Data

Train & Validate Model

Deploy

2 4 6 8

• AI Software and Hardware• Healthcare Workflow

Page 10: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

In reality..

Time(Month)

Identify Topic Collect, Process and Label Data Train & Validate Model

2 4 6 8

Page 11: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Houston, we’ve got a problem.

• So it takes ten months to make one AI model happen (if you’re lucky).

• But there are thousands of clinical tasks that could potentially benefit from the help of A.I. !

• (How on earth can we replace Drs. with A.I. ?)

Page 12: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

How Do We Get There ?

Time(Month)

2 4 6 81

Identify TopicCollect Data

Train and Validate Model

Deploy

Page 13: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

What’s holding us back? Infrastructure.

• Hospital Information System

• AI Software and Hardware

• Interdisciplinary Knowledge

• Healthcare Workflow

Page 14: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Interdisciplinary Knowledge

Page 15: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Essential Ingredient of a Successful Medical Image AI Project

• Interdisciplinary knowledge

• Intricacies of medical diagnostic procedures

• Capabilities of different neural network models

• How medical data can be digested by neural networks and turned into insight

Page 16: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Our first attempt at Digital Pathology AI• Lymphoma screening using whole slide image

Page 17: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Digging into data : examining raw input

Dark Zone

Light Zone

Follicular Lymphoma

Mantle Zone

Tinged-Body Macrophage

Page 18: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Web interface for deep learning inferencing

Page 19: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Training statistics

Page 20: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Lymphoma Screening Model Used on Whole Slide Image

Page 21: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Improved Tools for Whole Slide Image Labeling

Page 22: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Dataset Statistics

• Labeled Training Slides : 56 Cancer, 56 Benign

• Total number of extracted patches

• Validation: ~40,000 patches

• Testing : ~40,000 patches

Benign Cancer Background

4,460,452 147,533 87,974

Page 23: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Neural Network Architecture

• Modified ResNet-50:

• Dense layer after Global Average Pooling for tissue / background binary classification

• Separate path with additional dense layers for cell type (cancer / benign) classification

Page 24: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Neural Network Training

• Heavy data augmentation

• Flipping (Up-down, left-right), Add, Multiply, Add to Hue and Saturation, Contrast Normalization, Gaussian Blur, Gaussian Noise

• Class balancing : random sampling of equal number from each class

• Optimizer : Adam Optimizer

• Early Stopping

Page 25: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Training Result

Foreground / background classification

Benign / Cancer classification

Loss

Accuracy

Page 26: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Statistics Of Validation Result

Page 27: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Testing Result

Recall = SensitivityPrecision = Positive Predictive Rate

Page 28: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Prediction on Separate Test SlidePrediction by Neural NetworkGround Truth

Yellow : Cancer, Blue : Benign Red : Predicted cancer region

Accuracy : 90.4 %, Precision : 93.4% , Recall : 93.0 %

Page 29: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Class Activation Map

Page 30: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

AI Software and Hardware

Page 31: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

• 1 Digital slide is larger than the entire CIFAR-10 dataset

• Digital slide : 80000*60000

• CIFAR-10 : 32*32*60000

Page 32: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Medical Images AI Needs a Lot of Memory

• Medical images have very high spatial resolution:

• Radiography image : 5000*4000 uint16

• CT image : 512*512*300 uint16

• Digital Slide : 60000*60000*3 uint8

• Average ImageNet image : 469*387*3 uint8

Page 33: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

GPU memory alone is not sufficientfor Medical Image AI

• For VGG-16, during training

• A GTX-1080Ti can take an image up to 1200*1200

• A Tesla P40 can take an image up to 1700*1700

• A Tesla V100 can take an image up to 2100*2100

• CUDA unified memory

Page 34: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

CUDA Unified Memory in Tensorflow

Page 35: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Specialized Hardware for AI Compute

A BREAKTHROUGH IN TRAINING AND INFERENCEEach of Tesla V100's 640 Tensor Cores operates on a 4x4 matrix, and their associated data paths are custom-designed to dramatically increase floating-point compute throughput with high-energy efficiency.

This key capability enables Volta to deliver 3X performance speedups in training and inference over the previous generation.

Page 36: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

The Power of Tensor Cores

0

2

4

6

8

10

12

14

16

GTX 1080 TI TITAN XP TITAN V

Ba

tch

es

pe

r se

con

d

Float 16 Batchsize 512

Development environment:

GTX 1080 Ti : Tensorflow 1.4, CUDA 8, cuDNN 5, nvidia-381 driver

Titan Xp : Tensorflow 1.4, CUDA 9, cuDNN 7, nvidia-387 driver

Titan V : Tensorflow 1.4, CUDA 9, cuDNN 7, nvidia-387 driver

Neural Network : Convolution * 6 + fully connected * 2 , trained on cifar-10* 2

0

2

4

6

8

10

12

14

16

GTX 1080 TI TITAN XP TITAN V

Ba

tch

es

pe

r se

con

dFloat32 Batchsize 512

Page 37: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

GPU is often thirsty : The Importance of Pipelining

9.7

15.2

8.1

4.2

2.33 2.28

0

2

4

6

8

10

12

14

16

1 CPU 2 CPU 4 CPU 8CPU 16 CPU

Training time per epoch

Without Queue

With Queue

Without Queue

With Queue

Page 38: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Healthcare Information System

Page 39: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Problems with Existing Hospital Information System

• Databases are not tightly connected

• Limited search functions

• The majority of data exists in unstructured format (.txt, .pdf, etc)

Page 40: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Unified Web Interface for Medical Image AI• Web-based system that integrates:

• Clinical data

• Digital slides

• DICOM images / videos

• Deep learning annotation, training and inferencing

Page 41: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Annotation Interface with Structured Reporting

Page 42: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Annotation and Image Markup (AIM)

• An NCI initiated project that provides a solution to the following imaging challenges:

• No agreed upon syntax for annotation and markup

• No agreed upon semantics to describe annotations

• No standard format (for example, DICOM, XML, HL7) for annotations and markup

• The link between the semantics and image annotation will help make more useful and more interpretable medical image AI.

https://wiki.nci.nih.gov/display/AIM/Annotation+and+Image+Markup+-+AIM

Page 43: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

AIM Example

Page 44: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Medical Record De-Identification

• Due to privacy concerns, AI research requires that personal identification information be removed from medical record.

• It’s hard to achieve satisfactory result using regular expression or other rule-based methods.

• Using tools like NeuroNER (name entity recognition), we’ve successfully achieved an F1 score of >97% on public dataset.

Page 45: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Next Generation IT Infrastructure for AI-Powered Hospital

Clinical Terminal• Structured Report for Both Clinical and AI use

Hybrid Storage• Fast : Cache for AI training• Slow : Data Archive

AI Training Server• High Compute Capacity• Job Queues for Non-Stop Learning

Main Server• High Availability• Advanced Database System• Job Flow Control

AI Inferencing Server•Virtualization for On-Demand AI Inferencing • Optimized for Inferencing Speed

Clinical Data Clinical Data

AI Model

AI Model

AI-Powered Diagnostic Aid

Page 46: Toward the Future of AI-Driven Medicine€¦ · •Authored by Google, Verily Life Sciences, and Stanford School of Medicine •Inception-V3 Model trained on data from 236,234 patients

Acknowledgement

• 長庚醫院病理科莊文郁副教授

• 長庚醫院巨量資料及統計中心張尚宏主任

• 臺大醫院心臟內科王宗道教授

• 臺大醫院影像醫學科李文正醫師

• 雲象科技張哲惟

• 雲象科技游為翔

• 雲象科技楊証琨

• 雲象科技蔡岳霖