Let’s Talk Informatics - Nova Scotia Health Authority...Let’s Talk Informatics Translational...

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Let’s Talk Informatics Translational Research in Medical Imaging Informatics in Nova Scotia with a focus on Machine Learning Drs. S. Beyea, S. Clarke and A. Guida [14-11-2019] Bethune Ballroom, Halifax, Nova Scotia

Transcript of Let’s Talk Informatics - Nova Scotia Health Authority...Let’s Talk Informatics Translational...

Page 1: Let’s Talk Informatics - Nova Scotia Health Authority...Let’s Talk Informatics Translational Research in Medical Imaging Informatics in Nova Scotia with a focus on Machine Learning

Let’s Talk Informatics

Translational Research in Medical Imaging Informatics in Nova Scotia with a focus on Machine Learning

Drs. S. Beyea, S. Clarke and A. Guida

[14-11-2019]

Bethune Ballroom, Halifax, Nova Scotia

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Please be advised that we are currently in a controlled vendor environment for the

One Person One Record project.

Please refrain from questions or discussion related to the

One Person One Record project.

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Informatics…

utilizes health information and health care technology to enable patients to receive best treatment and best outcome possible.

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Clinical Informatics…is the application of informatics and information technology to deliver

health care. AMIA. (2017, January 13). Retrieved from https://www.amia.org/applications-infomatics/clinical-

informatics

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Objectives At the conclusion of this activity, participants will be able to…

▫ Identify what knowledge and skills health care providers will need to use information now and in the future.

▫ Prepare health care providers by introducing them to concepts and local experiences in Informatics.

▫ Acquire knowledge to remain current with new trends, terminology , studies, data and breaking news.

▫ Cooperate with a network of colleagues establishing connections and leaders that will provide assistance and advice for business issues, as well as for best-practice and knowledge sharing.

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• Session specific objective #1: Have a representative overview of medical imaging informatics research at NSHA

• Session specific objective #2: Understand how machine learning can potentially impact clinical care

• Session specific objective #3: Gain an intuition on how Convolutional Neural Networks work

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Conflict of Interest Declaration

• The presenters have received investigator sponsored research funding from GE Healthcare, and in-kind contributions to research from Synaptive Medical

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The Biomedical Translational

Imaging Centre (BIOTIC)

Prof. Steven Beyea, Ph.D.

An overview of imaging & informatics research

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What is BIOTIC?

BIOmedical Translational Imaging Centre

✔ Research facility of the hospitals with a mandate to translate

medical innovations through clinical and industry partnership

✔ Integrated leadership in both science and innovation/business

development

✔ Straddle the academic, clinical and commercial worlds

✔ An open access centre in which equipment and expertise can be

utilized by researchers across the hospitals and universities

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Purposefully crossing the siloes

Embedded in the region’s largest

tertiary care hospitals

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Clinical Imaging Research Infrastructure

* Clinical imaging facilities provide access

to non-invasive technologies for brain

and body imaging in humans

* Access to pediatric and adult patient

populations

* Connections with clinicians to explore

clinical research opportunities

* 3T MRI (MR750), 306-channel MEG,

Point of Care MRI (coming soon in

2019!)

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Pre-Clinical Research Infrastructure

* Pre-clinical imaging facilities provide

access to non-invasive technologies

for imaging in rodent models

* A fully-equipped biological level 2

lab and an onsite animal care facility

with a special quarantine area

allows for longitudinal studies

* Simultaneous MRI/PET, and

PET/SPECT/CT

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Improving Treatment Planning

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Studying Health System “Value” of New Tech

* MRI will be installed Fall 2019 - $2.1M

in external funding

* Primarily dedicated to patients with

new onset neurological symptoms

arriving in the ED

* Can a rapid screening MR improve

diagnostic confidence, in particular for

“negative” scans

* 4-year study of “value” to health

system

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Diagnostic Biomarkers

Day 0 Day 4 Day 11

Fat Fraction

(TR corrected)

Surrogate

Unsaturation Index

(UIs)

Quantitative Mapping of Fatty

Acid Composition using Free-

Breathing Spectroscopic

Imaging with Blind Compressed

Sensing (accepted to NMR in

Biomedicine)

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AI/ML: Computer Assisted Diagnosis

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Clinical Motivation for AIProstate Cancer

Sharon Clarke, MD PhD

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• 2nd most frequently diagnosed cancer and the 6th leading cause of cancer death among men worldwide

• ~24,000 new cases in 2015; 25% of new cancers in men

• Diagnosis - random biopsy of the prostate gland based on clinical suspicion and/or rising PSA

• Cancers can be missed, resulting in delayed diagnosis, and in some cases, a missed chance for cure; conversely, overtreatment can occur

Scope of the Problem

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What is Multi-parametric MRI?

MRI can obtain detailed images of the prostate with several different contrasts

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Why Multi-parametric MRI?

• MRI can non-invasively identify suspicious lesions that can subsequently be targeted for biopsy

T2 ADC DCE

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Why Multi-parametric MRI?

• Cancer Staging and Localization

Case 1 Case 2

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MRI 2017 MRI 2019

Why Multi-parametric MRI?

Active Surveillance

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• PROMIS trial - Lancet. 2017 Feb 25;389(10071):815-822.

▫ “.... data provide a strong argument for recommending MP-MRI to all men with an elevated serum PSA before biopsy.”

• PRECISION trial - N Engl J Med. 2018 Mar 18.

▫ “MRI, with or without targeted biopsy, led to fewer men undergoing biopsy, more clinically significant cancers being identified, less over-detection of clinically insignificant cancer… than did TRUS-guided biopsy.”

Paradigm Shift

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• PROMIS trial ▫ “there was only moderate agreement of MP-MRI scores between

two independent radiologists.… highlights the necessity for a robust training programme for radiologists.”

• PRECISION trial ▫ …moderate agreement between the site and the central

radiologist… highlights the need for further research regarding improvements to the standardization, reproducibility, and reporting of MP-MRIs.”

Room for improvement

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• Evaluation is time-consuming for radiologists, and a natural candidate for machine learning approaches

Detection of Prostate Cancer

T2

ADC

DCE

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Machine Learning PCa Detection

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• Develop a protocol and validate CAD system for 1.5T MRI

• Scans done elsewhere could be used to further train and improve the

model

• Improve Radiologists’ diagnostic accuracy, efficiency and inter-

observer variability; evaluate changes over time in tumour

• Application to measuring tumour volume over time in other organs

Value and Clinical Impact

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Convolutional Neural Networks (CNN)to identify and localize prostate cancer

Alex Guida, Ph.D.

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Feature engineering

input

feature

engineeringfeatures classifier prediction

person

domain

knowledge

manual extraction, selection,

mathematical modelling

lines, curves, edges

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Feature engineering

input prediction

person

end-to-end learning

(representation learning)

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CNN classification

Input: image

Output: object class

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The “Anatomy” of an image

black and

white image

0

0 1 1 1 0

0 1 0 0 0

0 1 1 1 0

0 1 0 0 0

0 1 1 1 0

image matrix

pixel

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Convolutions

Image matrix

1 1 1 0 0

0 1 1 1 0

0 0 1 1 1

0 0 1 1 0

0 1 1 0 0

1 0 1

0 1 0

1 0 1

Filters (also called Kernels or

receptive fields)

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1 0 1

0 1 0

1 0 1

1 1 1 0 0

0 1 1 1 0

0 0 1 1 1

0 0 1 1 0

0 1 1 0 0

Convolutions

Convolution

Convolution FunctionSummary(element wise image and filter matrix multiplication)

Filters (also called Kernels or

receptive fields)

Image matrix

1*1 + 1*0 + 1*1 +0*0 + 1*1 + 1*0 +0*1 + 0*0 + 1*1 = 4

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Convolutions

Convolution

Convolution FunctionSummary(element wise image and filter matrix multiplication)

1 1 1 0 0

0 1 1 1 0

0 0 1 1 1

0 0 1 1 0

0 1 1 0 0

1 0 1

0 1 0

1 0 1

Filters (also called Kernels or

receptive fields)

Image matrix

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Convolutions

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Convolutions

Horizontal line filter

-1 -1 -1

2 2 2

-1 -1 -1

original convolved

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Convolutions

Horizontal line filter

0 -1 0

-1 4 -1

0 -1 0

Laplacian operator

-1 -1 -1

2 2 2

-1 -1 -1

original convolved

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Convolutions

? ? ?

? ? ?

? ? ?

What filters do we need for

our model?

feature

engineering

domain

knowledge

manual extraction, selection,

mathematical modelling

let the model find the

optimal filter that optimizes

the prediction

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CNN classification

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CNN classificationCommon CNN deep network architectures:

● LeNet-5

● AlexNet

● VGG

● GoogLeNet

● ResNet

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CNN classificationCommon CNN deep network architectures:

● LeNet-5

● AlexNet

● VGG

● GoogLeNet

● ResNet

ImageNet Challenge:

3.2 million labelled images, 5247

categories

From 2010 started with 71.8% score

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CNN classificationCommon CNN deep network architectures:

● LeNet-5

● AlexNet - 2012 - 84.6 %

● VGG

● GoogLeNet

● ResNet● ReLU

● 5 convs + maxpool

● 3 Fully connected layers

● Dropout

● Local response normalization

About ~12% discard

over 2nd best

performing model

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CNN classificationCommon CNN deep network architectures:

● LeNet-5

● AlexNet - 2012 - 84.6 %

● VGG - 2013 - 92.7 %

● GoogLeNet

● ResNet

● Many small filters instead of few large filters in

the first layers

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CNN classificationCommon CNN deep network architectures:

● LeNet-5

● AlexNet - 2012 - 84.6 %

● VGG - 2013 - 92.7 %

● GoogLeNet - 2014 - 93.3 %

● ResNet - 2016 - 96.4%

ImageNet Challenge:

3.2 million labelled images, 5247

categories

From 2010 to 2017, accuracy improved

from 71.8% to 97.3%

2017 - 97.3%

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Machine learning tasks

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non-cancer

Cancer

Ground-truth

Non prostate tissue

Cancer prediction heatmap

● Build a predictive model capable of identifying, with voxel level resolution, cancer regions in the

prostate

● Integrate the model in the clinical routine to evaluate effectiveness

Semantic Segmentation

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Car 60%

Trees 70%

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Car 60%

Trees 70%

INFORMATION IS

ENCODED

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Car 60%

Trees 70%

INFORMATION IS

ENCODEDINFORMATION IS

ENCODED

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Deconvolution..also called “upsampling” or “fractionally strided convolution” and “sub-pixel”, “transposed convolutional layer”

http://warmspringwinds.github.io/tensorflow/tf-slim/2016/11/22/upsampling-and-image-segmentation-with-tensorflow-and-tf-slim/

Low resolution High resolution

image

filter

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Semantic Segmentation

what

wherewhere

convolution de-convolution

Biomedical application

2015

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Dataset

● 16 subjects

● All subjects underwent radical prostatectomy

● Contrasts: T2, ADC, Ktrans

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Dataset

● 16 subjects

● All subjects underwent radical prostatectomy

● Contrasts: T2, ADC, Ktrans

T2

ADC

Ktranst1

T2

ADC

DCE

t2 t3 t4 ...

Acquired contrasts

transformationfrom 4D -> 3D

Preprocessed Dataset16 volumetric images

(512,512,48) with 3 contrast

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Dataset

● 16 subjects

● All subjects underwent radical prostatectomy

● Contrasts: T2, ADC, Ktrans

T2

ADC

Ktrans

Preprocessed Dataset16 x 4D images (512,512,48,3)

{ … }

Slicing along the axial plane48 (axial slices) * 16 patients = (512,512,3)

204 images of size (512,512,3) of the prostate

where 3 is the dimension that encodes the T2, ADC

and Ktrans contrasts

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Workflow

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Our CNN

what

wherewhere

convolution de-convolution

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No TTA

Test-Time Augmentation (TTA)

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With TTA

Test-Time Augmentation (TTA)

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Test-Time Augmentation (TTA)

No TTA with TTA

● regularizes the prediction● improves robustness of the model

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Predictions comparison

between different models

Subject S26

Subject S39

Logistic Regression

Random Forest

CNN + TTA + transfer learning

T2 contrast

non-cancer

Cancer

Ground-truth

Non prostate tissue

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Next Step - Comparing to human performance

error0%

10%

20%

30%

40%

...

Ground truth

Radiologist panel

Single radiologist

CNN

?

?

?

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MRIOrthanc

server

New

Dicom files

preprocessing Prostate

segmentation

Tumor

segmentation

CNN prediction pipeline

radiologist

New images

trigger launch

pipeline

Tumor

predictions as

dicom files

CNN deployed in Production

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preprocessing Prostate

segmentation

Tumor

segmentation

CNN prediction pipeline

Next Step - CNN Pipeline in Production

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preprocessing Prostate

segmentation

Tumor

segmentation

CNN prediction pipeline

Next Step - CNN Pipeline in Production

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Credits

Biotic Team involved in the project

● Peter Lee - coop student● David Hoar - coop student● Alex Guida - Data Scientist ● Steven Beyea - Biotic Scientific Director● Chris Bowen - Biotic Senior Researcher● Sharon Clarke - Project PI

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Nova Scotia Chapter for 1 Mainpro+ credit.▫ Digital Health Canada for 1CE hour for each

presentation attended. Attendees can track their continuing education hours through the HIMSS online tracking certification application, which is linked to their HIMSS account.

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