finding delphi in medical imaging - fondation the ark · 2015. 6. 12. · •prophylactic...

Finding Delphi in Medical

Imaging

Eldad Elnekave, MD

Chief Medical Officer

Zebra Medical Vision

“Because coronary heart disease is often manifested as sudden unexpected death… a preventative program is necessary”

-William B Kannel, MD, MPH

Who will die of CHD?

How can we change the course of a person’s future?

1948 Hypotheses on CVD

• Blood pressure? • Serum cholesterol levels? • Tobacco smoking? • Occasional alcohol intake? • Thyroid function? • Hemoglobin levels? • Body weight? • Diabetes? • Gout?

• 50 years (1950-1999)

• 811 Cardiac Deaths

• 400+ publications

• “The risk of Sudden Cardiac Death and nonsudden Coronary Heart Disease mortality have decreased by 49% to 64% over the past 50 years.”

Finding Delphi in Medical Imaging

600 BC – 400 AD 1948 2015

Big Data beginning to impact healthcare

Detrano et al., NEJM 2008

title

Wells et al., NEJM 2012

title

Pickhardtet al., Ann Int Med2013

“Predictive Analytics” & Finding Insight in the Voxels

• Which lung nodules are benign and which are malignant?

• Which heart failure patients are at highest risk for repeat exacerbations?

• Which COPD patients will respond best to steroids and who to antibiotics?

• Which colon cancers are surgically curable?

• Who is at highest risk for osteoporotic fractures and will benefit from prophylaxis?

We know the answers are there, in the voxels…

The Challenge: Extracting Insights Using Medical Imaging Algorithms

• Why? – The pace of radiology examinations is far outgrowing the

supply of radiologists – Even trained radiologists are often unable to decipher

imaging patterns detectable via machine learning

• How? – Creating the worlds largest indexed and annotated imaging

database – Allowing open access & collaborative space for

multidiscipline research teams and clinicians – Creating a regulatory pipeline and distribution channel to

bring innovations to real-world practice

Silos of Medical Imaging Datasets Limits Innovation and Validation

Public radiology databases remain relatively small & disease - modality specific

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Zebra launches the worlds largest database of de-identified, longitudinal medical imaging

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• ImageNet Large Scale

Visual Recognition Challenge 2014: • 38 Entrants from 13

Countries • Training: 456,567 Images •Validation: 20,121 Images

###,###,###

Talent-Silos Impede the Pace of Breakthrough Discoveries

Image Process Segmentation Registration

Transformation

Quantitative imaging

Unsupervised ML

Radiomics

Texture analysis

Semantic

Image Process Segmentation Registration

Transformation

Unsupervised ML

Radiomics

Clinical Rad

visualiz-ation

Semantic

Quantitative imaging Texture analysis

“Indication: Lung Cancer Screening”

1. No Acute Findings 2. Emphysema and coronary calcium

noted 3. 5mm x 6mm RUL nodule, 5mm x

4mm LLL nodule; recommend follow up exam in 6-12 months to assess for change.





1. RUL Nodule Feature Characterization = 98.6% Malignant

2. LLL Nodule Feature Assessment: 90% Benign Post Inflammatory

3. Left Adrenal Nodule Feature Characterization: 99.99% Benign Adenoma

4. Coronary risk stratification: 8.4 5. Lung parenchymal changes since

23 months prior: Overall 8.3 +6% 1. Bronchiectasis: 7.2, +12% 2. Emphysema 8.8, +9% 3. Bronchial wall thickening:

6.0 +2%

6. Osteoporotic risk score: -2.3 1. BMD: -2.0 2. Cortical thickness: 4 3. Medullary uniformity: 6 4. Trabecular thickness

7. Metabolic assessment: 7.33 1. Intra-abdominal fat 2. Liver Density

8. Cardiac chamber biometrics: 12.4 1. LV Thickness 2. Total Volume

The Radiologist, 1990

The Radiologist, 2015

!

The Zebra- Backed Radiologist (the Zebradiologist)

Thanks ;)

Questions?

[email protected]

Zebra//

is the medical slang for arriving at an exotic

medical diagnosis when a more

commonplace explanation is more likely.





1. RUL Nodule Feature Characterization = 98.6% Malignant

2. LLL Nodule Feature Assessment: 90% Benign Post Inflammatory

3. Left Adrenal Nodule Feature Characterization: 99.99% Benign Adenoma

4. Coronary risk stratification: 8.4 5. Lung parenchymal changes since

23 months prior: Overall 8.3 +6% 1. Bronchiectasis: 7.2, +12% 2. Emphysema 8.8, +9% 3. Bronchial wall thickening:

6.0 +2%

6. Osteoporotic risk score: -2.3 1. BMD: -2.0 2. Cortical thickness: 4 3. Medullary uniformity: 6 4. Trabecular thickness

7. Metabolic assessment: 7.33 1. Intra-abdominal fat 2. Liver Density

8. Cardiac chamber biometrics: 12.4 1. LV Thickness 2. Total Volume

Tourette

Hepatocellular Carcinoma Lymphoma Cholangiocarcinoma

Addisons ALS Beckwith-Wiedemann

Behcets

Pancreatic Adenocarcinoma Leukemia

Burkitt Lymphoma Craniofacial Dysostosis

Cushings

Osteomyelitis Osteoarthritis Coronary Artery Disease

DiGeorge Ebsteins Gardners Sturge-Weber

Peutz-Jeghers

Sarcoma Diabetes Colon Cancer Breast Cancer

Zollinger-Ellison Lesch-Nyhan Hirschsprung

Moyamoya

Rheumatoid Arthritis Aortic stenosis

Wegener Granulomatosis

Tolosa-Hunt

Wolff-Parkinson-White

Multiple Sclerosis Osteoporosis

Stroke

Hepatolenticular Degeneration

Hodgkins Lymphoma

Emphysema Non-small Cell Lung Cancer

Islet Cell Tumors

Results

• Subjects in the highest risk category had an almost six-fold risk of coronary artery events compared with those without detectable CAC.

• “Approximately 55% of study participants with intermediate to high risk and 43% of participants with very high risk of CVD events do not receive optimal treatment of CVD risk factors (antihypertensives or statins) – “Around 50% of these subjects actually had elevated BP or

lipids… all are likely to benefit from risk factor treatment because of their high CAC score alone…”

• In 1000 participants without a history of CHD, one would detect 175 subjects with a massively increased risk basee don CAC >1000 and of these, 84 subjects could benefit from starting preventative medical treatment.

• >1 million Osteoporosis-related fractures occur each year in the US alone.

• Prophylactic bisphosphonate treatment can reduce fracture risk by ~50% in osteoporotic individuals

• DEXA is the standard screening examination but it is severely underutilized:

• Fewer than 20% of fractures occur in people who have undergone DEXA and are under prophylaxis treatment.

• >100 million CT studies are performed in the US annually • Could CT scans obtained for whatever clinical indication be

used to assess bone mineral density and fracture risk? • 1867 Patients with CT and DEXA obtained within 6 months

from one another were assessed

Pickhart et al, Annals Internal Med 2013

Pickhart et al, Annals Internal Med 2013

Results

• An L1 CT-attenuation threshold of 160 HU or less was 90% sensitive and a threshold of 110 HU was more than 90% specific for distinguishing osteoporosis from osteopenia and normal BMD.

• Among 119 patients with at least 1 moderate-to-severe vertebral fracture, 62 (52.1%) had nonosteoporotic T-scores (DXA false-negative results), and most (97%) had L1 or mean T12 to L5 vertebral attenuation of 145 HU or less.

• Abdominal CT images obtained for other reasons that include the lumbar spine can be used to identify patients with osteoporosis or normal BMD without additional radiation exposure or cost.

• 1019 Patients with NSCLC or SCC

• 440 CT features • “Radiomics identifies a

general prognostic phenotype existing in both lung and head-and-neck cancer. This may provide an uprecedented opportunity to improve decision-support in cancer treatment at low cost.”

Results

“Texture parameters derived from CT images of NSCLC have the potential to act as imaging correlates for tumor hypoxia and angiogenesis”

CT Texure of Primary Colorectal Cancer predicts 5 year survival

• 140,000 people are diagnosed with colon cancer every year in the US.

• Of those who undergo surgery, (approximately 100,000) 30% will develop recurrence, usually within 3 years. Median time from recurrence to death is 12 months and most of these patients will recur with liver metastases.

• At present we have no way to predict which tumors have already released metastatic cells at the time of surgery. Current guidelines rely upon TNM staging to determine surgical and chemotherapy management, but can we improve?

Goh et al, Radiology 2014

“Texture analysis of primary colorectal cancers were predictive of 5-year survival as good as, and independent of, tumor staging. If this were validated, we might be able to change surveillance or even proactively treat at risk patients following surgical resection.”

finding delphi in medical imaging - fondation the ark · 2015. 6. 12. · •prophylactic...

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