BIOwulf

BIOwulf Radiology

Radiology

BIOwulf

RADIOLOGY

BIOwulf

TechnologiesGenomics

Radiology

BIOwulf

•Company Overview•Analytics•Current Projects•Future Applications

AgendaBIOwulf

RADIOLOGY

Company OverviewBIOwulf

BIOwulf

RADIOLOGY

People

Technology

Applications

Intellectual Property

Company OverviewBIOwulf

BIOwulf

RADIOLOGY

People

•Washington University

•St. Louis University

•Chief of Diagnostic Radiology

•25 years of practice

Garry Carls,M.D., M.B.A.

Garry Carls has Radiology experience in both the academic

and private practice arenas.

Company OverviewBIOwulf

BIOwulf

RADIOLOGY

People

•University of Pittsburgh

•Purdue University

•20+ Medical and Technical journals

•NCI – Ovarian cancer detection

Hong Zhang,Ph.D.

While attending college, Hong Zhang won a national

math competition in China.

Company OverviewBIOwulf

BIOwulf

RADIOLOGY

People

•Academy of Sciences in USSR

•Institute of Electrical Communications

•150+ published papers

•Pattern recognition

Shelia Guberman, Ph.D.

Shelia Guberman authored the first applied pattern

recognition program.

Company OverviewBIOwulf

BIOwulf

RADIOLOGY

People

•Illinois State University

•Merck Pharmaceuticals

•Analytical biochemistry

•Finance and marketing

Tony Barnes,Ph.D., M.B.A.

Tony Barnes holds a Ph.D. in analytical biochemistry from the

University of Illinois.

PHOTO

Company OverviewBIOwulf

BIOwulf

RADIOLOGY

PeoplePeople

Management Team

Peter Farley, M.D., MBA

Tony Barnes, Ph.D., MBA

Garry Carls, M.D., MBA

Russ Clark, JD

Katherine DeYoung, Ph.D.

Isabelle Guyon, Ph.D.

Ramananda Madyastha, M.D., Ph.D

Mary Napier, MS

Tim O’Hayer

Trey Rossiter, MBA

Michael Stern, MBA

Company OverviewBIOwulf

BIOwulf

RADIOLOGY

PeoplePeople

Mathematical Team

Peter Bartlett, Ph.D.

Asa Ben-Hur, Ph.D.

Olivier Bousquet, Ph.D.

Olivier Chappelle, Ph.D.

Nello Christianini, Ph.D.

Rene Doursat, Ph.D.

Andre Elisseeff, Ph.D.

Shelia Guberman, Ph.D.

Isabelle Guyon, Ph.D.

Bernhard Schoelkopf, Ph.D.

Vladimir Vapnik, Ph.D.

Jason Weston, Ph.D.

Hong Zhang, Ph.D.

Company OverviewBIOwulf

BIOwulf

RADIOLOGY

PeoplePeople

Science Advisory BoardVladimir N. Vapnik, Ph.D. (Co-Chairman)

AT&T Labs - Research

Herbert A. Fritsche, Jr., Ph.D. (Co-Chairman) University of Texas M.D. Anderson Cancer Center

Daniel W. Chan, Ph.D.John Hopkins University School of MedicineThe John Hopkins Hospital

Alexey Chervonenkis, Ph.D.Institute of Control Sciences, Russian Academy of

Sciences

Jeffery Cossman, M.D.Georgetown University Medical Center

Alex Gammerman, Ph.D.Royal Holloway College, University of London

Company OverviewBIOwulf

BIOwulf

RADIOLOGY

PeoplePeople

Science Advisory BoardFederico Girosi, PH.D.

Harvard University

Kelvin G. Lynn, Ph.D. Boeing Chair, Washington State University

Tomaso A. Poggio, Ph.D.Massachusetts Institute of Technology

Thomas A. Stamey, M.D.Stanford University School of Medicine

Morton Schwartz, Ph.D.Memorial Sloan-Kettering Cancer Center

John F.R. Robertson, M.D.The University of Nottingham

Company OverviewBIOwulf

BIOwulf

RADIOLOGY

PeoplePeople

Collaborations

Johns Hopkins University

M.D. Anderson Cancer Center

Stanford University

University of Nottingham

University of Cincinnati

Company OverviewBIOwulf

BIOwulf

RADIOLOGY

TechnologyTechnology

Supervised machine learning techniques

including Support Vector Machines.

Company OverviewBIOwulf

BIOwulf

RADIOLOGY

Applications

Life Sciences

Imaging

Financial

Seismic Geological

Telecom Internet

QualityManagement

Military

Company OverviewBIOwulf

BIOwulf

RADIOLOGY

Intellectual Property

Patents Issued & Pending 09/303,386 Pre-Processing and Post Processing for Enhancing Knowledge Discovery

Using Support Vector Machines.

09/303,387 Enhancing Knowledge Discovery Using Multiple Support Vector Machines.

09/303,389 Optimal Categorization of a Continuous Variable.

09/305,345 Enhancing Knowledge Discovery Using Support Vector Machines in a

Distributed Network Environment.

PCT/US99/09666 Pre-processing and Post Processing for Enhancing Knowledge DiscoveryUsing Support Vector Machines.

09/568,301 Enhancing Knowledge Discovery From Multiple Data Sets Using Multiple

Support Vector Machines.

09/578,011 Enhancing Knowledge Discovery from Multiple Datasets using Multiple

Support Vector Machines.

Company OverviewBIOwulf

BIOwulf

RADIOLOGY

Intellectual Property

Patents Issued & Pending60/161,806 Applications of SVMs in Genomics and Cancer Research.

PCT/US00/14326 Enhancing Knowledge Discovery from Multiple Datasets using Multiple Support Vector Machines.

09/633,850 Methods of Identifying Patterns in Biological Systems and Methods of Uses Thereof.

09/633,616 Enhancing Biological Knowledge Discovery Using Multiple Support Vector Machines.

09/633,615 Methods of Identifying Biological Patterns Using Optimal Categorization of a continuous variable.

09/633,627 Methods of Identifying Biological Patterns in a Distributed Network andMultiple Data sets.

60/168,703 Applications of SVMs in Genomics and Cancer Research ALL/AMLLeukemia Classifier.

Company OverviewBIOwulf

BIOwulf

RADIOLOGY

Intellectual Property

Patents Issued & Pending60/184,596 Applications of SVMs in Genomics and Cancer Research (Colon Cancer).

60/191,219 Gene Selection for Cancer Classification Using Support Vector Machines.

60/207,026 Applications of SVMs in Genomics and Cancer Research ALL/AMLLeukemia Classifier.

AnalyticsBIOwulf

BIOwulf

RADIOLOGY

AnalyticsBIOwulf

BIOwulf

RADIOLOGY

Machine Learning

Advantages of Machine Learning

•Data driven, automated learning

•May handle highly complex systems

•Can detect subtle patterns

AnalyticsBIOwulf

BIOwulf

RADIOLOGY

Machine Learning

Inversion of Convoluted Data

AnalyticsBIOwulf

BIOwulf

RADIOLOGY

Machine Learning

Methodologies

Holistic

Analytic

AnalyticsBIOwulf

BIOwulf

RADIOLOGY

Machine Learning

Holistic Methods

AnalyticsBIOwulf

BIOwulf

RADIOLOGY

Machine Learning

Analytic Methods

Preprocessing Learning Machine

AnalyticsBIOwulf

BIOwulf

RADIOLOGY

Machine Learning

Analytic Tools

Radon

WaveletFFT

ANNKernel PCA

PCA LDA

SVM

Perceptron

HMM

Learning Machines

Feature Extraction

RKHS …

…

Hough Splines

AnalyticsBIOwulf

BIOwulf

RADIOLOGY

Machine Learning

Designer Math: An Evolutional Process

•Custom designed mathematical techniques focused on specific

real problems

•Cross-training between mathematicians and

biologists/physicians/other experts

•Applications of cutting edge mathematical theories

•Integration of expert domain knowledge

AnalyticsBIOwulf

BIOwulf

RADIOLOGY

Machine Learning

Domain Specific Solutions

TheoreticalFoundation

BIOwulf will extract pertinent knowledge by using the raw data, incorporating domain specific expertise in biology, applying leading mathematical theory, developing customized algorithms, and including the outcome feedback to fine tune predictive solutions.

Fine TuneTo Problem

AlgorithmDevelopment

DataDomain Expertise

Problem Solving Cycle

AnalyticsBIOwulf

BIOwulf

RADIOLOGY

Imaging

Example: Imaging

•Combination of radiology, machine learning, image processing,

and mathematical analysis

•Effective algorithm based on radiologists’ knowledge

•Customized SVM for “transduction”

AnalyticsBIOwulf

BIOwulf

RADIOLOGY

Imaging

Example: Imaging

•Modified SVM with variable input size and adjustable

regularizations

•Innovative feature extractions (e.g., Radon transform)

•Unparalleled accuracy in initial calcification detection system

AnalyticsBIOwulf

BIOwulf

RADIOLOGY

Imaging

Imaging Related IP

• A holistic method for computer aided automatic detection of micro calcification clusters in mammogram images.• Support vector machine based system for multi-spectra image analyses.• Mammogram feature selection based on Radon transform.• Combining image data with clinical information using kernel techniques for comprehensive diagnostic systems.• An efficient automatic border detection method for mammogram images.• Orientation detection based on orthogonal group representation and support vector machine.• Multi-scale histogram method for preprocessing of image data in support vector based classification systems.• A transduction method for variable point evaluations in image analyses.• Asymmetry detection using graph theoretic models in mammogram images.• Accurate calculations of geometric invariants in parameters from planar and volumetric image data.• •

Current Project(s)BIOwulf

BIOwulf

RADIOLOGY

Current Project(s)BIOwulf

BIOwulf

RADIOLOGY

Mammography

- Calcification detection

- Mass detection

- Structure distortion detection

Current Project(s)BIOwulf

BIOwulf

RADIOLOGY

Mammography

Breast Cancer

•700,000 deaths in the world in 2000

•41,000 deaths in USA in 2000

•1 in 8 probability that a woman will develop breast cancer

in her lifetime

•1 in 30 probability she will die as a result

Current Project(s)BIOwulf

BIOwulf

RADIOLOGY

Mammography

Scope of the Problem

•False negative rate as high as 25%

•Double reading improves diagnosis by 15%

•70% of lesions are benign at biopsy

•Up to 75% of cancers visible in retrospect

•Sensitivity of current CAD programs 85%,

but specificity is less than 40%

Current Project(s)BIOwulf

BIOwulf

RADIOLOGY

Mammography

Computer Aided Diagnosis

•Consistency:Reduce missed interpretations due to fatigue and

distraction

•Improved Confidence:An additional diagnostic tool

•Enhanced Performance:Draws attention to suspicious microcalcifications,

masses, and architectural distortion

Current Project(s)BIOwulf

BIOwulf

RADIOLOGY

Mammography

Market

•44.5 million mammograms in USA in 2000

•6% increase compared to 1999

•CAD in its infancy

•10,000 registered mammography sites in US

•9% currently use CAD

•8% indicate intent to purchase CAD in next 3 years

Current Project(s)BIOwulf

BIOwulf

RADIOLOGY

Mammography

Local SVM analyzer

Calcification segmentation

Speculation detector

Mass segmentation

Feature extraction

Asymmetry detection

SVM classifier

Overall SVM analyzer

Feature extraction

Global SVM classifier

SVM classifier

Feature extraction

Mammogram Images

Calcification detection subsystem

Structure distortion detection subsystem

Mass detection subsystem

Current Project(s)BIOwulf

BIOwulf

RADIOLOGY

Mammography

Mammogram Images

Overall SVM Analyzer

CalcificationDetection

Subsystem

MassDetection

Subsystem

Structure DistortionDetection

Subsystem

Current Project(s)BIOwulf

BIOwulf

RADIOLOGY

Mammography

Mammogram Images

Overall SVM Analyzer

CalcificationDetection

Subsystem

MassDetection

Subsystem

Structure DistortionDetection

Subsystem

Current Project(s)BIOwulf

BIOwulf

RADIOLOGY

Mammography

Calcification Detection

CalcificationSegmentation

FeatureExtraction

Local SVMAnalyzer

GlobalSVM Classifier

MammogramImages

Overall SVMAnalyzer

Current Project(s)BIOwulf

BIOwulf

RADIOLOGY

Mammography

Calcification Detection

Current Project(s)BIOwulf

BIOwulf

RADIOLOGY

Mammography

Feature Extraction

Current Project(s)BIOwulf

BIOwulf

RADIOLOGY

Mammography

Preliminary Statistics

Negative Positive Total

Normal 106 4 110

Malignant 15 152 167

Total 121 156 277

Current Project(s)BIOwulf

BIOwulf

RADIOLOGY

Mammography

Mammogram Images

Overall SVM Analyzer

CalcificationDetection

Subsystem

MassDetection

Subsystem

Structure DistortionDetection

Subsystem

Current Project(s)BIOwulf

BIOwulf

RADIOLOGY

Mammography

Mammogram Images

Overall SVM Analyzer

CalcificationDetection

Subsystem

MassDetection

Subsystem

Structure DistortionDetection

Subsystem

Current Project(s)BIOwulf

BIOwulf

RADIOLOGY

Mammography

Mass Detection

AsymmetryDetection

FeatureExtraction

MassSegmentation

SVMClassifier

MammogramImages

Overall SVMAnalyzer

Current Project(s)BIOwulf

BIOwulf

RADIOLOGY

Mammography

Mammogram Images

Overall SVM Analyzer

CalcificationDetection

Subsystem

MassDetection

Subsystem

Structure DistortionDetection

Subsystem

Current Project(s)BIOwulf

BIOwulf

RADIOLOGY

Mammography

Mammogram Images

Overall SVM Analyzer

CalcificationDetection

Subsystem

MassDetection

Subsystem

Structure DistortionDetection

Subsystem

Current Project(s)BIOwulf

BIOwulf

RADIOLOGY

Mammography

Structure Distortion Detection

SpiculationDetector

FeatureExtraction

SVMClassifier

MammogramImages

Overall SVMAnalyzer

Current Project(s)BIOwulf

BIOwulf

RADIOLOGY

Mammography

Mammogram Images

Overall SVM Analyzer

CalcificationDetection

Subsystem

MassDetection

Subsystem

Structure DistortionDetection

Subsystem

Future ApplicationsBIOwulf

BIOwulf

RADIOLOGY

Computerized Axial Tomography (CAT)

Magnetic Resonance Imaging (MRI)

•Computer Aided Diagnosis•Tumor Volume Analysis

•Diagnosis/Prognosis•Response to Therapy

•Functional Molecular Imaging

Life Science Imaging Science

Future ApplicationsBIOwulf

BIOwulf

RADIOLOGY

General Radiology

Positron Emission Tomography (PET)

Computer Aided Diagnosis

Ultrasound

Future ApplicationsBIOwulf

BIOwulf

RADIOLOGY

MRI

• Edema (bone)• Joint fluid• Loose bodies• Capsule thickening• Intact meniscus evaluation• Ligament evaluation• Cartilage integrity• Trauma• Clinical