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Electrical Property Evaluation Technology(EPET); Breast Cancer Detection

[A UWM-Aurora-NovaScan Joint Project]

William D Gregory, PhD, PEUWM and NovaScan, LLC (CSO)

UWM: J. Shell, PhD; Prof. V. Raicu, PhDAurora: J. Marx, PhD; W. Mikkelson, MD;J. Tjoe, MDNovaScan: L. Wells, CEO; C. Gregory, PhDCommercialization: TechStar, WiSys, Voith Consulting

Telaric, CAMCARE, WIBHT,WI DOCGovernor’s BP Contest

Dedicated with gratitude to our selfless patient volunteers!

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Impedance (V/I) of Tissue (Collection of Cells)

Interstitial Fluid

Protoplasm

Membrane

Cell

Current

NovaScan, LLC – ConfidentialApril 2008

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R3

Cm

R1

CellInterstitial

Fluid

Impedance of Tissue (Cells), cont.

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NovaScan

EPET I

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EPET I Apparatus

Tissue Probe Set-Up

4-Lead Probe

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Cole Function

"' jZZ ZCole Function, Fc=50kHz

0.0E+00

5.0E+02

1.0E+03

1.5E+03

1.E+00 1.E+02 1.E+04 1.E+06 1.E+08

F (Hz)

Z'

Alpha=1.0

Alpha=0.5

Cole Function, Fc=50kHz

0.0E+001.0E+022.0E+023.0E+024.0E+025.0E+026.0E+02

1.E+00 1.E+02 1.E+04 1.E+06 1.E+08

F (Hz)

-Z" Alpha=1.0

Alpha=0.5

1;])/[(1 3

31

jR

ffj

RR

cZ

NovaScan, LLC – ConfidentialApril 2008

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Cole Plot ResultsBenign Cancer

85.0

54.3

kHzfc

496.0

2.113

kHzfc

NovaScan, LLC – ConfidentialApril 2008

8NovaScan, LLC – ConfidentialApril 2008

Analyzed two ways: 1) Fc from fit to data below@ 100kHz to the Cole function and 2) peaks for data corrected for loading and roll-off effects

Fc Distribution(Fc = -Z" peak frequency from fit to Cole function)

-20

0

20

40

60

1.E+02 1.E+03 1.E+04 1.E+05 1.E+06 1.E+07 1.E+08 1.E+09

Fc (Hz)

Per

-cen

t

% of total Cancer % of total Normal

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Cell Membrane*

*Bioimpedance & Bioelectricity Basics, S. Grimnes and O. G. Martinsen, Academic Press (2005)

NovaScan, LLC – ConfidentialApril 2008

10NovaScan, LLC – ConfidentialApril 2008

# CA # DU %CA %DU CA DU0 1 0.00 4.55 Present Absent0 5 0.00 22.73 Test=+ 57 30 11 0.00 50.00 Test=- 2 185 5 9.26 22.73 total 59 21

28 0 51.85 0.00 Sensitivity= 0.96619 0 35.19 0.00 Specficity = 0.8572 0 3.70 0.00 PPV= 0.95

Totals: 54 22 100.00 100.00 NPV= 0.9

Statistics for "pre-cancer" hypothesisFpeak Hypothetical Distribution Target Disorder

Number of each path type vs Fpeak(Hpyothetical Distribution)

-5

0

5

10

15

20

25

30

1.E+02 1.E+03 1.E+04 1.E+05 1.E+06 1.E+07 1.E+08 1.E+09

Fc1(Hz)

# o

f ca

ses

# of type CA (cancer) # of type DU (normal duct)

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NovaScan

EPET II

NovaScan, LLC – ConfidentialApril 2008

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EPET AlgorithmInterface charges

Two principles:1) Charges only at interfaces2) Electrode charges give unique charge distribution inside

ElectrodesGel

-1.0

… V

righ

t …+

1.0

0 0, a,0

0,b Vtop=1.0

Vbottom=-1.0

-1.0

… V

left …

+1.

0

NovaScan, LLC – ConfidentialApril 2008

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EPET Convergence1,2,3

0.01

0.1

1

10

1 2 3 4 5 6 7 8

Iteration Number

Lo

g(R

MS

Err

or

in %

)

1.Theory: Gregory, W D & Gregory, C W in Eng. in Med. and Bio. Soc., Proc. of the 22nd Int. Conf. of IEEE, 4, 2632 – 2635, 23-28 July 20002.Experiment: “The use of charge-charge correlation in impedance

Measurements: a test of the EPET method”, Gregory, C W, PhD thesis,Morgantown WV, 2005

3.Theory & Experiment: “Device for Improved Cancer Detection: Computer Model and Experimental Test with Phantoms”, W Gregory, C Gregory, P Voith and S Kroeger, Technical Report (NovaScan, LLC, February, 2006)

NovaScan, LLC – ConfidentialApril 2008

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EPET II Apparatus

Drive Plane

Sensor Plate (16x16)

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Breast

Determining Lesion Depth

Caudal-Cranial

SignalIntensity

Cranial-Caudal

Cancer

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Spatial Confirmation

Lateral View Medial View

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EPET II Results

Mass #1

Mass #2

EPET L-breast

EPET scan in ML orientation. Mass #1 is poorly differentiated invasive ductal carcinoma; mass #2 is metastatic carcinoma involving lymph node tissue.

NovaScan, LLC – ConfidentialApril 2008

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EPET II Results

TissueResults

Pathology Findings

3 or 4 Scans

2 Scans

1Scan

Benign1 10 10 9 6

Cancer2 10 10 11 14

NovaScan FindingsThresholds (@ 4 Scans Taken/Patient)

1 = Benign tissue includes FA, BBD, I Pap2= Cancerous tissue includes IDC/DCIS+, DCIS, ILC/DCIS+ or

IDC/LCIS or LCIS, IDC/DCIS-

Chi-Square 0.000 0.200 3.200

Probability 1.000 0.655 0.074

NovaScan, LLC – ConfidentialApril 2008