Design and initial testing of system for simultaneous bilateral dynamic optical tomographic mammography

Design and Initial Testing of Imager for Simultaneous Bilateral Optical

Mammography

OSA Biomedical Optics Topical Meeting April 13-17th, 2004

Miami, Florida

Randall L. Barbour, Ph.D.SUNY Downstate Med. Ct.,

Brooklyn, NY

CONFLICT

•NIRx Medical Technologies, LLC

Motivation for Time-Series Imaging

• Basic Physiology: Tissue-Vascular Coupling – Oxygen delivery to tissue

• Blood Volume • Blood Oxygenation

– Regulation of vascular response• Neural, hormonal, metabolic• Vascular rhythms

• Clinical Applications: Functional changes precede structural changes

Motivation for Time Series Breast Imaging

Figure 1. Corrosion Cast of Tumor Vasculature. ‘tp’, = tumor periphery, ‘st’ = surrounding tissue. From Ref. , p. 16.

Corrosion Cast of Tumor Vasculature

Technology Development

Approach to System Design• Goal: Systems that have turn-key functionality that are suitable for a range of applications.

• Problem Areas– Data Collection.– Data Integrity.– Image Recovery.– Time-Series Image Analysis.– Image Display.

System Design Approach• Large dynamic range (109)• Variable framing rate (2 - 90 Hz)• Multiwavelength (2-4 color)• Automated set-up and control• Real-time visualization• System-data integrity checks• Custom configured measuring heads• Comprehensive software:

– System control, image recovery, signal analysis, image display.

• Integrated vital sign monitoring.

Time Series Optical Tomography

1

2

3

Frame

SUNY DYNOT Breast Imager

• Single, Dual Breast Measurement Heads• Time multiplexed DC Illumination• 32 source x 64 detector channels per breast.• 64 channel optical switch • 2-90 Hz framing rate

• Advantage of Dual Breast Measurement: - Provides for differential measurement!

Breast Measurement HeadsSingle Breast - Medieval Style

Dual Breast - Madonna Style

Detector fibers Detector fibers

760 nm

830 nm

Detector setup

Detector setup

Source fibers

Source fibers

LEFT RIGHT

Dual Breast Set-up Screen

Dual Breast Display Screen

CASE STUDIES

Tumor Detection by Response to Transient

Hypoxemia

1 2

3 41 2

3 4

Time point Time point

Norm

aliz

ed d

etec

tor

read

ing

Norm

aliz

ed d

etec

tor

read

ing

Healthy Tumor bearing

HbO2

Hb

Image of Transient Hypoxemia

1.00

0.75

0.50

0.25

Relative Contrast

Figure 5. Right, 3D DYNOT image of tumor identifying imbalance in tissue oxygen supply/demand. Image was produced without need of contrast agents or compression. Left, sonogram image of same breast showing location of tumor. Note close agreement in size and location.

Tumor

Valsalva Maneuver

Vascular Response to Valsalva Maneuver

100

50

1

GLM Analysis: Percentage of Variance Accounted for by Model

Function

1.5e-8

0

-9.3e-9

2.1e-8

0

-1.2e-8

P1: Left Breast

P1: Right Breast

1 2 3 4 5 6 7

1

2

3

456 7

1st derivative of the deoxyhemoglobin image time series at indicated time points indicated along the

Valsalva maneuver (1) (tumor-bearing patient: P1)

Ductal Carcinoma

1.1 e-8

0

-1.46e-8

4.7 e-8

0

-1.1e-8

N1: Left Breast

N1: Right Breast

1 2 3 4 5 6 7

1

2

3

456 7

1st derivative of the deoxyhemoglobin image time series at indicated time points indicated along the

Valsalva maneuver (2) (Healthy Volunteer)

Simultaneous Bilateral Measurements

Look for differential responses in baseline and in response to provocation!

Spatially averaged, low-pass filtered (0-0.38 Hz) total Hb (i.e., blood volume) baseline signals(left breast, right breast)

0 100 200 300 400 500 600 700 800-5

0

5x 10-5

Tim e(Sec)

Dete

ctor

Rea

ding

0 0.05 0.1 0.15 0.2 0.25 0.30

0.5

1

1.5

2x 10-11

Frequency(Hz)

Ampli

tude

of C

SD

0 100 200 300 400 500 600 700 800-5

0

5x 10-5

Tim e(Sec)

Dete

ctor

Rea

ding

0 0.05 0.1 0.15 0.2 0.25 0.3

-150

-100

-50

0

50

100

150

Frequency(Hz)

Phas

e of

CSD

0 100 200 300 400 500 600 700 800-5

0

5x 10-5

Tim e(Sec)

Dete

ctor

Rea

ding

0 0.05 0.1 0.15 0.2 0.25 0.30

0.5

1

1.5

2

2.5

x 10-13

Frequency(Hz)

Ampli

tude

of C

SDBaseline Comparisons

Amplitude CSD

Phase CSD

Patient with active breast cancer: Baseline

0 100 200 300 400 500 600 700 800-4

-2

0

2

4x 10-5

Tim e(Sec)

Detector R

eadin

g

0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4 0.450

0.5

1

1.5

2x 10-6

Frequency(Hz)

Ampli

tude

0 100 200 300 400 500 600 700 800-4

-2

0

2

4x 10-5

Tim e(Sec)

Detector R

eadin

g

0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4 0.450

0.2

0.4

0.6

0.8

1x 10-6

Frequency(Hz)

Ampli

tude

Spatially averaged, bandpass filtered (0.005-0.43 Hz) total Hb baseline signals

0 100 200 300 400 500 600 700 800-1

-0.5

0

0.5

1x 10-5

Tim e(Sec)

Detector Readin

g

0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4 0.450

0.5

1

1.5

2

2.5x 10-7

Frequency(Hz)

Amplitude

Breast Cancer PatientTime-dependent, spatial standard deviation of bandpass filtered total Hb baseline signals

• Is the respiratory rhythm simply absent from the left breast?

• No! Presence of respiratory peak in SD time series indicates that there is, instead, loss of coordinated activity in the breast at this frequency.

• FT phase is spatially heterogen-eous, and contributions from all parts of the breast cancel out in the mean time series.

0 100 200 300 400 500 600 700 800-4

-2

0

2

4

6x 10-5

Tim e(Sec)

Detector Readin

g

0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4

-150

-100

-50

0

50

100

150

Frequency(Hz)

Phase of CSD

CSD Phase of Mean time series

Bilateral Response to Valsalva: Healthy Subject

2232 2243 2277 2292 2305 2362

1st Derivative Images for Deoxy Hb: Healthy Subject

Time Points

Bilateral Response to Valsalva: Cancer Patient

Time Point

2610 2634 2677 2700 2750 2818

Left

Right

3050

Time Point2500 2600 2700 2800 2900 3000 3100 3200

(deoxy-Hb Concentration) [a.u.]

-3.50E-8

-1.50E-8

5.00E-9

2.50E-8

4.50E-8

6.50E-8

8.50E-8

1.05E-7LeftRight

2610

2634

2677

2700

2750

2818

3050

Tumor

Summary• Developed a integrated measuring system capable of simultaneous bilateral time-series breast imaging.

• Preliminary studies have shown evidence of characteristic changes to both baseline and response to provocation.

• The form of these changes include disturbances in basal rhythms, and localized rates of change following a respiratory maneuver.

SUNY-NIRx Development Team

• Key Personnel Degree Expertise Responsibility

Randall Barbour Ph.D. Biochem, Lab. Med., Biomedical Optics PIHarry Graber Ph.D. Biophysics, Theory, Signal analysis Senior Appl. Specialist

Yaling Pei Ph.D. Engineering, Numerical Methods, Algorithm Dev. Dir. Software Eng.Christoph Schmitz Ph.D. Physics, System design and integration Dir. EngineeringDavid Klemer M.D., Ph.D. Int. Med., Elec. Eng., Application DevelopmentMedical DirectorMikhail Levin Ph.D. Physics, Physical Optics Optical System DesignMargarita Levin Ph.D. Physics, Physical Optics Sys. Testing, ValidationYong Xu Ph.D. Physics, Numerical Methods Algorithm DevelopmentRaphael Aronson Ph.D. Physics, Theory Adv. Theory Studies

Nelson Franco M.D. Surgical Resident Breast StudiesRosemarie Hardin M.D. Surgical Resident Breast StudiesMichael Katz M.D. Surgical Resident Limb StudiesAlessandro Smeraldi M.D. Vascular Fellow (Staten Island U. Hosp) Limb Studies

Acknowledgements

•NYS Department of Health•Army Research Office•NIH: NIBIB, NIHLB, NINDS, NCI, NIDDK

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— Thomas Jefferson (1822)