design and performance of a near-infrared, spectral...

1
Introduction Optical absorption reveals both angiogenesis and hypermetabolism, both of which are hallmarks of cancer. Near infrared (NIR) imaging relies mainly on the absorption of hemoglobin for the source of image contrast, and is highly sensitive to the oxygen saturation of hemoglobin (SO 2 ). [1-4]. We recently developed a paired-wavelength spectral approach to quantify the oxygen saturation of the hemoglobin in breast tumors [5]. The basic idea is that an appropriate choice of a pair of wavelengths (λ 1 , λ 2 ), which depends on the oxygenation level of the tumor and on the optical properties of the background healthy breast tissue, leads to a measurement of the tumor oxygenation that is largely independent of the tumor size, shape, and location inside the breast [5]. Here, we present the scanning system and experimental results to show the performance of our new system. Yang Yu, Ning Liu, Angelo Sassaroli, and Sergio Fantini Tufts University, Department of Biomedical Engineering, 4 Colby Street, Medford, MA 02155, USA Abstract A tunable band-pass(500nm to 1000nm) Xenon arc lamp is coupled to a source fiber which delivers the light to the sample. The light transmitted through the sample is sent through a detector fiber to a spectrograph and then spatially dispersed onto the charged-coupled device(CCD) array. The source and detector fibers are collinear to each other and perform a tandem 2D scan. The spatial sampling rate is controlled by changing the speed of stepper motors and CCD acquisition time in a LabVIEW program. We are optimizing the system in terms of signal-to-noise ratio(SNR) at different wavelengths under the condition that the maximum scanning time is 5 minutes for a typical breast scanning. Fundamental tests are performed by using homogenous diffusive media with optical properties similar to breast tissue. Incorporated with the novel pair-wavelength approach, our breast imaging system can provide relevant oxygenation information that can ultimately result in a higher specificity for tumor detection or more efficient follow-up to treatment. Block Diagram for Block Diagram for Optical Mammography Instrument Optical Mammography Instrument Essential Components corresponding to the Block Diagram 5-phase step motor –(adjust scanning speed (starting from 1cm/s)) Xenon Arc lamp (maximum output power 350W, provide broadband light from 500nm to 1000nm after UV-filtering, ) Charged-coupled device detector(record spectral information at each detection point with 1024*1024 pixel array) LabVIEW program (control the scanning and data acquisition process) Spectrograph (spectral dispersion 20nm/mm) Optical fibers (deliver and receive photons with internal diameter: 4mm, radiation exposure measured after the fiber attenuation) SIEMENS scanning platform (adjustable height to accommodate various subjects with parallel glass to achieve mild compression. equipped with gliding scanner and detector where the optic fibers are embedded) DAQ board (interface where analog trigger and TTL pulse signals are sent and received) Mammography instrumentation picture corresponding to block diagram The cooling system for the Arc Lamp and CCD camera, which is critical to reduce the electronic noise generated inside the detector and source, does not show in the figure above. Spectrograph CCD Computer Filters (500nm- 1000nm) Xenon Arc Lamp Illumination fiber bundle Collection fiber bundle 6.3cm 30.4cm 14.3cm 10cm 1cm diameter, 12cm long cylindrical hole 6cm Solid phantom Solid phantom Solid phantom Shot Noise Description--- Poisson Distribution Signal is the mean value of data points from one specific location Noise is the standard deviation of data points from the same location As a result, the detected signal level should be maximized in order to achieve the optimal SNR with the regulation of CIE S 009: 2002. CCD exposure time, which is limited by the maximum scanning time, is another critical parameter that can affect the detected signal level. Preliminary experiment setup Preliminary experiment setup on solid phantom on solid phantom Discussion Noise can be characterized into three categories: Electronic Noise stems from the CCD dark current, readout noise and amplifier noise. It is independent upon the signal level and its effect can be significantly reduced by background acquisition in dark ambience. Structural noise comes from the slight misalignment between scanner and detector, and different scratches among different glass positions. To sum up, the structural noise is due to the instrumentation inhomogeneity. Currently we are correcting this noise by flat-field method. After all the correction methods, the shot noise is the dominant noise source to concern about. According to the definition of Poisson Distribution, ANSI stardards, the light intensity should be increased to the largest extent with the compliance to the current ANSI standards. Under the 5-minute maximum scanning time, the CCD exposure time should be increased given specific pixel size and subject breast size. Conclusions We have built a mammography spectral imaging system that provides a large flexibility in terms of pixel size (in the order of millimeters), scanning speed (starting from 1.0cm/s) and light radiance. We are planning to assess the robustness of the pair-wavelength method on human subjects and make comparisons with other spectral methods. Combining with this newly-developed instrument we will measure the oxygen saturation of hemoglobin in human breast tumors on patients from different races. Acknowledgments This research is supported by the National Institutes of Health (Grant CA95885), and by the National Science Foundation (Award BES- 93840). References [1] B. W. Pogue, S. Jiang, H. Dehghani, C. Kogel, S. Soho, S. Srinivasan, X. Song, T. D. Tosteson, S. P. Poplack, and K. D. Paulsen, “Characterization of hemoglobin, water, and NIR scattering in breast tissue: analysis of intersubject variability and menstrual cycle changes,” J. Biomed. Opt. 9, 541-552 (2004). [2] Shah N, Cerussi AE, Jakubowski D, Hsiang D, Butler J, Tromberg BJ, “Spatial variations in optical and physiological properties of healthy breast tissue,” J. Biomed Opt. 9(3), 534-40, (2004) [3] Pifferi A, Swartling J, Chikoidze E, Torricelli A, Taroni P, Bassi A, Andersson-Engels, Cubeddu R., “Spectroscopic time-resolved diffuse reflectance and transmittance measurements of the female breast at different interfiber distances,” J. Biomed Opt. 9(6), 1143-51, (2004) [4] Rinneberg H, Grosenick D, Moesta KT, Mucke J, Gebauer B, Stroszczynski C, Wabnitz H, Moeller M, Wassermann B, Schlag PM, “Scanning time-domain optical mammography: detection and characterization of breast tumors in vivo,” Technol Cancer Res. Treat, 4(5), 483-96, (2005). [5] E. L. Heffer and S. Fantini, “Quantitative oximetry of breast tumors: a near-infrared method that identifies two optimal wavelengths for each tumor,” Appl. Opt. 41, 3827-3839, (2002). Design and Performance of a Near Design and Performance of a Near - - Infrared, Spectral Imaging System Infrared, Spectral Imaging System For Optical Mammography For Optical Mammography 0 2 4 6 8 10 12 14 16 18 20 0 50 100 150 200 250 x/cm y/ summed CCD intensity along column Summed One Scanning line of Uniform Phantom X: 82 Y: 147.3 10.4cm 10cm uniform phantom iamge with optical properties similar to human breast (Pixel size: 2.0mm×2.0mm; Contrast-to-Noise Ratio: 8.4) the averaged intensity for one scanning line The two valleys here correspond to inhomogeneity in the phantom which is represented by dark parts in the left image Key Experiment Parameters 0.015 0.02 0.025 0.03 0.035 0.04 0.045 1200 1400 1600 1800 2000 2200 2400 2600 2800 3000 CCD Exposure Time(second) The Square of SNR SNR has a linearity relationship with CCD exposure time 2 4 6 8 10 12 14 16 18 20 2 4 6 8 10 12 14 16 18 20 x/cm y/cm Uniform Phantom Scanning3(Apr 27,2007) 0 50 100 150 200 ( ) ( ) , cm 1 . 0 6 . 10 nm 690 , cm 0003 . 0 0110 . 0 nm 690 1 ' 0 1 ± = ± = s a μ μ The optical properties of the phantom at 690nm and 830nm are ( ) ( ) 1 ' 0 1 cm 1 . 0 5 . 9 nm 830 cm 0003 . 0 0130 . 0 nm 830 ± = ± = s a μ μ

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Page 1: Design and Performance of a Near-Infrared, Spectral ...engineering.tufts.edu/gradResearch/documents/2007/yu.pdf · The cooling system for the Arc Lamp and CCD camera, which is critical

Introduction

Optical absorption reveals both angiogenesis and

hypermetabolism, both of which are hallmarks of cancer. Near

infrared (NIR) imaging relies mainly on the absorption of

hemoglobin for the source of image contrast, and is highly

sensitive to the oxygen saturation of hemoglobin (SO2). [1-4]. We

recently developed a paired-wavelength spectral approach to

quantify the oxygen saturation of the hemoglobin in breast tumors

[5]. The basic idea is that an appropriate choice of a pair of

wavelengths (λ1, λ2), which depends on the oxygenation level of

the tumor and on the optical properties of the background healthy

breast tissue, leads to a measurement of the tumor oxygenation

that is largely independent of the tumor size, shape, and location

inside the breast [5].

Here, we present the scanning system and experimental results to

show the performance of our new system.

Yang Yu, Ning Liu, Angelo Sassaroli, and Sergio Fantini

Tufts University, Department of Biomedical Engineering, 4 Colby Street, Medford, MA 02155, USA

Abstract

A tunable band-pass(500nm to 1000nm) Xenon arc lamp is

coupled to a source fiber which delivers the light to the sample.

The light transmitted through the sample is sent through a

detector fiber to a spectrograph and then spatially dispersed onto

the charged-coupled device(CCD) array. The source and detector

fibers are collinear to each other and perform a tandem 2D scan.

The spatial sampling rate is controlled by changing the speed of

stepper motors and CCD acquisition time in a LabVIEW program.

We are optimizing the system in terms of signal-to-noise

ratio(SNR) at different wavelengths under the condition that the

maximum scanning time is 5 minutes for a typical breast scanning.

Fundamental tests are performed by using homogenous diffusive

media with optical properties similar to breast tissue. Incorporated

with the novel pair-wavelength approach, our breast imaging

system can provide relevant oxygenation information that can

ultimately result in a higher specificity for tumor detection or more

efficient follow-up to treatment.

Block Diagram for Block Diagram for

Optical Mammography InstrumentOptical Mammography Instrument

Essential Components corresponding to the Block Diagram

5-phase step motor –(adjust scanning speed (starting from 1cm/s))

Xenon Arc lamp (maximum output power 350W, provide broadband light

from 500nm to 1000nm after UV-filtering, )

Charged-coupled device detector(record spectral information at each

detection point with 1024*1024 pixel array)

LabVIEW program (control the scanning and data acquisition process)

Spectrograph (spectral dispersion 20nm/mm)

Optical fibers (deliver and receive photons with internal diameter: 4mm,

radiation exposure measured after the fiber attenuation)

SIEMENS scanning platform (adjustable height to accommodate various

subjects with parallel glass to achieve mild compression. equipped with gliding

scanner and detector where the optic fibers are embedded)

DAQ board (interface where analog trigger and TTL pulse signals are sent

and received)

Mammography instrumentation picture

corresponding to block diagram

The cooling system for the Arc Lamp and CCD camera, which is critical to

reduce the electronic noise generated inside the detector and source, does

not show in the figure above.

Spectrograph

CCD

Computer

Filters (500nm-

1000nm)

Xenon Arc

Lamp

Illumination

fiber bundleCollection fiber

bundle

6.3cm

30.4cm14.3cm

10cm

1cm diameter,

12cm long

cylindrical hole

6cm

Solid phantomSolid phantomSolid phantom

Shot Noise Description--- Poisson Distribution

Signal is the mean value of data points from one specific location

Noise is the standard deviation of data points from the same location

As a result, the detected signal level should be maximized in order to

achieve the optimal SNR with the regulation of CIE S 009: 2002.

CCD exposure time, which is limited by the maximum scanning time, is

another critical parameter that can affect the detected signal level.

Preliminary experiment setup Preliminary experiment setup

on solid phantomon solid phantom

Discussion

Noise can be characterized into three categories:

� Electronic Noise stems from the CCD dark current, readout noise and

amplifier noise. It is independent upon the signal level and its effect can

be significantly reduced by background acquisition in dark ambience.

� Structural noise comes from the slight misalignment between scanner and

detector, and different scratches among different glass positions. To sum

up, the structural noise is due to the instrumentation inhomogeneity.

Currently we are correcting this noise by flat-field method.

� After all the correction methods, the shot noise is the dominant noise

source to concern about. According to the definition of Poisson

Distribution, ANSI stardards, the light intensity should be increased to the

largest extent with the compliance to the current ANSI standards. Under

the 5-minute maximum scanning time, the CCD exposure time should be

increased given specific pixel size and subject breast size.

Conclusions

We have built a mammography spectral imaging system that provides a

large flexibility in terms of pixel size (in the order of millimeters), scanning

speed (starting from 1.0cm/s) and light radiance.

We are planning to assess the robustness of the pair-wavelength method

on human subjects and make comparisons with other spectral methods.

Combining with this newly-developed instrument we will measure the

oxygen saturation of hemoglobin in human breast tumors on patients from

different races.

Acknowledgments

This research is supported by the National Institutes of Health (Grant

CA95885), and by the National Science Foundation (Award BES-

93840).

References

[1] B. W. Pogue, S. Jiang, H. Dehghani, C. Kogel, S. Soho, S.

Srinivasan, X. Song, T. D. Tosteson, S. P. Poplack, and

K. D. Paulsen, “Characterization of hemoglobin, water, and NIR

scattering in breast tissue: analysis of intersubject variability and

menstrual cycle changes,” J. Biomed. Opt. 9, 541-552 (2004).

[2] Shah N, Cerussi AE, Jakubowski D, Hsiang D, Butler J, Tromberg BJ,

“Spatial variations in optical and physiological properties of healthy

breast tissue,” J. Biomed Opt. 9(3), 534-40, (2004)

[3] Pifferi A, Swartling J, Chikoidze E, Torricelli A, Taroni P, Bassi A,

Andersson-Engels, Cubeddu R., “Spectroscopic time-resolved diffuse

reflectance and transmittance measurements of the female breast at

different interfiber distances,” J. Biomed Opt. 9(6), 1143-51, (2004)

[4] Rinneberg H, Grosenick D, Moesta KT, Mucke J, Gebauer B,

Stroszczynski C, Wabnitz H, Moeller M, Wassermann B, Schlag PM,

“Scanning time-domain optical mammography: detection and

characterization of breast tumors in vivo,” Technol Cancer Res. Treat,

4(5), 483-96, (2005).

[5] E. L. Heffer and S. Fantini, “Quantitative oximetry of breast tumors: a

near-infrared method that identifies two optimal wavelengths for each

tumor,” Appl. Opt. 41, 3827-3839, (2002).

Design and Performance of a NearDesign and Performance of a Near--Infrared, Spectral Imaging SystemInfrared, Spectral Imaging System

For Optical MammographyFor Optical Mammography

0 2 4 6 8 10 12 14 16 18 200

50

100

150

200

250

x /cm

y/ summed C

CD intensity along column

S umm ed O ne S c ann ing line o f U n iform P han tom

X : 82

Y : 147 .3

10 .4c m10cm

uniform phantom iamge with

optical properties

similar to human breast

(Pixel size: 2.0mm×2.0mm;

Contrast-to-Noise Ratio: 8.4)

the averaged intensity for one scanning line

The two valleys here correspond

to inhomogeneity in the phantom which

is represented by dark parts in the left image

Key Experiment Parameters0 . 0 1 5 0 . 0 2 0 . 0 2 5 0 . 0 3 0 . 0 3 5 0 . 0 4 0 . 0 4 5

1 2 0 0

1 4 0 0

1 6 0 0

1 8 0 0

2 0 0 0

2 2 0 0

2 4 0 0

2 6 0 0

2 8 0 0

3 0 0 0

C C D E x p o s u r e T im e ( s e c o n d )

The Square of SNR

S N R h a s a l i n e a r i t y r e l a t i o n s h i p w i t h C C D e x p o s u r e t i m e

2 4 6 8 10 12 14 16 18 20

2

4

6

8

10

12

14

16

18

20

x/cm

y/cm

Uniform Phantom Scanning3(Apr 27,2007)

0

50

100

150

200

( )

( ) ,cm1.06.10nm690

,cm0003.00110.0nm690

1'

0

1

±=

±=

s

a

µ

µ

The optical properties of the phantom at 690nm and 830nm are

( )

( ) 1'

0

1

cm1.05.9nm830

cm0003.00130.0nm830

±=

±=

s

a

µ

µ