Optimal laser wavelength for photoacoustic imaging of breast microcalcificationsJeeun Kang, Eun-Kyung Kim, Jin Young Kwak, Yangmo Yoo, Tai-Kyong Song, and Jin Ho Chang Citation: Applied Physics Letters 99, 153702 (2011); doi: 10.1063/1.3651333 View online: http://dx.doi.org/10.1063/1.3651333 View Table of Contents: http://scitation.aip.org/content/aip/journal/apl/99/15?ver=pdfcov Published by the AIP Publishing Articles you may be interested in Dedicated 3D photoacoustic breast imaging Med. Phys. 40, 113301 (2013); 10.1118/1.4824317 High-resolution photoacoustic imaging with focused laser and ultrasonic beams Appl. Phys. Lett. 94, 033902 (2009); 10.1063/1.3073749 Noninvasive monitoring of traumatic brain injury and post-traumatic rehabilitation with laser-inducedphotoacoustic imaging Appl. Phys. Lett. 90, 243902 (2007); 10.1063/1.2749185 Imaging of joints with laser-based photoacoustic tomography: An animal study Med. Phys. 33, 2691 (2006); 10.1118/1.2214166 Photoacoustic imaging in biomedicine Rev. Sci. Instrum. 77, 041101 (2006); 10.1063/1.2195024

This article is copyrighted as indicated in the article. Reuse of AIP content is subject to the terms at: http://scitation.aip.org/termsconditions. Downloaded to IP:

137.149.200.5 On: Tue, 02 Dec 2014 14:58:11

Optimal laser wavelength for photoacoustic imaging of breastmicrocalcifications

Jeeun Kang,1 Eun-Kyung Kim,2 Jin Young Kwak,2 Yangmo Yoo,3,4 Tai-Kyong Song,3

and Jin Ho Chang1,4,a)

1Medical Solutions Institute, Sogang Institute of Advanced Technology, Sogang University,Seoul 121-742, Korea2Department of Radiology, Research Institute of Radiological Science, Yonsei University College of Medicine,Seoul 120-749, Korea3Department of Electronic Engineering, Sogang University, Seoul 121-742, Korea4Interdisciplinary Program of Integrated Biotechnology, Sogang University, Seoul 121-742, Korea

(Received 8 August 2011; accepted 22 September 2011; published online 11 October 2011)

This paper presents photoacoustic imaging (PAI) for real-time detection of micro-scale calcifications

(e.g., <1 mm) in the breast, which are an indicator of the cancer occurrence. Optimal wavelength of

incident laser for the microcalcification imaging was ascertained through ex vivo experiments with

seven breast specimens of volunteers. In the ex vivo experiments, the maximum amplitude of

photoacoustic signals from the microcalcifications occurred when the laser wavelength ranged from

690 to 700 nm. This result demonstrated that PAI can serve as a real-time imaging and guidance tool

for diagnosis and biopsy of the breast microcalcifications. VC 2011 American Institute of Physics.

[doi:10.1063/1.3651333]

Breast cancer screening is generally conducted by mam-

mography, followed by ultrasound (US) imaging. Microcal-

cifications have been serving as an indicator of early stage

cancer, and mammography is an excellent tool for detecting

microcalcifcations.1,2 If suspicious microcalcificaions are

observed in mammography, a biopsy is performed to confirm

the malignancy. For the diagnosis of microcalcifications, ei-

ther core needle biopsy with stereotactic guidance or surgical

excision after mammographically guided wire localization is

used. However, these techniques not only require mammo-

graphic compression of breast that is uncomfortable for the

patients, but also have drawbacks such as incapability of

real-time imaging and risks associated with radiation expo-

sure. On the other hand, US imaging is a non-radiation imag-

ing modality capable of providing real-time imaging and

comfortable for the patients so that it is frequently used to

guide percutaneous core biopsy. However, it suffers from a

low detectability of microcalcifications due to its relative

low contrast resolution.

Since photoacoustic imaging (PAI) is a real-time molec-

ular imaging modality with high spatial and contrast

resolutions,3–5 it may be a candidate for imaging of micro-

calcifications in real time if photoacoustic (PA) signals are

generated only inside the targets. Different molecules such

as oxygenated- and deoxygenated-hemoglobin in blood have

different characteristic absorption spectra in response to inci-

dent laser. The absorption spectrum is a function of laser

wavelength. If laser pulse with peak absorption wavelength

is emitted, the only corresponding molecule maximally

absorbs the laser energy that is subsequently converted into

heat. When the laser pulse width is shorter than thermal

transport time of the absorbed energy, defined as thermal

confinement, the energy brings about transient thermoelastic

expansion. Therefore, the PA signal detected as a form of

US is generated. As a result, the pivotal condition to utilize

PAI for visualization of microcalcifications is that the char-

acteristic absorption spectrum of microcalcifications should

be known. From this condition, we can determine a specific

wavelength of laser pulse to generate maximal PA signals

inside the microcalcifications higher than the surrounding

tissues.

In this paper, we report the optimal laser wavelength

ascertained by an indirect method instead of measuring the

characteristic absorption spectrum of microcalcifications. By

varying wavelength from 680 to 1000 nm, we measured PA

signal amplitudes generated from ex vivo calcification-

contained breast cancer specimens of volunteer patients. For

this study, US-guided 8-gauge vacuum assisted biopsies

were conducted and seven core samples were acquired. The

optimal laser wavelength was determined when PA signal

had the maximum amplitude at a certain wavelength. Note

that the rationale behind the indirect method will be

explained later. In addition, we confirmed that the PA signals

were generated from the microcalcifications by comparing a

combined PA/US image with mammography.

The strength of PA signals produced in a target molecule

is proportional to the amount of the energy absorbed by the

target. The total absorption energy is determined by ClaFwhere C is the dimensionless Gruneisen parameter, la is the

optical absorption coefficient, and F is the optical fluence at

the absorber.6 After the target absorbs the laser energy, PA

signals are generated and propagates in a medium. This can

be formulated by7,8

r2 � 1

vs

@2

@t2

� �p ¼ � C

v2s

@H

@t; (1)

where p is the acoustic pressure, vs is the longitudinal wave

speed in a medium, t is time, and H is the heating function

a)Author to whom correspondence should be addressed. Electronic mail:

jhchang@sogang.ac.kr.

0003-6951/2011/99(15)/153702/3/$30.00 VC 2011 American Institute of Physics99, 153702-1

APPLIED PHYSICS LETTERS 99, 153702 (2011)

This article is copyrighted as indicated in the article. Reuse of AIP content is subject to the terms at: http://scitation.aip.org/termsconditions. Downloaded to IP:

137.149.200.5 On: Tue, 02 Dec 2014 14:58:11

representing thermal energy deposited per unit volume and

per unit time. Also, C is expressed as

bv2s

Cp; (2)

where b is the thermal coefficient of volume expansion of a

medium and Cp is the heat capacity at constant acoustic pres-

sure. If incident energy density is fixed, F can be considered

as a constant. C can be maintained as a constant by keeping

the temperature of the medium constant although it increases

after absorbing energy of emitted laser. Under the condi-

tions, therefore, the amount of the energy absorbed by the

target relies upon only la and the strength of PA signals is

directly proportional to la of microcalcifications. la deter-

mines the characteristic absorption spectrum, so that the

indirect method can be used to find the optimal laser

wavelength.

Figure 1 shows the schematic diagram of the experimen-

tal arrangement. To acquire PA signals from the specimens,

radio-frequency (RF) data were captured with a commercial

US scanner equipped with a SonixTouch research package

(Ultrasonix Corp., Vancouver, BC, Canada) and a 7-MHz

linear array (L14-5/38) connected to a SonixDAQ parallel

system. The distance between the array and the specimen

was 30 mm that was longer than its elevational focal depth of

16 mm. The Q-switch trigger of an Nd:YAG laser excitation

system (Surelite III-10 and Surelite OPO Plus, Continuum

Inc., Santa Clara, CA, USA) was sent to a function generator

(AFG3252, Tektronix Corp., Beaverton, OR, USA) at the

rate of 10 Hz. The function generator was connected to the

US scanner with external scanline-generation trigger after

changing the Q-switch trigger level of 12 Vp-p to 5 Vp-p.

Whenever the US scanner received the scanline-generation

trigger, one scanline RF data were acquired. The pulse length

of the emitted laser was 7 ns. The wavelength of the laser

pulse and RF data acquisition process were controlled by a

software program in a personal computer. For the ex vivoexperiments, the specimen of calcification-contained breast

tissue was fixed on a scatter-free PVC phantom with staples,

which was immersed in a 0.9% saline-filled container [see

Fig. 2(a)]. Also, the temperature of the container was stably

maintained to be 24 �C. Note that laser was emitted directly

to the specimen as shown in Fig. 2(b). Energy density of the

laser was fixed around 19 mJ/cm2 during the experiment to

satisfy the regulation of ANSI Z136 radiation safety limit of

20 mJ/cm2.

A representative result from the ex vivo experiments

with seven specimens is shown in Fig. 3. In Fig. 3(b), the PA

image of nine cohesive particles distributed within the speci-

men was obtained when 690-nm laser pulse was used, which

did not appear in the US image [see Fig. 3(a)]. From the

mammography image in Fig. 3(d), it was learned that the

breast core specimen contained nine calcifications, indicated

by the arrows. The minimum size of the calcifications was

around 50 lm. Although PAI provides a cross-sectional

image, the same number of calcifications on the mammog-

raphy appeared on the PA image [see Figs. 3(b) and 3(c)].

This is so because the slice thickness of PA detection area

FIG. 1. (Color online) Schematic dia-

gram for the ex vivo experiments.

Energy of the excited laser is consis-

tently maintained to be 19 mJ/cm2. Also,

the temperature of the container is stably

maintained to be 24 �C.

FIG. 2. (Color online) Experiment arrangement: (a) a specimen fixed on a

speckle-free PVC phantom and (b) traveling direction of laser pulse emitted

from the OPO. The PA signals generated are received by the ultrasound lin-

ear array.

153702-2 Kang et al. Appl. Phys. Lett. 99, 153702 (2011)

This article is copyrighted as indicated in the article. Reuse of AIP content is subject to the terms at: http://scitation.aip.org/termsconditions. Downloaded to IP:

137.149.200.5 On: Tue, 02 Dec 2014 14:58:11

was broad enough to receive PA signals from the nine tar-

gets. This was possible by placing the specimen at the depth

of 30 mm that was longer than the elevational focal depth of

the array, i.e., 16 mm. Note that the PA signals from the sta-

ple could be identified because the change in the signal

strength was negligible as laser wavelength was changed.

Also, the combined PA/US image shown in Fig. 3(c) con-

firmed that the PA signals were of the staple.

During the ex vivo experiments, PA signals were gener-

ated by transmitting laser pulse with different wavelengths

varying from 680 nm to 750 nm at a 10 nm increment and

from 800 to 1000 at a 50 nm increment. At each wavelength,

PA signals from the microcalcifications were repetitively

acquired 16 times, and their peak amplitudes were measured

for each specimen. Their normalized means and standard

deviations of the measured amplitudes at each wavelength

were calculated as shown in Fig. 4. The result indicated that

the microcalcifications in the breast tissue highly absorb the

laser pulse with the wavelength of 690-700 nm. In conclusion,

this study demonstrated the feasibility of PAI as a real-time

imaging modality to construct the images of microcalcification

with high spatial and contrast resolutions. The outstanding

advantages of PAI over the conventional imaging modalities

may allow for efficient diagnosis of early stage breast cancer

and real-time guidance of biopsy.

This work was supported by International Collaborative

R&D Program (2010-TD-500409-001) funded by the Minis-

try of Knowledge Economy (MKE), Korea.

1H. S. Kim, M. J. Kim, E. K. Kim, J. Y. Kwak, E. J. Son, and K. K. Oh, Ko-

rean J. Radiol. 9, 503 (2008).2C. Mazouni, R. Rouzier, C. Balleyguier, L. Sideris, F. Rochard, S. Dela-

loge, H. Marsiglia, M.-C. Mathieu, M. Spielman, and J.-R. Garbay, Clin.

Radiol. 61, 789 (2006).3M. Baker, Nature (London) 463, 977 (2010).4H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, Nat. Biotechnol. 24,

848 (2007).5F. Kong, Y. C. Chen, H. O. Lloyd, R. H. Silverman, H. H. Kim, J. M. Can-

nata, and K. K. Shung, Appl. Phys. Lett. 94, 033902 (2009).6S. Y. Emelianov, P. C. Li, and M. O’Donnell, Phys. Today 62(5), 34

(2009).7A. C. Tam, Rev. Mod. Phys. 58, 381 (1986).8G. J. Diebold and T. Sun, Acoustica 80, 339 (1994).

FIG. 3. (Color online) Representative

results from the ex vivo experiments

with seven specimens: (a) B-mode US

image with a dynamic range of 60 dB,

(b) PA image with a dynamic range of

25 dB, (c) combined PA/US image, and

(d) mammography image of the speci-

men. The arrows indicate the microcalci-

fication in the specimen.

FIG. 4. Normalized mean and standard deviation of the maximum PA signal

at each wavelength.

153702-3 Kang et al. Appl. Phys. Lett. 99, 153702 (2011)

This article is copyrighted as indicated in the article. Reuse of AIP content is subject to the terms at: http://scitation.aip.org/termsconditions. Downloaded to IP:

137.149.200.5 On: Tue, 02 Dec 2014 14:58:11