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Anatomical and metabolic small-

animal whole-body imaging using

ring-shaped confocal photoacoustic

computed tomography

Jun Xia, Muhammad Chatni, Konstantin Maslov, Lihong

V. Wang

Jun Xia, Muhammad Chatni, Konstantin Maslov, Lihong V. Wang,

"Anatomical and metabolic small-animal whole-body imaging using ring-

shaped confocal photoacoustic computed tomography," Proc. SPIE 8581,

Photons Plus Ultrasound: Imaging and Sensing 2013, 85810K (4 March

2013); doi: 10.1117/12.2004937

Event: SPIE BiOS, 2013, San Francisco, California, United States

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Anatomical and metabolic small-an

imal whole-body imaging using

ring-shaped confocal photoacou

stic computed tomography

Jun Xia, Muhammad Chatni, Konsta

ntin Maslov, and Lihong V. Wang*

Department of Biomedical Engineering, One Brookings

Drive, Washington University in St. Louis,

St. Louis, MO, USA 63130

*Correspondence should be addressed to lhwang@biomed.wustl.edu

ABSTRACT

Due to the wide use of animals for human disease studies,

small animal whole-body im

aging plays an increasingly

important role in biomedical research. Currently, none of the existing imaging modalities can provide both anatomical

and glucose metabolic information, leading to higher costs of building dual-modality systems. Even with image co-

registration, the spatial resolution of the metabolic imaging modality is not improved. We present a ring-shaped confocal

photoacoustic computed tomography (RC-PACT) system that can provide both assessments in a single modality.

Utilizing the novel design of confocal full-ring light deliv

ery and ultrasound transducer

array detection, RC-PACT

provides full-view cross-sectional imaging with high spatial resolution. Scanning along the orthogonal direction provides

three-dimensional imaging. While the mouse anatomy was imaged with endogenous hemoglobin contrast, the glucose

metabolism was imaged with a near-infrared dye-labeled 2-deoxyglucose. Through mouse tumor models, we

demonstrate that RC-PACT may be a paradigm shifting imaging method for preclinical research.

Keywords:

Photoacoustic computed tomography, small-animal whole-body imaging, metabolic imaging

INTRODUCTION

The importance of imaging tumor metabolism establishes itself

from the premise that anatom

ical changes alone are not

an accurate metric for diagnosis, progno

sis, and therapy. In particular, tumor

metabolic imaging provides a spatial and

temporal map of therapeutic response and guides treatment planning and selection. Therefore, simultaneous metabolic

and anatomical imaging is very desirable, and necessary no

t only in clinical settings, but also in preclinical cancer

models to improve our understanding of cancer, metastasis, and drug efficacy in vivo [1, 2].

Currently, X-ray computed tomography (CT) [3] and magnetic resonance imaging (MRI) [4] provide high-resolution

anatomical images, but they cannot prov

ide sufficient metabolic contrast without combining with metabolic imaging

modalities. Despite the high cost of dual-modality imaging systems and the need for image registration, metabolic

imaging systems have their own limitations. For instance, positron emission tomography (PET) is very expensive, and

the radioisotopes are difficult to manufacture and have short ha

lf-lives. In addition, the accumulated radiation dosage of

the combined PET/CT may be carcinogenic and

will confound results in oncology [5, 6].

Here, we present a ring-shaped confocal photoacoustic computed tomography (RC-PACT) scanner that can image both

anatomy and tumor glucose metabolism at high spatial resolution in a single imaging modality [7, 8]. In RC-PACT,

anatomical images were produced by endogenous hemoglobin contrast, and tumor glucose metabolism was imaged and

quantified using spectral separation of the absorption of IRDye800-2DG, a near-infrared fluorophore-labeled glucose

analog, from that of hemoglobin [9].

With the unique design of confocal fre

e-space full-ring light illumination and full-

ring ultrasound transducer array detection, our RC-PACT system generates

in vivo

cross-sectional images with

simultaneous anatomical and metabolic assessments at high spatial resolution [10].

SYSTEM DESIGN

Figure 1 shows the schematic of the RC-PACT system [11]. A tunable Ti-Sapphire laser with 12 ns pulse duration and

10 Hz pulse repetition rate was used as the irradiation source. The laser beam passed through a conical lens to form a

ring-shaped light, which was then focused using an optical condenser to project a thin light band around the object. The

light incident area was aligned to be slightly above the acoustic focal plane to minimize the detection of strong surface

Photons Plus Ultrasound: Imaging and Sensing 2013, edited by Alexander A. Oraevsky, Lihong V. Wang,

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Conical lens

Anesthesia gas tube

c -

Optical condenser

! Water

Transducer array

Animal

Heater

Flexible

membrane

agnetic base

512 preamps

8:1 multiplexers

64- channel

amplifier& DAQ

Ti- sapphire laser

Computer

,,,..,

signals. The photoacoustic signals were detected by a 5

12-element full-ring transducer

array with 5 MHz central

frequency (80% bandwidth) and 50 mm ring diameter. Each elem

ent in the array was mechanica

lly shaped into an arc to

produce an axial focal depth of 19 mm within the imaging pl

ane. The combined foci of all elements generated a central

imaging region of 20 mm diameter and 1 mm thickness [11, 12]. Since the light incidence was oblique, the light formed

a weak focus inside the animal body. This focal region overlapped with the acoustic focal plane to improve the

efficiency of detecting photoacoustic signals generated in deep tissues [7].

Figure 1. Experimental setup of the full-ring confocal

whole-body photoacoustic com

puted tomography system.

SYSTEM CALIBRATION

In spectral experiments, the beam profile of the laser varied

at different wavelengths, which led to changes in the fluence

distribution, adding complexities on spectral separation. This

problem can be solved either by aligning the optics after

each wavelength tuning, which requires a

tremendous amount of time in three-dime

nsional scanning, or more efficiently,

by post-experimental compensation. In this research, we used a phantom calibration method to compensate for both the

laser power and the light band uniformity of different

wavelengths. The phantom wa

s made from a gelatin-water

suspension mixed with 0.1% black ink. The suspension was put in a cylindrical container, whose inner diameter was

similar to the mouse cross-sectional diameter (20 mm), and was then cooled in the fridge until gelled. The gelled

phantom was then mounted on the RC-PACT scanner and imaged using the same scheme as the animal experiment.

Cross-sectional photoacoustic images of

the phantom were reconstructed at each

wavelength, and th

e ring-shaped light

variation was obtained based on the surface signal of the phantom image. The matrix of light variation was then used as

a weighting function to calibrate the spectral

in vivo

images. The calibration results are demonstrated in Figure 2. The

compensated images have similar signal intensity at differe

nt wavelengths and a more uniform signal distribution around

the illumination ring.

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5 mm

(a)

(b)

(c)

(d)

(e)

(f)

(g)

(h)

(i)

776 nm

796 nm

820 nm

PA amplitude (a.u.)

Max

Min

Figure 2. Image compensation for the wavelength-dependent laser

power and ring-shaped-light distribution. Top row (a-c), un-

compensated images. Middle row (d-f), phantom

images. Bottom row (g-i), compensated im

ages. Left column: images acquired at

776 nm. Middle column: images acquired at 796 nm

. Right column: images acquired at 820 nm.

IN VIVO

ANATOMICAL IMAGING

To demonstrate the

in vivo

anatomical imaging capability of our RC-PACT

system, we imaged healthy athymic (nude)

mice. Figure 3 shows serial cross-sectional images of 5-6-

week-old healthy athymic mice

in axial views. The brain

cortex, heart, liver, spleen, an

d kidneys are clearly visible. Additionally, detailed vascular structures within these organs

are visible, demonstrating that the system can be used for whole-body angiographic imaging without injecting

exogenous contrasts. The spinal cord, stomach, and gast

rointestinal tracts are imag

ed due to the surrounding

microvasculature. Major blood vessels, such as the vena cava

, are also clearly visible. Us

ing exogenous optical contrast

(e.g., near-infrared dyes), the system can also image or

gans with little blood. The bladder image was acquired 30

minutes after tail vein administration of IRDye800-2DG. The

urinary bladder showed strong contrast as it was filled

with the dye excret

ed by the kidneys.

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