All-optical imaging has high contrast but poor spatial resolution beyond the ballistic and quasiballistic regimes. All-ultrasonic imaging has high spatial resolution but poor contrast for early stage tumors. Photoacoustic tomography combines the high optical contrast and the high ultrasonic resolution. Our work in this emerging area of research will be summarized in this invited talk. In this technology, a diffraction-based inverse-source problem is solved in the image reconstruction, for which our group developed the rigorous reconstruction theory. We developed a prototype and accomplished noninvasive transdermal and transcranial functional imaging of small-animal brains in vivo

Ku, Geng

Stoica, George

Wang, Lihong V.

Wang, Xueding

Caltech Authors - Main

  
HIGH-RESOLUTION FUNCTIONAL PHOTOACOUSTIC TOMOGRAPHY 
 
Lihong V. Wang*, Xueding Wang, Geng Ku, George Stoica 
 
Optical Imaging Laboratory, Department of Biomedical Engineering 
Texas A&M University, 3120 TAMU, College Station, Texas 77843-3120 
URL: http://oilab.tamu.edu; Email: LWang@tamu.edu 
* Corresponding author. 
 
Abstract:  All-optical imaging has high contrast but 
poor spatial resolution beyond the ballistic and quasi-
ballistic regimes.  All-ultrasonic imaging has high 
spatial resolution but poor contrast for early stage 
tumors.  Photoacoustic tomography combines the high 
optical contrast and the high ultrasonic resolution.  Our 
work in this emerging area of research will be 
summarized in this invited talk.  In this technology, a 
diffraction-based inverse-source problem is solved in 
the image reconstruction, for which our group 
developed the rigorous reconstruction theory.  We 
developed a prototype and accomplished non-invasive 
transdermal and transcranial functional imaging of 
small-animal brains in vivo. 
 
Keywords – Photoacoustic tomography, ultrasonic 
resolution, optical contrast, inverse-source 
reconstruction 
 
 
I. INTRODUCTION 
 
Photoacoustic tomography (PAT, also called optoacoustic 
or thermoacoustic tomography) involves both photons and 
ultrasound.  A short-pulsed laser source is used to irradiate 
the biological tissue samples under investigation.  A 
temperature rise of the order of mK will be produced in a 
short time frame.  Consequently, thermoelastic expansion 
will cause emission of acoustic waves, referred to as 
photoacoustic waves.  The photoacoustic waves are 
measured by wideband ultrasonic transducers around the 
sample, and the acquired photoacoustic waves are used to 
reconstruct the optical absorption distributions.  Because 
the laser pulse is short, proportionately high frequency 
ultrasonic waves will be produced and used to provide 
diffraction-limited spatial resolution. 
 Based on the above principle, the contrast in PAT 
is determined primarily by the optical properties of the 
biological tissues, and the spatial resolution in PAT is 
determined primarily by the photoacoustic waves 
originating from within the biological tissues.  
Photoacoustic tomography thereby combines the high 
optical contrast and the high ultrasonic resolution.  This 
point is summarized in Table 1.   
 
Table 1.  Motivation for PAT. 
 
 All-optical 
imaging 
(Non-
ballistic) 
All-ultrasonic 
imaging 
 
PAT 
Contrast Excellent Poor for early 
cancers 
Excellent 
Resolution Poor Excellent & 
scalable 
Excellent 
Depth Excellent Good & 
scalable 
Good & 
scalable 
Speckle 
artifacts 
None Strong None 
Scattering Strong Weak  
 
II. FUNDAMENTALS OF PHOTOACOUSTICS: 
THE FORWARD PROBLEM 
 
The basic equations in photoacoustic theory will be 
summarized here.  If the electromagnetic pumping pulse 
duration is much shorter than the thermal diffusion time, 
thermal diffusion can be neglected; this is known as the 
assumption of thermal confinement. In this case, the 
acoustic wave ),( tp r  is related to electromagnetic 
absorption, ),( tH r , by the following wave equation: 
 ,
),(),(),( 22
2
t
tH
C
v
tp
t
tp s
∂
∂
=∇−
∂
∂ r
r
r β
 (1) 
where stvt = ; sv  is the acoustic speed, assumed to be 
constant; C is the specific heat; and β  is the coefficient of 
volume thermal expansion. Eq. (1) can be rewritten in 
terms of ),( tH r : 
 ∫∫∫ ′−
′
′∂
′′∂
= ,
),(
4
),(
rr
rr
r
d
t
tH
C
v
tp s
π
β
 (2) 
where rr ′−−=′ tt . The source term ),( tH r  can further 
be written as the product of a purely spatial and a purely 
temporal component, i.e.: 
 ),()(),( 0 tItH ηrr ϕ=  (3) 
14790-7803-8388-5/04/$20.00  ©2004 IEEE
 where 0I  is a scaling factor proportional to the incident 
radiation intensity; )(rϕ  describes the electromagnetic 
absorption properties of the medium at r; and )(tη  
describes the shape of the irradiating pulse. Substituting Eq. 
(3) into Eq. (2) results in 
 ∫∫∫ ′−
′
′
′
′ϕ= .)()(
4
),( 0
rr
r
rr
d
td
td
C
vI
tp s η
π
β
 (4) 
This equation provides the solution to the forward 
problem—prediction of the pressure outside the tissue if the 
absorption properties of the medium and the profile of the 
electromagnetic pulse are known.  Its inverse problem 
needs to be solved for imaging. 
 
III. PHOTOACOUSTIC RECONSTRUCTION: THE 
INVERSE PROBLEM 
 
Our group derived the exact inverse solutions in planar, 
spherical, and cylindrical geometries [1–3].  These exact 
solutions are computationally intensive and were 
approximated to more efficient solutions in practical cases 
[4].  Usually, the distance between the photoacoustic 
sources and the detector is much longer than the 
wavelengths of the high-frequency photoacoustic waves 
that are useful for imaging.  Under this far-field condition, 
the following approximate inverse solution holds: 
 ∫∫
−=
∂
∂
=
0 0
/||
0
0
),(1)cos()(
S t
d
s
t
tp
t
dSC
ν
θϕ
rr
r
r , (5) 
where C is a constant; 0S  is the surface of detection; and θd 
is the angle between the normal of dS0 and 0rr −  (the 
vector pointing from a point of detection to a point of 
reconstruction). It should be noted that Eq. (5) is a modified 
back-projection of quantity 
t
tp
t ∂
∂ ),(1 0r
. 
 This back-projection is analogous to that in x-ray 
computed tomography (CT).  In x-ray CT, the back-
projection is along the paths of the x-ray propagation.  In 
PAT, the back-projection however is along the spherical 
shells that are centered at each of the ultrasonic detectors 
and that have a radius determined by the acoustic time of 
flight. 
 
IV. EXPERIMENTS 
 
A configuration of the key components in our PAT system 
is shown in Fig. 1.  An Nd:YAG laser was used to provide 
532-nm laser pulses with a width of 6.5 ns.  The laser beam 
was expanded and homogenized to provide an incident 
energy density of <10 mJ/cm2 on the skin of the rat head, 
which induced a temperature rise in the skin estimated to be 
<20 mK.  The photoacoustic waves were coupled into an 
ultrasonic transducer and were acquired around the head by 
scanning the ultrasonic transducer around the animal head 
in the horizontal imaging plane.  The initial system required 
the immersion of the animal in the water tank for ultrasonic 
coupling, where the animal breathed through a tube.  An 
improved system placed the animal below the water tank 
and coupled the ultrasonic signals through a deformable 
membrane at the bottom of the tank.  When an ultrasound 
array becomes available to this technology, conventional 
gel coupling will be used to avoid the use of water 
coupling. 
 We used our PAT system to image the functional 
response of the cerebral cortex of rats to changes from 
hyperoxia to hypoxia.  Non-invasive PAT images of the 
brain were taken when the animal inspired gas at 100% O2 
and 5% O2, respectively.  Subtracting the two PAT images 
produced a map corresponding to the functional changes of 
the cerebral cortex (Fig. 2) [5]. 
 
V. SUMMARY 
 
We developed rigorous reconstruction algorithms, the 
foundation for PAT.  We accomplished non-invasive 
transdermal and transcranial imaging of small-animal 
brains in vivo showing both structures and functions.  
Imaged structures include primarily the vasculature.  
Imaged functions include hemodynamic responses to 
various stimuli such as whisker stimulations, hyperoxia, 
and hypoxia. 
 
VI. ACKNOWLEDGEMENTS 
 
This project was sponsored in part by the U.S. Army 
Medical Research and Materiel Command Grant No. 
DAMD17-00-1-0455, the National Institutes of Health 
Grants No. R01 EB000712 and No. R01 NS46214, and 
Texas Higher Education Coordinating Board Grant No. 
ARP 000512-0063-2001. 
 
VII. REFERENCES 
 
 
1. M. Xu and L.-H. Wang, "Time-domain reconstruction for 
thermoacoustic tomography in a spherical geometry," IEEE 
Transactions on Medical Imaging 21 (7), 814–822 (2002). 
2. Y. Xu, D. Feng, and L.-H. Wang, "Exact frequency-domain 
reconstruction for thermoacoustic tomography—I: Planar 
geometry," IEEE Transactions on Medical Imaging 21 (7), 
823–828 (2002). 
3. Y. Xu, M. Xu, and L.-H. Wang, "Exact frequency-domain 
reconstruction for thermoacoustic tomography—II: 
Cylindrical geometry," IEEE Transactions on Medical 
Imaging 21 (7), 829–833 (2002). 
4. M. Xu, Y. Xu, and L.-H. V. Wang, “Thermo-acoustic 
imaging in biological tissues: Time-domain reconstruction 
algorithms”, in preparation (2003). 
5. X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L.-H. 
Wang, "Non-invasive laser-induced photoacoustic 
tomography for structural and functional imaging of the brain 
in vivo," Nature Biotechnology[0] 21 (7), 803–806 (2003). 
 
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Mirror Nd:YAG laser 
Lens  
Ground glass 
Ultrasonic 
 transducer 
 
 
Fig. 1.  Prototype PAT for non-invasive 
transdermal and transcranial imaging of the 
small-animal brain in vivo with the skin and 
skull intact. 
 
 
(cm) 
0 0.5 1.0 
2.
0 
1.
5 
1.
0 
0 
0.
5 
1.5 
Optical absorption, A Max Min 
 
A 
(cm) 
0 0.5 1.0 
2.
0 
1.
5 
1.
0 
0 
0.
5 
1.5 
Differential absorption, ∆A Max Min 
 
B 
 
Fig. 2.  Non-invasive photoacoustic tomography (PAT) of cerebral hemodynamic responses to the alteration from 
hyperoxia to hypoxia.   (A) Non-invasive PAT image of vascular distribution in the rat cerebral cortex, which was 
acquired with the skin and skull intact.  (B) Non-invasive functional PAT image of cerebral hemodynamic responses 
to altering the inspired gas from 100% O2 to 5% O2 acquired with the skin and skull intact.  This functional map is 
superimposed on the image of the vascular distribution shown in (A).   
 
 
 
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High-resolution functional photoacoustic tomography

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High-resolution functional photoacoustic tomography

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