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Photoacoustic Tomography Principles and Applicatio PDF
Photoacoustic Tomography Principles and Applicatio PDF
Photoacoustic Tomography Principles and Applicatio PDF
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Etienne De Montigny
Polytechnique Montréal
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1. Introduction
The photoacoustic (PA), also referred as optoacoustic, effect was first introduced by
Alexander Graham Bell in 1880. He found that absorption of electromagnetic waves
by a medium generated sound waves. Even though the PA effect was known for a long
time, it was not until 1994 that Kruger [1] demonstrated application of this phenomenon
in highly scattering media. It was applied a few years later to biomedical imaging [2].
The PA effect explains how electromagnetic energy can be absorbed and converted into
acoustic waves. PA imaging benefits from the advantages of pure optical or ultrasound
imaging, without the major disadvantages of each technique [3]. PAT combines the
high contrast from absorption of light with the high resolution and penetration depth
of ultrasound imaging.
Optical modalities benefit from high contrast due to electromagnetic interaction with
materials, particularly absorption. Absorption in a biological tissue can be modeled
with the well-known Beer-Lambert law:
I = I0 × exp(−µa L) (1)
where I is the intensity after light has traveled L meters, I0 is the initial intensity and
µa is the absorption coefficient.
High resolution (1 − 10µm) can be obtained in optical imaging because of the short
wavelengths used, typically between 650 and 1350 nm. The major problem in optical
imaging is the penetration depth. Biological tissue scatters light a lot. By replacing µa
by µs , the Beer-Lambert law presented in Eq:1 can also be used to model scattering.
This coefficient (µs )is around 1-10 mm−1 [4] in biological tissue. This means that the
major part of the incident light has scattered after one millimeter. Scattering increases
with shorter wavelengths, this is why near infrared (NIR) light is mostly used in optical
biomedical imaging. Since photons that have not scattered form the signal of interest,
maximal imaging depth rarely exceeds 3 mm. Diffuse optical tomography extends the
penetration depth by detecting diffuse photons. This requires complex algorithms and
suffers from poor spatial resolution [4].
On the other hand, ultrasound imaging, also known as echography, relies on acous-
tic waves to study a tissue. High resolution (100µm)can also be obtained with short
wavelengths, because they can resolve smaller details. In addition, penetration depth
is in the order of centimeters to a few tens of centimeters [5]. The down side is that
the signal of interest is reflected waves due to changes in the speed of sound and these
changes are relatively small. Therefore, contrast is poor in ultrasound imaging. Func-
tional information is provided by Doppler imaging, where the velocity of fluids such as
blood is imaged.
Photoacoustic tomography (PAT) aims to use the advantages of both optical and
ultrasound imaging, without the disadvantages. This is done by illuminating the sam-
ple with diffuse, short pulses and collecting the ultrasound waves generated by the
PA effect. This review article covers the basis of the PA effect and the generation,
propagation and detection of the photoacoustic waves. The third section describes the
inverse source problem in PAT and shows how a reconstruction algorithm can solve it.
Finally, biomedical applications of this new imaging modality in cancer detection and
atherosclerosis study are discussed.
Piezoelectric transducer
Incident light (detector)
Photoacoustic source
Fig. 1. Basic principle of the photoacoustic effect. Incident light is absorbed and
converted in acoustic waves by thermal expansion. The acoustic waves are de-
tected by a piezoelectric transducer.
2.3. Absorption
Blood is the major absorbent in biological tissues, as depicted in Fig. 2(b). Therefore,
the signal comes mainly from regions where there is a high concentration of blood.
Since hemoglobin linked with oxygen (oxyhemoglobin) and hemoglobin without oxygen
(deoxyhemoglobin) have different absorption spectra, careful selection of the excitation
wavelength can bring important information of the oxygenation ratio. Their respective
absorption spectra are presented in Fig. 2(a). Fig. 2(b) shows the absorption spectra of
the major absorbents in biological tissues : water, melanin and blood. This figure shows
why NIR is preferred over other wavelengths : absorption by water is minimal in this
region of the spectra, and absorption by blood is large.
4. Reconstruction
4.1. Inverse problem definition
The major challenge in PAT resides in image reconstruction. Reconstruction algorithms
used in PAT mostly have already been used in other imaging modalities such as com-
puted tomography (CT), magnetic resonance imaging (MRI) and ultrasound [6]. This
challenge arises from the fact that the location of the source of the acoustic waves is
unknown. It is in fact what we wish to know. To illustrate this source problem, let’s
examine the following example [11]. How can we identify where thunder originated in
a lightning storm? Knowing the time delay between the flash of light and the hearing
of the thunder can help restrain the source in a circle. The radius of this circle is the
product of the time delay and the speed of sound. It would take three measurements to
triangulate the exact source. When many lightnings strike at the same time, it becomes
increasingly difficult to localize each source. The same inverse problem is the basis of
photoacoustic imaging. This can be seen in Fig. 3(a) where the detector sees signals
coming from a circle of radius vst. In Fig. 3(b), the N-shape of the signal shows the
densification and rarefaction sections of the pressure wave. PAT uses a reconstruction
algorithm to correlate the measurements taken with the source of the signal.
Fig. 3. (a) Source location ambiguity arises from the fact that only the time
between the laser pulse and the arrival of the pressure waves to the detector is
known. (b) Typical N-shape of the pressure waves. (Ref. [6], Fig. 2).
4.2. Reconstruction
Many different approaches have been suggested to solve the inverse problem of PAT. An-
alytic back-projection algorithm [12], finite-elements [13], Radon transform [14], Fourier
domain analysis [15, 16], diffusion equation based reconstruction [17] are all successful
methods, but they require extensive mathematical analysis to be explained. In this sec-
tion, an explanation of a widely used method named weighted delay-and-sum [18], or
synthetic aperture, is provided. The first section explains dynamic focusing with an
array of transducers. The second part explains how to use focusing to reconstruct an
image of the PA source.
4.2.1. Focusing
A flat linear array of transducers can be used to produce a focused beam or alternatively,
detect signal coming from a particular region. The obvious way to do this is to fire all
transducers at the same time and use an acoustic lens, which will act the same way as
an optical lens and focus the waves at the focal spot. The other way to do this is to
fire each transducer in the array separately with a variable delay. When the distance
between the transducer and the desired focal spot shortens, the induced delay increases.
In this way, all pulses emitted by the transducers arrive at the same time at the focal
spot. This is called electronic focusing. Reciprocally, adding a delay to the detected
signals can lead to a greater sensitivity to a particular area of the sample. This is the
basis of the delay and sum reconstruction algorithm. Focused detection is illustrated in
figure 4.
5. Applications
This section reviews the most promising applications of photoacoustic tomography in
medical imaging. The main application is cancer detection, which will be covered in the
first section, with a focus on breast cancer. The next section covers the identification of
atherosclerotic plaques by intravascular PAT.
Fig. 5. Thin slices of a 3D volume (1-10) performed 3 days (a), 7 days (b), 8 days
(c) and 10 days (d) after inoculation of cancerous cells on a rat. The evolution
of the tumor and associated angiogenesis can be clearly seen in (b), (c) and (d).
(Ref. [19], Fig. 3).
The use of contrast agents has also shown promising results in cancer detection. The
contrast can be enhanced by using particles that bind selectively to cancerous cells such
as nanorods [21] and carbon nanotubes [22] which show high absorption at the laser
wavelength.
Fig. 6. I :(a) X-ray mammography of a dense breast does not show signs of a tumor;
(b) Doppler ultrasonography shows an increased blood flow(c) PAT clearly shows
a tumor; II a) X-ray mammography shows a tumor which is confirmed by the two
other imaging modalities ((b) and (c))(Ref. [29], Fig. 16-17).
5.2. Identification of atherosclerotic plaques
Atherosclerosis is a systemic disease in which lipid accumulates in arterial walls and
form atherosclerotic plaques. Inflammation also occurs and leads to an increase in blood
content in the plaque. The major complication of atherosclerosis is a rupture of the
plaque which will form a thrombus that can block blood flow in the artery, leading
to the death of the tissue fed by the artery. The vulnerability of a plaque to rupture
depends on the content of the plaque. Thus, information on the content of the plaque
will allow identification of the vulnerable plaques and take action before it ruptures. In
[30, 31, 32], a group from the University of Texas showed a new device for intravascular
photoacoustic (IVPA) using a commercial intravascular ultrasound probe, usually used
for ultrasound imaging. This probe consists of a catheter with a high frequency (40
MHz) transducer at the tip. Such high frequency can be used because the required
imaging depth is small since the plaques are usually a few millimeters thick. Ex vivo
studies on cholesterol fed rabbits show that PAT can be used to identify atherosclerotic
plaques. An artery was taken from the rabbit and immersed in water. The catheter
was inserted in the artery and laser pulses were sent on the artery from the outside.
An integrated system using an optical fiber to deliver light was proposed by Hsieh
et al. [33]. By using a frequency-doubled Nd:YAG, a decrease in signal was observed
in the lipid rich region [31]. Complementary structural information was provided by
using the probe in ultrasound mode. Further study [32] using an OPO to change the
wavelength between 680 and 900 nm showed that spectroscopic PA imaging can provide
more information. The transducer could also be used for standard ultrasound imaging.
Thus, structural and functional information can be retrieved.
6. Conclusion
A review of photoacoustic tomography was presented. While the photoacoustic phe-
nomenon has been known for a long time, photoacoustic medical imaging is a recent
domain and we have yet to see all of the possible applications. Breast cancer detection
and identification of atherosclerotic plaques are but a few of the pathologies PAT can be
applied to. PAT is being extended to the study of a number of pathologies such as trau-
matic brain injury [34], retinal diseases [35] and arthritis [36]. Furthermore, multimodal
imaging seems to be the way to improve overall diagnosis efficiency. Since no technique
is perfect, combining the advantages and contrast mechanisms of different technolo-
gies leads to more relevant information. PAT retrieves functional information related
mostly to blood concentration. Combining this with a structural imaging technique such
as ultrasound or X-ray, or novel techniques such as optical coherence tomography and
confocal microscopy will provide more efficient, faster and earlier diagnosis, all for the
well-being of the patient.
Acknowledgments
The author thanks Dr. Guy Lamouche for invaluable advices and remarks.