1. Introduction
Photoacoustic tomography (PAT), which is also called optoacoustic or thermoacoustic tomography, is based on the generation of ultrasound following a temperature rise after the illumination of light-absorbing structures within a semitransparent and turbid material, such as a biological tissue. It provides optical images with specific absorption contrast [
1,
2,
3]. Therefore, it offers greater specificity than conventional ultrasound imaging with the ability to detect hemoglobin, lipids, water, and other light-absorbing chromophores, but with greater penetration depth than purely optical imaging modalities that rely on ballistic photons. In PAT, the temporal evolution of the acoustic pressure field is sampled using an array of ultrasound detectors placed on the tissue surface or by moving a single detector across the detection surface. Images of the optical absorption within the tissue are then reconstructed by solving an inverse source problem [
3,
4,
5].
In this work, the influence of acoustic attenuation on the achievable spatial resolution is investigated. At depths larger than the range of the ballistic photons, i.e., more than a few hundreds of microns in tissue, light is multiply scattered, and the spatial resolution is limited by acoustics. As higher acoustic frequencies, which have smaller wavelengths and allow a better resolution, are more strongly damped than lower frequencies, the spatial resolution decreases with depth. The spatial resolution is limited at such depths by the acoustic diffraction limit that corresponds to the highest detectable frequency. The ratio of the imaging depth to the best spatial resolution is roughly a constant of 200 [
3]. Only recently published non-linear imaging methods, which use additional information such as the sparsity of the imaged structure, can overcome the acoustic diffraction limit, and are therefore called “super-resolution” [
6,
7]. Technical limitations, such as a bandwidth mismatch between the acoustic transducer and the acoustic signal on the sample surface or the noise of an amplifier, can reduce the resolution in addition, but can be avoided in principle.
There have been several attempts for mathematically compensating the acoustic attenuation to obtain images with a higher spatial resolution. Already in 2005, La Riviere et al. proposed an integral equation that related the measured acoustic signal at a given transducer location in the presence of attenuation to the ideal signal in the absence of attenuation [
8,
9]. Ammari et al. later gave a compact derivation of this integral equation directly through using the wave equations, which is valid for all of the dimensions [
10]. Dean-Ben et al. described the effects of acoustic attenuation (amplitude reduction and signal broadening), compared these effects to the influence of the transducer bandwidth and space-dependent speed of sound, and established a correction term similar to La Riviere, but for space-dependent attenuation [
11]. Kowar and Scherzer used a similar formulation for other lossy wave equations [
12].
Burgholzer et al. have directly compensated for the attenuation in photoacoustic tomography by using a time reversal finite differences method with a lossy wave equation [
4,
13,
14,
15,
16]. The time reversal of the attenuation term causes the acoustic waves in the finite differences model to grow, as they propagate back in time through the tissue. At each time step, the total acoustic energy is controlled by cutting high-frequency signals, which would otherwise grow too quickly. This approach was later extended by Treeby et al. to account for the general power law absorption behavior [
17,
18]. Inspired by attenuation compensation in seismology, Treeby proposed a new method for attenuation compensation in photoacoustic tomography using time-variant filtering [
19].
All of these attempts have one thing in common: the compensation of the frequency-dependent attenuation is an ill-posed problem that needs regularization. The physical reason for this ill-posedness is thermodynamics: acoustic attenuation is an irreversible process and the entropy production, which is the dissipated energy of the attenuated acoustic wave divided by the temperature, is equal to the information loss for the reconstructed image [
16]. This also limits the spatial resolution, which correlates with the information content of the reconstructed image. To reach this thermodynamic resolution limit for the compensation of acoustic attenuation, it is necessary to measure the broadband ultrasonic attenuation parameters of tissues or liquids very accurately [
20], and evaluate the existing mathematical models in order to get an accurate description of the attenuation [
21].
In
Section 2, the experimental set-up to measure the laser-induced acoustic wave at a varying distance is described.
Section 3 gives the theoretical resolution limit for the acoustic attenuated waves in water. In
Section 4, the measured acoustic wave signals are presented, the acoustic attenuation is compensated, and the theoretical limits are verified. In
Section 5, the results are summarized, and the extension to other materials, such as biological tissue, is discussed.
3. Compensation of Acoustic Attenuation and the Limits of Resolution
For a plane wave, a Dirac’s delta pulse
after traveling a distance
in a liquid, such as water, the pressure
can be described as (e.g., [
11]):
in which
is the attenuation constant,
is the time, and
is the sound velocity. The amplitude of the pulse is decreased, and the width of the Gaussian pulse is increased by a factor of
. Without attenuation, the ideal wave is:
where the shape of the pulse does not change. According to [
11], for a one-dimensional plane wave, a relationship between the non-attenuated plane wave
and the attenuated wave
can be established:
where
denotes the time convolution.
In the frequency domain, acoustic attenuation in water is described by a power-law dependence, as can be seen by the Fourier transformation of Equation (3):
where the Fourier transformation of the time convolution is the product of the Fourier transformations. Acoustic attenuation in a liquid is proportional to the square of the frequency
. The Kramers–Kronig relationship states that for a power-law with an exponent of two, no dispersion occurs, and therefore the sound velocity
does not depend of the frequency
. This makes the equations simpler than those for other exponents, such as a linear frequency behavior of attenuation, which is often assumed for biological tissues [
11]. However, despite these mathematical difficulties, the same arguments that are presented here can be used for any materials and mathematical models for acoustic attenuation.
The limit in spatial resolution caused by frequency-dependent attenuation can be compensated numerically only up to a certain limit given by thermodynamics. The entropy production, which is the dissipated energy of the acoustic wave divided by the temperature, is equal to the information loss, which cannot be compensated by any reconstruction method. The compensation of acoustic attenuation is according to Equation (3) a deconvolution to get
from the measured pressure
, which is mathematically an ill-posed inverse problem. Regularization methods, such as the truncated singular value decomposition (T-SVD) method, can solve this inverse problem. Before actually inverting Equation (3), the physical argument of entropy production as the cause for the “ill-posed-ness” of this inverse problem is elaborated in a similar way as we could do already for heat diffusion [
24,
25].
Thermodynamic fluctuations are the reason for the entropy production, which reduces the available information about the subsurface structures in the measured surface data. They are extremely small for macroscopic samples, but are highly amplified due to the ill-posed problem of the inversion of Equation (4) in the frequency domain. The factor for higher frequencies gets extremely small; therefore, for the inversion, the factor gets very large, which is also the factor for the amplification of the fluctuations.
Non-equilibrium thermodynamics has made enormous progress over the last decade. Heating light absorbing structures with a laser pulse and observing the induced pressure wave is definitely a process in which the system state is far from equilibrium. One comprehensive letter about non-equilibrium thermodynamics, the second law, and the connection between entropy production and information loss was published in 2011 by M. Esposito and C. van den Broeck [
26]. They gave a proof that for two different non-equilibrium states evolving to the same equilibrium state, the entropy production
ΔiS during the evolution from one state to the other is equal to the information loss
ΔI =
kBΔD, with the Boltzmann constant
kB and
ΔD being the difference of the Kullback–Leibler divergence
D, which is also called the relative entropy of these states.
D is a measure of how “far” a certain state is away from equilibrium, see e.g., [
27]. The entropy production for macroscopic states with small fluctuations around equilibrium turns out to be a good approximation that is equal to the dissipated energy
ΔQ divided by the mean temperature
T, so
ΔiS = ΔQ/T = kB ΔD [
24,
25].
In the frequency domain, the information loss with increasing time can be described by a cut-off frequency
, which is calculated similar to that which is done for heat diffusion in thermography [
24,
25]. Equation (4) shows that after some distance
r, the acoustic attenuation reduces the amplitude of
by a factor of
. The energy of the acoustic wave with frequency
is proportional to the square of the pressure amplitude:
can be found e.g., in Morse and Ingard [
28], where
is the adiabatic compressibility with the density
, and
is the measurement volume. Since
corresponds to the variance of the pressure (e.g., from Landau and Lifshitz [
29]), one gets for the information content, which is the negative entropy of each frequency component
. Note, that the signal-to-noise ratio (
SNR) at the distance
is the reciprocal value of the square root of the variance of the pressure, as the signal amplitude in the frequency domain is normalized to one (Equation (4)). Now, the cut-off frequency
is defined so that the information content in this frequency component is so low that its distribution cannot be distinguished from the equilibrium distribution within a certain statistical error level (Chernoff–Stein Lemma, see e.g., [
27]). This error level can be set such that the amplitude of
is damped below the noise level for frequencies higher than
[
24]. Using this error level, the acoustic wave at a distance
cannot be distinguished from equilibrium if
gets less than
, which gives:
For the spatial resolution in photoacoustic imaging, the width of the acoustic signal in the time domain is essential. A small width enables a high spatial resolution, which corresponds to a broad frequency bandwidth. If the frequency bandwidth is limited by thermodynamic fluctuations according to Equation (5), the spatial resolution limit according to Nyquist is half the wavelength at this frequency:
For our experimental set-up described in
Section 2, the acoustic pulse is measured by a piezoelectric transducer. Its impulse response
is taken into account in the time domain by an additional convolution in Equation (3), or in Equation (4) by an additional factor
in the frequency domain. The transducer limits the frequency bandwidth. This technical limit can be overcome (in principle) by using better transducers with higher bandwidths. As shown in the next section, our used transducer can measure the frequency components only up to approximately 100 MHz, which is for smaller propagation distances
significantly lower than the cut-off frequency
from Equation (5). Therefore, it is expected that a degradation of the resolution
with increasing distance
according to Equation (6) can only be found for higher distances, where
is in the order of—or lower—than 100 MHz.
5. Discussion, Conclusions, and Outlook
The numerical compensation of acoustic attenuation is an ill-posed inverse problem that needs regularization. Here, for the reconstruction of the ideal waves without acoustic attenuation from the measured pressure data of plane waves at a varying distance, the truncated singular value decomposition (T-SVD) method in the frequency domain was applied for regularization.
Choosing an adequate regularization parameter, which is for the T-SVD method the truncation frequency
, is essential. If this frequency is too high, reconstruction artifacts come up due to the amplification of fluctuations (noise), as shown in
Figure 5 (dashed line). If it is taken too low, resolution is lost (
Figure 5, dotted line). A physical argument from thermodynamics for choosing the regularization parameter could be given. For a certain propagation distance
of the acoustic wave in water, the truncation frequency
is the frequency where the acoustic wave is just damped to the noise level. Lower frequencies are damped less, and therefore, these frequency components can contribute to the reconstruction of the ideal wave. Higher frequencies are damped below the noise level, and therefore, they are truncated and cannot contribute to the reconstruction of the ideal wave.
It was shown that for this truncation frequency
, the absorbed acoustic energy divided by the temperature, which is the entropy production for this frequency component, is equal to the information loss described by the relative entropy (Kullback–Leibler divergence
D). The close connection of entropy production (dissipation) to the signal noise (fluctuation) is an example of the fluctuation–dissipation theorem in non-equilibrium thermodynamics [
24,
25]. This enables us to give a physical argument for the choice of the regularization parameter
: either when the frequency components of the acoustic signal are just damped to the noise level, or, which is equivalent according to the fluctuation–dissipation theorem, where the information content gets smaller than a certain level, and then this component cannot be distinguished from thermodynamic equilibrium (Chernoff–Stein–Lemma).
For the chosen transducer with a truncation frequency of 125 MHz, it turns out that the acoustic attenuation in water is too low to detect a significant degradation in resolution for a propagation distance up to 20 mm, where according to Equation (5), the truncation frequency only for acoustic attenuation is equal to the truncation frequency of the transducer. This is different for a propagation distance of 24.65 mm. Then, the truncation frequency for acoustic attenuation is 112 MHz, and in combination with the transducer, it is 93 MHz (
Table 1). For future work, either a transducer with a higher bandwidth or a liquid with higher attenuation, such as glycerin, may be used. The proposed method could be used for media other than water, such as biological tissue where acoustic attenuation is higher and has a different power-law frequency dependence. In a first approximation, the change of the sound velocity with frequency, which is called dispersion, could be neglected compared to attenuation [
11]. Acoustic attenuation in biological tissue is caused by a combination of dissipation and scattering, and the power law describing the frequency-dependent attenuation should describe both dissipation and scattering. If the frequency dependence of scattering and dissipation is significantly different than that in the observed frequency range, the power law needs to be modified.
In this manuscript, only one-dimensional wave propagation in a plane wave model is presented. The results only refer to the axial resolution in the direction of propagation. The relationship between the non-attenuated plane wave
and the attenuated wave
as shown in Equation (3) is local, which means that for
and for
, the same location in the sample is used, and the relation is the same for one, two, or three-dimensional wave propagation [
10]. We have shown this explicitly by simulating the attenuated signal at a distance of 10 mm from a 200-micron thick layer (1D), a cylinder (2D), and a sphere (3D) as an acoustic source. Reconstruction in the axial direction was the same [
14,
15]. Therefore, it is sufficient to describe plane wave propagation. Of course, the resolution in higher dimensions varies for different directions. For one-dimensional propagation, no reconstruction is necessary, because the resolution is directly given by
in Equation (11). For two or three-dimensional wave propagation, reconstruction methods such as time reversal reconstruction [
4] can be used for image reconstruction from
. For lateral reconstruction perpendicular to the axial direction, propagation directions that have an angle
to the axial direction are necessary. For such propagation directions, the distance to the sample surface increases with
, which especially broadens the resolution in the lateral direction.