Photoacoustic Imaging In Biomedicine
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Photoacoustic imaging or optoacoustic imaging is a biomedical imaging modality based on the
photoacoustic effect The photoacoustic effect or optoacoustic effect is the formation of sound waves following light absorption in a material sample. In order to obtain this effect the light intensity must vary, either periodically (''modulated light'') or as a singl ...
. Non-ionizing
laser A laser is a device that emits light through a process of optical amplification based on the stimulated emission of electromagnetic radiation. The word ''laser'' originated as an acronym for light amplification by stimulated emission of radi ...
pulses are delivered into biological tissues and part of the energy will be absorbed and converted into heat, leading to transient thermoelastic expansion and thus wideband (i.e., megahertz-order bandwidth) ultrasonic emission. The generated ultrasonic waves are detected by
ultrasonic transducer Ultrasonic transducers and ultrasonic sensors are devices that generate or sense ultrasound energy. They can be divided into three broad categories: transmitters, receivers and transceivers. Transmitters convert signal (electrical engineering), ...
s and then analyzed to produce images. It is known that optical absorption is closely associated with physiological properties, such as
hemoglobin Hemoglobin (haemoglobin, Hb or Hgb) is a protein containing iron that facilitates the transportation of oxygen in red blood cells. Almost all vertebrates contain hemoglobin, with the sole exception of the fish family Channichthyidae. Hemoglobin ...
concentration and
oxygen saturation Oxygen saturation (symbol SO2) is a relative measure of the concentration of oxygen that is Dissolution (chemistry), dissolved or carried in a given medium as a proportion of the maximal concentration that can be dissolved in that medium at the g ...
. As a result, the magnitude of the ultrasonic emission (i.e. photoacoustic signal), which is proportional to the local energy deposition, reveals physiologically specific optical absorption contrast. 2D or 3D images of the targeted areas can then be formed.


Biomedical imaging

The optical absorption in biological tissues can be due to
endogenous Endogeny, in biology, refers to the property of originating or developing from within an organism, tissue, or cell. For example, ''endogenous substances'', and ''endogenous processes'' are those that originate within a living system (e.g. an ...
molecules such as hemoglobin or
melanin Melanin (; ) is a family of biomolecules organized as oligomers or polymers, which among other functions provide the pigments of many organisms. Melanin pigments are produced in a specialized group of cells known as melanocytes. There are ...
, or exogenously delivered
contrast agent A contrast agent (or contrast medium) is a substance used to increase the contrast of structures or fluids within the body in medical imaging. Contrast agents absorb or alter external electromagnetism or ultrasound, which is different from radiop ...
s. As an example, Fig. 2 shows the optical absorption spectra of oxygenated hemoglobin (HbO2) and
deoxygenated hemoglobin Hemoglobin (haemoglobin, Hb or Hgb) is a protein containing iron that facilitates the transportation of oxygen in red blood cells. Almost all vertebrates contain hemoglobin, with the sole exception of the fish family Channichthyidae. Hemoglobin ...
(Hb) in the visible and near infrared region. Since blood usually has orders of magnitude higher absorption than surrounding tissues, there is sufficient endogenous contrast for photoacoustic imaging to visualize blood vessels. Recent studies have shown that photoacoustic imaging can be used ''
in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, an ...
'' for tumor
angiogenesis Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature mainly by processes of sprouting and ...
monitoring,
blood oxygenation Pulse oximetry is a Invasiveness of surgical procedures, noninvasive method for monitoring blood oxygen saturation (medicine), oxygen saturation. Oxygen saturation, Peripheral oxygen saturation (SpO2) readings are typically within 2% accuracy (wi ...
mapping, functional brain imaging, skin
melanoma Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In very rare case ...
detection,
methemoglobin Methemoglobin (British: methaemoglobin, shortened MetHb) (pronounced "met-hemoglobin") is a hemoglobin ''in the form of metalloprotein'', in which the iron in the heme group is in the Fe3+ (ferric) state, not the Fe2+ (ferrous) of normal hemoglobin ...
measuring, etc. Two types of photoacoustic imaging systems, ''photoacoustic/thermoacoustic computed tomography'' (also known as photoacoustic/thermoacoustic tomography, i.e., PAT/TAT) and '' photoacoustic microscopy'' (PAM), have been developed. A typical PAT system uses an unfocused ultrasound detector to acquire the photoacoustic signals, and the image is reconstructed by inversely solving the photoacoustic equations. A PAM system, on the other hand, uses a spherically focused ultrasound detector with 2D point-by-point scanning, and requires no reconstruction algorithm.


Photoacoustic computed tomography


General equation

Given the heating function H(\boldsymbol,t), the generation and propagation of photoacoustic wave pressure p(\boldsymbol,t) in an acoustically homogeneous inviscid medium is governed by :\nabla^2p(\boldsymbol,t)-\frac\fracp(\boldsymbol,t)=-\frac\fracH(\boldsymbol,t) \qquad \qquad \quad \quad (1), where v_s is the speed of sound in medium, \beta is the thermal expansion coefficient, and C_p is the specific heat capacity at constant pressure. Eq. (1) holds under thermal confinement to ensure that heat conduction is negligible during the laser pulse excitation. The thermal confinement occurs when the laser pulsewidth is much shorter than the thermal relaxation time. The forward solution of Eq. (1) is given by :\left.p(\boldsymbol,t)=\frac \int \frac \frac \_ \qquad \quad \,\,\,\,(2). In stress confinement, which occurs when the laser pulsewidth is much shorter than the stress relaxation time, Eq. (2) can be further derived as :p(\boldsymbol,t)=\frac \frac \left frac \int d \boldsymbol' p_0(\boldsymbol') \delta \left (t-\frac \right) \right\qquad \,(3), where p_0 is the initial photoacoustic pressure.


Universal reconstruction algorithm

In a PAT system, the
acoustic pressure Sound pressure or acoustic pressure is the local pressure deviation from the ambient (average or equilibrium) atmospheric pressure, caused by a sound wave. In air, sound pressure can be measured using a microphone, and in water with a hydrophone ...
is detected by scanning an ultrasonic transducer over a surface that encloses the photoacoustic source. To reconstruct the internal source distribution, we need to solve the inverse problem of equation (3) (i.e. to obtain p_0). A representative method applied for PAT reconstruction is known as the universal backprojection algorithm. This method is suitable for three imaging geometries: planar, spherical, and cylindrical surfaces. The universal back projection formula is where \Omega_0 is the solid angle subtended by the entire surface S_0 with respect to the reconstruction point \boldsymbol inside S_0, and


Simple system

A simple PAT/TAT/OAT system is shown in the left part of Fig. 3. The laser beam is expanded and diffused to cover the whole region of interest. Photoacoustic waves are generated proportional to the distribution of optical absorption in the target, and are detected by a single scanned ultrasonic transducer. A TAT/OAT system is the same as PAT except that it uses a microwave excitation source instead of a laser. Although single-element transducers have been employed in these two systems, the detection scheme can be extended to use ultrasound arrays as well.


Biomedical applications

Intrinsic optical or microwave absorption contrast and diffraction-limited high spatial resolution of ultrasound make PAT and TAT promising imaging modalities for wide biomedical applications:


Brain lesion detection

Soft tissues with different optical absorption properties in the brain can be clearly identified by PAT.


Hemodynamics monitoring

Since HbO2 and Hb are the dominant absorbing compounds in biological tissues in the visible spectral range, multiple wavelength photoacoustic measurements can be used to reveal the relative concentration of these two
chromophore A chromophore is the part of a molecule responsible for its color. The word is derived . The color that is seen by our eyes is that of the light not Absorption (electromagnetic radiation), absorbed by the reflecting object within a certain wavele ...
s. Thus, the relative total concentration of hemoglobin (HbT) and the hemoglobin
oxygen saturation Oxygen saturation (symbol SO2) is a relative measure of the concentration of oxygen that is Dissolution (chemistry), dissolved or carried in a given medium as a proportion of the maximal concentration that can be dissolved in that medium at the g ...
(sO2) can be derived. Therefore, cerebral hemodynamic changes associated with brain function can be successfully detected with PAT.


Breast cancer diagnosis

By utilizing low scattered microwave for excitation, TAT is capable of penetrating thick (several cm) biological tissues with less than mm spatial resolution. Since cancerous tissue and normal tissue have about the same responses to radio frequency radiation, TAT has limited potential in early breast cancer diagnosis.


Photoacoustic microscopy

The imaging depth of photoacoustic microscopy is mainly limited by the ultrasonic attenuation. The spatial (i.e. axial and lateral) resolutions depend on the ultrasonic transducer used. An ultrasonic transducer with high central frequency and broader bandwidth are chosen to obtain high axial resolution. The lateral resolution is determined by the focal diameter of the transducer. For instance, a 50 MHz ultrasonic transducer provides 15 micrometre axial and 45 micrometre lateral resolution with ~3 mm imaging depth. Photoacoustic microscopy has multiple important applications in functional imaging: it can detect changes in oxygenated/deoxygenated hemoglobin in small vessels.


Other applications

Photoacoustic imaging was introduced recently in the context of
artwork A work of art, artwork, art piece, piece of art or art object is an artistic creation of aesthetic value. Except for "work of art", which may be used of any work regarded as art in its widest sense, including works from literature ...
diagnostics with emphasis on the uncovering of hidden features such as underdrawings or original sketch lines in
painting Painting is a Visual arts, visual art, which is characterized by the practice of applying paint, pigment, color or other medium to a solid surface (called "matrix" or "Support (art), support"). The medium is commonly applied to the base with ...
s. Photoacoustic images, collected from miniature
oil painting Oil painting is a painting method involving the procedure of painting with pigments combined with a drying oil as the Binder (material), binder. It has been the most common technique for artistic painting on canvas, wood panel, or oil on coppe ...
s on
canvas Canvas is an extremely durable Plain weave, plain-woven Cloth, fabric used for making sails, tents, Tent#Marquees and larger tents, marquees, backpacks, Shelter (building), shelters, as a Support (art), support for oil painting and for other ite ...
, illuminated with a pulsed laser on their reverse side, revealed clearly the presence of pencil sketch lines coated over by several paint layers.


Advances in photoacoustic imaging

Gold nanocages have been presented as a promising contrast agent for photoacoustic tomography due to their tunable optical properties. Photoacoustic imaging has seen recent advances through the integration of deep learning principles and compressed sensing. For more information, see Deep learning in photoacoustic imaging.


See also

* Multispectral optoacoustic tomography * Photoacoustic microscopy * Deep learning in photoacoustic imaging *
Photoacoustic effect The photoacoustic effect or optoacoustic effect is the formation of sound waves following light absorption in a material sample. In order to obtain this effect the light intensity must vary, either periodically (''modulated light'') or as a singl ...


References


External links


Recent advances in application of acoustic, acousto-optic and photoacoustic methods in biology and medicine
{{DEFAULTSORT:Photoacoustic Imaging In Biomedicine Medical imaging