Photoacoustic Imaging - AbsoluteAstronomy.com

Photoacoustic imaging, as a hybrid biomedical imaging modality, is developed based on the photoacoustic effect

Photoacoustic spectroscopy

Photoacoustic spectroscopy is the measurement of the effect of absorbed electromagnetic energy on matter by means of acoustic detection. The discovery of the photoacoustic effect dates to 1880 when Alexander Graham Bell showed that thin discs emitted sound when exposed to a beam of sunlight that...

. In photoacoustic imaging, non-ionizing laser

Laser

A laser is a device that emits light through a process of optical amplification based on the stimulated emission of photons. The term "laser" originated as an acronym for Light Amplification by Stimulated Emission of Radiation...

pulses are delivered into biological tissues (when radio frequency

Radio frequency

Radio frequency is a rate of oscillation in the range of about 3 kHz to 300 GHz, which corresponds to the frequency of radio waves, and the alternating currents which carry radio signals...

pulses are used, the technology is referred to as thermoacoustic imaging). Some of the delivered energy will be absorbed and converted into heat, leading to transient thermoelastic expansion and thus wideband (e.g. MHz) ultrasonic

Ultrasound

Ultrasound is cyclic sound pressure with a frequency greater than the upper limit of human hearing. Ultrasound is thus not separated from "normal" sound based on differences in physical properties, only the fact that humans cannot hear it. Although this limit varies from person to person, it is...

emission. The generated ultrasonic waves are then detected by ultrasonic transducers to form images. It is known that optical absorption is closely associated with physiological properties, such as hemoglobin

Hemoglobin

Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...

concentration and oxygen saturation

Oxygen saturation

Oxygen saturation or dissolved oxygen is a relative measure of the amount of oxygen that is dissolved or carried in a given medium. It can be measured with a dissolved oxygen probe such as an oxygen sensor or an optode in liquid media, usually water.It has particular significance in medicine and...

. 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. Fig. 1 is a schematic illustration showing the basic principles of photoacoustic imaging.

The optical absorption in biological tissues can be due to endogenous

Endogenous

Endogenous substances are those that originate from within an organism, tissue, or cell. Endogenous retroviruses are caused by ancient infections of germ cells in humans, mammals and other vertebrates...

molecules such as hemoglobin or melanin

Melanin

Melanin is a pigment that is ubiquitous in nature, being found in most organisms . In animals melanin pigments are derivatives of the amino acid tyrosine. The most common form of biological melanin is eumelanin, a brown-black polymer of dihydroxyindole carboxylic acids, and their reduced forms...

, or exogenously delivered contrast agents. As an example, Fig. 2 shows the optical absorption spectra of oxygenated hemoglobin

Hemoglobin

(HbO₂) and deoxygenated hemoglobin

Hemoglobin

(Hb) in the visible and near infrared region. Since blood usually has orders of magnitude larger 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
In vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...

for tumor angiogenesis

Angiogenesis

Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...

monitoring, blood oxygenation

Oxygenation (medical)

Oxygenation occurs when oxygen molecules enter the tissues of the body. For example, blood is oxygenated in the lungs, where oxygen molecules travel from the air and into the blood...

mapping, functional brain imaging, and skin melanoma

Melanoma

Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...

detection etc.

Advantages

	Δf	Primary contrast	Δz	δz	δx	Speed
	Hz		mm	µm	µm	Mvx/s
Photoacoustic microscopy	50 M	Optical absorption	3	15	45	0.5
Photoacoustic microscopy	5 M	Optical absorption	50	700	700	0.5
Confocal microscopy Confocal microscopy Confocal microscopy is an optical imaging technique used to increase optical resolution and contrast of a micrograph by using point illumination and a spatial pinhole to eliminate out-of-focus light in specimens that are thicker than the focal plane. It enables the reconstruction of...		Fluorescence, scattering	0.2	3-20	0.3-3	10-100
Two-photon microscopy		Fluorescence	0.5-1.0	1-10	0.3-3	10-100
Optical coherence tomography Optical coherence tomography Optical coherence tomography is an optical signal acquisition and processing method. It captures micrometer-resolution, three-dimensional images from within optical scattering media . Optical coherence tomography is an interferometric technique, typically employing near-infrared light...	50 T	Optical scattering	1-2	0.5-10	1-10	20-4.000
Scanning Laser Acoustic Microscopy	300 M	Ultrasonic scattering	1-2	20	20	10
Acoustic microscopy Acoustic microscopy Acoustic microscopy is microscopy that employs very high or ultra high frequency ultrasound. Acoustic microscopes operate nondestructively and penetrate most solid materials to make visible images of internal features, including defects such as cracks, delaminations and voids.-Types of acoustic...	50 M	Ultrasonic scattering	20	20-100	80-160	0.1
Ultrasonography	5 M	Ultrasonic scattering	60	300	300	1
Table 1. Comparison of contrast mechanisms, penetration depth (Δz), axial resolution (δz), lateral resolution (δx=δy) and imaging speed of confocal microscopy, two-photon microscopy, optical coherence tomography (50 THz), ultrasound microscopy (50 MHz), ultrasound imaging (5 MHz), photoacoustic microscopy (50 MHz), and photoacoustic tomography (3.5 MHz). Speeds in Megavoxel per second of non-parallel techniques.

Imaging systems

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.

General equation

Given the heating function

, the generation and propagation of photoacoustic wave pressure

in an acoustically homogeneous inviscid medium is governed by

where

is the speed of sound in medium,

is the thermal expansion coefficient, and

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

In stress confinement, which occurs when the laser pulsewidth is much shorter than the stress relaxation time, Eq. (2) can be further derived as

where

is the initial photoacoustic pressure.

Universal reconstruction algorithm

In PAT system, the acoustic pressure is detected by scanning an ultrasound 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

).
A representative method applied for PAT reconstruction is known as the universal back projection algorithm. This method is suitable for three imaging geometries: planar, spherical, and cylindrical surfaces.

The universal backprojection formula is

where

is the solid angle subtended by the entire surface

with respect to the reconstruction point

inside

, and

A typical PAT/TAT system

A typical PAT system is shown as the left part in 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 an ultrasonic transducer. TAT system is the same as PAT system except using a microwave excitation source instead of laser. A typical TAT system is shown as the right part in Fig. 3. Although single-element transducers have been employed in these two systems, the detection scheme can be extended to using ultrasound arrays as well.

Biomedical applications of PAT/TAT

Intrinsic optical/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. For example, the absorption contrast between the lesion area and the background parenchyma is significant as shown in Fig. 4(a). Fig. 4(b) is the corresponding open-skull photograph after experiment.

Hemodynamics
Hemodynamics
Hemodynamics, meaning literally "blood movement" is the study of blood flow or the circulation.All animal cells require oxygen for the conversion of carbohydrates, fats and proteins into carbon dioxide , water and energy in a process known as aerobic respiration...

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 chromophores. Thus, the relative total concentration of hemoglobin (HbT) and the hemoglobin oxygen saturation

Oxygen saturation

(sO₂) can be derived. Therefore, cerebral hemodynamic changes associated with brain function can be successfully detected with PAT.

Fig. 5 is the functional imaging of cerebral hemodynamic changes in response to whisker stimulation. In Fig.5, (a) is the noninvasive PAT image of the vascular pattern in the superficial layer of the rat cortex acquired with the skin and skull intact. (b) and (c) are functional PAT images corresponding to left-side and right-side whisker stimulation, respectively. (d) is the open-skull photograph of the rat cortical surface (B, bregma

Parietal bone

The parietal bones are bones in the human skull which, when joined together, form the sides and roof of the cranium. Each bone is roughly quadrilateral in form, and has two surfaces, four borders, and four angles. It is named from the Latin pariet-, wall....

; L, lambda; M, midline; A, activated regions corresponding to whisker stimulation).

Fig. 6 shows functional changes of sO₂ and HbT in the rat cerebral cortex as a result of the physiological modulations. Under the hyperoxia status, the averaged sO₂ level, 2>, in the areas of the imaged cortical venous vessels in the rat brain, is higher than that under the normoxia status, and the difference <ΔsO₂> is ~10%; while under the hypoxia status, the 2> is lower than that under the normoxia status, and the difference <ΔsO₂> is ~13%. While the averaged HbT value, , presents a relative increase of ~12%, denoted by <ΔHbT>/, as a result of the change from normoxia to hypoxia, which was comparatively larger than the ~4% relative increase in as a result of the change from hyperoxia to normoxia.

Breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...

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 the cancer tissue and normal tissue have very different response to radio frequency, TAT has great potential in early breast cancer diagnosis. Fig. 7 shows the TAT image of a mastectomy specimen, where malignant breast tissue generates a much stronger thermoacoustic signal than the surrounding benign tissue due to its high microwave absorption.

Photoacoustic microscopy (PAM)

Fig. 8 shows a representative PAM set-up. A tunable dye laser is pumped by a Q-switched pulsed Nd:YAG (neodymium: yttrium aluminum garnet) laser. A short laser pulse at a certain wavelength between 532-770 nm is generated to irradiate the target tissue to induce acoustic pressure waves. Laser pulses of ~6 mJ/cm² at the focus will be delivered at 10 Hz repetition rate. An optical fiber

Optical fiber

An optical fiber is a flexible, transparent fiber made of a pure glass not much wider than a human hair. It functions as a waveguide, or "light pipe", to transmit light between the two ends of the fiber. The field of applied science and engineering concerned with the design and application of...

of 0.6 mm core diameter is coaxially positioned on a three-dimensional mechanical stage with changeable ultrasound

Ultrasound

transducers between 25-75 MHz.

The imaging depth of PAM is mainly limited by the ultrasonic attenuation. The spatial and lateral resolutions depend on the ultrasound transducer used. An ultrasound 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 ultrasound transducer provides 15 micrometre axial and 45 micrometre lateral resolution with ~3 mm imaging depth.

PAM has multiple important applications in functional imaging. Two examples are shown in Figs. 9 and 10. PAM can detect changes in oxygenated/deoxygenated hemoglobin in small vessels. As shown in Fig. 9, arterioles (red) and venules (blue) are clearly delineated with high spatial resolution. Fig. 10 shows the capability of PAM to image skin melanoma by using dual wavelength to obtain the morphological relationship between the melanoma and its surrounding blood vessels structures in vivo.

External links

http://labs.seas.wustl.edu/bme/Wang/index.html Optical Imaging Laboratory, Department of Biomedical Engineering, Washington University in St. Louis
http://www.medphys.ucl.ac.uk/research/mle/index.htm Photoacoustic Imaging Group, Department of Medical Physics and Bioengineering, University College London
http://fluor.unibe.ch/optoacoustics/index.htm Optoacoustic Imaging Lab, Department of Biomedical Photonics, Institute of Applied Physics, University of Bern
http://bmo.tnw.utwente.nl/bmo/techniques.htm Biomedical Optics, Biophysical Engineering group, Faculty of Science and Technology, University of Twente, Enschede, The Netherlands
http://foil.northwestern.edu Functional Optical Imaging Laboratory (FOIL), Department of Biomedical Engineering, Northwestern University
http://www.bme.ogi.edu/biomedicaloptics/wang/ Biophotonics and Imaging Laboratory (BAIL), Department of Biomedical Engineering, Oregon Health & Science University
http://www.optosonics.com/ OptoSonics, Inc.
http://www.fairwaymed.com/ Fairway Medical Technologies, Inc.
http://www.engr.uconn.edu/ece/labs/optlab/ Biomedical Optical Imaging Laboratory, Department of Electrical & Computer Engineering, University of Connecticut
http://csc.mat.univie.ac.at/pai/ An interdisciplinary consortium of experts in photoacoustic imaging in Austria where research in physics and mathematics is heavily driven by input from biology and medicine
http://www3.interscience.wiley.com/journal/116325199/abstract Recent advances in application of acoustic, acousto-optic and photoacoustic methods in biology and medicine
http://ultrasound.bme.utexas.edu/ Ultrasound Imaging and Therapeutics Research Laboratory, Department of Biomedical Engineering, University of Texas at Austin

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