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| [[File:PASchematics v2.png|thumb|300px|left|Fig. 1. Schematic illustration of photoacoustic imaging.]]
| | Alyson is the name people use to call me and I believe it sounds quite good when you say it. My spouse and I live psychic reading - [http://www.sirudang.com/siroo_Notice/2110 just click the following webpage] - in Mississippi and I love every day residing here. What me and my family love is bungee jumping but I've been taking on new things lately. Invoicing is what I do for a living but I've always wanted my personal business. |
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| [[File:Melanoma3DMovie.gif|thumb|300px|right|3D photoacoustic imaging of melanoma ''in vivo''.<ref name = Hao_NatureBio_PAM>{{cite journal |author=Zhang, H. F. et al.|title=Functional photoacoustic microscopy for high-resolution and noninvasive ''in vivo'' imaging|journal=Nature Biotechnology|volume=24|pages=848–851|year=2006|doi=10.1038/nbt1220 |pmid=16823374 |issue=7}}</ref>]]
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| '''Photoacoustic imaging''', as a hybrid biomedical imaging modality, is developed based on the [[Photoacoustic spectroscopy|photoacoustic effect]]. In photoacoustic imaging, non-ionizing [[laser]] pulses are delivered into biological tissues (when [[radio frequency]] 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) [[Ultrasound|ultrasonic]] 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]] concentration and [[oxygen saturation]].<ref name="A. Grinvald_1986">{{cite journal |author=A. Grinvald et al. |title=Functional architecture of cortex revealed by optical imaging of intrinsic signals |journal=Nature |volume=324|pages=361–364 |year=1986 |doi=10.1038/324361a0 |pmid=3785405 |issue=6095}}</ref> 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.<ref name = Wang_2006>{{cite journal |author=M. Xu and L.H. Wang |title=Photoacoustic imaging in biomedicine|journal=Review of Scientific Instruments|volume=77 |issue=4|pages=041101|year=2006 |doi=10.1063/1.2195024}}</ref> Fig. 1 is a schematic illustration showing the basic principles of photoacoustic imaging.
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| [[File:HbAbs v3.png|thumb|300px|Fig. 2. Absorption spectra of oxy- and deoxy-hemoglobin.]]
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| The optical absorption in biological tissues can be due to [[endogenous]] molecules such as hemoglobin or [[melanin]], or exogenously delivered contrast agents. As an example, Fig. 2 shows the optical absorption spectra of [[Hemoglobin|oxygenated hemoglobin]] (HbO<sub>2</sub>) and [[Hemoglobin|deoxygenated hemoglobin]] (Hb) in the visible and near infrared region.<ref>[http://omlc.ogi.edu/spectra/ Optical Properties Spectra<!-- Bot generated title -->]</ref> 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]]'' for tumor [[angiogenesis]] monitoring, [[Oxygenation (medical)|blood oxygenation]] mapping, functional brain imaging, and skin [[melanoma]] detection etc.<ref name = Wang_2006>{{cite journal |author=M. Xu and L.H. Wang |title=Biomedical photoacoustics |journal=Review of Scientific Instruments|volume=77 |issue=4|pages=041101|year=2006 |doi=10.1063/1.2195024}}</ref>
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| ==Advantages==
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| {| class="wikitable" style="text-align:right;"
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| |-
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| ! !! Δf !! Primary contrast !! Δz !! δz !! δx !! Speed
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| |-
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| !
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| | ''Hz'' || || ''mm'' || ''µm'' || ''µm'' || ''Mvx/s''
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| |-
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| ! '''Photoacoustic microscopy'''
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| | 50 M
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| | Optical absorption
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| | 3
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| | 15
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| | 45
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| | 0.5
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| |-
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| ! '''Photoacoustic microscopy'''
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| | 5 M
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| | Optical absorption
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| | 50
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| | 700
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| | 700
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| | 0.5
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| |-
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| ! [[Confocal microscopy]]
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| | Fluorescence, scattering
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| | 0.2
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| | 3-20
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| | 0.3-3
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| | 10-100
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| |-
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| ! [[Two-photon microscopy]]
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| | Fluorescence
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| | 0.5-1.0
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| | 1-10
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| | 0.3-3
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| | 10-100
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| |-
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| ! [[Optical coherence tomography]]
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| | 50 T
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| | Optical scattering
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| | 1-2
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| | 0.5-10
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| | 1-10
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| | 20-4.000
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| |-
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| ! [[Scanning Laser Acoustic Microscopy]]
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| | 300 M
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| | Ultrasonic scattering
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| | 1-2
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| | 20
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| | 20
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| | 10
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| |-
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| ! [[Acoustic microscopy]]
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| | 50 M
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| | Ultrasonic scattering
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| | 20
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| | 20-100
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| | 80-160
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| | 0.1
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| |-
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| ! [[Ultrasonography]]
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| | 5 M
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| | Ultrasonic scattering
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| | 60
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| | 300
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| | 300
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| | 1
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| |-
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| | colspan=7 align ="center"| 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.
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| |}
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| ==Imaging systems==
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| 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.
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| ===Photoacoustic/thermoacoustic/optoacoustic computed tomography (PAT/TAT/OAT)===
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| ====General equation====
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| Given the heating function <math> H(\vec{r},t)</math>, the generation and propagation of photoacoustic wave pressure <math>p(\vec{r},t)</math> in an acoustically homogeneous inviscid medium is governed by
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| :<math>\nabla^2p(\vec{r},t)-\frac{1}{v_s^2}\frac{\partial^2}{\partial{t^2}}p(\vec{r},t)=-\frac{\beta}{C_p}\frac{\partial}{\partial t}H(\vec{r},t) \qquad \qquad \quad \quad (1), </math>
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| where <math>v_s</math> is the speed of sound in medium, <math>\beta</math> is the thermal expansion coefficient, and <math>C_p</math> 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.<ref name = Wang_BioMedBooK>{{cite book |author=L.H. Wang and H.I. Wu |title=Biomedical Optics|publisher=Wiley |year=2007|isbn=978-0-471-74304-0}}</ref>
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| The forward solution of Eq. (1) is given by
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| :<math>\left.p(\vec{r},t)=\frac{\beta}{4 \pi C_p} \int \frac{d \vec{r'}}{|\vec{r}-\vec{r'}|} \frac{\partial H(\vec{r'},t')}{\partial t'} \right|_{t'=t-|\vec{r}-\vec{r'}|/v_s} \qquad \quad \,\,\,\,(2). </math>
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| In stress confinement, which occurs when the laser pulsewidth is much shorter than the stress relaxation time,<ref name="Wang_BioMedBooK"/> Eq. (2) can be further derived as
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| :<math>p(\vec{r},t)=\frac{1}{4 \pi v_s^2} \frac{\partial}{\partial t} \left [\frac{1}{v_s t} \int d \vec{r'} p_0(\vec{r'}) \delta \left (t-\frac{|\vec{r}-\vec{r'}|}{v_s} \right) \right] \qquad \,(3), </math>
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| where <math>p_0</math> is the initial photoacoustic pressure.
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| ====Universal reconstruction algorithm====
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| In a 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 <math>p_0</math>).
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| A representative method applied for PAT reconstruction is known as the universal backprojection algorithm.<ref name = Xu_2005>{{cite journal |author=M. Xu et al.|title=Universal back-projection algorithm for photoacoustic-computed tomography|journal=Physical Review E|volume=71|pages=016706|year=2005|doi=10.1103/PhysRevE.71.016706 | issue=1}}</ref> This method is suitable for three imaging geometries: planar, spherical, and cylindrical surfaces.
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| The universal backprojection formula is
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| <center><math>\left.p_0(\vec{r})=\int_{\Omega_0} \frac{d \Omega_0}{\Omega_0} \left [2 p(\vec{r_0},v_s t) - 2 v_s t \frac{\partial p(\vec{r_0},v_s t)}{\partial (v_s t)} \right]\right|_{t=|\vec{r} - \vec{r_0}|/v_s},\qquad \quad(4), </math></center>
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| where <math>\Omega_0</math> is the solid angle subtended by the entire surface <math>S_0</math> with respect to the reconstruction point <math>\vec{r}</math> inside <math>S_0</math>, and
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| <center><math>d \Omega_0 = \frac{d S_0}{|\vec{r} - \vec{r_0}|^2} \frac{\hat n_0^s . (\vec{r} - \vec{r_0})}{|\vec{r} - \vec{r_0}|}. </math></center>
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| ====A simple PAT/TAT/OAT system====
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| 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. A typical TAT system is shown in the right part of Fig. 3. Although single-element transducers have been employed in these two systems, the detection scheme can be extended to use ultrasound arrays as well.
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| [[File:Setup of PAT and TAT.png|thumb|center|700px|Fig. 3. Schematic of single-element transducer PAT/TAT system.<ref name = XDW_2006>{{cite journal |author=X. Wang, et al.|title=Non-invasive imaging of hemoglobin concentration and oxygenation in the rat brain using high-resolution photoacoustic tomography|journal=Journal of Biomedical Optics|volume=11|pages=024015|year=2006|doi=10.1117/1.2192804 |pmid=16674205 |issue=2}}</ref><ref name = XJ_2006>{{cite journal |author=X. Jin, et al.|title=Thermoacoustic tomography with correction for acoustic speed variations|journal=Physics in Medicine and Biology|volume=51|pages=6437–6448|year=2006|doi=10.1088/0031-9155/51/24/010 |pmid=17148827 |issue=24}}</ref>]]
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| ====Biomedical applications of PAT/TAT====
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| Intrinsic optical/microwave absorption contrast and diffraction-limited high spatial resolution of ultrasound make PAT and TAT promising imaging modalities for wide biomedical applications:
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| =====Brain lesion detection<ref name = XDW_2003>{{cite journal |author=X. Wang, et al.|title=Non-invasive laser-induced photoacoustic tomography for structural and functional imaging of the brain ''in vivo''|journal=Nature Biotechnology|volume=21|pages=803–806|year=2003|doi=10.1038/nbt839 |pmid=12808463 |issue=7}}</ref>=====
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| [[File:Brain lesion PAT.png|thumb|200px|Fig. 4. PAT imaging of rat brain lesion ''in situ''.<ref name="XDW_2003"/>]]
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| 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.
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| =====[[Hemodynamics]] monitoring <ref name="XDW_2006"/><ref name="XDW_2003"/>=====
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| Since HbO<sub>2</sub> 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]] (sO<sub>2</sub>) can be derived. Therefore, cerebral hemodynamic changes associated with brain function can be successfully detected with PAT.
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| [[File:Brain stimulation PAT.png|thumb|left|200px|Fig. 5. Cerebral hemodynamic changes in response to whisker stimulation.<ref name="XDW_2003"/>]]
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| [[File:O2 saturation PAT.png|thumb|200px|Fig. 6. Image of the sO2 and HbT change in the cortical venous vessels between different physiological status.<ref name="XDW_2006"/>]]
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| 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, [[Parietal bone|bregma]]; L, lambda; M, midline; A, activated regions corresponding to whisker stimulation).
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| Fig. 6 shows functional changes of sO<sub>2</sub> and HbT in the rat cerebral cortex as a result of the physiological modulations. Under the hyperoxia status, the averaged sO<sub>2</sub> level, <sO<sub>2</sub>>, in the areas of the imaged cortical venous vessels in the rat brain, is higher than that under the normoxia status, and the difference <ΔsO<sub>2</sub>> is ~10%; while under the hypoxia status, the <sO<sub>2</sub>> is lower than that under the normoxia status, and the difference <ΔsO<sub>2</sub>> is ~13%. While the averaged HbT value, <HbT>, presents a relative increase of ~12%, denoted by <ΔHbT>/<HbT>, as a result of the change from normoxia to hypoxia, which was comparatively larger than the ~4% relative increase in <HbT> as a result of the change from hyperoxia to normoxia.
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| =====[[Breast cancer]] diagnosis<ref name = GK_2005>{{cite journal |author=G. Ku, et al.|title=Thermoacoustic and photoacoustic tomography of thick biological tissues toward breast imaging|journal=Technology in Cancer Research and Treatment|volume=4|pages=559–566|year=2005 | issue=5 |pmid=16173826}}</ref>=====
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| [[File:Breast cancer TAT.png|thumb|right|150px|Fig. 7. Thermoacoustic image of a mastectomy specimen.<ref name="GK_2005"/>]]
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| 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 very different responses to radio frequency radiation, 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.
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| ===Photoacoustic microscopy (PAM)===
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| Fig. 8 shows a representative PAM set-up.<ref name = Hao_NatureBio_PAM>{{cite journal |author=Zhang, H. F. et al.|title=Functional photoacoustic microscopy for high-resolution and noninvasive ''in vivo'' imaging|journal=Nature Biotechnology|volume=24|pages=84851|year=2006|doi=10.1038/nbt1220 |pmid=16823374 |issue=7}}</ref> 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/cm<sup>2</sup> at the focus will be delivered at 10 Hz repetition rate. An [[optical fiber]] of 0.6 mm core diameter is coaxially positioned on a three-dimensional mechanical stage with changeable [[ultrasound]] transducers between 25-75 MHz.
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| [[File:Setup of PAM.png|thumb|center|500px|Fig. 8. Experimental set-up of dark field reflection mode PAM system.<ref name="Hao_NatureBio_PAM"/>]]
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| [[File:O2 saturation PAM.png|thumb|200px|left|Fig. 9. Multi-wavelength PAM imaging for blood oxygenation mapping of rat skin.<ref name = Hao_APL>{{cite journal |author=Zhang, H. F. et al.|title=Imaging of hemoglobin oxygen saturation variations in single vessels ''in vivo'' using photoacoustic microscopy|journal=Applied Physics Letters|volume=90 |issue=5|pages=053901|year=2007|doi=10.1063/1.2435697}}</ref>]]
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| [[File:Melanoma PAM.png|thumb|200px|Fig. 10. Multi-wavelength PAM imaging for ''in vivo'' melanoma detection.<ref name="Hao_NatureBio_PAM"/>]]
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| 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.
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| 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.<ref name="Hao_APL"/> 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''.<ref name="Hao_NatureBio_PAM"/>
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| ==See also==
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| * [[Photoacoustic tomography]]
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| * [[Multispectral Optoacoustic Tomography]]
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| ==References==
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| {{reflist}}
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| ==External links==
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| *[http://labs.seas.wustl.edu/bme/Wang/index.html] Optical Imaging Laboratory, Department of Biomedical Engineering, Washington University in St. Louis
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| *[http://www.medphys.ucl.ac.uk/research/mle/index.htm] Photoacoustic Imaging Group, Department of Medical Physics and Bioengineering, University College London
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| *[http://fluor.unibe.ch/optoacoustics/index.htm] Optoacoustic Imaging Lab, Department of Biomedical Photonics, Institute of Applied Physics, University of Bern
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| *[http://www.utwente.nl/tnw/bmpi/] Biomedical Photonic Imaging Group, BioPhysical Engineering Group, Faculty of Science and Technology, University of Twente, Enschede, The Netherlands
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| *[http://foil.northwestern.edu] Functional Optical Imaging Laboratory (FOIL), Department of Biomedical Engineering, Northwestern University
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| *[http://www.bme.ogi.edu/biomedicaloptics/wang/] Biophotonics and Imaging Laboratory (BAIL), Department of Biomedical Engineering, Oregon Health & Science University
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| *[http://www.optosonics.com/] OptoSonics, Inc.
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| *[http://www.tomowave.com/] Tomowave Laboratories, Inc.
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| *[http://www.engr.uconn.edu/ece/labs/optlab/] Biomedical Optical Imaging Laboratory, Department of Electrical & Computer Engineering, University of Connecticut
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| *[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
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| *[http://www3.interscience.wiley.com/journal/116325199/abstract] Recent advances in application of acoustic, acousto-optic and photoacoustic methods in biology and medicine
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| *[http://ultrasound.bme.utexas.edu/] Ultrasound Imaging and Therapeutics Research Laboratory, Department of Biomedical Engineering, University of Texas at Austin
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| {{DEFAULTSORT:Photoacoustic Imaging In Biomedicine}}
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| [[Category:Medical imaging]]
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