Biomedical Photoacoustic Imaging: Technologies and Methods

A special issue of Journal of Imaging (ISSN 2313-433X).

Deadline for manuscript submissions: closed (15 November 2018) | Viewed by 57600

Special Issue Editor


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Guest Editor
Institute of Physics, Martin-Luther-University Halle-Wittenberg, Von-Danckelmann-Platz 3, 06120 Halle (Saale), Germany
Interests: photoacoustic imaging; photoacoustic spectroscopy; quantitative imaging; reporter gene imaging

Special Issue Information

Dear Colleagues,

I would like to invite you to contribute to a Special Issue on Biomedical Photoacoustic Imaging (PA), which will be published in the MDPI Journal of Imaging. Recent technological advances have shown that PA imaging is capable of acquiring images at high resolution and frame rates using a single excitation pulse, which minimizes tissue motion artifacts and paves the way for high speed functional and molecular imaging. In addition, novel experimental methods, such as the development of novel genetic reporters, and computational approaches, such as model-based inversions and deep learning, have produced promising initial results that may enable truly quantitative imaging. These technologies and methods are vital components for functional and molecular PA imaging, and the successful translation of PA modalities to clinical applications. Contributions are invited that address the range of current challenges, which may include novel PA signal generation approaches, PA detection and scanner technologies, methods for quantitative PA imaging, functional and molecular PA imaging, and in vivo applications in preclinical and clinical studies.

Prof. Jan Laufer
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Imaging is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Photoacoustic imaging
  • Spectroscopy
  • Functional imaging
  • Molecular imaging
  • Instrumentation

Published Papers (9 papers)

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Research

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12 pages, 2518 KiB  
Article
Comparison of Piezoelectric and Optical Projection Imaging for Three-Dimensional In Vivo Photoacoustic Tomography
by Robert Nuster and Günther Paltauf
J. Imaging 2019, 5(1), 15; https://doi.org/10.3390/jimaging5010015 - 11 Jan 2019
Cited by 10 | Viewed by 6550
Abstract
Ultrasound sensor arrays for photoacoustic tomography (PAT) are investigated that create line projections of the pressure generated in an object by pulsed light illumination. Projections over a range of viewing angles enable the reconstruction of a three-dimensional image. Two line-integrating arrays are compared [...] Read more.
Ultrasound sensor arrays for photoacoustic tomography (PAT) are investigated that create line projections of the pressure generated in an object by pulsed light illumination. Projections over a range of viewing angles enable the reconstruction of a three-dimensional image. Two line-integrating arrays are compared in this study for the in vivo imaging of vasculature, a piezoelectric array, and a camera-based setup that captures snapshots of the acoustic field emanating from the sample. An array consisting of 64 line-shaped sensors made of piezoelectric polymer film, which was arranged on a half-cylindrical area, was used to acquire spatiotemporal data from a human finger. The optical setup used phase contrast to visualize the acoustic field generated in the leg of a mouse after a selected delay time. Time-domain back projection and frequency-domain back propagation were used for image reconstruction from the piezoelectric and optical data, respectively. The comparison yielded an about threefold higher resolution for the optical setup and an about 13-fold higher sensitivity of the piezoelectric array. Due to the high density of data in the camera images, the optical technique gave images without streak artifacts, which were visible in the piezo array images due to the discrete detector positions. Overall, both detection concepts are suited for almost real-time projection imaging and three-dimensional imaging with a data acquisition time of less than a minute without averaging, which was limited by the repetition rate of the laser. Full article
(This article belongs to the Special Issue Biomedical Photoacoustic Imaging: Technologies and Methods)
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11 pages, 1876 KiB  
Article
Resolution Limits in Photoacoustic Imaging Caused by Acoustic Attenuation
by Peter Burgholzer, Johannes Bauer-Marschallinger, Bernhard Reitinger and Thomas Berer
J. Imaging 2019, 5(1), 13; https://doi.org/10.3390/jimaging5010013 - 10 Jan 2019
Cited by 16 | Viewed by 7156
Abstract
In conventional photoacoustic tomography, several effects contribute to the loss of resolution, such as the limited bandwidth and the finite size of the transducer, or the space-dependent speed of sound. They can all be compensated (in principle) technically or numerically. Frequency-dependent acoustic attenuation [...] Read more.
In conventional photoacoustic tomography, several effects contribute to the loss of resolution, such as the limited bandwidth and the finite size of the transducer, or the space-dependent speed of sound. They can all be compensated (in principle) technically or numerically. Frequency-dependent acoustic attenuation also limits spatial resolution by reducing the bandwidth of the photoacoustic signal, which can be numerically compensated only up to a theoretical limit given by thermodynamics. The entropy production, which is the dissipated energy of the acoustic wave divided by the temperature, turns out to be equal to the information loss, which cannot be compensated for by any reconstruction method. This is demonstrated for the propagation of planar acoustic waves in water, which are induced by short laser pulses and measured by piezoelectric acoustical transducers. It turns out that for water, where the acoustic attenuation is proportional to the squared frequency, the resolution limit is proportional to the square root of the distance and inversely proportional to the square root of the logarithm of the signal-to-noise ratio. The proposed method could be used in future work for media other than water, such as biological tissue, where acoustic attenuation has a different power-law frequency dependence. Full article
(This article belongs to the Special Issue Biomedical Photoacoustic Imaging: Technologies and Methods)
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18 pages, 5410 KiB  
Article
In Vivo 3D Imaging of Retinal Neovascularization Using Multimodal Photoacoustic Microscopy and Optical Coherence Tomography Imaging
by Van Phuc Nguyen, Yanxiu Li, Michael Aaberg, Wei Zhang, Xueding Wang and Yannis M. Paulus
J. Imaging 2018, 4(12), 150; https://doi.org/10.3390/jimaging4120150 - 12 Dec 2018
Cited by 23 | Viewed by 7215
Abstract
The pathological process of neovascularization of the retina plays a critical role in causing vision loss in several diseases, including diabetes, retinal vein occlusion, and sickle cell disease. Retinal neovascularization can lead to vitreous hemorrhage and retinal detachment, yet the pathological process of [...] Read more.
The pathological process of neovascularization of the retina plays a critical role in causing vision loss in several diseases, including diabetes, retinal vein occlusion, and sickle cell disease. Retinal neovascularization can lead to vitreous hemorrhage and retinal detachment, yet the pathological process of neovascularization is a complex phenomenon under active investigation. Understanding and monitoring retinal neovascularization is critically important in clinical ophthalmology. This study describes a novel multimodal ocular imaging system which combines photoacoustic microscopy (PAM) and a spectral domain optical coherence tomography (SD-OCT) to improve the visualization of retinal neovascularization (RNV), their depth, and the surrounding anatomy in living rabbits. RNV was induced in New Zealand rabbits by intravitreal injection of vascular endothelial growth factor (VEGF). The retinal vasculature before and after injection at various times was monitored and evaluated using multimodal imaging including color fundus photography, fluorescein angiography (FA), OCT, and PAM. In vivo experiments demonstrate that PAM imaging distinctly characterized the location as well as the morphology of individual RNV with high contrast at a safe laser energy of 80 nJ. SD-OCT was used to identify a cross-sectional structure of RNV. In addition, dynamic changes in the retinal morphology and retinal neovascularization were observed at day 4, 5, 6, 7, 9, 11, 14, 28, and day 35 after VEGF injection. PAM demonstrated high-resolution optical absorption of hemoglobin and vascular imaging of the retina and choroid with increased depth of penetration. With the current multimodal imaging system, RNV can be easily visualized in both 2D and 3D angiography. This multimodal ocular imaging system provides improved characterization of the microvasculature in a safe manner in larger rabbit eyes. Full article
(This article belongs to the Special Issue Biomedical Photoacoustic Imaging: Technologies and Methods)
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19 pages, 3735 KiB  
Article
Image Reconstruction with Reliability Assessment in Quantitative Photoacoustic Tomography
by Niko Hänninen, Aki Pulkkinen and Tanja Tarvainen
J. Imaging 2018, 4(12), 148; https://doi.org/10.3390/jimaging4120148 - 11 Dec 2018
Cited by 10 | Viewed by 5427
Abstract
Quantitative photoacoustic tomography is a novel imaging method which aims to reconstruct optical parameters of an imaged target based on initial pressure distribution, which can be obtained from ultrasound measurements. In this paper, a method for reconstructing the optical parameters in a Bayesian [...] Read more.
Quantitative photoacoustic tomography is a novel imaging method which aims to reconstruct optical parameters of an imaged target based on initial pressure distribution, which can be obtained from ultrasound measurements. In this paper, a method for reconstructing the optical parameters in a Bayesian framework is presented. In addition, evaluating the credibility of the estimates is studied. Furthermore, a Bayesian approximation error method is utilized to compensate the modeling errors caused by coarse discretization of the forward model. The reconstruction method and the reliability of the credibility estimates are investigated with two-dimensional numerical simulations. The results suggest that the Bayesian approach can be used to obtain accurate estimates of the optical parameters and the credibility estimates of these parameters. Furthermore, the Bayesian approximation error method can be used to compensate for the modeling errors caused by a coarse discretization, which can be used to reduce the computational costs of the reconstruction procedure. In addition, taking the modeling errors into account can increase the reliability of the credibility estimates. Full article
(This article belongs to the Special Issue Biomedical Photoacoustic Imaging: Technologies and Methods)
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15 pages, 1605 KiB  
Article
Confidence Estimation for Machine Learning-Based Quantitative Photoacoustics
by Janek Gröhl, Thomas Kirchner, Tim Adler and Lena Maier-Hein
J. Imaging 2018, 4(12), 147; https://doi.org/10.3390/jimaging4120147 - 10 Dec 2018
Cited by 26 | Viewed by 6621
Abstract
In medical applications, the accuracy and robustness of imaging methods are of crucial importance to ensure optimal patient care. While photoacoustic imaging (PAI) is an emerging modality with promising clinical applicability, state-of-the-art approaches to quantitative photoacoustic imaging (qPAI), which aim to solve the [...] Read more.
In medical applications, the accuracy and robustness of imaging methods are of crucial importance to ensure optimal patient care. While photoacoustic imaging (PAI) is an emerging modality with promising clinical applicability, state-of-the-art approaches to quantitative photoacoustic imaging (qPAI), which aim to solve the ill-posed inverse problem of recovering optical absorption from the measurements obtained, currently cannot comply with these high standards. This can be attributed to the fact that existing methods often rely on several simplifying a priori assumptions of the underlying physical tissue properties or cannot deal with realistic noise levels. In this manuscript, we address this issue with a new method for estimating an indicator of the uncertainty of an estimated optical property. Specifically, our method uses a deep learning model to compute error estimates for optical parameter estimations of a qPAI algorithm. Functional tissue parameters, such as blood oxygen saturation, are usually derived by averaging over entire signal intensity-based regions of interest (ROIs). Therefore, we propose to reduce the systematic error of the ROI samples by additionally discarding those pixels for which our method estimates a high error and thus a low confidence. In silico experiments show an improvement in the accuracy of optical absorption quantification when applying our method to refine the ROI, and it might thus become a valuable tool for increasing the robustness of qPAI methods. Full article
(This article belongs to the Special Issue Biomedical Photoacoustic Imaging: Technologies and Methods)
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13 pages, 4294 KiB  
Article
Exploiting Nonlinear Photoacoustic Signal Generation in Gold Nanospheres for Selective Detection in Serial 3D PA Tomography
by Susanne Schrof, Genny A. Pang, Jens Buchmann and Jan Laufer
J. Imaging 2018, 4(12), 146; https://doi.org/10.3390/jimaging4120146 - 08 Dec 2018
Cited by 11 | Viewed by 5622
Abstract
The photoacoustic (PA) signal amplitude measured in gold nanosphere suspensions has been shown to increase nonlinearly with the incident excitation fluence. In this work, this effect is exploited to recover the spatial distribution of gold nanoparticles in tomographic 3D photoacoustic (PA) images against [...] Read more.
The photoacoustic (PA) signal amplitude measured in gold nanosphere suspensions has been shown to increase nonlinearly with the incident excitation fluence. In this work, this effect is exploited to recover the spatial distribution of gold nanoparticles in tomographic 3D photoacoustic (PA) images against the background contrast provided by absorbers that exhibit a linear relationship between the PA signal amplitude and the fluence. Serial tomographic PA images of a tissue phantom containing gold nanospheres and a tissue-mimicking absorber were acquired. By assessing the linearity of the PA intensity voxel by voxel, the spatial distribution of the gold nanosphere suspension was recovered. The method is shown to enable the robust detection of gold nanoparticles. Full article
(This article belongs to the Special Issue Biomedical Photoacoustic Imaging: Technologies and Methods)
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11 pages, 1185 KiB  
Article
Receive Beam-Steering and Clutter Reduction for Imaging the Speed-of-Sound Inside the Carotid Artery
by Maju Kuriakose, Jan-Willem Muller, Patrick Stähli, Martin Frenz and Michael Jaeger
J. Imaging 2018, 4(12), 145; https://doi.org/10.3390/jimaging4120145 - 07 Dec 2018
Cited by 3 | Viewed by 4445
Abstract
Handheld imaging of the tissue’s speed-of-sound (SoS) is a promising multimodal addition to diagnostic ultrasonography for the examination of tissue composition. Computed ultrasound tomography in echo mode (CUTE) probes the spatial distribution of SoS, conventionally via scanning the tissue under a varying angle [...] Read more.
Handheld imaging of the tissue’s speed-of-sound (SoS) is a promising multimodal addition to diagnostic ultrasonography for the examination of tissue composition. Computed ultrasound tomography in echo mode (CUTE) probes the spatial distribution of SoS, conventionally via scanning the tissue under a varying angle of ultrasound transmission, and quantifying—in a spatially resolved way—phase variations of the beamformed echoes. So far, this technique is not applicable to imaging the lumen of vessels, where blood flow and tissue clutter inhibit phase tracking of the blood echoes. With the goal to enable the assessment of atherosclerotic plaque composition inside the carotid artery, we propose two modifications to CUTE: (a) use receive (Rx) beam-steering as opposed to transmit (Tx) beam-steering to increase acquisition speed and to reduce flow-related phase decorrelation, and (b) conduct pairwise subtraction of data obtained from repetitions of the scan sequence, to highlight blood echoes relative to static echo clutter and thus enable the phase tracking of blood echoes. These modifications were tested in a phantom study, where the echogenicity of the vessel lumen was chosen to be similar to the one of the background medium, which allows a direct comparison of SoS images obtained with the different techniques. Our results demonstrate that the combination of Rx-steering with the subtraction technique results in an SoS image of the same quality as obtained with conventional Tx-steering. Together with the improved acquisition speed, this makes the proposed technique a key step towards successful imaging of the SoS inside the carotid artery. Full article
(This article belongs to the Special Issue Biomedical Photoacoustic Imaging: Technologies and Methods)
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12 pages, 1855 KiB  
Article
Signed Real-Time Delay Multiply and Sum Beamforming for Multispectral Photoacoustic Imaging
by Thomas Kirchner, Franz Sattler, Janek Gröhl and Lena Maier-Hein
J. Imaging 2018, 4(10), 121; https://doi.org/10.3390/jimaging4100121 - 17 Oct 2018
Cited by 33 | Viewed by 5477
Abstract
Reconstruction of photoacoustic (PA) images acquired with clinical ultrasound transducers is usually performed using the Delay and Sum (DAS) beamforming algorithm. Recently, a variant of DAS, referred to as Delay Multiply and Sum (DMAS) beamforming has been shown to provide increased contrast, signal-to-noise [...] Read more.
Reconstruction of photoacoustic (PA) images acquired with clinical ultrasound transducers is usually performed using the Delay and Sum (DAS) beamforming algorithm. Recently, a variant of DAS, referred to as Delay Multiply and Sum (DMAS) beamforming has been shown to provide increased contrast, signal-to-noise ratio (SNR) and resolution in PA imaging. The main reasons for the use of DAS beamforming in photoacoustics are its simple implementation, real-time capability, and the linearity of the beamformed image to the PA signal. This is crucial for the identification of different chromophores in multispectral PA applications. In contrast, current DMAS implementations are not responsive to the full spectrum of sound frequencies from a photoacoustic source and have not been shown to provide a reconstruction linear to the PA signal. Furthermore, due to its increased computational complexity, DMAS has not been shown yet to work in real-time. Here, we present an open-source real-time variant of the DMAS algorithm, signed DMAS (sDMAS), that ensures linearity in the original PA signal response while providing the increased image quality of DMAS. We show the applicability of sDMAS for multispectral PA applications, in vitro and in vivo. The sDMAS and reference DAS algorithms were integrated in the open-source Medical Imaging Interaction Toolkit (MITK) and are available as real-time capable implementations. Full article
(This article belongs to the Special Issue Biomedical Photoacoustic Imaging: Technologies and Methods)
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Review

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24 pages, 67496 KiB  
Review
Photoacoustic Ophthalmoscopy: Principle, Application, and Future Directions
by Van Phuc Nguyen and Yannis M. Paulus
J. Imaging 2018, 4(12), 149; https://doi.org/10.3390/jimaging4120149 - 12 Dec 2018
Cited by 25 | Viewed by 8310
Abstract
Photoacoustic ophthalmoscopy (PAOM) is a novel, hybrid, non-ionizing, and non-invasive imaging technology that has been used to assess the retina. PAOM can provide both anatomic and functional retinal characterizations with high resolution, high sensitivity, high contrast, and a high depth of penetration. Thus, [...] Read more.
Photoacoustic ophthalmoscopy (PAOM) is a novel, hybrid, non-ionizing, and non-invasive imaging technology that has been used to assess the retina. PAOM can provide both anatomic and functional retinal characterizations with high resolution, high sensitivity, high contrast, and a high depth of penetration. Thus, ocular diseases can be precisely detected and visualized at earlier stages, resulting in an improved understanding of pathophysiology, improved management, and the improved monitoring of retinal treatment to prevent vision loss. To better visualize ocular components such as retinal vessels, choroidal vessels, choroidal neovascularization, retinal neovascularization, and the retinal pigment epithelium, an advanced multimodal ocular imaging platform has been developed by a combination of PAOM with other optical imaging techniques such as optical coherence tomography (OCT), scanning laser ophthalmoscopy (SLO), and fluorescence microscopy. The multimodal images can be acquired from a single imaging system and co-registered on the same image plane, enabling an improved evaluation of disease. In this review, the potential application of photoacoustic ophthalmoscopy in both research and clinical diagnosis are discussed as a medical screening technique for the visualization of various ocular diseases. The basic principle and requirements of photoacoustic ocular imaging are introduced. Then, various photoacoustic microscopy imaging systems of the retina in animals are presented. Finally, the future development of PAOM and multimodal imaging is discussed. Full article
(This article belongs to the Special Issue Biomedical Photoacoustic Imaging: Technologies and Methods)
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