Photoacoustic Tomography Applications Research Articles

Parallel interrogation of the chalcogenide-based micro-ring sensor array for photoacoustic tomography

Photoacoustic tomography (PAT), also known as optoacoustic tomography, is an attractive imaging modality that provides optical contrast with acoustic resolutions. Recent progress in the applications of PAT largely relies on the development and employment of ultrasound sensor arrays with many elements. Although on-chip optical ultrasound sensors have been demonstrated with high sensitivity, large bandwidth, and small size, PAT with on-chip optical ultrasound sensor arrays is rarely reported. In this work, we demonstrate PAT with a chalcogenide-based micro-ring sensor array containing 15 elements, while each element supports a bandwidth of 175 MHz (−6 dB) and a noise-equivalent pressure of 2.2 mPaHz−1/2. Moreover, by synthesizing a digital optical frequency comb (DOFC), we further develop an effective means of parallel interrogation to this sensor array. As a proof of concept, parallel interrogation with only one light source and one photoreceiver is demonstrated for PAT with this sensor array, providing images of fast-moving objects, leaf veins, and live zebrafish. The superior performance of the chalcogenide-based micro-ring sensor array and the effectiveness of the DOFC-enabled parallel interrogation offer great prospects for advancing applications in PAT.

Nanodroplet vaporization with pulsed-laser excitation repeatedly amplifies photoacoustic signals at low vaporization thresholds.

Nanodroplets' explosive vaporization triggered by absorption of laser pulses produces very large volume changes. These volume changes are two orders of magnitude higher than those of thermoelastic expansion generated by equivalent laser pulses, and should generate correspondingly higher photoacoustic waves (PAW). The generation of intense PAWs is desirable in photoacoustic tomography (PAT) to increase sensitivity. The biocompatibility and simplicity of nanodroplets obtained by sonication of perfluoropentane (PFP) in an aqueous solution of bovine serum albumin (BSA) containing a dye make them particularly appealing for use as contrast agents in clinical applications of PAT. Their usefulness depends on stability and reproducible vaporization of nanodroplets (liquid PFP inside) to microbubbles (gaseous PFP inside), and reversible condensation to nanodroplets. This work incorporates porphyrins with fluorinated chains and BSA labelled with fluorescent probes in PFP nanodroplets to investigate the structure and properties of such nanodroplets. Droplets prepared with average diameters in the 400-1000 nm range vaporize when exposed to nanosecond laser pulses with fluences above 3 mJ cm-2 and resist coalescence. The fluorinated chains are likely responsible for the low vaporization threshold, ∼2.5 mJ cm-2, which was obtained from the laser fluence dependence of the photoacoustic wave amplitudes. Only ca. 10% of the droplets incorporate fluorinated porphyrins. Nevertheless, PAWs generated with nanodroplets are ten times higher than those generated by aqueous BSA solutions containing an equivalent amount of porphyrin. Remarkably, successive laser pulses result in similar amplification, indicating that the microbubbles revert back to nanodroplets at a rate faster than the laser repetition rate (10 Hz). PFP nanodroplets are promising contrast agents for PAT and their performance increases with properly designed dyes.

Image reconstruction for endoscopic photoacoustic tomography including effects of detector responses.

In photoacoustic tomography (PAT), conventional image reconstruction methods are generally based on the assumption of an ideal point-like ultrasonic detector. This assumption is appropriate when the receiving surface of the detector is sufficiently small and/or the distance between the imaged object and the detector is large enough. However, it does not hold in endoscopic applications of PAT. In this study, we propose a model-based image reconstruction method for endoscopic photoacoustic tomography (EPAT), considering the effect of detector responses on image quality. We construct a forward model to physically describe the imaging process of EPAT, including the generation of the initial pressure due to optical absorption and thermoelastic expansion, the propagation of photoacoustic waves in tissues, and the acoustic measurement. The model outputs the theoretical sampling voltage signal, which is the response of the ultrasonic detector to the acoustic pressure reaching its receiving surface. The images representing the distribution map of the optical absorption energy density on cross-sections of the imaged luminal structures are reconstructed from the sampling voltage signals output by the detector through iterative inversion of the forward model. Compared with the conventional approaches based on back-projection and other imaging models, our method improved the quality and spatial resolution of the resulting images.

Quantitative Reconstruction of Absorption Coefficients for Photoacoustic Tomography

Photoacoustic (PA) tomography (PAT) is a cutting-edge imaging modality for visualizing the internal structure and light-absorption distribution in tissue. However, reconstruction of the absorption distribution has been limited by nonuniform light fluence. This paper introduces a novel method for quantitative reconstruction of the distribution of optical absorption coefficients in tissue. In this method, we implement an iterative algorithm for recovering absorption coefficients from optical absorbed energy maps based on a 3D Monte Carlo simulation of light transport and integrated with fluence compensation to obtain the initialization parameters. In the iteration algorithm, we calculate the deviation between the detected and the computed absorbed energy distribution at each iteration. By minimizing the deviation in the absorbed energy, the recovered values converge to the true absorption distribution. The results of numerical simulation and phantom experiment theoretically and experimentally demonstrate that the proposed method performs an accurately quantitative estimate of the distribution of optical absorption coefficients. This work expects to provide accurate quantitative information for absorbers within tissues or organs, and thereby broaden the clinical applications of PAT.

Acoustic Wave Field Reconstruction From Compressed Measurements With Application in Photoacoustic Tomography

We present a method for the recovery of compressively sensed acoustic fields using patterned, instead of point-by-point, detection. From a limited number of such compressed measurements, we propose to reconstruct the field on the sensor plane in each time step independently assuming its sparsity in a Curvelet frame. A modification of the Curvelet frame is proposed to account for the smoothing effects of data acquisition and motivated by a frequency domain model for photoacoustic tomography. An ADMM type algorithm, split augmented Lagrangian shrinkage algorithm, is used to recover the pointwise data in each individual time step from the patterned measurements. For photoacoustic applications, the photoacoustic image of the initial pressure is reconstructed using time reversal in $ {\mathbf k}$ -Wave Toolbox.

Numerical investigation of nonlinear sound propagation of photoacoustic tomography imaging.

Almost all reconstruction methods in photoacoustic tomography (PAT) have been developed by assuming that sound propagation is linear, which is valid for ordinary PAT applications but would become inappropriate when the sound amplitude is higher than a certain threshold level. In the current study, we investigate the effect of nonlinear sound propagation on PAT by using a numerical method which utilizes the time-reversal (TR) technique. In the forward stage, the Euler equations are solved to simulate nonlinear sound propagation, and the flow variables (pressure, velocity and density) are recorded by an array of virtual sensors. The recorded data are used to reconstruct the initial fields within the computational domain by using both linear and nonlinear TR techniques. Furthermore, TR results constructed with and without the recorded flow velocity field, which is difficult to measure for practical applications, have also been compared. The current results show that nonlinear reconstructions produce images with superior clarity, resolution and contrast compared to those reconstructed by the linear method, particularly when the recorded velocity field is used in the reconstruction.

Design of high energy laser pulse delivery in a multimode fiber for photoacoustic tomography.

In photoacoustic tomography (PAT), delivering high energy pulses through optical fiber is critical for achieving high quality imaging. A fiber coupling scheme with a beam homogenizer is demonstrated for coupling high energy pulses in a single multimode fiber. This scheme can benefit PAT applications that require miniaturized illumination or internal illumination with a small fiber. The beam homogenizer is achieved by using a cross cylindrical lens array, which provides a periodic spatial modulation on the phase of the input light. Thus the lens array acts as a phase grating which diffracts the beam into a 2D diffraction pattern. Both theoretical analysis and experiments demonstrate that the focused beam can be split into a 2D spot array that can reduce the peak power on the fiber tip surface and thus enhance the coupling performance. The theoretical analysis of the intensity distribution of the focused beam is carried out by Fourier optics. In experiments, coupled energy at 48 mJ/pulse and 60 mJ/pulse have been achieved and the corresponding coupling efficiency is 70% and 90% in a 1000-μm and a 1500-μm-core-diameter fiber, respectively. The high energy pulses delivered by the multimode fiber are further tested for PAT imaging in phantoms. PAT imaging of a printed dot array shows a large illumination area of 7 cm2 under 5 mm thick chicken breast tissue. In vivo imaging is also demonstrated on the human forearm. The large improvement in coupling energy can potentially benefit PAT with single fiber delivery to achieve large area imaging and deep penetration detection.

Noninvasive in vivo monitoring of collagenase induced intracerebral hemorrhage by photoacoustic tomography.

Photoacoustic tomography (PAT) is an emerging noninvasive biomedical imaging modality that can be used for visualizing the structure and function of brain in high resolution. Here we report an application of PAT to imaging intracerebral hemorrhage (ICH) in a mouse model. In vivo photoacoustic images were obtained in mice with right basal ganglia hemorrhage induced by microinjection of collagenase. With multi-spectral light excitation, cortical vascular network was clearly revealed at 532 nm, and ICH associated hematoma lesions and perihemmatoma regions were accurately mapped over time at 750 nm and 875 nm, respectively. Our results suggest that PAT provides a unique tool for visualizing hemodynamics involved in brain diseases such as ICH.

A practical guide to photoacoustic tomography in the life sciences.

The life sciences can benefit greatly from imaging technologies that connect microscopic discoveries with macroscopic observations. One technology uniquely positioned to provide such benefits is photoacoustic tomography (PAT), a sensitive modality for imaging optical absorption contrast over a range of spatial scales at high speed. In PAT, endogenous contrast reveals a tissue's anatomical, functional, metabolic, and histologic properties, and exogenous contrast provides molecular and cellular specificity. The spatial scale of PAT covers organelles, cells, tissues, organs, and small animals. Consequently, PAT is complementary to other imaging modalities in contrast mechanism, penetration, spatial resolution, and temporal resolution. We review the fundamentals of PAT and provide practical guidelines for matching PAT systems with research needs. We also summarize the most promising biomedical applications of PAT, discuss related challenges, and envision PAT's potential to lead to further breakthroughs.

Broadening the detection view of 2D photoacoustic tomography using two linear array transducers.

Although commercial linear array transducers are widely used in clinical ultrasound, their application in photoacoustic tomography (PAT) is still limited due to the limited-view problem that restricts the image quality. In this paper, we propose a simple approach to address the limited-view problem in 2D by using two linear array transducers to receive PAT signal from different orientations. The positions of the two transducers can be adjusted to fit the specific geometry of an imaging site. This approach is made possible by using a new calibration method, where the relative position between the two transducers can be calibrated using ultrasound by transmitting ultrasound wave with one transducer while receiving with the other. The calibration results are then applied in the subsequent PAT imaging to incorporate the detected acoustic signals from both transducers and thereby increase the detection view. In this calibration method, no calibration phantom is required which largely simplifies and shortens the process. The efficacy of the calibration and improvement on the PAT image quality are demonstrated through phantom studies and in vivo imaging.

Aggregation-induced near-infrared absorption of squaraine dye in an albumin nanocomplex for photoacoustic tomography in vivo.

Photoacoustic tomography (PAT) is a newly emerging noninvasive imaging modality that could be further enhanced using near-infrared (NIR)-absorbing materials as contrast agents. To date, the most extensively studied photoacoustic imaging agents are inorganic nanomaterials because organic materials with NIR-absorption capabilities are limited. In this study, a NIR-absorbing nanocomplex composed of a squaraine dye (SQ) and albumin was prepared based on the aggregation-induced NIR absorption of SQ. Through aggregation, the absorption spectrum of SQ was widened from the visible-light region to the NIR region, which facilitated photoacoustic signal generation in the tissue-transparent NIR optical window (700-900 nm). Blood analysis and histology measurements revealed that the nanocomplex can be used for PAT applications in vivo without obvious toxicity to living mice.

Model-Based Reconstruction Integrated With Fluence Compensation for Photoacoustic Tomography

Photoacoustic (PA) tomography (PAT) is a rapidly developing imaging modality that can provide high contrast and spatial-resolution images of light-absorption distribution in tissue. However, reconstruction of the absorption distribution is affected by nonuniform light fluence. This paper introduces a reconstruction method for reducing amplification of noise and artifacts in low-fluence regions. In this method, fluence compensation is integrated into model-based reconstruction, and the absorption distribution is iteratively updated. At each iteration, we calculate the residual between detected PA signals and the signals computed by a forward model using the initial pressure, which is the product of estimated voxel value and light fluence. By minimizing the residual, the reconstructed values converge to the true absorption distribution. In addition, we developed a matrix compression method for reducing memory requirements and accelerating reconstruction speed. The results of simulation and phantom experiments indicate that the proposed method provides a better contrast-to-noise ratio (CNR) in low-fluence regions. We expect that the capability of increasing imaging depth will broaden the clinical applications of PAT.

Non-contact photoacoustic tomography and ultrasonography for tissue imaging

The detection of ultrasound in photoacoustic tomography (PAT) and ultrasonography (US) usually relies on ultrasonic transducers in contact with the biological tissue. This is a major drawback for important potential applications such as surgery and small animal imaging. Here we report the use of remote optical detection, as used in industrial laser-ultrasonics, to detect ultrasound in biological tissues. This strategy enables non-contact implementation of PAT and US without exceeding laser exposure safety limits. The method uses suitably shaped laser pulses and a confocal Fabry-Perot interferometer in differential configuration to reach quantum-limited sensitivity. Endogenous and exogenous inclusions exhibiting optical and acoustic contrasts were detected ex vivo in chicken breast and calf brain specimens. Inclusions down to 0.5 mm in size were detected at depths well exceeding 1 cm. The method could significantly expand the scope of applications of PAT and US in biomedical imaging.

Image reconstruction in photoacoustic tomography involving layered acoustic media

Photoacoustic tomography (PAT), also known as thermoacoustic or optoacoustic tomography, is a rapidly emerging biomedical imaging technique that combines optical image contrast with ultrasound detection principles. Most existing reconstruction algorithms for PAT assume the object of interest possesses homogeneous acoustic properties. The images produced by such algorithms can contain significant distortions and artifacts when the object's acoustic properties are spatially variant. In this work, we establish an image reconstruction formula for PAT applications in which a planar detection surface is employed and the to-be-imaged optical absorber is embedded in a known planar layered acoustic medium. The reconstruction formula is exact in a mathematical sense and accounts for multiple acoustic reflections between the layers of the medium. Computer-simulation studies are conducted to demonstrate and investigate the proposed method.

Neurovascular photoacoustic tomography

Neurovascular coupling refers to the relationship between neuronal activities and downstream hemodynamic responses. Photoacoustic tomography (PAT), enabling comprehensive label-free imaging of hemodynamic activities with highly scalable penetration and spatial resolution, has great potential in the study of neurovascular coupling. In this review, we first introduce the technical basis of hemodynamic PAT – including label-free quantification of total hemoglobin concentration, blood oxygenation, and blood flow – as well as its applications in hemodynamic monitoring. Then, we demonstrate the potential application of PAT in neurovascular imaging by highlighting representative studies on cerebral vascular responses to whisker stimulation and Alzheimer's disease. Finally, potential research directions and associated technical challenges are discussed.

High-numerical-aperture-based virtual point detectors for photoacoustic tomography

The focal point of a high-numerical-aperture (NA) ultrasonic transducer can be used as a virtual point detector. This virtual point detector detects omnidirectionally over a wide acceptance angle. It also combines a large active transducer surface and a small effective virtual detector size. Thus the sensitivity is high compared with that of a real point detector, and the aperture effect is small compared with that of a finite size transducer. We present two kinds of high-NA-based virtual point detectors and their successful application in photoacoustic tomography. They can also be applied in other ultrasound-related fields.