Frequency-domain Photoacoustic Research Articles

Hybrid Fluorescence and Frequency-Domain Photoacoustic Microscopy for Imaging Development of Parhyale hawaiensis Embryos

Parhyale hawaiensis is a marine crustacean which has emerged as a powerful model organism to study molecular and cellular mechanisms linked to embryonic development and regenerative processes. Recently, several fluorescence-based optical microscopy techniques have been employed for the study of Parhyale to obtain anatomical descriptions, analyze gene expression patterns and reconstruct cell lineages. Aiming at the expansion of the imaging repertoire for this emerging model organism, we introduce a low-cost hybrid diagnostic system which integrates confocal fluorescence and frequency domain photoacoustic (FDPA) microscopy modalities, concurrently capturing both the radiative and radiationless relaxations of molecules following their excitation by an intensity-modulated laser source. We initially characterize the hybrid microscope in terms of PA signal generation efficiency and lateral spatial resolution, and subsequently evaluate its capabilities for the in vivo imaging of unlabelled and fluorescently labelled Parhyale embryos found at different stages of development. The recorded hybrid images have revealed a remarkable contrast complementarity between the integrated imaging modes, providing valuable information regarding cells’ structure, nuclei location, cellular membranes and yolk distribution. Our findings may pave the way for the broader adoption of inexpensive hybrid optical and PA microscopy methods in developmental biology, significantly upgrading the capabilities of the currently used technologies.

Complex Valued Long Short Term Memory Based Architecture for Frequency Domain Photoacoustic Imaging

Frequency domain photoacoustic (FDPA) imaging has great potential in a clinical setting compared to time-domain photoacoustic imaging due to its reduced cost and small form factors. However FDPA system struggles with lower signal to noise ratio, necessitating the need for advanced image reconstruction methods. Most of the image reconstruction approaches in FDPA imaging are based on analytical or model based schemes. Very less emphasis has been placed on developing deep learning based approaches for FDPA imaging. In this work, a image translation network was developed with the ability to directly map from sinogram data (complex-valued) to the initial pressure rise distribution (real-valued) for FD-PA imaging. This architecture was based on a Long Short Term Memory (LSTM) backbone (with adjoined real and imaginary parts of the complex sinogram data as input) followed by a fully connected layer, which is then passed through a convolution and transposed convolution layer pair. The result of the FDPA-LSTM architecture was compared with direct translational networks based on ResNet, UNet and AUTOMAP and found to have an improvement of about 15% in terms of PSNR and 10% in terms of SSIM with <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$150^{\circ }$</tex-math></inline-formula> data acquisition limited-view angle. Further, the FDPA-LSTM was also compared with post-processing UNet architecture on backprojection and Tikhonov regularized reconstruction. A 20% improvement in terms of PSNR with backprojection and post-processing UNet was observed. Further FDPA-LSTM had similar performance as Tikhonov and post-processing UNet (with 75 times acceleration). The developed scheme will indeed be very useful for achieving accelerated and accurate frequency domain photoacoustic imaging.

Investigation on Reconstruction for Frequency Domain Photoacoustic Imaging via TVAL3 Regularization Algorithm

Photoacoustic imaging (PAI) has been widely investigated by researchers from a range of areas. According to the differences between excitation laser sources, PAI can be categorized into two main types, namely the time-domain and frequency-domain PAI. Although the frequency-domain approach is more portable and economic than the other alternative, the low intensity of excitation source may lead to a lower signal-to-noise ratio (SNR). This paper aiming to propose the suitable scheme for image reconstruction, we focus on the model-based PAI system and make great efforts to reduce the impact of noise algorithmically. Three regularization algorithms, i.e., Least Square QR-factorization, Tikhonov, and Total Variation minimization by Augmented Lagrangian and alternating direction algorithms (TVAL3) are studied. By choosing three important parameters as criteria, i.e., the peak SNR, image quality index, and time consumption during different situations, the most effective regularization algorithm amongst has been selected. Based on simulation results and detailed discussions, TVAL3 algorithm performs better than the other two for model-based signal reconstruction. The result is pivotal for effective PAI in high quality and highly efficient biomedical tomography and microimaging.

Combined frequency domain photoacoustic and ultrasound imaging for intravascular applications.

Intravascular photoacoustic (IVPA) imaging has the potential to characterize lipid-rich structures based on the optical absorption contrast of tissues. In this study, we explore frequency domain photoacoustics (FDPA) for intravascular applications. The system employed an intensity-modulated continuous wave (CW) laser diode, delivering 1W over an intensity modulated chirp frequency of 4-12MHz. We demonstrated the feasibility of this approach on an agar vessel phantom with graphite and lipid targets, imaged using a planar acoustic transducer co-aligned with an optical fibre, allowing for the co-registration of IVUS and FDPA images. A frequency domain correlation method was used for signal processing and image reconstruction. The graphite and lipid targets show an increase in FDPA signal as compared to the background of 21dB and 16dB, respectively. Use of compact CW laser diodes may provide a valuable alternative for the development of photoacoustic intravascular devices instead of pulsed laser systems.

Self temperature regulation of photothermal therapy by laser-shared photoacoustic feedback.

This article describes a laser-shared photothermal system that achieves tight temperature regulation by frequency-domain photoacoustic (FD-PA) feedback. To this end, a continuous-wave laser system was designed with arbitrarily modulatable laser intensity. And, by fast alternating in the time domain between a constant laser intensity for photothermal heating and a modulated laser intensity for FD-PA temperature measurement, photothermal temperature variations are captured by FD-PA in real time. A proportional-integral-derivative (PID) controller monitors the feedback from FD-PA measurements and controls photothermal heating dose accordingly, thus stabilizing the temperature at preset values. The proposed system is demonstrated to achieve ultrafast temperature measurement at a 4 kHz rate, and with proper averaging, the measurement and regulation accuracy are 0.75 deg and 0.9 deg respectively.

A cost-efficient frequency-domain photoacoustic imaging system

Photoacoustic (PA) imaging techniques have recently attracted much attention and can be used for noninvasive imaging of biological tissues. Most PA imaging systems in research laboratories use the time domain method with expensive nanosecond pulsed lasers that are not affordable for most educational laboratories. Using an intensity modulated light source to excite PA signals is an alternative technique, known as the frequency domain method, with a much lower cost. In this paper, we describe a simple frequency domain PA system and demonstrate its imaging capability. The system provides opportunities not only to observe PA signals in tissue phantoms, but also to acquire hands-on skills in PA signal detection. It also provides opportunities to explore the underlying mechanisms of the PA effect.

Study of Tissue Phantoms, Tissues, and Contrast Agent with the Biophotoacoustic Radar and Comparison to Ultrasound Imaging for Deep Subsurface Imaging

In this study, the imaging capability of our wide-spectrum frequency-domain photoacoustic (FD-PA) imaging alias “photoacoustic radar” methodology for imaging of soft tissues is explored. A practical application of the mathematical correlation processing method with relatively long (1 ms) frequency-modulated optical excitation is demonstrated for reconstruction of the spatial location of the PA sources. Image comparison with ultrasound (US) modality was investigated to see the complementarity between the two techniques. The obtained results with a phased array probe on tissue phantoms and their comparison to US images demonstrated that the FD-PA technique has strong potential for deep subsurface imaging with excellent contrast and high signal-to-noise ratio. FD-PA images of blood vessels in a human wrist and an in vivo subcutaneous tumor in a rat model are presented. As in other imaging modalities, the employment of contrast agents is desirable to improve the capability of medical diagnostics. Therefore, this study also evaluated and characterized the use of Food and Drug Administration (FDA)-approved superparamagnetic iron oxide nanoparticles (SPION) as PA contrast agents.

Reconstruction of sectional images in frequency-domain based photoacoustic imaging

Photoacoustic (PA) imaging is based upon the generation of an ultrasound pulse arising from subsurface tissue absorption due to pulsed laser excitation, and measurement of its surface time-of-arrival. Expensive and bulky pulsed lasers with high peak fluence powers may provide shortcomings for applications of PA imaging in medicine and biology. These limitations may be overcome with the frequency-domain PA measurements, which employ modulated rather than pulsed light to generate the acoustic wave. In this contribution, we model the single modulation frequency based PA pressures on the measurement plane through the diffraction approximation and then employ a convolution approach to reconstruct the sectional image slices. The results demonstrate that the proposed method with appropriate data post-processing is capable of recovering sectional images while suppressing the defocused noise resulting from the other sections.

Frequency domain photoacoustics using intensity-modulated laser sources

In this paper, we present an overview of research in the area of narrow-bandwidth generation and detection of ultrasound using a technique referred to as frequency domain photoacoustics. An intensity-modulated continuous wave laser is used for narrowband ultrasound generation, and an interferometer coupled to a radio frequency lock-in amplifier is used for detection. Excellent sensitivity is achieved using sinusoidal modulation of the excitation laser over long time scales, thereby focusing the acoustic energy at the excitation frequency. We describe an experimental approach for the direct detection of narrowband signals at the ultrasound excitation frequency, and a superheterodyne technique in which the signal is optically down-converted to a low and fixed intermediate frequency prior to detection. Two approaches for materials characterisation using frequency domain photoacoustic measurements are presented. In the first approach, the modulation frequency of the excitation laser is scanned over the bandwidth of interest, and a transient sample response is constructed from the frequency-domain data. Ultrasound arrivals that are separated in the time domain can then be time gated for further analysis. In the second approach, the modulation frequency of the excitation laser is fixed, but the source-to-receiver distance is varied. The spatial frequencies of the ultrasound modes generated by the laser are detected by analysing the spatial variation of the phase, allowing for the velocity of each mode at a given frequency to be determined. Experimental measurements in thin films, plates and nanomechanical structures are presented.

Frequency domain photothermoacoustic signal amplitude dependence on the optical properties of water: turbid polyvinyl chloride-plastisol system

Photoacoustic (more precisely, photothermoacoustic) signals generated by the absorption of photons can be related to the incident laser fluence rate. The dependence of frequency domain photoacoustic (FD-PA) signals on the optical absorption coefficient (micro(a)) and the effective attenuation coefficient (micro(eff)) of a turbid medium [polyvinyl chloride-plastisol (PVCP)] with tissuelike optical properties was measured, and empirical relationships between these optical properties and the photoacoustic (PA) signal amplitude and the laser fluence rate were derived for the water (PVCP system with and without optical scatterers). The measured relationships between these sample optical properties and the PA signal amplitude were found to be linear, consistent with FD-PA theory: micro(a)=a(A/Phi)-b and micro(eff)=c(A/Phi)+d, where Phi is the laser fluence, A is the FD-PA amplitude, and a, ...,d are empirical coefficients determined from the experiment using linear frequency-swept modulation and a lock-in heterodyne detection technique. This quantitative technique can easily be used to measure the optical properties of general turbid media using FD-PAs.