Laser spectroscopy & imaging
Decades of experience and close relationships with researchers enabled to create laser systems designed for specific laser spectroscopy and imaging applications.
Laser sources for photoacoustic imaging
Photoacoustic imaging is one of the fastest-growing research areas
of non-invasive, high-resolution and high-contrast visualization of both superficial and deep tissues.
This method has a number of advantages over widely used conventional research and diagnostic methods as unlike X-ray, it does not use hazardous irradiation and has a significantly higher imaging resolution compared to conventional ultrasound. Photoacoustic imaging is proven to be very effective in diagnosing breast tumors, skin cancer, thyroid nodules, osteoarthritis and rheumatoid arthritis, early diagnosis of blood vessel disorders and many more. Photoacoustic imaging can also be used for visualization of non-living objects, such as nondestructive inspection of the internal structure and property changes of composite materials and food inspection.
Photoacoustic imaging employs the physical property of molecules to briefly heat up and cool down while absorbing a short pulse of light
(couple of nanoseconds) of a certain wavelength. While heating up, molecules expand and while cooling down, they contract. This creates an ultrasound wave which can be captured by ultrasound transducers enabling the ability to locate the origin of sound. The penetration of light into tissue depends on the tissue properties and the pulse energy of the light. Moreover, different chromophores in the tissue can absorb light of different wavelengths, thus giving functional visual information.
Comparison table of photoacoustic imaging sources
Model | Available output wavelengths | Pulse duration 1) | Max repetition rate | Max pulse energy |
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Diode pumped laser source | ||||
PhotoSonus X | 650 – 1300 nm (signal) 1065 – 2600 nm (idler) | 2 – 5 ns | 100 Hz | 90 mJ |
Mobile flashlamp pumped laser source | ||||
PhotoSonus M | 660 – 1320 nm (signal) 330 – 659 nm (SH) 1065 – 2300 nm (idler) | 3 – 5 ns | 20 Hz | 180 mJ |
PhotoSonus M+ | 660 – 1064 nm (signal) 2) 330 – 530 nm (SH) 3) 1065 – 2300 nm (idler) | 3 – 5 ns | 10 Hz | 250 mJ |
Table-top flashlamp pumped laser source | ||||
PhotoSonus T | 660 – 1320 nm (signal) 330 – 659 nm (SH) 1065 – 2300 nm (idler) | 3 – 5 ns | 20 Hz | 150 mJ |
PhotoSonus T+ | 660 – 1064 nm (signal) 2) 330 – 530 nm (SH) 3) 1065 – 2300 nm (idler) | 3 – 5 ns | 10 Hz | 230 mJ |
Model | Available output wavelengths | Pulse duration 1) | Max repetition rate | Max pulse energy |
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- FWHM measured with photodiode featuring 1 ns rise time and 300 MHz bandwidth oscilloscope.
- Optional signal extended range: 660 – 1320 nm.
- When extended signal range is selected, wavelength range is 330 – 659 nm.
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Sum frequency generation spectroscopy systems
Vibrational Spectroscopy (SFG-VS) is powerful and versatile method for in-situ investigation of surfaces and interfaces. In SFG-VS experiment a pulsed tunable infrared IR (ωIR) laser beam is mixed with a visible VIS (ωVIS) beam to produce an output at the sum frequency (ωSFG = ωIR + ωVIS). SFG is second order nonlinear process, which is allowed only in media without inversion symmetry.
At surfaces or interfaces inversion symmetry is necessarily broken, that makes SFG highly surface specific. As the IR wavelength is scanned, active vibrational modes of molecules at the interface give a resonant contribution to SF signal. The resonant enhancement provides spectral information on surface characteristic vibrational transitions.
Vibrational sum frequency generation (SFG) spectroscopy holds several important advantages over traditional spectroscopy methods for the molecular level analysis of interfaces, including (i) surface sensitivity, (ii) vibrational specificity, and (iii) the possibility to extract detailed information on the ordering and orientation of molecular groups at the interface by analysis of polarization-dependent SFG spectra.
Narrowband picosecond scanning SFG spectrometer
In order to get SFG spectrum during measurement wavelength of narrowband mid-IR pulse is changed point-by-point throughout the range of interest. Narrowband SFG signal is recorded by the time-gated photomultiplier. Energy of each mid-IR, VIS and SFG pulse is measured. After the measurement, the SFG spectrum can be normalised according to IR and VIS energy. Spectral resolution is determined by the bandwidth of the mid-IR light source. The narrower mid-IR pulse bandwidth, the better the SFG spectral resolution. Separate vibrational modes are excited during the measurement.
Broadband femtosecond SFG spectrometer
A broadband mid-IR pulse is mixed with a narrowband VIS pulse. The result is broadband SFG spectrum which is recorded using a monochromator and a sensitive CCD camera. The full spectrum is acquired simultaneously by integrating signal over time. Spectral resolution is determined by the bandwidth of the VIS pulse and on the monochromator-camera combination. The narrower the bandwidth of VIS pulse, the better the SFG spectral resolution.
Comparison of different SFG spectrometres
Narrowband Picosecond Scanning Spectrometer | Broadband Femtosecond High Resolution Spectrometer |
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Narrowband mid-IR excitation, only one band is excited. Coupled states can be separated. | Simultaneous exsitation and recording of broad vibration spectrum with high resolution. |
High mid-IR pulse energy. Less influence of IR absorbtion in the air. | High mid-IR intensity at low pulse energy – suitable for biological or other water containing samples. |
No reference spectrum needed, IR energy measured at each spectral point. | Optically coupled IR and VIS channels. Reduced complexity and increased stability of the system. |
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Publications
A fast all-optical 3D photoacoustic scanner for clinical vascular imaging
The clinical assessment of microvascular pathologies (in diabetes and in inflammatory skin diseases, for example) requires the visualization of superficial vascular anatomy. Photoacoustic tomography (PAT) scanners based on an all-optical Fabry–Perot ultrasound sensor can provide highly detailed 3D microvascular images, but minutes-long acquisition times have precluded their clinical use. Here we show that scan times can be reduced to a few seconds and even hundreds of milliseconds by parallelizing the optical architecture of the sensor readout, by using excitation lasers with high pulse-repetition frequencies and by exploiting compressed sensing. A PAT scanner with such fast acquisition minimizes motion-related artefacts and allows for the volumetric visualization of individual arterioles, venules, venous valves and millimetre-scale arteries and veins to depths approaching 15 mm, as well as for dynamic 3D images of time-varying tissue perfusion and other haemodynamic events. In exploratory case studies, we used the scanner to visualize and quantify microvascular changes associated with peripheral vascular disease, skin inflammation and rheumatoid arthritis. Fast all-optical PAT may prove useful in cardiovascular medicine, oncology, dermatology and rheumatology.
An Investigation of Signal Preprocessing for Photoacoustic Tomography
Photoacoustic tomography (PAT) is increasingly being used for high-resolution biological imaging at depth. Signal-to-noise ratios and resolution are the main factors that determine image quality. Various reconstruction algorithms have been proposed and applied to reduce noise and enhance resolution, but the efficacy of signal preprocessing methods which also affect image quality, are seldom discussed. We, therefore, compared common preprocessing techniques, namely bandpass filters, wavelet denoising, empirical mode decomposition, and singular value decomposition. Each was compared with and without accounting for sensor directivity. The denoising performance was evaluated with the contrast-to-noise ratio (CNR), and the resolution was calculated as the full width at half maximum (FWHM) in both the lateral and axial directions. In the phantom experiment, counting in directivity was found to significantly reduce noise, outperforming other methods. Irrespective of directivity, the best performing methods for denoising were bandpass, unfiltered, SVD, wavelet, and EMD, in that order. Only bandpass filtering consistently yielded improvements. Significant improvements in the lateral resolution were observed using directivity in two out of three acquisitions. This study investigated the advantages and disadvantages of different preprocessing methods and may help to determine better practices in PAT reconstruction.
Bimetallic Hyaluronate-Modified Au@Pt Nanoparticles for Noninvasive Photoacoustic Imaging and Photothermal Therapy of Skin Cancer
Although spherical gold (Au) nanoparticles have remarkable photothermal conversion efficiency and photostability, their weak absorption in the near-infrared (NIR) region and poor penetration into deep tissues have limited further applications to NIR light-mediated photoacoustic (PA) imaging and noninvasive photothermal cancer therapy. Here, we developed bimetallic hyaluronate-modified Au–platinum (HA-Au@Pt) nanoparticles for noninvasive cancer theranostics by NIR light-mediated PA imaging and photothermal therapy (PTT). The growth of Pt nanodots on the surface of spherical Au nanoparticles enhanced the absorbance in the NIR region and broadened the absorption bandwidth of HA-Au@Pt nanoparticles by the surface plasmon resonance (SPR) coupling effect. In addition, HA facilitated the transdermal delivery of HA-Au@Pt nanoparticles through the skin barrier and enabled clear tumor-targeted PA imaging. Compared to conventional PTT via injection, HA-Au@Pt nanoparticles were noninvasively delivered into deep tumor tissues and completely ablated the targeted tumor tissues by NIR light irradiation. Taken together, we could confirm the feasibility of HA-Au@Pt nanoparticles as a NIR light-mediated biophotonic agent for noninvasive skin cancer theranostics.
Characterizing a photoacoustic and fluorescence imaging platform for preclinical murine longitudinal studies
Significance. To effectively study preclinical animal models, medical imaging technology must be developed with a high enough resolution and sensitivity to perform anatomical, functional, and molecular assessments. Photoacoustic (PA) tomography provides high resolution and specificity, and fluorescence (FL) molecular tomography provides high sensitivity; the combination of these imaging modes will enable a wide range of research applications to be studied in small animals.
Aim. We introduce and characterize a dual-modality PA and FL imaging platform using in vivo and phantom experiments.
Approach. The imaging platform’s detection limits were characterized through phantom studies that determined the PA spatial resolution, PA sensitivity, optical spatial resolution, and FL sensitivity.
Results. The system characterization yielded a PA spatial resolution of 173 ± 17 μm in the transverse plane and 640 ± 120 μm in the longitudinal axis, a PA sensitivity detection limit not less than that of a sample with absorption coefficient μa = 0.258 cm − 1, an optical spatial resolution of 70 μm in the vertical axis and 112 μm in the horizontal axis, and a FL sensitivity detection limit not <0.9 μM concentration of IR-800. The scanned animals displayed in three-dimensional renders showed high-resolution anatomical detail of organs.
Conclusions. The combined PA and FL imaging system has been characterized and has demonstrated its ability to image mice in vivo, proving its suitability for biomedical imaging research applications.
Deep Learning Enhances Multiparametric Dynamic Volumetric Photoacoustic Computed Tomography In Vivo (DL-PACT)
Abstract Photoacoustic computed tomography (PACT) has become a premier preclinical and clinical imaging modality. Although PACT\’s image quality can be dramatically improved with a large number of ultrasound (US) transducer elements and associated multiplexed data acquisition systems, the associated high system cost and/or slow temporal resolution are significant problems. Here, a deep learning-based approach is demonstrated that qualitatively and quantitively diminishes the limited-view artifacts that reduce image quality and improves the slow temporal resolution. This deep learning-enhanced multiparametric dynamic volumetric PACT approach, called DL-PACT, requires only a clustered subset of many US transducer elements on the conventional multiparametric PACT. Using DL-PACT, high-quality static structural and dynamic contrast-enhanced whole-body images as well as dynamic functional brain images of live animals and humans are successfully acquired, all in a relatively fast and cost-effective manner. It is believed that the strategy can significantly advance the use of PACT technology for preclinical and clinical applications such as neurology, cardiology, pharmacology, endocrinology, and oncology.
Fast photoacoustic imaging technology for deep structure information of finger
In this paper, we exploited the fast-imaging technology for the deep structure of finger based on photoacoustic imaging, which adopted the self-designed 128-ring-array fast photoacoustic imaging system to acquire the latent inside information of finger. The home-made photoacoustic imaging system has the merits of fast imaging, high resolution and deep imaging depth. Specifically, our system could obtain a cross section scan of finger within 0.05 or 0.1s, achieve the resolution of approach 180 μm and image the latent inside information of finger as well as extend the imaging depth over 5 cm in chicken breast tissue at the laser density of 20 mJ/cm2 (≤ANSI safety limit). In this work, we obtained the finger anatomical information of skin tissue, blood vessel tissue, and the information of tendon tissue and phalanx tissue which is relatively difficult to obtain by means of photoacoustic imaging. So, we will be able to restore an overall internal structure of a finger including its external shape its internal tendon structure and its internal phalanx structure or containing its blood vessel structure. And that more information from different angles can make its identification more accurate. It is prospective that the deep structure of finger we get by our fast photoacoustic imaging technology will help to provide more possibilities for finger identification and lead to more credible technology for human about relevant information collection and resolution.
Fully three-dimensional sound speed-corrected multi-wavelength photoacoustic breast tomography
Photoacoustic tomography is a contrast agent-free imaging technique capable of visualizing blood vessels and tumor-associated vascularization in breast tissue. While sophisticated breast imaging systems have been recently developed, there is yet much to be gained in imaging depth, image quality and tissue characterization capability before clinical translation is possible. In response, we have developed a hybrid photoacoustic and ultrasound-transmission tomographic system PAM3. The photoacoustic component has for the first time three-dimensional multi-wavelength imaging capability, and implements substantial technical advancements in critical hardware and software sub-systems. The ultrasound component enables for the first time, a three-dimensional sound speed map of the breast to be incorporated in photoacoustic reconstruction to correct for inhomogeneities, enabling accurate target recovery. The results demonstrate the deepest photoacoustic breast imaging to date namely 48 mm, with a more uniform field of view than hitherto, and an isotropic spatial resolution that rivals that of Magnetic Resonance Imaging. The in vivo performance achieved, and the diagnostic value of interrogating angiogenesis-driven optical contrast as well as tumor mass sound speed contrast, gives confidence in the system’s clinical potential.
LED-based Schlieren system for full-field photoacoustic wave acquisition and image reconstruction
In this work, full-field detection of laser-induced ultrasound waves was performed with an off-axis LED-based Schlieren system. Sensing strobe light, pulsed laser dual light-sheet excitation, and CMOS sensor device were all synchronized to capture the pressure wave as it propagated through an elastic liquid surrounding the test sample. In addition, a reconstruction algorithm based on the Radon transform was applied to the digitally recorded field in order to obtain an image of the photoacoustic source. The proposed system is capable of retrieving the profile of cylindrical and hexagonal targets.
Microfluidic Fabrication of Highly Efficient Hydrogel Optical Fibers for In Vivo Fiber-Optic Applications
Abstract Although efficient light delivery is required for various biomedical applications, the high stiffness of traditional silica-based optical fibers limits their in vivo usage. In this study, highly deformable and stretchable soft optical fibers are prepared based on the mechanically tough hydrogels of a double network (DN) structure comprising covalently crosslinked acrylamide and ionically crosslinked alginate using a microfluidic device. Owing to the optimized chemical composition, the core/cladding structure, and the mechanical robustness of the prepared hydrogel optical fibers, highly efficient optical delivery is achieved even at highly deformed and elongated states. Furthermore, the microfluidic device further allowed the formation of dual-core, novel architectures for hydrogel optical fibers. With the aid of the dopamine moiety included in the cladding, the hydrogel optical fibers attached strongly to all surfaces tested. Light delivery is further confirmed by implantation in the biological tissues. The high light-guiding performance of the developed hydrogel optical fibers enables them to replace the conventional silica optical fibers used in UV/Vis, fluorescence, and photoacoustic spectroscopies. To demonstrate their in vivo fiber-optic application potential, they are placed inside mice, and the excitation and emission of the generated fluorescence signals are detected.
Photoacoustic tomography with a model-based approach involving realistic detector properties
A computational and experimental study is conducted to examine how directivity associated with a finite aperture sensor affects photoacoustic tomography (PAT) image reconstruction. Acoustic signals for the simulation work were computed using a discrete particle approach from three numerical phantoms including a vasculature. The theoretical framework and a Monte Carlo approach for construction of a tissue configuration are discussed in detail. While simulating forward data, the directivity of the sensor was taken into account. The image reconstruction was accomplished using system matrix based methods like l2 norm Tikhonov regularization, l1 norm regularization and total variation (TV) minimization. Accordingly, two different system matrices were constructed- (i) assuming transducer as a point detector (PD) and (ii) retaining properties of a finite detector with directivity (FDWD). Image reconstruction was also performed utilizing experimentally measured PA signals. Both the computational and experimental results demonstrate that blur-free PAT imaging can be achieved with the FDWD method. Additionally, TV minimization provides marginally better image reconstruction compared to the other schemes.