Photoacoustic imaging is a promising method for visualizing biological tissues with optical absorbers. This article provides an overview of the rapidly developing field of photoacoustic imaging. Photoacoustics, the physical basis of photoacoustic imaging, is analyzed briefly. The merits of photoacoustic technology, compared with optical imaging and ultrasonic imaging, are described. Various imaging techniques are also discussed, including scanning tomography, computed tomography and original detection of photoacoustic imaging. Finally, some biomedical applications of photoacoustic imaging are summarized.

Photoacoustic imaging in biomedicine

(1896). XV. On the theory of optical images, with special reference to the microscope. The London, Edinburgh, and Dublin Philosophical Magazine and Journal of Science: Vol. 42, No. 255, pp. 167-195.

On the theory of optical images, with special reference to the microscope

Over the past few decades, the synthetic development of ultra-small nanoparticles has become an important strategy in nano-medicine, where smaller-sized nanoparticles are known to be more easily excreted from the body, greatly reducing the risk caused by introducing nano-theranostic agents. Gold nanorods are one of the most important nano-theranostic agents because of their special optical and electronic properties. However, the large size (diameter > 6 nm) of most obtained gold nanorods limits their clinical application. In recent years, more and more researchers have begun to investigate the synthesis and application of small gold nanorods (diameter < 6 nm), which exhibit similar optical and electronic properties as larger gold nanorods. In this review, we summarize the recent advances of synthesis of the small gold nanorods and their application for near-infrared light-mediated bio-imaging and cancer therapy.

https://www.mdpi.com/1996-1944/10/12/1372/pdf

Small Gold Nanorods: Recent Advances in Synthesis, Biological Imaging, and Cancer Therapy.

Gold nanoparticles are widely exploited in phototherapy. Owing to their biocompatibility and their strong visible-light surface plasmonic resonance, these particles also serve as contrast agents for cell image enhancement and super-resolved imaging. Yet, their optical signal is still insufficiently strong for many important real-life applications. Also, the differentiation between adjacent nanoparticles is usually limited by the optical resolution and the orientations of non-spherical particles are unknown. These limitations hamper the progress in cell research by direct optical microscopy and narrow the range of phototherapy applications. Here we demonstrate exploiting the optical anisotropy of non-spherical nanoparticles to achieve super-resolution in live cell imaging and to resolve the intracellular nanoparticle orientations. In particular, by modulating the light polarization and taking advantage of the polarization-dependence of gold nanorod optical properties, we realize the ‘lock-in amplification’, widely-used in electronic engineering, to achieve image enhancement in live cells and in cells that undergo apoptotic changes.

/pdf/imaging-of-nanoparticle-dynamics-in-live-and-apoptotic-cells-31rgjgb0rs.pdf

Imaging of nanoparticle dynamics in live and apoptotic cells using temporally-modulated polarization.

Quantitative phase microscopy (QPM), a technique combining phase imaging and microscopy, enables visualization of the 3D topography in reflective samples, as well as the inner structure or refractive index distribution of transparent and translucent samples. Similar to other imaging modalities, QPM is constrained by the conflict between numerical aperture (NA) and field of view (FOV): an imaging system with a low NA has to be employed to maintain a large FOV. This fact severely limits the resolution in QPM up to 0.82λ/NA, λ being the illumination wavelength. Consequently, finer structures of samples cannot be resolved by using modest NA objectives in QPM. Aimed to that, many approaches, such as oblique illumination, structured illumination, and speckle illumination (just to cite a few), have been proposed to improve the spatial resolution (or the space–bandwidth product) in phase microscopy by restricting other degrees of freedom (mostly time). This paper aims to provide an up-to-date review on the resolution enhancement approaches in QPM, discussing the pros and cons of each technique as well as the confusion on resolution definition claims on QPM and other coherent microscopy methods. Through this survey, we will review the most appealing and useful techniques for superresolution in coherent microscopy, working with and without lenses and with special attention to QPM. Note that, throughout this review, with the term “superresolution” we denote enhancing the resolution to surpass the limit imposed by diffraction and proportional to λ/NA, rather than the physics limit λ/(2n
	 med
	), with n
	 med
	 being the refractive index value of the immersion medium.

Resolution enhancement in quantitative phase microscopy

In this paper, a design for a 1 × 4 optical power splitter based on the multimode interference (MMI) coupler in a silicon (Si)–gallium nitride (GaN) slot waveguide structure is presented—to our knowledge, for the first time. Si and GaN were found as suitable materials for the slot waveguide structure. Numerical optimizations were carried out on the device parameters using the full vectorial-beam propagation method (FV-BPM). Simulation results show that the proposed device can be useful to divide optical signal energy uniformly in the C-band range (1530–1565 nm) into four output ports with low insertion losses (0.07 dB).

/pdf/a-photonic-1-4-power-splitter-based-on-multimode-zjoepf4aiv.pdf

A Photonic 1 × 4 Power Splitter Based on Multimode Interference in Silicon–Gallium-Nitride Slot Waveguide Structures

Utilizing the surface plasmon resonance effect in gold nanoparticles enables their use as contrast agents in a variety of applications for compound cellular imaging. However, most techniques suffer from poor signal to noise ratio (SNR) statistics due to high shot noise that is associated with low photon count in addition to high background noise. We demonstrate an effective way to improve the SNR, in particular when the inspected signal is indistinguishable in the given noisy environment. We excite the temporal flickering of the scattered light from gold nanoparticle that labels a biological sample. By preforming temporal spectral analysis of the received spatial image and by inspecting the proper spectral component corresponding to the modulation frequency, we separate the signal from the wide spread spectral noise (lock-in amplification).

/pdf/cellular-imaging-using-temporally-flickering-nanoparticles-49nh2nabpw.pdf

Cellular imaging using temporally flickering nanoparticles

Currently available cancer therapies can cause damage to healthy tissue. We developed a unique method for specific mechanical lysis of cancer cells using superparamagnetic iron oxide nanoparticle rotation under a weak alternating magnetic field. Iron oxide core nanoparticles were coated with cetuximab, an anti-epidermal growth factor receptor antibody, for specific tumor targeting. Nude mice bearing a head and neck tumor were treated with cetuximab-coated magnetic nanoparticles (MNPs) and then received a 30 min treatment with a weak external alternating magnetic field (4 Hz) applied on alternating days (total of seven treatments, over 14 days). This treatment, compared to a pure antibody, exhibited a superior cell death effect over time. Furthermore, necrosis in the tumor site was detected by magnetic resonance (MR) images. Thermal camera images of head and neck squamous cell carcinoma cultures demonstrated that cell death occurred purely by a mechanical mechanism.

Targeted Magnetic Nanoparticles for Mechanical Lysis of Tumor Cells by Low-Amplitude Alternating Magnetic Field.

In this paper we present a technique aimed for simultaneous detection of multiple types of gold nanoparticles (GNPs) within a biological sample, using lock-in detection. We image the sample using a number of modulated laser beams that correspond to the number of GNP species that label a given sample. The final image where the GNPs are spatially separated is obtained computationally. The proposed method enables the simultaneous superresolved imaging of different areas of interest within biological sample and also the spatial separation of GNPs at sub-diffraction distances, making it a useful tool in the study of intracellular trafficking pathways in living cells.

/pdf/cellular-superresolved-imaging-of-multiple-markers-using-3t9odhvlgf.pdf

Cellular superresolved imaging of multiple markers using temporally flickering nanoparticles.

Optical filters are required to have narrow band-pass filtering in the spectral C-band for applications such as signal tracking, sub-band filtering or noise suppression. These requirements lead to a variety of filters that offer thermo-optic effect for optical switching, however, some of which without proper thermal and optical efficiency. In this paper we propose a tunable thermo-optic filtering device based on a coated silicon slab resonator with an increased Q-factor to allow for an efficient thermo-optical switching in the C-band. The device can be designed either for long range wavelength tuning or for short range with increased wavelength resolution. Theoretical examination of the thermal parameters affecting the filtering process is shown together with experimental results. Proper channel isolation with an extinction ratio of 20 dB is achieved with a spectral bandpass width of 0.07 nm. This Si slab based filter characteristics make it suitable for wavelength switching systems such as dense wavelength division multiplexing. In addition, the filter is fiber integrated in order for it to be more compatible with other optics communication devices.

/pdf/design-of-fiber-integrated-tunable-thermo-optic-c-band-8xuqtv9lxk.pdf

Yossef Danan

Papers

A Photonic 1 × 4 Power Splitter Based on Multimode Interference in Silicon–Gallium-Nitride Slot Waveguide Structures

Cellular imaging using temporally flickering nanoparticles

Targeted Magnetic Nanoparticles for Mechanical Lysis of Tumor Cells by Low-Amplitude Alternating Magnetic Field.

Cellular superresolved imaging of multiple markers using temporally flickering nanoparticles.

Design of fiber-integrated tunable thermo-optic C-band filter based on coated silicon slab