Hybrid optical parametrically-oscillating emitter at 1930 nm for volumetric photoacoustic imaging of water content

Schematic diagram of the hybrid optical parametrically-oscillating emitter (HOPE) at 1930 nm.

eLight 2, 6 (2022)
Jiawei Shi, Mingsheng Li, Huajun Tang, Jiqiang Kang, Najia Sharmin, Amir Rosenthal & Kenneth K. Y. Wong

Abstract:

Water plays a vital role in biological metabolism and it would be essential to trace the water content non-invasively, such as leveraging the vibrational absorption peak of the O–H bond. However, due to the lack of an efficient laser source, it was challenging to image the water content in the deep tissue with micron-level spatial resolution. To address this problem, we develop a high-power hybrid optical parametrically-oscillating emitter (HOPE) at 1930 nm, at which the vibrational absorption peak of the O–H bond locates. The maximum pulse energy is over 1.74 μJ with a pulse repetition rate of 50 kHz and a pulse width of 15 ns. We employ this laser source in the optical-resolution photoacoustic microscopy (OR-PAM) system to image the water content in the phantom and the biological tissue in vitro. Our 1930-nm OR-PAM could map the water content in the complex tissue environment at high spatial resolution, deep penetration depth, improved sensitivity, and suppressed artifact signal of the lipid.

PA image of (a) water acquired by 1930-nm OR-PAM

Fig. PA image of (a) water acquired by 1930-nm OR-PAM and b lipid acquired by 1750-nm OR-PAM; c Overlaid PA image of (a) and (b). d Photography of the adipose tissue. e–f Three-dimensional rendering view of (a, b). Scale bars, 500 µm

Read more – eLight 2, 6 (2022) 
Jiawei Shi, Mingsheng Li, Huajun Tang, Jiqiang Kang, Najia Sharmin, Amir Rosenthal & Kenneth K. Y. Wong

Silicon-photonics acoustic detector for optoacoustic micro-tomography.

Yoav _mouse_ear_left1_shr_450X450

© 2022 Nature  Communications

Technology developed at the Andrew and Erna Viterbi Faculty of Electrical and Computer Engineering will allow the miniaturization of ultrasound transducers, thereby improving their resolution
New technology that allows for very high-resolution medical imaging (close to 10 µm) is expected to lead to the development of tiny and effective ultrasound systems and other medical applications. The innovative technology, SPADE, is based on research led by Professor Amir Rosenthal and Ph.D. student Yoav Hazan of the Andrew and Erna Viterbi Faculty of Electrical and Computer Engineering at the Technion-Israel Institute of Technology. Their findings were published in Nature Communications.

Prof. Amir Rosenthal (left) and Ph.D. student Yoav Hazan of the Andrew and Erna Viterbi Faculty of Electrical and Computer Engineering
Prof. Amir Rosenthal (left) and Ph.D. student Yoav Hazan of the Andrew and Erna Viterbi Faculty of Electrical and Computer Engineering

Medical ultrasound is an accepted and common tool for monitoring various physiological conditions in internal tissues. Its great advantage is that unlike CT scans and x-rays, it is not based on ionizing radiation, which is considered dangerous in high doses. The main component of ultrasound systems is the transducer – an electro-mechanical device that transmits and receives ultrasound waves.

One of the technological challenges in the world of ultrasound is the development of endoscopic transducers – miniature transducers inserted through a tiny hole in the skin, or from one of the body’s natural orifices in a minimally invasive procedure. Such transducers are essential because the scan of deep tissue regions often requires a small transducer that comes close to the target tissue.

The challenge in developing these transducers stems in part from the fact that miniaturization impairs their sensitivity, making it difficult to create high-quality images. The SPADE (Silicon-Photonics Acoustic Detector) technology developed by the Technion researchers is based on optical components instead of electrical components that literally alter the image. It provides the possibility to perform ultrasound tests in resolutions not previously achieved. The researchers stress that the new technology could dramatically improve the resolution of additional diagnostic methods such as vascular imaging using optoacoustics. In this regard, the article in Nature Communications presents mapping of blood vessels in a mouse’s ear at an unprecedented resolution (about 10 microns).

image ear comparation

The study was supported by the Russell Berrie Nanotechnology Institute (RBNI), the National Science Foundation, the Polak Foundation, the Israel Innovation Authority,  the Israel Science Foundation and the Ollendorf Minerva Center.

Read more – © 2022 Nature Comunication -Silicon-photonics acoustic detector for optoacoustic micro-tomography. 

High-resolution silicon photonics focused ultrasound transducer with a sub-millimeter aperture.

Schematic illustration of the developed transducer

2023 Optics Letters Vol. 48, Issue 10, pp. 2668-2671

Michael Nagli, Jürgen Koch, Yoav Hazan, Ahiad Levi, Orna Ternyak, Ludger Overmeyer, and Amir Rosenthal

Abstract
We present an all-optical focused ultrasound transducer with a sub-millimeter aperture and demonstrate its capability for high-resolution imaging of tissue ex vivo. The transducer is composed of a wideband silicon photonics ultrasound detector and a miniature acoustic lens coated with a thin optically absorbing metallic layer used to produce laser-generated ultrasound. The demonstrated device achieves axial resolution and lateral resolutions of 12 μm and 60 μm, respectively, well below typical values achieved by conventional piezoelectric intravascular ultrasound. The size and resolution of the developed transducer may enable its use for intravascular imaging of thin fibrous cap atheroma.

[Read more…]

Imaging experiments.

Fig. Imaging experiments. (a),(c) Optical images of acoustic targets. (b),(d) Ultrasound images of the targets shown in panels (a),(c). (a),(b) Images of 50-µm tungsten wires. (c),(d) Images of lamb meat and fat tissue; (d) is a 1D line scan image along the dotted line shown in panel (c); on the right side are three 0.5 mm × 0.5 mm close-up images. The image in panel (d) is “rolled” and shown in the polar coordinate system.

Michael Nagli, Jürgen Koch, Yoav Hazan, Ahiad Levi, Orna Ternyak, Ludger Overmeyer, and Amir Rosenthal

2023 Optics Letters Vol. 48, Issue 10, pp. 2668-2671
https://doi.org/10.1364/OL.486567

All-optical optoacoustic micro-tomography in reflection mode.

System Setup.

2023 Biomedical Engineering Letters

Tamar Harary, Yoav Hazan & Amir Rosenthal

Abstract
High-resolution optoacoustic imaging at depths beyond the optical diffusion limit is conventionally performed using a microscopy setup where a strongly focused ultrasound transducer samples the image object point-by-point. Although recent advancements in miniaturized ultrasound detectors enables one to achieve microscopic resolution with an unfocused detector in a tomographic configuration, such an approach requires illuminating the entire object, leading to an inefficient use of the optical power, and imposing a trans-illumination configuration that is limited to thin objects. We developed an optoacoustic micro-tomography system in an epi-illumination configuration, in which the illumination is scanned with the detector. The system is demonstrated in phantoms for imaging depths of up to 5 mm and in vivo for imaging the vasculature of a mouse ear. Although image-formation in optoacoustic tomography generally requires static illumination, our numerical simulations and experimental measurements show that this requirement is relaxed in practice due to light diffusion, which homogenizes the fluence in deep tissue layers.

[Read more…]

In-vivo Tomographic imaging.

Fig. In-vivo Tomographic imaging. Figure 8-a: Microscope images of mouse ear (left) and corresponding MIP of the optoacoustic image (right). Figure 8-b: Montage of four different tomographic depth. The depth difference between each consecutive slice was 50 μm. Figure 8-c. Typical raw OA signals from a mouse ear. Scale bar: 1 mm

Tamar Harary, Yoav Hazan & Amir Rosenthal

2023 Biomedical Engineering Letters
https://doi.org/10.1007/s13534-023-00278-8

Hand-Held Optoacoustic System for the Localization of Mid-Depth Blood Vessels.

A photograph of the assembled optoacoustic probe.

Photonics 2022, 9(12), 907

Zohar Or,  Ahiad R.Levi,  Yoav Hazan and Amir Rosenthal

Abstract
The ability to rapidly locate blood vessels in patients is important in many clinical applications, e.g., in catheterization procedures. Optical techniques, including visual inspection, generally suffer from a reduced performance at depths below 1 mm, while ultrasound and optoacoustic tomography are better suited to a typical depth on the scale of 1 cm and require an additional spacer between the tissue and transducer in order to image the superficial structures at the focus plane. For this work, we developed a hand-held optoacoustic probe, designed for localizing blood vessels from the contact point down to a depth of 1 cm, without the use of a spacer. The probe employs a flat lens-free ultrasound array, enabling a largely depth-independent response down to a depth of 1 cm, at the expense of low elevational resolution. Specifically, while in lens-based probes, the acoustic signals from outside the focal region suffer from distortion, in our probe, only the amplitude of the signal varies with depth, thus leading to an imaging quality that is largely depth-independent in the imaged region. To facilitate miniaturization, dark-field illumination is used, whereby light scattering from the tissue is exploited to homogenize the sensitivity field.

[Read more…]

Optoacoustic images of the blood vessels in a human wrist.

Figure-Optoacoustic images of the blood vessels in a human wrist, at different depths and orientations. A cross-section of the radial artery can be seen clearly in real time at depths up to 7 mm, as in (a,c). A deep vein can be seen in (b) at a depth of 8 mm. In (d), we can see a vein diving from 3 to 7 mm in a longitudinal cross-section. The scale bar in subfigure (a) applies to all subfigures.

Zohar Or, Ahiad R.Levi, Yoav Hazan and Amir Rosenthal

Photonics 2022, 9(12), 907; https://doi.org/10.3390/photonics9120907

Miniaturized ultrasound detector arrays in silicon photonics using pulse transmission amplitude monitoring.

Tomographic imaging via PTAM.

© 2022 Optica Publishing Group 

Yoav Hazan, Michael Nagli, Ahiad Levi, and Amir Rosenthal

Abstract
Silicon photonics holds promise for a new generation of ultrasound-detection technology, based on optical resonators, with unparalleled miniaturization levels, sensitivities, and bandwidths, creating new possibilities for minimally invasive medical devices. While existing fabrication technologies are capable of producing dense resonator arrays whose resonance frequency is pressure sensitive, simultaneously monitoring the ultrasound-induced frequency modulation of numerous resonators has remained a challenge. Conventional techniques, which are based on tuning a continuous wave laser to the resonator wavelength, are not scalable due to the wavelength disparity between the resonators, requiring a separate laser for each resonator. In this work, we show that the Q-factor and transmission peak of silicon-based resonators can also be pressure sensitive, exploit this phenomenon to develop a readout scheme based on monitoring the amplitude, rather than frequency, at the output of the resonators using a single-pulse source, and demonstrate its compatibility with optoacoustic tomography.

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PTAM pressure measurements

Fig. PTAM pressure measurements. (a) Transmission spectrum of π-BG at different static pressures. The legend notes the pressure in kPa. (b) Normalized power transmission, (c) peak transmission, (d) resonance width, and (e) resonance wavelength of π-BG at different pressure calculated from the spectrum plotted in panel (a). (f) Schematic configuration of simultaneous ultrasound signal detection. Ultrasound signal, generated by a transducer, impinges the detection array at an angle. The setup results in a slight delay difference of the ultrasound signal along the detector array. (g) and (h) Measured ultrasound signals of the setup in panel (f), for resonators presented in Figs. 1(e) and 1(f), respectively.

Yoav Hazan, Michael Nagli, Ahiad Levi, and Amir Rosenthal

© 2022 Optica Publishing Group
Optics Letters Vol. 47, Issue 21, pp. 5660-5663 (2022) https://doi.org/10.1364/OL.467652https://doi.org/10.1038/s44172-022-00030-7

Single-detector 3D optoacoustic tomography via coded spatial acoustic modulation.

the measurement system setup

2022 Communications Engineering

Evgeny Hahamovich, Sagi Monin, Ahiad Levi, Yoav Hazan & Amir Rosenthal

Abstract
Optoacoustic tomography (OAT) is a hybrid imaging modality that combines optical excitation with ultrasound detection and enables high-resolution visualization of optical contrasts at tissue depths in which light is completely diffused. Despite its promise in numerous research and clinical applications, OAT is limited by the technological immaturity of ultrasound detection systems. It suffers from limited element count, narrow field of view and lack of technology for spatial modulation of acoustic signals. Here we report single-detector OAT capable of high-fidelity imaging using an amplitude mask in planar geometry coded with cyclic patterns for structured spatial acoustic modulation. Our image reconstruction method maximises sensitivity, is compatible with planar signal detection, and uses only linear operations, thus avoiding artefacts associated with the nonlinear compressed-sensing inversion. We demonstrate our method for 3D OAT of complex objects and living tissue performed with only a single ultrasound detector, effectively coded into a 2D array with 1763 elements. Our method paves the way for a new generation of high-fidelity, low-cost OAT systems.

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a photograph of the leg

Fig. A is a photograph of the leg. B is a subset over a vertical line of the measured signals, C is the de-multiplexed signals, and D is the MAP of the reconstructed optical density as a function of depth (z). The amplitudes are in arbitrary units.

Evgeny Hahamovich, Sagi Monin, Ahiad Levi, Yoav Hazan & Amir Rosenthal

2022 Communications Engineeringhttps://doi.org/10.1038/s44172-022-00030-7

Grüneisen-relaxation photoacoustic microscopy at 1.7 µm and its application in lipid imaging.

Schematic of the GR-PAM experimental system

© 2020 Optical Society of America

Abstract
We report the first, to the best of our knowledge, demonstration of Grüneisen relaxation photoacoustic microscopy (GR-PAM) of lipid-rich tissue imaging at the 1.7 µm band, implemented with a high-energy thulium-doped fiber laser and a fiber-based delay line. GR-PAM enhances the image contrast by intensifying the region of strong absorbers and suppressing out-of-focus signals. Using GR-PAM to image swine-adipose tissue at 1725 nm, an 8.26-fold contrast enhancement is achieved in comparison to conventional PAM. GR-PAM at the 1.7 µm band is expected to be a useful tool for label-free high-resolution imaging of lipid-rich tissue, such as atherosclerotic plaque and nerves.

[Read more…]

Swine muscular tissue images

Fig. Swine muscular tissue images under (a)-(c) OR-PAM and (d)-(f) GR-PAM at (a), (d) 1700; (b), (e) 1725; and (c), (f) 1750 nm. (g) Reference confocal microscopy image at the same region.

Jiawei Shi, Can Li, Huade Mao, Yuxuan Ren, Zhi-Chao Luo, Amir Rosenthal, and Kenneth K. Y. Wong

© 2020 Optical Society of America   Vol. 45, Issue 12, pp. 3268-3271 (2020)

Increased SNR in acousto-optic imaging via coded ultrasound transmission.

© 2020 Optical Society of America

Abstract

Acousto-optic imaging (AOI) is a non-invasive method that uses acoustic modulation to map the light fluence inside biological tissue. In many AOI implementations, ultrasound pulses are used in a time-gated measurement to perform depth-resolved imaging without the need for mechanical scanning. However, to achieve high axial resolution, it is required that ultrasound pulses with few cycles are used, limiting the modulation strength. In this Letter, we develop a new approach to pulse-based AOI in which coded ultrasound transmission is used. In coded-transmission AOI (CT-AOI), one may achieve an axial resolution that corresponds to a single cycle, but with a signal-to-noise ratio (SNR) that scales as the square root of the number of cycles. Using CT-AOI with 79 cycles, we experimentally demonstrate over four-fold increase in SNR in comparison to a single-cycle AOI scheme.

One of the fundamental limitations of optical imaging of biological tissue is light scattering due to optical heterogeneity. At depths exceeding several transport lengths, scattering leads to the diffusion of light, which severely limits the imaging resolution that may be achieved [1]. Additionally, optical imaging with diffused light often requires solving nonlinear optimization problems in order to map tissue parameters.

Acousto-optic imaging (AOI) is a hybrid approach that overcomes the limitations of light diffusion by using acoustic modulation [2]. Conventionally, AOI is performed by illuminating the tissue with a highly coherent continuous-wave (CW) laser and using ultrasound to locally modulate the phase of the laser light inside the tissue. In AOI, the ultrasound-induced phase modulation is a result of two mechanisms [3]: pressure-induced modulation of the refractive index and periodic movement of the optical scatterers. When the coherence length of the laser is sufficiently long, the local ultrasound-induced phase modulation inside the tissue is translated into an intensity modulation of the speckle pattern on the tissue boundary. Thus, by measuring the modulation depth of the speckle on the tissue boundary, it is possible to quantify the light fluence within the tissue at the positions in which the acoustic modulation was performed [4].

AOI is capable of identifying both highly absorbing and highly scattering structures through their effect on the light fluence [5], facilitating applications such as early assessment of osteoporosis [6]. Additionally, AOI can provide information on blood flow in the acoustically modulated regions through analysis of the spectral broadening of the speckle modulation [7]. While in most applications AOI is used as an independent technique for assessing tissue parameters, it may also be used as a complimentary technique to optoacoustic tomography (OAT). In previous works [8,9], it has been shown that the information provided by AOI can remove the bias in OAT images due to light attenuation, thus enabling OAT-image quantification.

[Read more…]

1D profile of the modulated light along the ultrasound propagation path for single-pulse.

Fig. 1D profile of the modulated light along the ultrasound propagation path for single-pulse AOI (blue) and CT-AOI (red) with corresponding FWMH values of 4.32 mm and 4.07 mm, respectively.

 

Ahiad Levi, Sagi Monin, Evgeny Hahamovich, Aner Lev, Bruno G. Sfez, and Amir Rosenthal

© 2020 Optical Society of America Vol. 45, Issue 10, pp. 2858-2861 (2020)

Ultrasound Detection Arrays Via Coded Hadamard Apertures.

Experimental setup.

© 2020 IEEE

Abstract
In the medical fields, ultrasound detection is often performed with piezoelectric arrays that enable one to simultaneously map the acoustic fields at several positions. In this work, we develop a novel method for transforming a single-element ultrasound detector into an effective detectionarray by spatially filtering the incoming acoustic fields using a binary acoustic mask coded with cyclic Hadamard patterns. By scanning the mask in front of the detector, we obtain a multiplexed measurement dataset from which a map of the acoustic field is analyticallyconstructed. We experimentally demonstrate our method by transforming a single-element ultrasound detector into 1D arrays with up to 59 elements.

[Read more…]

Fig. Normalized waveform shape comprasion of the strongest signal for a single vs. multiplexed aperture detection. The plots are for (a) an aperture with 1.5 mm diameter and 31 elements and (b) an aperture with 1 mm diameter and 59 elements. 

E. Hahamovich and A. Rosenthal, “Ultrasound Detection Arrays Via Coded Hadamard Apertures,” in IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control, doi: 10.1109/TUFFC.2020.2993583.

© 2020 IEEE