Large-field-of-view optical-resolution optoacoustic microscopy using a stationary silicon-photonics acoustic detector.

Significance: Optical-resolution optoacoustic microscopy (OR-OAM) enables label-free imaging of the microvasculature by using optical pulse excitation and acoustic detection, commonly performed by a focused optical beam and an ultrasound transducer. One of the main challenges of OR-OAM is the need to combine the excitation and detection in a coaxial configuration, often leading to a bulky setup that requires physically scanning the ultrasound transducer to achieve a large field of view. Aim: The aim of this work is to develop an OR-OAM configuration that does not require physically scanning the ultrasound transducer or the acoustic beam path. Approach: Our OR-OAM system is based on a non-coaxial configuration in which the detection is performed by a silicon-photonics acoustic detector (SPADE) with a semi-isotropic sensitivity. The system is demonstrated in both epi- and trans-illumination configurations, where in both configurations SPADE remains stationary during the imaging procedure and only the optical excitation beam is scanned. Results: The system is showcased for imaging resolution targets and for the in vivo visualization of the microvasculature in a mouse ear. Optoacoustic imaging with focal spots down to 1.3 µm, lateral resolution of 4 µm, and a field of view higher than 4 mm in both lateral dimensions were demonstrated. Conclusions: We showcase a new OR-OAM design, compatible with epi-illumination configuration. This setup enables relatively large fields of view without scanning the acoustic detector or acoustic beam path. Furthermore, it offers the potential for high-speed imaging within compact, miniature probe and could potentially facilitate the clinical translation of OR-OAM technology.

Silicon photonic acoustic detector (SPADE) using a silicon nitride microring resonator.

Silicon photonics is an emerging platform for acoustic sensing, offering exceptional miniaturization and sensitivity. While efforts have focused on silicon-based resonators, silicon nitride resonators can potentially achieve higher Q-factors, further enhancing sensitivity. In this work, a 30 µm silicon nitride microring resonator was fabricated and coated with an elastomer to optimize acoustic sensitivity and signal fidelity. The resonator was characterized acoustically, and its capability for optoacoustic tomography was demonstrated. An acoustic bandwidth of 120 MHz and a noise-equivalent pressure of ∼ 7 mPa/Hz1/2 were demonstrated. The spatially dependent impulse response agreed with theoretical predictions, and spurious acoustic signals, such as reverberations and surface acoustic waves, had a marginal impact. High image fidelity optoacoustic tomography of a 20 µm knot was achieved, confirming the detector's imaging capabilities. The results show that silicon nitride offers low signal distortion and high-resolution optoacoustic imaging, proving its versatility for acoustic imaging applications.

All-optical optoacoustic micro-tomography in reflection mode.

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.

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

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.

Homodyne time-of-flight acousto-optic imaging for low-gain photodetector.

Acousto-optics imaging (AOI) is a hybrid imaging modality that is capable of mapping the light fluence rate in deep tissue by local ultrasound modulation of the diffused photons. Since the intensity of the modulated photons is relatively low, AOI systems often rely on high-gain photodetectors, e.g. photomultiplier tubes (PMTs), which limit scalability due to size and cost and may significantly increase the relative shot-noise in the detected signal due to low quantum yields or gain noise. In this work, we have developed a homodyne AOI scheme in which the modulated photons are amplified by interference with a reference beam, enabling their detection with a single low-gain photodetector in reflection-mode configuration. We experimentally demonstrate our approach with a silicon photodiode, achieving over a 4-fold improvement in SNR in comparison to a PMT-based setup. The increased SNR manifested in lower background noise level thus enabling deeper imaging depths. The use of a fiber-based configuration enables the integration of our scheme in a hand-held AOI probe.

Silicon-photonics acoustic detector for optoacoustic micro-tomography.

Medical ultrasound and optoacoustic (photoacoustic) imaging commonly rely on the concepts of beam-forming and tomography for image formation, enabled by piezoelectric array transducers whose element size is comparable to the desired resolution. However, the tomographic measurement of acoustic signals becomes increasingly impractical for resolutions beyond 100 µm due to the reduced efficiency of piezoelectric elements upon miniaturization. For higher resolutions, a microscopy approach is preferred, in which a single focused ultrasound transducer images the object point-by-point, but the bulky apparatus and long acquisition time of this approach limit clinical applications. In this work, we demonstrate a miniaturized acoustic detector capable of tomographic imaging with spread functions whose width is below 20 µm. The detector is based on an optical resonator fabricated in a silicon-photonics platform coated by a sensitivity-enhancing elastomer, which also effectively eliminates the parasitic effect of surface acoustic waves. The detector is demonstrated in vivo in high-resolution optoacoustic tomography.

Burst-mode pulse interferometry for enabling low-noise multi-channel optical detection of ultrasound.

Ultrasound detection via optical resonators can achieve high levels of miniaturization and sensitivity as compared to piezoelectric detectors, but its scale-up from a single detector to an array is highly challenging. While the use of wideband sources may enable parallel interrogation of multiple resonators, it comes at the cost of reduction in the optical power, and ultimately in sensitivity, per channel. In this work we have developed a new interferometric approach to overcome this signal loss by using high-power bursts that are synchronized with the time window in which ultrasound detection is performed. Each burst is composed of a train of low-noise optical pulses which are sufficiently wideband to interrogate an array of resonators with non-overlapping spectra. We demonstrate our method, termed burst-mode pulse interferometry, for interrogating a single resonator in which the optical power was reduced to emulate the power loss per channel that occurs in parallel interrogation of 20 to 200 resonators. The use of bursts has led to up 25-fold improvement in sensitivity without affecting the shape of the acoustic signals, potentially enabling parallel low-noise interrogation of resonator arrays with a single source.

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

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.

Silicon-photonics focused ultrasound detector for minimally invasive optoacoustic imaging.

One of the main challenges in miniaturizing optoacoustic technology is the low sensitivity of sub-millimeter piezoelectric ultrasound transducers, which is often insufficient for detecting weak optoacoustic signals. Optical detectors of ultrasound can achieve significantly higher sensitivities than their piezoelectric counterparts for a given sensing area but generally lack acoustic focusing, which is essential in many minimally invasive imaging configurations. In this work, we develop a focused sub-millimeter ultrasound detector composed of a silicon-photonics optical resonator and a micro-machined acoustic lens. The acoustic lens provides acoustic focusing, which, in addition to increasing the lateral resolution, also enhances the signal. The developed detector has a wide bandwidth of 84 MHz, a focal width smaller than 50 µm, and noise-equivalent pressure of 37 mPa/Hz1/2 - an order of magnitude improvement over conventional intravascular ultrasound. We show the feasibility of the approach and the detector's imaging capabilities by performing high-resolution optoacoustic microscopy of optical phantoms with complex geometries.

Single pixel imaging at megahertz switching rates via cyclic Hadamard masks.

Optical imaging is commonly performed with either a camera and wide-field illumination or with a single detector and a scanning collimated beam; unfortunately, these options do not exist at all wavelengths. Single-pixel imaging offers an alternative that can be performed with a single detector and wide-field illumination, potentially enabling imaging applications in which the detection and illumination technologies are immature. However, single-pixel imaging currently suffers from low imaging rates owing to its reliance on configurable spatial light modulators, generally limited to 22 kHz rates. We develop an approach for rapid single-pixel imaging which relies on cyclic patterns coded onto a spinning mask and demonstrate it for in vivo imaging of C. elegans worms. Spatial modulation rates of up to 2.4 MHz, imaging rates of up to 72 fps, and image-reconstruction times of down to 1.5 ms are reported, enabling real-time visualization of dynamic objects.

Single-pixel imaging of dynamic objects using multi-frame motion estimation.

Single-pixel imaging (SPI) enables the visualization of objects with a single detector by using a sequence of spatially modulated illumination patterns. For natural images, the number of illumination patterns may be smaller than the number of pixels when compressed-sensing algorithms are used. Nonetheless, the sequential nature of the SPI measurement requires that the object remains static until the signals from all the required patterns have been collected. In this paper, we present a new approach to SPI that enables imaging scenarios in which the imaged object, or parts thereof, moves within the imaging plane during data acquisition. Our algorithms estimate the motion direction from inter-frame cross-correlations and incorporate it in the reconstruction model. Moreover, when the illumination pattern is cyclic, the motion may be estimated directly from the raw data, further increasing the numerical efficiency of the algorithm. A demonstration of our approach is presented for both numerically simulated and measured data.

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

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.

Ultrasound Detection Arrays via Coded Hadamard Apertures.

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 detection array 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 data set from which a map of the acoustic field is analytically constructed. We experimentally demonstrate our method by transforming a single-element ultrasound detector into 1-D arrays with up to 59 elements.

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

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.

Simultaneous multi-channel ultrasound detection via phase modulated pulse interferometry.

In optical detection of ultrasound, resonators with high Q-factors are often used to maximize sensitivity. However, in order to perform parallel interrogation, conventional interferometric techniques require an overlap between the spectra of all the resonators, which is difficult to achieve with high Q-factor resonators. In this paper, a new method is developed for parallel interrogation of optical resonators with non-overlapping spectra. The method is based on a phase-modulation scheme for pulse interferometry (PM-PI) and requires only a single photodetector and sampling channel per ultrasound detector. Using PM-PI, parallel ultrasound detection is demonstrated with four high Q-factor resonators.

Optoacoustic model-based inversion using anisotropic adaptive total-variation regularization.

In optoacoustic tomography, image reconstruction is often performed with incomplete or noisy data, leading to reconstruction errors. Significant improvement in reconstruction accuracy may be achieved in such cases by using nonlinear regularization schemes, such as total-variation minimization and L 1-based sparsity-preserving schemes. In this paper, we introduce a new framework for optoacoustic image reconstruction based on adaptive anisotropic total-variation regularization, which is more capable of preserving complex boundaries than conventional total-variation regularization. The new scheme is demonstrated in numerical simulations on blood-vessel images as well as on experimental data and is shown to be more capable than the total-variation-L 1 scheme in enhancing image contrast.

The Impulse Response of Negatively Focused Spherical Ultrasound Detectors and Its Effect on Tomographic Optoacoustic Reconstruction.

In optoacoustic tomography, negatively focused detectors have been shown to improve the tangential image resolution without sacrificing sensitivity. Since no exact inversion formulas exist for optoacoustic image reconstruction with negatively focused detectors, image reconstruction in such cases is based on using the virtual-detector approximation, in which it is assumed that the response of the negatively focused detector is identical, up to a constant time delay, to that of a point-like detector positioned in the detector's center of curvature. In this paper, we analyze the response of negatively focused spherical ultrasound detectors in three dimensions and demonstrate how their properties affect the optoacoustic reconstruction. Our analysis sheds new light on commonly reported experimental reconstruction artifacts in optoacoustic systems that employ negatively focused detectors. Based on our analysis, we introduce a simple correction to the virtual-detector approximation that significantly enhances image contrast and reduces artifacts.

Algebraic determination of back-projection operators for optoacoustic tomography.

The simplicity and computational efficiency of back-projection formulae have made them a popular choice in optoacoustic tomography. Nonetheless, exact back-projection formulae exist for only a small set of tomographic problems. This limitation is overcome by algebraic algorithms, but at the cost of higher numerical complexity. In this paper, we present a generic algebraic framework for calculating back-projection operators in optoacoustic tomography. We demonstrate our approach in a two-dimensional optoacoustic-tomography example and show that once the algebraic back-projection operator has been found, it achieves a comparable run time to that of the conventional back-projection algorithm, but with the superior image quality of algebraic methods.

Ultrasound detection via low-noise pulse interferometry using a free-space Fabry-Pérot.

Coherence-restored pulse interferometry (CRPI) is a recently developed method for optical detection of ultrasound that achieves shot-noise-limited sensitivity and high dynamic range. In principle, the wideband source employed in CRPI may enable the interrogation of multiple detectors by using wavelength multiplexing. However, the noise-reduction scheme in CRPI has not been shown to be compatible with wideband operation. In this work, we introduce a new scheme for CRPI that relies on a free-space Fabry-Pérot filter for noise reduction and a pulse stretcher for reducing nonlinear effects. Using our scheme, we demonstrate that shot-noise-limited detection may be achieved for a spectral band of 80 nm and powers of up to 5 mW.

Passive-demodulation pulse interferometry for ultrasound detection with a high dynamic range.

In the optical detection of ultrasound, resonators with high Q-factors are often used to maximize sensitivity. However, increasing the Q-factor of a resonator may reduce the linear range of the interrogation scheme, making it more susceptible to strong external perturbations and incapable of measuring strong acoustic signals. In this Letter, a passive-demodulation scheme for pulse interferometry was developed for high dynamic-range measurements. The passive scheme was based on an unbalanced Mach-Zehnder interferometer and a 90° optical hybrid, which was implemented in a dual-polarization all-fiber setup. We demonstrated the passive scheme for detecting ultrasound bursts with pressure levels for which the response of conventional, active interferometric techniques became nonlinear.