Distance and Angle Correction System (DACS) for a kHz A-Scan Rate Pump-Probe Laser-Ultrasound Inspection.

Non-contact optical detection of ultrasound critically depends on the amount of light collected from the detection surface. Although it can be optimized in multiple ways for an ideal flat polished surface, industrial non-destructive testing and evaluation (NDT&E) usually requires optical detectors to be robust for unpolished material surfaces that are usually rough and curved. Confocal detectors provide the best light collection but must trade off sensitivity with depth of field. Specifically, detection efficiency increases with the numerical aperture (NA) of the detector, but the depth of field drops. Therefore, fast realignment of the detector focal point is critical for in-field applications. Here, we propose an optical distance and angle correction system (DACS) and demonstrate it in a kHz-rate laser-ultrasound inspection system. It incorporates a Sagnac interferometer on receive for the fast scanning of aircraft composites, which minimizes the required initial alignment. We show that DACS performs stably for different composite surfaces while providing ±2° angular and ±2 mm axial automatic correction with a maximum 100 ms realignment time.

A small-angle scattering environment for in situ ultrasound studies.

Ultrasonic devices are common tools in laboratory and industrial settings to produce cavitation events for cleaning, emulsification, cell lysis and other materials applications. Effects of sonication at the macroscopic scale can be visible while effects at the molecular and nano-scales are not easily probed and, therefore, not fully understood. We present a new small angle scattering sample environment designed specifically to study structural changes occurring in various types of dispersions at the nano-scale due to ultrasonic acoustic waves. The sample environment features two face-to-face high-intensity focused ultrasound transducers coaxially aligned and normal to the neutron/X-ray beam propagation direction. A third broadband transducer is fixed beneath the scattering volume to acoustically monitor for cavitation events. By correlating acoustic data to scattering data, measured structural changes can be correlated to changes in parameters such as frequency, acoustic pressure, or cavitation pressure threshold. Several example applications of colloidal systems effectively influenced by ultrasound fields are also presented to demonstrate the capabilities of the device and to motivate future work on in situ scattering analysis of ultrasound materials processing methods.

Polypyrrole-Coated Perfluorocarbon Nanoemulsions as a Sono-Photoacoustic Contrast Agent.

A new contrast agent for combined photoacoustic and ultrasound imaging is presented. It has a liquid perfluorocarbon (PFC) core of about 250 nm diameter coated by a 30 nm thin polypyrrole (PPy) doped polymer shell emulsion that represents a broadband absorber covering the visible and near-infrared ranges (peak optical extinction at 1050 nm). When exposed to a sufficiently high intensity optical or acoustic pulse, the droplets vaporize to form microbubbles providing a strong increase in imaging sensitivity and specificity. The threshold for contrast agent activation can further drastically be reduced by up to 2 orders of magnitude if simultaneously exposing them with optical and acoustic pulses. The selection of PFC core liquids with low boiling points (i.e., perfluorohexane (56 °C), perfluoropentane (29 °C), and perfluorobutane (-2 °C)) facilitates activation and reduces the activation threshold of PPy-coated emulsion contrast agents to levels well within clinical safety limits (as low as 0.2 MPa at 1 mJ/cm2). Finally, the potential use of these nanoemulsions as a contrast agent is demonstrated in a series of phantom imaging studies.

Laser-induced cavitation in nanoemulsion with gold nanospheres for blood clot disruption: in vitro results.

Optically activated cavitation in a nanoemulsion contrast agent is proposed for therapeutic applications. With a 56°C boiling point perfluorohexane core and highly absorptive gold nanospheres at the oil-water interface, cavitation nuclei in the core can be efficiently induced with a laser fluence below medical safety limits (70 mJ/cm2 at 1064 nm). This agent is also sensitive to ultrasound (US) exposure and can induce inertial cavitation at a pressure within the medical diagnostic range. Images from a high-speed camera demonstrate bubble formation in these nanoemulsions. The potential of using this contrast agent for blood clot disruption is demonstrated in an in vitro study. The possibility of simultaneous laser and US excitation to reduce the cavitation threshold for therapeutic applications is also discussed.

Non-contact detection of ultrasound with light - Review of recent progress.

In this article, we present an overview of recent progress in non-contact remote optical detection of ultrasound in application to nondestructive testing and evaluation of materials. The focus of the review is on the latest advances in optical detection that offer mature and robust field-applicable solutions for diagnostics and imaging of engineered structures. We provide a detailed description of these solutions, including their operation principles, their evolution from the previously known designs to commercial devices, and their contribution to solving the most important problems associated with non-contact optical detection of ultrasound. Several application examples are presented to demonstrate the capabilities of optical detection and provide ideas to a reader on how it can be used in practice. We also discuss the main challenges of modern non-contact detectors which have not yet been addressed, as well as the directions and prospects for their development.

Review of Deep Learning Approaches for Interleaved Photoacoustic and Ultrasound (PAUS) Imaging.

Photoacoustic (PA) imaging provides optical contrast at relatively large depths within the human body, compared to other optical methods, at ultrasound (US) spatial resolution. By integrating real-time PA and US (PAUS) modalities, PAUS imaging has the potential to become a routine clinical modality bringing the molecular sensitivity of optics to medical US imaging. For applications where the full capabilities of clinical US scanners must be maintained in PAUS, conventional limited view and bandwidth transducers must be used. This approach, however, cannot provide high-quality maps of PA sources, especially vascular structures. Deep learning (DL) using data-driven modeling with minimal human design has been very effective in medical imaging, medical data analysis, and disease diagnosis, and has the potential to overcome many of the technical limitations of current PAUS imaging systems. The primary purpose of this article is to summarize the background and current status of DL applications in PAUS imaging. It also looks beyond current approaches to identify remaining challenges and opportunities for robust translation of PAUS technologies to the clinic.

Noncontact Acoustic Micro-Tapping Optical Coherence Elastography for Quantification of Corneal Anisotropic Elasticity: In Vivo Rabbit Study.

Purpose: The purpose of this study was to demonstrate accurate measurement of corneal elastic moduli in vivo with noncontact and noninvasive optical coherence elastography. Methods: Elastic properties (in-plane Young's modulus, E, and both in-plane, µ, and out-of-plane, G, shear moduli) of rabbit cornea were quantified in vivo using noncontact dynamic acoustic micro-tapping optical coherence elastography (AµT-OCE). The intraocular pressure (IOP)-dependence of measured mechanical properties was explored in extracted whole globes following in vivo measurement. A nearly incompressible transverse isotropic (NITI) model was used to reconstruct moduli from AµT-OCE data. Independently, cornea elastic moduli were also measured ex vivo with traditional, destructive mechanical tests (tensile extensometry and shear rheometry). Results: Our study demonstrates strong anisotropy of corneal elasticity in rabbits. The in-plane Young's modulus, computed as E = 3µ, was in the range of 20 MPa to 44 MPa, whereas the out-of-plane shear modulus was in the range of 34 kPa to 261 kPa. Both pressure-dependent ex vivo OCE and destructive mechanical tests performed on the same samples within an hour of euthanasia strongly support the results of AµT-OCE measurements. Conclusions: Noncontact AµT-OCE can noninvasively quantify cornea anisotropic elastic properties in vivo. Translational Relevance: As optical coherence tomography (OCT) is broadly accepted in ophthalmology, these results suggest the potential for rapid translation of AµT-OCE into clinical practice. In addition, AµT-OCE can likely improve diagnostic criteria of ectatic corneal diseases, leading to early diagnosis, reduced complications, customized surgical treatment, and personalized biomechanical models of the eye.

Non-contact acoustic micro-tapping optical coherence elastography for quantification of corneal anisotropic elasticity: in vivo rabbit study.

PURPOSE: To demonstrate accurate measurement of corneal elastic moduli in vivo with non-contact and non-invasive optical coherence elastography. METHODS: Elastic properties (in-plane Young's modulus E and both in-plane, u, and out-of-plane, G, shear moduli) of rabbit cornea were quantified in vivo using non-contact dynamic Acoustic micro-Tapping Optical Coherence Elastography (AuT-OCE). The IOP-dependence of measured mechanical properties was explored in extracted whole globes following in vivo measurement. A nearly-incompressible transverse isotropic (NITI) model was used to reconstruct moduli from AuT-OCE data. Independently, cornea elastic moduli were also measured ex vivo with traditional, destructive mechanical tests (tensile extensometry and shear rheometry). RESULTS: Our study demonstrates strong anisotropy of corneal elasticity in rabbits. The in-plane Young's modulus, computer as E=3u, was in the range of 20-44 MPa, whereas the out-of-plane shear modulus was in the range of 34-261 kPa. Both pressure-dependent ex vivo OCE and destructive mechanical tests performed on the same samples within an hour of euthanasia strongly support the results of AuT-OCE measurements. CONCLUSIONS: Non-contact AuT-OCE can non-invasively quantify cornea anisotropic elastic properties in vivo. TRANSLATIONAL RELEVANCE: As OCT is broadly accepted in Ophthalmology, these results suggest the potential for rapid translation of AuT-OCE into clinical practice. In addition, AuT-OCE can likely improve diagnostic criteria of ectatic corneal diseases, leading to early diagnosis, reduced complications, customized surgical treatment, and personalized biomechanical models of the eye.

Possible depth-resolved reconstruction of shear moduli in the cornea following collagen crosslinking (CXL) with optical coherence tomography and elastography.

Corneal collagen crosslinking (CXL) is commonly used to prevent or treat keratoconus. Although changes in corneal stiffness induced by CXL surgery can be monitored with non-contact dynamic optical coherence elastography (OCE) by tracking mechanical wave propagation, depth dependent changes are still unclear if the cornea is not crosslinked through the whole depth. Here, phase-decorrelation measurements on optical coherence tomography (OCT) structural images are combined with acoustic micro-tapping (A$\mu$T) OCE to explore possible reconstruction of depth-dependent stiffness within crosslinked corneas in an ex vivo human cornea sample. Experimental OCT images are analyzed to define the penetration depth of CXL into the cornea. In a representative ex vivo human cornea sample, crosslinking depth varied from $\sim 100\mu m$ in the periphery to $\sim 150\mu m$ in the cornea center and exhibited a sharp in-depth transition between crosslinked and untreated areas. This information was used in an analytical two-layer guided wave propagation model to quantify the stiffness of the treated layer. We also discuss how the elastic moduli of partially CXL-treated cornea layers reflect the effective engineering stiffness of the entire cornea to properly quantify corneal deformation.

Possible depth-resolved reconstruction of shear moduli in the cornea following collagen crosslinking (CXL) with optical coherence tomography and elastography.

Corneal collagen crosslinking (CXL) is commonly used to prevent or treat keratoconus. Although changes in corneal stiffness induced by CXL surgery can be monitored with non-contact dynamic optical coherence elastography (OCE) by tracking mechanical wave propagation, depth dependent changes are still unclear if the cornea is not crosslinked through the whole depth. Here, phase-decorrelation measurements on optical coherence tomography (OCT) structural images are combined with acoustic micro-tapping (AµT) OCE to explore possible reconstruction of depth-dependent stiffness within crosslinked corneas in an ex vivo human cornea sample. Experimental OCT images are analyzed to define the penetration depth of CXL into the cornea. In a representative ex vivo human cornea sample, crosslinking depth varied from ∼100 µm in the periphery to ∼150 µm in the cornea center and exhibited a sharp in-depth transition between crosslinked and untreated areas. This information was used in an analytical two-layer guided wave propagation model to quantify the stiffness of the treated layer. We also discuss how the elastic moduli of partially CXL-treated cornea layers reflect the effective engineering stiffness of the entire cornea to properly quantify corneal deformation.

Acoustic Micro-Tapping Optical Coherence Elastography to Quantify Corneal Collagen Cross-Linking: An Ex Vivo Human Study.

Purpose: To evaluate changes in the anisotropic elastic properties of ex vivo human cornea treated with ultraviolet cross-linking (CXL) using noncontact acoustic micro-tapping optical coherence elastography (AµT-OCE). Design: Acoustic micro-tapping OCE was performed on normal and CXL human donor cornea in an ex vivo laboratory study. Subjects: Normal human donor cornea (n = 22) divided into 4 subgroups. All samples were stored in optisol. Methods: Elastic properties (in-plane Young's, E, and out-of-plane, G, shear modulus) of normal and ultraviolet CXL-treated human corneas were quantified using noncontact AµT-OCE. A nearly incompressible transverse isotropic model was used to reconstruct moduli from AµT-OCE data. Independently, cornea elastic moduli were also measured with destructive mechanical tests (tensile extensometry and shear rheometry). Main Outcome Measures: Corneal elastic moduli (in-plane Young's modulus, E, in-plane, µ, and out-of-plane, G, shear moduli) can be evaluated in both normal and CXL treated tissues, as well as monitored during the CXL procedure using noncontact AµT-OCE. Results: Cross-linking induced a significant increase in both in-plane and out-of-plane elastic moduli in human cornea. The statistical mean in the paired study (presurgery and postsurgery, n = 7) of the in-plane Young's modulus, E = 3 µ , increased from 19 MPa to 43 MPa, while the out-of-plane shear modulus, G, increased from 188 kPa to 673 kPa. Mechanical tests in a separate subgroup support CXL-induced cornea moduli changes and generally agree with noncontact AµT-OCE measurements. Conclusions: The human cornea is a highly anisotropic material where in-plane mechanical properties are very different from those out-of-plane. Noncontact AµT-OCE can measure changes in the anisotropic elastic properties in human cornea as a result of ultraviolet CXL.

Spatial resolution in optical coherence elastography of bounded media.

Dynamic optical coherence elastography (OCE) tracks mechanical wave propagation in the subsurface region of tissue to image its shear modulus. For bulk shear waves, the lateral resolution of the reconstructed modulus map (i.e., elastographic resolution) can approach that of optical coherence tomography (OCT), typically a few tens of microns. Here we perform comprehensive numerical simulations and acoustic micro-tapping OCE experiments to show that for the typical situation of guided wave propagation in bounded media, such as cornea, the elastographic resolution cannot reach the OCT resolution and is mainly defined by the thickness of the bounded tissue layer. We considered the excitation of both broadband and quasi-harmonic guided waves in a bounded, isotropic medium. Leveraging the properties of broadband pulses, a robust method for modulus reconstruction with minimum artifacts at interfaces is demonstrated. In contrast, tissue bounding creates large instabilities in the phase of harmonic waves, leading to serious artifacts in modulus reconstructions.

Probing elastic anisotropy of human skin in vivo with light using non-contact acoustic micro-tapping OCE and polarization sensitive OCT.

Skin broadly protects the human body from undesired factors such as ultraviolet radiation and abrasion and helps conserve body temperature and hydration. Skin's elasticity and its level of anisotropy are key to its aesthetics and function. Currently, however, treatment success is often speculative and subjective, and is rarely based on skin's elastic properties because there is no fast and accurate non-contact method for imaging of skin's elasticity. Here we report on a non-contact and non-invasive method to image and characterize skin's elastic anisotropy. It combines acoustic micro-tapping optical coherence elastography (AµT-OCE) with a nearly incompressible transversely isotropic (NITI) model to quantify skin's elastic moduli. In addition, skin sites were imaged with polarization sensitive optical coherence tomography (PS-OCT) to help define fiber orientation. Forearm skin areas were investigated in five volunteers. Results clearly demonstrate elastic anisotropy of skin in all subjects. AµT-OCE has distinct advantages over competitive techniques because it provides objective, quantitative characterization of skin's elasticity without contact, which opens the door for broad translation into clinical use. Finally, we demonstrate that a combination of multiple OCT modalities (structural OCT, OCT angiography, PS-OCT and AµT-OCE) may provide rich information about skin and can be used to characterize scar.

Nonlinear optoacoustic transformation in the system of dielectric substrate/submicron metal coating/liquid.

The optoacoustic method has been shown to be an accurate technique for the measurement of the properties of submicron metal coatings deposited on a dielectric substrate, i.e., mirrors. The method has been previously theoretically described in terms of a linear model of optoacoustic transformation in a system substrate/coating/liquid. The goal of the present work was to determine the limits at which the linear model is still applicable. The modification of the laser induced acoustic signal profiles and transfer functions of optoacoustic transformation versus the laser fluence was studied for two liquids: ethanol and water.

Detection of disbonds in adhesively bonded aluminum plates using laser-generated shear acoustic waves.

Adhesively bonded metals are increasingly used in many industries. Inspecting these parts remains challenging for modern non-destructive testing techniques. Laser ultrasound (LU) has shown great potential in high-resolution imaging of carbon-reinforced composites. For metals, excitation of longitudinal waves is inefficient without surface ablation. However, shear waves can be efficiently generated in the thermo-elastic regime and used to image defects in metallic structures. Here we present a compact LU system consisting of a high repetition rate diode-pumped laser to excite shear waves and noncontact detection with a highly sensitive fiber optic Sagnac interferometer to inspect adhesively bonded aluminum plates. Multiphysics finite difference simulations are performed to optimize the measurement configuration. Damage detection is performed for a structure consisting of three aluminum plates bonded with an epoxy film. Defects are simulated by a thin Teflon film. It is shown that the proposed technique can efficiently localize defects in both adhesion layers.

Real-time interleaved spectroscopic photoacoustic and ultrasound (PAUS) scanning with simultaneous fluence compensation and motion correction.

For over two decades photoacoustic imaging has been tested clinically, but successful human trials have been limited. To enable quantitative clinical spectroscopy, the fundamental issues of wavelength-dependent fluence variations and inter-wavelength motion must be overcome. Here we propose a real-time, spectroscopic photoacoustic/ultrasound (PAUS) imaging approach using a compact, 1-kHz rate wavelength-tunable laser. Instead of illuminating tissue over a large area, the fiber-optic delivery system surrounding an US array sequentially scans a narrow laser beam, with partial PA image reconstruction for each laser pulse. The final image is then formed by coherently summing partial images. This scheme enables (i) automatic compensation for wavelength-dependent fluence variations in spectroscopic PA imaging and (ii) motion correction of spectroscopic PA frames using US speckle tracking in real-time systems. The 50-Hz video rate PAUS system is demonstrated in vivo using a murine model of labelled drug delivery.

Delineating Corneal Elastic Anisotropy in a Porcine Model Using Noncontact OCT Elastography and Ex Vivo Mechanical Tests.

Purpose: To compare noncontact acoustic microtapping (AµT) OCT elastography (OCE) with destructive mechanical tests to confirm corneal elastic anisotropy. Design: Ex vivo laboratory study with noncontact AµT-OCE followed by mechanical rheometry and extensometry. Participants: Inflated cornea of whole-globe porcine eyes (n = 9). Methods: A noncontact AµT transducer was used to launch propagating mechanical waves in the cornea that were imaged with phase-sensitive OCT at physiologically relevant controlled pressures. Reconstruction of both Young's modulus (E) and out-of-plane shear modulus (G) in the cornea from experimental data was performed using a nearly incompressible transversely isotropic (NITI) medium material model assuming spatial isotropy of corneal tensile properties. Corneal samples were excised and parallel plate rheometry was performed to measure shear modulus, G. Corneal samples were then subjected to strip extensometry to measure the Young's modulus, E. Main Outcome Measures: Strong corneal anisotropy was confirmed with both AµT-OCE and mechanical tests, with the Young's (E) and shear (G) moduli differing by more than an order of magnitude. These results show that AµT-OCE can quantify both moduli simultaneously with a noncontact, noninvasive, clinically translatable technique. Results: Mean of the OCE measured moduli were E = 12 ± 5 MPa and G = 31 ± 11 kPa at 5 mmHg and E = 20 ± 9 MPa and G = 61 ± 29 kPa at 20 mmHg. Tensile testing yielded a mean Young's modulus of 1 MPa - 20 MPa over a strain range of 1% to 7%. Shear storage and loss modulus (G'/G'') measured with rheometry was approximately 82/13 ± 12/4 kPa at 0.2 Hz and 133/29 ± 16/3 kPa at 16 Hz (0.1% strain). Conclusions: The cornea is confirmed to be a strongly anisotropic elastic material that cannot be characterized with a single elastic modulus. The NITI model is the simplest one that accounts for the cornea's incompressibility and in-plane distribution of lamellae. AµT-OCE has been shown to be the only reported noncontact, noninvasive method to measure both elastic moduli. Submillimeter spatial resolution and near real-time operation can be achieved. Quantifying corneal elasticity in vivo will enable significant innovation in ophthalmology, helping to develop personalized biomechanical models of the eye that can predict response to ophthalmic interventions.

Deep-Learning Image Reconstruction for Real-Time Photoacoustic System.

Recent advances in photoacoustic (PA) imaging have enabled detailed images of microvascular structure and quantitative measurement of blood oxygenation or perfusion. Standard reconstruction methods for PA imaging are based on solving an inverse problem using appropriate signal and system models. For handheld scanners, however, the ill-posed conditions of limited detection view and bandwidth yield low image contrast and severe structure loss in most instances. In this paper, we propose a practical reconstruction method based on a deep convolutional neural network (CNN) to overcome those problems. It is designed for real-time clinical applications and trained by large-scale synthetic data mimicking typical microvessel networks. Experimental results using synthetic and real datasets confirm that the deep-learning approach provides superior reconstructions compared to conventional methods.

Correction of wavelength-dependent laser fluence in swept-beam spectroscopic photoacoustic imaging with a hand-held probe.

Recently, we demonstrated an integrated photoacoustic (PA) and ultrasound (PAUS) system using a kHz-rate wavelength-tunable laser and a swept-beam delivery approach. It irradiates a medium using a narrow laser beam swept at high repetition rate (∼1 kHz) over the desired imaging area, in contrast to the conventional PA approach using broad-beam illumination at a low repetition rate (10-50 Hz). Here, we present a method to correct the wavelength-dependent fluence distribution and demonstrate its performance in phantom studies using a conventional limited view/bandwidth hand-held US probe. We adopted analytic fluence models, extending diffusion theory for the case of a pencil beam obliquely incident on an optically homogenous turbid medium, and developed a robust method to estimate fluence attenuation in the medium using PA measurements acquired from multiple fiber-irradiation positions swept at a kHz rate. We conducted comprehensive simulation tests and phantom studies using well-known contrast-agents to validate the reliability of the fluence model and its spectral corrections.

Nearly-incompressible transverse isotropy (NITI) of cornea elasticity: model and experiments with acoustic micro-tapping OCE.

The cornea provides the largest refractive power for the human visual system. Its stiffness, along with intraocular pressure (IOP), are linked to several pathologies, including keratoconus and glaucoma. Although mechanical tests can quantify corneal elasticity ex vivo, they cannot be used clinically. Dynamic optical coherence elastography (OCE), which launches and tracks shear waves to estimate stiffness, provides an attractive non-contact probe of corneal elasticity. To date, however, OCE studies report corneal moduli around tens of kPa, orders-of-magnitude less than those (few MPa) obtained by tensile/inflation testing. This large discrepancy impedes OCE's clinical adoption. Based on corneal microstructure, we introduce and fully characterize a nearly-incompressible transversely isotropic (NITI) model depicting corneal biomechanics. We show that the cornea must be described by at least two shear moduli, contrary to current single-modulus models, decoupling tensile and shear responses. We measure both as a function of IOP in ex vivo porcine cornea, obtaining values consistent with both tensile and shear tests. At pressures above 30 mmHg, the model begins to fail, consistent with non-linear changes in cornea at high IOP.