Background and motivation -
Conventional Optical Coherence Elastography (OCE) methods consist in launching controlled shear waves in tissues, and measuring their propagation speed using an ultrafast imaging system. However, the use of external shear sources limits transfer to clinical practice, especially for ophthalmic applications. Here, we propose a totally passive OCE method for ocular tissues based on time-reversal of the natural vibrations.
Methods -
Experiments were first conducted on a tissue-mimicking phantom containing a stiff inclusion. Pulsatile motions were reproduced by stimulating the phantom surface with two piezoelectric actuators excited asynchronously at low frequencies (50-500 Hz). The resulting random displacements were tracked at 190 frames/sec using spectral-domain optical coherence tomography (SD-OCT), with a 10x5µm² resolution over a 3x2mm² field-of-view (lateral x depth). The shear wavefield was numerically refocused (i.e. time-reversed) at each pixel using noise-correlation algorithms. The focal spot size yields the shear wavelength. Results were validated by comparison with shear wave speed measurements obtained from conventional active OCE. In vivo tests were then conducted on anesthetized rats.
Results -
The stiff inclusion of the phantom was delineated on the wavelength map with a wavelength ratio between the inclusion and the background (1.6) consistent with the speed ratio (1.7). This validates the wavelength measurements. In vivo, natural shear waves were detected in the eye and wavelength maps of the anterior segment showed a clear elastic contrast between the cornea, the sclera and the iris.
Conclusion -
We validated the time-reversal approach for passive elastography using SD-OCT imaging at low frame-rate. This method could accelerate the clinical transfer of ocular elastography.
Optical coherence tomography (OCT) can map the stiffness of biological tissue by imaging mechanical perturbations (shear waves) propagating in the tissue. Most shear wave elastography (SWE) techniques rely on active shear sources to generate controlled displacements that are tracked at ultrafast imaging rates. Here, we propose a noise-correlation approach to retrieve stiffness information from the imaging of diffuse displacement fields using low-frame rate spectral-domain OCT. We demonstrated the method on tissue-mimicking phantoms and validated the results by comparison with classic ultrafast SWE. Then we investigated the in vivo feasibility on the eye of an anesthetized rat by applying noise correlation to naturally occurring displacements. The results suggest a great potential for passive elastography based on the detection of natural pulsatile motions using conventional spectral-domain OCT systems. This would facilitate the transfer of OCT-elastography to clinical practice, in particular, in ophthalmology or dermatology.
Optical coherence tomography (OCT)-based elasticity imaging can map soft tissue elasticity based on speckle-tracking of elastic wave propagation using highly sensitive phase measurements of OCT signals. Using a fixed elastic wave source and moving detection, current imaging sequences have difficulty in reconstructing tissue elasticity within speckle-free regions, for example, within the crystalline lens of the eye. We present a moving acoustic radiation force imaging sequence to reconstruct elastic properties within a speckle-free region by tracking elastic wave propagation from multiple laterally moving sources across the field of view. We demonstrate the proposed strategy using heterogeneous and partial speckle-free tissue-mimicking phantoms. Harder inclusions within the speckle-free region can be detected, and the contrast-to-noise ratio slightly enhanced compared to current OCE imaging sequences. The results suggest that a moving source approach may be appropriate for OCE studies within the large speckle-free regions of the crystalline lens.
Phase-sensitive optical coherence tomography (PhS-OCT) can be utilized for quantitative shear-wave elastography using speckle tracking. However, current approaches cannot directly reconstruct elastic properties in speckle-less or speckle-free regions, for example within the crystalline lens in ophthalmology. Investigating the elasticity of the crystalline lens could improve understanding and help manage presbyopia-related pathologies that change biomechanical properties. We propose to reconstruct the elastic properties in speckle-less regions by sequentially launching shear waves with moving acoustic radiation force (mARF), and then detecting the displacement at a specific speckle-generating position, or limited set of positions, with PhS-OCT. A linear ultrasound array (with a center frequency of 5 MHz) interfaced with a programmable imaging system was designed to launch shear waves by mARF. Acoustic sources were electronically translated to launch shear waves at laterally shifted positions, where displacements were detected by speckle tracking images produced by PhS-OCT operating in M-B mode with a 125-kHz A-line rate. Local displacements were calculated and stitched together sequentially based on the distance between the acoustic source and the detection beam. Shear wave speed, and the associated elasticity map, were then reconstructed based on a time-of-flight algorithm. In this study, moving-source shear wave elasticity imaging (SWEI) can highlight a stiff inclusion within an otherwise homogeneous phantom but with a CNR increased by 3.15 dB compared to a similar image reconstructed with moving-detector SWEI. Partial speckle-free phantoms were also investigated to demonstrate that the moving-source sequence could reconstruct the elastic properties of speckle-free regions. Results show that harder inclusions within the speckle-free region can be detected, suggesting that this imaging method may be able to detect the elastic properties of the crystalline lens.
Magnetomotive photoacoustic/ultrasound imaging has shown superior specificity in visualizing targeted objects at cellular and molecular levels. By detecting magnet-induced displacements, magnetic-particles-targeted objects can be differentiated from background signals insensitive to the magnetic field. Unfortunately, background physiologic motion interferes during measurement, such as cardiac-induced motion and respiration, greatly reducing the robustness of the technique. In this paper, we proposed cyclic magnetomotive imaging with narrowband magnetic excitation. By synchronizing magnetic motion with the excitations, targeted objects moving coherently can be distinguished from background static signals and signals moving incoherently. HeLa cells targeted with magnetic nanoparticle-polymer core-shell particles were used as the targets for an initial test. A linear ultrasound array was interfaced with a commercial scanner to acquire a photoacoustic/ultrasound image sequence (maximum 1000 frames per second) during multi-cycle magnetic excitation (0.5 – 40 Hz frequency range) with an electromagnet. An image mask defined by a threshold on the displacement-coherence map was applied to the original images for background suppression. The results show that contrast was increased by more than 60 dB in an in-vitro experiment with the tagged cells fixed in a polyvinyl-alcohol gel and sandwiched between porcine liver tissues. Using a single sided system, cells injected subcutaneously on the back of a mouse were successfully differentiated from the background, with less than 20 µm coherent magnetic induced displacements isolated from millimetric background breathing motion. These results demonstrate the technique’s motion robustness for highly sensitive and specific diagnosis.
Ultrasound-guided photoacoustic imaging has shown great potential for many clinical applications including vascular visualization, detection of nanoprobes sensing molecular profiles, and guidance of interventional procedures. However, bulky and costly lasers are usually required to provide sufficient pulse energies for deep imaging. The low pulse repetition rate also limits potential real-time applications of integrated photoacoustic/ultrasound (PAUS) imaging. With a compact and low-cost laser operating at a kHz repetition rate, we aim to integrate photoacoustics (PA) into a commercial ultrasound (US) machine utilizing an interleaved scanning approach for clinical translation, with imaging depth up to a few centimeters and frame rates > 30 Hz. Multiple PA sub-frames are formed by scanning laser firings covering a large scan region with a rotating galvo mirror, and then combined into a final frame. Ultrasound pulse-echo beams are interleaved between laser firings/PA receives. The approach was implemented with a diode-pumped laser, a commercial US scanner, and a linear array transducer. Insertion of an 18-gauge needle into a piece of chicken tissue, with subsequent injection of an absorptive agent into the tissue, was imaged with an integrated PAUS frame rate of 30 Hz, covering a 2.8 cm × 2.8 cm imaging plane. Given this real-time image rate and high contrast (> 40 dB at more than 1-cm depth in the PA image), we have demonstrated that this approach is potentially attractive for clinical procedure guidance.
Tissue stiffness can be measured from the propagation speed of shear waves. Acoustic radiation force (ARF) can generate shear waves by focusing ultrasound in tissue for ~100 μs. Safety considerations and electronics abilities limit ultrasound pressures. We previously presented shear wave elastography combining ARF and phase-sensitive optical coherence tomography (PhS-OCT) [1]. Here, we use amplitude-modulated ARF to enhance shear wave signal-to-noise ratio (SNR) at low pressures. Experiments were performed on tissue-mimicking phantoms. ARF was applied using a single-element transducer, driven by a 7.5 MHz, 3-ms, sine wave modulated in amplitude by a linear-swept frequency (1 to 7 kHz). Pressures between 1 to 3 MPa were tested. Displacements were tracked using PhS-OCT and numerically compressed using pulse compression methods detailed in previous work [2]. SNR was compared to that of 200-μs bursts. Stiffness maps were reconstructed using time-of-flight computations. 200-μs bursts give barely detectable displacements at 1 MPa (3.7 dB SNR). Pulse compression gives 36.2 dB at 1.5 MPa. In all cases with detectable displacements, shear wave speeds were determined in 5%-gelatin and 10%-gelatin phantoms and compared to literature values. Applicability to ocular tissues (cornea, intraocular lens) is under investigation.
KEYWORDS: Elastography, Tissues, Optical coherence tomography, Signal to noise ratio, Acoustics, Wave propagation, Transducers, Cornea, Ultrasonography, In vivo imaging
Investigating the elasticity of ocular tissue (cornea and intraocular lens) could help the understanding and management of pathologies related to biomechanical deficiency. In previous studies, we introduced a setup based on optical coherence tomography for shear wave elastography (SWE) with high resolution and high sensitivity. SWE determines tissue stiffness from the propagation speed of shear waves launched within tissue. We proposed acoustic radiation force to remotely induce shear waves by focusing an ultrasound (US) beam in tissue, similar to several elastography techniques. Minimizing the maximum US pressure is essential in ophthalmology for safety reasons. For this purpose, we propose a pulse compression approach. It utilizes coded US emissions to generate shear waves where the energy is spread over a long emission, and then numerically compressed into a short, localized, and high-energy pulse. We used a 7.5-MHz single-element focused transducer driven by coded excitations where the amplitude is modulated by a linear frequency-swept square wave (1 to 7 kHz). An inverse filter approach was used for compression. We demonstrate the feasibility of performing shear wave elastography measurements in tissue-mimicking phantoms at low US pressures (mechanical index <0.6).
KEYWORDS: Cornea, Optical coherence tomography, Elastography, Tissues, Actuators, Signal to noise ratio, In vivo imaging, Wave propagation, Spatial resolution, Range imaging
Optical coherence tomography (OCT) provides high spatial resolution and sensitivity that are ideal for imaging the cornea and lens. Quantifying the biomechanical properties of these tissues could add clinically valuable information. Thus, we propose a dynamic elastography method combining OCT detection and a mechanical actuator to map the shear modulus of soft tissues. We used a piezoelectric actuator driven in the kHz range and we used phase-sensitive OCT (PhS-OCT) to track the resulting shear waves at an equivalent frame rate of 47 kHz. We mapped the shear wave speed of anesthetized mice cornea using monochromatic excitations. We found a significant difference between a group of knock-out (3.92 ± 0.35 m/s, N=4) and wild-type mice (5.04 ± 0.51 m/s, N=3). These preliminary results demonstrate the feasibility of using PhS-OCT to perform in vivo shear wave elastography of the cornea. We then implemented a shear pulse compression approach on ex vivo human cornea. For that purpose, frequency- modulated excitations were used and the resulting displacement field was digitally compressed in a short broadband pulse with a 7 dB gain in signal-to-noise ratio (SNR).
Due to the high scattering coefficient of tissue over the wavelength range used for photoacoustic (PA) imaging, most studies employ bulky, low repetition rate lasers to provide sufficient pulse energies at depth to image within the body. The size and cost of these lasers has impeded integration of photoacoustics into conventional, routinely-used ultrasound (US) scanners. Here, we present an approach leveraging the capabilities of modern, high repetition rate fiber lasers to produce a clinically translatable system providing integrated US/PA images at frame rates > 30 Hz. The system uses a portable, low-cost, low pulse-energy (1 mJ/pulse), high repetition rate (1 kHz), 1064 nm laser and is designed for integrated US/PA imaging of the peripheral vasculature or any relevant diseased region, such as a tumor. Using a rotating galvo-mirror system, the incident laser beam is quickly scanned over the imaging area. Multiple PA images covering the scan area are integrated to form a single PA image. Additionally, ultrasound firings are integrated into the scan sequence to provide an US image reconstructed over the same frame period. We acquired PA images of a 1.5-mmdiameter cylindrical absorber (absorption coefficient 5 cm-1) embedded in a tissue-mimicking gelatin phantom at 6-cm depth. A 2 cm × 1 cm (depth × lateral) area was reconstructed. We obtained a signal-to-noise ratio of more than 30 dB, comparable to conventional PA methods using high energy, low repetition rate lasers. The current system produces an integrated US/PA frame at a 32 Hz rate, and 100 Hz frame rates are possible with our present approach.
Shear wave elastography measures the stiffness of soft tissues from the speed of propagating shear waves induced in tissue. Optical coherence tomography (OCT) is a promising detection modality given its high sensitivity and spatial resolution, making it suitable for elastic characterization of skin, peripheral vasculature or ocular tissues. For clinical applications, it would be valuable to use a non-contact shear source. Thus, we propose acoustic radiation force as a remote shear source combined with OCT for visualization. A single-element focused transducer (central frequency 7.5 MHz) was used to apply a maximal pressure of ~3 MPa for 100 μs in agar phantoms. It induced shear waves with an amplitude of several hundreds of nanometers and a broadband spectrum in the kilohertz range. Phasesensitive OCT was used to track shear waves at an equivalent frame rate of 47 kHz. We reconstructed shear modulus maps in a heterogeneous phantom. In addition, we use 3-ms long coded excitation to increase the displacement signal-to-noise ratio. We applied digital pulse compression to the resulting displacement field to obtain a gain of ~15 dB compared to standard pulse excitation while maintaining the US pressure level and the shear wave spatial and temporal resolution. This is a promising result for shear wave generation at low US pressures (~ 1 MPa).
Assessing the biomechanical properties of soft tissue provides clinically valuable information to supplement conventional structural imaging. In the previous studies, we introduced a dynamic elastography technique based on phase-sensitive optical coherence tomography (PhS-OCT) to characterize submillimetric structures such as skin layers or ocular tissues. Here, we propose to implement a pulse compression technique for shear wave elastography. We performed shear wave pulse compression in tissue-mimicking phantoms. Using a mechanical actuator to generate broadband frequency-modulated vibrations (1 to 5 kHz), induced displacements were detected at an equivalent frame rate of 47 kHz using a PhS-OCT. The recorded signal was digitally compressed to a broadband pulse. Stiffness maps were then reconstructed from spatially localized estimates of the local shear wave speed. We demonstrate that a simple pulse compression scheme can increase shear wave detection signal-to-noise ratio (>12 dB gain) and reduce artifacts in reconstructing stiffness maps of heterogeneous media.
Elasticity maps of tissue have proved to be particularly useful in providing complementary contrast to ultrasonic imaging, e.g., for cancer diagnosis at the millimeter scale. Optical coherence tomography (OCT) offers an endogenous contrast based on singly backscattered optical waves. Adding complementary contrast to OCT images by recording elasticity maps could also be valuable in improving OCT-based diagnosis at the microscopic scale. Static elastography has been successfully coupled with full-field OCT (FF-OCT) in order to realize both micrometer-scale sectioning and elasticity maps. Nevertheless, static elastography presents a number of drawbacks, mainly when stiffness quantification is required. Here, we describe the combination of two methods: transient elastography, based on speed measurements of shear waves induced by ultrasonic radiation forces, and FF-OCT, an en face OCT approach using an incoherent light source. The use of an ultrafast ultrasonic scanner and an ultrafast camera working at 10,000 to 30,000 images/s made it possible to follow shear wave propagation with both modalities. As expected, FF-OCT is found to be much more sensitive than ultrafast ultrasound to tiny shear vibrations (a few nanometers and micrometers, respectively). Stiffness assessed in gel phantoms and an ex vivo rat brain by FF-OCT is found to be in good agreement with ultrasound shear wave elastography.
We propose an integrated method combining low-frequency mechanics with optical imaging to map the shear modulus within the biological tissue. Induced shear wave propagating in tissue is tracked in space and time using phase-sensitive optical coherence tomography (PhS-OCT). Local estimates of the shear-wave speed obtained from tracking results can image the local shear modulus. A PhS-OCT system remotely records depth-resolved, dynamic mechanical waves at an equivalent frame rate of ∼47 kHz with the high spatial resolution. The proposed method was validated by examining tissue-mimicking phantoms made of agar and light scattering material. Results demonstrate that the shear wave imaging can accurately map the elastic moduli of these phantoms.
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