Thu-Mai Nguyen

Visualizing ultrasonically induced shear wave propagation using phase-sensitive optical coherence tomography for dynamic elastography.

We report on the use of phase-sensitive optical coherence tomography (PhS-OCT) to detect and track temporal and spatial shear wave propagation within tissue, induced by ultrasound radiation force. Kilohertz-range shear waves are remotely generated in samples using focused ultrasound emission and their propagation is tracked using PhS-OCT. Cross-sectional maps of the local shear modulus are reconstructed from local estimates of shear wave speed in tissue-mimicking phantoms. We demonstrate the feasibility of combining ultrasound radiation force and PhS-OCT to perform high-resolution mapping of the shear modulus.

Magneto-optical nanoparticles for cyclic magnetomotive photoacoustic imaging.

Photoacoustic imaging has emerged as a highly promising tool to visualize molecular events with deep tissue penetration. Like most other modalities, however, image contrast under in vivo conditions is far from optimal due to background signals from tissue. Using iron oxide-gold core-shell nanoparticles, we have previously demonstrated the concept of magnetomotive photoacoustic (mmPA) imaging, which is capable of dramatically reducing the influence of background signals and producing high-contrast molecular images. Here, we report two significant advances toward clinical translation of this technology. First, we introduce a new class of compact, uniform, magneto-optically coupled core-shell nanoparticles, prepared through localized copolymerization of polypyrrole (PPy) on an iron oxide nanoparticle surface. The resulting iron oxide-PPy nanoparticles feature high colloidal stability and solve the photoinstability and small-scale synthesis problems previously encountered by the gold coating approach. In parallel, we have developed a new generation of mmPA featuring cyclic magnetic motion and ultrasound speckle tracking (USST), whose imaging capture frame rate is several hundred times faster than the photoacoustic speckle tracking (PAST) method we demonstrated previously. These advances enable robust artifact elimination caused by physiologic motions and demonstrate the application of the mmPA technology for in vivo sensitive tumor imaging.

Shear wave elastography using amplitude-modulated acoustic radiation force and phase-sensitive optical coherence tomography

Abstract. 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).

Moving-source elastic wave reconstruction for high-resolution optical coherence elastography

Abstract. 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.

Elasticity imaging of speckle-free tissue regions with moving acoustic radiation force and phase-sensitive optical coherence tomography

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.

Real-time interleaved photoacoustic/ultrasound (PAUS) imaging for interventional procedure guidance

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.

Cyclic magnetomotive photoacoustic/ultrasound imaging

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.