Imaging light fluence in blood vessels by combining photoacoustic fluctuation imaging and ultrasound power Doppler.

Numerous optical biomedical imaging or therapeutic modalities suffer from unknown light fluence distribution at depths. Photoacoustic (PA) imaging, which enables imaging blood vessels at the acoustic resolution, probes the product between the fluence and effective optical absorption that depends on the size or density of blood vessels. In the case of unresolved vessels, fluence and absorption can not be decoupled using PA imaging alone without the use of inverse problems.

Full-visibility 3D imaging of oxygenation and blood flow by simultaneous multispectral photoacoustic fluctuation imaging (MS-PAFI) and ultrasound Doppler.

We present a method and setup that provide complementary three-dimensional (3D) images of blood oxygenation (via quantitative photoacoustic imaging) and blood flow dynamics (via ultrasound Doppler). The proposed approach is label-free and exploits blood-induced fluctuations, and is implemented on a sparse array with only 256 elements, driven with a commercially available ultrasound electronics. We first implement 3D photoacoustic fluctuation imaging (PAFI) to image chicken embryo, and obtain full-visibility images of the vascular morphology.

Compensating for visibility artefacts in photoacoustic imaging with a deep learning approach providing prediction uncertainties.

Conventional photoacoustic imaging may suffer from the limited view and bandwidth of ultrasound transducers. A deep learning approach is proposed to handle these problems and is demonstrated both in simulations and in experiments on a multi-scale model of leaf skeleton. We employed an experimental approach to build the training and the test sets using photographs of the samples as ground truth images.

Super-resolution photoacoustic and ultrasound imaging with sparse arrays.

It has previously been demonstrated that model-based reconstruction methods relying on a priori knowledge of the imaging point spread function (PSF) coupled to sparsity priors on the object to image can provide super-resolution in photoacoustic (PA) or in ultrasound (US) imaging. Here, we experimentally show that such reconstruction also leads to super-resolution in both PA and US imaging with arrays having much less elements than used conventionally (sparse arrays). As a proof of concept, we obtained super-resolution PA and US cross-sectional images of microfluidic channels with only 8 elements of a 128-elements linear array using a reconstruction approach based on a linear propagation forward model and assuming sparsity of the imaged structure.

Self-adaptive ultrasonic beam amplifiers: application to transcostal shock wave therapy.

Ultrasound shock wave therapy is increasingly used for non-invasive surgery. It requires the focusing of very high pressure amplitude in precisely controlled focal spots. In transcostal therapy of the heart or the liver, the high impedance mismatch between the bones and surrounding tissues gives rise to strong aberrations and attenuation of the therapeutic wavefront, with potential risks of injury at the tissue-bone interface.

Adaptive Spatiotemporal SVD Clutter Filtering for Ultrafast Doppler Imaging Using Similarity of Spatial Singular Vectors.

Singular value decomposition of ultrafast imaging ultrasonic data sets has recently been shown to build a vector basis far more adapted to the discrimination of tissue and blood flow than the classical Fourier basis, improving by large factor clutter filtering and blood flow estimation. However, the question of optimally estimating the boundary between the tissue subspace and the blood flow subspace remained unanswered. Here, we introduce an efficient estimator for automatic thresholding of subspaces and compare it to an exhaustive list of thirteen estimators that could achieve this task based on the main characteristics of the singular components, namely the singular values, the temporal singular vectors, and the spatial singular vectors.

Pulsed Cavitational Ultrasound Softening: a new non-invasive therapeutic approach of calcified bioprosthetic valve stenosis.

Background: The majority of prosthetic heart valves currently implanted are tissue valves that can be expected to calcify with time and eventually fail. Surgical or percutaneous redux valve replacement is associated with higher rate of complications. We propose a novel non-invasive therapeutic approach based on the use of pulsed cavitational ultrasound (PCU) to improve the valvular function of degenerative calcified bioprosthesis.

Overcoming the acoustic diffraction limit in photoacoustic imaging by the localization of flowing absorbers.

The resolution of photoacoustic imaging deep inside scattering media is limited by the acoustic diffraction limit. In this Letter, taking inspiration from super-resolution imaging techniques developed to beat the optical diffraction limit, we demonstrate that the localization of individual optical absorbers can provide super-resolution photoacoustic imaging well beyond the acoustic diffraction limit. As a proof-of-principle experiment, photoacoustic cross-sectional images of microfluidic channels were obtained with a 15 MHz linear capacitive micromachined ultrasonic transducer array, while absorbing beads were flown through the channels.

Pulsed cavitational therapy using high-frequency ultrasound for the treatment of deep vein thrombosis in an in vitro model of human blood clot.

Post-thrombotic syndrome, a frequent complication of deep venous thrombosis, can be reduced with early vein recanalization. Pulsed cavitational therapy (PCT) using ultrasound is a recent non-invasive approach. We propose to test the efficacy and safety of high-frequency focused PCT for drug-free thrombolysis (thrombotripsy) in a realistic in vitro model of venous thrombosis.

In vivo real-time cavitation imaging in moving organs.

The stochastic nature of cavitation implies visualization of the cavitation cloud in real-time and in a discriminative manner for the safe use of focused ultrasound therapy. This visualization is sometimes possible with standard echography, but it strongly depends on the quality of the scanner, and is hindered by difficulty in discriminating from highly reflecting tissue signals in different organs. A specific approach would then permit clear validation of the cavitation position and activity.

A 3D time reversal cavity for the focusing of high-intensity ultrasound pulses over a large volume.

Shock wave ultrasound therapy techniques, increasingly used for non-invasive surgery, require extremely high pressure amplitudes in precise focal spots, and large high-power transducers arranged on a spherical shell are usually used to achieve that. This solution allows limited steering of the beam around the geometrical focus of the device at the cost of a large number of transducer elements, and the treatment of large and moving organs like the heart is challenging or impossible. This paper validates numerically and experimentally the possibility of using a time reversal cavity (TRC) for the same purpose.

Pulsed cavitational ultrasound for non-invasive chordal cutting guided by real-time 3D echocardiography.

Aims: Basal chordae surgical section has been shown to be effective in reducing ischaemic mitral regurgitation (IMR). Achieving this section by non-invasive mean can considerably decrease the morbidity of this intervention on already infarcted myocardium. We investigated in vitro and in vivo the feasibility and safety of pulsed cavitational focused ultrasound (histotripsy) for non-invasive chordal cutting guided by real-time 3D echocardiography.

Highly sensitive magneto-motive photoacoustic and ultrasound (PAUS) imaging with cyclic excitations.

Highly specific molecular imaging with photoacoustics (PA) must suppress background endogenous signals while maintaining signals from target nanoagents. Magneto-motive PA was introduced to perform motion-based background suppression using a low frequency magnetic field. Previous studies show suppression based on displacement magnitude can suffer if significant physiological motion is present.

Optimization of the laser irradiation pattern in a high frame rate integrated photoacoustic / ultrasound (PAUS) imaging system.

To integrate real-time photoacoustics (PA) into ultrasound (US) scanners and accelerate clinical translation of combined PAUS imaging, we previously developed a system using a portable, low-cost, low pulse energy, high-repetition rate laser (~1kHz) with a 1D galvo-mirror for rapid laser beam scanning over the imaging area. However, the frame rate and pulse energy are limited because of regulations on the radiance (1 W/cm). Therefore, a laser scan scheme needs to be optimized to provide high frame rate within this safety limit.

Sono-photoacoustic imaging of gold nanoemulsions: Part II. Real time imaging.

Photoacoustic (PA) imaging using exogenous agents can be limited by degraded specificity due to strong background signals. This paper introduces a technique called sono-photoacoustics (SPA) applied to perfluorohexane nanodroplets coated with gold nanospheres. Pulsed laser and ultrasound (US) excitations are applied simultaneously to the contrast agent to induce a phase-transition ultimately creating a transient microbubble.

Sono-photoacoustic imaging of gold nanoemulsions: Part I. Exposure thresholds.

Integrating high contrast bubbles from ultrasound imaging with plasmonic absorbers from photoacoustic imaging is investigated. Nanoemulsion beads coated with gold nanopsheres (NEB-GNS) are excited with simultaneous light (transient heat at the GNS's) and ultrasound (rarefactional pressure) resulting in a phase transition achievable under different scenarios, enhancing laser-induced acoustic signals and enabling specific detection of nanoprobes at lower concentration. An automated platform allowed dual parameter scans of both pressure and laser fluence while recording broadband acoustic signals.

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.

Real-time integrated photoacoustic and ultrasound (PAUS) imaging system to guide interventional procedures: ex vivo study.

Because of depth-dependent light attenuation, bulky, low-repetition-rate lasers are usually used in most photoacoustic (PA) systems to provide sufficient pulse energies to image at depth within the body. However, integrating these lasers with real-time clinical ultrasound (US) scanners has been problematic because of their size and cost. In this paper, an integrated PA/US (PAUS) imaging system is presented operating at frame rates >30 Hz.

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-particle-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.

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.

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

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.

Toric focusing for radiation force applications using a toric lens coupled to a spherically focused transducer.

Dynamic elastography using radiation force requires that an ultrasound field be focused during hundreds of microseconds at a pressure of several megapascals. Here, we address the importance of the focal geometry. Although there is usually no control of the elevational focal width in generating a tissue mechanical response, we propose a tunable approach to adapt the focus geometry that can significantly improve radiation force efficiency.

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.

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.

Shear wave pulse compression for dynamic elastography using phase-sensitive optical coherence tomography.

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.