Aberrating Layer Research Articles

Feasibility of Phase Velocity Imaging Using Multi Frequency Oscillation-Shear Wave Elastography.

To assess viscoelasticity, a pathologically relevant biomarker, shear wave elastography (SWE) generally uses phase velocity (PV) dispersion relationship generated via pulsed acoustic radiation force (ARF) excitation pulse. In this study, a multi-frequency oscillation (MFO)- excitation pulse with higher weight to higher frequencies is proposed to generate PV images via the generation of motion with energy concentrated at the target frequencies in contrast to the broadband frequency motion generated in pulsed SWE (PSWE). The feasibility of MFO-SWE to generate PV images at 100 to 1000 Hz in steps of 100 Hz was investigated by imaging 6 and 70 kPa inclusions with 6.5 and 10.4 mm diameter and ex vivo bovine liver with and without the presence of an aberration layer and chicken muscle ex vivo, and 4T1 mouse breast tumor, in vivo with comparisons to PSWE. MFO-SWE-derived CNR was statistically higher than PSWE for 6 kPa (both with and without aberration) and 70 kPa (with aberration) inclusions and derived SNR of the liver was statistically higher than PSWE at higher frequency (600-1000 Hz). Quantitatively, at 600-1000 Hz, MFO-SWE improved CNR of inclusions (without and with) aberration on an average by (8.2 and 156)% and of the tumor by 122%, respectively, and improved SNR of the liver (without and with) aberration by (20.2 and 51.5)% and of chicken muscle by 72%, respectively compared to the PSWE. These results indicate the advantages of MFO-SWE to improve PV estimation at higher frequencies which could improve viscoelasticity quantification and feature delineation.

Computational wave-based photoacoustic imaging through an unknown thick aberrating layer

We introduce a physics-based computational reconstruction framework for non-invasive photoacoustic tomography through a thick aberrating layer. Our wave-based approach leverages an analytic formulation of diffraction to beamform a photoacoustic image, when the aberrating layer profile is known. When the profile of the aberrating layer is unknown, the same analytical formulation serves as the basis for an automatic-differentiation regularized optimization algorithm that simultaneously reconstructs both the profile of the aberrating layer and the optically absorbing targets. Results from numerical studies and proof-of-concept experiments show promise for fast beamforming that takes into account diffraction effects occurring in the propagation through thick, highly-aberrating layers.

Modeling early human cortical development and evaluating neurotoxicity with a forebrain organoid system

The complexity and subtlety of brain development renders it challenging to examine effects of environmental toxicants on human fetal brain development. Advances in pluripotent cell-derived organoid systems open up novel avenues for human development, disease and toxicity modeling. Here, we have established a forebrain organoid system and recapitulated early human cortical development spatiotemporally including neuroepithelium induction, apical-basal axis formation, neural progenitor proliferation and maintenance, neuronal differentiation and layer/region patterning. To explore whether this forebrain organoid system is suitable for neurotoxicity modeling, we subjected the organoids to bisphenol A (BPA), a common environmental toxicant of global presence and high epidemic significance. BPA exposure caused substantial abnormalities in key cortical developmental events, inhibited progenitor cell proliferation and promoted precocious neuronal differentiation, leading premature progenitor cell depletion and aberrant cortical layer patterning and structural organization. Consistent with an antagonistic mechanism between thyroid hormone and BPA, T3 supplementation attenuated BPA-mediated cortical developmental abnormalities. Altogether, our in vitro recapitulation of cortical development with forebrain organoids provides a paradigm for efficient neural development and toxicity modeling and related remedy testing/screening.

Seismic imaging of medical ultrasound data: Towards in vivo applications

This study presents the application to medical ultrasonography of a high value-added imaging method developed in the context of geophysical exploration and based on the undulatory description of the physical process. Currently, the most serious limitation of conventional medical ultrasound systems is the implicit assumption of constant-velocity media stemming from the widespread use of geometrical ray-based imaging algorithms and leading to phase aberration phenomena in the case typical of the human body of two or more tissues with different velocities. As a result, imaging of targets underlying tissue layers can be severely degraded. To address this problem, the proposed algorithm is designed expressly for variable-velocity media, providing high-resolution images by implementing the solution of the one-way wave equation. From a macro-velocity model, the illuminated structures are imaged by correlating, in the frequency domain and for each source element, the simulated emitted wavefield with the back-propagated echoes sensed by the ultrasound transducer. The pointwise sum of the correlations reveals, constructively, all diffraction points and reflectors in the image space. The experiments conducted on in vitro laboratory data reveal remarkable spatial resolution and very accurate target positioning, even in the presence of an aberrant layer. A preliminary in vivo test also demonstrates the method's effectiveness in imaging echoes recorded on human tissues, giving a glimpse of its potentiality for clinical purposes.

Ultrasonic Imaging Through Aberrating Layers Using Covariance Matching

Ultrasonic Imaging Through Aberrating Layers Using Covariance Matching

Aberrant Cortical Layer Development of Brain Organoids Derived from Noonan Syndrome-iPSCs.

Noonan syndrome (NS) is a genetic disorder mainly caused by gain-of-function mutations in Src homology region 2-containing protein tyrosine phosphatase 2 (SHP2). Although diverse neurological manifestations are commonly diagnosed in NS patients, the mechanisms as to how SHP2 mutations induce the neurodevelopmental defects associated with NS remain elusive. Here, we report that cortical organoids (NS-COs) derived from NS-induced pluripotent stem cells (iPSCs) exhibit developmental abnormalities, especially in excitatory neurons (ENs). Although NS-COs develop normally in their appearance, single-cell transcriptomic analysis revealed an increase in the EN population and overexpression of cortical layer markers in NS-COs. Surprisingly, the EN subpopulation co-expressing the upper layer marker SATB2 and the deep layer maker CTIP2 was enriched in NS-COs during cortical development. In parallel with the developmental disruptions, NS-COs also exhibited reduced synaptic connectivity. Collectively, our findings suggest that perturbed cortical layer identity and impeded neuronal connectivity contribute to the neurological manifestations of NS.

Complementary Acoustic Metamaterial for Penetrating Aberration Layers.

Impedance-matched acoustic materials were developed to improve ultrasound penetration through the aberration layer. The traditional ultrasound layer matching material is called a couplant, which can only enhance ultrasound transmission to soft biological media such as the cartilage and muscle but cannot penetrate hard media such as the bone. Here, we propose a phase-modulated complementary acoustic metamaterial based on the principle of impedance matching, which enables ultrasound to penetrate the bone, and use the equivalent parameter technology of acoustic metamaterials for parameter design. Ultrasonic layer adjustment is performed through 3D printing and corrects bone aberrations. Several configurations were investigated through numerical simulations and experiments in non-reflecting tanks. Specifically, the bone matching layer can be optimally designed for a specific bone thickness and a specific operating frequency of the ultrasound probe, thereby amplifying the ultrasound to penetrate the matching layer and bone. The experimental and simulation results show that the proposed acoustic metamaterial can improve the transmission efficiency of ultrasound through the aberration layer.

PLAC1 affects cell to cell communication by interacting with the desmosome complex

IntroductionX-linked PLAC1 is highly expressed in placenta during embryogenesis, and when ablated in mice, causes aberrant placental cell layer organization. It is also highly expressed in many types of cancer cell-lines. Although it has been shown that it promotes AKT phosphorylation in cancer cells, the exact mechanism by which it influences placental layer differentiation is unclear. MethodsTo investigate the mechanism of action of PLAC1 we did cell fractionation and immunoprecipitation of the protein and Mass Spectrometry analysis to identify its interaction partners. The associated proteins were directly tested for interactions by co-transfection with PLAC1 and immunoprecipitation. Mutations in the ZP-N domain of PLAC1 were introduced to assess its involvement in the interactions. ResultsWe provide evidence that Desmoglein-2 (DSG2), a component of the membrane-associated desmosomal complex, directly interacts with PLAC1. Mutations of cysteines in ZP-N domain disrupt the interaction between PLAC1 and DSG-2. DiscussionBecause desmosomes are responsible for establishing lateral cell-cell junctions, we suggest that direct interaction with the lateral junction protein complex may be implicated in the PLAC1 effects on cell-cell interactions, and thereby on the layer structure of the placenta.

Phase-Aberration Correction for HIFU Therapy Using a Multielement Array and Backscattering of Nonlinear Pulses.

Phase aberrations induced by heterogeneities in body wall tissues introduce a shift and broadening of the high-intensity focused ultrasound (HIFU) focus, associated with decreased focal intensity. This effect is particularly detrimental for HIFU therapies that rely on shock front formation at the focus, such as boiling histotripsy (BH). In this article, an aberration correction method based on the backscattering of nonlinear ultrasound pulses from the focus is proposed and evaluated in tissue-mimicking phantoms. A custom BH system comprising a 1.5-MHz 256-element array connected to a Verasonics V1 engine was used as a pulse/echo probe. Pulse inversion imaging was implemented to visualize the second harmonic of the backscattered signal from the focus inside a phantom when propagating through an aberrating layer. Phase correction for each array element was derived from an aberration-correction method for ultrasound imaging that combines both the beamsum and the nearest neighbor correlation method and adapted it to the unique configuration of the array. The results were confirmed by replacing the target tissue with a fiber-optic hydrophone. Comparing the shock amplitude before and after phase-aberration correction showed that the majority of losses due to tissue heterogeneity were compensated, enabling fully developed shocks to be generated while focusing through aberrating layers. The feasibility of using a HIFU phased-array transducer as a pulse-echo probe in harmonic imaging mode to correct for phase aberrations was demonstrated.

Transcranial Focusing of Ultrasonic Vortices by Acoustic Holograms

Acoustic vortex beams have great potential for contactless particle manipulation and torque-based biomedical applications. However, focusing acoustic waves through highly aberrating layers such as the human skull at ultrasonic frequencies results in strong phase aberrations, which prevent the generation of sharp acoustic images. In the case of a wavefront containing phase dislocations, skull aberrations can inhibit the focusing of acoustic vortex beams inside the cranial cavity. In this paper, we demonstrate that phase-conjugated acoustic holograms can encode time-reversed fields, allowing compensation of the aberrations of the skull and, simultaneously, the generation of a focused vortex inside an ex vivo human skull. The method is applied to single-element geometrically focused sources and results in a very simple and compact ultrasonic system. This work will pave the way to designing low-cost particle-trapping systems, clot manipulation, and the exertion of acoustic-radiation forces and torques in the brain for biomedical applications.

Seismic Imaging Method for Medical Ultrasound Systems

Medical ultrasound usually implements ray-based imaging algorithms, in which the most severe limitation involves the implicit assumption of constant-velocity media. When there are tissues with different velocities---typical for the human body---, the image of the underlying targets is strongly degraded in placement and resolution, due to $p\phantom{\rule{0}{0ex}}h\phantom{\rule{0}{0ex}}a\phantom{\rule{0}{0ex}}s\phantom{\rule{0}{0ex}}e$ $a\phantom{\rule{0}{0ex}}b\phantom{\rule{0}{0ex}}e\phantom{\rule{0}{0ex}}r\phantom{\rule{0}{0ex}}r\phantom{\rule{0}{0ex}}a\phantom{\rule{0}{0ex}}t\phantom{\rule{0}{0ex}}i\phantom{\rule{0}{0ex}}o\phantom{\rule{0}{0ex}}n$. To address this problem, the authors look to concepts developed in the context of seismic prospecting, relying upon an undulatory description of the physical process. Laboratory assessment of this imaging strategy, even in the presence of an aberrant layer, reveals remarkable spatial resolution and highly accurate target placement.

A modified mixed domain method for modeling acoustic wave propagation in strongly heterogeneous media.

In this paper, phase correction and amplitude compensation are introduced to a previously developed mixed domain method (MDM), which is only accurate for modeling wave propagation in weakly heterogeneous media. Multiple reflections are also incorporated with the one-way model to improve the accuracy. The resulting model is denoted as the modified mixed domain method (MMDM) and is numerically evaluated for its accuracy and efficiency using four distinct cases. It is found that the MMDM is significantly more accurate than the MDM for strongly heterogeneous media, especially when the phase aberrating layer is approximately perpendicular to the acoustic beam. Additionally, a convergence study suggests that the second-order reflection could be sufficient for cases involving high contrast inhomogeneities and large loss values (e.g., skulls). The method developed in this work could facilitate therapeutic ultrasound for treating brain-related diseases and disorders.

Coding Mask Design for Single Sensor Ultrasound Imaging

We study the design of a coding mask for pulse-echo ultrasound imaging. We are interested in the scenario of a single receiving transducer with an aberrating layer, or ‘mask,’ in front of the transducer's receive surface, with a separate co-located transmit transducer. The mask encodes spatial measurements into a single output signal, containing more information about a reflector's position than a transducer without a mask. The amount of information in such measurements is dependent on the mask geometry, which we propose to optimize using an image reconstruction mean square error (MSE) criterion. We approximate the physics involved to define a linear measurement model, which we use to find an expression for the image error covariance matrix. By discretizing the mask surface and defining a discrete number of mask thickness levels per point on its surface, we show how finding the best mask can be posed as a variation of a sensor selection problem. We propose a convex relaxation in combination with randomized rounding, as well as a greedy optimization algorithm to solve this problem. We show empirically that both algorithms come close to the global optimum. Our simulations further show that the optimized masks have better a MSE than nearly all randomly shaped masks. We observe that an optimized mask amplifies echoes coming from within the region of interest (ROI), and strongly reduces the correlation between echoes of pixels within the ROI.

Aberration correction using nonlinear backscattered signals from the focus of an ultrasound beam

High intensity focused ultrasound (HIFU) therapies are often affected by aberrations, which can severely limit treatments. For multi-element arrays, applying phase corrections for each element could mitigate these effects. Here, an aberration correction method based on cross-correlation of nonlinear HIFU waves, backscattered from the focus is proposed and tested. A spherically focused 1.5 MHz 256-element HIFU array powered by Verasonics system was used for both emitting and receiving backscattered ultrasound waves. A short (3-cycle) high-amplitude pulse was transmitted through an aberrating layer into an ex vivo clotted bovine blood sample. The backscattered signal was recorded by individual array elements and high-pass filtered at 4 MHz. The layer introduced different acoustic path lengths for individual elements leading to a decrease in the peak-positive pressure of ~70%. The time delay required for each element to restore the nonlinear waveform at the focus was calculated based on the cross-correlation between the backscattered filtered signals. The results were confirmed by replacing the sample with a hydrophone. Using the corrected time delays, peak-positive focal pressure increased over 75% from uncorrected aberrated levels. These results demonstrate that the proposed focal “nonlinear beacon” can be used for phase correction feedback in HIFU treatments of soft tissue. [Work supported by NIH R01GM122859, R01EB007643, and RSF19-12-00148.]

Ultrasonic imaging of static objects through an aberrating layer using harmonic phase conjugation approach

The main goal of this study is to develop a new image reconstruction approach for the ultrasonic detection of small objects (comparable to or smaller than the ultrasonic wavelength) behind an aberrating layer. Instead of conventional pulse-echo experimental setup we used through transmission, as the backscattered field after going twice through the layer becomes much weaker than the through-transmitted field. The proposed solution is based on the Harmonic Phase Conjugation (HPC) technique. The developed numerical model allows to calculate the amplitude and phase distributions of the through-transmitted acoustic field interacting with the objects and received by a linear transducer array either directly or after passing through an additional aberrating layer. Then, the digitized acoustic field received by the array is processed, phase-conjugated, and finally, numerically propagated back through the medium in order to reconstruct the image of the target objects.The reconstruction quality of the algorithm was systematically tested on a numerical model, which included a barrier, a medium behind it, and a group of three scatterers, by varying scatterer distances from the source transducer, their mutual arrangement, and the angle of the incident field. Subsequently, a set of laboratory experiments was conducted (at transmit frequency of 2MHz) to verify the accuracy of the developed simulation. The results demonstrate feasibility of imaging multiple scattering objects through a barrier using the HPC method with better than 1mm accuracy. The results of these tests are presented, and the feasibility of implementing this approach for various biomedical and NDT imaging applications is discussed.

Effect of Ultrahigh Frequency Radiation Emitted from 2G Cell Phone on Developing Lens of Chick Embryo: A Histological Study

A Mobile phone in operation emits a pulsed radiofrequency electromagnetic field which is absorbed into the user’s body particularly the head region. Contradictory scientific reports on the health effect of nonionizing radiations on biological tissues have prompted to undertake the present study to evaluate the damage in the developing lens of a chick embryo following exposure to radiation emitted from a 2G cell phone. Fertilized chick embryos were incubated in two groups in a standard egg incubator. The experiment group was exposed to radiation emitted from a 2G cell phone. On completion of scheduled duration, the embryos were collected and processed for routine histological studies. The 9th to 12th day chick embryo eyes were processed for assessment of DNA damage using the alkaline comet assay technique. The lens thickness and the equatorial diameter were measured using oculometer and statistically compared for both groups. In the present study, the exposure of chick embryos to a 2G cell phone caused structural changes in lens epithelial cells, formation of cystic cells and spaces, distortion of lens fibers, and formation of posterior aberrant nuclear layer. The DNA damage in the developing eyes of the experiment group assessed by comet assay was highly significant.

Organ fusion and defective shoot development in oni3 mutants of rice

Maintenance of organ separation is one of the essential phenomena for normal plant development. We have identified and analyzed ONION3 (ONI3), which is required for avoiding organ fusions in rice. Loss-of-function mutations of ONI3, which were identified as mutants with ectopic expression of KNOX genes in leaves and morphologically resembling KNOX overexpressors, showed abnormal organ fusions in developing shoots. The mutant seedlings showed fusions between neighboring organs and also within an organ; they stopped growing soon after germination and subsequently died. ONI3 was shown to encode an enzyme that is most similar to Arabidopsis HOTHEAD and is involved in biosynthesis of long-chain fatty acids. Expression analyses showed that ONI3 was specifically expressed in the outermost cell layer in the shoot apex throughout life cycle, and the oni3 mutants had an aberrant outermost cell layer. Our results together with previous studies suggest that long-chain fatty acids are required for avoiding organ fusions and promoting normal shoot development in rice.

Exploiting the Time-Reversal Operator for Adaptive Optics, Selective Focusing, and Scattering Pattern Analysis

We report on the experimental measurement of the backscattering matrix of a weakly scattering medium in optics, composed of a few dispersed gold nanobeads. The decomposition of the time-reversal operator is applied to this matrix and we demonstrate selective and efficient focusing on individual scatterers, even through an aberrating layer. Moreover, we show that this approach provides the decomposition of the scattering pattern of a single nanoparticle. These results open important perspectives for optical imaging, characterization, and selective excitation of nanoparticles.

Acoustic stone localization during lithotripsy.

It is desirable to mitigate damage to kidney tissue induced by shock waves administered during lithotripsy. Stone movement due to patient respiration causes a fraction of the shock waves to miss the stone. The goal here is to ensure that shock waves are delivered to the kidney only when the kidney stone is in the focal region of the lithotripter. We present the design of a collar with an array of ultrasound transducers that can be retrofitted to a clinical lithotripter. The transducers are used in a pulse‐echo mode and a hybrid technique combining numeric time‐reversal and MUSIC (MUltiple‐SIgnal‐Classification) is employed to determine the location of a kidney stone relative to the focus of the lithotripter. A model of the acoustic collar was used to select system parameters including the transducer count, center frequency, and transducer placement. The performance of the collar was assessed by translating artificial kidney stones in water and using porcine body wall as an aberrating layer. Performance wi...

MR-guided adaptive focusing of ultrasound

Adaptive focusing of ultrasonic waves under the guidance of a magnetic resonance (MR) system is demonstrated for medical applications. This technique is based on the maximization of the ultrasonic wave intensity at one targeted point in space. The wave intensity is indirectly estimated from the local tissue displacement induced at the chosen focus by the acoustic radiation force of ultrasonic beams. Coded ultrasonic waves are transmitted by an ultrasonic array and an MRI scanner is used to measure the resulting local displacements through a motion-sensitive MR sequence. After the transmission of a set of spatially encoded ultrasonic waves, a non-iterative inversion process is employed to accurately estimate the spatial-temporal aberration induced by the propagation medium and to maximize the acoustical intensity at the target.Both programmable and physical aberrating layers introducing strong distortions (up to 2pi radians) were recovered within acceptable errors (<0.8 rad). This noninvasive technique is shown to accurately correct phase aberrations in a phantom gel with negligible heat deposition and limited acquisition time. These refocusing performances demonstrate a major potential in the field of MR-guided ultrasound therapy in particular for transcranial brain high-intensity focused ultrasound.