Aberration Correction Research Articles

In vivo soft tissue aberration correction for histotripsy using acoustic cavitation emissions

Phase aberration by heterogeneous soft tissues decreases the focusing quality of transabdominal histotripsy, thereby increasing the energy required to generate cavitation for therapy and elevating the risk of unsafe tissue heating. In vitro studies have shown that the acoustic signals emitted by histotripsy cavitation bubbles can serve as ‘point sources’ for aberration correction (AC). This study assessed the efficacy of cavitation emission-based AC in vivo. A 750-kHz, 260-element, receive-capable histotripsy phased array was used to generate cavitation at 3 locations in the livers of 3 pigs (n = 9). For each location, cavitation emission signals were received and cross correlated to determine a set of corrective phase delays. Then, the array was re-fired at increasing increments of driving power both with and without aberration correction. It was found that AC decreased the transducer power required to generate cavitation by 16%–48%. This result suggests that AC using the cavitation emissions from an initial test pulse can substantially reduce the energy delivered to intervening tissues during histotripsy therapy and thus increase treatment safety.

Passive acoustic mapping within the cranial vault during microbubble-mediated ultrasound brain therapy

Over the past 15 years, the use of passive sensor arrays combined with established beamforming algorithms to image acoustic activity during ultrasound therapies, so-called passive acoustic mapping (PAM), has been increasingly investigated for cavitation-based treatment monitoring and control purposes. Our group is interested in applications of microbubble-mediated ultrasound therapy in the brain, during which the skull bone presents unique challenges for both treatment delivery and acoustic emissions monitoring. We have demonstrated that skull-specific transcranial aberration correction methods can be applied during receive beamforming to augment PAM image quality through the skull bone, borrowing techniques developed originally for transmit beam focusing. Using custom clinical-prototype transmit/receive phased arrays, we have performed 3D microbubble imaging in vivo through ex vivo human skullcaps, and have exploited the resulting spatiotemporal cavitation information for real-time exposure level calibration and offline bioeffect distribution prediction. Ultrafast processing of acoustic emissions data can uncover cavitation dynamics hidden by conventional whole-burst temporal averaging, as well as inform temporal under-sampling strategies when millisecond-long tone bursts are applied. This talk will provide a historical overview of PAM for ultrasound therapy monitoring throughout the body, followed by a summary of recent progress made in mapping cavitation activity within the cranial vault during brain applications.

Small animal cerebral microvascular imaging with super-resolution ultrasound: Techniques and applications

Super-resolution ultrasound (SR-US) is an emerging microvascular imaging technology that provides a micron-scale spatial resolution with tens of millimeters of depth of imaging penetration. The unmatched combination of high spatial resolution and deep imaging penetration opened new doors for many brain imaging applications that benefit from cerebrovascular biomarkers. Recently, SR-US has found its niche in small animal brain applications thanks to its unique capabilities of extending the optical-imaging-level spatial resolution to subcortical, deep brain regions. In this presentation, I will first introduce existing SR-US imaging techniques that are tailored to small animal brain imaging applications. Topics include fast SR-US methods, 3D SR-US imaging, and phase aberration correction for intact skull imaging. I will then focus on reviewing brain imaging applications that use SR-US to characterize cerebral mirovasculature in the aging, stroke, and Alzheimer’s Disease brain. Finally, I will introduce the new functional super-resolution imaging technique that combines SR-US with functional ultrasound (fUS) to realize whole-brain neural activity recording at a micron-scale spatial resolution.

Instrumentation for histotripsy ultrasound therapy: Evolution toward the clinic

Histotripsy is a method of ultrasound therapy using very intense, focused sound fields to fragment tissue causing controlled and localized necrosis principally through mechanical actions of cavitation. Highly specialized instrumentation (transducers and electrical drivers) is required to produce these extreme sound fields for research into cavitation physics and therapeutic applications of histotripsy. This paper will describe the evolution of histotripsy instrumentation from the first devices up to the latest phased-array systems with hundreds of channels and transmit-receive capability. While early histotripsy systems used tone bursts generators with limited bandwidth (called “class-D” circuits) for transducer excitation, more recent ones are based on a switched inductor principle to produce shorter duration acoustic emissions. This method has been tested for peak excitation voltages up to 5 kV and 40 A in compact modular systems suitable for phased-arrays. Receive of acoustic signals by the therapeutic array for aberration correction and cavitation mapping is achieved by sensing current generated by the transducer greatly simplifying transmit-receive circuitry while maintaining very large dynamic range. A novel distributed architecture was developed for data handling and signal processing using off-the-shelf FPGA evaluation modules interfaced by ethernet. These latest features will be key to successful clinical translation and widespread adoption of histotripsy.

Binary acoustic metasurfaces for transcranial focused ultrasound

Transcranial focused ultrasound is a promising technique for noninvasive and spatially targeted diagnosis and treatment of brain diseases. Acoustic lenses were designed to correct the skull-induced beam aberration, but these designs could only generate static focused ultrasound beams inside the brain. Here, we designed and 3D printed binary acoustic metasurfaces (BAMs) for skull aberration correction and dynamic ultrasound beam focusing. BAMs were designed by binarizing the phase distribution at the surface of the metasurfaces. The phase distribution was calculated based on time reversal to correct the skull-induced phase aberration. The binarization enabled the ultrasound beam to be dynamically steered along wave propagation direction by adjusting the operation frequency of the incident ultrasound wave. The designed BAMs were manufactured by 3D printing with two coding bits, a polylactic acid unit for bit “1” and a water unit for bit “0.” BAMs for single- and multi-point focusing through the human skull were designed, 3D printed, and validated numerically and experimentally. In summary, the proposed BAMs with subwavelength scale in thickness are simple to design, easy to fabric, and capable of correcting skull aberration and achieving dynamic beam steering.

Dynamic ultrasound localization microscopy

Ultrasound localization microscopy (ULM) can map the vasculature at large depth with unprecedented resolution by localizing millions of injected microbubbles in hundreds of thousands of images acquired over a few minutes. The current state of the art in ULM is to use low concentrations to achieve the best possible spatial resolution without providing temporal information, which limits the development of functional biomarkers such as pulsality or the imaging of moving organs like the heart. In this work, we will present dynamic ultrasound localization microscopy (DULM), which enables the generation of dynamic images of the vasculature of periodic phenomena by using a combination of enhanced image formation and processing techniques to drastically increase the number of microbubbles that can be detected in each image. Specifically, we will describe how the detection of microbubbles directly in space time along with novel aberration correction algorithms and a motion-invariant Lagrangian beamforming approach can be used to increase the concentration of microbubbles 5-fold with a limited degradation in resolution. Examples of application for the mapping of pulsatility in the brain and the dynamics of the intramyocardial blood flow in 2D + t and 3D + t will be shown.

High-Accuracy Depth Estimation of Nematic Liquid Crystal Microlens Arrays Based on Convex Optimization Theory

We have proposed an iterative feedback method based on a nematic liquid crystal microlens array (LC-MLA) light-field system, which can obtain highly accurate depth maps. A preliminary reconstruction of the all-in-focus map of the scene is produced to obtain a high-precision depth map. A natural image sparsity prior and a chromatic aberration correction are used to ensure high-quality deblurring in the presence of inaccurate depth estimation. Subsequently, a high-quality all-in-focus image is used as a constraint to obtain a high-accuracy depth estimation result. After the experiment, it can be demonstrated that the proposed method can provide good estimation results under texture-free conditions.

Differentiable optimization of the Debye-Wolf integral for light shaping and adaptive optics in two-photon microscopy.

Control of light through a microscope objective with a high numerical aperture is a common requirement in applications such as optogenetics, adaptive optics, or laser processing. Light propagation, including polarization effects, can be described under these conditions using the Debye-Wolf diffraction integral. Here, we take advantage of differentiable optimization and machine learning for efficiently optimizing the Debye-Wolf integral for such applications. For light shaping we show that this optimization approach is suitable for engineering arbitrary three-dimensional point spread functions in a two-photon microscope. For differentiable model-based adaptive optics (DAO), the developed method can find aberration corrections with intrinsic image features, for example neurons labeled with genetically encoded calcium indicators, without requiring guide stars. Using computational modeling we further discuss the range of spatial frequencies and magnitudes of aberrations which can be corrected with this approach.

Design and modeling of corneal aberration correction with diffractive IOL based on ZEMAX

This paper estimates a specific detailed diffractive aspheric bifocal intraocular lens (IOL) used to correct and reduce corneal aberration and a patient’s standard surgical implantation. Foldable acrylic hydrophobic materials have promising properties and are thus used in IOLs. Calculations and analyses were performed using the optical software design program Zemax, and important criteria, such as modulation transfer function and Seidel aberration, were tested over a range of fields of view (20°, 30° or 40°) and different values of entrance pupil diameter (1.5, 3 and 4 mm). Results showed that a significant amount of corneal spherical aberration can be compensated for. The diffractive hydrophobic IOL customizes and corrects the spherical aberration performance of the individual crystalline lens.

Process Controlled Ruthenium on 2D Engineered V-MXene via Atomic Layer Deposition for Human Healthcare Monitoring.

In searching for unique and unexplored 2D materials, the authors try to investigate for the very first time the use of delaminated V-MXene coupled with precious metal ruthenium (Ru) through atomic layer deposition (ALD) for various contact and noncontact mode of real-time temperature sensing applications at the human-machine interface. The novel delaminated V-MXene (DM-V2 CTx ) engineered ruthenium-ALD (Ru-ALD) temperature sensor demonstrates a competitive sensing performance of 1.11%°C-1 as of only V-MXene of 0.42%°C-1 . A nearly threefold increase in sensing and reversibility performance linked to the highly ordered few-layered V-MXene and selective, well-controlled Ru atomic doping by ALD for the successful formation of Ru@DM-V2 CTX heterostructure. The advanced heterostructure formation, the mechanism, and the role of Ru have been comprehensively investigated by ultra-high-resolution transmission/scanning transmission electron microscopies coupled with next-generation spherical aberration correction technology and fast, accurate elemental mapping quantifications, also by ultraviolet photoelectron spectroscopy. To the knowledge, this work is the first to use the novel, optimally processed V-MXene over conventionally used Ti-MXene and its surface-internal structure engineering by Ru-ALD process-based temperature-sensing devices function and operational demonstrations. The current work could potentially motivate the development of multifunctional, future, next-generation, safe, personal healthcare electronic devices by the industrially scalable ALD technique.

Adaptive aberration correction using an electrowetting array.

We demonstrate a method that permits wavefront aberration correction using an array of electrowetting prisms. A fixed high fill factor microlens array followed by a lower fill factor adaptive electrowetting prism array is used to correct wavefront aberration. The design and simulation of such aberration correction mechanism is described. Our results show significant improvement to the Strehl ratio by using our aberration correction scheme which results in diffraction limited performance. Compactness and effectiveness of our design can be implemented in many applications that require aberration correction, such as microscopy and consumer electronics.

Imaging mitochondria through bone in live mice using two-photon fluorescence microscopy with adaptive optics.

Mitochondria are extremely important organelles in the regulation of bone marrow and brain activity. However, live imaging of these subcellular features with high resolution in scattering tissues like brain or bone has proven challenging. In this study, we developed a two-photon fluorescence microscope with adaptive optics (TPFM-AO) for high-resolution imaging, which uses a home-built Shack-Hartmann wavefront sensor (SHWFS) to correct system aberrations and a sensorless approach for correcting low order tissue aberrations. Using AO increases the fluorescence intensity of the point spread function (PSF) and achieves fast imaging of subcellular organelles with 400 nm resolution through 85 μm of highly scattering tissue. We achieved ~1.55×, ~3.58×, and ~1.77× intensity increases using AO, and a reduction of the PSF width by ~0.83×, ~0.74×, and ~0.9× at the depths of 0, 50 μm and 85 μm in living mouse bone marrow respectively, allowing us to characterize mitochondrial health and the survival of functioning cells with a field of view of 67.5× 67.5 μm. We also investigate the role of initial signal and background levels in sample correction quality by varying the laser power and camera exposure time and develop an intensity-based criteria for sample correction. This study demonstrates a promising tool for imaging of mitochondria and other organelles in optically distorting biological environments, which could facilitate the study of a variety of diseases connected to mitochondrial morphology and activity in a range of biological tissues.

Large numerical aperture off-axis reflective telescope design with a freeform mirror based on aperture expansion strategy.

Currently, the emission of greenhouse gases is one of humanity's leading threats. To accurately and efficiently measure greenhouse gas levels in the atmosphere, we must develop imaging spectrometer systems with larger numerical apertures (NAs). However, designing a telescope with a large NA is difficult in this system. This paper presents a design strategy for aperture expansion to create a freeform telescope with a large NA. We compared different off-axis reflective telescopes and chose the Korsch structure, which has obvious advantages because of its wide field of view (FoV), large NA, and low stray light. Moreover, based on the influence of the position of the freeform surface in the aberration correction, we propose to use a single freeform surface to reduce the cost and increase manufacturability. A freeform telescope with an effective focal length of 84mm, a large NA of 0.25, and a wide FoV of 20° is successfully designed. The modulation transfer function of the system is better than 0.62, the maximum distortion is controlled to be less than 0.486%, and the incident angle of the beam on the image plane is less than 10°. The design result shows that the instrument has wide FoV, large NA, low stray light, and high performance. At the same time, the design strategy in this paper provides an effective method for the telescope design of the imaging spectrometer with a large NA.

A mathematical framework for nonlinear wavefront reconstruction in adaptive optics systems with Fourier-type wavefront sensing

Advanced adaptive optics (AO) instruments have applications in ophthalmic imaging, free-space optical communications and the future generation of extremely large telescopes. These AO systems are designed to perform real-time corrections of dynamic wavefront aberrations. The corrections can be performed by converting wavefront measurements into deformable mirror (DM) actuator commands. The role of the DM is to mitigate aberrations by restoring a planar wavefront. Optimal DM actuator commands therefore require precise phase measurements across the entire wavefront. Reconstructing a wavefront from wavefront sensor (WFS) data is an inverse problem that depends on the type of WFS implemented. Nonlinear Fourier-type WFSs are included in the design of many current and upcoming AO systems. Conventionally, these sensors perform AO control based on simplifications and linearisations of the underlying models. However, in nonlinear regimes, approximation errors critically degrade image quality. This study looks at overcoming nonlinear wavefront sensing regimes by introducing a nonlinear, iterative algorithm for Fourier-type wavefront reconstruction. The algorithm used is well-known in the field of inverse problems. The underlying mathematical theory for modelling Fourier-type WFSs is provided, along with how these models can be used to perform nonlinear wavefront reconstruction. A significant advantage of the analysis presented is its generalised applicability to any Fourier-type sensor. The only input required is the mathematical expression for the optical element transfer function. The generalised and full mathematical model of Fourier-type WFSs is introduced in a Sobolev space setting. Necessary inputs are derived for the nonlinear iterative algorithms, such as Fréchet derivatives and adjoints. The generalised theory is then expanded to solve the inverse problem of wavefront reconstruction for all Fourier-type WFSs. Moreover, the study concentrates on the pyramid WFS (PWFS)—one of the most well-known Fourier-type WFSs—and shows a Hilbert transform representation of the amplitude of the incoming light on its detector. The developed theory is demonstrated using a simulated PWFS to measure an example wavefront.

An aberration correction approach for single and dual aperture ultrasound imaging of the abdomen

Abdominal ultrasound image quality is hampered by phase aberration, that is mainly caused by the large speed-of-sound (SoS) differences between fat and muscle tissue in the abdominal wall. The mismatch between the assumed and actual SoS distribution introduces general blurring of the ultrasound images, and acoustic refraction can lead to geometric distortion of the imaged features. Large aperture imaging or dual-transducer imaging can improve abdominal imaging at deep locations by providing increased contrast and resolution. However, aberration effects for large aperture imaging can be even more severe, which limits its full potential. In this study, a model-based aberration correction method for arbitrary acquisition schemes is introduced for delay-and-sum (DAS) beamforming and its performance was analyzed for both single- and dual-transducer ultrasound imaging. The method employs aberration corrected wavefront arrival times, using manually assigned local SoS values. Two wavefront models were compared. The first model is based on a straight ray approximation, and the second model on the Eikonal equation, which is solved by a multi-stencils fast marching method. Their accuracy for abdominal imaging was evaluated in acoustic simulations and phantom experiments involving tissue-mimicking and porcine material with large SoS contrast (∼100 m/s). The lateral resolution was improved by up to 90% in simulations and up to 65% in experiments compared to standard DAS, in which the use of Eikonal beamforming generally outperformed straight ray beamforming. Moreover, geometric distortions were mitigated in multi-aperture imaging, leading to a reduction in position error of around 80%. A study on the sensitivity of the aberration correction to shape and SoS of aberrating layers was performed, showing that even with imperfect segmentations or SoS values, aberration correction still outperforms standard DAS.

Light field displays with computational vision correction for astigmatism and high-order aberrations with real-time implementation.

Vision-correcting near-eye displays are necessary concerning the large population with refractive errors. However, varifocal optics cannot effectively address astigmatism (AST) and high-order aberration (HOAs); freeform optics has little prescription flexibility. Thus, a computational solution is desired to correct AST and HOA with high prescription flexibility and no increase in volume and hardware complexity. In addition, the computational complexity should support real-time rendering. We propose that the light field display can achieve such computational vision correction by manipulating sampling rays so that rays forming a voxel are re-focused on the retina. The ray manipulation merely requires updating the elemental image array (EIA), being a fully computational solution. The correction is first calculated based on an eye's wavefront map and then refined by a simulator performing iterative optimization with a schematic eye model. Using examples of HOA and AST, we demonstrate that corrected EIAs make sampling rays distributed within ±1 arcmin on the retina. Correspondingly, the synthesized image is recovered to nearly as clear as normal vision. We also propose a new voxel-based EIA generation method considering the computational complexity. All voxel positions and the mapping between voxels and their homogeneous pixels are acquired in advance and stored as a lookup table, bringing about an ultra-fast rendering speed of 10 ms per frame with no cost in computing hardware and rendering accuracy. Finally, experimental verification is carried out by introducing the HOA and AST with customized lenses in front of a camera. As a result, significantly recovered images are reported.

MAXPEEM: a spectromicroscopy beamline at MAX IV laboratory.

MAXPEEM, a dedicated photoemission electron microscopy beamline at MAX IV Laboratory, houses a state-of-the-art aberration-corrected spectroscopic photoemission and low-energy electron microscope (AC-SPELEEM). This powerful instrument offers a wide range of complementary techniques providing structural, chemical and magnetic sensitivities with a single-digit nanometre spatial resolution. The beamline can deliver a high photon flux of≥1015 photons s-1 (0.1% bandwidth)-1 in the range 30-1200 eV with full control of the polarization from an elliptically polarized undulator. The microscope has several features which make it unique from similar instruments. The X-rays from the synchrotron pass through the first beam separator and impinge the surface at normal incidence. The microscope is equipped with an energy analyzer and an aberration corrector which improves both the resolution and the transmission compared with standard microscopes. A new fiber-coupled CMOS camera features an improved modulation transfer function, dynamic range and signal-to-noise ratio compared with the traditional MCP-CCD detection system.

Design and theoretical analysis of the image-side telecentric zoom system using focus tunable lenses based on Gaussian brackets and lens modules

For now, telecentric system and zoom system have been extensively implemented in machine vision, industrial inspection, etc. However, studies on optical systems with both telecentric and zoom functions are still rare. To improve this situation, we present the design method of the telecentric zoom system with four focus tunable lenses (FTL) and a moving aperture stop (STOP) by applying Gaussian brackets and lens modules. We first improve the Gaussian brackets to achieve the initial parameter solution of the telecentric zoom FTL system, then we introduce a selection method to find the initial structural parameters with sufficient potential for optical design. After that, we use the lens module method to design the initial structure of the optical system, we also expand the combination method of the lens modules which contains an FTL. Finally, the initial structures of a 4X image-side telecentric zoom FTL system are constructed as an example and then optimized using CODEV. As a result, we get an image-side telecentric zoom FTL system with an F/# of 4, a zoom range of 20 mm to 80 mm, an image plane size of 8 mm, and a total length of 218 mm, which performs well in telecentricity control, distortion control, and aberration correction.

Analysis and correction of misalignment-induced aberrations in two-mirror telescopes with stop on the secondary mirror.

We study the problem of misalignment aberration analysis and correction of the two-mirror telescopes with stop on the secondary mirror. The variation law of the system's aberration field is analyzed with nodal aberration theory when the primary mirror with an astigmatic figure error is misaligned. The analytic expression among the system wave aberration, misalignments, and astigmatism figure error is given, and the correction model of system misalignment aberration is established. The simulation experiment shows that the relative error of the prediction of system misalignment coma and astigmatism based on this model is less than 4.1%.

DHM-viewer: Comprehensive, open-source image processing suite for digital holographic microscopy.

In recent years, digital holographic microscopy (DHM) has witnessed extensive use in quantitative phase imaging (QPI) applications such as live cell dynamics imaging, and 3D particle tracking owing to its ability to reconstruct optical fields based on a single exposure. As a computational imaging technique, DHM is highly specific to the processing pipeline depending on optical configuration and processing requirements. Commercial DHM systems additionally rely on proprietary user interfaces and specific workflows that prohibit user modification, limiting their appeal for users who wish to explore different optical configurations or implement the latest processing algorithms. To address these demands, we present a comprehensive open-source software suite (DHM-viewer) compatible with most commercially available and bespoke DHM systems. DHM-viewer provides user-facing functionalities such as optical alignment assistance, stage actuation control, real-time live image acquisition, and post-processing visualization with a Graphical User Interface (GUI) system. Notably, the GUI is driven by a Standard Operation Procedure (SOP) processing layout that assist users and can accommodate various optical configurations and operating modes. From a system control perspective, DHM-viewer exploits the Micro-Manager framework to ensure compatibility with many existing microscope automation toolkits. From a post-processing perspective, the core software supports a variety of state-of-the-art phase aberration correction and Fourier filtering algorithms as well as deep learning-accelerated phase unwrapping and 3D tracking functionality leveraging the computational power of GPU-based processing. Finally, the DHM-viewer backend supports large batch offline processing through dedicated server-side distribution. The functionality and usability of the software were verified on three different DHM platforms, including one hybrid DHM-fluorescence system.