Acoustodynamic Covalent Materials Engineering for the Remote Control of Physical Properties Inside Materials.

Advances in vat photopolymerization (VP) 3D printing (3DP) technology enable the production of highly precise 3D objects. However, it is a major challenge to create dynamic functionalities and to manipulate the physical properties of the inherently insoluble and infusible cross-linked material generated from VP-3DP without reproduction. The fabrication of light- and high-intensity focused ultrasound (HIFU)-responsive cross-linked polymeric materials linked with hexaarylbiimidazole (HABI) in polymer chains based on VP-3DP is reported here. Although the photochemistry of HABI produces triphenylimidazolyl radicals (TPIRs) during the process of VP-3DP, the orthogonality of the photochemistry of HABI and photopolymerization enables the introduction of reversible cross-links derived from HABIs in the resulting 3D-printed objects. While photostimulation cleaves a covalent bond between two imidazoles in HABI to generate TPIRs only near the surface of the 3D-printed objects, HIFU triggers cleavage in the interior of materials. In addition, HIFU travels beyond an obstacle to induce a response of HABI-embedded cross-linked polymers, which cannot be attainable with photostimulation. The present system would be beneficial for tuning the physical properties and recycling of various polymeric materials, but it will also open the door for pinpoint modification, healing, and reshaping of materials when coupled to various dynamic covalent materials.

Simultaneous transrectal ultrasound and photoacoustic human prostate imaging.

Imaging technologies that simultaneously provide anatomical, functional, and molecular information are emerging as an attractive choice for disease screening and management. Since the 1980s, transrectal ultrasound (TRUS) has been routinely used to visualize prostatic anatomy and guide needle biopsy, despite limited specificity. Photoacoustic imaging (PAI) provides functional and molecular information at ultrasonic resolution based on optical absorption. Combining the strengths of TRUS and PAI approaches, we report the development and bench-to-bedside translation of an integrated TRUS and photoacoustic (TRUSPA) device. TRUSPA uses a miniaturized capacitive micromachined ultrasonic transducer array for simultaneous imaging of anatomical and molecular optical contrasts [intrinsic: hemoglobin; extrinsic: intravenous indocyanine green (ICG)] of the human prostate. Hemoglobin absorption mapped vascularity of the prostate and surroundings, whereas ICG absorption enhanced the intraprostatic photoacoustic contrast. Future work using the TRUSPA device for biomarker-specific molecular imaging may enable a fundamentally new approach to prostate cancer diagnosis, prognostication, and therapeutic monitoring.

Radiation Force as a Physical Mechanism for Ultrasonic Neurostimulation of the Ex Vivo Retina.

Focused ultrasound has been shown to be effective at stimulating neurons in many animal models, both in vivo and ex vivo Ultrasonic neuromodulation is the only noninvasive method of stimulation that could reach deep in the brain with high spatial-temporal resolution, and thus has potential for use in clinical applications and basic studies of the nervous system. Understanding the physical mechanism by which energy in a high acoustic frequency wave is delivered to stimulate neurons will be important to optimize this technology. We imaged the isolated salamander retina of either sex during ultrasonic stimuli that drive ganglion cell activity and observed micron scale displacements, consistent with radiation force, the nonlinear delivery of momentum by a propagating wave. We recorded ganglion cell spiking activity and changed the acoustic carrier frequency across a broad range (0.5-43 MHz), finding that increased stimulation occurs at higher acoustic frequencies, ruling out cavitation as an alternative possible mechanism. A quantitative radiation force model can explain retinal responses and could potentially explain previous in vivo results in the mouse, suggesting a new hypothesis to be tested in vivo Finally, we found that neural activity was strongly modulated by the distance between the transducer and the electrode array showing the influence of standing waves on the response. We conclude that radiation force is the dominant physical mechanism underlying ultrasonic neurostimulation in the ex vivo retina and propose that the control of standing waves is a new potential method to modulate these effects.SIGNIFICANCE STATEMENT Ultrasonic neurostimulation is a promising noninvasive technology that has potential for both basic research and clinical applications. The mechanisms of ultrasonic neurostimulation are unknown, making it difficult to optimize in any given application. We studied the physical mechanism by which ultrasound is converted into an effective energy form to cause neurostimulation in the retina and find that ultrasound acts via radiation force leading to a mechanical displacement of tissue. We further show that standing waves have a strong modulatory effect on activity. Our quantitative model by which ultrasound generates radiation force and leads to neural activity will be important in optimizing ultrasonic neurostimulation across a wide range of applications.

Applications of airborne ultrasound in human-computer interaction.

Airborne ultrasound is a rapidly developing subfield within human-computer interaction (HCI). Touchless ultrasonic interfaces and pen tracking systems are part of recent trends in HCI and are gaining industry momentum. This paper aims to provide the background and overview necessary to understand the capabilities of ultrasound and its potential future in human-computer interaction. The latest developments on the ultrasound transducer side are presented, focusing on capacitive micro-machined ultrasonic transducers, or CMUTs. Their introduction is an important step toward providing real, low-cost multi-sensor array and beam-forming options. We also provide a unified mathematical framework for understanding and analyzing algorithms used for ultrasound detection and tracking for some of the most relevant applications.

Reconfigurable mosaic annular arrays.

Mosaic annular arrays (MAA) based on reconfigurable array (RA) transducer electronics assemblies are presented as a potential solution for future highly integrated ultrasonic transducer subsystems. Advantages of MAAs include excellent beam quality and depth of field resulting from superior elevational focus compared with 1-D electronically scanned arrays, as well as potentially reduced cost, size, and power consumption resulting from the use of a limited number of beamforming channels for processing a large number of subelements. Specific design tradeoffs for these highly integrated arrays are discussed in terms of array specifications for center frequency, element pitch, and electronic switch-on resistance. Large-area RAs essentially function as RC delay lines. Efficient architectures which take into account RC delay effects are presented. Architectures for integration of the transducer and electronics layers of large-area array implementations are reviewed.

Precise neural stimulation in the retina using focused ultrasound.

Focused ultrasound is a promising noninvasive technology for neural stimulation. Here we use the isolated salamander retina to characterize the effect of ultrasound on an intact neural circuit and compared these effects with those of visual stimulation of the same retinal ganglion cells. Ultrasound stimuli at an acoustic frequency of 43 MHz and a focal spot diameter of 90 µm delivered from a piezoelectric transducer evoked stable responses with a temporal precision equal to strong visual responses but with shorter latency. By presenting ultrasound and visual stimulation together, we found that ultrasonic stimulation rapidly modulated visual sensitivity but did not change visual temporal filtering. By combining pharmacology with ultrasound stimulation, we found that ultrasound did not directly activate retinal ganglion cells but did in part activate interneurons beyond photoreceptors. These results suggest that, under conditions of strong localized stimulation, timing variability is largely influenced by cells beyond photoreceptors. We conclude that ultrasonic stimulation is an effective and spatiotemporally precise method to activate the retina. Because the retina is the most accessible part of the CNS in vivo, ultrasonic stimulation may have diagnostic potential to probe remaining retinal function in cases of photoreceptor degeneration, and therapeutic potential for use in a retinal prosthesis. In addition, because of its noninvasive properties and spatiotemporal resolution, ultrasound neurostimulation promises to be a useful tool to understand dynamic activity in pharmacologically defined neural pathways in the retina.

Packaging and modular assembly of large-area and fine-pitch 2-D ultrasonic transducer arrays.

A promising transducer architecture for largearea arrays employs 2-D capacitive micromachined ultrasound transducer (CMUT) devices with backside trench-frame pillar interconnects. Reconfigurable array (RA) application-specified integrated circuits (ASICs) can provide efficient interfacing between these high-element-count transducer arrays and standard ultrasound systems. Standard electronic assembly techniques such as flip-chip and ball grid array (BGA) attachment, along with organic laminate substrate carriers, can be leveraged to create large-area arrays composed of tiled modules of CMUT chips and interface ASICs. A large-scale, fully populated and integrated 2-D CMUT array with 32 by 192 elements was developed and demonstrates the feasibility of these techniques to yield future large-area arrays. This study demonstrates a flexible and reliable integration approach by successfully combining a simple under-bump metallization (UBM) process and a stacked CMUT/interposer/ASIC module architecture. The results show high shear strength of the UBM (26.5 g for 70-µm balls), high interconnect yield, and excellent CMUT resonance uniformity (s = 0.02 MHz). A multi-row linear array was constructed using the new CMUT/interposer/ASIC process using acoustically active trench-frame CMUT devices and mechanical/ nonfunctional Si backside ASICs. Imaging results with the completed probe assembly demonstrate a functioning device based on the modular assembly architecture.

First in vivo use of a capacitive micromachined ultrasound transducer array-based imaging and ablation catheter.

OBJECTIVES: The primary objective was to test in vivo for the first time the general operation of a new multifunctional intracardiac echocardiography (ICE) catheter constructed with a microlinear capacitive micromachined ultrasound transducer (ML-CMUT) imaging array. Secondarily, we examined the compatibility of this catheter with electroanatomic mapping (EAM) guidance and also as a radiofrequency ablation (RFA) catheter. Preliminary thermal strain imaging (TSI)-derived temperature data were obtained from within the endocardium simultaneously during RFA to show the feasibility of direct ablation guidance procedures. METHODS: The new 9F forward-looking ICE catheter was constructed with 3 complementary technologies: a CMUT imaging array with a custom electronic array buffer, catheter surface electrodes for EAM guidance, and a special ablation tip, that permits simultaneous TSI and RFA. In vivo imaging studies of 5 anesthetized porcine models with 5 CMUT catheters were performed. RESULTS: The ML-CMUT ICE catheter provided high-resolution real-time wideband 2-dimensional (2D) images at greater than 8 MHz and is capable of both RFA and EAM guidance. Although the 24-element array aperture dimension is only 1.5 mm, the imaging depth of penetration is greater than 30 mm. The specially designed ultrasound-compatible metalized plastic tip allowed simultaneous imaging during ablation and direct acquisition of TSI data for tissue ablation temperatures. Postprocessing analysis showed a first-order correlation between TSI and temperature, permitting early development temperature-time relationships at specific myocardial ablation sites. CONCLUSIONS: Multifunctional forward-looking ML-CMUT ICE catheters, with simultaneous intracardiac guidance, ultrasound imaging, and RFA, may offer a new means to improve interventional ablation procedures.

The feasibility of using thermal strain imaging to regulate energy delivery during intracardiac radio-frequency ablation.

A method is introduced to monitor cardiac ablative therapy by examining slope changes in the thermal strain curve caused by speed of sound variations with temperature. The sound speed of water-bearing tissue such as cardiac muscle increases with temperature. However, at temperatures above about 50°C, there is no further increase in the sound speed and the temperature coefficient may become slightly negative. For ablation therapy, an irreversible injury to tissue and a complete heart block occurs in the range of 48 to 50°C for a short period in accordance with the well-known Arrhenius equation. Using these two properties, we propose a potential tool to detect the moment when tissue damage occurs by using the reduced slope in the thermal strain curve as a function of heating time. We have illustrated the feasibility of this method initially using porcine myocardium in vitro. The method was further demonstrated in vivo, using a specially equipped ablation tip and an 11-MHz microlinear intracardiac echocardiography (ICE) array mounted on the tip of a catheter. The thermal strain curves showed a plateau, strongly suggesting that the temperature reached at least 50°C.

Large Area MEMS Based Ultrasound Device for Cancer Detection.

We present image results obtained using a prototype ultrasound array which demonstrates the fundamental architecture for a large area MEMS based ultrasound device for detection of breast cancer. The prototype array consists of a tiling of capacitive Micro-Machined Ultrasound Transducers (cMUTs) which have been flip-chip attached to a rigid organic substrate. The pitch on the cMUT elements is 185 um and the operating frequency is nominally 9 MHz. The spatial resolution of the new probe is comparable to production PZT probes, however the sensitivity is reduced by conditions that should be correctable. Simulated opposed-view image registration and Speed of Sound volume reconstruction results for ultrasound in the mammographic geometry are also presented.

CMUT With Substrate-Embedded Springs For Non-Flexural Plate Movement.

A conventional capacitive micromachined ultrasonic transducer (CMUT) is composed of many cells connected in parallel. Since the plate in each CMUT cell is anchored at its perimeter, the average displacement is several times smaller than the displacement of an equivalent ideal piston transducer. In addition, the post areas, where the plates are anchored to, are non-active and, thus, do not contribute to the transduction. We propose a CMUT structure that resembles an ideal capacitive piston transducer, where the movable top plate only undergoes translation rather than deflection. Our proposed CMUT structure is composed of a rigid plate connected to a substrate using relatively long and narrow posts, providing the spring constant for the movement of the plate. Rather than the flexure of the plate as in a conventional CMUT, this device operates based on the compression of the compliant posts. For a capacitive transducer, a thin electrostatic gap is provided under the top plate. We used finite element analysis (FEA) to design and verify the structure's functionality. The simulation results show a fractional bandwidth of over 100% in immersion for all the designs. They also confirm that the average displacement of the top plate is above 90% of its peak displacement. We fabricated the first prototype based on this idea, which only requires a simple 3-mask fabrication process. In addition to 128-element 1-D arrays, we fabricated a variety of 240 µm × 240 µm, single-element transducers with different post configurations. We successfully measured the electrical input impedance of the fabricated devices and confirmed their resonant behavior in air. Further, we measured the acoustic pressure using a calibrated hydrophone at a known distance. Using this measurement, we calculated a peak-to-peak pressure of 1.5 MPa at the face of the transducer. Our results show that it is possible to fabricate CMUTs that exhibit ideal piston-like plate movement. Because of the substrate-embedded spring elements, the plate does not need to be operated in flexural mode, as in a conventional CMUT, resulting in a significantly improved fill-factor, and, thus, a more efficient device.

Design Optimization for a 2-D Sparse Transducer Array for 3-D Ultrasound Imaging.

In 3-D ultrasound imaging where 2-D transducer arrays with more than hundreds of elements are used, sparse arrays can be used to reduce the number of active ultrasound channels. Under a restriction of desired number of active channels, we can maximize the image quality by optimally choosing the positions of active elements. Here we use the method of simulated annealing to find the optimal configuration of a 2-D sparse array. This algorithm tries to minimize the value of an objective function defined as the energy ratio between the nonfocal and focal regions in the point spread function (PSF). Optimal configurations were found for the cases of choosing 16, 20, 24, 28, and 32 transmit and receive elements from a 16×16-element rectangular transducer array. With only 32 transmit and 32 receive elements, we could achieve an energy ratio of 16%, compared to 6% of the full array, which is the gold standard utilizing all the 256 elements for both transmit and receive. Using Field II, we simulated imaging with the optimal sparse arrays, for off-axis targets as well as on-axis targets, and the resulting images were compared with those from some other configurations, such as full-transmit full-receive, full-transmit x-receive, x-transmit boundary-receive, and so on.

Experimental studies with a 9F forward-looking intracardiac imaging and ablation catheter.

OBJECTIVE: The purpose of this study was to develop a high-resolution, near-field-optimized 14-MHz, 24-element broad-bandwidth forward-looking array for integration on a steerable 9F electrophysiology (EP) catheter. METHODS: Several generations of prototype imaging catheters with bidirectional steering, termed microlinear (ML), were built and tested as integrated catheter designs with EP sensing electrodes near the tip. The wide-bandwidth ultrasound array was mounted on the very tip, equipped with an aperture of only 1.2 by 1.58 mm. The array pulse echo performance was fully simulated, and its construction offered shielding from ablation noise. Both ex vivo and in vivo imaging with a porcine animal model were performed. RESULTS: The array pulse echo performance was concordant with Krimholtz-Leedom-Matthaei model simulation. Three generations of prototype devices were tested in the right atrium and ventricle in 4 acute pig studies for the following characteristics: (1) image quality, (2) anatomic identification, (3) visualization of other catheter devices, and (4) for a mechanism for stabilization when imaging ablation. The ML catheter is capable of both low-artifact ablation imaging on a standard clinical imaging system and high-frame rate myocardial wall strain rate imaging for detecting changes in cardiac mechanics associated with ablation. CONCLUSIONS: The imaging resolution performance of this very small array device, together with its penetration beyond 2 cm, is excellent considering its very small array aperture. The forward-looking intracardiac catheter has been adapted to work easily on an existing commercial imaging platform with very minor software modifications.

Medical imaging using capacitive micromachined ultrasonic transducer arrays.

We are investigating the use of capacitive micromachined ultrasonic transducers (cMUT's) for use in medical imaging. We propose an ultrasound probe architecture designed to provide volumetric ultrasound imaging from within an endoscope channel. A complete automated experimental system has been implemented for testing the imaging performance of cMUT arrays. This PC-based system includes custom-designed circuit boards, a software interface, and resolution test phantoms. We have already fabricated 1D and 2D cMUT arrays, and tested the pulse-echo imaging characteristics of 1D arrays. Beamforming and image formation algorithms that aim to reduce the complexity of data acquisition hardware are tested via numerical simulations and using real data acquired from our system.