Pierre Khuri-Yakub

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.

Medical imaging using capacitive micromachined ultrasonic transducer arrays

We are investigating the use of capacitive micromachined ultrasonic transducers (cMUTs) 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.

Forward-looking volumetric intracardiac imaging using a fully integrated CMUT ring array

Atrial fibrillation is the most common type of cardiac arrhythmia that now affects over 2.2 million adults in the United States alone. Currently fluoroscopy is the most common method for guiding interventional electrophysiological procedures. We are developing a 9-F forward-looking intracardiac ultrasound catheter for real-time volumetric imaging. We designed and fabricated a 64-element 10-MHz CMUT ring array with through-wafer via interconnects. We also designed custom front-end electronics to be closely integrated with the CMUT array at the tip of the catheter for improved SNR. This integrated circuit (IC) is composed of preamplifiers and protection circuitry, and can directly interface a standard imaging system. This multi-channel IC is capable of passing up to ±50-V bipolar pulses. An 8-channel front-end IC was fabricated based on this circuit topology. Additionally, a flexible PCB was designed for the integration of ring array with front-end electronics. We have acquired a PC-based real-time imaging platform and demonstrated real-time imaging with the ring array. We have also shown volume images using off-line full synthetic aperture image reconstruction method. The presented experimental results demonstrate the performance of our forward-looking volumetric intracardiac imaging approach. We are currently working on the final catheter integration and further development of our real-time imaging methods.

Forward-looking intracardiac imaging catheters using fully integrated CMUT arrays

Atrial fibrillation, the most common type of cardiac arrhythmia, now affects more than 2.2 million adults in the US alone. Currently, electrophysiological interventions are performed under fluoroscopy guidance, which besides its harmful ionizing radiation does not provide adequate soft-tissue resolution. Intracardiac echocardiography (ICE) provides realtime anatomical information that has proven valuable in reducing the fluoroscopy time and enhancing procedural success. We developed two types of forward-looking ICE catheters using capacitive micromachined ultrasonic transducer (CMUT) technology: MicroLinear (ML) and ring catheters. The ML catheter enables real-time forward-looking 2-D imaging using a 24-element 1-D CMUT phased-array that is designed for a center frequency of 10 MHz. The ring catheter uses a 64-element ring CMUT array that is also designed for a center frequency of 10 MHz. However, this ring-shaped 2-D array enables real-time forward-looking volumetric imaging. In addition, this catheter provides a continuous central lumen that enables convenient delivery of other devices such as RF ablation catheter, EP diagnostic catheter, biopsy devices, etc. Both catheters are equipped with custom front-end ICs that are integrated with the CMUT arrays at the tip of the catheters. The integration of the ICs with the CMUT arrays was accomplished using custom flexible PCBs. We also developed several image reconstruction schemes for the ring catheter on a PC-based imaging platform from VeraSonics. We performed a variety of bench-top characterizations to validate the functionality and performance of our fully integrated CMUT arrays. Using both catheters, we demonstrated in vivo images of the heart in a porcine animal model. We have successfully prototyped the first CMUT-based ICE catheters and proven the capabilities of the CMUT technology for implementing high-frequency miniature transducer arrays with integrated electronics.

A multichannel pipeline analog-to-digital converter for an integrated 3-D ultrasound imaging system

An 8-channel 10-bit pipeline analog-to-digital converter, designed for use in an integrated three-dimensional ultrasound imaging system, has been implemented in a 0.25-/spl mu/m CMOS technology. Two parallel multiplexing sample-and-hold stages are employed to multiplex a total of eight adjacent ultrasound channels, each sampled at 20 MHz. The sampled and multiplexed signals are fed into two parallel time-interleaved pipeline paths, each operating at 80 MHz. The two parallel pipelines are subsequently multiplexed into a single pipeline operating at 160 MHz to conserve area and reduce complexity. An experimental prototype of the proposed architecture occupies less than 4 mm/sup 2/ of active silicon area and shows a peak signal-to-noise-plus-distortion ratio more than 54 dB for a 2.1-MHz input signal, while dissipating only 20 mW of analog power per input channel from a 2.5-V supply.

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.

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.

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

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.

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 non-focal 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.

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 structures 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.