Intravascular ultrasound (IVUS) and intracardiac echography (ICE) catheters with real-time volumetric ultrasound imaging capability can provide unique benefits to many interventional procedures used in the diagnosis and treatment of coronary and structural heart diseases. Integration of CMUT arrays with front-end electronics in single-chip configuration allows for implementation of such catheter probes with reduced interconnect complexity, miniaturization, and high mechanical flexibility. We implemented a single-chip forward-looking (FL) ultrasound imaging system by fabricating a 1.4-mm-diameter dual-ring CMUT array using CMUT-on-CMOS technology on a front-end IC implemented in 0.35-µm CMOS process. The dual-ring array has 56 transmit elements and 48 receive elements on two separate concentric annular rings. The IC incorporates a 25-V pulser for each transmitter and a low-noise capacitive transimpedance amplifier (TIA) for each receiver, along with digital control and smart power management. The final shape of the silicon chip is a 1.5-mm-diameter donut with a 430-µm center hole for a guide wire. The overall front-end system requires only 13 external connections and provides 4 parallel RF outputs while consuming an average power of 20 mW. We measured RF A-scans from the integrated single-chip array which show full functionality at 20.1 MHz with 43% fractional bandwidth. We also tested and demonstrated the image quality of the system on a wire phantom and an ex-vivo chicken heart sample. The measured axial and lateral point resolutions are 92 µm and 251 µm, respectively. We successfully acquired volumetric imaging data from the ex-vivo chicken heart with 60 frames per second without any signal averaging. These demonstrative results indicate that single-chip CMUT-on-CMOS systems have the potential to produce real-time volumetric images with image quality and speed suitable for catheter based clinical applications.
One of the most important promises of capacitive micromachined ultrasonic transducer (CMUT) technology is integration with electronics. This approach is required to minimize the parasitic capacitances in the receive mode, especially in catheter based volumetric imaging arrays where the elements need to be small. Furthermore, optimization of the available silicon area and minimized number of connections occurs when the CMUTs are fabricated directly above the associated electronics. Here, we describe successful fabrication and performance evaluation of CMUT arrays for intravascular imaging on custom designed CMOS receiver electronics from a commercial IC foundry. The CMUT on CMOS process starts with surface isolation and mechanical planarization of the CMOS electronics to reduce topography. The rest of the CMUT fabrication is achieved by modifying a low temperature micromachining process through the addition of a single mask and developing a dry etching step to produce sloped sidewalls for simple and reliable CMUT to CMOS interconnection. This CMUT to CMOS interconnect method reduced the parasitic capacitance by a factor of 200 when compared with a standard wire bonding method. Characterization experiments indicate that the CMUT on CMOS elements are uniform in frequency response and are similar to CMUTs simultaneously fabricated on standard silicon wafers without electronics integration. Experiments on a 1.6 mm diameter dual-ring CMUT array with a 15 MHz center frequency show that both the CMUTs and the integrated CMOS electronics are fully functional. The SNR measurements indicate that the performance is adequate for imaging CTOs located 1 cm away from the CMUT array.
A large signal, transient model has been developed to predict the output characteristics of a CMUT array operated in the non-collapse mode. The model is based on separation of the nonlinear electrostatic voltage-to-force relation and the linear acoustic array response. For linear acoustic radiation and crosstalk effects, the boundary element method is used. The stiffness matrix in the vibroacoustics calculations is obtained using static finite element analysis of a single membrane which can have arbitrary geometry and boundary conditions. A lumped modeling approach is used to reduce the order of the system for modeling the transient nonlinear electrostatic actuation. To accurately capture the dynamics of the non-uniform electrostatic force distribution over the CMUT electrode during large deflections, the membrane electrode is divided into patches shaped to match higher order membrane modes, each introducing a variable to the system model. This reduced order nonlinear lumped model is solved in the time domain using Simulink. The model has two linear blocks to calculate the displacement profile of the electrode patches and the output pressure for a given force distribution over the array, respectively. The force to array displacement block uses the linear acoustic model, and the Rayleigh integral is evaluated to calculate the pressure at any field point. Using the model, the transient transmitted pressure can be simulated for different large signal drive signal configurations. The acoustic model is verified by comparison to harmonic FEA in vacuum and fluid for high and low aspect ratio membranes as well as mass-loaded membranes. The overall Simulink model is verified by comparison to transient 3D FEA and experimental results for different large drive signals; and an example for a phased array simulation is given.
The nonlinear relationship between the electrical input signal and electrostatic force acting on the capacitive micromachined ultrasonic transducer (CMUT) membrane limits its harmonic imaging performance. Several input shaping methods were proposed in order to compensate for the nonlinearity originating from the electrostatic force dependence on the square of the applied voltage. Here we analyze harmonic generation in CMUTs with a time domain model. The model explains the basis of the input shaping methods and suggests that the nonlinearity due to gap dependence of the electrostatic force is also significant. It also suggests that the harmonic distortion in the output pressure can be eliminated by subharmonic AC only excitation of the CMUT in addition to scaling the input voltage with the instantaneous gap. This gap feedback configuration can be approximated by the simple addition of a series impedance to the CMUT capacitance. We analyze several types of series impedance feedback topologies for gap feedback linearization. We show that for subharmonic AC excitation while resistive and capacitive impedances result in a trade-off between input voltage and harmonic distortion for a desired pressure output, harmonic generation can be suppressed while increasing the Pa/V transmit sensitivity for proper series inductance and resistance feedback. We experimentally demonstrate the feedback method by reducing harmonic generation by 10dB for the same output pressure at the fundamental frequency by using a simple series resistor feedback with a CMUT operating at a center frequency of 3 MHz. The proposed methods also allow for utilization of the full CMUT gap for transmit operation and hence should be useful in high intensity ultrasonic applications in addition to harmonic imaging.
Ultrasound contrast agents (UCAs) have tremendous potential for in vivo molecular imaging because of their high sensitivity. However, the diagnostic potential of UCAs has been difficult to exploit because current UCAs are based on pre-formed microbubbles, which can only detect cell surface receptors. Here, we demonstrate that chemical reactions that generate gas forming molecules can be used to perform molecular imaging by ultrasound in vivo. This new approach was demonstrated by imaging reactive oxygen species in vivo with allylhydrazine, a liquid compound that is converted into nitrogen and propylene gas after reacting with radical oxidants. We demonstrate that allylhydrazine encapsulated within liposomes can detect a 10 micromolar concentration of radical oxidants by ultrasound, and can image oxidative stress in mice, induced by lipopolysaccharide, using a clinical ultrasound system. We anticipate numerous applications of chemically-generated microbubbles for molecular imaging by ultrasound, given ultrasound’s ability to detect small increments above the gas saturation limit, its spatial resolution and widespread clinical use.
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