Omer Oralkan

Carbon nanotubes as photoacoustic molecular imaging agents in living mice

Photoacoustic imaging of living subjects offers higher spatial resolution and allows deeper tissues to be imaged compared with most optical imaging techniques. As many diseases do not exhibit a natural photoacoustic contrast, especially in their early stages, it is necessary to administer a photoacoustic contrast agent. A number of contrast agents for photoacoustic imaging have been suggested previously, but most were not shown to target a diseased site in living subjects. Here we show that single-walled carbon nanotubes conjugated with cyclic Arg-Gly-Asp (RGD) peptides can be used as a contrast agent for photoacoustic imaging of tumours. Intravenous administration of these targeted nanotubes to mice bearing tumours showed eight times greater photoacoustic signal in the tumour than mice injected with non-targeted nanotubes. These results were verified ex vivo using Raman microscopy. Photoacoustic imaging of targeted single-walled carbon nanotubes may contribute to non-invasive cancer imaging and monitoring of nanotherapeutics in living subjects.

Capacitive micromachined ultrasonic transducers: next-generation arrays for acoustic imaging?

Piezoelectric materials have dominated the ultrasonic transducer technology. Recently, capacitive micromachined ultrasonic transducers (CMUTs) have emerged as an alternative technology offering advantages such as wide bandwidth, ease of fabricating large arrays, and potential for integration with electronics. The aim of this paper is to demonstrate the viability of CMUTs for ultrasound imaging. We present the first pulse-echo phased array B-scan sector images using a 128-element, one-dimensional (1-D) linear CMUT array. We fabricated 64- and 128-element 1-D CMUT arrays with 100% yield and uniform element response across the arrays. These arrays have been operated in immersion with no failure or degradation in performance over the time. For imaging experiments, we built a resolution test phantom roughly mimicking the attenuation properties of soft tissue. We used a PC-based experimental system, including custom-designed electronic circuits to acquire the complete set of 128/spl times/128 RF A-scans from all transmit-receive element combinations. We obtained the pulse-echo frequency response by analyzing the echo signals from wire targets. These echo signals presented an 80% fractional bandwidth around 3 MHz, including the effect of attenuation in the propagating medium. We reconstructed the B-scan images with a sector angle of 90 degrees and an image depth of 210 mm through offline processing by using RF beamforming and synthetic phased array approaches. The measured 6-dB lateral and axial resolutions at 135 mm depth were 0.0144 radians and 0.3 mm, respectively. The electronic noise floor of the image was more than 50 dB below the maximum mainlobe magnitude. We also performed preliminary investigations on the effects of crosstalk among array elements on the image quality. In the near field, some artifacts were observable extending out from the array to a depth of 2 cm. A tail also was observed in the point spread function (PSF) in the axial direction, indicating the existence of crosstalk. The relative amplitude of this tail with respect to the mainlobe was less than -20 dB.

Capacitive micromachined ultrasonic transducers: fabrication technology

Capacitive micromachined ultrasonic transducer (MUT) technology is a prime candidate for next generation imaging systems. Medical and underwater imaging and the nondestructive evaluation (NDE) societies have expressed growing interest in cMUTs over the years. Capacitive micromachined ultrasonic transducer technology is expected to make a strong impact on imaging technologies, especially volumetric imaging, and to appear in commercial products in the near future. This paper focuses on fabrication technologies for cMUTs and reviews and compares variations in the production processes. We have developed two main approaches to the fabrication of cMUTs: the sacrificial release process and the recently introduced wafer-bonding method. This paper gives a thorough review of the sacrificial release processes, and it describes the new wafer-bonding method in detail. Process variations are compared qualitatively and quantitatively whenever possible. Through these comparisons, it was concluded that wafer-bonded cMUT technology was superior in terms of process control, yield, and uniformity. Because the number of steps and consequent process time were reduced (from six-mask process to four-mask process), turn-around time was improved significantly.

Integration of 2D CMUT arrays with front-end electronics for volumetric ultrasound imaging

For three-dimensional (3D) ultrasound imaging, connecting elements of a two-dimensional (2D) transducer array to the imaging systems front-end electronics is a challenge because of the large number of array elements and the small element size. To compactly connect the transducer array with electronics, we flip-chip bond a 2D 16 times 16-element capacitive micromachined ultrasonic transducer (CMUT) array to a custom-designed integrated circuit (IC). Through-wafer interconnects are used to connect the CMUT elements on the top side of the array with flip-chip bond pads on the back side. The IC provides a 25-V pulser and a transimpedance preamplifier to each element of the array. For each of three characterized devices, the element yield is excellent (99 to 100% of the elements are functional). Center frequencies range from 2.6 MHz to 5.1 MHz. For pulse-echo operation, the average -6-dB fractional bandwidth is as high as 125%. Transmit pressures normalized to the face of the transducer are as high as 339 kPa and input-referred receiver noise is typically 1.2 to 2.1 rnPa/ radicHz. The flip-chip bonded devices were used to acquire 3D synthetic aperture images of a wire-target phantom. Combining the transducer array and IC, as shown in this paper, allows for better utilization of large arrays, improves receive sensitivity, and may lead to new imaging techniques that depend on transducer arrays that are closely coupled to IC electronics.

Capacitive micromachined ultrasonic transducers for medical imaging and therapy

Capacitive micromachined ultrasonic transducers (CMUTs) have been subject to extensive research for the last two decades. Although they were initially developed for air-coupled applications, today their main application space is medical imaging and therapy. This paper first presents a brief description of CMUTs, their basic structure, and operating principles. Our progression of developing several generations of fabrication processes is discussed with an emphasis on the advantages and disadvantages of each process. Monolithic and hybrid approaches for integrating CMUTs with supporting integrated circuits are surveyed. Several prototype transducer arrays with integrated frontend electronic circuits we developed and their use for 2-D and 3-D, anatomical and functional imaging, and ablative therapies are described. The presented results prove the CMUT as a MEMS technology for many medical diagnostic and therapeutic applications.

Characterization of one-dimensional capacitive micromachined ultrasonic immersion transducer arrays

We report on the characterization of 1D arrays of capacitive micromachined ultrasonic transducers (cMUT). A 275/spl times/5600 /spl mu/m 1D CMUT array element is experimentally characterized, and the results are found to be in agreement with theoretical predictions. As a receiver, the transducer has a 0.28-fm//spl radic/Hz displacement sensitivity, and, as a transmitter, it produces 5 kPa/V of output pressure at the transducer surface at 3 MHz with a DC bias of 35 V. The transducer has more than 100% fractional bandwidth around 3 MHz, which makes it suitable for ultrasound imaging. The radiation pattern of isolated single elements, as well as those of array elements are measured, and two major sources of acoustical crosstalk are identified. A weakly dispersive non-leaky interface wave (Stoneley wave) is observed to be propagating at the silicon substrate-fluid interface at a speed close to the speed of sound in the fluid. This wave causes internal reflections, spurious resonance, and radiation from the edges of the silicon substrate. The large lateral component of the particle velocity generated by the membranes at the edge of the cMUT array elements is found to be the source of this interface wave. Lowest order Lamb waves in the silicon substrate are also found to contribute to the crosstalk between elements. These waves are excited at the edges of individual vibrating membranes, where they are anchored to the substrate, and result in a narrowing of the beam profile of the array elements. Several methods, such as trench isolation and wafer thinning, are proposed and implemented to modify the acoustical cross coupling between array elements.

Volumetric ultrasound imaging using 2-D CMUT arrays

Recently, capacitive micromachined ultrasonic transducers (CMUTs) have emerged as a candidate to overcome the difficulties in the realization of 2-D arrays for real-time 3-D imaging. In this paper, we present the first volumetric images obtained using a 2-D CMUT array. We have fabricated a 128/spl times/128-element 2-D CMUT array with through-wafer via interconnects and a 420-/spl mu/m element pitch. As an experimental prototype, a 32/spl times/64-element portion of the 128/spl times/128-element array was diced and flip-chip bonded onto a glass fanout chip. This chip provides individual leads from a central 16/spl times/16-element portion of the array to surrounding bondpads. An 8/spl times/16-element portion of the array was used in the experiments along with a 128-channel data acquisition system. For imaging phantoms, we used a 2.37-mm diameter steel sphere located 10 mm from the array center and two 12-mm-thick Plexiglas plates located 20 mm and 60 mm from the array. A 4/spl times/4 group of elements in the middle of the 8/spl times/16-element array was used in transmit, and the remaining elements were used to receive the echo signals. The echo signal obtained from the spherical target presented a frequency spectrum centered at 4.37 MHz with a 100% fractional bandwidth, whereas the frequency spectrum for the echo signal from the parallel plate phantom was centered at 3.44 MHz with a 91% fractional bandwidth. The images were reconstructed by using RF beamforming and synthetic phased array approaches and visualized by surface rendering and multiplanar slicing techniques. The image of the spherical target has been used to approximate the point spread function of the system and is compared with theoretical expectations. This study experimentally demonstrates that 2-D CMUT arrays can be fabricated with high yield using silicon IC-fabrication processes, individual electrical connections can be provided using through-wafer vias, and flip-chip bonding can be used to integrate these dense 2-D arrays with electronic circuits for practical 3-D imaging applications.

3-D ultrasound imaging using a forward-looking CMUT ring array for intravascular/intracardiac applications

Forward-viewing ring arrays can enable new applications in intravascular and intracardiac ultrasound. This work presents compelling, full-synthetic, phased-array volumetric images from a forward-viewing capacitive micromachined ultrasonic transducer (CMUT) ring array wire bonded to a custom integrated circuit front end. The CMUT ring array has a diameter of 2 mm and 64 elements each 100 /spl mu/m /spl times/ 100 /spl mu/m in size. In conventional mode, echo signals received from a plane reflector at 5 mm had 70% fractional bandwidth around a center frequency of 8.3 MHz. In collapse mode, 69% fractional bandwidth is measured around 19 MHz. Measured signal-to-noise ratio (SNR) of the echo averaged 16 times was 29 dB for conventional operation and 35 dB for collapse mode. B-scans were generated of a target consisting of steel wires 0.3 mm in diameter to determine resolution performance. The 6 dB axial and lateral resolutions for the B-scan of the wire target are 189 /spl mu/m and 0.112 radians for 8 MHz, and 78 /spl mu/m and 0.051 radians for 19 MHz. A reduced firing set suitable for real-time, intravascular applications was generated and shown to produce acceptable images. Rendered three-dimensional (3-D) images of a Palmaz-Schatz stent also are shown, demonstrating that the imaging quality is sufficient for practical applications.

An integrated circuit with transmit beamforming flip-chip bonded to a 2-D CMUT array for 3-D ultrasound imaging

State-of-the-art 3-D medical ultrasound imaging requires transmitting and receiving ultrasound using a 2-D array of ultrasound transducers with hundreds or thousands of elements. A tight combination of the transducer array with integrated circuitry eliminates bulky cables connecting the elements of the transducer array to a separate system of electronics. Furthermore, preamplifiers located close to the array can lead to improved receive sensitivity. A combined IC and transducer array can lead to a portable, high-performance, and inexpensive 3-D ultrasound imaging system. This paper presents an IC flip-chip bonded to a 16times16-element capacitive micromachined ultrasonic transducer (CMUT) array for 3-D ultrasound imaging. The IC includes a transmit beamformer that generates 25-V unipolar pulses with programmable focusing delays to 224 of the 256 transducer elements. One-shot circuits allow adjustment of the pulse widths for different ultrasound transducer center frequencies. For receiving reflected ultrasound signals, the IC uses the 32-elements along the array diagonals. The IC provides each receiving element with a low-noise 25-MHz-bandwidth transimpedance amplifier. Using a field-programmable gate array (FPGA) clocked at 100 MHz to operate the IC, the IC generated properly timed transmit pulses with 5-ns accuracy. With the IC flip-chip bonded to a CMUT array, we show that the IC can produce steered and focused ultrasound beams. We present 2-D and 3-D images of a wire phantom and 2-D orthogonal cross-sectional images (Bscans) of a latex heart phantom.

Minimally Redundant 2-D Array Designs for 3-D Medical Ultrasound Imaging

In real-time ultrasonic 3-D imaging, in addition to difficulties in fabricating and interconnecting 2-D transducer arrays with hundreds of elements, there are also challenges in acquiring and processing data from a large number of ultrasound channels. The coarray (spatial convolution of the transmit and receive arrays) can be used to find efficient array designs that capture all of the spatial frequency content (a transmit-receive element combination corresponds to a spatial frequency) with a reduced number of active channels and firing events. Eliminating the redundancies in the transmit-receive element combinations and firing events reduces the overall system complexity and improves the frame rate. Here we explore four reduced redundancy 2-D array configurations for miniature 3-D ultrasonic imaging systems. Our approach is based on 1) coarray design with reduced redundancy using different subsets of linear arrays constituting the 2-D transducer array, and 2) 3-D scanning using fan-beams (narrow in one dimension and broad in the other dimension) generated by the transmit linear arrays. We form the overall array response through coherent summation of the individual responses of each transmit-receive array pairs. We present theoretical and simulated point spread functions of the array configurations along with quantitative comparison in terms of the front-end complexity and image quality.