State of the Art: Contrast Enhanced 4D Ultrasound to Monitor or Assess Locoregional Therapies

Locoregional therapies (LRTs) are an essential management tool in the treatment of primary liver cancers or metastatic liver disease. LRTs include curative and palliative modalities. Monitoring treatment response of LRTs is crucial for maximizing benefit and improving clinical outcomes. Clinical use of contrast-enhanced ultrasound (CEUS) was introduced more than two decades ago. Its portability, cost effectiveness, lack of contraindications and safety make it an ideal tool for treatment monitoring in numerous situations. Two-dimensional dynamic CEUS has been proved to be equivalent to the current imaging standard in the guidance of LRTs, assessment of their adequacy, and detection of early tumor recurrence. Recent technical advances in ultrasound transducers and image processing have made 3D CEUS scanning widely available on most commercial ultrasound systems. 3D scanning offers a broad multiplanar view of anatomic structures, overcoming many limitations of two-dimensional scanning. Furthermore, many ultrasound systems provide real-time dynamic 3D CEUS, also known as 4D CEUS. Volumetric CEUS has shown to perform better than 2D CEUS in the assessment and monitoring of some LRTs. CEUS presents a valid alternative to the current imaging standards with reduced cost and decreased risk of complications. Future efforts will be directed toward refining the utility of 4D CEUS through approaches such as multi-parametric quantitative analysis and machine learning algorithms.

A Wideband Noise and Harmonic Distortion Canceling Low-Noise Amplifier for High-Frequency Ultrasound Transducers

This paper presents a wideband low-noise amplifier (LNA) front-end with noise and distortion cancellation for high-frequency ultrasound transducers. The LNA employs a resistive shunt-feedback structure with a feedforward noise-canceling technique to accomplish both wideband impedance matching and low noise performance. A complementary CMOS topology was also developed to cancel out the second-order harmonic distortion and enhance the amplifier linearity. A high-frequency ultrasound (HFUS) and photoacoustic (PA) imaging front-end, including the proposed LNA and a variable gain amplifier (VGA), was designed and fabricated in a 180 nm CMOS process. At 80 MHz, the front-end achieves an input-referred noise density of 1.36 nV/sqrt (Hz), an input return loss (S11) of better than −16 dB, a voltage gain of 37 dB, and a total harmonic distortion (THD) of −55 dBc while dissipating a power of 37 mW, leading to a noise efficiency factor (NEF) of 2.66.

Enhancing AlN PMUTs’ Acoustic Responsivity within a MEMS-on-CMOS Process

In this paper, guidelines for the optimization of piezoelectrical micromachined ultrasound transducers (PMUTs) monolithically integrated over a CMOS technology are developed. Higher acoustic pressure is produced by PMUTs with a thin layer of AlN piezoelectrical material and Si3N4 as a passive layer, as is studied here with finite element modeling (FEM) simulations and experimental characterization. Due to the thin layers used, parameters such as residual stress become relevant as they produce a buckled structure. It has been reported that the buckling of the membrane due to residual stress, in general, reduces the coupling factor and consequently degrades the efficiency of the acoustic pressure production. In this paper, we show that this buckling can be beneficial and that the fabricated PMUTs exhibit enhanced performance depending on the placement of the electrodes. This behavior was demonstrated experimentally and through FEM. The acoustic characterization of the fabricated PMUTs shows the enhancement of the PMUT performance as a transmitter (with 5 kPa V−1 surface pressure for a single PMUT) and as a receiver (12.5 V MPa−1) in comparison with previously reported devices using the same MEMS-on-CMOS technology as well as state-of-the-art devices.

ZnO thin-film optimization towards the fabrication of high-frequency ultrasound transducers

<p>Zinc oxide is a popular wide bandgap semiconductor material with versatile electrical and optical properties. In its wurtzite crystal form, this semiconductor is piezoelectric, and has material properties that make it an attractive candidate for fabricating high frequency ultrasound transducers. This thesis describes the development of an RF sputtering process for creating zinc oxide films with thicknesses ranging from 3μm to 10μm, aiming for transducer frequencies of 300MHz to 1 GHz. Sputtering parameters are optimized to meet the dual requirements of a c-axis film orientation while maintaining a high deposition rate. These constraints and the dimensional characteristics of the utilized sputtering system, such as the short substrate-to-target distance, introduce high levels of strain in the deposited zinc oxide films. Various anneal procedures are developed to reduce film strain and optimize the resulting microstructure. It is found that annealing temperatures > 600°C eliminate the inherent film strain, but simultaneously result in the dewetting of the bottom metal contact, making this thermal treatment unsuitable for device processing. As an alternative to traditional metal contacts used in ultrasound transducers, the use of highly doped zinc oxide contacts is then investigated. It is shown that aluminium doped zinc oxide contacts provide an improved seed layer for device growth while eliminating the dewetting problems associated with metal contacts at high anneal temperatures. In addition, the use of such transparent conductive oxide contacts can lead to novel ultrasound applications, which benefit from the integration of optical and acoustic imaging in a single lens. A proof of concept all-zinc oxide single element ultrasound transducer structure is finally fabricated, to highlight the potential of an integrated optical-acoustic lens design.</p>

ZnO thin-film optimization towards the fabrication of high-frequency ultrasound transducers

<p>Zinc oxide is a popular wide bandgap semiconductor material with versatile electrical and optical properties. In its wurtzite crystal form, this semiconductor is piezoelectric, and has material properties that make it an attractive candidate for fabricating high frequency ultrasound transducers. This thesis describes the development of an RF sputtering process for creating zinc oxide films with thicknesses ranging from 3μm to 10μm, aiming for transducer frequencies of 300MHz to 1 GHz. Sputtering parameters are optimized to meet the dual requirements of a c-axis film orientation while maintaining a high deposition rate. These constraints and the dimensional characteristics of the utilized sputtering system, such as the short substrate-to-target distance, introduce high levels of strain in the deposited zinc oxide films. Various anneal procedures are developed to reduce film strain and optimize the resulting microstructure. It is found that annealing temperatures > 600°C eliminate the inherent film strain, but simultaneously result in the dewetting of the bottom metal contact, making this thermal treatment unsuitable for device processing. As an alternative to traditional metal contacts used in ultrasound transducers, the use of highly doped zinc oxide contacts is then investigated. It is shown that aluminium doped zinc oxide contacts provide an improved seed layer for device growth while eliminating the dewetting problems associated with metal contacts at high anneal temperatures. In addition, the use of such transparent conductive oxide contacts can lead to novel ultrasound applications, which benefit from the integration of optical and acoustic imaging in a single lens. A proof of concept all-zinc oxide single element ultrasound transducer structure is finally fabricated, to highlight the potential of an integrated optical-acoustic lens design.</p>

Microstructural control of ZnO films deposited by RF magnetron sputtering for ultrasound transducers

<p>The aim of this study was to develop a deposition process using RF magnetron sputtering for the production of zinc oxide (ZnO) thin films on glass substrates. These ZnO films were to be used as the active piezoelectric element in very high frequency ultrasound transducers (> 300 MHz). In order to achieve piezoelectric activity the films had to be oriented with the c-axis of the ZnO grains perpendicular to the substrate surface. At the same time, a moderately high, at least 1 m=hr (17 nm=min) deposition rate was required for the production of practical devices. Prior to a full investigation into the sputtering parameters, an initial evaluation of the HHV Auto500 RF magnetron sputter coater system was performed. Using the original chamber configuration it was not possible to deposit ZnO at the required deposition rates. A modification of the growth chamber to allow a reduced target-substrate distance was successful in producing ZnO films at the required deposition rates. A systematic study into the deposition parameters and their effect on the ZnO film quality and deposition rates was then performed and it was found that strong c-axis oriented films could be deposited only when depositing at rates below 15 nm=min at a low substrate temperature (< 50 C). Depositions above this rate resulted in the growth of polycrystalline films. A two-step deposition process was designed to preserve c-axis orientation at high deposition rates up to 28 nm=min. The ZnO films were found to be highly strained due to inherent stress from the sputtering process. The deposition pressure was identified as the most critical deposition parameter for stress control. It was found that deposition above a critical pressure of 1:2 x10-² mbar was essential to prevent mechanical failure of the films. Post growth annealing was investigated and determined to be a viable technique to relax stress and improve the crystalline quality of the films. Finally a four-step deposition process was proposed to facilitate the growth of c-axis oriented ZnO films at relatively high deposition rates whilst minimising film stress.</p>

Microstructural control of ZnO films deposited by RF magnetron sputtering for ultrasound transducers

<p>The aim of this study was to develop a deposition process using RF magnetron sputtering for the production of zinc oxide (ZnO) thin films on glass substrates. These ZnO films were to be used as the active piezoelectric element in very high frequency ultrasound transducers (> 300 MHz). In order to achieve piezoelectric activity the films had to be oriented with the c-axis of the ZnO grains perpendicular to the substrate surface. At the same time, a moderately high, at least 1 m=hr (17 nm=min) deposition rate was required for the production of practical devices. Prior to a full investigation into the sputtering parameters, an initial evaluation of the HHV Auto500 RF magnetron sputter coater system was performed. Using the original chamber configuration it was not possible to deposit ZnO at the required deposition rates. A modification of the growth chamber to allow a reduced target-substrate distance was successful in producing ZnO films at the required deposition rates. A systematic study into the deposition parameters and their effect on the ZnO film quality and deposition rates was then performed and it was found that strong c-axis oriented films could be deposited only when depositing at rates below 15 nm=min at a low substrate temperature (< 50 C). Depositions above this rate resulted in the growth of polycrystalline films. A two-step deposition process was designed to preserve c-axis orientation at high deposition rates up to 28 nm=min. The ZnO films were found to be highly strained due to inherent stress from the sputtering process. The deposition pressure was identified as the most critical deposition parameter for stress control. It was found that deposition above a critical pressure of 1:2 x10-² mbar was essential to prevent mechanical failure of the films. Post growth annealing was investigated and determined to be a viable technique to relax stress and improve the crystalline quality of the films. Finally a four-step deposition process was proposed to facilitate the growth of c-axis oriented ZnO films at relatively high deposition rates whilst minimising film stress.</p>

Development of an Instantaneous Velocity-Vector-Profile Method Using Conventional Ultrasonic Transducers

The velocity vector profile technique based on an ultrasound pulsed Doppler method can enrich the information of a flow field, however, it has shown a low availability because a new design of special transducers is required for each measurement case. This study proposes a new method of profiling the velocity vectors using conventional ultrasound transducers that are widely supplied to UVP (Ultrasound velocity profile) users. We constructed a configuration of the transducers to minimize the uncertainty of the detection points at the receivers, and a measurable distance was theoretically determined by the configuration. Two feasibility tests were carried out. One was a test for the assessment of the measurable distance, which agreed well with the theoretical distance. The other was the evaluation of the measurement of two-dimensional velocity vectors by the new method and it was performed in a towing tank facility without the velocity fluctuation. From the evaluation, it was confirmed that the measured vectors showed good agreement to the reference values, and their accuracy and precision were competitive compared to previous studies. The developed method was applied to two unsteady flows for demonstrations. The results clarified that the proposed method guarantees high availability and accuracy for the velocity vector profiles.

INNV-36. NON-INTRUSIVE, NON-INVASIVE AND PATIENT FRIENDLY FOCUSED ULTRASOUND DEVICE AS A DELIVERY VEHICLE FOR CNS TUMORS

A major impediment to treatment of brain cancers is the inability to transport drugs across the blood-brain barrier (BBB). The development of an effective, targeted, and non-invasive method to penetrate the BBB to deliver cancer therapeutics is an unmet need in the treatment of brain cancers. Large molecular weight chemo- and immuno-therapies such as doxorubicin and others may be potentially effective against brain cancers if such drugs are sufficiently bioavailable in the brain. Focused ultrasound techniques can safely and transiently open the BBB but current techniques require invasive/intrusive or expensive and high-touch procedures and are not optimal for wide adoption. To address this unmet need, we are developing an innovative technique to non-intrusively, non-invasively and transiently open the BBB in a specified location within the brain using guided ultrasound (US). Our device consists of a proprietary US generator that is controlled by a highly portable system that has a small physical footprint, enabling the US generator and system to be placed in confined spaces such as chemotherapy infusion centers. The US generator is cap-shaped device that is placed on a patient’s head that includes multiple sets of ultrasound transducers that are distributed within the cap according to the anatomy of the skull. With our proprietary technique, we calculate the position of the cap in relation to the internal anatomy in a real-time manner and in a non-intrusive and a non-invasive manner. We have recently concluded an extensive study that resulted in algorithms that can accurately guide the US to various targets within the brain across a spectrum of patients. We also have completed a pilot preclinical study on a large animal demonstrating our ability to open the BBB non-invasively and deposit a drug proxy (gadolinium and Evans Blue).