Transducer for harmonic intravascular ultrasound imaging

A recent study has shown the feasibility of tissue harmonic imaging (THI) using an intravascular ultrasound (IVUS) transducer. This correspondence describes the design, fabrication, and characterization of a THI-optimized piezoelectric transducer with oval aperture of 0.75 mm by 1 mm. The transducer operated at 20 MHz and 40 MHz, and was comprised of a single piezoelectric layer with additional passive layers. The Krimholtz-Leedom-Matthaei (KLM) model was used to iteratively find optimal material properties of the different layers. The transducer characterization showed -6 dB fractional bandwidths of 30% and 25%, and two-way insertion losses of -20 dB and -36 dB, respectively.     

An integrated semicompliant balloon ultrasound catheter for quantitative feedback and image guidance during stent deployment

An integrated balloon ultrasound catheter prototype was designed to image from inside the balloon for real-time guidance during stent deployment. It was fabricated using a semicompliant balloon material (polyethylene) and a 20 MHz, 64-element circumferential ultrasound array. A commercial stent, nominally 4.4 mm in diameter and 12 mm in length, was used for a phantom study and placed along the length of the integrated balloon ultrasound catheter. A rubber phantom was created with an elastic modulus of 175 kPa with a 4.36 mm diameter lumen. Real-time balloon pressure measurements were recorded using a digital pressure sensor, and real-time radio-frequency (RF) data were captured as the balloon was inflated. The slope of the area-pressure ratio (APR) was compared to a reference measure of the balloon and stent expanded in water to determine a measure for optimal stent deployment. The results clearly indicate stent deployment at 11.1 atm using this metric. The APR slope could serve as quantitative feedback parameter for guiding stent deployment to reduce arterial injury and subsequent restenosis. After the stent deployment experiment, RF data were captured as the balloon catheter was moved along the length of the stent in pullback mode to confirm successful stent deployment. Ultimately, an integrated balloon ultrasound catheter could serve as a single catheter intervention device by providing real-time intravascular ultrasound (IVUS) imaging and quantitative feedback during stent deployment.     

Dual-mode IVUS catheter for intracranial image-guided hyperthermia: feasibility study

In this study, we investigated the feasibility of modifying 3-Fr IVUS catheters in several designs to potentially achieve minimally-invasive, endovascular access for image-guided ultrasound hyperthermia treatment of tumors in the brain. Using a plane wave approximation, target frequencies of 8.7 and 3.5 MHz were considered optimal for heating at depths (tumor sizes) of 1 and 2.5 cm, respectively. First, a 3.5-Fr IVUS catheter with a 0.7-mm diameter transducer (30 MHz nominal frequency) was driven at 8.6 MHz. Second, for a low-frequency design, a 220-μm-thick, 0.35 x 0.35-mm PZT-4 transducer--driven at width-mode resonance of 3.85 MHz--replaced a 40-MHz element in a 3.5-Fr coronary imaging catheter. Third, a 5 x 0.5-mm PZT-4 transducer was evaluated as the largest aperture geometry possible for a flexible 3-Fr IVUS catheter. Beam plots and on-axis heating profiles were simulated for each aperture, and test transducers were fabricated. The electrical impedance, impulse response, frequency response, maximum intensity, and mechanical index were measured to assess performance. For the 5 x 0.5-mm transducer, this testing also included mechanically scanning and reconstructing an image of a 2.5-cm-diameter cyst phantom as a preliminary measure of imaging potential.     

Pulse inversion sequences for mechanically scanned transducers

Mechanically scanned transducers are currently used for tissue harmonic imaging (THI) and nonlinear microbubble imaging at high frequencies. The pulse inversion (PI) technique is widely used for suppressing the fundamental signal, but its effectiveness is reduced by relative tissue/ transducer motion. In this paper, we investigate multipulse inversion (MPI) sequences that achieve a significant improvement on the fundamental suppression for mechanically scanned single-element transducers. MPI was subsequently applied on simulated and measured RF-data and relative fundamental suppression was compared with the 2-pulse PI technique. Simulations showed, for example, an increased fundamental suppression of 6 and 10 dB for MPI-sequences that combined 3 and 7 pulses, respectively, for a rotating intravascular ultrasound transducer with an interpulse angle of 0.15deg. Initial application of MPI sequences on RF-data from in vivo acquisitions resulted in similar fundamental suppression levels. The investigated MPI technique will help to reduce relative tissue/transducer motion effects and might lead to improved sensitivity and spatial resolution in nonlinear tissue imaging and improved microbubble detection in contrast imaging for mechanically scanned transducers.     

An integrated compliant balloon ultrasound catheter for intravascular strain imaging

An integrated compliant balloon ultrasound catheter was developed to allow greater deformations in strain imaging with intravascular ultrasound. A 64-element circumferential array was placed inside a compliant silicone balloon catheter to capture real-time, phase-sensitive radio frequency (RF) data during deformation experiments. Strains over 40% could be applied to normal arterial wall tissue with intracatheter pressures as low as 200 kPa (2 atm). Strain images of a hard-soft rubber phantom, thrombus, and fibrotic plaque were produced using the integrated balloon ultrasound catheter. Results show that this catheter can apply large deformations at low pressures and image various vascular pathologies ex vivo. Potentially, it can serve as a multifunctional, intravascular therapeutic device to guide angioplasty and stent deployment.     

Motion compensation for intravascular ultrasound palpography

Rupture of vulnerable plaques in coronary arteries is the major cause of acute coronary syndromes. Most vulnerable plaques consist of a thin fibrous cap covering an atheromous core. These plaques can be identified using intravascular ultrasound (IVUS) palpography, which measures radial strain by cross-correlating RF signals at different intraluminal pressures. Multiple strain images (i.e., partial palpograms) are averaged per heart cycle to produce a more robust compounded palpogram. However, catheter motion due to cardiac activity causes misalignment of the RF signals and thus of the partial palpograms, resulting in less valid strain estimates. To compensate for in-plane catheter rotation and translation, we devised four methods based on block matching. The global rotation block matching (GRBM) and contour mapping (CMAP) methods measure catheter rotation, and local block matching (LBM) and catheter rotation and translation (CRT) estimate displacements of local tissue regions. These methods were applied to nine in vivo pullback acquisitions, made with a 20 MHz phased-array transducer. We found that all these methods significantly increase the number of valid strain estimates in the partial and compounded palpograms (P < 0.008). The best method, LBM, attained an average increase of 17% and 15%, respectively. Implementation of this method should improve the information coming from IVUS palpography, leading to better vulnerable plaque detection.     

应用血管内超声与X射线造影图像融合的血管三维重建

针对X射线血管造影和血管内超声各自显示血管形态的局限以及互补性问题,提出将两种数据进行融合,准确重建血管的方法。首先从在超声导管回撤路径起点拍摄的两个角度的造影图像对中提取出导管并进行三维重建。然后采用基于snake模型的半自动方法从各帧超声图像中提取出血管壁的内外膜边缘。最后,在Frenet-Serret标架中确定各相邻帧超声图像间的相对方位后,利用非迭代的统计优化方法确定各帧超声图像沿导管轴向的绝对方位,完成两种数据的融合。采用临床数据的实验结果验证了算法的可行性,并分析了可能存在的误差和计算成本。     

High frequency nonlinear B-scan imaging of microbubble contrast agents

It was previously shown that it is possible to produce nonlinear scattering from microbubble contrast agents using transmit frequencies in the 14-32 MHz range, suggesting the possibility of performing high-frequency, nonlinear microbubble imaging. In this study, we describe the development of nonlinear microbubble B-scan imaging instrumentation capable of operating at transmit center frequencies between 10 and 50 MHz. The system underwent validation experiments using transmit frequencies of 20 and 30 MHz. Agent characterization experiments demonstrate the presence of nonlinear scattering for the conditions used in this study. Using wall-less vessel phantoms, nonlinear B-scan imaging is performed using energy in one of the subharmonic, ultraharmonic, and second harmonic frequency regions for transmit frequencies of 20 and 30 MHz. Both subharmonic and ultraharmonic imaging modes achieved suppression of tissue signals to below the noise floor while achieving contrast to noise ratios of up to 26 and 17 dB, respectively. The performance of second harmonic imaging was compromised by nonlinear propagation and offered no significant contrast improvement over fundamental mode imaging. In vivo experiments using the subharmonic of a 20 MHz transmit pulse show the successful detection of microvessels in the rabbit ear and in the mouse heart. The results of this study demonstrate the feasibility of nonlinear microbubble imaging at high frequencies     

Intravascular photoacoustic imaging using an IVUS imaging catheter

Catheter-based imaging of atherosclerosis with high resolution, albeit invasive, is extremely important for screening and characterization of vulnerable plaques. Currently, there is a need for an imaging technique capable of providing comprehensive morphological and functional information of plaques. In this paper, we present an intravascular photoacoustic imaging technique to characterize vulnerable plaques by using optical absorption contrast between normal tissue and atherosclerotic lesions. Specifically, we investigate the feasibility of obtaining intravascular photoacoustic (IVPA) images using a high-frequency intravascular ultrasound (IVUS) imaging catheter. Indeed, the combination of IVPA imaging with clinically available IVUS imaging may provide desired functional and morphological assessment of the plaque. The imaging studies were performed with tissue-mimicking arterial vessel phantoms and excised samples of rabbit artery. The results of our study suggest that catheter-based intravascular photoacoustic imaging is possible, and the combination of IVPA with IVUS has the potential to detect and differentiate atherosclerosis based on both the structure and composition of the plaque.     

High-resolution ultrasonic imaging using fast two-dimensional homomorphic filtering.

A new method for two-dimensional deconvolution of medical ultrasonic images is presented. The spatial resolution of the deconvolved images is much higher compared to the common images of the fundamental and second harmonic. The deconvolution also results in a more distinct speckle pattern. Unlike the most published deconvolution algorithms for ultrasonic images, the presented technique can be implemented using currently available hardware in real-time imaging, with a rate up to 50 frames per second. This makes it attractive for application in the current ultrasound scanners. The algorithm is based on two-dimensional homomorphic deconvolution with simplified assumptions about the point spread function. Broadband radio frequency image data are deconvolved instead of common fundamental harmonic data. Thus, information of both the first and second harmonics is used. The method was validated on image data recorded from a tissue-mimicking phantom and on clinical image data.     

High-resolution ultrasonic imaging using two-dimensional homomorphic filtering

A new method for two-dimensional deconvolution of medical ultrasonic images is presented. The spatial resolution of the deconvolved images is much higher compared to the common images of the fundamental and second harmonic. The deconvolution also results in a more distinct speckle pattern. Unlike the most published deconvolution algorithms for ultrasonic images, the presented technique can be implemented using currently available hardware in real-time imaging, with a rate up to 50 frames per second. This makes it attractive for application in the current ultrasound scanners. The algorithm is based on two-dimensional homomorphic deconvolution with simplified assumptions about the point spread function. Broadband radio frequency image data are deconvolved instead of common fundamental harmonic data. Thus, information of both the first and second harmonics is used. The method was validated on image data recorded from a tissue-mimicking phantom and on clinical image data.     

Intravascular ultrasound detection and delivery of molecularly targeted microbubbles for gene delivery

We are investigating the combination of microbubble-based targeted drug delivery and intravascular ultrasound (IVUS) imaging as a potential therapy to reduce incidence of restenosis following stent placement in atherosclerotic coronary arteries. The goal of these studies was to determine whether IVUS could be used to detect targeted microbubbles and enhance drug/gene delivery through targeting. Quiescent vascular smooth muscle cells (SMCs) were stimulated with cytokine IL-1β to induce the inflammatory cell surface marker vascular cell adhesion molecule 1 (VCAM-1). Molecular-targeted (VCAM-1 Ab or IgG control Ab), fluorescent-labeled microbubbles were conjugated with plasmid DNA expressing green fluorescent protein (GFP, pMax-GFP) and exposed to the inflamed SMCs under flow to measure adhesion compared with control microbubbles. Gene delivery was performed using a modified IVUS catheter to generate 1.5-MHz ultrasound at 200 kPa. Detection of adherent microbubbles to inflamed SMCs in culture and flow chambers was measured using an IVUS catheter and scanner. VCAM-1-targeted microbubbles enhanced adhesion to inflamed SMCs 100-fold over nontargeted microbubbles. Compared with noninflamed SMCs, VCAM-1-targeted microbubbles exhibited a 7.9-fold increase in adhesion to IL-1β-treated cells. Targeted microbubbles resulted in a 5.5-fold increase in plasmid DNA transfection over nontargeted microbubbles in conjunction with a focused 2.54-cm (1-in) diameter 1-MHz transducer and also enhanced transfection by the modified IVUS transducer at 1.5 MHz. Targeted microbubbles (at a density of 3 × 10? microbubbles/mm2) increased IVUS image intensity 13.2 dB over non-microbubble-coated surfaces. Rupture of microbubbles from the modified IVUS transducer resulted in a 53% reduction in image intensity. Taken together, these results indicate that IVUS may be used to detect targeted microbubbles to inflamed vasculature and subsequently deliver a gene/drug locally.     

Identification of vulnerable atherosclerotic plaque using IVUS-based thermal strain imaging

Pathology and autopsy studies have demonstrated that sudden disruption of vulnerable atherosclerotic plaque is responsible for most acute coronary syndromes. These plaques are characterized by a lipid-rich core with abundant inflammatory cells and a thin fibrous cap. Thermal strain imaging (TSI) using intravascular ultrasound (IVUS) has been proposed for high-risk arterial plaque detection, in which image contrast results from the temperature dependence of sound speed. It has the potential to distinguish a lipid-laden lesion from the arterial vascular wall due to its strong contrast between water-bearing and lipid-bearing tissue. Initial simulations indicate plaque identification is possible for a 1 degrees C temperature rise. A phantom experiment using an IVUS imaging array further supports the concept, and results agree reasonably well with prediction.     

Experimental investigation of finite amplitude distortion-based, second harmonic pulse echo ultrasonic imaging

The computational predictions for the imaging potential of the second harmonic produced by finite amplitude distortion were investigated with a simple experiment. A focused transducer containing concentric 2.5 MHz and 5.0 MHz elements was used to obtain a sequence of radio-frequency (r-f) backscattered signals using a tissue equivalent phantom. The 2.5 MHz element was used as the transmitter and the 5.0 MHz element was used as the receiver. At 0.68 cm in front of the geometric focal point of the transducer, the phantom contained a 0.6 cm diameter cylindrical volume which contained no scatterers. Each of these r-f signals was then processed to produce the corresponding fundamental (2.5 MHz-centered) and second harmonic (5.0 MHz-centered) envelopes. The contrast resolution obtained for the scatterer-free or cyst region of the envelopes was compared against the computed prediction and good agreement was obtained. The results of this experiment also suggest that the simple one-pulse scheme may be adequate for second harmonic imaging.     

Low temperature fabrication of immersion capacitive micromachined ultrasonic transducers on silicon and dielectric substrates

A maximum processing temperature of 250/spl deg/C is used to fabricate capacitive micromachined ultrasonic transducers (CMUTs) on silicon and quartz substrates for immersion applications. Fabrication on silicon provides a means for electronics integration via post-complementary metal oxide semiconductor (CMOS) processing without sacrificing device performance. Fabrication on quartz reduces parasitic capacitance and allows the use of optical displacement detection methods for CMUTs. The simple, low-temperature process uses metals both as the sacrificial layer for improved dimensional control, and as the bottom electrode for good electrical conductivity and optical reflectivity. This, combined with local sealing of the vacuum cavity by plasma-enhanced chemical-vapor deposition of silicon nitride, provides excellent control of lateral and vertical dimensions of the CMUTs for optimal device performance. In this paper, the fabrication process is described in detail, including process recipes and material characterization results. The CMUTs fabricated for intravascular ultrasound (IVUS) imaging in the 10-20 MHz range and interdigital CMUTs for microfluidic applications in the 5-20 MHz range are presented as device examples. Intra-array and wafer-to-wafer process uniformity is evaluated via electrical impedance measurements on 64-element ring annular IVUS imaging arrays fabricated on silicon and quartz wafers. The resonance frequency in air and collapse voltage variations are measured to be within 1% and 5%, respectively, for both cases. Acoustic pressure and pulse echo measurements also have been performed on 128 /spl mu/m/spl times/32 /spl mu/m IVUS array elements in water, which reveal a performance suitable for forward-looking IVUS imaging at about 16 MHz.     

Dependence of the frequency spectrum of small amplitude vibrations superimposed on finite deformations of a nonlinear, cylindrical elastic body on residual stress

We model and analyze the response of nonlinear, residually stressed elastic bodies subjected to small amplitude vibrations superimposed upon large deformations. The problem derives from modeling the use of intravascular ultrasound (IVUS) imaging to interrogate atherosclerotic plaques in vivo in large arteries. The goal of this investigation is twofold: (i) introduce a modeling framework for residual stress that unlike traditional Fung type classical opening angle models may be used for a diseased artery, and (ii) investigate the sensitivity of the spectra of small amplitude high frequency time harmonic vibrations superimposed on a large deformation to the details of the residual stress stored in arteries through a numerical simulation using physiologic parameter values under both low and high blood pressure loadings. The modeling framework also points the way towards an inverse problem using IVUS techniques to estimate residual stress in healthy and diseased arteries.     

Native tissue imaging at superharmonic frequencies

The second harmonic imaging mode has been adapted to image tissue and shown considerable improvements in image quality in several applications compared to the fundamental mode. The improvements were attributed to the effects of wave distortion due to nonlinear propagation in tissue. However, imaging tissue at the second harmonic frequency only has various drawbacks. Because the energy in the second harmonic frequency band is much lower than that in the fundamental frequency band, there must be excellent sensitivity and dynamic range in the receiving system to achieve an acceptable amount of signal-to-noise ratio. To increase the sensitivity, the spectral overlap between the fundamental and the second harmonic has to be diminished, which in return deteriorates the imaging resolution. Consequently, a trade-off is mandatory between resolution and sensitivity. Using simulations and measurements, we show that, at appropriate scanning acoustic settings, higher harmonics are generated in tissue. The higher harmonics represent additional, relevant information for tissue imaging and characterization. An elegant way to take advantage of the higher harmonics and to bring all the information together is to combine and incorporate all the multiple higher harmonics into a single component that we call the superharmonic component. Using a newly developed array transducer having a wide frequency band, B-mode images of a phantom were made in the superharmonic mode transmitting at 1.2 MHz. These images have exceptionally improved clarity and yield a dramatically cleaner and sharper contrast between the different structures being imaged. In addition to increased signal-to-noise ratio, superharmonic imaging shows better contrast and axial resolution as well as acceptable penetration depth.     

Annular-ring CMUT arrays for forward-looking IVUS: transducer characterization and imaging

In this study, a 64-element, 1.15-mm diameter annular-ring capacitive micromachined ultrasonic transducer (CMUT) array was characterized and used for forward-looking intravascular ultrasound (IVUS) imaging tests. The array was manufactured using low-temperature processes suitable for CMOS electronics integration on a single chip. The measured radiation pattern of a 43 X 140-microm2 array element depicts a 40 degrees view angle for forward-looking imaging around a 15-MHz center frequency in agreement with theoretical models. Pulse-echo measurements show a -10-dB fractional bandwidth of 104% around 17 MHz for wire targets 2.5 mm away from the array in vegetable oil. For imaging and SNR measurements, RF A-scan data sets from various targets were collected using an interconnect scheme forming a 32-element array configuration. An experimental point spread function was obtained and compared with simulated and theoretical array responses, showing good agreement. Therefore, this study demonstrates that annular-ring CMUT arrays fabricated with CMOS-compatible processes are capable of forward-looking IVUS imaging, and the developed modeling tools can be used to design improved IVUS imaging arrays.     

High-frequency membrane hydrophone

A membrane hydrophone with a 37-μm diameter spot poled electrode has been fabricated on a 4-μm-thick film of the piezoelectric copolymer, polyvinylidene fluoride trifluoroethylene (PVDF-TrFE), and initially characterized. The hydrophone has an effective spot size of less than 100 μm, an on-membrane +7-dB gain buffer amplifier, and a -3-dB bandwidth of 150 MHz. The acoustic properties of the hydrophone were investigated with a transducer equivalent circuit model, the electric fringe fields due to poling were characterized with a finite difference electrostatic field model, and the effective spot diameters 2a₃ and 2a₆ were estimated. Measurements on the bandwidth, effective spot size, and sensitivity are presented. This hydrophone appears suitable for the characterization of both the frequency and spatial parameters of high-frequency transducers such as intravascular ultrasound (IVUS) catheter transducers operating in the 10-40 MHz range     

Optimizing the beam pattern of a forward-viewing ring-annular ultrasound array for intravascular imaging

Intravascular ultrasound (IVUS) imaging systems using circumferential arrays mounted on cardiac catheter tips fire beams orthogonal to the principal axis of the catheter. The system produces high resolution cross-sectional images but must be guided by conventional angioscopy. A real-time forward-viewing array, integrated into the same catheter, could greatly reduce radiation exposure by decreasing angiographic guidance. Unfortunately, the mounting requirement of a catheter guide wire prohibits a full-disk imaging aperture. Given only an annulus of array elements, prior theoretical investigations have only considered a circular ring of point transceivers and focusing strategies using all elements in the highly dense array, both impractical assumptions. In this paper, we consider a practical array geometry and signal processing architecture for a forward-viewing IVUS system. Our specific design uses a total of 210 transceiver firings with synthetic reconstruction for a given 3-D image frame. Simulation results demonstrate this design can achieve side-lobes under -40 dB for on-axis situations and under -30 dB for steering to the edge of a 60/spl deg/ cone.