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.     

Improving IVUS palpography by incorporation of motion compensation based on block matching and optical flow

Intravascular ultrasound (IVUS) strain imaging of the luminal layer in coronary arteries, coined as IVUS palpography, utilizes conventional radio frequency (RF) signals acquired at 2 different levels of a compressional load. The signals are cross-correlated to obtain the microscopic tissue displacements, which can be directly translated into local strain of the vessel wall. However, (apparent) tissue motion and nonuniform deformation of the vessel wall, due to catheter wiggling, reduce signal correlation and result in invalid strain estimates. Implications of probe motion were studied on the tissue-mimicking phantom. The measured circumferential tissue displacement and level of the speckle decorrelation amounted to 12° and 0.58, respectively, for the catheter displacement of 456 μm. To compensate for the motion artifacts in IVUS palpography, a novel method based on the feature-based scale-space optical flow (OF), and classical block matching (BM) algorithm, were employed. The computed OF vector and BM displacement fields quantify the amount of local tissue misalignment in consecutive frames. Subsequently, the extracted circumferential displacements are used to realign the signals before strain computation. Motion compensation reduces the RF signal decorrelation and increases the number of valid strain estimates. The advantage of applying the motion correction in IVUS palpography was demonstrated in a midscale validation study on 14 in vivo pullbacks. Both methods substantially increase the number of valid strain estimates in the partial and compounded palpograms. Mean relative improvement in the number of valid strain estimates with motion compensation in comparison to one without motion compensation amounts to 28% and 14%, respectively. Implementation of motion compensation methods boosts the diagnostic value of IVUS palpography.     

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.     

Image-based cardiac phase retrieval in intravascular ultrasound sequences

Longitudinal motion during in vivo pullbacks acquisition of intravascular ultrasound (IVUS) sequences is a major artifact for 3-D exploring of coronary arteries. Most current techniques are based on the electrocardiogram (ECG) signal to obtain a gated pullback without longitudinal motion by using specific hardware or the ECG signal itself. We present an image-based approach for cardiac phase retrieval from coronary IVUS sequences without an ECG signal. A signal reflecting cardiac motion is computed by exploring the image intensity local mean evolution. The signal is filtered by a band-pass filter centered at the main cardiac frequency. Phase is retrieved by computing signal extrema. The average frame processing time using our setup is 36 ms. Comparison to manually sampled sequences encourages a deeper study comparing them to ECG signals.     

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.     

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.     

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.     

Intravascular ultrasound tissue harmonic imaging in vivo

Tissue harmonic imaging (THI) has been shown to increase image quality of medical ultrasound in the frequency range from 2 to 10 MHz and might, therefore, also be used to improve image quality in intravascular ultrasound (IVUS). In this study we constructed a prototype IVUS system that could operate in both fundamental frequency and second harmonic imaging modes. This system uses a conventional, continuously rotating, single-element IVUS catheter and was operated in fundamental 20 MHz, fundamental 40 MHz, and harmonic 40 MHz modes (transmit 20 MHz, receive 40 MHz). Hydrophone beam characterization measurements demonstrated the build-up of a second harmonic signal as a function of increasing pressure. Imaging experiments were conducted in both a tissue-mimicking phantom and in an atherosclerotic animal model in vivo. Acquisitions of fundamental 20 and 40 MHz and second harmonic acquisitions resulted in cross sections of the phantom and a rabbit aorta. The harmonic results of the imaging experiments showed the feasibility of intravascular THI with a conventional IVUS catheter both in a phantom and in vivo. The harmonic acquisitions also showed the potential of THI to reduce image artifacts compared to fundamental 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.     

On the effects of reflected waves in transient shear wave elastography

In recent years, novel quantitative techniques have been developed to provide noninvasive and quantitative stiffness images based on shear wave propagation. Using radiation force and ultrafast ultrasound imaging, the supersonic shear imaging technique allows one to remotely generate and follow a transient plane shear wave propagating in vivo in real time. The tissue shear modulus, i.e., its stiffness, can then be estimated from the shear wave local velocity. However, because the local shear wave velocity is estimated using a time-of- flight approach, reflected shear waves can cause artifacts in the estimated shear velocity because the incident and reflected waves propagate in opposite directions. Such effects have been reported in the literature as a potential drawback of elastography techniques based on shear wave speed, particularly in the case of high stiffness contrasts, such as in atherosclerotic plaque or stiff lesions. In this letter, we present our implementation of a simple directional filter, previously used for magnetic resonance elastography, which separates the forward- and backward-propagating waves to solve this problem. Such a directional filter could be applied to many elastography techniques based on the local estimation of shear wave speed propagation, such as acoustic radiation force imaging (ARFI), shearwave dispersion ultrasound vibrometry (SDUV), needle-based elastography, harmonic motion imaging, or crawling waves when the local propagation direction is known and high-resolution spatial and temporal data are acquired.     

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.     

Synthetic aperture-based beam compression for intravascular ultrasound imaging

In this paper, intravascular ultrasound (IVUS) images acquired with a 64-element array transducer using a multistatic acquisition scheme are presented. The images are reconstructed from a collection of pulse-echo measurements using a synthetic aperture array imaging technique. The main limitations of IVUS imaging are a poor lateral resolution and elevated grating lobes caused by the imaging geometry. We propose a Synthetic Aperture Focusing Technique (SAFT), which uses a limited number of A-scan signals. The focusing process, which is performed in the Fourier domain, requires far less computation time than conventional delay-and-sum methods. Two different reconstruction kernel functions have been derived and are compared for the processing of experimental data     

Compressive imaging system design using task-specific information

We present a task-specific information (TSI) based framework for designing compressive imaging (CI) systems. The task of target detection is chosen to demonstrate the performance of the optimized CI system designs relative to a conventional imager. In our optimization framework, we first select a projection basis and then find the associated optimal photon-allocation vector in the presence of a total photon-count constraint. Several projection bases, including principal components (PC), independent components, generalized matched-filter, and generalized Fisher discriminant (GFD) are considered for candidate CI systems, and their respective performance is analyzed for the target-detection task. We find that the TSI-optimized CI system design based on a GFD projection basis outperforms all other candidate CI system designs as well as the conventional imager. The GFD-based compressive imager yields a TSI of 0.9841 bits (out of a maximum possible 1 bit for the detection task), which is nearly ten times the 0.0979 bits achieved by the conventional imager at a signal-to-noise ratio of 5.0. We also discuss the relation between the information-theoretic TSI metric and a conventional statistical metric like probability of error in the context of the target-detection problem. It is shown that the TSI can be used to derive an upper bound on the probability of error that can be attained by any detection algorithm.     

Monitoring of thermal therapy based on shear modulus changes: II. Shear wave imaging of thermal lesions

The clinical applicability of high-intensity focused ultrasound (HIFU) for noninvasive therapy is currently hampered by the lack of robust and real-time monitoring of tissue damage during treatment. The goal of this study is to show that the estimation of local tissue elasticity from shear wave imaging (SWI) can lead to a precise mapping of the lesion. HIFU treatment and monitoring were respectively performed using a confocal setup consisting of a 2.5-MHz single element transducer focused at 34 mm on ex vivo samples and an 8-MHz ultrasound diagnostic probe. Ultrasound-based strain imaging was combined with shear wave imaging on the same device. The SWI sequences consisted of 2 successive shear waves induced at different lateral positions. Each wave was created with pushing beams of 100 μs at 3 depths. The shear wave propagation was acquired at 17,000 frames/s, from which the elasticity map was recovered. HIFU sonications were interleaved with fast imaging acquisitions, allowing a duty cycle of more than 90%. Thus, elasticity and strain mapping was achieved every 3 s, leading to real-time monitoring of the treatment. When thermal damage occurs, tissue stiffness was found to increase up to 4-fold and strain imaging showed strong shrinkages that blur the temperature information. We show that strain imaging elastograms are not easy to interpret for accurate lesion characterization, but SWI provides a quantitative mapping of the thermal lesion. Moreover, the concept of shear wave thermometry (SWT) developed in the companion paper allows mapping temperature with the same method. Combined SWT and shear wave imaging can map the lesion stiffening and temperature outside the lesion, which could be used to predict the eventual lesion growth by thermal dose calculation. Finally, SWI is shown to be robust to motion and reliable in vivo on sheep muscle.     

Reduced peak-hopping artifacts in ultrasonic strain estimation using the Viterbi algorithm

Internal strain resulting from tissue deformation can be estimated by correlation processing of speckle patterns within complex (i.e., radio frequency) ultrasound images acquired during deformation. At large deformations, the magnitude of the correlation coefficient peak can be significantly lower than unity, so that random speckle correlations will exceed the true peak. This effect is called ?peak hopping? and causes significant errors in displacement and deformation estimates. Here we investigate the Viterbi algorithm, a dynamic programming procedure, to overcome peak-hopping artifacts by finding the most likely sequence of hidden states in a sequence of observed events. It is well suited to motion estimation in elasticity- imaging studies because adjacent tissue elements remain adjacent following deformation. Particularly, tissue elements along an ultrasonic beam in one image lie along a 3-D continuous curve in the next image instant. The observed event in this case is the correlation coefficient of a pixel at a certain displacement. Radio-frequency data were generated before and after deformation with an average strain of 6%. Simulations were performed for a homogenous medium and for a medium with a stiffer inclusion. Results show that Viterbi processing of speckle-tracking outputs can significantly reduce peak-hopping artifacts.     

Monitoring of thermal therapy based on shear modulus changes: I. shear wave thermometry

The clinical applicability of high-intensity focused ultrasound (HIFU) for noninvasive therapy is today hampered by the lack of robust and real-time monitoring of tissue damage during treatment. The goal of this study is to show that the estimation of local tissue elasticity from shear wave imaging (SWI) can lead to the 2-D mapping of temperature changes during HIFU treatments. This new concept of shear wave thermometry is experimentally implemented here using conventional ultrasonic imaging probes. HIFU treatment and monitoring were, respectively, performed using a confocal setup consisting of a 2.5-MHz single-element transducer focused at 30 mm on ex vivo samples and an 8-MHz ultrasound diagnostic probe. Thermocouple measurements and ultrasound-based thermometry were used as a gold standard technique and were combined with SWI on the same device. The SWI sequences consisted of 2 successive shear waves induced at different lateral positions. Each wave was created using 100-μs pushing beams at 3 depths. The shear wave propagation was acquired at 17,000 frames/s, from which the elasticity map was recovered. HIFU sonications were interleaved with fast imaging acquisitions, allowing a duty cycle of more than 90%. Elasticity and temperature mapping was achieved every 3 s, leading to realtime monitoring of the treatment. Tissue stiffness was found to decrease in the focal zone for temperatures up to 43°C. Ultrasound-based temperature estimation was highly correlated to stiffness variation maps (r2 = 0.91 to 0.97). A reversible calibration phase of the changes of elasticity with temperature can be made locally using sighting shots. This calibration process allows for the derivation of temperature maps from shear wave imaging. Compared with conventional ultrasound-based approaches, shear wave thermometry is found to be much more robust to motion artifacts.     

漫反射光谱测量压力作用下皮肤组织中水含量变化

在体漫反射光谱测量中常采用接触式测量方式,光纤测头压力对测量精度有很大影响.本文基于生物组织固液两相模型,研究了光纤测头压力作用下组织形变和成分变化机理.分别测量生物组织随压力大小和作用时间变化的漫反射光谱,并进行二阶导数处理,根据1 160 nm和1 220 nm两个波长吸收峰变化,得到生物组织中自由水和结合水含量改变,从而得到组织形变过程.实验结果表明,生物组织中的自由水和结合水体积变化与压力大小以及作用时间呈非线性关系,并与生物组织生理状态密切相关.在体光谱测量中应控制光纤测头压力小于200 kPa,以避免组织中结合水转化成自由水.本文的研究结果为漫反射光谱测量部位和测量策略选择提供了参考.     

Harmonic motion detection in a vibrating scattering medium

Elasticity imaging is an emerging medical imaging modality that seeks to map the spatial distribution of tissue stiffness. Ultrasound radiation force excitation and motion tracking using pulse-echo ultrasound have been used in numerous methods. Dynamic radiation force is used in vibrometry to cause an object or tissue to vibrate, and the vibration amplitude and phase can be measured with exceptional accuracy. This paper presents a model that simulates harmonic motion detection in a vibrating scattering medium incorporating 3-D beam shapes for radiation force excitation and motion tracking. A parameterized analysis using this model provides a platform to optimize motion detection for vibrometry applications in tissue. An experimental method that produces a multifrequency radiation force is also presented. Experimental harmonic motion detection of simultaneous multifrequency vibration is demonstrated using a single transducer. This method can accurately detect motion with displacement amplitude as low as 100 to 200 nm in bovine muscle. Vibration phase can be measured within 10° or less. The experimental results validate the conclusions observed from the model and show multifrequency vibration induction and measurements can be performed simultaneously.     

Usefulness of ultrasonic strain measurement-based shear modulus reconstruction for diagnosis and thermal treatment

We previously reported an ultrasonic strain measurement-based one-dimensional (1-D) shear modulus reconstruction technique using a regularization method for differential diagnosis of malignancies on human superficial tissues (e.g., breast tissues). Here, ultrasonic strain measurement-based 2-D and 3-D shear modulus reconstruction techniques are described, and the 1-D technique is reviewed and subsequently applied to various human in vivo tissues, including deeply situated tissues (e.g., liver). Because soft tissues are deformed in 3-D space by externally situated arbitrary mechanical sources, the accuracy of the low-dimensional (i.e., 1-D or 2-D) reconstructions is lower to that of 3-D reconstruction due to occurrence of erroneous reconstruction artifacts (i.e., the reconstructed modulus is different than reality). These artifacts are confirmed on simulated inhomogeneous cubic phantoms containing a spherical homogenous inclusion using numerically calculated deformation data. The superiority of quasi-real-time imaging of the shear modulus is then demonstrated by comparing it with conventional B-mode imaging and strain imaging from the standpoints of monitoring the effectiveness of minimally invasive thermal therapy as well as differential diagnosis. Because the 2-D and 3-D techniques require special ultrasonic (US) equipment, the 1-D technique using conventional US imaging equipment is used, even though erroneous artifacts will occur. Specifically, the 1-D technique is applied as a diagnostic tool for differentiating malignancies in human in vivo liver and breast tissue, and a monitoring technique for determining the effectiveness of interstitial electromagnetic wave (micro and rf) thermal therapy on human in vivo liver and calf in vitro liver. Even when using the 1-D technique, reconstructed shear moduli were confirmed to be a suitable measure for monitoring thermal treatment as well as differential diagnosis. These results are encouraging in that they will promote use of 2-D and 3-D reconstruction techniques.     

Regularized autoregressive analysis of intravascular ultrasound backscatter: improvement in spatial accuracy of tissue maps

Autoregressive (AR) models are qualified for analysis of stochastic, short-time data, such as intravascular ultrasound (IVUS) backscatter. Regularization is required for AR analysis of short data lengths with an aim to increase spatial accuracy of predicted plaque composition and was achieved by determining suitable AR orders for short data records. Conventional methods of determining order were compared to the use of trend in the mean square error for determining order. Radio-frequency data from 101 fibrous, 56 fibro-lipidic, 50 calcified, and 70 lipid-core regions of interest (ROIs) were collected ex vivo from 51 human coronary arteries with 30 MHz unfocused IVUS transducers. Spectra were computed for AR model orders between 3-20 for data representing ROIs of two sizes (32 and 16 samples at 100 MHz sampling frequency) and were analyzed in the 17-42 MHz bandwidth. These spectra were characterized based on eight previously identified parameters. Statistical classification schemes were computed from 75% of the data and cross-validated with the remaining 25% using matched histology. The results determined the suitable AR order numbers for the two ROI sizes. Conventional methods of determining order did not perform well. Trend in the mean square error was identified as the most suitable factor for regularization of short record lengths.