Vessel Phantom Research Articles

Can quantitative synthetic aperture vascular elastography predict the stress distribution within the fibrous cap non-invasively

An imaging system that can detect and predict the propensity of an atherosclerotic plaque to rupture would reduce stroke. Radial and circumferential strain elastograms can reveal vulnerable regions within the fibrous cap. Circumferential stress imaging could predict the propensity of rupture. However, circumferential stress imaging demands either accurate knowledge of the geometric location of the fibrous cap or high quality strain information. We corroborated this hypothesis by performing studies on simulated vessel phantoms. More precisely, we computed stress elastograms with (1) precise knowledge of the fibrous cap, (2) no knowledge of the fibrous cap, (3) imprecise knowledge of the fibrous cap. We computed stress elastograms with accuracy of 8%, 15%, and 23% from high precision axial and lateral strain elastograms (i.e., 25 dB SNR) when precise, imprecise, and no geometric information was included the stress recovery method. The stress recovery method produced erroneous elastograms at lower noise level (i.e., 15 dB SNR), when no geometric information was included. Similarly, it produced elastograms with accuracy of 13% and 30% when precise and imprecise geometric information was included. The stress imaging method described in this paper performs well enough to warrant further studies with phantoms and ex-vivo samples.

Mechanical bioeffects of acoustic droplet vaporization in vessel-mimicking phantoms

This study investigated the mechanical bioeffects exerted by acoustic droplet vaporization (ADV) under different experimental conditions using vessel phantoms with a 200-μm inner diameter but different stiffness for imitating the microvasculature in various tumors. High-speed microscopy, passive cavitation detection, and ultrasound attenuation measurement were conducted to determine the morphological characteristics of vascular damage and clarify the mechanisms by which the damage was initiated and developed. The results show that phantom erosion was initiated under successive ultrasound exposure (2MHz, 3 cycles) at above 8-MPa peak negative pressures (PNPs) when ADV occurred with inertial cavitation (IC), producing lesions whose morphological characteristics were dependent on the amount of vaporized droplets. Slight injury occurred at droplet concentrations below (2.6±0.2)×106droplets/mL, forming shallow and rugged surfaces on both sides of the vessel walls. Increasing the droplet concentration to up to (2.6±0.2)×107droplets/mL gradually suppressed the damage on the distal wall, and turned the rugged surface on the proximal wall into tunnels rapidly elongating in the direction opposite to ultrasound propagation. Increasing the PNP did not increase the maximum tunnel depth after the ADV efficiency reached a plateau (about 71.6±2.7% at 10MPa). Increasing the pulse duration effectively increased the maximum tunnel depth to more than 10 times the diameter of the vessel even though there was no marked enhancement in IC dose. It can be inferred that substantial bubble generation in single ADV events may simultaneously distort the acoustic pressure distribution. The backward ultrasound reinforcement and forward ultrasound shielding relative to the direction of wave propagation augment the propensity of backward erosion. The results of the present work provide information that is valuable for the prevention or utilization of ADV-mediated mechanical bioeffects in clinical applications.

Endovascular Shear Strain Elastography for the Detection and Characterization of the Severity of Atherosclerotic Plaques: In Vitro Validation and In Vivo Evaluation

This work explores the potential of shear strain elastograms to identify vulnerable atherosclerotic plaques. The Lagrangian speckle model estimator (LSME) elasticity imaging method was further developed to estimate shear strain elasticity (SSE). Three polyvinyl alcohol cryogel vessel phantoms were imaged with an intravascular ultrasound (IVUS) scanner. The estimated SSE maps were validated against finite-element results. Atherosclerosis was induced in carotid arteries of eight Sinclair mini-pigs using a combination of surgical techniques, diabetes and a high-fat diet. IVUS images were acquired in vivo in 14 plaques before euthanasia and histology. All plaques were characterized by high magnitudes in SSE maps that correlated with American Heart Association atherosclerosis stage classifications (r = 0.97, p < 0.001): the worse the plaque condition the higher was the absolute value of SSE, i.e. |SSE| (e.g., mean |SSE| was 3.70 ± 0.40% in Type V plaques, whereas it was reduced to 0.11 ± 0.01% in normal walls). This study indicates the feasibility of using SSE to highlight atherosclerotic plaque vulnerability characteristics.

Geometrical consequences of kissing stents and the Covered Endovascular Reconstruction of the Aortic Bifurcation configuration in an in vitro model for endovascular reconstruction of aortic bifurcation

Kissing stents (KS) are commonly used to treat aortoiliac occlusive disease, but patency results are often lower than those of isolated stents. The Covered Endovascular Reconstruction of the Aortic Bifurcation (CERAB) technique was recently introduced to reconstruct the aortic bifurcation in a more anatomical and physiological fashion. The aim of this study is to compare the geometrical consequences of various stent configurations in vitro. Anatomic vessel phantoms of the aortoiliac bifurcation were created to accommodate stent configurations. Self-expandable nitinol KS, balloon-expandable covered KS, and two versions of the CERAB configuration were deployed, one with the iliac legs positioned inside the tapered part of the aortic cuff (1) and one with the legs deployed above this level (2). Computed tomography data were obtained to assess the geometry. The conformation ratio (D-ratio) was calculated by use of the ratio of the major and minor axes. The proximal mismatch area, mean mismatch area, and total mismatch volume were calculated. The highest D-ratios were observed in the nitinol KS and the CERAB configuration, implying an ideal "double-D" shape. The proximal and mean mismatch areas were four- to sixfold lower in the CERAB (1) configuration when compared with nitinol KS and CERAB (2), respectively, whereas the covered KS had the highest mismatch area. Nitinol and covered KS had the largest mismatch volume, whereas the mismatch volume was the lowest in the CERAB (1) configuration. Although nitinol self-expandable stents have a high stent conformation, the lowest radial mismatch was found in the CERAB (1) configuration, supporting the hypothesis that the CERAB configuration is the most anatomical and physiological reconstruction of the aortic bifurcation. Within the CERAB configuration, the two limbs are ideally positioned inside the tapering portion of the cuff, minimizing mismatch.

Ultrafast vascular strain compounding using plane wave transmission

Deformations of the atherosclerotic vascular wall induced by the pulsating blood can be estimated using ultrasound strain imaging. Because these deformations indirectly provide information on mechanical plaque composition, strain imaging is a promising technique for differentiating between stable and vulnerable atherosclerotic plaques. This paper first explains 1-D radial strain estimation as applied intravascularly in coronary arteries. Next, recent methods for noninvasive vascular strain estimation in a transverse imaging plane are discussed. Finally, a compounding technique that our group recently developed is explained. This technique combines motion estimates of subsequently acquired focused ultrasound images obtained at various insonification angles. However, because the artery moves and deforms during the multi-angle acquisition, errors are introduced when compounding. Recent advances in computational power have enabled plane wave ultrasound acquisition, which allows 100 times faster image acquisition and thus might resolve the motion artifacts. In this paper the performance of strain imaging using plane wave compounding is investigated using simulations of an artery with a vulnerable plaque and experimental data of a two-layered vessel phantom. The results show that plane wave compounding outperforms 0° focused strain imaging. For the simulations, the root mean squared error reduced by 66% and 50% for radial and circumferential strain, respectively. For the experiments, the elastographic signal-to-noise and contrast-to-noise ratio (SNRe and CNRe) increased with 2.1dB and 3.7dB radially, and 5.6dB and 16.2dB circumferentially. Because of the high frame rate, the plane wave compounding technique can even be further optimized and extended to 3D in future.

Non-invasive Vascular Radial/Circumferential Strain Imaging and Wall Shear Rate Estimation Using Video Images of Diagnostic Ultrasound

The aim of this work was to develop a convenient method for radial/circumferential strain imaging and shear rate estimation that could be used as a supplement to the current routine screening for carotid atherosclerosis using video images of diagnostic ultrasound. A reflection model-based correction for gray-scale non-uniform distribution was applied to B-mode video images before strain estimation to improve the accuracy of radial/circumferential strain imaging when applied to vessel transverse cross sections. The incremental and cumulative radial/circumferential strain images can then be calculated based on the displacement field between consecutive B-mode images. Finally, the transverse Doppler spectra acquired at different depths along the vessel diameter were used to construct the spatially matched instantaneous wall shear values in a cardiac cycle. Vessel phantom simulation results revealed that the signal-to-noise ratio and contrast-to-noise ratio of the radial and circumferential strain images were increased by 2.8 and 5.9 dB and by 2.3 and 4.4 dB, respectively, after non-uniform correction. Preliminary results for 17 patients indicated that the accuracy of radial/circumferential strain images was improved in the lateral direction after non-uniform correction. The peak-to-peak value of incremental strain and the maximum cumulative strain for calcified plaques are evidently lower than those for other plaque types, and the echolucent plaques had higher values, on average, than the mixed plaques. Moreover, low oscillating wall shear rate values, found near the plaque and stenosis regions, are closely related to plaque formation. In conclusion, the method described can provide additional valuable results as a supplement to the current routine ultrasound examination for carotid atherosclerosis and, therefore, has significant potential as a feasible screening method for atherosclerosis diagnosis in the future.

Synthesis and Characterization of Transiently Stable Albumin-Coated Microbubbles via a Flow-Focusing Microfluidic Device

We describe a method for synthesizing albumin-shelled, large-diameter (>10 μm), transiently stable microbubbles using a flow-focusing microfluidic device (FFMD). The microfluidic device enables microbubbles to be produced immediately before insonation, thus relaxing the requirements for stability. Both reconstituted fractionated bovine serum albumin (BSA) and fresh bovine blood plasma were investigated as shell stabilizers. Microbubble coalescence was inhibited by the addition of either dextrose or glycerol and propylene glycol. Microbubbles were observed to have an acoustic half-life of approximately 6 s. Microbubbles generated directly within a vessel phantom containing flowing blood produced a 6.5-dB increase in acoustic signal within the lumen. Microbubbles generated in real time upstream of in vitro rat aortic smooth muscle cells under physiologic flow conditions successfully permeabilized 58% of the cells on insonation at a peak negative pressure of 200 kPa. These results indicate that transiently stable microbubbles produced via flow-focusing microfluidic devices are capable of image enhancement and drug delivery. In addition, successful microbubble production with blood plasma suggests the potential to use blood as a stabilizing shell.

Photoacoustic imaging of human coronary atherosclerosis in two spectral bands

Spectroscopic intravascular photoacoustic imaging (sIVPA) has shown promise to detect and distinguish lipids in atherosclerotic plaques. sIVPA generally utilizes one of the two high absorption bands in the lipid absorption spectrum at 1.2μm and 1.7μm. Specific absorption signatures of various lipid compounds within the bands in either wavelength range can potentially be used to differentiate between plaque lipids and peri-adventitial lipids. With the aim to quantify any differences between the two bands, we performed combined sIVPA imaging in both absorption bands on a vessel phantom and an atherosclerotic human coronary artery ex vivo. Lipid detection in a human atherosclerotic lesion with sIVPA required lower pulse energy at 1.7μm than at 1.2μm (0.4mJ versus 1.2mJ). The imaging depth was twice as large at 1.2μm compared to 1.7μm. Adequate differentiation between plaque and peri-adventitial lipids was achieved at 1.2μm only.

Shear Wave Elastography Assessment of Carotid Plaque Stiffness: In Vitro Reproducibility Study

This study assessed inter- and intra-observer reproducibility of shear wave elastography (SWE) measurements in vessel phantoms simulating soft and hard carotid plaque under steady and pulsatile flow conditions. Supersonic SWE was used to acquire cine-loop data and quantify Young’s modulus in cryogel vessel phantoms. Data were acquired by two observers, each performing three repeat measurements. Mean Young’s modulus was quantified within 2-mm regions of interest averaged across five frames and, depending on vessel model and observer, ranged from 28 to 240 kPa. The mean inter-frame coefficient of variation (CV) was 0.13 (range: 0.07–0.18) for observer 1 and 0.14 (range: 0.12–0.16) for observer 2, with mean intra-class correlation coefficients (ICCs) of 0.84 and 0.83, respectively. The mean inter-operator CV was 0.13 (range: 0.08–0.20), with a mean ICC of 0.76 (range: 0.69-0.82). Our findings indicate that SWE can quantify Young’s modulus of carotid plaque phantoms with good reproducibility, even in the presence of pulsatile flow.

Detection of unique acoustic signatures for phase-change contrast agents used in medical imaging and therapy

Phase-change contrast agents (PCCAs) provide a dynamic platform to approach problems in medical ultrasound (US). Upon US-mediated activation, the liquid core vaporizes and expands to produce a gas bubble ideal for US imaging and therapy. In this study, we demonstrate through underlying theory, high-speed microscopy, and US interrogation that PCCAs composed of highly volatile perfluorocarbons (PFCs) exhibit unique acoustic behavior that can be differentiated from tissue and standard microbubble contrast agents. Experimental results show that when activated with short pulses PCCAs will over-expand (6.3× to 7.7× the droplet diameter, PFC dependent) due to momentum of expansion, and undergo unforced, under-damped radial oscillation while settling to a final bubble diameter (5.1× to 5.5× the droplet diameter). Oscillation frequency is inversely related to droplet size—near 100 kHz for droplets ≥ 4 μm in diameter, and 2.5 MHz for droplets near 500 nm. Results from in vitro vessel phantoms using confocal piston transducers with an “activate high” (8 MHz, 2 cycles), “listen low” (1 MHz) scheme show that droplet-specific signals can be detected in both time and frequency domain, and that the magnitude of the acoustic “signature” increases with PFC volatility. These signatures may aid in development of droplet-specific detection techniques.

Flowing microbubble manipulation in blood vessel phantom using ultrasonic standing wave with stepwise frequency

An approach was demonstrated to gather, fix, and controllably shift flowing microbubbles in a blood vessel phantom. An ultrasonic standing wave field was generated by the superposition of the emission of a 5 MHz conventional transducer and the reflection from a bone surface. The acoustic radiation force gathered flowing microbubbles into the nodes, fixed some accumulated microbubble clusters in the flow condition, and shifted microbubbles to target site with stepwise frequency. The resolution of microbubble shift was approximately 4 μm, and the low acoustic pressure range was from 4 to 16 kPa to avoid microbubble rupture.

Deconvolution-based deblurring of reconstructed images in photoacoustic/thermoacoustic tomography

Photoacoustic/thermoacoustic tomography is an emerging hybrid imaging modality combining optical/microwave imaging with ultrasound imaging. Here, a k-wave MATLAB toolbox was used to simulate various configurations of excitation pulse shape, width, transducer types, and target object sizes to see their effect on the photoacoustic/thermoacoustic signals. A numerical blood vessel phantom was also used to demonstrate the effect of various excitation pulse waveforms and pulse widths on the reconstructed images. Reconstructed images were blurred due to the broadening of the pressure waves by the excitation pulse width as well as by the limited transducer bandwidth. The blurring increases with increase in pulse width. A deconvolution approach is presented here with Tikhonov regularization to correct the photoacoustic/thermoacoustic signals, which resulted in improved reconstructed images by reducing the blurring effect. It is observed that the reconstructed images remain unaffected by change in pulse widths or pulse shapes, as well as by the limited bandwidth of the ultrasound detectors after the use of the deconvolution technique.

Template‐based CTA to x‐ray angio rigid registration of coronary arteries in frequency domain with automatic x‐ray segmentation

A key challenge for image guided coronary interventions is accurate and absolutely robust image registration bringing together preinterventional information extracted from a three-dimensional (3D) patient scan and live interventional image information. In this paper, the authors present a novel scheme for 3D to two-dimensional (2D) rigid registration of coronary arteries extracted from preoperative image scan (3D) and a single segmented intraoperative x-ray angio frame in frequency and spatial domains for real-time angiography interventions by C-arm fluoroscopy. Most existing rigid registration approaches require a close initialization due to the abundance of local minima and high complexity of search algorithms. The authors' method eliminates this requirement by transforming the projections into translation-invariant Fourier domain for estimating the 3D pose. For 3D rotation recovery, template Digitally Reconstructed Radiographs (DRR) as candidate poses of 3D vessels of segmented computed tomography angiography are produced by rotating the camera (image intensifier) around the DICOM angle values with a specific range as in C-arm setup. The authors have compared the 3D poses of template DRRs with the segmented x-ray after equalizing the scales in three domains, namely, Fourier magnitude, Fourier phase, and Fourier polar. The best rotation pose candidate was chosen by one of the highest similarity measures returned by the methods in these domains. It has been noted in literature that frequency domain methods are robust against noise and occlusion which was also validated by the authors' results. 3D translation of the volume was then recovered by distance-map based BFGS optimization well suited to convex structure of the authors' objective function without local minima due to distance maps. A novel automatic x-ray vessel segmentation was also performed in this study. Final results were evaluated in 2D projection space for patient data; and with ground truth values and landmark distances for the images acquired with a solid phantom vessel. Results validate that rotation recovery in frequency domain is robust against differences in segmentations in two modalities. Distance-map translation is successful in aligning coronary trees with highest possible overlap. Numerical and qualitative results show that single view rigid alignment in projection space is successful. This work can be extended with multiple views to resolve depth ambiguity and with deformable registration to account for nonrigid motion in patient data.

Lipid detection in atherosclerotic human coronaries by spectroscopic intravascular photoacoustic imaging

The presence of lipids in atherosclerotic coronary lesions is an important determinant of their potential to trigger acute coronary events. Spectroscopic intravascular photoacoustic imaging (sIVPA) has the potential to automatically detect lipids in atherosclerotic lesions. For real-time in vivo imaging, limiting the number of excitation wavelengths is crucial. We explored methods for plaque lipid detection using sIVPA, with the aim to minimize the number of laser pulses per image line. A combined intravascular ultrasound (IVUS) and photoacoustic imaging system was used to image a vessel phantom and human coronary arteries ex vivo. We acquired co-registered cross-sectional images at several wavelengths near 1200 nm, a lipid-specific absorption band. Correlating the photoacoustic spectra at 6 or 3 wavelengths from 1185 to 1235 nm with the absorption spectrum of cholesterol and peri-adventitial tissue, we could detect and differentiate the lipids in the atherosclerotic plaque and peri-adventitial lipids, respectively. With two wavelengths, both plaque and peri-adventitial lipids were detected but could not be distinguished.

Stenosis Quantification of Coronary Arteries in Coronary Vessel Phantoms With Second-Generation Dual-Source CT: Influence of Measurement Parameters and Limitations

The purpose of this study was to use second-generation dual-source CT to assess the influence of size, degree of stenosis, luminal contrast attenuation, and plaque geometry on stenosis quantification in a coronary artery phantom. Six vessel phantoms with three outer diameters (2, 3, and 4 mm), each containing three radiolucent plaques (72.2 HU) that simulated eccentric and concentric 43.8%, 75%, and 93.8% stenoses were made with a 3D printer system. These phantoms were filled with an iodine-saline solution mixture at luminal attenuations of 150, 200, 250, 300, and 350 HU and were attached to a cardiac motion simulator. Dual-source CT was performed with a standardized ECG-gated protocol (120 kV, 360 mAs per rotation) at a simulated heart rate of 70 beats/min. Two independent readers quantified the degree of stenosis using area-based measurements. All measurements were highly reproducible (intraclass correlation, ≥ 0.791; p < 0.001). The mean measured degree of stenosis for a phantom with a 3-mm outer diameter at 250-HU luminal attenuation was 49.0% ± 10.0% for 43.8% stenosis, 71.7% ± 9.6% for 75.0% stenosis, and 85.4% ± 5.9% for 93.8% stenosis. With decreasing phantom size, measurement error increased for all degrees of stenosis. The absolute error increased for measurements at a low luminal attenuation of 150 HU (p < 0.001) and for low-grade stenoses compared with medium-and high-grade stenoses (p < 0.001). The results are an overview of factors that influence stenosis quantification in simulated coronary arteries. Dual-source CT is highly reproducible and accurate for quantification of low-density stenosis in vessels with a diameter of 3 mm and attenuation of at least 200 HU for different degrees of stenosis and plaque geometry.

Least squares QR-based decomposition provides an efficient way of computing optimal regularization parameter in photoacoustic tomography

A computationally efficient approach that computes the optimal regularization parameter for the Tikhonov-minimization scheme is developed for photoacoustic imaging. This approach is based on the least squares-QR decomposition which is a well-known dimensionality reduction technique for a large system of equations. It is shown that the proposed framework is effective in terms of quantitative and qualitative reconstructions of initial pressure distribution enabled via finding an optimal regularization parameter. The computational efficiency and performance of the proposed method are shown using a test case of numerical blood vessel phantom, where the initial pressure is exactly known for quantitative comparison.

Photoacoustic tomography using a Michelson interferometer with quadrature phase detection

We present a pressure sensor based on a Michelson interferometer, for use in photoacoustic tomography. Quadrature phase detection is employed allowing measurement at any point on the mirror surface without having to retune the interferometer, as is typically required by Fabry-Perot type detectors. This opens the door to rapid full surface detection, which is necessary for clinical applications. Theory relating acoustic pressure to detected acoustic particle displacements is used to calculate the detector sensitivity, which is validated with measurement. Proof-of-concept tomographic images of blood vessel phantoms have been taken with sub-millimeter resolution at depths of several millimeters.

Development of Dual Beam High Speed Doppler OFDI

This paper describes development of a high speed Doppler OFDI system for non-invasive vascular imaging. Doppler OFDI (optical frequency domain imaging) is one of the phase-resolved second generation OCT (optical coherence tomography) techniques for high resolution imaging of moving elements in biological tissues. To achieve a phase-resolved imaging, two temporally separated measurements are required. In a conventional Doppler OCT, a pair of massively oversampled successive A-lines is used to minimize de-correlation noise at the expense of significant imaging speed reduction. To minimize a de-correlation noise between targeted two measurements without suffering from significant imaging speed reduction, several methods have been developed such as an optimized scanning pattern and polarization multiplexed dual beam scanning. This research represent novel imaging technique using frequency multiplexed dual beam illumination to measure exactly same position with aimed time interval. Developed system has been verified using a tissue phantom and mouse vessel imaging.

3-D Locomotive and Drilling Microrobot Using Novel Stationary EMA System

For 3-D locomotion and drilling of a microrobot, we proposed an electromagnetic actuation (EMA) system consisting of three pairs of stationary Helmholtz coils, a pair of stationary Maxwell coils, and a pair of rotating Maxwell coils in the previous research . However, this system could have limited medical applications because of the pair of rotational Maxwell coils. In this paper, we propose a new EMA system with three pairs of stationary Helmholtz coils, a pair of stationary Maxwell coils, and a new locomotive mechanism for the same 3-D locomotion and drilling of the microrobot as achieved by the previously proposed EMA system. For the performance evaluation of the proposed EMA system, we perform a 3-D locomotion and drilling test in a blood vessel phantom. In addition, the two EMA systems are compared to show that the newly proposed EMA system has 440% wider working space and 49% less power consumption than the previous EMA system.

Dual-wavelength photothermal optical coherence tomography for imaging microvasculature blood oxygen saturation

A swept-source dual-wavelength photothermal (DWP) optical coherence tomography (OCT) system is demonstrated for quantitative imaging of microvasculature oxygen saturation. DWP-OCT is capable of recording three-dimensional images of tissue and depth-resolved phase variation in response to photothermal excitation. A 1,064-nm OCT probe and 770-nm and 800-nm photothermal excitation beams are combined in a single-mode optical fiber to measure microvasculature hemoglobin oxygen saturation (SO(2)) levels in phantom blood vessels with a range of blood flow speeds (0 to 17 mm/s). A 50-μm-diameter blood vessel phantom is imaged, and SO(2) levels are measured using DWP-OCT and compared with values provided by a commercial oximeter at various blood oxygen concentrations. The influences of blood flow speed and mechanisms of SNR phase degradation on the accuracy of SO(2) measurement are identified and investigated.