In silico simulation of liver crack detection using ultrasonic shear wave imaging.

BACKGROUND: Liver trauma is an important source of morbidity and mortality worldwide. A timely detection and precise evaluation of traumatic liver injury and the bleeding site is necessary. There is a need to develop better imaging modalities of hepatic injuries to increase the sensitivity of ultrasonic imaging techniques for sites of hemorrhage caused by cracks. In this study, we conduct an in silico simulation of liver crack detection and delineation using an ultrasonic shear wave imaging (USWI) based method. METHODS: We simulate the generation and propagation of the shear wave in a liver tissue medium having a crack using COMSOL. Ultrasound radio frequency (RF) signal synthesis and the two-dimensional speckle tracking algorithm are applied to simulate USWI in a medium with randomly distributed scatterers. Crack detection is performed using the directional filter and the edge detection algorithm rather than the conventional inversion algorithm. Cracks with varied sizes and locations are studied with our method and the crack localization results are compared with the given crack. RESULTS: Our pilot simulation study shows that, by using USWI combined with a directional filter cum edge detection technique, the near-end edge of the crack can be detected in all the three cracks that we studied. The detection errors are within 5%. For a crack of 1.6 mm thickness, little shear wave can pass through it and the far-end edge of the crack cannot be detected. The detected crack lengths using USWI are all slightly shorter than the actual crack length. The robustness of our method in detecting a straight crack, a curved crack and a subtle crack of 0.5 mm thickness is demonstrated. CONCLUSIONS: In this paper, we simulate the use of a USWI based method for the detection and delineation of the crack in liver. The in silico simulation helps to improve understanding and interpretation of USWI measurements in a physical scattered liver medium with a crack. This pilot study provides a basis for improved insights in future crack detection studies in a tissue phantom or liver.

An adaptive displacement estimation algorithm for improved reconstruction of thermal strain.

Thermal strain imaging (TSI) can be used to differentiate between lipid and water-based tissues in atherosclerotic arteries. However, detecting small lipid pools in vivo requires accurate and robust displacement estimation over a wide range of displacement magnitudes. Phase-shift estimators such as Loupas' estimator and time-shift estimators such as normalized cross-correlation (NXcorr) are commonly used to track tissue displacements. However, Loupas' estimator is limited by phase-wrapping and NXcorr performs poorly when the SNR is low. In this paper, we present an adaptive displacement estimation algorithm that combines both Loupas' estimator and NXcorr. We evaluated this algorithm using computer simulations and an ex vivo human tissue sample. Using 1-D simulation studies, we showed that when the displacement magnitude induced by thermal strain was >λ/8 and the electronic system SNR was >25.5 dB, the NXcorr displacement estimate was less biased than the estimate found using Loupas' estimator. On the other hand, when the displacement magnitude was ≤λ/4 and the electronic system SNR was ≤25.5 dB, Loupas' estimator had less variance than NXcorr. We used these findings to design an adaptive displacement estimation algorithm. Computer simulations of TSI showed that the adaptive displacement estimator was less biased than either Loupas' estimator or NXcorr. Strain reconstructed from the adaptive displacement estimates improved the strain SNR by 43.7 to 350% and the spatial accuracy by 1.2 to 23.0% (P < 0.001). An ex vivo human tissue study provided results that were comparable to computer simulations. The results of this study showed that a novel displacement estimation algorithm, which combines two different displacement estimators, yielded improved displacement estimation and resulted in improved strain reconstruction.

Methods for using 3-D ultrasound speckle tracking in biaxial mechanical testing of biological tissue samples.

Being multilayered and anisotropic, biological tissues such as cardiac and arterial walls are structurally complex, making the full assessment and understanding of their mechanical behavior challenging. Current standard mechanical testing uses surface markers to track tissue deformations and does not provide deformation data below the surface. In the study described here, we found that combining mechanical testing with 3-D ultrasound speckle tracking could overcome this limitation. Rat myocardium was tested with a biaxial tester and was concurrently scanned with high-frequency ultrasound in three dimensions. The strain energy function was computed from stresses and strains using an iterative non-linear curve-fitting algorithm. Because the strain energy function consists of terms for the base matrix and for embedded fibers, spatially varying fiber orientation was also computed by curve fitting. Using finite-element simulations, we first validated the accuracy of the non-linear curve-fitting algorithm. Next, we compared experimentally measured rat myocardium strain energy function values with those in the literature and found a matching order of magnitude. Finally, we retained samples after the experiments for fiber orientation quantification using histology and found that the results satisfactorily matched those computed in the experiments. We conclude that 3-D ultrasound speckle tracking can be a useful addition to traditional mechanical testing of biological tissues and may provide the benefit of enabling fiber orientation computation.

Detecting hepatic steatosis using ultrasound-induced thermal strain imaging: an ex vivo animal study.

Hepatic steatosis or fatty liver disease occurs when lipids accumulate within the liver and can lead to steatohepatitis, cirrhosis, liver cancer and eventual liver failure requiring liver transplant. Conventional brightness mode (B-mode) ultrasound (US) is the most common noninvasive diagnostic imaging modality used to diagnose hepatic steatosis in clinics. However, it is mostly subjective or requires a reference organ such as the kidney or spleen with which to compare. This comparison can be problematic when the reference organ is diseased or absent. The current work presents an alternative approach to noninvasively detecting liver fat content using US-induced thermal strain imaging (US-TSI). This technique is based on the difference in the change in the speed of sound as a function of temperature between water- and lipid-based tissues. US-TSI was conducted using two system configurations including a mid-frequency scanner with a single linear array transducer (5-14 MHz) for both imaging and heating and a high-frequency (13-24 MHz) small animal imaging system combined with a separate custom-designed US heating transducer array. Fatty livers (n = 10) with high fat content (45.6 ± 11.7%) from an obese mouse model and control livers (n = 10) with low fat content (4.8 ± 2.9%) from wild-type mice were embedded in gelatin. Then, US imaging was performed before and after US induced heating. Heating time periods of ∼ 3 s and ∼ 9.2 s were used for the mid-frequency imaging and high-frequency imaging systems, respectively, to induce temperature changes of approximately 1.5 °C. The apparent echo shifts that were induced as a result of sound speed change were estimated using 2D phase-sensitive speckle tracking. Following US-TSI, histology was performed to stain lipids and measure percentage fat in the mouse livers. Thermal strain measurements in fatty livers (-0.065 ± 0.079%) were significantly (p < 0.05) higher than those measured in control livers (-0.124 ± 0.037%). Using histology as a gold standard to classify mouse livers, US-TSI had a sensitivity and specificity of 70% and 90%, respectively. The area under the receiver operating characteristic curve was 0.775. This ex vivo study demonstrates the feasibility of using US-TSI to detect fatty livers and warrants further investigation of US-TSI as a diagnostic tool for hepatic steatosis.

In vivo monitoring of structural and mechanical changes of tissue scaffolds by multi-modality imaging.

Degradable tissue scaffolds are implanted to serve a mechanical role while healing processes occur and putatively assume the physiological load as the scaffold degrades. Mechanical failure during this period can be unpredictable as monitoring of structural degradation and mechanical strength changes at the implant site is not readily achieved in vivo, and non-invasively. To address this need, a multi-modality approach using ultrasound shear wave imaging (USWI) and photoacoustic imaging (PAI) for both mechanical and structural assessment in vivo was demonstrated with degradable poly(ester urethane)urea (PEUU) and polydioxanone (PDO) scaffolds. The fibrous scaffolds were fabricated with wet electrospinning, dyed with indocyanine green (ICG) for optical contrast in PAI, and implanted in the abdominal wall of 36 rats. The scaffolds were monitored monthly using USWI and PAI and were extracted at 0, 4, 8 and 12 wk for mechanical and histological assessment. The change in shear modulus of the constructs in vivo obtained by USWI correlated with the change in average Young's modulus of the constructs ex vivo obtained by compression measurements. The PEUU and PDO scaffolds exhibited distinctly different degradation rates and average PAI signal intensity. The distribution of PAI signal intensity also corresponded well to the remaining scaffolds as seen in explant histology. This evidence using a small animal abdominal wall repair model demonstrates that multi-modality imaging of USWI and PAI may allow tissue engineers to noninvasively evaluate concurrent mechanical stiffness and structural changes of tissue constructs in vivo for a variety of applications.

Nerve regeneration and elastin formation within poly(glycerol sebacate)-based synthetic arterial grafts one-year post-implantation in a rat model.

The objective of this study was to evaluate the long-term performance of cell-free vascular grafts made from a fast-degrading elastic polymer. We fabricated small arterial grafts from microporous tubes of poly(glycerol sebacate) (PGS) reinforced with polycaprolactone (PCL) nanofibers on the outer surface. Grafts were interpositioned in rat abdominal aortas and characterized at 1 year post-implant. Grafts remodeled into "neoarteries" (regenerated arteries) with similar gross appearance to native rat aortas. Neoarteries mimic arterial tissue architecture with a confluent endothelium and media and adventita-like layers. Patent vessels (80%) showed no significant stenosis, dilation, or calcification. Neoarteries contain nerves and have the same amount of mature elastin as native arteries. Despite some differences in matrix organization, regenerated arteries had similar dynamic mechanical compliance to native arteries in vivo. Neoarteries responded to vasomotor agents, albeit with different magnitude than native aortas. These data suggest that an elastic vascular graft that resorbs quickly has potential to improve the performance of vascular grafts used in small arteries. This design may also promote constructive remodeling in other soft tissues.

Motion Artifact Reduction in Ultrasound Based Thermal Strain Imaging of Atherosclerotic Plaques Using Time Series Analysis.

Large lipid pools in vulnerable plaques, in principle, can be detected using US based thermal strain imaging (US-TSI). One practical challenge for in vivo cardiovascular application of US-TSI is that the thermal strain is masked by the mechanical strain caused by cardiac pulsation. ECG gating is a widely adopted method for cardiac motion compensation, but it is often susceptible to electrical and physiological noise. In this paper, we present an alternative time series analysis approach to separate thermal strain from the mechanical strain without using ECG. The performance and feasibility of the time-series analysis technique was tested via numerical simulation as well as in vitro water tank experiments using a vessel mimicking phantom and an excised human atherosclerotic artery where the cardiac pulsation is simulated by a pulsatile pump.

Non-invasive assessment of elastic modulus of arterial constructs during cell culture using ultrasound elasticity imaging.

Mechanical strength is a key design factor in tissue engineering of arteries. Most existing techniques assess the mechanical property of arterial constructs destructively, leading to sacrifice of a large number of animals. We propose an ultrasound-based non-invasive technique for the assessment of the mechanical strength of engineered arterial constructs. Tubular scaffolds made from a biodegradable elastomer and seeded with vascular fibroblasts and smooth muscle cells were cultured in a pulsatile-flow bioreactor. Scaffold distension was computed from ultrasound radiofrequency signals of the pulsating scaffold via 2-D phase-sensitive speckle tracking. Young's modulus was then calculated by solving the inverse problem from the distension and the recorded pulse pressure. The stiffness thus computed from ultrasound correlated well with direct mechanical testing results. As the scaffolds matured in culture, ultrasound measurements indicated an increase in Young's modulus, and histology confirmed the growth of cells and collagen fibrils in the constructs. The results indicate that ultrasound elastography can be used to assess and monitor non-invasively the mechanical properties of arterial constructs.

Noninvasive detection of lipids in atherosclerotic plaque using ultrasound thermal strain imaging: in vivo animal study.

OBJECTIVES: This study sought to examine the feasibility of in vivo detection of lipids in atherosclerotic plaque (AP) by ultrasound (US) thermal (or temporal) strain imaging (TSI). BACKGROUND: Intraplaque lipid content is thought to contribute to plaque stability. Lipid exhibits a distinctive physical characteristic of temperature-dependent US speed compared with water-bearing tissues. As tissue temperature changes, US radiofrequency (RF) echoes shift in time of flight, which produces an apparent strain (thermal or temporal strain [TS]). METHODS: US heating-imaging pulse sequences and transducers were designed and integrated into commercial US scanners for US-TSI of arterial segments. US-RF data were collected while gradually increasing tissue temperature. Phase-sensitive speckle tracking was applied to reconstruct TS maps coregistered to B-scans. Segments from injured atherosclerotic and uninjured nonatherosclerotic common femoral arteries (CFA) in cholesterol-fed New Zealand rabbits, and segments from control normal diet-fed rabbits (N =14) were scanned in vivo at different time points up to 12 weeks. RESULTS: Lipid-rich atherosclerotic lesions exhibited distinct positive TS (+0.19 ± 0.08%) compared with that in nonatherosclerotic (-0.10 ± 0.13%) and control (-0.09 ± 0.09%) segments (p < 0.001). US-TSI enabled serial monitoring of lipids during atherosclerosis development. The coregistered set of morphological and compositional information of US-TSI showed good agreement with histology. CONCLUSIONS: US-TSI successfully detected and longitudinally monitored lipid progression in atherosclerotic CFA. US-TSI of relatively superficial arteries may be a modality that could be integrated into a commercial US system for noninvasive lipid detection in AP.

Flexible integration of high-imaging-resolution and high-power arrays for ultrasound-induced thermal strain imaging (US-TSI).

Ultrasound-induced thermal strain imaging (USTSI) for carotid artery plaque detection requires both high imaging resolution (<100 µm) and sufficient US-induced heating to elevate the tissue temperature (~1°C to 3°C within 1 to 3 cardiac cycles) to produce a noticeable change in sound speed in the targeted tissues. Because the optimization of both imaging and heating in a monolithic array design is particularly expensive and inflexible, a new integrated approach is presented which utilizes independent ultrasound arrays to meet the requirements for this particular application. This work demonstrates a new approach in dual-array construction. A 3-D printed manifold was built to support both a high-resolution 20 MHz commercial imaging array and 6 custom heating elements operating in the 3.5 to 4 MHz range. For the application of US-TSI in carotid plaque characterization, the tissue target site is 20 to 30 mm deep, with a typical target volume of 2 mm (elevation) × 8 mm (azimuthal) × 5 mm (depth). The custom heating array performance was fully characterized for two design variants (flat and spherical apertures), and can easily deliver 30 W of total acoustic power to produce intensities greater than 15 W/cm(2) in the tissue target region.