Urban, Matthew W.

Osteochondritis dissecans (OCD) is a joint disease that is prevalent among youth athletes. Medical ultrasound is currently limited in its ability to detect and monitor OCD due to limitations of current Delay-and-Sum (DAS) reconstruction algorithms. In this work, we used a Delay-Multiply-and-Sum (DMAS) reconstruction algorithm to improve medical ultrasound’s ability to diagnose OCD. We artificially generated OCD lesions in unfixed cadaveric elbows and imaged them with a research ultrasound machine. We also imaged these cadaveric limbs with x-ray computed tomography (CT) with a high-resolution acquisition. These CT images were used as a gold standard for OCD geometry. We reconstructed the ultrasound images using both DAS and DMAS algorithms and compared them quantitatively by taking several profiles across the images of the artificial OCD lesions. The image metrics that we measured within these profiles were OCD lesion contrast, bone interface clarity, and lesion crack thickness accuracy. We found that the DMAS algorithm improved OCD lesion contrast by up to 26% when compared to DAS. We also found that the DMAS algorithm reduced the variability of bone interface clarity overall. Future work will involve an in vivo study, as well as optimization, of the DMAS algorithm for OCD lesion imaging.

Introduction: Shear Wave Elastography (SWE) is a recently developed noninvasive method for elastography assessment using ultrasound. The technique consists of sending an acoustic radiation force into the tissue that in turn generates an orthogonal low frequency propagating shear wave. The shear wave propagation speed, which is calculated from B-mode images, is correlated to the tissues mechanical properties. Currently, SWE is primarily used in breast and liver to detect tumors easily missed with normal B-mode ultrasound. SWE could potentially aid in the characterization of plaques in the carotid artery, which is critical for the prevention of ischemic stroke. Methods: Six polyvinyl alcohol (PVA) phantoms were created with soft and hard plaque mimicking inclusions. The plaques were excited with acoustic radiation force and the shear wave was measured using high speed B-mode imaging. The data was post-processed with a custom in-house algorithm fitting a model of a Lamb wave propagating through a plate to the shear wave dispersion curve, which allowed the shear modulus to be estimated. The results were validated by measuring the phantom plaque shear modulus with mechanical testing. Results: SWE measured a mean shear modulus of 6 ± 1 kPa and 106 ± 17 kPa versus 3 kPa and 95 kPa measured by mechanical testing in the soft and hard plaques respectively. The results show good agreement between the shear modulus measured with SWE and mechanical testing. In this study simplified homogenous phantom plaque models were examined in a static experimental setup with results validated by mechanical testing. Algorithm improvements for measurements in a dynamic environment are being developed for a future in vivo pilot study. Conclusion: The results show good agreement between the shear modulus measured with SWE and mechanical testing and indicate the possibility for an in vivo application.

Ultrasound is a key imaging tool for evaluating the kidney. Over the last two decades, methods to measure the mechanical properties of soft tissues have been developed and used in clinical practice, although use in the kidney has not been as widespread as for other applications. The mechanical properties of the kidney are determined by the structure and composition of the renal parenchyma and perfusion characteristics. Because pathologic processes change these factors, the mechanical properties change and can be used for diagnostic purposes and for monitoring treatment or disease progression. Ultrasound-based elastography methods for evaluating the mechanical properties of the kidney use focused ultrasound beams to perturb the kidney and then high frame-rate ultrasound methods are used to measure the resulting motion. The motion is analyzed to estimate the mechanical properties. This review will describe the principles of these methods and discuss several seminal studies related to characterizing the kidney. Additionally, an overview of the clinical use of elastography methods in native and kidney allografts will be provided. Perspectives on future developments and uses of elastography technology along with other complementary ultrasound imaging modalities will be provided.

Ischemic stroke results from thrombus becoming lodged in a vessel in the cerebrovascular circulation. The constituents of the thrombus can vary widely and have direct effects on the mechanical properties of the thrombus. Thrombectomy procedures could potentially be improved if the mechanical properties of the thrombus could be determined prior to treatment. In the study, we developed a new non-contact method associated with Rayleigh wave propagations for evaluating mechanical properties of human clotted blood, referred to as ultrasound-mediated optical coherence elastography (UOCE). Due to clot mechanical properties being associated with fibrin and platelet content, eight different clot analogues with varying fibrin/platelets concentrations, from 0.6% (control group) to 19.0%, were produced, and the clot analog in each concentration was repeatedly measured five times. A highly focused transducer with a center frequency of 7.5 MHz was used to generate acoustic radiation forces exerted on the surface of clotted blood to induce Rayleigh wave propagations. The transducer was driven by a 50 dB radio frequency amplifier a 4 ms pulse which was repeated at a rate of 19 Hz. The optical coherence tomography (OCT) acquisition was set to 50 lateral positions and 4000 A-scans for each lateral position at a 76 kHz scan rate for total acquisition time of 52.6 ms. The results demonstrated that the Rayleigh wave group velocities positively correlated with the concentrations of fibrin/platelets. The group velocities ranged from 0.78 ± 0.02 m/s for 0.6% fibrin/platelets and increased to 2.42 ± 0.06 m/s at a fibrin/platelets concentration of 19.0%. There are statistically significant difference ( p <0.05) between control group and all clot analogues with a fibrin/platelets concentration of greater than 2.3%. In conclusion, we propose UOCE as a novel approach capable of evaluating mechanical properties of human blood clots based on Rayleigh wave propagation. This sensitive method can be used for the evaluation of the mechanical properties of human blood clot analogues and thrombectomy samples.

Esophageal diseases often necessitate resection of tissue. Current reconstruction options using autologous conduits such as stomach, colon, and small bowel have significant morbidity. Given these limitations in current therapy, we have developed a large animal model to regenerate short segments of esophageal tissue after circumferential full thickness resection. This is performed by implantation of an electrospun polyurethane tissue engineered graft which results in esophageal regrowth. These implantations have been performed both with cell based seeding the polymer scaffold and without with comparable regenerative results. It is possible that esophageal regeneration in this model has unequal contributions from either the proximal or distal esophagus. To determine preferential directionality of regeneration we aim to utilize biomechanical markers to suggest that there are unequal proximal and distal contributions to regenerated tissue. Given limited availability of regenerated tissue, use of a non‐destructive method to perform this testing would have significant utility. Through using our previously validated non‐destructive sonometric ex vivo method we aim to determine differences in mechanical behavior of the regenerated tissue in comparison to proximal and distal esophageal tissues. Using this method we are able to determine longitudinal and circumferential moduli and derive strain energy functions and parameters. Within this work we demonstrate that there are differences in mechanical behavior and that the regenerated tissue behaves more comparably to proximal esophageal tissue suggesting preferential regrowth and unequal contribution to regenerated tissue. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Abstract Arterial stiffness is an important biomarker for many cardiovascular diseases. Shear wave elastography is a recent technique aimed at estimating local arterial stiffness using guided wave inversion (GWI), i.e. matching the computed and measured wave dispersion. This paper develops and validates a new GWI approach by synthesizing various recent observations and algorithms: (a) refinements to signal processing to obtain more accurate experimental dispersion curves; (b) an efficient forward model to compute theoretical dispersion curves for immersed, incompressible cylindrical waveguides; (c) an optimization framework based on the recent observation that the measured dispersion curve is multimodal, i.e. it matches for not one but two different wave modes in two different frequency ranges. The resulting inversion approach is validated using extensive experimental data from rubber tube phantoms, not only for modulus estimation but also to simultaneously estimate modulus and wall thickness. The observations indicate that the modulus estimates are best performed with the information on wall thickness. The approach, which takes less than half a minute to run, is shown to be accurate, with the modulus estimated with less than 4% error for 70% of the experiments.

We report a technique, named optical coherence viscometry (OCV), to measure the viscosity of Newtonian fluids in a noncontact manner. According to linear wave theory with small amplitudes, capillary waves are associated with fluid mechanical properties. To perform this measurement and avoid the overdamped effects of capillary waves in viscous fluids, transient acoustic radiation force was applied to generate capillary waves. Within a very limited field-of-view using optical coherence tomography, wave motion acquired in the time domain was analyzed using Fourier methods to study the wave velocity dispersion and attenuation relationships for capillary waves, which can reduce the fluid quantity drastically into tissue culture scale. We measure the viscosities of water, water–glycerol solutions with three concentrations, and biological plasma using the proposed OCV and compare the experimental results to theoretical calculations. OCV is sensitive to wave perturbations and can be a promising technique for measuring the viscosity of biological fluids and could be applied in future applications for measurements for lipid membranes in cell biology and tissue engineering investigation.

Significance Statement Expression of immediate early response gene X-1 ( Iex-1 ), also known as Ier-3, is increased in venous neointimal hyperplasia (VNH) and stenosis in hemodialysis arteriovenous fistulas (AVF). In a porcine model, 1α,25(OH) 2 D 3 , an inhibitor of Ier3, reduced VNH/stenosis formation. The 1α,25(OH) 2 D 3 released in the perivascular AVF space from poly(lactic-co-glycolic acid) nanoparticles embedded in a Pluronic F127 hydrogel (1,25 NP) reduced Ier3 gene and protein expression, MCP-1, CD68, HIF-1α, and VEGF-A immunostaining. Concomitantly, blood flow, lumen area, pulse wave velocity, and Young’s modulus increased, and neointima area, peak systolic velocity, and wall shear stress decreased in 1,25 NP–treated vessels. RNA sequencing analysis identified 242 genes involved in inflammatory and apoptotic pathways that had decreased expression in 1,25 NP vessels. Background Few therapies prevent venous neointimal hyperplasia (VNH) and venous stenosis (VS) formation in arteriovenous fistulas (AVF). Expression of the immediate early response gene X-1 ( Iex-1 ), also known as Ier3, is associated with VNH and stenosis in murine AVFs. The study aimed to determine if local release of Ier3 long-acting inhibitor 1α,25(OH) 2 D 3 from poly(lactic-co-glycolic acid) (PLGA) nanoparticles embedded in a thermosensitive Pluronic F127 hydrogel (1,25 NP) could affect VNH/VS formation in a large animal model. Methods Immediately after AVF creation in a porcine model of renal failure, 1,25 NP or vehicle control was injected into the adventitia space of AVF outflow veins. Scanning electron microscopy and dynamic light scattering characterized drug and control nanoparticles. Animals were sacrificed 3 and 28 days later for gene expression, immunohistologic, magnetic resonance imaging and angiography, and ultrasound analyses. Whole transcriptome RNA sequencing with differential gene expression analysis was performed on outflow veins of AVF. Results Encapsulation of 1α,25(OH) 2 D 3 in PLGA nanoparticles formed nanoparticles of uniform size that were similar to nanoparticles without 1α,25(OH) 2 D 3 . The 1,25 NP–treated AVFs exhibited lower VNH/VS, Ier3 gene expression, and IER-3, MCP-1, CD68, HIF-1α, and VEGF-A immunostaining, fibrosis, and proliferation. Blood flow and lumen area increased significantly, whereas peak systolic velocity and wall shear stress decreased. Treatment increased Young’s modulus and correlated with histologic assessment of fibrosis and with no evidence of vascular calcification. RNA sequencing analysis showed changes in the expression of genes associated with inflammatory, TGFβ1, and apoptotic pathways. Conclusions Local release of 1,25 NP improves AVF flow and hemodynamics, and reduces stenosis in association with reduction in inflammation, apoptosis, and fibrosis in a porcine model of arteriovenous fistula.

Mechanical properties in tissues are an important indicator because they are associated with disease states. One of the well-known excitation sources in optical coherence elastography (OCE) to determine mechanical properties is acoustic radiation force (ARF); however, a complicated focusing alignment cannot be avoided. Another excitation source is a piezoelectric (PZT) stack to obtain strain images via compression, which can affect the intrinsic mechanical properties of tissues in tissue engineering. In this study, we report a new technique called two-dimensional (2D) dynamic vibration OCE (DV-OCE) to evaluate 2D wave velocities without tedious focusing alignment procedures and is a non-contact method with respect to the samples. The three-dimensional (3D) Fourier transform was utilized to transfer the traveling waves (x, y, t) into 3D k-space (kx, ky, f). A spatial 2D wavenumber filter and multi-angle directional filter were employed to decompose the waves with omni-directional components into four individual traveling directions. The 2D local wave velocity algorithm was used to calculate a 2D wave velocity map. Six materials, two homogeneous phantoms with 10 mm thickness, two homogeneous phantoms with 2 mm thickness, one heterogeneous phantom with 2 mm diameter inclusion and an ex vivo porcine kidney, were examined in this study. In addition, the ARF-OCE was used to evaluate wave velocities for comparison. Numerical simulations were performed to validate the proposed 2D dynamic vibration OCE technique. We demonstrate that the experimental results were in a good agreement with the results from ARF-OCE (transient OCE) and numerical simulations. Our proposed 2D dynamic vibration OCE could potentially pave the way for mechanical evaluation in tissue engineering and for laboratory translation with easy-to-setup and contactless advantages.

ObjectivesTo quantify the bias of shear wave speed (SWS) measurements between different commercial ultrasonic shear elasticity systems and a magnetic resonance elastography (MRE) system in elastic and viscoelastic phantoms.MethodsTwo elastic phantoms, representing healthy through fibrotic liver, were measured with 5 different ultrasound platforms, and 3 viscoelastic phantoms, representing healthy through fibrotic liver tissue, were measured with 12 different ultrasound platforms. Measurements were performed with different systems at different sites, at 3 focal depths, and with different appraisers. The SWS bias across the systems was quantified as a function of the system, site, focal depth, and appraiser. A single MRE research system was also used to characterize these phantoms using discrete frequencies from 60 to 500 Hz.ResultsThe SWS from different systems had mean difference 95% confidence intervals of ±0.145 m/s (±9.6%) across both elastic phantoms and ± 0.340 m/s (±15.3%) across the viscoelastic phantoms. The focal depth and appraiser were less significant sources of SWS variability than the system and site. Magnetic resonance elastography best matched the ultrasonic SWS in the viscoelastic phantoms using a 140 Hz source but had a − 0.27 ± 0.027‐m/s (−12.2% ± 1.2%) bias when using the clinically implemented 60‐Hz vibration source.ConclusionsShear wave speed reconstruction across different manufacturer systems is more consistent in elastic than viscoelastic phantoms, with a mean difference bias of < ±10% in all cases. Magnetic resonance elastographic measurements in the elastic and viscoelastic phantoms best match the ultrasound systems with a 140‐Hz excitation but have a significant negative bias operating at 60 Hz. This study establishes a foundation for meaningful comparison of SWS measurements made with different platforms.