Impact of isolation method on cellular activation and presence of specific tendon cell subpopulations during in vitro culture.

Tendon injuries are common and heal poorly, due in part to a lack of understanding of fundamental tendon cell biology. A major impediment to the study of tendon cells is the absence of robust, well-characterized in vitro models. Unlike other tissue systems, current tendon cell models do not account for how differences in isolation methodology may affect the activation state of tendon cells or the presence of various tendon cell subpopulations. The objective of this study was to characterize how common isolation methods affect the behavior, fate, and lineage composition of tendon cell cultures. Tendon cells isolated by explant exhibited reduced proliferative capacity, decreased expression of tendon marker genes, and increased expression of genes associated with fibroblast activation compared to digested cells. Consistently, explanted cells also displayed an increased propensity to differentiate to myofibroblasts compared to digested cells. Explanted cultures from multiple different tendons were substantially enriched for the presence of scleraxis-lineage (Scx-lin+) cells compared to digested cultures, while the overall percentage of S100a4-lineage (S100a4-lin+) cells was dependent on both isolation method and tendon of origin. Neither isolation methods preserved the ratios of Scx-lin+ or S100a4-lin+ to non-lineage cells seen in tendons in vivo. Combined, these data indicate that further refinement of in vitro cultures models is required in order to more accurately understand the effects of various stimuli on tendon cell behavior. Statement of clinical significance: The development of informed in vitro tendon cell models will facilitate enhanced screening of potential therapeutic candidates to improve tendon healing.

Evidence that reduction in volume protects in situ articular chondrocytes from mechanical impact.

Chondrocytes, the resident cells in articular cartilage, carry the burden of producing and maintaining the extracellular matrix (ECM). However, as these cells have a low proliferative capacity and are not readily replaced, chondrocyte death due to extreme forces may contribute to the pathogenesis of osteoarthritis (OA) after injury or may inhibit healing after osteochondral transplantation, a restorative procedure for damaged cartilage that requires a series of mechanical impacts to insert the graft. Consequently, there is a need to understand what factors influence the vulnerability of in situ chondrocytes to mechanical trauma. To this end, the objective of this study was to investigate how altering cell volume by different means (hydrostatic pressure, uniaxial load, and osmotic challenge with and without inhibition of regulatory volume decrease) affects the vulnerability of in situ chondrocytes to extreme mechanical forces. Using a custom experimental platform enabling testing of viable and intact murine cartilage-on-bone explants, we established a strong correlation between chondrocyte volume and vulnerability to impact injury wherein reduced volume was protective. Moreover, we found that the volume-perturbing interventions did not affect cartilage ECM mechanical properties, suggesting that their effects on chondrocyte vulnerability occurred at the cellular level. The findings of this study offer new avenues for novel strategies aimed at preventing chondrocyte loss during osteochondral grafting or to halting the progression of cell death after a joint destabilizing injury.

An Alternative Method to Characterize the Quasi-Static, Nonlinear Material Properties of Murine Articular Cartilage.

With the onset and progression of osteoarthritis (OA), articular cartilage (AC) mechanical properties are altered. These alterations can serve as an objective measure of tissue degradation. Although the mouse is a common and useful animal model for studying OA, it is extremely challenging to measure the mechanical properties of murine AC due to its small size (thickness < 50 µm). In this study, we developed novel and direct approach to independently quantify two quasi-static mechanical properties of mouse AC: the load-dependent (nonlinear) solid matrix Young's modulus (E) and drained Poisson's ratio (ν). The technique involves confocal microscope-based multiaxial strain mapping of compressed, intact murine AC followed by inverse finite element analysis (iFEA) to determine E and ν. Importantly, this approach yields estimates of E and ν that are independent of the initial guesses used for iterative optimization. As a proof of concept, mechanical properties of AC on the medial femoral condyles of wild-type mice were obtained for both trypsin-treated and control specimens. After proteolytic tissue degradation induced through trypsin treatment, a dramatic decrease in E was observed (compared to controls) at each of the three tested loading conditions. A significant decrease in ν due to trypsin digestion was also detected. These data indicate that the method developed in this study may serve as a valuable tool for comparative studies evaluating factors involved in OA pathogenesis using experimentally induced mouse OA models.

Ultrasound elastography to quantify average percent pressure-normalized strain reduction associated with different aortic endografts in 3D-printed hydrogel phantoms.

Objective: Strain has become a viable index for evaluating abdominal aortic aneurysm stability after endovascular aneurysm repair (EVAR). In addition, literature has shown that healthy aortic tissue requires a degree of strain to maintain homeostasis. This has led to the hypothesis that too much strain reduction conferred by a high degree of graft oversizing is detrimental to the aneurysm neck in the seal zone of abdominal aortic aneurysms after EVAR. We investigated this in a laboratory experiment by examining the effects that graft oversizing has on the pressure-normalized strain ( ε ρ + ¯ /pulse pressure [PP]) reduction using four different infrarenal EVAR endografts and our ultrasound elastography technique. Approximate graft oversizing percentages were 20% (30 mm phantom-graft combinations), 30% (28 mm phantom-graft combinations), and 50% (24 mm phantom-graft combinations). Methods: Axisymmetric, 10% by mass polyvinyl alcohol phantoms were connected to a flow simulator. Ultrasound elastography was performed before and after implantation with the four different endografts: (1) 36 mm polyester/stainless steel, (2) 36 mm polyester/electropolished nitinol, (3) 35 mm polytetrafluoroethylene (PTFE)/nitinol, and (4) 36 mm nitinol/polyester/platinum-iridium. Five ultrasound cine loops were taken of each phantom-graft combination. They were analyzed over two different cardiac cycles (end-diastole to end-diastole), yielding a total of 10 maximum mean principal strain ( ε ρ + ¯ ) values. ε ρ + ¯ was divided by pulse pressure to yield pressure-normalized strain ( ε ρ + ¯ /PP). An analysis of variance was performed for graft comparisons. We calculated the average percent ε ρ + ¯ /PP reduction by manufacturer and percent oversizing. These values were used for linear regression analysis. Results: Results from one-way analysis of variance showed a significant difference in ε ρ + ¯ /PP between the empty phantom condition and all oversizing conditions for all graft manufacturers (F(3, 56) = 106.7 [graft A], 132.7 [graft B], 106.5 [graft C], 105.7 [graft D], P < .0001 for grafts A-D). There was a significant difference when comparing the 50% condition with the 30% and 20% conditions across all manufacturers by post hoc analysis (P < .0001). No significant difference was found when comparing the 20% and 30% oversizing conditions for any of the manufacturers or when comparing ε ρ + ¯ /PP values across the manufacturers according to percent oversize. Linear regression demonstrated a significant positive correlation between the percent graft oversize and the all-graft average percent ε ρ + ¯ /PP reduction ( R 2  = 0.84, P < .0001). Conclusions: This brief report suggests that a 10% increase in graft oversizing leads to an approximate 5.9% reduction in ε ρ + ¯ /PP on average. Applied clinically, this increase may result in increased stiffness in axisymmetric vessels after EVAR. Further research is needed to determine if this is clinically significant.

Noninvasive vascular displacement estimation for relative elastic modulus reconstruction in transversal imaging planes.

Atherosclerotic plaque rupture can initiate stroke or myocardial infarction. Lipid-rich plaques with thin fibrous caps have a higher risk to rupture than fibrotic plaques. Elastic moduli differ for lipid-rich and fibrous tissue and can be reconstructed using tissue displacements estimated from intravascular ultrasound radiofrequency (RF) data acquisitions. This study investigated if modulus reconstruction is possible for noninvasive RF acquisitions of vessels in transverse imaging planes using an iterative 2D cross-correlation based displacement estimation algorithm. Furthermore, since it is known that displacements can be improved by compounding of displacements estimated at various beam steering angles, we compared the performance of the modulus reconstruction with and without compounding. For the comparison, simulated and experimental RF data were generated of various vessel-mimicking phantoms. Reconstruction errors were less than 10%, which seems adequate for distinguishing lipid-rich from fibrous tissue. Compounding outperformed single-angle reconstruction: the interquartile range of the reconstructed moduli for the various homogeneous phantom layers was approximately two times smaller. Additionally, the estimated lateral displacements were a factor of 2-3 better matched to the displacements corresponding to the reconstructed modulus distribution. Thus, noninvasive elastic modulus reconstruction is possible for transverse vessel cross sections using this cross-correlation method and is more accurate with compounding.

A Deep Learning Framework to Estimate Elastic Modulus from Ultrasound Measured Displacement Fields.

Ultrasound (US) elastography is a technique that enables non-invasive quantification of material properties, such as stiffness, from ultrasound images of deforming tissue. The displacement field is measured from the US images using image matching algorithms, and then a parameter, often the elastic modulus, is inferred or subsequently measured to identify potential tissue pathologies, such as cancerous tissues. Several traditional inverse problem approaches, loosely grouped as either direct or iterative, have been explored to estimate the elastic modulus. Nevertheless, the iterative techniques are typically slow and computationally intensive, while the direct techniques, although more computationally efficient, are very sensitive to measurement noise and require the full displacement field data (i.e., both vector components). In this work, we propose a deep learning approach to solve the inverse problem and recover the spatial distribution of the elastic modulus from one component of the US measured displacement field. The neural network used here is trained using only simulated data obtained via a forward finite element (FE) model with known variations in the modulus field, thus avoiding the reliance on large measurement data sets that may be challenging to acquire. A U-net based neural network is then used to predict the modulus distribution (i.e., solve the inverse problem) using the simulated forward data as input. We quantitatively evaluated our trained model with a simulated test dataset and observed a 0.0018 mean squared error (MSE) and a 1.14% mean absolute percent error (MAPE) between the reconstructed and ground truth elastic modulus. Moreover, we also qualitatively compared the output of our U-net model to experimentally measured displacement data acquired using a US elastography tissue-mimicking calibration phantom.

Intermediate pressure-normalized principal wall strain values are associated with increased abdominal aortic aneurysmal growth rates.

Introduction: Current abdominal aortic aneurysm (AAA) assessment relies on analysis of AAA diameter and growth rate. However, evidence demonstrates that AAA pathology varies among patients and morphometric analysis alone is insufficient to precisely predict individual rupture risk. Biomechanical parameters, such as pressure-normalized AAA principal wall strain (ερ+¯/PP, %/mmHg), can provide useful information for AAA assessment. Therefore, this study utilized a previously validated ultrasound elastography (USE) technique to correlate ερ+¯/PP with the current AAA assessment methods of maximal diameter and growth rate. Methods: Our USE algorithm utilizes a finite element mesh, overlaid a 2D cross-sectional view of the user-defined AAA wall, at the location of maximum diameter, to track two-dimensional, frame-to-frame displacements over a full cardiac cycle, using a custom image registration algorithm to produce ερ+¯/PP. This metric was compared between patients with healthy aortas and AAAs (≥3 cm) and compared between small and large AAAs (≥5 cm). AAAs were then separated into terciles based on ερ+¯/PP values to further assess differences in our metric across maximal diameter and prospective growth rate. Non-parametric tests of hypotheses were used to assess statistical significance as appropriate. Results: USE analysis was conducted on 129 patients, 16 healthy aortas and 113 AAAs, of which 86 were classified as small AAAs and 27 as large. Non-aneurysmal aortas showed higher ερ+¯/PP compared to AAAs (0.044 ± 0.015 vs. 0.034 ± 0.017%/mmHg, p = 0.01) indicating AAA walls to be stiffer. Small and large AAAs showed no difference in ερ+¯/PP. When divided into terciles based on ερ+¯/PP cutoffs of 0.0251 and 0.038%/mmHg, there was no difference in AAA diameter. There was a statistically significant difference in prospective growth rate between the intermediate tercile and the outer two terciles (1.46 ± 2.48 vs. 3.59 ± 3.83 vs. 1.78 ± 1.64 mm/yr, p = 0.014). Discussion: There was no correlation between AAA diameter and ερ+¯/PP, indicating biomechanical markers of AAA pathology are likely independent of diameter. AAAs in the intermediate tercile of ερ+¯/PP values were found to have nearly double the growth rates than the highest or lowest tercile, indicating an intermediate range of ερ+¯/PP values for which patients are at risk for increased AAA expansion, likely necessitating more frequent imaging follow-up.

Three-dimensional sonographic measurement of blood volume flow in the umbilical cord.

OBJECTIVES: Three-dimensional (3D) umbilical cord blood volume flow measurement with the intention of providing a straightforward, consistent, and accurate method that overcomes the limitations associated with traditional pulsed wave Doppler flow measurement and provides a means by which to recognize and manage at-risk pregnancies. METHODS: The first study involved 3D sonographic volume flow measurements in 7 healthy ewes whose pregnancies ranged from 18 to 19 weeks' gestation (7 singletons). Sonographic umbilical arterial and venous flow measurements from each fetus were compared to the corresponding average measured arterial/venous flow to assess the feasibility of measurement in a static vessel. A second complementary study involved 3D sonographic volume flow measurements in 7 healthy women whose pregnancies ranged from 17.9 to 36.3 weeks' gestation (6 singletons and 1 twin). Umbilical venous flow measurements were compared to similar flow measurements reported in the literature. Pregnancy outcomes were abstracted from the medical records of the recruited patients. RESULTS: In the fetal sheep model, arterial/venous flow comparisons yielded errors of 10% or less for 8 of the 9 measurements. In the clinical study, venous flow measurements showed agreement with the literature over a range of gestational ages. Two of the 7 patients in the clinical study had lower flow than anticipated for gestational age; one had a subsequent diagnosis of intrauterine growth restriction, and the other had preeclampsia. CONCLUSIONS: Accurate measurement of umbilical blood volume flow can be performed with relative ease in both the sheep model and in humans using the proposed 3D sonographic flow measurement technique. Results encourage further development of the method as a means for diagnosis and identification of at-risk pregnancies.

Ultrasound strain mapping of the mouse Achilles tendon during passive dorsiflexion.

Immediately prior to inserting into bone, many healthy tendons experience impingement from nearby bony structures. However, super-physiological levels of impingement are implicated in insertional tendinopathies. Unfortunately, the mechanisms underlying the connection between impingement and tendon pathology remain poorly understood, in part due to the shortage of well-characterized animal models of impingement at clinically relevant sites. As a first step towards developing a model of excessive tendon impingement, the objective of this study was to characterize the mechanical strain environment in the mouse Achilles tendon insertion under passive dorsiflexion and confirm that - like humans - mice experience impingement of the tendon insertion from the calcaneus (heel bone) in dorsiflexed ankle positions. Based on previous work in humans, we hypothesized that during dorsiflexion, the mouse Achilles tendon insertion would experience high levels of transverse compressive strain due to calcaneal impingement. A custom-built loading platform was used to apply passive dorsiflexion, while an ultrasound transducer positioned over the Achilles tendon captured radiofrequency images. A non-rigid image registration algorithm was then used to map the transverse compressive strain based on the acquired ultrasound image sequences. Our results demonstrate that during passive dorsiflexion, transverse compressive strains were produced throughout the Achilles tendon, with significantly larger strain magnitudes at the tendon insertion than at the midsubstance. Furthermore, there was increasing transverse compressive strain observed within the Achilles tendon as a function of increasing dorsiflexion angle. This study enhances our understanding of the unique mechanical loading environment of the Achilles tendon under physiologically relevant conditions.

Impingement in Insertional Achilles Tendinopathy Occurs Across a Larger Range of Ankle Angles and Is Associated With Increased Tendon Thickness.

BACKGROUND: Insertional Achilles tendinopathy (IAT) is characterized by tendon degeneration and thickening near the tendon-bone insertion.11 Calcaneal impingement is believed to contribute to the pathogenesis of IAT.5 However, it is unclear how increased tendon thickness in individuals with IAT influences impingement. This study aimed to compare Achilles tendon impingement in individuals with and without IAT. METHODS: Eight healthy adults and 12 adults with clinically diagnosed symptomatic IAT performed a passive flexion exercise during which ankle flexion angle, anterior-posterior (A-P) thickness, and an ultrasonographic image sequence of the Achilles tendon insertion were acquired. The angle of ankle plantarflexion at which the calcaneus first impinges the Achilles tendon, defined as the impingement onset angle, was identified by (1) a anonymized observer (visual inspection method) and (2) a computational image deformation-based approach (curvature method). RESULTS: Although the 2 methods provided different impingement onset angles, the measurements were strongly correlated (R2 = 0.751, P < .05). The impingement onset angle and the thickness of the Achilles tendon insertion were greater in subjects with clinically diagnosed IAT (P = .0048, P = .0047). Furthermore, impingement onset angle proved to have a moderate correlation with anterior-posterior thickness (R2 = 0.454, P < .05). CONCLUSION: Our findings demonstrated that increased tendon thickness in IAT patients is associated with larger impingement onset angles, raising the range of ankle angles over which the tendon is exposed to impingement. CLINICAL RELEVANCE: Increased susceptibility to impingement may exacerbate or perpetuate the pathology, highlighting the need for clinical strategies to reduce impingement in IAT patients.

Changes in intraoperative aortic strain as detected by ultrasound elastography in patients following abdominal endovascular aneurysm repair.

Objective: Predicting success after endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAAs) relies on measurements of aneurysm sac regression. However, in the absence of regression, morphometric analysis alone is insufficient to reliably predict the successful remodeling of AAAs after EVAR. Biomechanical parameters, such as pressure-normalized principal strain, might provide useful information in the post-EVAR AAA assessment. Our objective was to assess the feasibility of our novel ultrasound elastography (USE) technique to detect changes in the aortic wall principal strain in patients who had undergone EVAR and determine the temporal nature of the biomechanical changes in the aorta. Methods: USE images were obtained from patients undergoing elective EVAR intraoperatively, immediately before and after endograft implantation, and at their 30-day follow-up. The maximal mean principal strain ( ε ρ + ¯ ) for each scan was assessed using our novel technique, which uses a finite element mesh to track the frame-to-frame displacements of the aortic wall over one cardiac cycle. The ε ρ + ¯ in the user-defined aortic wall was then divided by the pulse pressure at the time of the scan to produce a pressure-normalized strain measurement ( ε ρ + ¯ /PP), a surrogate for tissue stiffness. Paired t tests were used to compare the pre- and postoperative ε ρ + ¯ /PP and the postoperative and 30-day ε ρ + ¯ /PP. Patient 30-day sac regression and endoleak data were collected by a review of 30-day follow-up computed tomography scans. Results: USE analysis of the data from 12 patients demonstrated a significant reduction in aortic wall ε ρ + ¯ /PP (average, 0.191% ± 0.09%/kPa vs 0.087% ± 0.04%/kPa; P = .002) immediately after graft implantation, with a nonsignificant change in the ε ρ + ¯ /PP (0.091% ± 0.04%/kPa vs 0.102% ± 0.05%/kPa; P = .47) from postoperatively to 30-day follow-up. This represents an average 46.5% reduction after stent placement, with a nonsignificant 18.1% increase at 30-day follow-up. All the patients showed sac stability, except for two patients who had demonstrated 7.3-mm and 6.8-mm sac regressions. Conclusions: Our analysis has demonstrated that the presented USE technique is a feasible method for detecting significant reductions in aortic ε ρ + ¯ /PP intraoperatively after EVAR. We found that patients undergoing EVAR will experience large reductions in the ε ρ + ¯ /PP intraoperatively after graft implantation, with stabilization found at their 30-day follow-up. These preliminary data have shown that an intraoperative ε ρ + ¯ /PP reduction could be a promising correlate of post-EVAR aneurysm remodeling. Our results have also suggested that endograft design likely plays a large role in determining the aneurysm biomechanical changes immediately after implantation.

Characterization of vascular strain during in-vitro angioplasty with high-resolution ultrasound speckle tracking.

BACKGROUND: Ultrasound elasticity imaging provides biomechanical and elastic properties of vascular tissue, with the potential to distinguish between tissue motion and tissue strain. To validate the ability of ultrasound elasticity imaging to predict structurally defined physical changes in tissue, strain measurement patterns during angioplasty in four bovine carotid artery pathology samples were compared to the measured physical characteristics of the tissue specimens. METHODS: Using computational image-processing techniques, the circumferences of each bovine artery specimen were obtained from ultrasound and pathologic data. RESULTS: Ultrasound-strain-based and pathology-based arterial circumference measurements were correlated with an R2 value of 0.94 (p = 0.03). The experimental elasticity imaging results confirmed the onset of deformation of an angioplasty procedure by indicating a consistent inflection point where vessel fibers were fully unfolded and vessel wall strain initiated. CONCLUSION: These results validate the ability of ultrasound elasticity imaging to measure localized mechanical changes in vascular tissue.

Venous elastography: validation of a novel high-resolution ultrasound method for measuring vein compliance using finite element analysis.

Ultrasonography for the noninvasive assessment of tissue properties has enjoyed widespread success. With the growing emphasis in recent years on arteriovenous fistulae (AVFs) for dialysis vascular access in patients with end-stage renal disease, and on reducing AVF failures, there is increasing interest in ultrasound for the preoperative evaluation of the mechanical and elastic properties of arteries and veins. This study used high-resolution ultrasound with phase-sensitive speckle tracking to obtain in vivo vein elasticity measurements during dilation. The results of this novel ultrasound technique were then compared to a computer model of venous strain. The computer model and ultrasound analysis of the vessel wall demonstrated internally consistent positive and negative longitudinal strain values as the vein wall underwent dilation. These results support further investigation of the use of phase-sensitive speckle tracking for ultrasound venous mapping for preoperative vascular access evaluation.

Arterial elasticity imaging: comparison of finite-element analysis models with high-resolution ultrasound speckle tracking.

BACKGROUND: The nonlinear mechanical properties of internal organs and tissues may be measured with unparalleled precision using ultrasound imaging with phase-sensitive speckle tracking. The many potential applications of this important noninvasive diagnostic approach include measurement of arterial stiffness, which is associated with numerous major disease processes. The accuracy of previous ultrasound measurements of arterial stiffness and vascular elasticity has been limited by the relatively low strain of nonlinear structures under normal physiologic pressure and the measurement assumption that the effect of the surrounding tissue modulus might be ignored in both physiologic and pressure equalized conditions. METHODS: This study performed high-resolution ultrasound imaging of the brachial artery in a healthy adult subject under normal physiologic pressure and the use of external pressure (pressure equalization) to increase strain. These ultrasound results were compared to measurements of arterial strain as determined by finite-element analysis models with and without a surrounding tissue, which was represented by homogenous material with fixed elastic modulus. RESULTS: Use of the pressure equalization technique during imaging resulted in average strain values of 26% and 18% at the top and sides, respectively, compared to 5% and 2%, at the top and sides, respectively, under physiologic pressure. In the artery model that included surrounding tissue, strain was 19% and 16% under pressure equalization versus 9% and 13% at the top and sides, respectively, under physiologic pressure. The model without surrounding tissue had slightly higher levels of strain under physiologic pressure compared to the other model, but the resulting strain values under pressure equalization were > 60% and did not correspond to experimental values. CONCLUSIONS: Since pressure equalization may increase the dynamic range of strain imaging, the effect of the surrounding tissue on strain should be incorporated into models of arterial strain, particularly when the pressure equalization technique is used.

Quantitative three-dimensional elasticity imaging from quasi-static deformation: a phantom study.

We present a methodology to image and quantify the shear elastic modulus of three-dimensional (3D) breast tissue volumes held in compression under conditions similar to those of a clinical mammography system. Tissue phantoms are made to mimic the ultrasonic and mechanical properties of breast tissue. Stiff lesions are created in these phantoms with size and modulus contrast values, relative to the background, that are within the range of values of clinical interest. A two-dimensional ultrasound system, scanned elevationally, is used to acquire 3D images of these phantoms as they are held in compression. From two 3D ultrasound images, acquired at different compressed states, a three-dimensional displacement vector field is measured. The measured displacement field is then used to solve an inverse problem, assuming the phantom material to be an incompressible, linear elastic solid, to recover the shear modulus distribution within the imaged volume. The reconstructed values are then compared to values measured independently by direct mechanical testing.

Non-Invasive Ultrasound Quantification of Scar Tissue Volume Identifies Early Functional Changes During Tendon Healing.

Tendon injuries are very common and disrupt the transmission of forces from muscle to bone, leading to impaired function and quality of life. Successful restoration of tendon function after injury is a challenging clinical problem due to the pathological, scar-mediated manner in which the tendons heal. Currently, there are no standard treatments to modulate scar tissue formation and improve tendon healing. A major limitation to the identification of therapeutic candidates has been the reliance on terminal endpoint metrics of healing in pre-clinical studies, which require a large number of animals and result in destruction of the tissue. To address this limitation, we have identified quantification of scar tissue volume (STV) from ultrasound (US) imaging as a longitudinal, non-invasive metric of tendon healing. STV was strongly correlated with established endpoint metrics of gliding function including gliding resistance and metatarsophalangeal (MTP) flexion angle. However, no associations were observed between STV and structural or material properties. To define the sensitivity of STV to identify differences between functionally discrete tendon healing phenotypes, we utilized S100a4 haploinsufficient mice (S100a4GFP/+ ), which heal with improved gliding function relative to wild-type (WT) littermates. A significant decrease in STV was observed in S100a4GFP/+ repairs, relative to WT at day 14. Taken together, these data suggest US quantification of STV as a means to facilitate the rapid screening of biological and pharmacological interventions to improve tendon healing, and identify promising therapeutic targets, in an efficient, cost-effective manner. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2476-2485, 2019.

Manufacturing Abdominal Aorta Hydrogel Tissue-Mimicking Phantoms for Ultrasound Elastography Validation.

Ultrasound (US) elastography, or elasticity imaging, is an adjunct imaging technique that utilizes sequential US images of soft tissues to measure the tissue motion and infer or quantify the underlying biomechanical characteristics. For abdominal aortic aneurysms (AAA), biomechanical properties such as changes in the tissue's elastic modulus and estimates of the tissue stress may be essential for assessing the need for the surgical intervention. Abdominal aortic aneurysms US elastography could be a useful tool to monitor AAA progression and identify changes in biomechanical properties characteristic of high-risk patients. A preliminary goal in the development of an AAA US elastography technique is the validation of the method using a physically relevant model with known material properties. Here we present a process for the production of AAA tissue-mimicking phantoms with physically relevant geometries and spatially modulated material properties. These tissue phantoms aim to mimic the US properties, material modulus, and geometry of the abdominal aortic aneurysms. Tissue phantoms are made using a polyvinyl alcohol cryogel (PVA-c) and molded using 3D printed parts created using computer aided design (CAD) software. The modulus of the phantoms is controlled by altering the concentration of PVA-c and by changing the number of freeze-thaw cycles used to polymerize the cryogel. The AAA phantoms are connected to a hemodynamic pump, designed to deform the phantoms with the physiologic cyclic pressure and flows. Ultra sound image sequences of the deforming phantoms allowed for the spatial calculation of the pressure normalized strain and the identification of mechanical properties of the vessel wall. Representative results of the pressure normalized strain are presented.

(PEAK) WALL STRESS AS AN INDICATOR OF ABDOMINAL AORTIC ANEURYSM SEVERITY.

Abdominal aortic aneurysms, which consist of dilatations of the infra-renal aorta by at least 1.5 times of its normal diameter, are becoming a leading cause of death worldwide. Rupture often occurs unexpectedly, before a repair procedure is conducted. The AAA maximum diameter has been used as a clinical criterion to monitor AAA severity. However, assessment of AAA rupture risk requires knowledge of wall stress and wall strength at the potential rupture location. We conducted a study on 37 patient specific CT datasets to investigate the benefits of using peak wall stress instead of Dmax for AAA rupture severity. Correlation between PWS and 24 geometric indices and biomechanical factors was studied where eleven of them showed a statistically significant correlation with PWS. A Finite Element Analysis Rupture Index was used to conclude that the use of D max as a single predictor of AAA behavior and severity may be insufficient based on our patient population with a Dmax smaller than the 5.5 cm, clinically recommended repair threshold.

Insertional achilles tendinopathy associated with altered transverse compressive and axial tensile strain during ankle dorsiflexion.

The purposes of this case-control study (N = 20) were to examine the effects of insertional Achilles tendinopathy (IAT) and tendon region on tendon strain in patients with IAT compared to a control group without tendinopathy. An ultrasound transducer was positioned over the Achilles tendon insertion during dorsiflexion tasks, which included standing and partial squat. A non-rigid image registration-based algorithm was used to estimate transverse compressive and axial tensile strains of the tendon from radiofrequency ultrasound images, which was segmented into two regions (superficial tendon and deep). For transverse compressive strain, two-way mixed effects ANOVAs demonstrated that there were interaction effects between group and tendon region for both dorsiflexion tasks (Heel lowering, p = 0.004; Partial squat, p = 0.008). For axial tensile strain, the IAT group demonstrated a main effect of lower tensile strain than the control group (Standing, p = 0.001; Partial squat, p = 0.033). There was also a main effect of greater tensile strain in the superficial region of the tendon compared to the deep during standing (p = 0.002), but not during partial squat (p = 0.603). Reduced transverse compressive and axial tensile strains in the IAT group indicate altered mechanical properties specific to the region of IAT pathology. Additionally, patterns of compressive strain are consistent with the theory of calcaneal impingement contributing to IAT pathology. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:910-915, 2017.

Detecting Regional Stiffness Changes in Aortic Aneurysmal Geometries Using Pressure-Normalized Strain.

Transabdominal ultrasound elasticity imaging could improve the assessment of rupture risk for abdominal aortic aneurysms by providing information on the mechanical properties and stress or strain states of vessel walls. We implemented a non-rigid image registration method to visualize the pressure-normalized strain within vascular tissues and adapted it to measure total strain over an entire cardiac cycle. We validated the algorithm's performance with both simulated ultrasound images with known principal strains and anatomically accurate heterogeneous polyvinyl alcohol cryogel vessel phantoms. Patient images of abdominal aortic aneurysm were also used to illustrate the clinical feasibility of our imaging algorithm and the potential value of pressure-normalized strain as a clinical metric. Our results indicated that pressure-normalized strain could be used to identify spatial variations in vessel tissue stiffness. The results of this investigation were sufficiently encouraging to warrant a clinical study measuring abdominal aortic pressure-normalized strain in a patient population with aneurysmal disease.