Meta Data Analysis of Sex Distribution of Study Samples Reported in Summer Biomechanics, Bioengineering, and Biotransport Annual Conference Abstracts.

The biased use of male subjects in biomedical research has created limitations, underscoring the importance of including women to enhance the outcomes of evidence-based medicine and to promote human health. While federal policies (e.g., the 1993 Revitalization Act and the 2016 Sex as a Biological Variable Act) have aimed to improve sex balance in studies funded by the National Institutes of Health (NIH), data on sex inclusivity in non-NIH funded research remain limited. The objective of this study was to analyze the trend of sex inclusion in abstracts submitted to the Summer Biomechanics, Bioengineering, & Biotransport Conference (SB3C) over 7 years. We scored every abstract accepted to SB3C, and the findings revealed that approximately 20% of total abstracts included sex-related information, and this trend remained stable. Surprisingly, there was no significant increase in abstracts, including both sexes and those with balanced female and male samples. The proportion of abstracts with balanced sexes was notably lower than those including both sexes. Additionally, we examined whether the exclusion of one sex from the corresponding studies was justified by the research questions. Female-only studies had a 50% justification rate, while male-only studies had only 2% justification. Disparity in sex inclusion in SB3C abstracts was apparent, prompting us to encourage scientists to be more mindful of the sex of the research samples. Addressing sex inclusivity in biomechanics and mechanobiology research is essential for advancing medical knowledge and for promoting better healthcare outcomes for everyone.

Vascular Remodeling During Late-Gestation Pregnancy: An In-Vitro Assessment of the Murine Ascending Thoracic Aorta.

Maternal mortality due to cardiovascular disease is a rising concern in the U.S. Pregnancy triggers changes in the circulatory system, potentially influencing the structure of the central vasculature. Evidence suggests a link between a woman's pregnancy history and future cardiovascular health, but our understanding remains limited. To fill this gap, we examined the passive mechanics of the murine ascending thoracic aorta during late gestation. By performing biaxial mechanical testing on the ascending aorta, we were able to characterize the mechanical properties of both control and late-gestation tissues. By examining mechanical, structural, and geometric properties, we confirmed that remodeling of the aortic wall occurred. Morphological and mechanical properties of the tissue indicated an outward expansion of the tissue, as reflected in changes in wall thickness (∼12% increase) and luminal diameter (∼6% increase) at its physiologically loaded state in the pregnant group. With these geometric adaptations and despite increased hemodynamic loads, pregnancy did not induce significant changes in the tensile wall stress at the similar physiological pressure levels of the pregnant and control tissues. The alterations also included reduced intrinsic stiffness in the circumferential direction (∼18%) and reduced structural stiffness (∼26%) in the pregnant group. The observed vascular remodeling maintained the elastic stored energy of the aortic wall under systolic loads, indicating preservation of vascular function. Data from our study of pregnancy-related vascular remodeling will provide valuable insights for future investigations of maternal cardiovascular health.

An Experiential Learning Opportunity in Norway: Computation for Bioengineering and Mechanical Engineering Students.

The global learning initiative at Northeastern University is focused on fostering intercultural communication skills. The Dialogue of Civilization (DOC) program serves as a mechanism to achieve such a goal by offering faculty-led international experiences. In this paper, we have presented a detailed account of a DOC program that took place in Norway. The primary objective of the program was to teach mechanical engineering and bio-engineering students computational skills while stimulating critical thinking about the cultural and social aspects of technology and engineering in Norway. The program focused on two courses: a technical course and a special topics course. The technical course introduced students to finite element analysis, with practical applications and site visits in Norway to enhance experiential learning. In the special topics course, the interplay between modern technologies, like green energy, state policies, and the rights and traditions of the indigenous Sámi people was explored. The course highlighted both the progressive social policies in Norway and the historical discrimination against the Sámi. Student feedback was positive and experiential learning components such as guest lectures and site visits were particularly appreciated. Additional surveys showed that students' self-confidence was higher following the DOC program. In addition, female-identifying students had higher confidence in their future success after completion of this program as compared to their male-identifying counterparts. Our paper is expected to serve as a resource for educators seeking to integrate technical education with intercultural experiences and discussions on social and cultural impacts in engineering.

Who bears the load? IOP-induced collagen fiber recruitment over the corneoscleral shell.

Collagen is the main load-bearing component of cornea and sclera. When stretched, both of these tissues exhibit a behavior known as collagen fiber recruitment. In recruitment, as the tissues stretch the constitutive collagen fibers lose their natural waviness, progressively straightening. Recruited, straight, fibers bear substantially more mechanical load than non-recruited, wavy, fibers. As such, the process of recruitment underlies the well-established nonlinear macroscopic behavior of the corneoscleral shell. Recruitment has an interesting implication: when recruitment is incomplete, only a fraction of the collagen fibers is actually contributing to bear the loads, with the rest remaining "in reserve". In other words, at a given intraocular pressure (IOP), it is possible that not all the collagen fibers of the cornea and sclera are actually contributing to bear the loads. To the best of our knowledge, the fraction of corneoscleral shell fibers recruited and contributing to bear the load of IOP has not been reported. Our goal was to obtain regionally-resolved estimates of the fraction of corneoscleral collagen fibers recruited and in reserve. We developed a fiber-based microstructural constitutive model that could account for collagen fiber undulations or crimp via their tortuosity. We used experimentally-measured collagen fiber crimp tortuosity distributions in human eyes to derive region-specific nonlinear hyperelastic mechanical properties. We then built a three-dimensional axisymmetric model of the globe, assigning region-specific mechanical properties and regional anisotropy. The model was used to simulate the IOP-induced shell deformation. The model-predicted tissue stretch was then used to quantify collagen recruitment within each shell region. The calculations showed that, at low IOPs, collagen fibers in the posterior equator were recruited the fastest, such that at a physiologic IOP of 15 mmHg, over 90% of fibers were recruited, compared with only a third in the cornea and the peripapillary sclera. The differences in recruitment between regions, in turn, mean that at a physiologic IOP the posterior equator had a fiber reserve of only 10%, whereas the cornea and peripapillary sclera had two thirds. At an elevated IOP of 50 mmHg, collagen fibers in the limbus and the anterior/posterior equator were almost fully recruited, compared with 90% in the cornea and the posterior sclera, and 70% in the peripapillary sclera and the equator. That even at such an elevated IOP not all the fibers were recruited suggests that there are likely other conditions that challenge the corneoscleral tissues even more than IOP. The fraction of fibers recruited may have other potential implications. For example, fibers that are not bearing loads may be more susceptible to enzymatic digestion or remodeling. Similarly, it may be possible to control tissue stiffness through the fraction of recruited fibers without the need to add or remove collagen.

Association between resistance to cerebrospinal fluid flow and cardiac-induced brain tissue motion for Chiari malformation type I.

PURPOSE: Chiari malformation type I (CMI) patients have been independently shown to have both increased resistance to cerebrospinal fluid (CSF) flow in the cervical spinal canal and greater cardiac-induced neural tissue motion compared to healthy controls. The goal of this paper is to determine if a relationship exists between CSF flow resistance and brain tissue motion in CMI subjects. METHODS: Computational fluid dynamics (CFD) techniques were employed to compute integrated longitudinal impedance (ILI) as a measure of unsteady resistance to CSF flow in the cervical spinal canal in thirty-two CMI subjects and eighteen healthy controls. Neural tissue motion during the cardiac cycle was assessed using displacement encoding with stimulated echoes (DENSE) magnetic resonance imaging (MRI) technique. RESULTS: The results demonstrate a positive correlation between resistance to CSF flow and the maximum displacement of the cerebellum for CMI subjects (r = 0.75, p = 6.77 × 10-10) but not for healthy controls. No correlation was found between CSF flow resistance and maximum displacement in the brainstem for CMI or healthy subjects. The magnitude of resistance to CSF flow and maximum cardiac-induced brain tissue motion were not statistically different for CMI subjects with and without the presence of five CMI symptoms: imbalance, vertigo, swallowing difficulties, nausea or vomiting, and hoarseness. CONCLUSION: This study establishes a relationship between CSF flow resistance in the cervical spinal canal and cardiac-induced brain tissue motion in the cerebellum for CMI subjects. Further research is necessary to understand the importance of resistance and brain tissue motion in the symptomatology of CMI.

Impact of Blood Rheology on Transition to Turbulence and Wall Vibration Downstream of a Stenosis.

Previous experimental flow studies have demonstrated a delay (∼20%) in transition to turbulence for whole blood compared to a Newtonian analog fluid in both a straight pipe and eccentric stenosis model with ridged walls. The impact of wall compliance on the transition to turbulence of blood compared to Newtonian analog and on wall vibration is unknown. The present study employed flexible walls downstream of an eccentric stenosis model and examined the wall vibration during the transition to turbulence with whole blood and a Newtonian analog. Measurements of tube wall vibration velocity (WVV) were used as an indicator of the turbulence level within the flexible tube. WVV was measured at 5, 10, and 15 diameters downstream of the stenosis using a laser Doppler vibrometer at Reynolds numbers 0, 200, 300, 350, 400, 450, 500, 550, 600, 650, 700, and 750. The root mean squares (RMS) of the measured WVV were utilized as an indirect measure of fluid velocity fluctuations present at that location, and hence, an indicator of transition to turbulence. WVV RMS was near-constant until approximately Reynolds number 400. It increased monotonically with Reynolds number for both whole blood and the Newtonian fluid. No differences in the transition to turbulence were observed between whole blood and the Newtonian fluid, as the WVV RMS curves were remarkably similar in shape. This result suggests that rheology had minimal impact on the WVV downstream of a stenosis for transition to turbulence since the fluids had a similar level of vibration.

The Relationship Between Imbalance Symptom and Cardiac Pulsation Induced Mechanical Strain in the Brainstem and Cerebellum for Chiari Malformation Type I.

Chiari malformation Type I (CMI) is known to have an altered biomechanical environment for the brainstem and cerebellum; however, it is unclear whether these altered biomechanics play a role in the development of CMI symptoms. We hypothesized that CMI subjects have a higher cardiac-induced strain in specific neurological tracts pertaining to balance, and postural control. We measured displacement over the cardiac cycle using displacement encoding with stimulated echoes magnetic resonance imaging in the cerebellum, brainstem, and spinal cord in 37 CMI subjects and 25 controls. Based on these measurements, we computed strain, translation, and rotation in tracts related to balance. The global strain on all tracts was small (<1%) for CMI subject and controls. Strain was found to be nearly doubled in three tracts for CMI subjects compared to controls (p < 0.03). The maximum translation and rotation were ∼150 µm and ∼1 deg, respectively and 1.5-2 times greater in CMI compared to controls in four tracts (p < 0.005). There was no significant difference between strain, translation, and rotation on the analyzed tracts in CMI subjects with imbalance compared to those without imbalance. A moderate correlation was found between cerebellar tonsillar position and strain on three tracts. The lack of statistically significant difference between strain in CMI subjects with and without imbalance could imply that the magnitude of the observed cardiac-induced strain was too small to cause substantial damage to the tissue (<1%). Activities such as coughing, or Valsalva may produce a greater strain.

Cerebellar and Brainstem Displacement Measured with DENSE MRI in Chiari Malformation Following Posterior Fossa Decompression Surgery.

Background Posterior fossa decompression (PFD) surgery is a treatment for Chiari malformation type I (CMI). The goals of surgery are to reduce cerebellar tonsillar crowding and restore posterior cerebral spinal fluid flow, but regional tissue biomechanics may also change. MRI-based displacement encoding with stimulated echoes (DENSE) can be used to assess neural tissue displacement. Purpose To assess neural tissue displacement by using DENSE MRI in participants with CMI before and after PFD surgery and examine associations between tissue displacement and symptoms. Materials and Methods In a prospective, HIPAA-compliant study of patients with CMI, midsagittal DENSE MRI was performed before and after PFD surgery between January 2017 and June 2020. Peak tissue displacement over the cardiac cycle was quantified in the cerebellum and brainstem, averaged over each structure, and compared before and after surgery. Paired t tests and nonparametric Wilcoxon signed-rank tests were used to identify surgical changes in displacement, and Spearman correlations were determined between tissue displacement and presurgery symptoms. Results Twenty-three participants were included (mean age ± standard deviation, 37 years ± 10; 19 women). Spatially averaged (mean) peak tissue displacement demonstrated reductions of 46% (79/171 µm) within the cerebellum and 22% (46/210 µm) within the brainstem after surgery (P < .001). Maximum peak displacement, calculated within a circular 30-mm2 area, decreased by 64% (274/427 µm) in the cerebellum and 33% (100/300 µm) in the brainstem (P < .001). No significant associations were identified between tissue displacement and CMI symptoms (r < .74 and P > .012 for all; Bonferroni-corrected P = .0002). Conclusion Neural tissue displacement was reduced after posterior fossa decompression surgery, indicating that surgical intervention changes brain tissue biomechanics. For participants with Chiari malformation type I, no relationship was identified between presurgery tissue displacement and presurgical symptoms. © RSNA, 2021 Online supplemental material is available for this article.

Accuracy of cardiac-induced brain motion measurement using displacement-encoding with stimulated echoes (DENSE) magnetic resonance imaging (MRI): A phantom study.

PURPOSE: The goal of this study was to determine the accuracy of displacement-encoding with stimulated echoes (DENSE) MRI in a tissue motion phantom with displacements representative of those observed in human brain tissue. METHODS: The phantom was comprised of a plastic shaft rotated at a constant speed. The rotational motion was converted to a vertical displacement through a camshaft. The phantom generated repeatable cyclical displacement waveforms with a peak displacement ranging from 92 µm to 1.04 mm at 1-Hz frequency. The surface displacement of the tissue was obtained using a laser Doppler vibrometer (LDV) before and after the DENSE MRI scans to check for repeatability. The accuracy of DENSE MRI displacement was assessed by comparing the laser Doppler vibrometer and DENSE MRI waveforms. RESULTS: Laser Doppler vibrometer measurements of the tissue motion demonstrated excellent cycle-to-cycle repeatability with a maximum root mean square error of 9 µm between the ensemble-averaged displacement waveform and the individual waveforms over 180 cycles. The maximum difference between DENSE MRI and the laser Doppler vibrometer waveforms ranged from 15 to 50 µm. Additionally, the peak-to-peak difference between the 2 waveforms ranged from 1 to 18 µm. CONCLUSION: Using a tissue phantom undergoing cyclical motion, we demonstrated the percent accuracy of DENSE MRI to measure displacement similar to that observed for in vivo cardiac-induced brain tissue.

Iris stromal cell nuclei deform to more elongated shapes during pharmacologically-induced miosis and mydriasis.

Nuclear shape alteration in ocular tissues, which can be used as a metric for overall cell deformation, may also lead to changes in gene expression and protein synthesis that could affect the biomechanics of the tissue extracellular matrix. The biomechanics of iris tissue is of particular interest in the study of primary angle-closure glaucoma. As the first step towards understanding the mutual role of the biomechanics and deformation of the iris on the activity of its constituent stromal cells, we conducted an ex-vivo study in freshly excised porcine eyes. Iris deformation was achieved by activating the constituent smooth muscles of the iris. Pupillary responses were initiated by inducing miosis and mydriasis, and the irides were placed in a fixative, bisected, and sliced into thin sections in a nasal and temporal horizontal orientation. The tissue sections were stained with DAPI for nucleus, and z-stacks were acquired using confocal microscopy. Images were analyzed to determine the nuclear aspect ratio (NAR) using both three-dimensional (3D) reconstructions of the nuclear surfaces as well as projections of the same 3D reconstruction into flat two-dimensional (2D) shapes. We observed that regardless of the calculation method (i.e., one that employed 3D surface reconstructions versus one that employed 2D projected images) the NAR increased in both the miosis group and the mydriasis group. Three-dimensional quantifications showed that NAR increased from 2.52 ± 0.96 in control group to 2.80 ± 0.81 and 2.74 ± 0.94 in the mydriasis and miosis groups, respectively. Notwithstanding the relative convenience in calculating the NAR using the 2D projected images, the 3D reconstructions were found to generate more physiologically realistic values and, thus, can be used in the development of future computational models to study primary angle-closure glaucoma. Since the iris undergoes large deformations in response to ambient light, this study suggests that the iris stromal cells are subjected to a biomechanically active micro-environment during their in-vivo physiological function.

Self-Efficacy Versus Gender: Project-Based Active Learning Techniques in Biomedical Engineering Introductory Computer Programming Courses.

Engineering education has increasingly embraced active learning techniques within a variety of curricula. In particular, project-based active learning techniques have a significant potential to enhance students' learning experience. In this study, we implemented project-based techniques in biomedical engineering (BME) classes, and we investigated the effects of active learning on students' self-efficacy as an effective predictor of students' academic persistence and their career decision-making. Differences in self-efficacy were compared across genders. A high level of internal consistency was observed for both academic and career-oriented scales, as determined by Cronbach's alpha values of 0.908 and 0.862, respectively. While average scores of all survey questions indicated improvement in students' academic and career-oriented self-efficacy measures, significant improvements were observed in "clearer vision of programming application in engineering" and "BME careers," as well as in "expectation of success in a future BME career that involves developing medical devices" after the completion of the project-based activity (p = 0.002, 0.023, and 0.034, respectively). For two of the survey questions, female students reflected a significantly lower "self-confidence about understanding the most complex course material" as well as a significantly lower "willingness to have a future career in BME that involves intensive computer programing" as compared to male students (p = 0.035 and 0.024, respectively). We have further discussed possible explanations for the observed differences and multiple potential ways to enhance gender equality in STEM fields from a self-efficacy standpoint.

Appropriate Objective Functions for Quantifying Iris Mechanical Properties Using Inverse Finite Element Modeling.

Quantifying the mechanical properties of the iris is important, as it provides insight into the pathophysiology of glaucoma. Recent ex vivo studies have shown that the mechanical properties of the iris are different in glaucomatous eyes as compared to normal ones. Notwithstanding the importance of the ex vivo studies, such measurements are severely limited for diagnosis and preclude development of treatment strategies. With the advent of detailed imaging modalities, it is possible to determine the in vivo mechanical properties using inverse finite element (FE) modeling. An inverse modeling approach requires an appropriate objective function for reliable estimation of parameters. In the case of the iris, numerous measurements such as iris chord length (CL) and iris concavity (CV) are made routinely in clinical practice. In this study, we have evaluated five different objective functions chosen based on the iris biometrics (in the presence and absence of clinical measurement errors) to determine the appropriate criterion for inverse modeling. Our results showed that in the absence of experimental measurement error, a combination of iris CL and CV can be used as the objective function. However, with the addition of measurement errors, the objective functions that employ a large number of local displacement values provide more reliable outcomes.

Engineered Airway Models to Study Liquid Plug Splitting at Bifurcations: Effects of Orientation and Airway Size.

Delivery of biological fluids, such as surfactant solutions, into lungs is a major strategy to treat respiratory disorders including respiratory distress syndrome that is caused by insufficient or dysfunctional natural lung surfactant. The instilled solution forms liquid plugs in lung airways. The plugs propagate downstream in airways by inspired air or ventilation, continuously split at airway bifurcations to smaller daughter plugs, simultaneously lose mass from their trailing menisci, and eventually rupture. A uniform distribution of the instilled biofluid in lung airways is expected to increase the treatments success. The uniformity of distribution of instilled liquid in the lungs greatly depends on the splitting of liquid plugs between daughter airways, especially in the first few generations from which airways of different lobes of lungs emerge. To mechanistically understand this process, we developed a bioengineering approach to computationally design three-dimensional bifurcating airway models using morphometric data of human lungs, fabricate physical models, and examine dynamics of liquid plug splitting. We found that orientation of bifurcating airways has a major effect on the splitting of liquid plugs between daughter airways. Changing the relative gravitational orientation of daughter tubes with respect to the horizontal plane caused a more asymmetric splitting of liquid plugs. Increasing the propagation speed of plugs partially counteracted this effect. Using airway models of smaller dimensions reduced the asymmetry of plug splitting. This work provides a step toward developing delivery strategies for uniform distribution of therapeutic fluids in the lungs.

Regional Quantification of Brain Tissue Strain Using Displacement-Encoding With Stimulated Echoes Magnetic Resonance Imaging.

Intrinsic cardiac-induced deformation of brain tissue is thought to be important in the pathophysiology of various neurological disorders. In this study, we evaluated the feasibility of utilizing displacement encoding with stimulated echoes (DENSE) magnetic resonance imaging (MRI) to quantify two-dimensional (2D) neural tissue strain using cardiac-driven brain pulsations. We examined eight adult healthy volunteers with an electrocardiogram-gated spiral DENSE sequence performed at the midsagittal plane on a 3 Tesla MRI scanner. Displacement, pixel-wise trajectories, and principal strains were determined in seven regions of interest (ROI): the brain stem, cerebellum, corpus callosum, and four cerebral lobes. Quantification of small neural tissue motion and strain along with their spatial and temporal variations in different brain regions was found to be feasible using DENSE. The medial and inferior brain structures (brain stem, cerebellum, and corpus callosum) had significantly larger motion and strain compared to structures located more peripherally. The brain stem had the largest peak mean displacement (PMD) (187 ± 50 µm, mean ± SD). The largest mean principal strains in compression and extension were observed in the brain stem (0.38 ± 0.08%) and the corpus callosum (0.37 ± 0.08%), respectively. Measured values in percent strain were altered by as much as 0.1 between repeated scans. This study showed that DENSE can quantify regional variations in brain tissue motion and strain and has the potential to be utilized as a tool to evaluate the changes in brain tissue dynamics resulting from alterations in biomechanical stresses and tissue properties.

Using Hands-On Physical Computing Projects to Teach Computer Programming to Biomedical Engineering Students.

Rapid advancements in the multidisciplinary field of biomedical engineering (BME) require competitive engineers with skill sets in a broad range of subjects including biology, physiology, mechanics, circuits, and programming. Accordingly, such a need should be reflected in the training of BME students. Among those skills, computer programming is an essential tool that is used in a wide variety of applications. In this paper, we have provided our experience in incorporating project-based learning, a promising approach in active learning, for teaching computer programming to BME students. We describe a low-cost method for using physical, hands-on computing that directly relates to BME. Additionally, we detail our efforts to teach multiple programming languages in one semester and provide a detailed analysis of the outcomes. We also provide basic materials for other instructors to adapt to fit their own needs.

Quantification of Material Constants for a Phenomenological Constitutive Model of Porcine Tricuspid Valve Leaflets for Simulation Applications.

The tricuspid valve is a one-way valve on the pulmonary side of the heart, which prevents backflow of blood during ventricular contractions. Development of computational models of the tricuspid valve is important both in understanding the normal valvular function and in the development/improvement of surgical procedures and medical devices. A key step in the development of such models is quantification of the mechanical properties of the tricuspid valve leaflets. In this study, after examining previously measured five-loading-protocol biaxial stress-strain response of porcine tricuspid valves, a phenomenological constitutive framework was chosen to represent this response. The material constants were quantified for all three leaflets, which were shown to be highly anisotropic with average anisotropy indices of less than 0.5 (an anisotropy index value of 1 indicates a perfectly isotropic response, whereas a smaller value of the anisotropy index indicates an anisotropic response). To obtain mean values of material constants, stress-strain responses of the leaflet samples were averaged and then fitted to the constitutive model (average R2 over 0.9). Since the sample thicknesses were not hugely different, averaging the data using the same tension levels and stress levels produced similar average material constants for each leaflet.

On the Biaxial Mechanical Response of Porcine Tricuspid Valve Leaflets.

Located on the right side of the heart, the tricuspid valve (TV) prevents blood backflow from the right ventricle to the right atrium. Similar to other cardiac valves, quantification of TV biaxial mechanical properties is essential in developing accurate computational models. In the current study, for the first time, the biaxial stress-strain behavior of porcine TV was measured ex vivo under different loading protocols using biaxial tensile testing equipment. The results showed a highly nonlinear response including a compliant region followed by a rapid transition to a stiff region for all of the TV leaflets both in the circumferential and in the radial directions. Based on the data analysis, all three leaflets were found to be anisotropic, and they were stiffer in the circumferential direction in comparison to the radial direction. It was also concluded that the posterior leaflet was the most anisotropic leaflet.

Surface Strains of Porcine Tricuspid Valve Septal Leaflets Measured in Ex Vivo Beating Hearts.

Quantification of the tricuspid valve (TV) leaflets mechanical strain is important in order to understand valve pathophysiology and to develop effective treatment strategies. Many of the traditional methods used to dynamically open and close the cardiac valves in vitro via flow simulators require valve dissection. Recent studies, however, have shown that restriction of the atrioventricular valve annuli could significantly change their in vivo deformation. For the first time, the porcine valve leaflets deformation was measured in a passive ex vivo beating heart without isolating and remounting the valve annuli. In particular, the right ventricular apexes of porcine hearts (n = 8) were connected to a pulse-duplicator pump that maintained a pulsatile flow from and to a reservoir connected to the right atrium and the pulmonary arteries. This pump provided a right ventricular pressure (RVP) waveform that closely matched physiological values, leading to opening and closure of the tricuspid and pulmonary valves (PVs). At the midsection of the valve leaflets, the peak areal strain was 9.8 ± 2.0% (mean±standard error). The peak strain was 5.6 ± 1.1% and 4.3 ± 1.0% in the circumferential and radial directions, respectively. Although the right ventricle was beating passively, the leaflet peak areal strains closely matched the values measured in other atrioventricular valves (i.e., the mitral valve (MV)) in vivo. This technique can be used to measure leaflet strains with and without the presence of valve lesions to help develop/evaluate treatment strategies to restore normal valve deformation.

A method for predicting collagen fiber realignment in non-planar tissue surfaces as applied to glenohumeral capsule during clinically relevant deformation.

Previously developed experimental methods to characterize micro-structural tissue changes under planar mechanical loading may not be applicable for clinically relevant cases. Such limitation stems from the fact that soft tissues, represented by two-dimensional surfaces, generally do not undergo planar deformations in vivo. To address the problem, a method was developed to directly predict changes in the collagen fiber distribution of nonplanar tissue surfaces following 3D deformation. Assuming that the collagen fiber distribution was known in the un-deformed configuration via experimental methods, changes in the fiber distribution were predicted using 3D deformation. As this method was solely based on kinematics and did not require solving the stress balance equations, the computational efforts were much reduced. In other words, with the assumption of affine deformation, the deformed collagen fiber distribution was calculated using only the deformation gradient tensor (obtained via an in-plane convective curvilinear coordinate system) and the associated un-deformed collagen fiber distribution. The new method was then applied to the glenohumeral capsule during simulated clinical exams. To quantify deformation, positional markers were attached to the capsule and their 3D coordinates were recorded in the reference position and three clinically relevant joint positions. Our results showed that at 60deg of external rotation, the glenoid side of the posterior axillary pouch had significant changes in fiber distribution in comparison to the other sub-regions. The larger degree of collagen fiber alignment on the glenoid side suggests that this region is more prone to injury. It also compares well with previous experimental and clinical studies indicating maximum principle strains to be greater on the glenoid compared to the humeral side. An advantage of the new method is that it can also be easily applied to map experimentally measured collagen fiber distribution (obtained via methods that require flattening of tissue) to their in vivo nonplanar configuration. Thus, the new method could be applied to many other nonplanar fibrous tissues such as the ocular shell, heart valves, and blood vessels.

Insights into regional adaptations in the growing pulmonary artery using a meso-scale structural model: effects of ascending aorta impingement.

As the next step in our investigations into the structural adaptations of the main pulmonary artery (PA) during postnatal growth, we utilized the extensive experimental measurements of the growing ovine PA from our previous study (Fata et al., 2013, "Estimated in vivo Postnatal Surface Growth Patterns of the Ovine Main Pulmonary Artery and Ascending Aorta," J. Biomech. Eng., 135(7), pp. 71010-71012). to develop a structural constitutive model for the PA wall tissue. Novel to the present approach was the treatment of the elastin network as a distributed fiber network rather than a continuum phase. We then utilized this model to delineate structure-function differences in the PA wall at the juvenile and adult stages. Overall, the predicted elastin moduli exhibited minor differences remained largely unchanged with age and region (in the range of 150 to 200 kPa). Similarly, the predicted collagen moduli ranged from ∼1,600 to 2700 kPa in the four regions studied in the juvenile state. Interestingly, we found for the medial region that the elastin and collagen fiber splay underwent opposite changes (collagen standard deviation juvenile = 17 deg to adult = 28 deg, elastin standard deviation juvenile = 35 deg to adult = 27 deg), along with a trend towards more rapid collagen fiber strain recruitment with age, along with a drop in collagen fiber moduli, which went from 2700 kPa for the juvenile stage to 746 kPa in the adult. These changes were likely due to the previously observed impingement of the relatively stiff ascending aorta on the growing PA medial region. Intuitively, the effects of the local impingement would be to lower the local wall stress, consistent with the observed parallel decrease in collagen modulus. These results suggest that during the postnatal somatic growth period local stresses can substantially modulate regional tissue microstructure and mechanical behaviors in the PA. We further underscore that our previous studies indicated an increase in effective PA wall stress with postnatal maturation. When taken together with the fact that the observed changes in mechanical behavior and structure in the growing PA wall were modest in the other three regions studied, our collective results suggest that the majority of the growing PA wall is subjected to increasing stress levels with age without undergoing major structural adaptations. This observation is contrary to the accepted theory of maintenance of homeostatic stress levels in the regulation of vascular function, and suggests alternative mechanisms might regulate postnatal somatic growth. Understanding the underlying mechanisms will help to improve our understanding of congenital defects of the PA and lay the basis for functional duplication in their repair and replacement.