Acoustics@Home: Laboratories and student-led projects conducted for an undergraduate engineering experimentation course during the COVID-19 pandemic.

Hands-on, project-based learning was difficult to achieve in online classes during the COVID-19 pandemic. The Engineering Experimentation course at Cooper Union teaches third-year mechanical engineering students practical experimental skills to measure physical phenomenon, which typically requires in-person laboratory classes. In response to COVID, a low-cost, at-home laboratory kit was devised to give students tools to conduct experiments. The kit included a microcontroller acting as a data-acquisition device and custom software to facilitate data transfer. A speed of sound laboratory was designed with the kit to teach skills in data collection, signal processing, and error analysis. The students derived the sound speed by placing two microphones a known distance apart and measuring the time for an impulsive signal to travel from one to the other. The students reported sound speeds from 180.7-477.8 m/s in a temperature range from 273.7-315.9 K. While these reported speeds contained a large amount of error, the exercise allowed the students to learn how to account for sources of error within experiments. This paper also presents final projects designed by the students at home, an impedance tube and two Doppler shift experiments, that exhibit successful and effective low-cost solutions to demonstrate and measure acoustic phenomenon.

Upper airway effective compliance during wakefulness and sleep in obese adolescents studied via two-dimensional dynamic MRI and semiautomated image segmentation.

Novel biomarkers of upper airway biomechanics may improve diagnosis of obstructive sleep apnea syndrome (OSAS). Upper airway effective compliance (EC), the slope of cross-sectional area versus pressure estimated using computational fluid dynamics (CFD), correlates with apnea-hypopnea index (AHI) and critical closing pressure (Pcrit). The study objectives are to develop a fast, simplified method for estimating EC using dynamic MRI and physiological measurements and to explore the hypothesis that OSAS severity correlates with mechanical compliance during wakefulness and sleep. Five obese children with OSAS and five control subjects with obesity aged 12-17 yr underwent anterior rhinomanometry, polysomnography, and dynamic MRI with synchronized airflow measurement during wakefulness and sleep. Airway cross section in retropalatal and retroglossal section images was segmented using a novel semiautomated method that uses optimized singular value decomposition (SVD) image filtering and k-means clustering combined with morphological operations. Pressure was estimated using rhinomanometry Rohrer's coefficients and flow rate, and EC was calculated from the area-pressure slope during five normal breaths. Correlations between apnea-hypopnea index (AHI), EC, and cross-sectional area (CSA) change were calculated using Spearman's rank correlation. The semiautomated method efficiently segmented the airway with average Dice Coefficient above 89% compared with expert manual segmentation. AHI correlated positively with EC at the retroglossal site during sleep (rs = 0.74, P = 0.014) and with change of EC from wake to sleep at the retroglossal site (rs = 0.77, P = 0.01). CSA change alone did not correlate significantly with AHI. EC, a mechanical biomarker which includes both CSA change and pressure variation, is a potential diagnostic biomarker for studying and managing OSAS.NEW & NOTEWORTHY This study investigated the dynamics of the upper airway at retropalatal and retroglossal sites during wakefulness and sleep by evaluating the effective compliance (EC) of each site and its correlation with apnea-hypopnea index (AHI) using novel semiautomated image processing. AHI correlated significantly with retroglossal EC during sleep and change of retroglossal EC from wake to sleep. The results suggest EC as a promising noninvasive diagnostic marker for estimating the mechanical properties of various upper airway regions in patients with OSAS.

Effect of sleep on upper airway dynamics in obese adolescents with obstructive sleep apnea syndrome.

STUDY OBJECTIVES: The biomechanical basis of obstructive sleep apnea syndrome (OSAS) may influence upper airway dynamics. In this study, we investigate dynamic changes during respiration in wakefulness and sleep in obese adolescents with and without OSAS. METHODS: Respiratory-gated dynamic magnetic resonance imaging (MRI) at the retropalatal and retroglossal regions was performed with simultaneous measurement of SpO2 and nasal-oral mask airflow and pressure. Airway cross-sectional area (CSA) was determined using AMIRA. Percent change in CSA was calculated from five continuous tidal breaths in states of wakefulness and sleep. Mixed effects models were used to evaluate interactions between group (OSAS/control), site (retropalatal/retroglossal), and stage (wake/sleep). RESULTS: We studied 24 children with OSAS (mean age 15.49 ± 2.00 years, mean apnea-hypopnea index [AHI] 16.53 ± 8.72 events/h) and 19 controls (mean age 14.86 ± 1.75 years, mean AHI 2.12 ± 1.69 events/h). Groups were similar in age, sex, height, weight, and BMI Z-score. Participants with OSAS had a 48.17% greater increase in percent change of airway CSA during sleep than controls (p < 0.0001), while there was no difference between groups during wakefulness (p = 0.6589). Additionally, participants with OSAS had a 48.80% increase in percent change of airway CSA during sleep as compared with wakefulness (p < 0.0001), whereas no such relationship was observed in controls (p = 0.5513). CONCLUSIONS: This study demonstrates significant effects of sleep on upper airway dynamics in obese children with OSAS. Dynamic MRI with physiological data can potentially provide further insight into the biomechanical basis of OSAS and assist in more effective management.

Biomechanics of the soft-palate in sleep apnea patients with polycystic ovarian syndrome.

Highly compliant tissue supporting the pharynx and low muscle tone enhance the possibility of upper airway occlusion in children with obstructive sleep apnea (OSA). The present study describes subject-specific computational modeling of flow-induced velopharyngeal narrowing in a female child with polycystic ovarian syndrome (PCOS) with OSA and a non-OSA control. Anatomically accurate three-dimensional geometries of the upper airway and soft-palate were reconstructed for both subjects using magnetic resonance (MR) images. A fluid-structure interaction (FSI) shape registration analysis was performed using subject-specific values of flow rate to iteratively compute the biomechanical properties of the soft-palate. The optimized shear modulus for the control was 38 percent higher than the corresponding value for the OSA patient. The proposed computational FSI model was then employed for planning surgical treatment for the apneic subject. A virtual surgery comprising of a combined adenoidectomy, palatoplasty and genioglossus advancement was performed to estimate the resulting post-operative patterns of airflow and tissue displacement. Maximum flow velocity and velopharyngeal resistance decreased by 80 percent and 66 percent respectively following surgery. Post-operative flow-induced forces on the anterior and posterior faces of the soft-palate were equilibrated and the resulting magnitude of tissue displacement was 63 percent lower compared to the pre-operative case. Results from this pilot study indicate that FSI computational modeling can be employed to characterize the mechanical properties of pharyngeal tissue and evaluate the effectiveness of various upper airway surgeries prior to their application.

Computational fluid dynamics upper airway effective compliance, critical closing pressure, and obstructive sleep apnea severity in obese adolescent girls.

Obstructive sleep apnea syndrome (OSAS) is associated with anatomical abnormalities restricting upper airway size and functional factors decreasing pharyngeal dilator activity in sleep. In this study we hypothesized that OSAS is also associated with altered pharyngeal mechanical compliance during wakefulness. Five OSAS and six control obese girls between 14 and 18 years of age were studied. All underwent polysomnography, critical closing pressure (Pcrit) studies, and dynamic MRI of the upper airway during awake tidal breathing. Effective airway compliance was defined as the slope of cross-sectional area vs. average pressure between maximum inspiration and maximum expiration along the pharyngeal airway. Pharyngeal pressure fields were calculated by using image-based computational fluid dynamics and nasal resistance. Spearman correlations were calculated to test associations between apnea-hypopnea index (AHI), Pcrit, and airway compliance. Effective compliances in the nasopharynx (CNP) and velopharynx (CVP) were lower and negative in OSAS compared with controls: -4.4 vs. 1.9 (mm2/cmH2O, P = 0.012) and -2.1 vs. 3.9 (mm2/cmH2O, P = 0.021), respectively, suggesting a strong phasic pharyngeal dilator activity during inspiration in OSAS compared with controls. For all subjects, CNP and AHI correlated negatively (rS = -0.69, P = 0.02), and passive Pcrit correlated with CNP (rS = -0.76, P = 0.006) and with AHI (rS = 0.86, P = 0.0006). Pharyngeal mechanics obtained during wakefulness could be used to characterize subjects with OSAS. Moreover, negative effective compliance during wakefulness and its correlation to AHI and Pcrit suggest that phasic dilator activity of the upper pharynx compensates for negative pressure loads in these subjects.

Computational fluid dynamics endpoints for assessment of adenotonsillectomy outcome in obese children with obstructive sleep apnea syndrome.

BACKGROUND: Improvements in obstructive sleep apnea syndrome (OSAS) severity may be associated with improved pharyngeal fluid mechanics following adenotonsillectomy (AT). The study objective is to use image-based computational fluid dynamics (CFD) to model changes in pharyngeal pressures after AT, in obese children with OSAS and adenotonsillar hypertrophy. METHODS: Three-dimensional models of the upper airway from nares to trachea, before and after AT, were derived from magnetic resonance images obtained during wakefulness, in a cohort of 10 obese children with OSAS. Velocity, pressure, and turbulence fields during peak tidal inspiratory flow were computed using commercial software. CFD endpoints were correlated with polysomnography endpoints before and after AT using Spearman׳s rank correlation (rs). RESULTS: Apnea hypopnea index (AHI) decreases after AT was strongly correlated with reduction in maximum pressure drop (dPTAmax) in the region where tonsils and adenoid constrict the pharynx (rs=0.78, P=0.011), and with decrease of the ratio of dPTAmax to flow rate (rs=0.82, P=0.006). Correlations of AHI decrease to anatomy, negative pressure in the overlap region (including nasal flow resistance), or pressure drop through the entire pharynx, were not significant. In a subgroup of subjects with more than 10% improvement in AHI, correlations between flow variables and AHI decrease were stronger than in all subjects. CONCLUSIONS: The correlation between change in dPTAmax and improved AHI suggests that dPTAmax may be a useful index for internal airway loading due to anatomical narrowing, and may be better correlated with AHI than direct airway anatomic measurements.

Anterior nasal resistance in obese children with obstructive sleep apnea syndrome.

OBJECTIVES/HYPOTHESIS: To evaluate nasal resistance in obese children with and without obstructive sleep apnea syndrome (OSAS), study the correlation between nasal resistance and severity of OSAS using the apnea-hypopnea index (AHI), and examine the association of gender and body mass index (BMI) with this measurement. STUDY DESIGN: Retrospective analysis. METHODS: Active anterior rhinomanometry was used to determine anterior nasal resistance (aNR) during wakefulness in the supine position during tidal breathing. Thirty obese children with OSAS (aged 13.8 ± 2.6 years, BMI z score 2.6 ± 0.4) and 32 matched obese controls (aged 13.6 ± 2.3 years, BMI z score 2.4 ± 0.4), were studied. Unpaired t tests and Spearman correlation were performed. RESULTS: The OSAS group had significantly higher aNR than the non-OSAS group during inspiration (P = .012) and expiration (P = .003). A significant correlation between inspiratory aNR and AHI was found for the OSAS group (r = 0.39, P = .04). The aNR did not correlate with BMI z score or with either gender. CONCLUSIONS: We noted a higher aNR in obese children with OSAS as compared to obese controls, and the aNR on inspiration correlated significantly with AHI. These findings suggest that a causal or augmentative effect of high inspiratory aNR may exist for obese children who exhibit OSAS. LEVEL OF EVIDENCE: 3b.

Mechanical study of polycaprolactone-hydroxyapatite porous scaffolds created by porogen-based solid freeform fabrication method.

MATERIALS AND METHODS: Polycaprolactone (PCL) and polycaprolactone-hydroxyapatite (PCL-HA) scaffolds with 600-µm pore size were fabricated by drop-on-demand printing (DDP) structured porogen method followed with injection molding. Specimens with special dimensions of 4.2×4.2×5.4 mm3 and 6.6×6.6×13.8 mm3 were designed and fabricated for compression and tensile tests, respectively. The mechanical study was performed on both solid and porous PCL and PCL-HA samples. The effect on mechanical properties of the HA content ratio in PCL-HA composites was investigated. RESULTS: Porous scaffold made of 80/20 PCL-HA composite had an ultimate compressive strength of 3.7±0.2 MPa and compression modulus of 61.4±3.4 MPa, which is in the range of reported trabecular bone's compressive strength. Increasing the concentration of HA in the composites raised compressive properties and stiffness significantly (P<0.05), which demonstrates that PCL-HA composites have the potential for application in bone regeneration. Tensile test of solid PCL and PCL-HA composites showed that the ultimate tensile strength and tensile modulus increased with increases of the concentration of HA in the composites. The tensile test was also conducted on PCL porous scaffold; the result indicated that the scaffold was slightly softer and weaker in tension compared with compression. CONCLUSIONS: Combining compression and tensile test results, our study may guide the possible application of these biomaterials in bone tissue engineering and support further development of microstructure-based models of scaffold mechanical properties.

Computational fluid dynamics endpoints to characterize obstructive sleep apnea syndrome in children.

Computational fluid dynamics (CFD) analysis may quantify the severity of anatomical airway restriction in obstructive sleep apnea syndrome (OSAS) better than anatomical measurements alone. However, optimal CFD model endpoints to characterize or assess OSAS have not been determined. To model upper airway fluid dynamics using CFD and investigate the strength of correlation between various CFD endpoints, anatomical endpoints, and OSAS severity, in obese children with OSAS and controls. CFD models derived from magnetic resonance images were solved at subject-specific peak tidal inspiratory flow; pressure at the choanae was set by nasal resistance. Model endpoints included airway wall minimum pressure (Pmin), flow resistance in the pharynx (Rpharynx), and pressure drop from choanae to a minimum cross section where tonsils and adenoids constrict the pharynx (dPTAmax). Significance of endpoints was analyzed using paired comparisons (t-test or Wilcoxon signed rank test) and Spearman correlation. Fifteen subject pairs were analyzed. Rpharynx and dPTAmax were higher in OSAS than control and most significantly correlated to obstructive apnea-hypopnea index (oAHI), r = 0.48 and r = 0.49, respectively (P < 0.01). Airway minimum cross-sectional correlation to oAHI was weaker (r = -0.39); Pmin was not significantly correlated. CFD model endpoints based on pressure drops in the pharynx were more closely associated with the presence and severity of OSAS than pressures including nasal resistance, or anatomical endpoints. This study supports the usefulness of CFD to characterize anatomical restriction of the pharynx and as an additional tool to evaluate subjects with OSAS.

Noninvasive estimation of pharyngeal airway resistance and compliance in children based on volume-gated dynamic MRI and computational fluid dynamics.

Computational fluid dynamics (CFD) analysis was used to model the effect of collapsing airway geometry on internal pressure and velocity in the pharyngeal airway of three sedated children with obstructive sleep apnea syndrome (OSAS) and three control subjects. Model geometry was reconstructed from volume-gated magnetic resonance images during normal tidal breathing at 10 increments of tidal volume through the respiratory cycle. Each geometry was meshed with an unstructured grid and solved using a low-Reynolds number k-ω turbulence model driven by flow data averaged over 12 consecutive breathing cycles. Combining gated imaging with CFD modeling created a dynamic three-dimensional view of airway anatomy and mechanics, including the evolution of airway collapse and flow resistance and estimates of the local effective compliance. The upper airways of subjects with OSAS were generally much more compliant during tidal breathing. Compliance curves (pressure vs. cross-section area), derived for different locations along the airway, quantified local differences along the pharynx and between OSAS subjects. In one subject, the distal oropharynx was more compliant than the nasopharynx (1.028 vs. 0.450 mm(2)/Pa) and had a lower theoretical limiting flow rate, confirming the distal oropharynx as the flow-limiting segment of the airway in this subject. Another subject had a more compliant nasopharynx (0.053 mm(2)/Pa) during inspiration and apparent stiffening of the distal oropharynx (C = 0.0058 mm(2)/Pa), and the theoretical limiting flow rate indicated the nasopharynx as the flow-limiting segment. This new method may help to differentiate anatomical and functional factors in airway collapse.

Upper airway structure and body fat composition in obese children with obstructive sleep apnea syndrome.

RATIONALE: Mechanisms leading to obstructive sleep apnea syndrome (OSAS) in obese children are not well understood. OBJECTIVES: The aim of the study was to determine anatomical risk factors associated with OSAS in obese children as compared with obese control subjects without OSAS. METHODS: Magnetic resonance imaging was used to determine the size of upper airway structure, and body fat composition. Paired analysis was used to compare between groups. Mixed effects regression models and conditional multiple logistic regression models were used to determine whether body mass index (BMI) Z-score was an effect modifier of each anatomic characteristic as it relates to OSAS. MEASUREMENTS AND MAIN RESULTS: We studied 22 obese subjects with OSAS (12.5 ± 2.8 yr; BMI Z-score, 2.4 ± 0.4) and 22 obese control subjects (12.3 ± 2.9 yr; BMI Z-score, 2.3 ± 0.3). As compared with control subjects, subjects with OSAS had a smaller oropharynx (P < 0.05) and larger adenoid (P < 0.01), tonsils (P < 0.05), and retropharyngeal nodes (P < 0.05). The size of lymphoid tissues correlated with severity of OSAS whereas BMI Z-score did not have a modifier effect on these tissues. Subjects with OSAS demonstrated increased size of parapharyngeal fat pads (P < 0.05) and abdominal visceral fat (P < 0.05). The size of these tissues did not correlate with severity of OSAS and BMI Z-score did not have a modifier effect on these tissues. CONCLUSIONS: Upper airway lymphoid hypertrophy is significant in obese children with OSAS. The lack of correlation of lymphoid tissue size with obesity suggests that this hypertrophy is caused by other mechanisms. Although the parapharyngeal fat pads and abdominal visceral fat are larger in obese children with OSAS we could not find a direct association with severity of OSAS or with obesity.

Rhino-sinus involvement in children with obstructive sleep apnea syndrome.

OBJECTIVE: Obstructive sleep apnea syndrome (OSAS) is commonly associated with adenotonsillar hypertrophy. We hypothesized that respiratory perturbations extend to other regions of the upper respiratory tract in such children, particularly to rhino-sinus regions. STUDY DESIGN: A prospective case control study using Magnetic Resonance Imaging (MRI) of the upper airway and surrounding tissues of OSAS and controls. Magnetic resonance imaging was used to evaluate radiographic changes within the: paranasal sinuses, middle ear and mastoid air cells, and the nasal passages. RESULTS: We studied 54 OSAS (age 5.7 ± 3.0 years) and 54 controls (age 6.2 ± 2.0 years, P = NS). Children with OSAS had significantly more opacification of: maxillary sinuses (P < 0.05), sphenoid sinuses (P < 0.01), and mastoid air cells (P < 0.01). They also had significantly more: middle ear effusions, (P < 0.001), prominence of inferior nasal turbinate(s) (P < 0.05), and deviation of the nasal septum (P < 0.05). CONCLUSIONS: Childhood OSAS is associated with a wide range of upper respiratory tract perturbations and is not limited to adenoid and tonsillar hypertrophy.

Modeling upper airway collapse by a finite element model with regional tissue properties.

This study presents a new computational system for modeling the upper airway in rats that combines tagged magnetic resonance imaging (MRI) with tissue material properties to predict three-dimensional (3D) airway motion. The model is capable of predicting airway wall and tissue deformation under airway pressure loading up to airway collapse. The model demonstrates that oropharynx collapse pressure depends primarily on ventral wall (tongue muscle) elastic modulus and airway architecture. An iterative approach that involves substituting alternative possible tissue elastic moduli was used to improve model precision. The proposed 3D model accounts for stress-strain relationships in the complex upper airway that should present new opportunities for understanding pathogenesis of airway collapse, improving diagnosis and developing treatments.

Porogen-based solid freeform fabrication of polycaprolactone-calcium phosphate scaffolds for tissue engineering.

Drop on demand printing (DDP) is a solid freeform fabrication (SFF) technique capable of generating microscale physical features required for tissue engineering scaffolds. Here, we report results toward the development of a reproducible manufacturing process for tissue engineering scaffolds based on injectable porogens fabricated by DDP. Thermoplastic porogens were designed using Pro/Engineer and fabricated with a commercially available DDP machine. Scaffolds composed of either pure polycaprolactone (PCL) or homogeneous composites of PCL and calcium phosphate (CaP, 10% or 20% w/w) were subsequently fabricated by injection molding of molten polymer-ceramic composites, followed by porogen dissolution with ethanol. Scaffold pore sizes, as small as 200 microm, were attainable using the indirect (porogen-based) method. Scaffold structure and porosity were analyzed by scanning electron microscopy (SEM) and microcomputed tomography, respectively. We characterized the compressive strength of 90:10 and 80:20 PCL-CaP composite materials (19.5+/-1.4 and 24.8+/-1.3 Mpa, respectively) according to ASTM standards, as well as pure PCL scaffolds (2.77+/-0.26 MPa) fabricated using our process. Human embryonic palatal mesenchymal (HEPM) cells attached and proliferated on all scaffolds, as evidenced by fluorescent nuclear staining with Hoechst 33258 and the Alamar Blue assay, with increased proliferation observed on 80:20 PCL-CaP scaffolds. SEM revealed multilayer assembly of HEPM cells on 80:20 PCL-CaP composite, but not pure PCL, scaffolds. In summary, we have developed an SFF-based injection molding process for the fabrication of PCL and PCL-CaP scaffolds that display in vitro cytocompatibility and suitable mechanical properties for hard tissue repair.

Computational fluid dynamics modeling of the upper airway of children with obstructive sleep apnea syndrome in steady flow.

Computational fluid dynamic (CFD) analysis was used to model the effect of airway geometry on internal pressure in the upper airway of three children with obstructive sleep apnea syndrome (OSAS), and three controls. Model geometry was reconstructed from magnetic resonance images obtained during quiet tidal breathing, meshed with an unstructured grid, and solved at normative peak resting flow. The unsteady Reynolds-averaged Navier-Stokes equations were solved with steady flow boundary conditions in inspiration and expiration, using a two-equation low-Reynolds number turbulence model. Model results were validated using an in-vitro scale model, unsteady flow simulation, and reported nasal resistance measurements in children. Pharynx pressure drop strongly correlated to airway area restriction. Inspiratory pressure drop was primarily proportional to the square of flow, consistent with pressure losses due to convective acceleration caused by area restriction. On inspiration, in OSAS pressure drop occurred primarily between the choanae and the region where the adenoids overlap the tonsils (overlap region) due to airway narrowing, rather than in the nasal passages; in controls the majority of pressure drop was in the nasal passages. On expiration, in OSAS the majority of pressure drop occurred between the oropharynx (posterior to the tongue) and overlap region, and local minimum pressure in the overlap region was near atmospheric due to pressure recovery in the anterior nasopharynx. The results suggest that pharyngeal airway shape in children with OSAS significantly affects internal pressure distribution compared to nasal resistance. The model may also help explain regional dynamic airway narrowing during expiration.

Changes in upper airway size during tidal breathing in children with obstructive sleep apnea syndrome.

UNLABELLED: We performed respiratory-gated magnetic resonance imaging to evaluate airway dynamics during tidal breathing in 10 children with obstructive sleep apnea syndrome (OSAS; age, 4.3 +/- 2.3 years) and 10 matched control subjects (age, 5.0 +/- 2.0 years). We hypothesized that respiratory cycle fluctuations in upper airway cross-sectional area would be larger in children with OSAS. METHODS: Studies were performed under sedation. Respiratory gating was performed automatically at 10, 30, 50, 70, and 90% of inspiratory and expiratory volume. Airway cross-sectional area was measured at four ascending oropharyngeal levels at each increment of the respiratory cycle. RESULTS: We noted the following in subjects with OSAS compared with control subjects: (1) a smaller upper airway cross-sectional area, particularly during inspiration; (2) airway narrowing occurred during inspiration without evidence of complete airway collapse; (3) airway dilatation occurred during expiration, particularly early in the phase; and (4) magnitude of cross-sectional areas fluctuations during tidal breathing noted in OSAS at levels 1 through 4 were 317, 422, 785, and 922%, compared with 19, 15 17, and 24% in control subjects (p < 0.001, p < 0.005, p < 0.001, and p < 0.001, respectively). CONCLUSIONS: Fluctuations in airway area during tidal breathing are significantly greater in subjects with OSAS compared with control subjects. Resistive pressure loading is a probable explanation, although increased airway compliance may be a contributing factor.

Platelet near-wall excess in porcine whole blood in artery-sized tubes under steady and pulsatile flow conditions.

Platelet margination (enhanced platelet concentration in the near wall region of a blood vessel) has been well documented in small vessels. In artery-sized vessels margination has only been demonstrated in one study, using ghost cell suspensions and under relatively non-physiologic conditions of steady flow and 50 cm development length. Local sampling experiments were performed to confirm platelet margination in artery-sized stainless steel tubes, for a typical anatomical length and under pulsatile flow, using fresh EDTA-anticoagulated porcine whole blood (N=21). Experiments were designed using three-dimensional Computational Fluid Dynamics (CFD) to model the sample region with greater fidelity. Steady flow experiments in 50 cm long tubes verify published laser Doppler measurements of platelet margination in 3 mm ID tubes at normal arterial shear rate (500 s(-1). Margination persists under pulsatile flow conditions (63.8 pulses/min), but in steady flow at length of 10 cm, margination is reduced. Platelet margination ratio (the ratio of the platelet concentration near the wall to bulk average platelet count) ranges from 1.21 to 2.48. No significant effects of calculated sampling thickness (20 microm and 50 microm) or pulsatility were detected. Hematocrit margination ratio is 0.68 to 0.90. Two model platelet concentration profiles are fit to the experimental results.

An experimental and theoretical study on the dissolution of mural fibrin clots by tissue-type plasminogen activator.

During thrombolytic therapy and after recanalization is achieved, reduction in the volume of mural thrombi is desirable. Mural thrombi are known to contribute to rethrombosis and reocclusion. The lysis rate of mural thrombi has been demonstrated to increase with fluid flow in different experimental models, but the mechanisms responsible are unknown. An experimental and a theoretical study were developed to determine the contribution of outer convective transport to the lysis of mural fibrin clots. Normal human plasma containing recombinant tissue-type plasminogen activator (tPA; 0.5 microg/mL) was (re)perfused over mural fibrin clots with fluorescently labeled fibrin at low arterial, arterial, or higher wall shear stresses (4, 18, or 41 dyn/cm(2), respectively) and lysis was monitored in real time. Flow accelerated lysis, but significantly only at the highest shear stress: The average lysis front velocity was 3 x 10(-5) cm/s at 41 dyn/cm(2) vs. almost half of that at the lower shear stresses. Confocal microscopy showed fibrin fibers dissolving only in a narrow region close to the surface when permeation velocity was predicted to be low. A heterogeneous transport-reaction finite element model was used to describe mural fibrinolysis. After scaling the effects of outer and inner convection, inner diffusion, and chemical reactions, a simplified inner diffusion/reaction model was used. Correlation to fibrin lysis data in purified systems dictated higher rates of plasmin(ogen) and tPA adsorption onto fibrin and a decreased catalytic rate of plasmin-mediated fibrin degradation, compared with published parameters. At each shear stress, the model predicted a temporal pattern of lysis of mural fibrin (similar to that observed experimentally), and protease accumulation in a narrow fibrin region and significant lysis inhibition by plasma alpha(2)-antiplasmin (according to the literature). Increasing outer convection accelerated mural fibrinolysis, but the model did not predict the big increase in lysis rate at the highest shear stress. At higher than arterial flows, additional mechanisms not accounted for in the current model, such as fibrin collapse at the fibrin front, may regulate the lysis of mural clots and determine the outcome of thrombolytic therapy.