Viscoelastic Characterization of Perfused Liver: Indentation Testing and Preliminary Modeling

Author(s):  
Amy E. Kerdok ◽  
Robert D. Howe ◽  
Simona Socrate

Computer-aided medical technologies are currently restricted by the limited understanding of the mechanical response of solid abdominal organs to finite loading conditions typical of surgical manipulation [5]. This limitation is a result of the difficulty in acquiring the necessary data on whole organs. To develop a constitutive model capable of predicting complex surgical scenarios, multiple testing modalities need to be simultaneously obtained to capture the fundamental nature of the tissue’s behavior under such conditions. In vivo tests are essential to obtain a realistic response, but their inherent difficulty and unknown boundary conditions makes them an impractical approach. Ex vivo tests are easy to control, but the response is unrealistic. A perfusion apparatus was previously developed that obtained near in vivo conditions for whole livers while allowing the ease of ex vivo testing [3]. This work presents the results from complete viscoelastic testing of whole-perfused livers with surgically relevant time-dependant indentation loading profiles to 35% nominal strain. These results will aid in the development of a constitutive model for the liver whose parameters can be related to the physical constituents of the tissue. As an intermediate modeling step, a 1D rheological modeling tool was used to identify the form and initial parameters for a constitutive model.

2020 ◽  
Vol 17 (170) ◽  
pp. 20200598 ◽  
Author(s):  
Mohammad S. Razavi ◽  
J. Brandon Dixon ◽  
Rudolph L. Gleason

The lymphatic system transports lymph from the interstitial space back to the great veins via a series of orchestrated contractions of chains of lymphangions. Biomechanical models of lymph transport, validated with ex vivo or in vivo experimental results, have proved useful in revealing novel insight into lymphatic pumping; however, a need remains to characterize the contributions of vasoregulatory compounds in these modelling tools. Nitric oxide (NO) is a key mediator of lymphatic pumping. We quantified the active contractile and passive biaxial biomechanical response of rat tail collecting lymphatics and changes in the contractile response to the exogenous NO administration and integrated these findings into a biomechanical model. The passive mechanical response was characterized with a three-fibre family model. Nonlinear regression and non-parametric bootstrapping were used to identify best-fit material parameters to passive cylindrical biaxial mechanical data, assessing uniqueness and parameter confidence intervals; this model yielded a good fit ( R 2 = 0.90). Exogenous delivery of NO via sodium nitroprusside (SNP) elicited a dose-dependent suppression of contractions; the amplitude of contractions decreased by 30% and the contraction frequency decreased by 70%. Contractile function was characterized with a modified Rachev–Hayashi model, introducing a parameter that is related to SNP concentration; the model provided a good fit ( R 2 = 0.89) to changes in contractile responses to varying concentrations of SNP. These results demonstrated the significant role of NO in lymphatic pumping and provide a predictive biomechanical model to integrate the combined effect of mechanical loading and NO on lymphatic contractility and mechanical response.


2020 ◽  
Vol 48 (12) ◽  
pp. 2901-2910 ◽  
Author(s):  
Hattie C. Cutcliffe ◽  
Keithara M. Davis ◽  
Charles E. Spritzer ◽  
Louis DeFrate

AbstractOsteoarthritis (OA) is a disease characterized by the degeneration of cartilage tissue, and is a leading cause of disability in the United States. The clinical diagnosis of OA includes the presence of pain and radiographic imaging findings, which typically do not present until advanced stages of the disease when treatment is difficult. Therefore, identifying new methods of OA detection that are sensitive to earlier pathological changes in cartilage, which may be addressed prior to the development of irreversible OA, is critical for improving OA treatment. A potentially promising avenue for developing early detection methods involves measuring the tissue’s in vivo mechanical response to loading, as changes in mechanical function are commonly observed in ex vivo studies of early OA. However, thus far the mechanical function of cartilage has not been widely assessed in vivo. Therefore, the purpose of this study was to develop a novel methodology that can be used to measure an in vivo mechanical property of cartilage: the characteristic recovery time. Specifically, in this study we quantified the characteristic recovery time of cartilage thickness after exercise in relatively young subjects with asymptomatic cartilage. Additionally, we measured baseline cartilage thickness and T1rho and T2 relaxation times (quantitative MRI) prior to exercise in these subjects to assess whether baseline MRI measures are predictive of the characteristic recovery time, to understand whether or not the characteristic recovery time provides independent information about cartilage’s mechanical state. Our results show that the mean recovery strain response across subjects was well-characterized by an exponential approach with a characteristic time of 25.2 min, similar to literature values of human characteristic times measured ex vivo. Further, we were unable to detect a statistically significant linear relationship between the characteristic recovery time and the baseline metrics measured here (T1rho relaxation time, T2 relaxation time, and cartilage thickness). This might suggest that the characteristic recovery time has the potential to provide additional information about the mechanical state of cartilage not captured by these baseline MRI metrics. Importantly, this study presents a noninvasive methodology for quantifying the characteristic recovery time, an in vivo mechanical property of cartilage. As mechanical response may be indicative of cartilage health, this study underscores the need for future studies investigating the characteristic recovery time and in vivo cartilage mechanical response at various stages of OA.


1997 ◽  
Vol 119 (1) ◽  
pp. 103-108 ◽  
Author(s):  
J. A. Ochoa ◽  
A. P. Sanders ◽  
T. W. Kiesler ◽  
D. A. Heck ◽  
J. P. Toombs ◽  
...  

The role that intertrabecular contents and their boundary conditions have on the dynamic mechanical response of canine femoral heads was investigated in vivo. Femoral heads from paired intact hind limbs of canine specimens were subjected to a sinusoidal strain excitation, at physiologic frequencies, in the cranio-caudal direction. The fluid boundary conditions for the contralateral limbs were changed by predrilling through the lateral femoral cortex and into the femoral neck. The drilling procedure did not invade the head itself. This femoral head fluid boundary alteration reduced the stiffness by 19 percent for testing at 1 Hz. The results of this study demonstrate that fluid stiffening occurs in vivo as previously observed ex vivo.


2019 ◽  
Vol 6 (3) ◽  
pp. 70 ◽  
Author(s):  
Samuel D. Salinas ◽  
Margaret M. Clark ◽  
Rouzbeh Amini

Since many soft tissues function in an isotonic in-vivo environment, it is expected that physiological osmolarity will be maintained when conducting experiments on these tissues ex-vivo. In this study, we aimed to examine how not adhering to such a practice may alter the mechanical response of the tricuspid valve (TV) anterior leaflet. Tissue specimens were immersed in deionized (DI) water prior to quantification of the stress–strain responses using an in-plane biaxial mechanical testing device. Following a two-hour immersion in DI water, the tissue thickness increased an average of 107.3% in the DI water group compared to only 6.8% in the control group, in which the tissue samples were submerged in an isotonic phosphate buffered saline solution for the same period of time. Tissue strains evaluated at 85 kPa revealed a significant reduction in the radial direction, from 34.8% to 20%, following immersion in DI water. However, no significant change was observed in the control group. Our study demonstrated the impact of a hypo-osmotic environment on the mechanical response of TV anterior leaflet. The imbalance in ions leads to water absorption in the valvular tissue that can alter its mechanical response. As such, in ex-vivo experiments for which the native mechanical response of the valves is important, using an isotonic buffer solution is essential.


Author(s):  
David Sachs ◽  
Adam Wahlsten ◽  
Sebastian Kozerke ◽  
Gaetana Restivo ◽  
Edoardo Mazza

AbstractThe present study investigates the layer-specific mechanical behavior of human skin. Motivated by skin’s histology, a biphasic model is proposed which differentiates between epidermis, papillary and reticular dermis, and hypodermis. Inverse analysis of ex vivo tensile and in vivo suction experiments yields mechanical parameters for each layer and predicts a stiff reticular dermis and successively softer papillary dermis, epidermis and hypodermis. Layer-specific analysis of simulations underlines the dominating role of the reticular dermis in tensile loading. Furthermore, it shows that the observed out-of-plane deflection in ex vivo tensile tests is a direct consequence of the layered structure of skin. In in vivo suction experiments, the softer upper layers strongly influence the mechanical response, whose dissipative part is determined by interstitial fluid redistribution within the tissue. Magnetic resonance imaging-based visualization of skin deformation in suction experiments confirms the deformation pattern predicted by the multilayer model, showing a consistent decrease in dermal thickness for large probe opening diameters.


2018 ◽  
Vol 85 (5) ◽  
Author(s):  
M. Hajhashemkhani ◽  
M. R. Hematiyan ◽  
S. Goenezen

Identification of material properties of hyper-elastic materials such as soft tissues of the human body or rubber-like materials has been the subject of many works in recent decades. Boundary conditions generally play an important role in solving an inverse problem for material identification, while their knowledge has been taken for granted. In reality, however, boundary conditions may not be available on parts of the problem domain such as for an engineering part, e.g., a polymer that could be modeled as a hyper-elastic material, mounted on a system or an in vivo soft tissue. In these cases, using hypothetical boundary conditions will yield misleading results. In this paper, an inverse algorithm for the characterization of hyper-elastic material properties is developed, which takes into consideration unknown conditions on a part of the boundary. A cost function based on measured and calculated displacements is defined and is minimized using the Gauss–Newton method. A sensitivity analysis is carried out by employing analytic differentiation and using the finite element method (FEM). The effectiveness of the proposed method is demonstrated through numerical and experimental examples. The novel method is tested with a neo–Hookean and a Mooney–Rivlin hyper-elastic material model. In the experimental example, the material parameters of a silicone based specimen with unknown boundary condition are evaluated. In all the examples, the obtained results are verified and it is observed that the results are satisfactory and reliable.


2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.


1994 ◽  
Vol 71 (01) ◽  
pp. 095-102 ◽  
Author(s):  
Désiré Collen ◽  
Hua Rong Lu ◽  
Jean-Marie Stassen ◽  
Ingrid Vreys ◽  
Tsunehiro Yasuda ◽  
...  

SummaryCyclic Arg-Gly-Asp (RGD) containing synthetic peptides such as L-cysteine, N-(mercaptoacetyl)-D-tyrosyl-L-arginylglycyl-L-a-aspartyl-cyclic (1→5)-sulfide, 5-oxide (G4120) and acetyl-L-cysteinyl-L-asparaginyl-L-prolyl-L-arginyl-glycyl-L-α-aspartyl-[0-methyltyrosyl]-L-arginyl-L-cysteinamide, cyclic 1→9-sulfide (TP9201) bind with high affinity to the platelet GPIIb/IIIa receptor.The relationship between antithrombotic effect, ex vivo platelet aggregation and bleeding time prolongation with both agents was studied in hamsters with a standardized femoral vein endothelial cell injury predisposing to platelet-rich mural thrombosis, and in dogs with a carotid arterial eversion graft inserted in the femoral artery. Intravenous administration of G4120 in hamsters inhibited in vivo thrombus formation with a 50% inhibitory bolus dose (ID50) of approximately 20 μg/kg, ex vivo ADP-induccd platelet aggregation with ID50 of 10 μg/kg, and bolus injection of 1 mg/kg prolonged the bleeding time from 38 ± 9 to 1,100 ± 330 s. Administration of TP9201 in hamsters inhibited in vivo thrombus formation with ID50 of 30 μg/kg, ex vivo platelet aggregation with an ID50 of 50 μg/kg and bolus injection of 1 mg/kg did not prolong the template bleeding time. In the dog eversion graft model, infusion of 100 μg/kg of G4120 over 60 min did not fully inhibit platelet-mediated thrombotic occlusion but was associated with inhibition of ADP-induccd ex vivo platelet aggregation and with prolongation of the template bleeding time from 1.3 ± 0.4 to 12 ± 2 min. Infusion of 300 μg/kg of TP9201 over 60 min completely prevented thrombotic occlusion, inhibited ex vivo platelet aggregation, but was not associated with prolongation of the template bleeding time.TP9201, unlike G4120, inhibits in vivo platelet-mediated thrombus formation without associated prolongation of the template bleeding time.


1992 ◽  
Vol 68 (06) ◽  
pp. 687-693 ◽  
Author(s):  
P T Larsson ◽  
N H Wallén ◽  
A Martinsson ◽  
N Egberg ◽  
P Hjemdahl

SummaryThe significance of platelet β-adrenoceptors for platelet responses to adrenergic stimuli in vivo and in vitro was studied in healthy volunteers. Low dose infusion of the β-adrenoceptor agonist isoprenaline decreased platelet aggregability in vivo as measured by ex vivo filtragometry. Infusion of adrenaline, a mixed α- and β-adrenoceptor agonist, increased platelet aggregability in vivo markedly, as measured by ex vivo filtragometry and plasma β-thromboglobulin levels. Adrenaline levels were 3–4 nM in venous plasma during infusion. Both adrenaline and high dose isoprenaline elevated plasma von Willebrand factor antigen levels β-Blockade by propranolol did not alter our measures of platelet aggregability at rest or during adrenaline infusions, but inhibited adrenaline-induced increases in vWf:ag. In a model using filtragometry to assess platelet aggregability in whole blood in vitro, propranolol enhanced the proaggregatory actions of 5 nM, but not of 10 nM adrenaline. The present data suggest that β-adrenoceptor stimulation can inhibit platelet function in vivo but that effects of adrenaline at high physiological concentrations are dominated by an α-adrenoceptor mediated proaggregatory action.


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