Understanding and quantifying the mechanical properties of breast tissues has been a subject of interest for the past two decades. This has been motivated in part by interest in modelling soft tissue ...response for surgery planning and virtual-reality-based surgical training. Interpreting elastography images for diagnostic purposes also requires a sound understanding of normal and pathological tissue mechanical properties. Reliable data on tissue elastic properties are very limited and those which are available tend to be inconsistent, in part as a result of measurement methodology. We have developed specialized techniques to measure tissue elasticity of breast normal tissues and tumour specimens and applied them to 169 fresh ex vivo breast tissue samples including fat and fibroglandular tissue as well as a range of benign and malignant breast tumour types. Results show that, under small deformation conditions, the elastic modulus of normal breast fat and fibroglandular tissues are similar while fibroadenomas were approximately twice the stiffness. Fibrocystic disease and malignant tumours exhibited a 3-6-fold increased stiffness with high-grade invasive ductal carcinoma exhibiting up to a 13-fold increase in stiffness compared to fibrogalndular tissue. A statistical analysis showed that differences between the elastic modulus of the majority of those tissues were statistically significant. Implications for the specificity advantages of elastography are reviewed.
Breast cancer is the most common and deadly cancer in women, where early detection is of the utmost importance as survival rates decrease with the advancement of the disease. Most available methods ...of breast cancer screening and evaluation lack the ability to effectively differentiate between benign and malignant lesions without a biopsy. Ultrasound elastography (USE) is a cost-effective method that can potentially provide an initial malignancy assessment at the bedside. One of the challenges, however, is the uncertainty of tissue displacement data when performing USE due to out-of-plane movement of the tissue during mechanical stimulation, in addition to the computational efficiency necessary for real-time image reconstruction. This work presents a comparison of four different theoretically sound displacement estimators for their ability in tissue Young’s modulus reconstruction level with an emphasis on quality-to-runtime ratio to determine which estimators are most suitable for real-time USE systems. The methods are known in literature as AM2D, GLUE, OVERWIND, and SOUL methods. The effectiveness of each method was assessed as a stand-alone method or in combination with a strain field enhancement technique known as STREAL, which was recently developed using tissue mechanics-based regularization. The study was performed using radiofrequency US data pertaining to in silico and tissue mimicking phantoms in addition to clinical data. This data was used to generate tissue displacement fields employed to generate axial and lateral strain images before Young’s modulus images were reconstructed. The study indicates that the AM2D displacement estimator, which is an older and computationally less involved method, along with a tissue-mechanics-based image processing algorithm, performs very well, with high CNR, SNR, and preservation of tumor heterogeneity obtained at both strain and stiffness image levels, while its computation run-time is much lower compared to other estimation methods. As such, it can be recommended for incorporation in real-time USE systems.
Menisci are fibrocartilaginous disks consisting of soft tissue with a complex biomechanical structure. They are critical determinants of the kinematics as well as the stability of the knee joint. ...Several studies have been carried out to formulate tissue mechanical behavior, leading to the development of a wide spectrum of constitutive laws. In addition to developing analytical tools, extensive numerical studies have been conducted on menisci modeling. This study reviews the developments of the most widely used continuum models of the meniscus mechanical properties in conjunction with emerging analytical and numerical models used to study the meniscus. The review presents relevant approaches and assumptions used to develop the models and includes discussions regarding strengths, weaknesses, and discrepancies involved in the presented models. The study presents a comprehensive coverage of relevant publications included in Compendex, EMBASE, MEDLINE, PubMed, ScienceDirect, Springer, and Scopus databases. This review aims at opening novel avenues for improving menisci modeling within the framework of constitutive modeling through highlighting the needs for further research directed toward determining key factors in gaining insight into the biomechanics of menisci which is crucial for the elaborate design of meniscal replacements.
IGF-I receptor (IGF-IR) signaling and functions are mediated through the activities of a complex molecular network of positive (e.g., type I IGF) and negative (e.g., the type II IGF receptor, ...IGF-IIR) effectors. Under normal physiological conditions, the balance between the expression and activities of these molecules is tightly controlled. Changes in this delicate balance (e.g., overexpression of one effector) may trigger a cascade of molecular events that can ultimately lead to malignancy. In recent years, evidence has been mounting that the IGF axis may be involved in human cancer progression and can be targeted for therapeutic intervention. Here we review old and more recent evidence on the role the IGF system in malignancy and highlight experimental and clinical studies that provide novel insights into the complex mechanisms that contribute to its oncogenic potential. Controversies arising from conflicting evidence on the relevance of IGF-IR and its ligands to human cancer are discussed. Our review highlights the importance of viewing the IGF axis as a complex multifactorial system and shows that changes in the expression levels of any one component of the axis, in a given malignancy, should be interpreted with caution and viewed in a wider context that takes into account the expression levels, state of activation, accessibility, and functionality of other interacting components. Because IGF targeting for anticancer therapy is rapidly becoming a clinical reality, an understanding of this complexity is timely because it is likely to have an impact on the design, mode of action, and clinical outcomes of newly developed drugs.
Abstract Decellularized adipose tissue (DAT) has shown potential as a regenerative scaffold for plastic and reconstructive surgery to augment or replace damaged or missing adipose tissue (e.g. ...following lumpectomy or mastectomy). The mechanical properties of soft tissue substitutes are of paramount importance in restoring the natural shape and appearance of the affected tissues, and mechanical mismatching can lead to unpredictable scar tissue formation and poor implant integration. The goal of this work was to assess the linear elastic and hyperelastic properties of decellularized human adipose tissue and compare them to those of normal breast adipose tissue. To assess the influence of the adipose depot source on the mechanical properties of the resultant decellularized scaffolds, we performed indentation tests on DAT samples sourced from adipose tissue isolated from the breast, subcutaneous abdominal region, omentum, pericardial depot and thymic remnant, and their corresponding force–displacement data were acquired. Elastic and hyperelastic parameters were estimated using inverse finite element algorithms. Subsequently, a simulation was conducted in which the estimated hyperelastic parameters were tested in a real human breast model under gravity loading in order to assess the suitability of the scaffolds for implantation. Results of these tests showed that in the human breast, the DAT would show similar deformability to that of native normal tissue. Using the measured hyperelastic parameters, we were able to assess whether DAT derived from different depots exhibited different intrinsic nonlinearities. Results showed that DAT sourced from varying regions of the body exhibited little intrinsic nonlinearity, with no statistically significant differences between the groups.
Abstract Despite the success of elastography in grading hepatic fibrosis by stiffness related noninvasive markers the relationship between viscoelastic constants in the liver and tissue structure ...remains unclear. We therefore studied the mechanical properties of 16 human liver specimens with different degrees of fibrosis, inflammation and steatosis by wideband magnetic resonance elastography (MRE) and static indentation experiments providing the specimens׳ static Young׳s modulus ( E ), dynamic storage modulus ( G ′) and dynamic loss modulus ( G ″). A frequency-independent shear modulus μ and a powerlaw exponent α were obtained by fitting G ′ and G ″ using the two-parameter sprinpot model. The mechanical parameters were compared to the specimens׳ histology derived parameters such as degree of Fibrosis ( F ), inflammation score and fat score, amount of hydroxyproline (HYP) used for quantification of collagen, blood markers and presurgery in vivo function tests. The frequency averaged parameters G ′, G ″ and μ were significantly correlated with F ( G ′: R =0.762, G ″: R =0.830; μ : R =0.744; all P <0.01) and HYP ( G ′: R =0.712; G ″: R =0.720; μ : R =0.731; all P <0.01). The powerlaw exponent α displayed an inverse correlation with F ( R =–0.590, P =0.034) and a trend of inverse correlation with HYP ( R =–0.470, P =0.089). The static Young׳s modulus E was less correlated with F ( R =0.587, P =0.022) and not sensitive to HYP. Although inflammation was highly correlated with F ( R =0.773, P <0.001), no interaction was discernable between inflammation and mechanical parameters measured in this study. Other histological and blood markers as well as liver function test were correlated with neither F nor the measured mechanical parameters. In conclusion, viscoelastic constants measured by wideband MRE are highly sensitive to histologically proven fibrosis. Our results suggest that, in addition to the amount of connective tissue, subtle structural changes of the viscoelastic matrix determine the sensitivity of mechanical tissue properties to hepatic fibrosis.
Finite element (FE)-based biomechanical simulations of the upper airway are promising computational tools to study abnormal upper airway deformations under obstructive sleep apnea (OSA) conditions ...and to help guide minimally invasive surgical interventions in case of upper airway collapse. To this end, passive biomechanical properties of the upper airway tissues, especially oropharyngeal soft tissues, are indispensable. This research aimed at characterizing the linear elastic mechanical properties of the oropharyngeal soft tissues including palatine tonsil, soft palate, uvula, and tongue base. For this purpose, precise indentation experiments were conducted on freshly harvested human tissue samples accompanied by FE-based inversion schemes. To minimize the impact of the probable nonlinearities of the tested tissue samples, only the first quarter of the measured force-displacement data corresponding to the linear elastic regime was utilized in the FE-based inversion scheme to improve the accuracy of the tissue samples’ Young's modulus calculations. Measured Young's moduli of the oropharyngeal soft tissues obtained in this study are presented. They include first estimates for palatine tonsil tissue samples while measured Young's moduli of other upper airway tissues were obtained for the first time using fresh human tissue samples.
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•Indentation testing of fresh oropharyngeal tissues harvested from patients undergoing surgery for obstructive sleep apnea.•Inverse finite-element modeling was performed to estimate the Young's modulus of each tissue.•Young's moduli for the palatine tonsils, soft palate, uvula and tongue base were estimated.
Developing suitable biomaterials for post-mastectomy or post-lumpectomy breast reconstruction is highly important. This study is aimed at evaluating biomechanical suitability of decellularized ...adipose tissue (DAT) for this purpose. The study involves computational experiments for evaluating deformation of the breast reconstructed using DAT under loading conditions pertaining to two common body position changes of prone-to-supine and prone-to-upright. This was conducted using nonlinear finite element models where the breast geometry was obtained from MRI image of a female breast. The experiments were performed using DAT sourced from various adipose tissue depots in comparison to natural adipose tissue. Data obtained from the conducted experiments showed no contour defects with various DAT materials for simulated post-mastectomy or post-lumpectomy breast reconstruction under the loading conditions. They also demonstrated that a breast reconstructed using DAT derived from the breast or subcutaneous abdominal depots exhibit significantly closer deformation, both qualitatively and quantitatively, to that of a normal breast under the same loading conditions. Similarity of DAT deformation to that of natural breast tissue in post-surgery breast reconstruction was assessed using nonlinear finite element analysis. Our results provide evidence that DAT derived from subcutaneous abdominal and breast depots yield more analogous deformation pattern to the natural tissue in post-mastectomy breast reconstruction applications. This is quite encouraging, as breast and subcutaneous adipose tissue can be readily obtained in large quantities from breast or abdominal lipo-reduction surgery procedures. Furthermore, in post-lumpectomy cases all DAT samples used in this research showed similar deformation, and thus are suitable as breast tissue substituents.
Purpose: The aortic time-enhancement curve obtained from dynamic CT myocardial perfusion imaging can be used to derive the cardiac output (CO) index based on the indicator dilution principle. The ...objective of this study was to investigate the effect of cardiac phase at which CT myocardial perfusion imaging is triggered on the CO index measurement with this approach. Methods: Electrocardiogram (ECG) gated myocardial perfusion imaging was performed on farm pigs with consecutive cardiac axial scans using a large-coverage CT scanner (Revolution, GE Healthcare) after intravenous contrast administration. Multiple sets of dynamic contrast-enhanced (DCE) cardiac images were reconstructed retrospectively from 30% to 80% R-R intervals with a 5% phase increment. The time-enhancement curve sampled from above the aortic orifice in each DCE image set was fitted with a modified gamma variate function (MGVF). The fitted curve was then normalized to the baseline data point unaffected by the streak artifact emanating from the contrast solution in the right heart chamber. The Stewart−Hamilton equation was used to calculate the CO index based on the integral of the fitted normalized aortic curve, and the results were compared among different cardiac phases. Results: The aortic time-enhancement curves sampled at different cardiac phases were different from each other, especially in the baseline portion of the curve where the effect of streak artifact was prominent. After properly normalizing and denoising with a MGVF, the integrals of the aortic curve were minimally different among cardiac phases (0.228 ± 0.001 Hounsfield Unit × second). The corresponding mean CO index was 4.031 ± 0.028 L/min. There were no statistical differences in either the integral of the aortic curve or CO index among different cardiac phases (p > 0.05 for all phases).
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