Multiaxial mechanical response and constitutive modeling of esophageal tissues: Impact on esophageal tissue engineering

Congenital defects of the esophagus are relatively frequent, with 1 out of 2500 babies suffering from such a defect. A new method of treatment by implanting tissue engineered esophagi into newborns is currently being developed and tested using ovine esophagi. For the reconstruction of the biological function of native tissues with engineered esophagi, their cellular structure as well as their mechanical properties must be considered. Since very limited mechanical and structural data for the esophagus are available, the aim of this study was to investigate the multiaxial mechanical behavior of the ovine esophagus and the underlying microstructure. Therefore, uniaxial tensile, biaxial tensile and extension-inflation tests on esophagi were performed. The underlying microstructure was examined in stained histological sections through standard optical microscopy techniques. Moreover, the uniaxial ultimate tensile strength and residual deformations of the tissue were determined. Both the mucosa-submucosa and the muscle layers showed nonlinear and anisotropic mechanical behavior during uniaxial, biaxial and inflation testing. Cyclical inflation of the intact esophageal tube caused marked softening of the passive esophagi in the circumferential direction. The rupture strength of the mucosa-submucosa layer was much higher than that of the muscle layer. Overall, the ovine esophagus showed a heterogeneous and anisotropic behavior with different mechanical properties for the individual layers. The intact and layer-specific multiaxial properties were characterized using a well-known three-dimensional microstructurally based strain-energy function. This novel and complete set of data serves the basis for a better understanding of tissue remodeling in diseased esophagi and can be used to perform computer simulations of surgical interventions or medical-device applications.     

Passive biaxial mechanical properties and in vivo axial pre-stretch of the diseased human femoropopliteal and tibial arteries

Surgical and interventional therapies for atherosclerotic lesions of the infrainguinal arteries are notorious for high rates of failure. Frequently, this leads to expensive reinterventions, return of disabling symptoms or limb loss. Interaction between the artery and repair material likely plays an important role in reconstruction failure, but data describing the mechanical properties and functional characteristics of human femoropopliteal and tibial arteries are currently not available. Diseased superficial femoral (SFA, n = 10), popliteal (PA, n = 8) and tibial arteries (TA, n = 3) from 10 patients with critical limb ischemia were tested to determine passive mechanical properties using planar biaxial extension. All specimens exhibited large nonlinear deformations and anisotropy. Under equibiaxial loading, all arteries were stiffer in the circumferential direction than in the longitudinal direction. Anisotropy and longitudinal compliance decreased distally, but circumferential compliance increased, possibly to maintain a homeostatic multiaxial stress state. Constitutive parameters for a four-fiber family invariant-based model were determined for all tissues to calculate in vivo axial pre-stretch that allows the artery to function in the most energy efficient manner while also preventing buckling during extremity flexion. Calculated axial pre-stretch was found to decrease with age, disease severity and more distal arterial location. Histological analysis of the femoropopliteal artery demonstrated a distinct sub-adventitial layer of longitudinal elastin fibers that appeared thicker in healthier arteries. The femoropopliteal artery characteristics and properties determined in this study may assist in devising better diagnostic and treatment modalities for patients with peripheral arterial disease.     

Validation of a fast method for quantification of intra‐abdominal and subcutaneous adipose tissue for large‐scale human studies

Central obesity is the hallmark of a number of non‐inheritable disorders. The advent of imaging techniques such as MRI has allowed for a fast and accurate assessment of body fat content and distribution. However, image analysis continues to be one of the major obstacles to the use of MRI in large‐scale studies. In this study we assess the validity of the recently proposed fat–muscle quantitation system (AMRA^TM Profiler) for the quantification of intra‐abdominal adipose tissue (IAAT) and abdominal subcutaneous adipose tissue (ASAT) from abdominal MR images. Abdominal MR images were acquired from 23 volunteers with a broad range of BMIs and analysed using sliceOmatic, the current gold‐standard, and the AMRA^TM Profiler based on a non‐rigid image registration of a library of segmented atlases. The results show that there was a highly significant correlation between the fat volumes generated by the two analysis methods, (Pearson correlation r = 0.97, p < 0.001), with the AMRA^TM Profiler analysis being significantly faster (~3 min) than the conventional sliceOmatic approach (~40 min). There was also excellent agreement between the methods for the quantification of IAAT (AMRA 4.73 ± 1.99 versus sliceOmatic 4.73 ± 1.75 l, p = 0.97). For the AMRA^TM Profiler analysis, the intra‐observer coefficient of variation was 1.6% for IAAT and 1.1% for ASAT, the inter‐observer coefficient of variation was 1.4% for IAAT and 1.2% for ASAT, the intra‐observer correlation was 0.998 for IAAT and 0.999 for ASAT, and the inter‐observer correlation was 0.999 for both IAAT and ASAT. These results indicate that precise and accurate measures of body fat content and distribution can be obtained in a fast and reliable form by the AMRA^TM Profiler, opening up the possibility of large‐scale human phenotypic studies. Copyright © 2015 John Wiley & Sons, Ltd.     

Chronic l-menthol-induced browning of white adipose tissue hypothesis: A putative therapeutic regime for combating obesity and improving metabolic health

IntroductionObesity constitutes a serious global health concern reaching pandemic prevalence rates. The existence of functional brown adipose tissue (BAT) in adult humans has provoked intense research interest in the role of this metabolically active tissue in whole-body energy balance and body weight regulation. A number of environmental, physiological, pathological, and pharmacological stimuli have been proposed to induce BAT-mediated thermogenesis and functional thermogenic BAT-like activity in white adipose tissue (WAT), opening new avenues for therapeutic strategies based on enhancing the number of beige adipocytes in WAT.HypothesisRecent evidence support a role of l-menthol cooling, mediated by TRPM8 receptor, on UCP1-dependent thermogenesis and BAT-like activity in classical WAT depots along with the recruitment of BAT at specific anatomical sites. l-Menthol-induced BAT thermogenesis has been suggested to occur by a β-adrenergic-independent mechanism, avoiding potential side-effects due to extensive β-adrenergic stimulation mediated by available beta receptor agonists. l-Menthol has been also linked to the activation of the cold-gated ion channel TRPA1. However, its role in l-menthol-induced UCP1-dependent thermogenic activity in BAT and WAT remains undetermined. White adipose tissue plasticity has important clinical implications for obesity prevention and/or treatment because higher levels of UCP1-dependent thermogenesis can lead to enhanced energy expenditure at a considerable extent. We hypothesize that chronic dietary l-menthol treatment could induce TRPM8- and TRPA1-dependent WAT adaptations, resembling BAT-like activity, and overall improve whole-body metabolic health in obese and overweight individuals.ConclusionsThe putative impact of chronic l-menthol dietary treatment on the stimulation of BAT-like activity in classical WAT depots in humans remains unknown. A detailed experimental design has been proposed to investigate the hypothesized l-menthol-induced browning of WAT. If our hypothesis was to be confirmed, TRPM8/TRPA1-induced metabolic adaptations of WAT to BAT-like activity could provide a promising novel therapeutic approach for increasing energy expenditure, regulating body weight, and preventing obesity and its related co-morbidities in humans.     

T1 and T2 temperature dependence of female human breast adipose tissue at 1.5 T: groundwork for monitoring thermal therapies in the breast

The T₁ and T₂ temperature dependence of female breast adipose tissue was investigated at 1.5 T in order to evaluate the applicability of relaxation‐based MR thermometry in fat for the monitoring of thermal therapies in the breast. Relaxation times T₁, T₂ and T_2TSE (the apparent T₂ measured using a turbo spin echo readout sequence) were measured in seven fresh adipose breast samples for temperatures from 25 to 65 °C. Spectral water suppression was used to reduce the influence of the residual water signal. The temperature dependence of the relaxation times was characterized. The expected maximum temperature measurement errors based on average calibration lines were calculated. In addition, the heating–cooling reversibility was investigated for two samples. The T₁ and T_2TSE temperature (T) dependence could be fitted well with an exponential function of 1/T. A linear relationship between T₂ and temperature was found. The temperature coefficients (mean ± inter‐sample standard deviation) of T₁ and T_2TSE increased from 25 °C (dT₁/dT = 5.35 ± 0.08 ms/°C, dT_2TSE/dT = 3.82 ± 0.06 ms/°C) to 65 °C (dT₁/dT = 9.50 ± 0.16 ms/°C, dT_2TSE/dT = 7.99 ± 0.38 ms/°C). The temperature coefficient of T₂ was 0.90 ± 0.03 ms/°C. The temperature‐induced changes in the relaxation times were found to be reversible after heating to 65 °C. Given the small inter‐sample variation of the temperature coefficients, relaxation‐based MR thermometry appears to be feasible in breast adipose tissue, and may be used as an adjunct to proton resonance frequency shift (PRFS) thermometry in aqueous tissue (glandular + tumor). Copyright © 2015 John Wiley & Sons, Ltd.