Plantar fasciopathy is a very common musculoskeletal complaint that leads to reduced physical activity and undermines the quality of life of patients. It is associated with changes in plantar fascia structure and biomechanics which are most often observed between the tissue\'s middle portion and the calcaneal insertion. Sonographic measurements of thickness and shear wave (SW) elastography are useful tools for detecting such changes and guide clinical decision making. However, their accuracy can be compromised by variability in the tissue\'s loading history. This study investigates the effect of loading history on plantar fascia measurements to conclude whether mitigation measures are needed for more accurate diagnosis. The plantar fasciae of 29 healthy participants were imaged at baseline and after different clinically relevant loading scenarios. The average (±standard deviation) SW velocity was 6.5 m/s (±1.5 m/s) and it significantly increased with loading. Indicatively, five minutes walking increased SW velocity by 14% (95% CI: -1.192, -0.298, t(27), p = 0.005). Thickness between the calcaneal insertion and the middle of the plantar fascia did not change with the tissues\' loading history. These findings suggest that preconditioning protocols are crucial for accurate SW elastography assessments of plantar fasciae and have wider implications for the diagnosis and management of plantar fasciopathy.

BACKGROUND: Chondrogenic differentiation medium (CDM) is usually used to maintain chondrogenic activity during chondrocyte sheet production. However, tissue qualities remain to be determined as to what factors improve cell functions. Moreover, the relationship between CDM and cell migration proteins has not been reported.
METHODS: In this study, the effect of CDM on the behavior of chondrocyte sheets was investigated. Structural analysis, mechanical testing and proteomics were performed to observe tissue qualities. The relationship between CDM and cell migration proteins were investigated using time-lapse observations and bioinformatic analysis.
RESULTS: During 48 h, CDM affected the chondrocyte behaviors by reducing cell migration. Compared to the basal medium, CDM impacted the contraction of monolayered chondrocyte sheets. At day 7, the contracted sheets increased tissue thickness and improved tissue stiffness. Cartilage specific proteins were also upregulated. Remarkedly, the chondrocyte sheets in CDM displayed downregulated proteins related to cell migration. Bioinformatic analysis revealed that TGFβ1 was shown to be associated with cartilage functions and cell migration. Pathway analysis of chondrocyte sheets in CDM also revealed the presence of a TGFβ pathway without activating actin production, which might be involved in synthesizing cartilage-specific proteins. Cell migration pathway showed MAPK signaling in both cultures of the chondrocyte sheets.
CONCLUSIONS: Reduced cell migration in the chondrocyte sheet affected the tissue quality. Using CDM, TGFβ1 might trigger cartilage protein production through the TGFβ pathway and be involved in cell migration via the MAPK signaling pathway. Understanding cell behaviors and their protein expression would be beneficial for developing high-quality tissue-engineered cartilage.

Epithelial-stromal interplay through chemomechanical cues from cells and matrix propels cancer progression. Elevated tissue stiffness in potentially malignant tissues suggests a link between matrix stiffness and enhanced tumor growth. In this study, employing chronic oral/esophageal injury and cancer models, it is demonstrated that epithelial-stromal interplay through matrix stiffness and Hedgehog (Hh) signaling is key in compounding cancer development. Epithelial cells actively interact with fibroblasts, exchanging mechanoresponsive signals during the precancerous stage. Specifically, epithelial cells release Sonic Hh, activating fibroblasts to produce matrix proteins and remodeling enzymes, resulting in tissue stiffening. Subsequently, basal epithelial cells adjacent to the stiffened tissue become proliferative and undergo epithelial-to-mesenchymal transition, acquiring migratory and invasive properties, thereby promoting invasive tumor growth. Notably, transcriptomic programs of oncogenic GLI2, mechano-activated by actin cytoskeletal tension, govern this process, elucidating the crucial role of non-canonical GLI2 activation in orchestrating the proliferation and mesenchymal transition of epithelial cells. Furthermore, pharmacological intervention targeting tissue stiffening proves highly effective in slowing cancer progression. These findings underscore the impact of epithelial-stromal interplay through chemo-mechanical (Hh-stiffness) signaling in cancer development, and suggest that targeting tissue stiffness holds promise as a strategy to disrupt chemo-mechanical feedback, enabling effective cancer treatment.

Cancer metastasis is the leading cause of death for those afflicted with cancer. In cancer metastasis, the cancer cells break off from the primary tumor, penetrate nearby blood vessels, and attach and extravasate out of the vessels to form secondary tumors at distant organs. This makes extravasation a critical step of the metastatic cascade. Herein, with a focus on triple-negative breast cancer, the role that the prospective secondary tumor microenvironment\'s mechanical properties play in circulating tumor cells\' extravasation is reviewed. Specifically, the effects of the physically regulated vascular endothelial glycocalyx barrier element, vascular flow factors, and subendothelial extracellular matrix mechanical properties on cancer cell extravasation are examined. The ultimate goal of this review is to clarify the physical mechanisms that drive triple-negative breast cancer extravasation, as these mechanisms may be potential new targets for anti-metastasis therapy.

BACKGROUND: Magnetic resonance elastography (MRE) is a rapidly developing medical imaging technique that allows for quantitative assessment of the biomechanical properties of the tissue. MRE is now regarded as the most accurate noninvasive test for detecting and staging liver fibrosis. A two-dimensional (2D MRE) acquisition version is currently deployed at >2000 locations worldwide. 2D MRE allows for the evaluation of the magnitude of the complex shear modulus, also referred to as stiffness. The development of 3D vector MRE has enabled researchers to assess the biomechanical properties of small organs where wave propagation cannot be adequately analyzed with the 2D MRE imaging approach used in the liver. In 3D vector MRE, the shear waves are imaged and processed throughout a 3D volume and processed with an algorithm that accounts for wave propagation in any direction. Additionally, the motion is also imaged in x, y, and z directions at each voxel, allowing for more advanced processing to be applied.
OBJECTIVE: This review describes the technical principles of 3D vector MRE, surveys its clinical applications in small organs, and discusses potential clinical significance of 3D vector MRE.
CONCLUSIONS: 3D vector MRE is a promising tool for characterizing the biomechanical properties of small organs such as the uterus, pancreas, thyroid, prostate, and salivary glands. However, its potential has not yet been fully explored.

Aortic stiffening is an inevitable manifestation of chronological aging, yet the mechano-molecular programs that orchestrate region- and layer-specific adaptations along the length and through the wall of the aorta are incompletely defined. Here, we show that the decline in passive cyclic distensibility is more pronounced in the ascending thoracic aorta (ATA) compared to distal segments of the aorta and that collagen content increases in both the medial and adventitial compartments of the ATA during aging. The single-cell RNA sequencing of aged ATA tissues reveals altered cellular senescence, remodeling, and inflammatory responses accompanied by enrichment of T-lymphocytes and rarefaction of vascular smooth muscle cells, compared to young samples. T lymphocyte clusters accumulate in the adventitia, while the activation of mechanosensitive Piezo-1 enhances vasoconstriction and contributes to the overall functional decline of ATA tissues. These results portray the immuno-mechanical aging of the ATA as a process that culminates in a stiffer conduit permissive to the accrual of multi-gerogenic signals priming to disease development.

The presence of molecular mutations in colorectal cancer (CRC) is a decisive factor in selecting the most effective first-line therapy. However, molecular analysis is routinely performed only in a limited number of patients with remote metastases. We propose to use tissue stiffness as a marker of the presence of molecular mutations in CRC samples. For this purpose, we applied compression optical coherence elastography (C-OCE) to calculate stiffness values in regions corresponding to specific CRC morphological patterns (n = 54). In parallel to estimating stiffness, molecular analysis from the same zones was performed to establish their relationships. As a result, a high correlation between the presence of KRAS/NRAS/BRAF driver mutations and high stiffness values was revealed regardless of CRC morphological pattern type. Further, we proposed threshold stiffness values for label-free targeted detection of molecular alterations in CRC tissues: for KRAS, NRAS, or BRAF driver mutation-above 803 kPa (sensitivity-91%; specificity-80%; diagnostic accuracy-85%), and only for KRAS driver mutation-above 850 kPa (sensitivity-90%; specificity-88%; diagnostic accuracy-89%). To conclude, C-OCE estimation of tissue stiffness can be used as a clinical diagnostic tool for preliminary screening of genetic burden in CRC tissues.

BACKGROUND: Although premature ejaculation (PE) is the most common male sexual dysfunction, the underlying mechanisms are not fully understood.
OBJECTIVE: The study sought to evaluate the possible associations among glans penis volume and tissue stiffness measured using penile ultrasonography and penile shear wave elastography (SWE) with PE.
METHODS: Men 18 to 65 years of age with normal International Index of Erectile Function scores (>25) and who were diagnosed with PE between June 2021 and June 2022 were enrolled. The Premature Ejaculation Diagnostic Tool score and intravaginal ejaculation latency times were recorded. Healthy volunteers constituted the control group. The study group was divided into lifelong PE (LLPE) and acquired PE (AqPE) subgroups. In all groups, the glans penis volume was measured via penile ultrasonography and tissue stiffness of the glans penis, penile frenulum, postcircumcision mucosal cuff, and penile shaft were measured via SWE. The findings of the groups were compared using appropriate statistical methods.
RESULTS: The outcomes included ultrasonographic and elastographic measurements of the glans penis.
RESULTS: Data on 140 men, including 70 PE patients and 70 healthy volunteers, were evaluated. Of the patients, 20 had LLPE and 50 had AqPE. The median glans penis volume was significantly greater in the LLPE group (14.1 [range, 6.6-19] mm3) compared with the AqPE group (11.7 [range, 5.1-27] mm3) and control group (11.4 [range, 6.1-32] mm3) (P = .03). According to the Youden index, the best cutoff value for glans penis volume in LLPE compared with non-LLPE (AqPE + control) was 12.65 mm3 (area under the curve, 0.684; 95% confidence interval, 0.556-0.812; P = .009). The risk of having LLPE in those with a glans penis volume ≥12.65 mm3 was 3.326 (95% confidence interval, 1.234-8.965) times higher than the non-LLPE group (P = .014). There were no significant differences between the groups in the SWE evaluation of glans penis, penile frenulum, mucosal cuff, and penile shaft tissue stiffness.
CONCLUSIONS: The high incidence of PE in those with high glans penis volume may make glans penis volume a predictor for the development of LLPE.
UNASSIGNED: This was the first study to show that PE is more common in individuals with a high glans penis volume. It was also the first to perform a penile elastographic evaluation in patients with PE. The most important limitation was that we did not evaluate glans penile nerve function with a test, but rather we made an indirect inference about the density of free nerve endings based on increased glans penile volume.
CONCLUSIONS: Glans penis volume was a significant predictor for LLPE. However, there are no associations between PE and the glans penis, postcircumcision mucosal cuff, penile frenulum, or penile shaft tissue stiffness and development.

BACKGROUND: Different MR elastography (MRE) systems may produce different stiffness measurements, making direct comparison difficult in multi-center investigations.
OBJECTIVE: To assess the repeatability and reproducibility of liver stiffness measured by three typical MRE systems.
METHODS: Prospective.
UNASSIGNED: Thirty volunteers without liver disease history (20 males, aged 21-28)/5 gel phantoms.
UNASSIGNED: 3.0 T United Imaging Healthcare (UIH), 1.5 T Siemens Healthcare, 3.0 T General Electric Healthcare (GE)/Echo planar imaging-based MRE sequence.
RESULTS: Wave images of volunteers and phantoms were acquired by three MRE systems. Tissue stiffness was evaluated by two observers, while phantom stiffness was assessed automatically by code. The reproducibility across three MRE systems was quantified based on the mean stiffness of each volunteer and phantom.
METHODS: Intraclass correlation coefficients (ICC), coefficients of variation (CV), and Bland-Altman analyses were used to assess the interobserver reproducibility, the interscan repeatability, and the intersystem reproducibility. Paired t-tests were performed to assess the interobserver and interscan variation. Friedman tests with Dunn\'s multiple comparison correction were performed to assess the intersystem variation. P values less than 0.05 indicated significant difference.
RESULTS: The reproducibility of stiffness measured by the two observers demonstrated consistency with ICC > 0.92, CV < 4.32%, Mean bias < 2.23%, and P > 0.06. The repeatability of measurements obtained using the electromagnetic system for the liver revealed ICC > 0.96, CV < 3.86%, Mean bias < 0.19%, P > 0.90. When considering the range of reproducibility across the three systems for liver evaluations, results ranged with ICCs from 0.70 to 0.87, CVs from 6.46% to 10.99%, and Mean biases between 1.89% and 6.30%. Phantom studies showed similar results. The values of measured stiffness differed across all three systems significantly.
CONCLUSIONS: Liver stiffness values measured from different MRE systems can be different, but the measurements across the three MRE systems produced consistent results with excellent reproducibility.
METHODS: 1 TECHNICAL EFFICACY: Stage 2.

Three-dimensional (3D) magnetic resonance elastography (MRE) is more accurate than two-dimensional (2D) MRE; however, it requires long-term acquisition. This study aimed to reduce the acquisition time of abdominal 3D MRE using a new sample interval modulation (short-SLIM) approach that can acquire all three motions faster while reducing the prolongation of echo time and flow compensation. To this end, two types of phantom studies and an in vivo test of the liver in three healthy volunteers were performed to compare the performances of conventional spin-echo echo-planar (SE-EPI) MRE, conventional SLIM and short-SLIM. One phantom study measured the mean amplitude and shear modulus within the overall region of a homogeneous phantom by changing the mechanical vibration power to assess the robustness to the lowered phase-to-noise ratio in short-SLIM. The other measured the mean shear modulus in the stiff and background materials of a phantom with an embedded stiffer rod to assess the performance of short-SLIM for complex wave patterns with wave interference. The Spearman\'s rank correlation coefficient was used to assess similarity of elastograms in the rod-embedded phantom and liver between methods. The results of the phantom study changing the vibration power indicated that there was little difference between conventional MRE and short-SLIM. Moreover, the elastogram pattern and the mean shear modulus in the rod-embedded phantom in conventional SLIM and short-SLIM did not change for conventional MRE; the liver test also showed a small difference between the acquisition techniques. This study demonstrates that short-SLIM can provide MRE results comparable to those of conventional MRE. Short-SLIM can reduce the total acquisition time by a factor of 2.25 compared to conventional 3D MRE time, leading to an improvement in the accuracy of shear modulus estimation by suppressing the patient movements.