Tissue Stiffness Research Articles

Intelligent ultrasonic aspirator: Advancing tissue differentiation through hierarchical classification during hand-held resection

Modern neurosurgery strives to maximize tumor removal while preserving healthy tissue integrity. Accurate intraoperative differentiation between tumor and healthy tissue is crucial yet challenging. Often neurosurgeons rely on their experience and haptic feedback during palpation to distinguish between tumor and healthy tissue. A commonly used hand-held tool for tissue removal during neurosurgery is the ultrasonic aspirator, which changes its electrical properties as it interacts with tissue. The goal is to equip the ultrasonic aspirator with the ability to differentiate between different types of tissue while at the same time not interfering with the surgical workflow and providing comprehensible outcomes. To this end, a hierarchical classification approach is employed as a proof of concept, enabling precise identification of tissue stiffness during resection.The hierarchical approach is compared with the standard flat classification, commonly used in machine learning. Within the hierarchical approach, two strategies are employed: mandatory leaf-node predictions (MLNP) and non-mandatory leaf-node predictions (NMLNP). The NMLNP allows prediction to revert to a parent node when certainty is low. Data are acquired on three artificial tissue models – differing in stiffness – with an ultrasonic aspirator in a hand-held manner. The dataset comprises 1,821 data points for training and 186 for testing after balancing.The results indicate a slight performance advantage for the hierarchical classification MLNP approach over the flat classification approach in the absence of confidence thresholds, with weighted F2-scores of 0.781 and 0.762, respectively. However, the application of confidence thresholds results in both approaches exhibiting comparable performance, with the hierarchical NMLNP approach achieving a weighted F1-score of 0.920, thereby demonstrating superior overall performance. The effects of enforcing these thresholds and excluding data with low certainty are thoroughly investigated. This work emphasizes the feasibility of tissue differentiation using a hand-held ultrasound aspirator while resecting tissue. Moreover, it highlights the capability of hierarchical classification in advancing tissue differentiation accuracy during neurosurgical procedures, which could ultimately aid surgeons and enhance the safety of intraoperative workflows.

Assessing Placental Shear Wave Elastography as a Tool for Evaluating Preeclampsia.

Background Hypertensive disorders of pregnancy, especially its dreaded complication preeclampsia, remain a major cause of morbidity and mortality for both the mother and the fetus. Existing tools for the prediction of preeclampsia remain inadequate in their sensitivity and specificity. Hence, there is an urgent need for a reliable, economically feasible, and objective marker for its diagnosis/early prediction. In this regard, shear wave elastography has shown great promise. Shear wave elastography is a novel method to quantify tissue stiffness, which is objective and has significantly lower inter-observer variability. Objectives We aim to quantify the tissue elasticity using point shear wave elastography (pSWE) in the placentas of diagnosed cases of preeclampsia and to compare them with the placentas of healthy controls in order to evaluate if there is a significant statistical difference between the two. Materials and methods This comparative study was conducted at the Department of Radiodiagnosis, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, India, from August 2022 to July 2024. The study included 60 participants, divided into two groups: 30 patients with preeclampsia and 30 healthy pregnancies. Placental stiffness was measured using a Samsung HS70A ultrasound machine (Samsung Electronics Pvt. Ltd., Seoul, South Korea), and pSWE was performed with a curvilinear probe. Data was analyzed using IBM SPSS Statistics for Windows, Version 21 (Released 2012; IBM Corp., Armonk, New York, United States), and the significance of differences between the two groups was assessed using an independent t-test with a p-value of <0.05, considered statistically significant. Results The mean placental stiffness, measured in kilopascals (kPa), was significantly higher in the preeclampsia group (11.71 ± 1.52 kPa) in comparison to the healthy group (3.36 ± 0.66 kPa) (p = 0.001). Patients suffering from preeclampsia were found to have significantly higher levels of placental stiffness. Conclusion Early diagnosis remains key to managing preeclampsia so that adequate monitoring and treatment could be provided to the patients. Our study showed that there is a significant statistical difference in the placental stiffness in patients with preeclampsia in comparison to a healthy placenta. Hence, shear wave elastography can be used as a supplementary tool to aid in the diagnosis/prediction of preeclampsia.

Increased needle passes for comparable diagnostic yield in endoscopic ultrasound-guided tissue acquisition for pancreatic stiff lesions measured by elastography

Background/objectivesPancreatic cancer is characterized by tissue stiffness due to the high concentration of cancer-associated fibroblasts and extracellular matrix. Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is performed to diagnose pancreatic cancer but yields false-negative results attributed to inadequate specimens. EUS-elastography is a real-time assessment method to pancreatic tissue stiffness. This study aims to investigate the correlation between diagnostic yield and the number of needle passes based on the stiffness measured by elastography. MethodsPatients who underwent EUS-TA for pancreatic solid mass were retrospectively reviewed and included in this study. The number of needle passes during EUS-TA was determined based on macroscopic on-site evaluation. Tissue stiffness measurements were taken using EUS-elastography. The primary study outcome was the diagnostic yield. The secondary outcome included the number of needle passes required for a diagnosis. ResultsA total of 652 patients were included. The average stiffness differed depending on the location of the tumor, and high-stiffness group had more malignant lesions. Although the diagnostic yield was not significantly different between groups, the number of needle passes was significantly higher in the high-stiffness group (3.6 ± 1.0 vs. 3.2 ± 0.9, p < 0.001). ConclusionsThe higher the stiffness of the pancreatic mass in EUS-elastography, the more needle passes are required to achieve a comparable diagnostic yield.

Quantifying canine tissue stiffness change patterns using shear-wave elastography: implications for time of death estimation

ABSTRACT This study investigates the applicability and reproducibility of shear-wave elastography (SWE) in detecting changes in tissue stiffness of canine carcasses. SWE was performed on six canines by two operators. The target organs were liver, spleen, kidney, and thigh muscles. SWE was performed ante-mortem and up to 48-hours post-mortem at specific intervals. The Mann-Whitney U-test and Spearman correlation coefficient showed insignificant correlation between gender and weight with shear-wave velocity (SWV) in ante-mortem scans. The Kruskal-Wallis H-test showed significant differences in SWV for all organs. Intraclass correlation coefficient (ICC) showed excellent correlation for all target organs except for kidneys. Pairwise comparison showed a similar SWV trend for abdominal organs. Accuracy metrics were calculated for determining the post-mortem interval using SWV values. The liver had the highest accuracy (0.69–0.83) across different post-mortem interval thresholds within the cut-off values of ≥2.0 m/s, 1.8–2.0 m/s, <1.8 m/s indicating ≤6 hours post-mortem, 12–18 hours post-mortem and >18 hours post-mortem. The spleen, kidney and thigh muscle demonstrated moderate-to-poor accuracy within the same cut-off parameters. Post-mortem SWV changes in canine solid organs, and soft tissues, particularly the liver, demonstrate a reproducible pattern, which may have value in determining the post-mortem interval.

Effects of a Manual Treatment on Lumbar Microcirculation and Tissue Stiffness Following Submaximal Eccentric Trunk Extensor Exercise: A Randomized Controlled Trial.

Recent studies have shown that the extramuscular connective tissue (ECT) is thickened and stiffened in delayed onset muscle soreness (DOMS). However, contrarily to the normal population, severe DOMS is rare in athletes or highly trained individuals. The present randomized, controlled trial therefore aimed to investigate pain as well as microcirculation and stiffness of the ECT and the erector spinae muscle following submaximal eccentric trunk extension exercise not causing DOMS. The effect of manual treatment by a therapist (myofascial release; MFR) on these parameters was to be studied. Trained healthy participants (n = 21; 31.3 ± 9.6 years; > 4 h exercise per week) performed submaximal eccentric exercise of the trunk extensors. One group was manually treated (n = 11), while the other group (n = 10) received placebo treatment with sham laser therapy. Stiffness of the ECT and the erector spinae muscle (shear wave elastography), microcirculation (white light and laser Doppler spectroscopy), palpation pain (100 mm visual analogue scale, VAS) and pressure pain threshold (indentometry, PPT) were assessed before (t0), 24 h (t24) and 48 h (t48) after conditions. Erector spinae muscle stiffness increased after eccentric exercise from t0 to t24 (0.875 m/s) and from t0 to t48 (0.869 m/s). After MFR, erector spinae muscle stiffness decreased in contrast to placebo treatment at t24 (-0.66 m/s), while ECT stiffness remained unchanged. Oxygen saturation increased (17-20.93%) and relative haemoglobin decreased (-9.1 - -12.76 AU) after eccentric exercise and MFR differed from placebo treatment at t48 (-3.71 AU). PPT differed after MFR from placebo treatment at t48 (20.69 N/mm), while VAS remained unchanged. Multiple linear regression showed that ECT stiffness and group membership predicted erector spinae muscle stiffness. MFR could have a positive effect on pain, microcirculation and muscle stiffness after submaximal eccentric exercise, suggesting better recovery, which needs to be confirmed by future work.

AI-Powered Synthesis of Structured Multimodal Breast Ultrasound Reports Integrating Radiologist Annotations and Deep Learning Analysis.

Breast cancer is the most prevalent cancer among women worldwide. B-mode ultrasound (US) is essential for early detection, offering high sensitivity and specificity without radiation exposure. This study introduces a semi-automatic method to streamline breast US report generation, aiming to reduce the burden on radiologists. Our method synthesizes comprehensive breast US reports by combining the extracted information from radiologists' annotations during routine screenings with the analysis results from deep learning algorithms on multimodal US images. Key modules in our method include image classification using visual features (ICVF), type classification via deep learning (TCDL), and automatic report structuring and compilation (ARSC). Experiments showed that the proposed method reduced the average report generation time to 3.8 min compared to manual processes, even when using relatively low-spec hardware. Generated reports perfectly matched ground truth reports for suspicious masses without a single failure on our evaluation datasets. Additionally, the deep-learning-based algorithm, utilizing DenseNet-121 as its core model, achieved an overall accuracy of 0.865, precision of 0.868, recall of 0.847, F1-score of 0.856, and area under the receiver operating characteristics of 0.92 in classifying tissue stiffness in breast US shear-wave elastography (SWE-mode) images. These improvements not only streamline the report generation process but also allow radiologists to dedicate more time and focus on patient care, ultimately enhancing clinical outcomes and patient satisfaction.

Strain-dependent dynamic re-alignment of collagen fibers in skeletal muscle extracellular matrix

Collagen fiber architecture within the skeletal muscle extracellular matrix (ECM) is significant to passive muscle mechanics. While it is thought that collagen fibers re-orient themselves in response to changes in muscle length, this has not been dynamically visualized and quantified within a muscle. The goal of this study was to measure changes in collagen alignment across a range of muscle lengths and compare the corresponding alignment to muscle mechanics. We hypothesized that collagen fibers dynamically increase alignment in response to muscle stretching, and this change in alignment is related to passive muscle stiffness. Further, we hypothesized that digesting collagen fibers with collagenase would reduce the re-alignment response to muscle stretching. Using DBA/2J and D2.mdx mice, we isolated extensor digitorum longus (EDL), soleus, and diaphragm muscles for collagenase or sham treatment and decellularization to isolate intact or collagenase-digested decellularized muscles (DCMs). These DCMs were mechanically tested and imaged using second harmonic generation microscopy to measure collagen alignment across a range of strains. We found that collagen alignment increased in a strain-dependent fashion, but collagenase did not significantly affect the strain-dependent change in alignment. We also saw that the collagen fibers in the diaphragm epimysium (surface ECM) and perimysium (deep ECM) started at different angles, but still re-oriented in the same direction in response to stretching. These robust changes in collagen alignment were weakly related to passive DCM stiffness. Overall, we demonstrated that the architecture of muscle ECM is dynamic in response to strain and is related to passive muscle mechanics. Statement of significanceOur study presents a unique visualization and quantification of strain-induced changes in muscle collagen fiber alignment as they relate to passive mechanics. Using dynamic imaging of collagen in skeletal muscle we demonstrate that as skeletal muscle is stretched, collagen fibers re-orient themselves along the axis of stretch and increase their alignment. The degree of alignment and the increase in alignment are each weakly related to passive muscle stiffness. Collagenase treatments further demonstrate that the basis for muscle Extracellular matrix stiffness is dependent on factors beyond collagen crosslinking and alignment. Together the study contributes to the knowledge of the structure-function relationships of muscle extracellular matrix to tissue stiffness relevant to conditions of fibrosis and aberrant stiffness.

Exploiting a tumor softening targeted bomb for mechanical gene therapy of chemoresistant Triple-Negative breast cancer

Triple-negative breast cancer (TNBC)-the most aggressive and refractory subtype of breast cancer-plagues many patients. The tumor physical microenvironment (TPME) is characterized by altered stromal composition and extracellular matrix (ECM), which may contribute to tissue stiffness and compromise therapeutic efficacy. Here, based on clinical data analysis and preclinical model validation, we discover that chemoresistant TNBC tends to have a stiffer TPME with a more aggressive genomic landscape, in which lysyl oxidase (LOX) exerts pivotal effects. Anlotinib (An), a multi-targeted tyrosine kinase inhibitor, has great promising potential in the treatment of TNBC. In this regard, we developed a tumor-softening nanobomb (An&siLOX@NPs) that remodels TPME by co-delivering small interfering siRNAs silencing LOX and the anti-angiogenic drug, anlotinib (An). The improved cytosolic delivery of siLOX enables TPME remodeling via reducing deposition and cross-linking between collagen and fibronectin, thereby promoting enrichment of An to improve its therapeutic outcomes. In chemoresistant TNBC, we confirm the An&siLOX@NPs nanobomb-mediated mechanical gene therapy results in obvious inhibition of local tumor outgrowth and prolongs survival. Additionally, softened TPME reactivates intratumoral immune milieu to bolster sensitivity to anti-PD-L1 immunotherapy, completely curing 33.3% of the metastatic tumors, further generating a synergistic anti-tumor efficacy. Collectively, our mechanical gene therapy strategy represents a highly efficient, safe, and versatile anti-drug resistance modality, which not only can solve the snag problem of TNBC treatment but also provides a new demonstration for other tumor treatments.

The Fibrotic Phenotype of Human Precision-Cut Lung Slices Is Maintained after Cryopreservation.

Human precision-cut lung slices (hPCLS) prepared from fibrotic lungs recapitulate the pathophysiological hallmarks of fibrosis. These hallmark features can also be induced by treating non-fibrotic hPCLS with a fibrotic cocktail (FC). As a result, the fibrotic and fibrosis-induced hPCLS are rapidly emerging as preferred models for disease modeling and drug discovery. However, current hPCLS models are limited by tissue viability in culture, as they are usually only viable for one week after harvesting. Here, we demonstrate that the fibrotic hPCLS can be cryopreserved, stored for months, and then thawed on demand without loss of hPCLS viability or protein content for 14 days post-thawing. Cryopreservation also preserves the pro-fibrotic potential of non-fibrotic hPCLS. Specifically, when we treated the thawed non-fibrotic hPCLS with an FC, we observed significant pro-fibrotic cytokine secretion and elevated tissue stiffness. These pro-fibrotic changes were inhibited by the small-molecule tyrosine kinase inhibitor, Nintedanib. Taken together, our work indicates that a feasible solution to prolong the pre-clinical utility of fibrotic and fibrosis-induced hPCLS is cryopreservation. We anticipate that cryopreserved hPCLS will serve as an advantageous predictive model for the evaluation of pro-fibrotic pathways during acute and chronic toxicity testing.

High-Frequency Ultrasound in the Assessment of Cellulite-Correlation between Ultrasound-Derived Measurements, Clinical Assessment, and Nürnberger-Müller Scale Scores.

Cellulite is a cosmetic defect of multifactorial etiology that affects over 90% of women worldwide. Cellulite-induced skin changes are undesirable and negatively affect self-esteem. Despite a plethora of cellulite-reducing treatments, we still lack objective tools to enable accurate diagnosis and treatment efficacy assessment. The aim of this study was to determine whether high-frequency ultrasound can be helpful in assessing cellulite and whether there is an association between ultrasound-derived measurements, parameters ascertained clinically, and cellulite assessment scale scores. The study group consisted of 114 women with cellulite in their posterior thighs, assessed using the Nürnberger-Müller scale. Two types of ultrasound devices were used in this study: a conventional scanner with a linear transducer and a skin-dedicated scanner equipped with a mechanical transducer. We used high-frequency ultrasonography to determine epidermal thickness, dermal thickness, the surface area of fat protrusions at the dermal subcutaneous junction, and the thickness and stiffness of the subcutaneous tissue (ultrasound elastography). There was a correlation between cellulite severity and subcutaneous tissue thickness (r = 0.63), the surface area of fat protrusions at the dermal subcutaneous junction (r = 0.64), and the elastographic strain ratio (r = 0.51). An association was also demonstrated between thigh circumference and subcutaneous tissue thickness (r = 0.48). There was a significant difference in the assessed parameters between the subgroups identified by cellulite severity scores. Ultrasound-determined surface area of fat protrusions at the dermal subcutaneous junction as well as the thickness and stiffness of the subcutaneous tissue seem useful in cellulite assessment. Thus, ultrasonography has the potential to become a common tool in aesthetic medicine and cosmetology.

Photo-induced changes in tissue stiffness alter epithelial budding morphogenesis in the embryonic lung.

Extracellular matrix (ECM) stiffness has been shown to influence the differentiation of progenitor cells in culture, but a lack of tools to perturb the mechanical properties within intact embryonic organs has made it difficult to determine how changes in tissue stiffness influence organ patterning and morphogenesis. Photocrosslinking of the ECM has been successfully used to stiffen soft tissues, such as the cornea and skin, which are optically accessible, but this technique has not yet been applied to developing embryos. Here, we use photocrosslinking with Rose Bengal (RB) to locally and ectopically stiffen the pulmonary mesenchyme of explanted embryonic lungs cultured ex vivo . This change in mechanical properties was sufficient to suppress FGF-10-mediated budding morphogenesis along the embryonic airway, without negatively impacting patterns of cell proliferation or apoptosis. A computational model of airway branching was used to determine that FGF-10-induced buds form via a growth-induced buckling mechanism and that increased mesenchymal stiffness is sufficient to inhibit epithelial buckling. Taken together, our data demonstrate that photocrosslinking can be used to create regional differences in mechanical properties within intact embryonic organs and that these differences influence epithelial morphogenesis and patterning. Further, this photocrosslinking assay can be readily adapted to other developing tissues and model systems.

Restoring mechanophenotype reverts malignant properties of ECM-enriched vocal fold cancer.

Increased extracellular matrix (ECM) and matrix stiffness promote solid tumor progression. However, mechanotransduction in cancers arising in mechanically active tissues remains underexplored. Here, we report upregulation of multiple ECM components accompanied by tissue stiffening in vocal fold cancer (VFC). We compare non-cancerous (NC) and patient-derived VFC cells - from early (mobile, T1) to advanced-stage (immobile, T3) cancers - revealing an association between VFC progression and cell-surface receptor heterogeneity, reduced laminin-binding integrin cell-cell junction localization and a flocking mode of collective cell motility. Mimicking physiological movement of healthy vocal fold tissue (stretching/vibration), decreases oncogenic nuclear β-catenin and YAP levels in VFC. Multiplex immunohistochemistry of VFC tumors uncovered a correlation between ECM content, nuclear YAP and patient survival, concordant with VFC sensitivity to YAP-TEAD inhibitors in vitro. Our findings present evidence that VFC is a mechanically sensitive malignancy and restoration of tumor mechanophenotype or YAP/TAZ targeting, represents a tractable anti-oncogenic therapeutic avenue for VFC.

Real-Time Wireless Sensing of Cardiomyocyte Contractility by Integrating Magnetic Microbeam and Oriented Nanofibers.

In vitro cardiomyocyte mechano-sensing platform is crucial for evaluating the mechanical performance of cardiac tissues and will be an indispensable tool for application in drug discovery and disease mechanism study. Magnetic sensing offers significant advantages in real-time, in situ wireless monitoring and resistance to ion interference. However, due to the mismatch between the stiffness of traditional rigid magnetic material and myocardial tissue, sensitivity is insufficient and it is difficult to achieve cell structure induction and three-dimensional cultivation. Herein, a magnetic sensing platform that integrates a neodymium-iron-boron/polydimethylsiloxane (NdFeB/PDMS) flexible microbeam with suspended and ordered polycaprolactone (PCL) nanofiber membranes was developed, providing a three-dimensional anisotropic culture environment for cardiomyocyte growth and simultaneously realizing in situ wireless contractility monitoring. The as-prepared sensor presented an ultrahigh sensitivity of 442.2 μV/μm and a deflection resolution of 2 μm. By continuously monitoring the cardiomyocyte growth status and drug stimulation feedback, we verified the capability of the platform to capture dynamic changes in cardiomyocyte contractility. This platform provides a perspective tool for evaluating cardiomyocyte maturity and drug performance.

Spatial transcriptomic validation of a biomimetic model of fibrosis enables re-evaluation of a therapeutic antibody targeting LOXL2

Matrix stiffening by lysyl oxidase-like 2 (LOXL2)-mediated collagen cross-linking is proposed as a core feedforward mechanism that promotes fibrogenesis. Failure in clinical trials of simtuzumab (the humanized version of AB0023, a monoclonal antibody against human LOXL2) suggested that targeting LOXL2 may not have disease relevance; however, target engagement was not directly evaluated. We compare the spatial transcriptome of active human lung fibrogenesis sites with different human cell culture models to identify a disease-relevant model. Within the selected model, we then evaluate AB0023, identifying that it does not inhibit collagen cross-linking or reduce tissue stiffness, nor does it inhibit LOXL2 catalytic activity. In contrast, it does potently inhibit angiogenesis consistent with an alternative, non-enzymatic mechanism of action. Thus, AB0023 is anti-angiogenic but does not inhibit LOXL2 catalytic activity, collagen cross-linking, or tissue stiffening. These findings have implications for the interpretation of the lack of efficacy of simtuzumab in clinical trials of fibrotic diseases.

Shear Wave Elastography of the Skin following Radial Forearm Free Flap Surgery in Transgender Patients: Observational Study.

Background: Ultrasound shear wave elastography (SWE) noninvasively measures the stiffness of tissue by producing and measuring tissue deformation. Scar formation, a crucial aspect of wound healing, can lead to functional and aesthetic complications when pathological. While SWE has shown promise in dermatological evaluations, its role in surgical scar assessment remains underestimated. Our study aims to investigate SWE in evaluating surgical scars at the donor site after forearm free flap surgery in transgender patients. Methods: After radial forearm free flap harvesting, the donor site was grafted with a split-thickness skin graft with or without interposition of Matriderm. Eleven patients were evaluated more than one year after surgery, using SWE alongside scar characteristics, sensory outcomes, and patient satisfaction surveys. Results: Our study revealed no significant difference in stiffness (p > 0.15), pigmentation (p = 0.32), or erythema (p = 0.06) between operated and non-operated sides. The interposition of Matriderm did not influence the stiffness. Patients significantly (p < 0.0001) reported a loss of discrimination. Patients' subjective scar evaluation appeared in line with our quantitative and objective results. Conclusions: This study contributes to the evolving understanding of SWE's role in scar assessment, highlighting its feasibility in evaluating surgical scars. However, continued research efforts are necessary to establish SWE as a reliable and objective method for surgical scar evaluation and management.

Retinoic acid-induced protein 14 links mechanical forces to Hippo signaling

Cells sense and respond to various mechanical forces from the extracellular matrix primarily by modulating the actin cytoskeleton. Mechanical forces can be translated into biochemical signals in a process called mechanotransduction. Yes-associated protein (YAP) is an effector of Hippo signaling and a mediator of mechanotransduction, but how mechanical forces regulate Hippo signaling is still an open question. We propose that retinoic acid-induced protein 14 (RAI14) responds to mechanical forces and regulates Hippo signaling. RAI14 positively regulates the activity of YAP. RAI14 interacts with NF2, a key component of the Hippo pathway, and the interaction occurs on filamentous actin. When mechanical forces are kept low in cells, NF2 dissociates from RAI14 and filamentous actin, resulting in increased interactions with LATS1 and activation of the Hippo pathway. Clinical data show that tissue stiffness and expression of RAI14 and YAP are upregulated in tumor tissues and that RAI14 is strongly associated with adverse outcome in patients with gastric cancer. Our data suggest that RAI14 links mechanotransduction with Hippo signaling and mediates Hippo-related biological functions such as cancer progression.

Postprandial cardiac hypertrophy is sustained by mechanics, epigenetic, and metabolic reprogramming in pythons

Constricting pythons, known for their ability to consume infrequent, massive meals, exhibit rapid and reversible cardiac hypertrophy following feeding. Our primary goal was to investigate how python hearts achieve this adaptive response after feeding. Isolated myofibrils increased force after feeding without changes in sarcomere ultrastructure and without increasing energy cost. Ca2+ transients were prolonged after feeding with no changes in myofibril Ca2+ sensitivity. Feeding reduced titin-based tension, resulting in decreased cardiac tissue stiffness. Feeding also reduced the activity of sirtuins, a metabolically linked class of histone deacetylases, and increased chromatin accessibility. Transcription factor enrichment analysis on transposase-accessible chromatin with sequencing revealed the prominent role of transcription factors Yin Yang1 and NRF1 in postfeeding cardiac adaptation. Gene expression also changed with the enrichment of translation and metabolism. Finally, metabolomics analysis and adenosine triphosphate production demonstrated that cardiac adaptation after feeding not only increased energy demand but also energy production. These findings have broad implications for our understanding of cardiac adaptation across species and hold promise for the development of innovative approaches to address cardiovascular diseases.

MYH11 rare variant augments aortic growth and induces cardiac hypertrophy and heart failure with pressure overload.

Smooth muscle cell-specific myosin heavy chain, encoded by MYH11, is selectively expressed in smooth muscle cells (SMCs). Pathogenic variants in MYH11 predispose to a number of disorders, including heritable thoracic aortic disease associated with patent ductus arteriosus, visceral myopathy, and megacystis-microcolon-intestinal hypoperistalsis syndrome. Rare variants of uncertain significance occur throughout the gene, including MYH11 p.Glu1892Asp, and we sought to determine if this variant causes thoracic aortic disease in mice. Genomic editing was used to generate Myh11 E1892D/E1892D mice. Wild-type (WT) and mutant mice underwent cardiovascular phenotyping and with transverse aortic constriction (TAC). Myh11 E1892D/E1892D and WT mice displayed similar growth, blood pressure, root and ascending aortic diameters, and cardiac function up to 13 months of age, along with similar contraction and relaxation on myographic testing. TAC induced hypertension similarly in Myh11 E1892D/E1892D and WT mice, but mutant mice showed augmented ascending aortic enlargement and increased elastic fragmentation on histology. Unexpectedly, male Myh11 E1892D/E1892D mice two weeks post-TAC had decreased ejection fraction, stroke volume, fractional shortening, and cardiac output compared to similarly treated male WT mice. Importantly, left ventricular mass increased significantly due to primarily posterior wall thickening, and cardiac histology confirmed cardiomyocyte hypertrophy and increased collagen deposition in the myocardium and surrounding arteries. These results further highlight the clinical heterogeneity associated with MYH11 rare variants. Given that MYH11 is selectively expressed in SMCs, these results implicate a role of vascular SMCs in the heart contributing to cardiac hypertrophy and failure with pressure overload.

Elastographic and vascular findings of uterine myomas assessed by ultrasound.

The objectives of this study were to evaluate the vascularization pattern of uterine myoma (UM) by ultrasonography using Superb Microvascular Imaging (SMI) and tissue stiffness elastography. A prospective and cross-sectional study was carried out between March 2020 and December 2022 among women with clinical and ultrasound diagnosis of UM who would subsequently undergo radiofrequency ablation. Ultrasound examination was performed using both transvaginal and transabdominal routes. UM vascularization pattern was assessed by power Doppler (PD) and SMI, while elastographic pattern was assessed by shear wave (SWE) and strain (STE). FIGO classification, location, and measurement of the largest UM were also described. A total of 21 women diagnosed with UM were evaluated. There was a predominance of nulliparous women and 20 women (95.2%) reported desire for pregnancy. Of the 18 women with abnormal uterine bleeding, 15 (83.3%) had abdominal cramping. As far as previous treatment, 7 (33.3%) had undergone myomectomy for other UM. The mean uterine and UM volumes were 341.9 cm3 (90-730) and 126.52 cm3 (6.0-430), respectively. There was a predominance of hypoechogenic lesions (90.5%). There was also preponderance of UM in the FIGO 2-5 classification (n = 9; 42.9%). Vascularization patter was mostly moderate (score 2) in 9 cases (42.9%). The majority of UM were considered to have intermediate stiffness (n = 10; 47.6%). The majority of UM showed vascularization and moderate stiffness. A relationship was observed between the stiffness of the UM assessed by elastography and its FIGO classification.

Acoustomotive diffuse correlation spectroscopy for sensing mechanical stiffness in tissue-mimicking phantoms.

Many diseases, such as inflammation, dropsy, or tumors, often cause alterations in the mechanical stiffness of human tissues. Ultrasound-based techniques are commonly adopted in clinics for stiffness assessment, whereas optical methodologies hold promise for sensing strain changes and providing optical information pertaining to the microcirculatory network, thereby facilitating comprehensive measurements of tissue physiopathology. Diffuse correlation spectroscopy (DCS), an emerging dynamic light scattering technique, has been used to capture the enhanced motion of light scatterers induced by acoustic radiation force (ARF). Theoretically, the amplitude of this enhanced scatterers motion is related to the medium stiffness. Based on this relationship, we report a light coherent technique that combines ARF and DCS to qualitatively evaluate changes in the stiffness of medium. We experimentally demonstrate the accuracy and feasibility of this technique for probing stiffness in homogeneous phantom by comparing it with independent ultrasound methods. Additionally, we explore a potential application of this technique in distinguishing between fluid filled lesion and homogeneous tissue through heterogeneous phantom experiments. This unique combination of ARF and DCS, namely, acoustomotive DCS (AM-DCS), would provide an alternative way to measure particle-motion related stiffness, thereby assisting in the diagnosis and treatment of diseases.