Tissue Mechanical Properties Research Articles

Cell Migration Chip (3DCM-chip): a New Tool Toward the Modelling of 3D Cellular Complex Systems.

3D hydrogel-based cell cultures provide models for studying cell behavior and can efficiently replicate the physiologic environment. Hydrogels can be tailored to mimic mechanical and biochemical properties of specific tissues and allow to produce gel-in-gel models. In this system, microspheres encapsulating cells are embedded in an outer hydrogel matrix, where cells are able to migrate. To enhance the efficiency of such studies, we design a lab-on-a-chip named 3D Cell Migration-chip (3DCM-chip) that offers substantial advantages over traditional methods. 3DCM-chip facilitates the analysis of biochemical and physical stimuli effects on cell migration/invasion in different cell types, including stem, normal and tumor cells. 3DCM-chip provides a smart platform for developing more complex cell co-cultures systems. Herein we investigate the impact of human fibroblasts on MDA-MB 231 breast cancer cells invasiveness. Moreover, how the presence of different cellular lines, including mesenchymal stem cells (hMSCs), normal human dermal fibroblasts (NHDFs), and human umbilical vein endothelial cells (HUVECs), affects the invasive behavior of cancer cells is investigated using 3DCM-chip and producing predictive tumoroid models with a more complex network of interactions between cells and microenvironment. 3DCM-chip moves us closer to creating in vitro systems that can potentially replicate key aspects of the physiological tumor microenvironment. This article is protected by copyright. All rights reserved.

Current challenges in imaging the mechanical properties of tissue engineered grafts

The mechanical performance of tissue-engineered grafts is crucial in determining their functional properties, integration with native tissue and long-term repair outcome post-implantation. To date, most approaches for testing the mechanical properties of tissue-engineered grafts are non-sterile and invasive. There is an urgent need to develop novel sterile approaches for online monitoring mechanical properties of engineered tissues in order to ensure these engineered products meet the desired mechanical strength prior to implantation. In this paper, we overview various approaches for mechanical testing of engineered tissues, which span from traditional methods to medical imaging concepts in magnetic resonance elastography, ultrasound elastography, and optical coherence elastography. We focused on the applicability of these methods to the manufacturing of tissue-engineered products online, e.g., if such approach provides a sterile monitoring capacity and is capable of defining mechanical heterogeneity in engineered tissues throughout their growth in vitro in real-time. The review delves into various imaging modalities that employ distinct methods for inducing displacement within the sample, utilizing either strain-based or shear wave-based approaches. This displacement can be achieved through external stimulation or by harnessing ambient vibrations. Subsequently, the imaging process captures and visualizes the resultant displacement. We specifically highlight the advantages of novel non-invasive imaging methods such as ultrasound elastography and optical coherence elastography to assess the mechanical properties of engineered tissues in vitro, as well as their potential applications in cancer study, drug screening and the in vivo evaluation of the engineered tissues.

Molybdesum selenide-based platelet-rich plasma containing carboxymethyl chitosan/polyvinyl pyrrolidone composite antioxidant hydrogels dressing promotes the wound healing

Excess free radicals at the wound site can cause an inflammatory response, which is not conducive to wound healing. Hydrogels with antioxidant properties can prevent inflammatory storms by scavenging free radicals from the wound site and inhibiting the release of inflammatory factors. In this study, we prepared the carboxymethyl chitosan (CMCS)/polyvinyl pyrrolidone (PVP)/Molybdenum (IV) Selenide (MoSe2), and platelet-rich plasma (PRP) (CMCS/PVP/MoSe2/PRP) hydrogels for accelerating the repair of wounds. In the hydrogels, the MoSe2 can scavenge various free radicals to reduce oxidative stress at the site of inflammation, endowed the hydrogels with antioxidant properties. Interestingly, growth factors released by PRP assisted the tissue repair by promoting the formation of new capillaries. CMCS as a backbone not only showed good biocompatibility and biodegradability but also played a significant role in maintaining the sustained release of growth factors. In addition, incorporating PVP enhanced the tissue adhesion and mechanical properties. The multifunctional composite antioxidant hydrogels have good swelling properties and biodegradability, which is completely degraded within 28 days. Thus, the antioxidant CMCS/PVP/MoSe2/PRP hydrogels provide a new idea for designing ideal multifunctional wound dressings.

An emerging role for tissue plasticity in developmental precision.

Reproducible tissue morphology is a fundamental feature of embryonic development. To ensure such robustness during tissue morphogenesis, inherent noise in biological processes must be buffered. While redundant genes, parallel signaling pathways and intricate network topologies are known to reduce noise, over the last few years, mechanical properties of tissues have been shown to play a vital role. Here, taking the example of somite shape changes, I will discuss how tissues are highly plastic in their ability to change shapes leading to increased precision and reproducibility.

Nano-ZnO modified hydroxyapatite whiskers with enhanced osteoinductivity for bone defect repair

Abstract Hydroxyapatite (HA) whisker (HAw) represents a distinct form of HA characterized by its high aspect ratio, offering significant potential for enhancing the mechanical properties of bone tissue engineering scaffolds. However, the limited osteoinductivity of HAw hampers its widespread application. In this investigation, we observed HAw punctured osteoblast membranes and infiltrated the cell body, resulting in mechanical damage to cells that adversely impacted osteoblast proliferation and differentiation. To address this challenge, we developed nano-zinc oxide particle-modified HAw (nano-ZnO/HAw). Acting as a reinforcing and toughening agent, nano-ZnO/HAw augmented the compressive strength and ductility of the matrix materials. At the same time, the surface modification with nano-ZnO particles improved osteoblast differentiation by reducing the mechanical damage from HAw to cells and releasing zinc ion, the two aspects collectively promoted the osteoinductivity of HAw. Encouragingly, the osteoinductive potential of 5%nano-ZnO/HAw and 10%nano-ZnO/HAw was validated in relevant rat models, demonstrating the efficacy of this approach in promoting new bone formation in vivo. Our findings underscore the role of nano-ZnO particle surface modification in enhancing the osteoinductivity of HAw from a physical standpoint, offering valuable insights into the development of bone substitutes with favorable osteoinductive properties while simultaneously bolstering matrix material strength and toughness.

Assessing the hydromechanical control of plant growth.

Multicellular organisms grow and acquire their shapes through the differential expansion and deformation of their cells. Recent research has addressed the role of cell and tissue mechanical properties in these processes. In plants, it is believed that growth rate is a function of the mechanical stress exerted on the cell wall, the thin polymeric layer surrounding cells, involving an effective viscosity. Nevertheless, recent studies have questioned this view, suggesting that cell wall elasticity sets the growth rate or that uptake of water is limiting for plant growth. To assess these issues, we developed a microfluidic device to quantify the growth rates, elastic properties and hydraulic conductivity of individual Marchantia polymorpha plants in a controlled environment with a high throughput. We characterized the effect of osmotic treatment and abscisic acid on growth and hydromechanical properties. Overall, the instantaneous growth rate of individuals is correlated with both bulk elastic modulus and hydraulic conductivity. Our results are consistent with a framework in which the growth rate is determined primarily by the elasticity of the wall and its remodelling, and secondarily by hydraulic conductivity. Accordingly, the coupling between the chemistry of the cell wall and the hydromechanics of the cell appears as key to set growth patterns during morphogenesis.

Ultrasound Viscoelastography by Acoustic Radiation Force: A State-of-the-Art Review.

Ultrasound elastography (USE) is a promising tool for tissue characterization as several diseases result in alterations of tissue structure and composition, which manifest as changes in tissue mechanical properties. By imaging the tissue response to an applied mechanical excitation, USE mimics the manual palpation performed by clinicians to sense the tissue elasticity for diagnostic purposes. Next to elasticity, viscosity has recently been investigated as an additional, relevant, diagnostic biomarker. Moreover, since biological tissues are inherently viscoelastic, accounting for viscosity in the tissue characterization process enhances the accuracy of the elasticity estimation. Recently, methods exploiting different acquisition and processing techniques have been proposed to perform ultrasound viscoelastography. After introducing the physics describing viscoelasticity, a comprehensive overview of the currently available USE acquisition techniques is provided, followed by a structured review of the existing viscoelasticity estimators classified according to the employed processing technique. These estimators are further reviewed from a clinical usage perspective, and current outstanding challenges are discussed.

Mechanical and morphological characterization of the emphysematous lung tissue

Irreversible alveolar airspace enlargement is the main characteristic of pulmonary emphysema, which has been extensively studied using animal models. While the alterations in lung mechanics associated with these morphological changes have been documented in the literature, the study of the mechanical behavior of parenchymal tissue from emphysematous lungs has been poorly investigated. In this work, we characterize the mechanical and morphological properties of lung tissue in elastase-induced emphysema rat models under varying severity conditions. We analyze the non-linear tissue behavior using suitable hyperelastic constitutive models that enable to compare different non-linear responses in terms of hyperelastic material parameters. We further analyze the effect of the elastase dose on alveolar morphology and tissue material parameters and study their connection with respiratory-system mechanical parameters. Our results show that while the lung mechanical function is not significantly influenced by the elastase treatment, the tissue mechanical behavior and alveolar morphology are markedly affected by it. We further show a strong association between alveolar enlargement and tissue softening, not evidenced by respiratory-system compliance. Our findings highlight the importance of understanding tissue mechanics in emphysematous lungs, as changes in tissue properties could detect the early stages of emphysema remodeling.

Passive mechanical properties of adipose tissue and skeletal muscle from C57BL/6J mice

Skeletal muscle and adipose tissue are characterized by unique structural features finely tuned to meet specific functional demands. In this study, we investigated the passive mechanical properties of soleus (SOL), extensor digitorum longus (EDL) and diaphragm (DIA) muscles, as well as subcutaneous (SAT), visceral (VAT) and brown (BAT) adipose tissues from 13 C57BL/6J mice. Thereto, alongside stress-relaxation assessments we subjected isolated muscles and adipose tissues (ATs) to force-extension tests up to 10% and 30% of their optimal length, respectively. Peak passive stress was highest in the DIA, followed by the SOL and lowest in the EDL (p<0.05). SOL displayed also the highest Young’s modulus and hysteresis among muscles (p<0.05). BAT demonstrated highest peak passive stress and Young’s modulus followed by VAT (p<0.05), while SAT showed the highest hysteresis (p<0.05). When comparing data across all six biological specimens at fixed passive force intervals (i.e., 20-40 and 50-70 mN), skeletal muscles exhibited significantly higher peak stresses and strains than ATs (p<0.05). Young’s modulus was higher in skeletal muscles than in ATs (p<0.05). Muscle specimens exhibited slower force relaxation in the first phase compared to ATs (p<0.05), while there was no significant difference in behavior between muscles and AT in the second phase of relaxation. The study revealed distinctive mechanical behaviors specific to different tissues, and even between different muscles and ATs. These variations in mechanical properties are likely such to optimize the specific functions performed by each biological tissue.

In Vivo Optical Coherence Elastography Unveils Spatial Variation of Human Corneal Stiffness.

The mechanical properties of corneal tissues play a crucial role in determining corneal shape and have significant implications in vision care. This study aimed to address the challenge of obtaining accurate in vivo data for the human cornea. We have developed a high-frequency optical coherence elastography (OCE) technique using shear-like antisymmetric (A0)-mode Lamb waves at frequencies above 10 kHz. By incorporating an anisotropic, nonlinear constitutive model and utilizing the acoustoelastic theory, we gained quantitative insights into the influence of corneal tension on wave speeds and elastic moduli. Our study revealed significant spatial variations in the shear modulus of the corneal stroma on healthy subjects for the first time. Over an age span from 21 to 34 (N = 6), the central corneas exhibited a mean shear modulus of 87 kPa, while the corneal periphery showed a significant decrease to 44 kPa. The central cornea's shear modulus decreases with age with a slope of -19 +/- 8 kPa per decade, whereas the periphery showed non-significant age dependence. The limbus demonstrated an increased shear modulus exceeding 100 kPa. We obtained wave displacement profiles that are consistent with highly anisotropic corneal tissues. Our approach enabled precise measurement of corneal tissue elastic moduli in situ with high precision (<7%) and high spatial resolution (<1 mm). Our results revealed significant stiffness variation from the central to peripheral corneas. The high-frequency OCE technique holds promise for biomechanical evaluation in clinical settings, providing valuable information for refractive surgeries, degenerative disorder diagnoses, and intraocular pressure assessments.

Ultrasound Shear Elastography With Expanded Bandwidth (USEWEB): A Novel Method for 2D Shear Phase Velocity Imaging of Soft Tissues.

Ultrasound shear wave elastography (SWE) is a noninvasive approach for evaluating mechanical properties of soft tissues. In SWE either group velocity measured in the time-domain or phase velocity measured in the frequency-domain can be reported. Frequency-domain methods have the advantage over time-domain methods in providing a response for a specific frequency, while time-domain methods average the wave velocity over the entire frequency band. Current frequency-domain approaches struggle to reconstruct SWE images over full frequency bandwidth. This is especially important in the case of viscoelastic tissues, where tissue viscoelasticity is often studied by analyzing the shear wave phase velocity dispersion. For characterizing cancerous lesions, it has been shown that considerable biases can occur with group velocity-based measurements. However, using phase velocities at higher frequencies can provide more accurate evaluations. In this paper, we propose a new method called Ultrasound Shear Elastography with Expanded Bandwidth (USEWEB) used for two-dimensional (2D) shear wave phase velocity imaging. We tested the USEWEB method on data from homogeneous tissue-mimicking liver fibrosis phantoms, custom-made viscoelastic phantom measurements, phantoms with cylindrical inclusions experiments, and in vivo renal transplants scanned with a clinical scanner. We compared results from the USEWEB method with a Local Phase Velocity Imaging (LPVI) approach over a wide frequency range, i.e., up to 200-2000 Hz. Tests carried out revealed that the USEWEB approach provides 2D phase velocity images with a coefficient of variation below 5% over a wider frequency band for smaller processing window size in comparison to LPVI, especially in viscoelastic materials. In addition, USEWEB can produce correct phase velocity images for much higher frequencies, up to 1800 Hz, compared to LPVI, which can be used to characterize viscoelastic materials and elastic inclusions.

A method for analyzing AFM force mapping data obtained from soft tissue cryosections

Atomic force microscopy (AFM) is a valuable tool for assessing mechanical properties of biological samples, but interpretations of measurements on whole tissues can be difficult due to the tissue’s highly heterogeneous nature. To overcome such difficulties and obtain more robust estimates of tissue mechanical properties, we describe an AFM force mapping and data analysis pipeline to characterize the mechanical properties of cryosectioned soft tissues. We assessed this approach on mouse optic nerve head and rat trabecular meshwork, cornea, and sclera. Our data show that the use of repeated measurements, outlier exclusion, and log-normal data transformation increases confidence in AFM mechanical measurements, and we propose that this methodology can be broadly applied to measuring soft tissue properties from cryosections.

High-precision 3D printing of multi-branch vascular scaffold with plasticized PLCL thermoplastic elastomer

Three-dimensional (3D) printing has emerged as a transformative technology for tissue engineering, enabling the production of structures that closely emulate the intricate architecture and mechanical properties of native biological tissues. However, the fabrication of complex microstructures with high accuracy using biocompatible, degradable thermoplastic elastomers poses significant technical obstacles. This is primarily due to the inherent soft-matter nature of such materials, which complicates real-time control of micro-squeezing, resulting in low fidelity or even failure. In this study, we employ Poly (L-lactide-co-ϵ-caprolactone) (PLCL) as a model material and introduce a novel framework for high-precision 3D printing based on the material plasticization process. This approach significantly enhances the dynamic responsiveness of the start-stop transition during printing, thereby reducing harmful errors by up to 93%. Leveraging this enhanced material, we have efficiently fabricated arrays of multi-branched vascular scaffolds that exhibit exceptional morphological fidelity and possess elastic moduli that faithfully approximate the physiological modulus spectrum of native blood vessels, ranging from 2.5 to 45 MPa. The methodology we propose for the compatibilization and modification of elastomeric materials addresses the challenge of real-time precision control, representing a significant advancement in the domain of melt polymer 3D printing. This innovation holds considerable promise for the creation of detailed multi-branch vascular scaffolds and other sophisticated organotypic structures critical to advancing tissue engineering and regenerative medicine.

Continuous Softening as a State of Hyperelasticity: Examples of Application to the Softening Behavior of the Brain Tissue.

The continuous softening behavior of the brain tissue, i.e., the softening in the primary loading path with an increase in deformation, is modeled in this work as a state of hyperelasticity up to the onset of failure. That is, the softening behavior is captured via a core hyperelastic model without the addition of damage variables and/or functions. Examples of the application of the model will be provided to extant datasets of uniaxial tension and simple shear deformations, demonstrating the capability of the model to capture the whole-range deformation of the brain tissue specimens, including their softening behavior. Quantitative and qualitative comparisons with other models within the brain biomechanics literature will also be presented, showing the clear advantages of the current approach. The application of the model is then extended to capturing the rate-dependent softening behavior of the tissue by allowing the parameters of the core hyperelastic model to evolve, i.e., vary, with the deformation rate. It is shown that the model captures the rate-dependent and softening behaviors of the specimens favorably and also predicts the behavior at other rates. These results offer a clear set of advantages in favor of the considered modeling approach here for capturing the quasi-static and rate-dependent mechanical properties of the brain tissue, including its softening behavior, over the existing models in the literature, which at best may purport to capture only a reduced set of the foregoing behaviors, and with ill-posed effects.

The mechanisms of exercise improving cardiovascular function by stimulating Piezo1 and TRP ion channels: a systemic review.

Mechanosensitive ion channels are widely distributed in the heart, lung, bladder and other tissues, and plays an important role in exercise-induced cardiovascular function promotion. By reviewing the PubMed databases, the results were summarized using the terms "Exercise/Sport", "Piezo1", "Transient receptor potential (TRP)" and "Cardiovascular" as the keywords, 124-related papers screened were sorted and reviewed. The results showed that: (1) Piezo1 and TRP channels play an important role in regulating blood pressure and the development of cardiovascular diseases such as atherosclerosis, myocardial infarction, and cardiac fibrosis; (2) Exercise promotes cardiac health, inhibits the development of pathological heart to heart failure, regulating the changes in the characterization of Piezo1 and TRP channels; (3) Piezo1 activates downstream signaling pathways with very broad pathways, such as AKT/eNOS, NF-κB, p38MAPK and HIPPO-YAP signaling pathways. Piezo1 and Irisin regulate nuclear localization of YAP and are hypothesized to act synergistically to regulate tissue mechanical properties of the cardiovascular system and (4) The cardioprotective effects of exercise through the TRP family are mostly accomplished through Ca2+ and involve many signaling pathways. TRP channels exert their important cardioprotective effects by reducing the TRPC3-Nox2 complex and mediating Irisin-induced Ca2+ influx through TRPV4. It is proposed that exercise stimulates the mechanosensitive cation channel Piezo1 and TRP channels, which exerts cardioprotective effects. The activation of Piezo1 and TRP channels and their downstream targets to exert cardioprotective function by exercise may provide a theoretical basis for the prevention of cardiovascular diseases and the rehabilitation of clinical patients.

Mechanical state transitions in the regulation of tissue form and function.

From embryonic development, postnatal growth and adult homeostasis to reparative and disease states, cells and tissues undergo constant changes in genome activity, cell fate, proliferation, movement, metabolism and growth. Importantly, these biological state transitions are coupled to changes in the mechanical and material properties of cells and tissues, termed mechanical state transitions. These mechanical states share features with physical states of matter, liquids and solids. Tissues can switch between mechanical states by changing behavioural dynamics or connectivity between cells. Conversely, these changes in tissue mechanical properties are known to control cell and tissue function, most importantly the ability of cells to move or tissues to deform. Thus, tissue mechanical state transitions are implicated in transmitting information across biological length and time scales, especially during processes of early development, wound healing and diseases such as cancer. This Review will focus on the biological basis of tissue-scale mechanical state transitions, how they emerge from molecular and cellular interactions, and their roles in organismal development, homeostasis, regeneration and disease.

Ultrasonic surface acoustic wave elastography: A review of basic theories, technical developments, and medical applications.

Physiological and pathological changes in tissues often cause changes in tissue mechanical properties, making tissue elastography an effective modality in medical imaging. Among the existing elastography methods, ultrasound elastography is of great interest due to the inherent advantages of ultrasound imaging technology, such as low cost, portability, safety, and wide availability. However, most current ultrasound elastography methods are based on the bulk shear wave; they can image deep tissues but cannot image superficial tissues. To address this challenge, ultrasonic elastography methods based on surface acoustic waves have been proposed. In this paper, we present a comprehensive review of ultrasound-based surface acoustic wave elastography techniques, including their theoretical foundations, technical implementations, and existing medical applications. The goal is to provide a concise summary of the state-of-the-art of this field, hoping to offer a reliable reference for the further development of these techniques and foster the expansion of their medical applications.

Investigation of crystalline lens overshooting: ex vivo experiment and optomechanical simulation results.

Introduction: Crystalline lens overshooting refers to a situation in which the lens momentarily shifts too much from its typical location immediately after stopping the rotational movement of the eye globe. This movement can be observed using an optical technique called Purkinje imaging. Methods: In this work, an experimental setup was designed to reproduce this effect ex vivo using a fresh porcine eye. The sample was rotated 90° around its centroid using a high-velocity rotation stage, and the Purkinje image sequences were recorded, allowing us to quantify the overshooting effect. The numerical part of the study consisted of developing a computational model of the eye, based on the finite element method, that allowed us to understand the biomechanical behavior of the different tissues in this dynamic scenario. A 2D fluid-structure interaction model of the porcine eye globe, considering both the solid parts and humors, was created to reproduce the experimental outcomes. Results: Outputs of the simulation were analyzed using an optical simulation software package to assess whether the mechanical model behaves optically like the real ex vivo eye. The simulation predicted the experimental results by carefully adjusting the mechanical properties of the zonular fibers and the damping factor. Conclusion: This study effectively demonstrates the importance of characterizing the dynamic mechanical properties of the eye tissues to properly comprehend and predict the overshooting effect.

Matricellular proteins: Potential biomarkers in head and neck cancer

AbstractThe extracellular matrix (ECM) is a complex network of diverse multidomain macromolecules, including collagen, proteoglycans, and fibronectin, that significantly contribute to the mechanical properties of tissues. Matricellular proteins (MCPs), as a family of non‐structural proteins, play a crucial role in regulating various ECM functions. They exert their biological effects by interacting with matrix proteins, cell surface receptors, cytokines, and proteases. These interactions govern essential cellular processes such as differentiation, proliferation, adhesion, migration as well as multiple signal transduction pathways. Consequently, MCPs are pivotal in maintaining tissue homeostasis while orchestrating intricate molecular mechanisms within the ECM framework. The expression level of MCPs in adult steady‐state tissues is significantly low; however, under pathological conditions such as inflammation and cancer, there is a substantial increase in their expression. In recent years, an increasing number of studies have focused on elucidating the role and significance of MCPs in the development and progression of head and neck cancer (HNC). During HNC progression, there is a remarkable upregulation in MCP expression. Through their distinctive structure and function, they actively promote tumor growth, invasion, epithelial‐mesenchymal transition, and lymphatic metastasis of HNC cells. Moreover, by binding to integrins and modulating various signaling pathways, they effectively execute their biological functions. Furthermore, MCPs also hold potential as prognostic indicators. Although the star proteins of various MCPs have been extensively investigated, there remains a plethora of MCP family members that necessitate further scrutiny. This article comprehensively examines the functionalities of each MCP and highlights the research advancements in the context of HNC, with an aim to identify novel biomarkers for HNC and propose promising avenues for future investigations.

Sensitivity of magnetic resonance elastography to extracellular matrix and cell motility in human prostate cancer cell line-derived xenograft models

Prostate cancer (PCa) is a significant health problem in the male population of the Western world. Magnetic resonance elastography (MRE), an emerging medical imaging technique sensitive to mechanical properties of biological tissues, detects PCa based on abnormally high stiffness and viscosity values. Yet, the origin of these changes in tissue properties and how they correlate with histopathological markers and tumor aggressiveness are largely unknown, hindering the use of tumor biomechanical properties for establishing a noninvasive PCa staging system.To infer the contributions of extracellular matrix (ECM) components and cell motility, we investigated fresh tissue specimens from two PCa xenograft mouse models, PC3 and LNCaP, using magnetic resonance elastography (MRE), diffusion-weighted imaging (DWI), quantitative histology, and nuclear shape analysis. Increased tumor stiffness and impaired water diffusion were observed to be associated with collagen and elastin accumulation and decreased cell motility. Overall, LNCaP, while more representative of clinical PCa than PC3, accumulated fewer ECM components, induced less restriction of water diffusion, and exhibited increased cell motility, resulting in overall softer and less viscous properties. Taken together, our results suggest that prostate tumor stiffness increases with ECM accumulation and cell adhesion - characteristics that influence critical biological processes of cancer development.MRE paired with DWI provides a powerful set of imaging markers that can potentially predict prostate tumor development from benign masses to aggressive malignancies in patients. Statement of significanceXenograft models of human prostate tumor cell lines, allowing correlation of microstructure-sensitive biophysical imaging parameters with quantitative histological methods, can be investigated to identify hallmarks of cancer.