Tissue Viscoelastic Properties Research Articles

Surface excitation of focused shear wave beams in soft elastic media: Theory

Shear wave propagation is employed in medical ultrasound imaging, because it reveals variation in the viscoelastic properties of tissue. Frequencies below 1 kHz are required for imaging with shear waves in soft tissue due to their high attenuation and low propagation speeds, compared to compressional waves with frequencies above 1 MHz used for ultrasound imaging. Shear waves exhibiting particle motion in the direction of propagation, referred to as longitudinally polarized shear waves, can be generated by applying longitudinal motion of a circular disk to the surface of a soft elastic medium. This approach is used in practice because it permits imaging of the longitudinal shear wave with a conventional ultrasound transducer that is coaxial with the source of the shear wave. Presented here are the theoretical framework and numerical simulations that illustrate effects of focusing on longitudinally polarized shear waves. Longitudinal, transverse, radial, and torsional source polarizations are considered. The present investigation was motivated initially by an experimental study in optics due to Dorn et al. [Phys. Rev. Lett. 91, 233901 (2003)]. Our predictions for shear wave beams support their measurements of light beams revealing that the longitudinal electric field component produces a smaller focal spot than the transverse field component.

Surface excitation of focused shear wave beams in soft elastic media: Experiment

Shear waves are employed in medical imaging to reveal variations in the viscoelastic properties of soft tissues, which are useful biomarkers for pathologies such as breast lesions and liver disease. Shear wave excitation methods that employ acoustic radiation force or surface vibration with a small piston have limitations associated with imaging depth and shear wave amplitude. We introduce a new method for surface excitation of shear waves that employs longitudinal motion of a concave-shaped piston source to generate a focused shear wave beam, thereby increasing shear wave amplitude and penetration depth. Focused shear waves are excited in a gel phantom in the frequency range of 200 Hz to 400 Hz using a concave piston with 40 mm radius of curvature and 50 mm diameter. The wave field comprises both transverse and longitudinal displacement components, which are polarized perpendicular and parallel to the propagation direction, respectively. Transversely and longitudinally polarized wave fields are measured using ultrasound speckle tracking. The longitudinally polarized shear wave is of interest because it is measured in elastography applications. Preliminary comparisons exhibit good agreement between measured beam patterns and those predicted by an analytical theory for shear wave beam propagation due to surface excitation with a piston source.

Dynamic viscoelastic properties of porcine gastric tissue: Effects of loading frequency, region and direction

The gastric biomechanics influences digestive function as well as a range of topics of medical and scientific interests such as interaction between the stomach and gastric devices. Hence, the mechanical properties are essential for understanding gastric tissue and function in health and disease, and for the development of diagnostic or therapeutic devices. A key characteristic to be characterized is the time dependent mechanical tissue properties. The aim of this study was to characterize viscoelastic properties of the stomach across a frequency range. Longitudinal and circumferential stomach samples from the porcine fundus, corpus and antrum were pre-stretched 10 % and sinusoidally loaded with 10 % dynamic strain. The viscoelastic properties were assessed from 0.01 − 15 Hz using dynamic mechanical analysis. The storage moduli, loss moduli and tan δ had a significant second-order polynomial trend with increasing frequency. For the loss moduli, significant differences were observed between 0.01 and 15 Hz and between 0.05 and 15 Hz (p = 0.023 to 0.041). Significant differences were not found for storage moduli. Tan δ was frequency-independent, indicating that the two moduli varied proportionally. Fundus had significantly smaller storage moduli for longitudinal samples compared to corpus (p = 0.034) and antrum (p = 0.014) but was not significantly different for circumferential samples. Analysis of direction-dependency showed significant differences between longitudinal and circumferential samples (p = 0.002 to 0.042). The presented work provides insight into tensile viscoelastic properties of gastric tissue, which is useful for developing biomaterials, devices and computational models for device development specification calibrations.

Structure-Function Dissociations of Human Hippocampal Subfield Stiffness and Memory Performance.

Aging and neurodegenerative diseases lead to decline in thinking and memory ability. The subfields of the hippocampus (HCsf) play important roles in memory formation and recall. Imaging techniques sensitive to the underlying HCsf tissue microstructure can reveal unique structure-function associations and their vulnerability in aging and disease. The goal of this study was to use magnetic resonance elastography (MRE), a noninvasive MR imaging-based technique that can quantitatively image the viscoelastic mechanical properties of tissue to determine the associations of HCsf stiffness with different cognitive domains across the lifespan. Eighty-eight adult participants completed the study (age 23-81 years, male/female 36/51), in which we aimed to determine which HCsf regions most strongly correlated with different memory performance outcomes and if viscoelasticity of specific HCsf regions mediated the relationship between age and performance. Our results revealed that both interference cost on a verbal memory task and relational memory task performance were significantly related to cornu ammonis 1-2 (CA1-CA2) stiffness (p = 0.018 and p = 0.011, respectively), with CA1-CA2 stiffness significantly mediating the relationship between age and interference cost performance (p = 0.031). There were also significant associations between delayed free verbal recall performance and stiffness of both the dentate gyrus-cornu ammonis 3 (DG-CA3; p = 0.016) and subiculum (SUB; p = 0.032) regions. This further exemplifies the functional specialization of HCsf in declarative memory and the potential use of MRE measures as clinical biomarkers in assessing brain health in aging and disease.SIGNIFICANCE STATEMENT Hippocampal subfields are cytoarchitecturally unique structures involved in distinct aspects of memory processing. Magnetic resonance elastography is a technique that can noninvasively image tissue viscoelastic mechanical properties, potentially serving as sensitive biomarkers of aging and neurodegeneration related to functional outcomes. High-resolution in vivo imaging has invigorated interest in determining subfield functional specialization and their differential vulnerability in aging and disease. Applying MRE to probe subfield-specific cognitive correlates will indicate that measures of subfield stiffness can determine the integrity of structures supporting specific domains of memory performance. These findings will further validate our high-resolution MRE method and support the potential use of subfield stiffness measures as clinical biomarkers in classifying aging and disease states.

Data-driven Gait-predictive Model for Anticipatory Prosthesis Control.

Physiological movement is pre-planned based on current movement state, proprioception, and environmental cues. This preplanning is necessary to allow efficient use of the viscoelastic properties of musculoskeletal tissues in a 4D-environment. Similarly, efficient use of prosthetic devices needs to compensate for the time it takes to control the system. In this study, we propose a gated recurrent net-based gait predictive model to continuously predict the ankle angles and moments fifty milliseconds in advance based on the past trajectory of the input signals. It was observed that using a single input signal (the shank angle), high accuracy of prediction $(R^{2}\gt 0.91)$ was achieved for both ankle angle and moments on walking trials at a self-selected comfortable speed. The results of our study can be utilised for anticipatory lower-limb prosthesis control where embedded sensor information that reflects a prosthetic user's locomotive intent can be used to predict the required angles and moments in advance for actuating a prosthetic joint.

An in-House System for the Precise Measurement of Electrical Potentials and Mechanical Properties of Soft Tissues: Design and Validation Using Adult Mammalian Tendon Fascicle Bundles.

Tissues, such as skin, bones, and tendons, exhibit a piezoelectric effect, which may be an important phenomenon in terms of tissue renewal and regeneration as well as the possibility of modifying their mechanical behavior. In this article, we present the design and development of an in-house system for the precise measurement of electrical potentials and mechanical properties of tendons. The system was validated using tendon fascicle bundles derived from positional as well as energy-storing tendons from various adult mammals (porcine, bovine, and deer samples). The presented system is able to capture changes in elastic and viscoelastic properties of tissue as well as its time–voltage response and, thus, may be used in a broad spectrum of future studies to uncover factors influencing piezoelectric phenomena in tendons. This, in turn, will help to optimize current methods used in physiotherapy and postoperative treatment for effective tendon recovery.

Comparison of inversion methods in MR elastography: An open-access pipeline for processing multifrequency shear-wave data and demonstration in a phantom, human kidneys, and brain.

Magnetic resonance elastography (MRE) maps the viscoelastic properties of soft tissues for diagnostic purposes. However, different MRE inversion methods yield different results, which hinder comparison of values, standardization, and establishment of quantitative MRE markers. Here, we introduce an expandable, open-access, webserver-based platform that offers multiple inversion techniques for multifrequency, 3D MRE data. The platform comprises a data repository and standard MRE inversion methods including local frequency estimation (LFE), direct-inversion based multifrequency dual elasto-visco (MDEV) inversion, and wavenumber-based (k-) MDEV. The use of the platform is demonstrated in phantom data and in vivo multifrequency MRE data of the kidneys and brains of healthy volunteers. Detailed maps of stiffness were generated by all inversion methods showing similar detail of anatomy. Specifically, the inner renal cortex had higher shear wave speed (SWS) than renal medulla and outer cortex without lateral differences. k-MDEV yielded higher SWS values than MDEV or LFE (full kidney/brain k-MDEV: 2.71 ± 0.19/1.45 ± 0.14 m/s, MDEV: 2.14 ± 0.16/0.99 ± 0.11 m/s, LFE: 2.12 ± 0.15/0.89 ± 0.06 m/s). The freely accessible platform supports the comparison of MRE results obtained with different inversion methods, filter thresholds, or excitation frequencies, promoting reproducibility in MRE across community-developed methods.

Viscoelastic Characterization of Soft Tissue-Mimicking Gelatin Phantoms using Indentation and Magnetic Resonance Elastography.

Characterization of biomechanical properties of soft biological tissues is important to understand the tissue mechanics and explore the biomechanics-related mechanisms of disease, injury, and development. The mechanical testing method is the most straightforward way for tissue characterization and is considered as verification for in vivo measurement. Among the many ex vivo mechanical testing techniques, the indentation test provides a reliable way, especially for samples that are small, hard to fix, and viscoelastic such as brain tissue. Magnetic resonance elastography (MRE) is a clinically used method to measure the biomechanical properties of soft tissues. Based on shear wave propagation in soft tissues recorded using MRE, viscoelastic properties of soft tissues can be estimated in vivo based on wave equation. Here, the viscoelastic properties of gelatin phantoms with two different concentrations were measured by MRE and indentation. The protocols of phantom fabrication, testing, and modulus estimation have been presented.

ANALYSIS OF INDUCED ISOMETRIC FATIGUING CONTRACTIONS IN BICEPS BRACHII MUSCLES USING MYOTONOMETRY AND SURFACE ELECTROMYOGRAPHIC MEASUREMENTS

Viscoelastic properties of skeletal muscle tissue are known to be impacted by fatiguing contractions. In this study, an attempt has been made to utilize myotonometry for analyzing the relationship between muscle viscoelasticity and contractile behaviors in a fatiguing task. For this purpose, thirteen young healthy volunteers are recruited to perform the fatiguing isometric task and the time to task failure (TTF) is recorded. Myotonometric parameters and simultaneous surface electromyographic (sEMG) signals are recorded from the Biceps Brachii muscle of the flexed arm. The correlation between myotonometric parameters and TTF is further analyzed. Cross-validation with sEMG features is also performed. Stiffness of muscle has a positive correlation with TTF in the left hand ([Formula: see text]). Damping property of the nonfatigued muscle is positively associated with the fatigue-induced changes in amplitude features of sEMG signal in the right hand ([Formula: see text]). The normalized rate of change of mean frequency of sEMG signal has a positive correlation with stiffness values in both of the hands ([Formula: see text]). Muscle viscoelasticity is demonstrated to influence the progression of fatigue, although the difference in motor control due to handedness is also found to be an important factor. The results are promising to improve the understanding of the effect of muscle mechanics in fatigue-induced task failure.

The effect of stiffness and impurities on bubble nucleation in polyacrylamide hydrogels

Tissue mimicking hydrogels can help us understand how viscoelastic properties (stiffness, elastic modulus, etc.) of biological tissues impact bubble nucleation. Adding impurities to hydrogels introduces inhomogeneities and increases their similarity to biological tissues. In this study, we evaluated the effect of stiffness and impurities on bubble nucleation in polyacrylamide (PA) hydrogels. Bubble nuclei were evaluated in 17.5%, 20%, and 22.5% v/v PA hydrogels, after which 0.25% w/v cholesterol crystals (maximum dimension = 0.6 mm) were embedded in the gels (n = 3 each). A 1.5 MHz focused ultrasound transducer was used to induce cavitation using 10-ms pulses with pressures ranging up to p+ = 89 MPa, and p− = 26 MPa and −6 dB focal dimensions of 9.4 × 1.2 mm (p−). Image analysis from high-speed photography showed bubble nucleation increases with increasing peak negative pressure and decreasing hydrogel stiffness. Adding cholesterol crystals largely decreases the acoustic cavitation threshold from p− = 19 MPa for 17.5% v/v hydrogels with no added impurities to p− = 12 MPa for the same concentration hydrogel with added cholesterol crystals. This suggests that hydrophobic cholesterol crystals weaken the gel or trap bubble nuclei, thus lowering the cavitation threshold. Future work includes investigating bubble nuclei in rat hepatocytes. [Work supported by NSF CAREER 1943937 and PSU Riess Fellowship.]

The combined importance of finite dimensions, anisotropy, and pre-stress in acoustoelastography.

Dynamic elastography, whether based on magnetic resonance, ultrasound, or optical modalities, attempts to reconstruct quantitative maps of the viscoelastic properties of biological tissue, properties that are altered by disease and injury, by noninvasively measuring mechanical wave motion in the tissue. Most reconstruction strategies that have been developed neglect boundary conditions, including quasistatic tensile or compressive loading resulting in a nonzero prestress. Significant prestress is inherent to the functional role of some biological tissues currently being studied using elastography, such as skeletal and cardiac muscle, arterial walls, and the cornea. In the present article, we review how prestress alters both bulk mechanical wave motion and wave motion in one- and two-dimensional waveguides. Key findings are linked to studies on skeletal muscle and the human cornea, as one- and two-dimensional waveguide examples. This study highlights the underappreciated combined acoustoelastic and waveguide challenge to elastography. Can elastography truly determine viscoelastic properties of a material when what it is measuring is affected by both these material properties and unknown prestress and other boundary conditions?

Improved two-point frequency shift power method for measurement of shear wave attenuation

Quantitative assessment of mechanical properties of biological soft tissues is frequently evaluated using a noninvasive modality, called ultrasound shear wave elastography (SWE). SWE typically exerts an acoustic radiation force (ARF) to produce shear waves propagating in the lateral direction for which velocities and attenuations are measured. The tissue viscoelasticity is commonly studied by investigating the shear wave phase velocity curves. Viscoelastic tissue properties can also be characterized through utilizing various shear wave attenuation techniques. In this study, we propose an improved method for measuring the shear wave attenuation, called two-point frequency shift power (2P-FSP), which is an improved version of the two-point frequency shift (2P-FS) method. The technique is fully data driven and does not use a rheological model for mathematical modeling. The 2P-FSP method utilizes the power spectra frequency shift of shear waves measured at two spatial positions, which provides robustness to noise. The conceptual basis for the 2P-FSP is provided and tested with numerical and experimental data. We investigated how the location of the first signal and the distance interval between the two locations influence the shear wave attenuation measurement in the 2P-FSP technique. We utilized the 2P-FSP method on numerical phantom data generated using a finite-difference-based method in tissue-mimicking viscoelastic media. Moreover, we tested the 2P-FSP method with data from custom-made tissue-mimicking viscoelastic phantom experiments, and ex vivo porcine liver. We compared results from the proposed technique with results from 2P-FS and analytical values in the case of simulations. The results showed that the 2P-FSP method provides improved results over the 2P-FS technique for lower signal-to-noise ratio (SNR) and locations farther from the push location considered, and can be used to measure attenuation of viscoelastic soft tissues.

Imaging the Local Nonlinear Viscoelastic Properties of Soft Tissues: Initial Validation and Expected Benefits.

Imaging tissue mechanical properties has shown promise in noninvasive assessment of numerous pathologies. Researchers have successfully measured many linear tissue mechanical properties in laboratory and clinical settings. Currently, multiple complex mechanical effects such as frequency-dependence, anisotropy, and nonlinearity are being investigated separately. However, a concurrent assessment of these complex effects may enable more complete characterization of tissue biomechanics and offer improved diagnostic sensitivity. In this work, we report for the first time a method to map the frequency-dependent nonlinear parameters of soft tissues on a local scale. We recently developed a nonlinear elastography model that combines strain measurements from arbitrary tissue compression with radiation-force-based broadband shear wave speed (WS) measurements. Here, we extended this model to incorporate local measurements of frequency-dependent shear modulus. This combined approach provides a local frequency-dependent nonlinear parameter that can be obtained with arbitrary, clinically realizable tissue compression. Initial assessments using simulations and phantoms validate the accuracy of this approach. We also observed improved contrast in nonlinearity parameter at higher frequencies. Results from ex-vivo liver experiments show 32, 25, 34, and 38 dB higher contrast in elastograms than traditional linear elasticity, elastic nonlinearity, viscosity, and strain imaging methods, respectively. A lesion, artificially created by injection of glutaraldehyde into a liver specimen, showed a 59% increase in the frequency-dependent nonlinear parameter and a 17% increase in contrast ratio.

Relationship between Viscoelastic Properties of Tissues and Bioimpedance Spectroscopy in Breast-Cancer-Related Lymphedema.

The aim of this study was to assess the relationship between the viscoelastic properties of tissues and breast-cancer-related lymphedema (BCRL). After a mastectomy, 46 females were allocated into a lymphedema group (L; n = 15, lymphedema occurred) and a control group (C; n = 31, lack of lymphedema). Bioimpedance spectroscopy was used to test BCRL. The mechanical properties of the tissues in both upper limbs were tested using myotonometry. In group L, tone, stiffness, relaxation time, and creep measured on the biceps brachii of the impaired limb significantly differed from the results on the unimpaired limb. In group C, the differences were not significant. Moreover, both tone and stiffness were inversely correlated with the level of lymphedema (r = −0.72 and r = −0.88, respectively), and both relaxation and creep were significantly related to the level of lymphedema (r = 0.71 and r = 0.59, respectively), when myotonometry was completed on the biceps brachii of the impaired limb in group L. The relationships were not significant in group C. Measurements of viscoelastic properties can provide useful information concerning lymphedema. Our findings suggest that significant correlations between selected mechanical properties of the tissues and BCRL can be used in BCRL detection and treatment.

A mathematical model for viscoelastic properties of biological soft tissue.

A quaternary viscoelastic structure model with two characteristic times is presented to describe the viscoelastic properties of parallel-fibered collagen tissue. The comparison results of model prediction and experimental data of rabbit medial collateral ligaments show that the model could accurately describe viscoelastic behavior such as stress-relaxation, strain-strengthening and creep of bio-soft-tissue within a small scope of errors. To study the biomechanical mechanism of viscoelasticity that biological soft tissue shows, the influence of model parameters on viscoelastic behavior of bio-soft-tissue is analyzed and researched, which indicated that the major influential elements of stress-relaxation in bio-soft-tissue are elastic modulus, relaxation time and strain rate of proteoglycan-rich matrix. The influence of elastic modulus of collagen fibers on stress-relaxation is not significant. However, the nonlinearity of stress-strain curve and viscoelastic behavior of bio-soft-tissue mostly depends on recruitment and reorientation of collagen fibers under external loading.

Nonlinear microscopy using impulsive stimulated Brillouin scattering for high-speed elastography.

The impulsive stimulated Brillouin microscopy promises fast, non-contact measurements of the elastic properties of biological samples. The used pump-probe approach employs an ultra-short pulse laser and a cw laser to generate Brillouin signals. Modeling of the microscopy technique has already been carried out partially, but not for biomedical applications. The nonlinear relationship between pulse energy and Brillouin signal amplitude is proven with both simulations and experiments. Tayloring of the excitation parameters on the biologically relevant polyacrylamide hydrogels outline sub-ms temporal resolutions at a relative precision of <1%. Brillouin microscopy using the impulsive stimulated scattering therefore exhibits high potential for the measurements of viscoelastic properties of cells and tissues.

Investigating the heterogeneity of viscoelastic properties in prostate cancer using MR elastography at 9.4T in fresh prostatectomy specimens

PurposeTo quantify the heterogeneity of viscoelastic tissue properties in prostatectomy specimens from men with prostate cancer (PC) using MR elastography (MRE) with histopathology as reference. MethodsTwelve fresh prostatectomy specimens were examined in a preclinical 9.4T MRI scanner. Maps of the complex shear modulus (|G*| in kPa) with its real and imaginary part (G' and G" in kPa) were calculated at 500 Hz. Prostates were divided into 12 segments for segment-wise measurement of viscoelastic properties and histopathology. Coefficients of variation (CVs in %) were calculated for quantification of heterogeneity. ResultsGroup-averaged values of cancerous vs. benign segments were significantly increased: |G*| of 12.13 kPa vs. 6.14 kPa, G' of 10.84 kPa vs. 5.44 kPa and G" of 5.45 kPa vs. 2.92 kPa, all p < 0.001. In contrast, CVs were significantly increased for benign segments: 23.59% vs. 26.32% (p = 0.014) for |G*|, 27.05% vs. 37.84% (p < 0.003) for G', and 36.51% vs. 50.37% (p = 0.008) for G". DiscussionPC is characterized by a stiff yet homogeneous biomechanical signature, which may be due to the unique nondestructive growth pattern of PC with intervening stroma, providing a rigid scaffold in the affected area. In turn, increased heterogeneity in benign prostate segments may be attributable to the presence of different prostate zones with involvement by specific nonmalignant pathology.

Design, inverted vat photopolymerization 3D printing, and initial characterization of a miniature force sensor for localized in vivo tissue measurements

BackgroundTissue healthiness could be assessed by evaluating its viscoelastic properties through localized contact reaction force measurements to obtain quantitative time history information. To evaluate these properties for hard to reach and confined areas of the human body, miniature force sensors with size constraints and appropriate load capabilities are needed. This research article reports on the design, fabrication, integration, characterization, and in vivo experimentation of a uniaxial miniature force sensor on a human forearm.MethodsThe strain gauge based sensor components were designed to meet dimensional constraints (diameter ≤3.5mm), safety factor (≥3) and performance specifications (maximum applied load, resolution, sensitivity, and accuracy). The sensing element was fabricated using traditional machining. Inverted vat photopolymerization technology was used to prototype complex components on a Form3 printer; micro-component orientation for fabrication challenges were overcome through experimentation. The sensor performance was characterized using dead weights and a LabVIEW based custom developed data acquisition system. The operational performance was evaluated by in vivo measurements on a human forearm; the relaxation data were used to calculate the Voigt model viscoelastic coefficient.ResultsThe three dimensional (3D) printed components exhibited good dimensional accuracy (maximum deviation of 183μm). The assembled sensor exhibited linear behavior (regression coefficient of R2=0.999) and met desired performance specifications of 3.4 safety factor, 1.2N load capacity, 18mN resolution, and 3.13% accuracy. The in vivo experimentally obtained relaxation data were analyzed using the Voigt model yielding a viscoelastic coefficient τ=12.38sec and a curve-fit regression coefficient of R2=0.992.ConclusionsThis research presented the successful design, use of 3D printing for component fabrication, integration, characterization, and analysis of initial in vivo collected measurements with excellent performance for a miniature force sensor for the assessment of tissue viscoelastic properties. Through this research certain limitations were identified, however the initial sensor performance was promising and encouraging to continue the work to improve the sensor. This micro-force sensor could be used to obtain tissue quantitative data to assess tissue healthiness for medical care over extended time periods.

Quasi-linear viscoelastic behavior of fresh porcine ureter.

To evaluate the viscoelastic properties of the fresh porcine ureter. Prove the QLV theory can sufficiently model the stress relaxation function of porcine ureters, and determine the QLV model constants which may provide insight into the synthesis of ureteral scaffolds with biomimetic viscoelastic properties in tissue engineering. Hysteresis tests were applied to study the differences in dissipated energy ratio for each different strain group. In stress relaxation tests, samples were sub-grouped and quickly ramping up to 5%, 20%, and 30% strain in each group and gradually relaxed to a corresponding level. Bringingtogether the quasi-linear viscoelasticity (QLV) theory and stress relaxation function to determine the eight constants of the ureteral tissue, and fitting the raw data with the model via MATLAB. The hysteresis response measurement results revealed that the porcine ureter was a highly dissipative material and there were differences between toe and linear region in stress-stain curve. The stress relaxation results revealed ureters responded with time-dependent decay of stress. The eight constants of the ureteral QLV model were determined for three different strain groups, and we proved that the QLV model can sufficiently adapt the experimental data of the ureter stress relaxation. This study investigated the time-dependent properties of the porcine ureter, and demonstrated the QLV theory could be used to evaluate the viscoelastic properties of the porcine ureteral tissue.

Age-dependent viscoelastic characterization of rat brain cortex

Recent efforts in biomaterial-assisted brain tissue engineering suggest that match of mechanical properties of biomaterials to those of native brain tissue may be crucial for brain regeneration. In particular, the mechanical properties of native brain tissue vary as a function of age. To date, detailed characterization of age-dependent viscoelastic properties of brain tissue throughout the postnatal development to adulthood is only available at sparse age points in animal studies. To fill this gap, we have characterized the linear viscoelastic properties of the cerebral cortex in rats at well-spaced ages from postnatal day 4 to 4 months old, the age range that is widely used in neural regeneration studies. Using an oscillatory rheometer, the viscoelastic properties of rat cortical slices were measured independently by storage moduli (G′) and loss moduli (G″). The data demonstrated increases in both the storage moduli and the loss moduli of cortex tissue over post-natal age in rats. At all ages, the damping factor (G″/G′ ratio) remained constant at low oscillatory strain frequencies (<10 rad/s) before it started to decline at medium frequency range (10-100 rad/s). Such changes were not age-dependent. The stress-relaxation response increased over post-natal age, consistent with the increasing tissue stiffness. Taken together, our study demonstrates that age is a crucial factor determining the mechanical properties of the cerebral cortex in rats during early postnatal development. This data may provide the guidelines for age-specific biomechanics study of brain tissue and help to define the mechanical properties of biomaterials for biomaterial-assisted brain tissue regeneration studies. Statement of significanceStudies about age-dependent viscoelastic properties of rat brain tissue throughout the postnatal development to adulthood is sparsely available. To fill up the gap of knowledge, in this study, we have characterized the age-dependent viscoelastic properties and the linear viscoelastic properties of the cerebral cortex throughout the postnatal development stage to adulthood in rats by measuring storage moduli (G′), loss moduli (G″), damping factor (G″/G′ ratio) and stress-relaxation response. We have found that age is a crucial factor determining the mechanical properties of the cerebral cortex in rats during early postnatal development. The findings of this study could provide guidelines for age-specific biomechanical study of brain tissue and help to define the mechanical properties of biomaterials for biomaterial-assisted brain tissue regeneration in experimental models in rats.