Noninvasive assessment of the rheological behavior of human organs using multifrequency MR elastography: a study of brain and liver viscoelasticity

MR elastography (MRE) enables the noninvasive determination of the viscoelastic behavior of human internal organs based on their response to oscillatory shear stress. An experiment was developed that combines multifrequency shear wave actuation with broad-band motion sensitization to extend the dynamic range of a single MRE examination. With this strategy, multiple wave images corresponding to different driving frequencies are simultaneously received and can be analyzed by evaluating the dispersion of the complex modulus over frequency. The technique was applied on the brain and liver of five healthy volunteers. Its repeatability was tested by four follow-up studies in each volunteer. Five standard rheological models (Maxwell, Voigt, Zener, Jeffreys and fractional Zener model) were assessed for their ability to reproduce the observed dispersion curves. The three-parameter Zener model was found to yield the most consistent results with two shear moduli mu(1) = 0.84 +/- 0.22 (1.36 +/- 0.31) kPa, mu(2) = 2.03 +/- 0.19 (1.86 +/- 0.34) kPa and one shear viscosity of eta = 6.7 +/- 1.3 (5.5 +/- 1.6) Pa s (interindividual mean +/- SD) in brain (liver) experiments. Significant differences between the rheological parameters of brain and liver were found for mu(1) and eta (P < 0.05), indicating that human brain is softer and possesses a higher viscosity than liver.     

Viscoelastic properties of soft gels: comparison of magnetic resonance elastography and dynamic shear testing in the shear wave regime

Magnetic resonance elastography (MRE) is used to quantify the viscoelastic shear modulus, G*, of human and animal tissues. Previously, values of G* determined by MRE have been compared to values from mechanical tests performed at lower frequencies. In this study, a novel dynamic shear test (DST) was used to measure G* of a tissue-mimicking material at higher frequencies for direct comparison to MRE. A closed-form solution, including inertial effects, was used to extract G* values from DST data obtained between 20 and 200 Hz. MRE was performed using cylindrical 'phantoms' of the same material in an overlapping frequency range of 100-400 Hz. Axial vibrations of a central rod caused radially propagating shear waves in the phantom. Displacement fields were fit to a viscoelastic form of Navier's equation using a total least-squares approach to obtain local estimates of G*. DST estimates of the storage G' (Re[G*]) and loss modulus G″ (Im[G*]) for the tissue-mimicking material increased with frequency from 0.86 to 0.97 kPa (20-200 Hz, n = 16), while MRE estimates of G' increased from 1.06 to 1.15 kPa (100-400 Hz, n = 6). The loss factor (Im[G*]/Re[G*]) also increased with frequency for both test methods: 0.06-0.14 (20-200 Hz, DST) and 0.11-0.23 (100-400 Hz, MRE). Close agreement between MRE and DST results at overlapping frequencies indicates that G* can be locally estimated with MRE over a wide frequency range. Low signal-to-noise ratio, long shear wavelengths and boundary effects were found to increase residual fitting error, reinforcing the use of an error metric to assess confidence in local parameter estimates obtained by MRE.     

Frequency-dependent viscoelastic parameters of mouse brain tissue estimated by MR elastography

Viscoelastic properties of mouse brain tissue were estimated non-invasively, in vivo, using magnetic resonance elastography (MRE) at 4.7 T to measure the dispersive properties of induced shear waves. Key features of this study include (i) the development and application of a novel MR-compatible actuation system which transmits vibratory motion into the brain through an incisor bar, and (ii) the investigation of the mechanical properties of brain tissue over a 1200 Hz bandwidth from 600-1800 Hz. Displacement fields due to propagating shear waves were measured during continuous, harmonic excitation of the skull. This protocol enabled characterization of the true steady-state patterns of shear wave propagation. Analysis of displacement fields obtained at different frequencies indicates that the viscoelastic properties of mouse brain tissue depend strongly on frequency. The average storage modulus (G') increased from approximately 1.6 to 8 kPa over this range; average loss modulus (G″) increased from approximately 1 to 3 kPa. Both moduli were well approximated by a power-law relationship over this frequency range. MRE may be a valuable addition to studies of disease in murine models, and to pre-clinical evaluations of therapies. Quantitative measurements of the viscoelastic parameters of brain tissue at high frequencies are also valuable for modeling and simulation of traumatic brain injury.     

Three-dimensional analysis of shear wave propagation observed by in vivo magnetic resonance elastography of the brain

Dynamic magnetic resonance elastography (MRE) is a non-invasive method for the quantitative determination of the mechanical properties of soft tissues in vivo. In MRE, shear waves are generated in the tissue and visualized using phase-sensitive MR imaging methods. The resulting two-dimensional (2-D) wave images can reveal in-plane elastic properties when possible geometrical biases of the wave patterns are taken into account. In this study, 3-D MRE experiments of in vivo human brain are analyzed to gain knowledge about the direction of wave propagation and to deduce in-plane elastic properties. The direction of wave propagation was determined using a new algorithm which identifies minimal wave velocities along rays from the surface into the brain. It was possible to quantify biases of the elastic parameters due to projections onto coronal, sagittal and transversal image planes in 2-D MRE. It was found that the in-plane shear modulus is increasingly overestimated when the image slice is displaced from narrow slabs of 2-5cm through the center of the brain. The mean shear modulus of the brain was deduced from 4-D wave data with about 3.5kPa. Using the proposed slice positions in 2-D MRE, this shear modulus can be reproduced with an acceptable error within a fraction of the full 3-D examination time.     

Viscoelasticity-based MR elastography of skeletal muscle

An in vivo multifrequency magnetic resonance elastography (MRE) protocol was developed for studying the viscoelastic properties of human skeletal muscle in different states of contraction. Low-frequency shear vibrations in the range of 25-62.5 Hz were synchronously induced into the femoral muscles of seven volunteers and measured in a cross-sectional view by encoding the fast-transverse shear wave component parallel to the muscle fibers. The so-called springpot model was used for deriving two viscoelastic constants, μ and α, from the dispersion functions of the complex shear modulus in relaxed and in loaded muscle. Representing the shear elasticity parallel to the muscle fibers, μ increased in all volunteers upon contraction from 2.68 ± 0.23 kPa to 3.87 ± 0.50 kPa. Also α varied with load, indicating a change in the geometry of the mechanical network of muscle from relaxation (α = 0.253 ± 0.009) to contraction (α = 0.270 ± 0.009). These results provide a reference for a future assessment of muscular dysfunction using rheological parameters.     

In vivo elasticity measurements of extremity skeletal muscle with MR elastography

MR elastography (MRE) has been shown to be capable of non-invasively measuring tissue elasticity even in deep-lying regions. Although limited studies have already been published examining in vivo muscle elasticity, it is still not clear over what range the in vivo elasticity values vary. The present study intends to produce further information by examining four different skeletal muscles in a group of 12 healthy volunteers in the age range of 27-38 years. The examinations were performed in the biceps brachii, the flexor digitorum profundus, the soleus and the gastrocnemius. The average shear modulus was determined to be 17.9 (+/- 5.5), 8.7 (+/- 2.8), 12.5 (+/- 7.3) and 9.9 (+/- 6.8) kPa for each muscle, respectively. To ascertain the reproducibility of the examination, the stiffness measurements in two volunteers were repeated seven times for the biceps brachii. These examinations yielded a mean shear modulus of 11.3 +/-.7 and 13.3 +/- 4.7 kPa for the two subjects. For elasticity reconstruction, an automated reconstruction algorithm is introduced which eliminates variation due to subjective manual image analysis. This study yields new information regarding the expected variation in muscle elasticity in a healthy population, and also reveals the expected variability of the MRE technique in skeletal muscle.     

In vivo brain viscoelastic properties measured by magnetic resonance elastography

Magnetic resonance elastography (MRE) is a non-invasive imaging technique used to visualise and quantify mechanical properties of tissue, providing information beyond what can be currently achieved with standard MR sequences and could, for instance, provide new insight into pathological processes in the brain. This study uses the MRE technique at 3 T to extract the complex shear modulus for in vivo brain tissue utilizing a full three-dimensional approach to reconstruction, removing contributions of the dilatational wave by application of the curl operator. A calibrated phantom is used to benchmark the MRE measurements, and in vivo results are presented for healthy volunteers. The results provide data for in vivo brain storage modulus (G'), finding grey matter (3.1 kPa) to be significantly stiffer than white matter (2.7 kPa). The first in vivo loss modulus (G') measurements show no significant difference between grey matter (2.5 kPa) and white matter (2.5 kPa).     

Cerebral multifrequency MR elastography by remote excitation of intracranial shear waves

The aim of this study was to introduce remote wave excitation for high‐resolution cerebral multifrequency MR elastography (mMRE). mMRE of 25–45‐Hz drive frequencies by head rocker stimulation was compared with mMRE by remote wave excitation based on a thorax mat in 12 healthy volunteers. Maps of the magnitude |G*| and phase φ of the complex shear modulus were reconstructed using multifrequency dual elasto‐visco (MDEV) inversion. After the scan, the subjects and three operators assessed the comfort and convenience of cerebral mMRE using two methods of stimulating the brain. Images were acquired in a coronal view in order to identify anatomical regions along the spinothalamic pathway. In mMRE by remote actuation, all subjects and operators appreciated an increased comfort and simplified procedural set‐up. The resulting strain amplitudes in the brain were sufficiently large to analyze using MDEV inversion, and yielded high‐resolution viscoelasticity maps which revealed specific anatomical details of brain mechanical properties: |G*| was lowest in the pons (0.97 ± 0.08 kPa) and decreased within the corticospinal tract in the caudal–cranial direction from the crus cerebri (1.64 ± 0.26 kPa) to the capsula interna (1.29 ± 0.14 kPa). By avoiding onerous mechanical stimulation of the head, remote excitation of intracranial shear waves can be used to measure viscoelastic parameters of the brain with high spatial resolution. Therewith, the new mMRE method is suitable for neuroradiological examinations in the clinic. Copyright © 2015 John Wiley & Sons, Ltd.     

In vivo viscoelastic properties of the brain in normal pressure hydrocephalus

Nearly half a century after the first report of normal pressure hydrocephalus (NPH), the pathophysiological cause of the disease still remains unclear. Several theories about the cause and development of NPH emphasize disease-related alterations of the mechanical properties of the brain. MR elastography (MRE) uniquely allows the measurement of viscoelastic constants of the living brain without intervention. In this study, 20 patients (mean age, 69.1 years; nine men, 11 women) with idiopathic (n = 15) and secondary (n = 5) NPH were examined by cerebral multifrequency MRE and compared with 25 healthy volunteers (mean age, 62.1 years; 10 men, 15 women). Viscoelastic constants related to the stiffness (μ) and micromechanical connectivity (α) of brain tissue were derived from the dynamics of storage and loss moduli within the experimentally achieved frequency range of 25-62.5 Hz. In patients with NPH, both storage and loss moduli decreased, corresponding to a softening of brain tissue of about 20% compared with healthy volunteers (p < 0.001). This loss of rigidity was accompanied by a decreasing α parameter (9%, p < 0.001), indicating an alteration in the microstructural connectivity of brain tissue during NPH. This disease-related decrease in viscoelastic constants was even more pronounced in the periventricular region of the brain. The results demonstrate distinct tissue degradation associated with NPH. Further studies are required to investigate the source of mechanical tissue damage as a potential cause of NPH-related ventricular expansions and clinical symptoms.     

MR elastography in a murine stroke model reveals correlation of macroscopic viscoelastic properties of the brain with neuronal density

The aim of this study was to investigate the influence of neuronal density on viscoelastic parameters of living brain tissue after ischemic infarction in the mouse using MR elastography (MRE). Transient middle cerebral artery occlusion (MCAO) in the left hemisphere was induced in 20 mice. In vivo 7‐T MRE at a vibration frequency of 900 Hz was performed on days 3, 7, 14 and 28 (n = 5 per group) after MCAO, followed by the analysis of histological markers, such as neuron counts (NeuN). MCAO led to a significant reduction in the storage modulus in the left hemisphere relative to contralateral values (p = 0.03) without changes over time. A correlation between storage modulus and NeuN in both hemispheres was observed, with correlation coefficients of R = 0.648 (p = 0.002, left) and R = 0.622 (p = 0.003, right). The loss modulus was less sensitive to MCAO, but correlated with NeuN in the left hemisphere (R = 0.764, p = 0.0001). In agreement with the literature, these results suggest that the shear modulus in the brain is reduced after transient ischemic insult. Furthermore, our study provides evidence that the in vivo shear modulus of brain tissue correlates with neuronal density. In diagnostic applications, MRE may thus have diagnostic potential as a tool for image‐based quantification of neurodegenerative processes. Copyright © 2013 John Wiley & Sons, Ltd.     

磁共振弹性成像的初步实验研究

目的：研究磁共振弹性成像（MRE）技术。方法：研制外部激发装置，设计成像脉冲序列，制作模拟人体软组织的体模。激发装置由序列控制，于体模表面产生低频率剪切波。脉冲序列采用梯度回波序列，在x、y或z轴上施加运动敏感梯度（MSG）。剪切波导致的介质内的周期性移位可使接收信号产生周期性相位位移，从测得的相位位移就能计算出每个体素的移位值，直接显示介质内剪切波的传播。通过调整相位偏置，获得一个完整周期内剪切波的动态传播图像。相位图经局部频率估算法（LFE）处理后计算出量化的弹性模景图。实验采用浓度为1．0％和1．5％不同弹性的琼脂凝胶体模，激发频率分别采用150Hz、200Hz、250Hz和300Hz。结果：MRE的相位图显示了剪切波在体模内的传播，剪切波的波长随激发频率和体模弹性变化。波长与激发频率呈反比，与体模弹性呈正比。剪切波的波长在不同激发频率和不同浓度体模之间呈严格的比例关系。计算出的弹性模量图清楚显示了两种浓度介质的弹性对比。结论：MRE的相位图可显示剪切波在介质内的传播，弹性图可量化和显示介质的弹性模量。     

Multifrequency inversion in magnetic resonance elastography

Time-harmonic shear wave elastography is capable of measuring viscoelastic parameters in living tissue. However, finite tissue boundaries and waveguide effects give rise to wave interferences which are not accounted for by standard elasticity reconstruction methods. Furthermore, the viscoelasticity of tissue causes dispersion of the complex shear modulus, rendering the recovered moduli frequency dependent. Therefore, we here propose the use of multifrequency wave data from magnetic resonance elastography (MRE) for solving the inverse problem of viscoelasticity reconstruction by an algebraic least-squares solution based on the springpot model. Advantages of the method are twofold: (i) amplitude nulls appearing in single-frequency standing wave patterns are mitigated and (ii) the dispersion of storage and loss modulus with drive frequency is taken into account by the inversion procedure, thereby avoiding subsequent model fitting. As a result, multifrequency inversion produces fewer artifacts in the viscoelastic parameter map than standard single-frequency parameter recovery and may thus support image-based viscoelasticity measurement. The feasibility of the method is demonstrated by simulated wave data and MRE experiments on a phantom and in vivo human brain. Implemented as a clinical method, multifrequency inversion may improve the diagnostic value of time-harmonic MRE in a large variety of applications.     

Fractal network dimension and viscoelastic powerlaw behavior: II. An experimental study of structure-mimicking phantoms by magnetic resonance elastography

The dynamics of the complex shear modulus, G*, of soft biological tissue is governed by the rigidity and topology of multiscale mechanical networks. Multifrequency elastography can measure the frequency dependence of G* in soft biological tissue, providing information about the structure of tissue networks at multiple scales. In this study, the viscoelastic properties of structure-mimicking phantoms containing tangled paper stripes embedded in agarose gel are investigated by multifrequency magnetic resonance elastography within the dynamic range of 40–120 Hz. The effective media viscoelastic properties are analyzed in terms of the storage modulus (the real part of G*), the loss modulus (the imaginary part of G*) and the viscoelastic powerlaw given by the two-parameter springpot model. Furthermore, diffusion tensor imaging is used for investigating the effect of network structures on water mobility. The following observations were made: the random paper networks with fractal dimensions between 2.481 and 2.755 had no or minor effects on the storage modulus, whereas the loss modulus was significantly increased about 2.2 kPa per fractal dimension unit (R = 0.962, P < 0.01). This structural sensitivity of the loss modulus was significantly correlated with the springpot powerlaw exponent (0.965, P < 0.01), while for the springpot elasticity modulus, a trend was discernable (0.895, P < 0.05). No effect of the paper network on water diffusion was observed. The gel phantoms with embedded paper stripes presented here are a feasible way for experimentally studying the effect of network topology on soft-tissue viscoelastic parameters. In the dynamic range of in vivo elastography, the fractal network dimension primarily correlates to the loss behavior of soft tissue as can be seen from the loss modulus or the powerlaw exponent of the springpot model. These findings represent the experimental underpinning of structure-sensitive elastography for an improved characterization of various soft-tissue diseases.     

Tissue characterization using magnetic resonance elastography: preliminary results

The well-documented effectiveness of palpation as a diagnostic technique for detecting cancer and other diseases has provided motivation for developing imaging techniques for noninvasively evaluating the mechanical properties of tissue. A recently described approach for elasticity imaging, using propagating acoustic shear waves and phase-contrast MRI, has been called magnetic resonance elastography (MRE). The purpose of this work was to conduct preliminary studies to define methods for using MRE as a tool for addressing the paucity of quantitative tissue mechanical property data in the literature. Fresh animal liver and kidney tissue specimens were evaluated with MRE at multiple shear wave frequencies. The influence of specimen temperature and orientation on measurements of stiffness was studied in skeletal muscle. The results demonstrated that all of the materials tested (liver, kidney, muscle and tissue-simulating gel) exhibit systematic dependence of shear stiffness on shear rate. These data are consistent with a viscoelastic model of tissue mechanical properties, allowing calculation of two independent tissue properties from multiple-frequency MRE data: shear modulus and shear viscosity. The shear stiffness of tissue can be substantially affected by specimen temperature. The results also demonstrated evidence of shear anisotropy in skeletal muscle but not liver tissue. The measured shear stiffness in skeletal muscle was found to depend on both the direction of propagation and polarization of the shear waves.     

Comparison of Dynamic Shear Properties of the Porcine Molar and Incisor Periodontal Ligament

The role of the periodontal ligament (PDL) is to support the tooth during function and resist external forces applied to it. The dominant vertical component of these forces is associated with shear in the PDL. The mechanical response to vertical force may, however, be different between the molar and incisor as their loading regimen is different. The present study was designed to determine the viscoelastic behavior in shear of the PDL of the porcine molar and incisor (n = 10 for each). From dissected mandibles transverse sections including the mesial root of first molar and the incisal root were obtained and used for dynamic shear tests. Shear strain of 1.0% was applied in superoinferior direction parallel to the root axis with a wide range of frequencies (0.01–100 Hz). The viscoelastic behavior was characterized by the storage and loss modulus and loss tangent as a function of the frequency. For the incisor and molar, the complex and storage moduli increased significantly with the frequency. For the incisor, the loss modulus also increased with the frequency. The loss modulus and loss tangent were significantly (p < 0.05) larger in the incisor than in the molar. The present results suggest that the incisal PDL revealed more viscous behavior during dynamic shear than the molar one, which might have important implications for the principal role of the anterior teeth such as PDL sensation.     

Measuring anisotropic muscle stiffness properties using elastography

Physiological and pathological changes to the anisotropic mechanical properties of skeletal muscle are still largely unknown, with only a few studies quantifying changes in vivo. This study used the noninvasive MR elastography (MRE) technique, in combination with diffusion tensor imaging (DTI), to measure shear modulus anisotropy in the human skeletal muscle in the lower leg. Shear modulus measurements parallel and perpendicular to the fibre direction were made in 10 healthy subjects in the medial gastrocnemius, soleus and tibialis anterior muscles. The results showed significant differences in the medial gastrocnemius (μ_‖ =0.86 ± 0.15 kPa; μ_⊥ = 0.66 ± 0.19 kPa, P < 0.001), soleus (μ_‖ = 0.83 ± 0.22 kPa; μ_⊥ = 0.65 ± 0.13 kPa, P < 0.001) and the tibialis anterior (μ_‖ = 0.78 ± 0.24 kPa; μ_⊥ = 0.66 ± 0.16 kPa, P = 0.03) muscles, where the shear modulus measured in the direction parallel is greater than that measured in the direction perpendicular to the muscle fibres. No significant differences were measured across muscle groups. This study provides the first direct estimates of the anisotropic shear modulus in the triceps surae muscle group, and shows that the technique may be useful for the probing of mechanical anisotropy changes caused by disease, aging and injury. Copyright © 2013 John Wiley & Sons, Ltd.     

Magnetic resonance elastography of the lumbar back muscles: A preliminary study

Back pain is associated with increased lumbar paraspinal muscle (LPM) stiffness identified by manual palpation and strain elastography. Recently, magnetic resonance elastography (MRE) has allowed the stiffness of muscle to be characterized noninvasively in vivo, providing quantitative 3D stiffness maps (elastograms). The aim of this study was to characterize the stiffness (shear modulus, SM) of the LPM (multifidus and erector spinae) using MRE. MRE of the lumbar region was performed on seven adults in supine position. MRE was acquired in three muscular states: relaxed with outstretched legs, stretched with passive pelvis flexion, and contracted with outstretched legs and tightened trunk muscles. The mean SM was measured within a region of interest manually defined in the multifidus, erector spinae, and the entire paraspinal compartment. The intermuscular difference and the effects of stretching and contraction were assessed by ANOVA and t‐tests. At rest, the mean SM of the paraspinal compartment was 1.6 ± 0.2 kPa. It increased significantly with stretching to 1.65 ± 0.3 kPa, and with contraction to 2.0 ± 0.7 kPa. Irrespective of muscular state, the erector spinae was significantly stiffer than the multifidus. The multifidus underwent proportionally higher stiffness changes from rest to contraction and stretching. MRE can be used to measure the stiffness of the LPM in different muscular states. We hypothesize that, irrespective of posture, the erector spinae behaves as semi‐rigid beam, and ensures permanent stiffness of the spine. The multifidus behaves as an adaptable muscle that provides segmental flexibility to the spine and tunes the spine stiffness. Clin. Anat. 31:514–520, 2018. © 2018 Wiley Periodicals, Inc.     

Liver fibrosis: non-invasive assessment with MR elastography

The aim of this study was to assess the feasibility of using non-invasive MR elastography for determining the stage of liver fibrosis. Twenty-five consecutive patients who had liver biopsy for suspicion of chronic liver disease were included in the study. The stage of fibrosis on the biopsies was assessed according to the METAVIR scoring system from F0, no fibrosis, to F4, cirrhosis. MR elastography was performed by transmitting low-frequency (65 Hz) mechanical waves into the liver with a transducer placed at the back of the patients. The MR pulse sequence was a motion-sensitized spin-echo sequence, phase-locked to the mechanical excitation. The phase maps were processed to obtain shear elasticity and shear viscosity maps. The mean hepatic shear elasticity increased with increasing stage of fibrosis. The mean elasticity was 2.24 +/- 0.23 kPa in the 11 patients without substantial fibrosis (F0-F1 grades), 2.56 +/- 0.24 kPa in the four patients with substantial fibrosis (F2-F3) and 4.68 +/- 1.61 kPa in the 10 patients with cirrhosis (F4). The differences between groups were statistically significant (p 相似文献   

Nonlinear viscoelastic effects in oscillatory shear deformation of brain tissue.

Two nonlinear constitutive models were used to describe the dynamic viscoelastic behavior of brain tissue. Small disc-shaped samples of bovine brain tissue were tested in simple shear using forced vibrations (0.5 to 200 Hz) with finite amplitudes (up to 20% Lagrangian shear strain). The samples response to simple, double, and triple harmonic inputs was determined in order to characterize the nonlinearities up to the third-order. A quasilinear viscoelastic model was proposed to describe the spatial nonlinearity. A fully nonlinear viscoelastic model with product-form multiple hereditary integrals was proposed to describe the spatial as well as the temporal nonlinearities. The fully nonlinear model demonstrated superiority at high frequencies (above 44 Hz). Under finite strains, the linear complex modulus showed nonrecoverable asymptotic strain conditioning behavior. Discrepancies observed in previously published studies and the threshold of functional failure of the neural tissue were shown to be related to this strain conditioning effect.     

Reproducibility of the mechanical properties of Vivostat system patient-derived fibrin sealant

Conventional "autologous" fibrin sealants, prepared from fibrinogen concentrates are inconsistent in their physical properties; this reflects the wide variation in the fibrinogen level of the single donor plasma from which they are made. In contrast, the Vivostat System produces a fibrin sealant of reproducible concentration and mechanical properties that are independent of the source plasma fibrinogen concentration. Fibrin solution concentrations prepared with the Vivostat System were 22.0 +/- 0.7 mg/ml (95% CI) with a coefficient of variation [CV] of 10.6% from samples of source plasma with a range of fibrinogen concentration between I and 6 mg/ml (mean 3.28 +/- 0.38 mg/ml (95% CI), 37% CV). Values of viscoelastic and tensile parameters after 11 min and 1 h, respectively, were: storage modulus (G') 891.5 +/- 72.9 Pa, 16.2% CV; loss modulus (G") 98.7 +/- 9.8 Pa, 23.2% CV; loss tangent (tan delta) 0.1093 +/- 0.0054, 9.8% CV; tensile strength 33.2 +/- 2.6kPa, 24.7% CV; extension at break 103 +/- 13%, 22.6% CV; Young's modulus 12.0 +/- 1.0 kPa, 16.6% CV. In the clinical setting this reproducibility provides the surgeon with a patient-derived fibrin sealant that can be expected to perform similarly from patient to patient.