Compartmental relaxation and diffusion tensor imaging measurements in vivo in lambda-carrageenan-induced edema in rat skeletal muscle.
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ABSTRACT:
SUBMITTER: Fan RH
PROVIDER: S-EPMC2694448 | biostudies-other | 2008 Jul
REPOSITORIES: biostudies-other
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Project description:Musculoskeletal (dys-)function relies for a large part on muscle architecture which can be obtained using Diffusion-Tensor MRI (DT-MRI) and fiber tractography. However, reconstructed tracts often continue along the tendon or aponeurosis when using conventional methods, thus overestimating fascicle lengths. In this study, we propose a new method for semiautomatic segmentation of tendinous tissue using tract density (TD). We investigated the feasibility and repeatability of this method to quantify the mean fascicle length per muscle. Additionally, we examined whether the method facilitates measuring changes in fascicle length of lower leg muscles with different foot positions. Five healthy subjects underwent two DT-MRI scans of the right lower leg, with the foot in 15° dorsiflexion, neutral, and 30° plantarflexion positions. Repeatability of fascicle length measurements was assessed using Bland-Altman analysis. Changes in fascicle lengths between the foot positions were tested using a repeated multivariate analysis of variance (MANOVA). Bland-Altman analysis showed good agreement between repeated measurements. The coefficients of variation in neutral position were 8.3, 16.7, 11.2, and 10.4% for soleus (SOL), fibularis longus (FL), extensor digitorum longus (EDL), and tibialis anterior (TA), respectively. The plantarflexors (SOL and FL) showed significant increase in fascicle length from plantarflexion to dorsiflexion, whereas the dorsiflexors (EDL and TA) exhibited a significant decrease. The use of a tract density for semiautomatic segmentation of tendinous structures provides more accurate estimates of the mean fascicle length than traditional fiber tractography methods. The method shows moderate to good repeatability and allows for quantification of changes in fascicle lengths due to passive stretch.
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Project description:When diffusion biomarkers display transient changes, i.e. in muscle following exercise, traditional diffusion-tensor imaging (DTI) methods lack the temporal resolution to resolve the dynamics. This article presents an MRI method for dynamic diffusion-tensor acquisitions on a clinical 3T scanner. This method, the Single-Line Multiple-Echo Diffusion-Tensor Acquisition Technique (SL-MEDITATE), achieves a high temporal resolution (4 s) by rapid diffusion encoding through the acquisition of multiple echoes with unique diffusion sensitization and limiting the readout to a single line volume. The method is demonstrated in a rotating anisotropic phantom, a flow phantom with adjustable flow speed and in vivo skeletal calf muscle of healthy volunteers following a plantar flexion exercise. The rotating and flow-varying phantom experiments show that SL-MEDITATE correctly identifies the rotation of the first diffusion eigenvector and the changes in diffusion-tensor parameter magnitudes, respectively. Immediately following exercise, the in vivo mean diffusivity (MD) time courses show, before the well-known increase, an initial decrease that is not typically observed in traditional DTI. In conclusion, SL-MEDITATE can be used to capture transient changes in tissue anisotropy in a single line. Future progress might allow for dynamic DTI when combined with appropriate k-space trajectories and compressed sensing reconstruction.
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Project description:PURPOSE:To establish a series of relationships defining how muscle microstructure and diffusion tensor imaging (DTI) are related. METHODS:The relationship among key microstructural features of skeletal muscle (fiber size, fibrosis, edema, and permeability) and the diffusion tensor were systematically simulated over physiologically relevant dimensions individually, and in combination, using a numerical simulation application. Stepwise multiple regression was used to identify which microstructural features of muscle significantly predict the diffusion tensor using single-echo and multi-echo DTI pulse sequences. Simulations were also performed in models with histology-informed geometry to investigate the relationship between fiber size and the diffusion tensor in models with real muscle geometry. RESULTS:Fiber size is the strongest predictor of ?2, ?3, mean diffusivity, and fractional anisotropy in skeletal muscle, accounting for approximately 40% of the variance in the diffusion model when calculated with single-echo DTI. This increased to approximately 70% when diffusion measures were calculated from the short T2 component of the multi-echo DTI sequence. This nonlinear relationship begins to plateau in fibers with greater than 60-?m diameter. CONCLUSIONS:As the normal fiber size of a human muscle fiber is 40 to 60??m, this suggests that DTI is a sensitive tool to monitor muscle atrophy, but may be limited in measurements of muscle with larger fibers. Magn Reson Med 80:317-329, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
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Project description:Alloferon-1 have been proposed as an effective peptide to enhance antitumoral immunity, antiviral defense and anti-inflammatory activity. This work aimed to assess anti-inflammatory effects of alloferon-1 against acute inflammation and histopathological deformations in λ-carrageenan-induced paw edema in mice. Systemic pretreatment with alloferon-1 (22.0 mg/kg) intraperitoneally injected mice showed a significant reduction in paw thickness and vascular permeability. Alloferon-1 prevented λ-carrageenan-evoked exudation and the neutrophil influx to the mouse pleura and the neutrophil migration into carrageenan-stimulated mouse air pouches based on the histopathological changes in the paw tissues. Administration of alloferon-1 also suppressed the expression of the inflammatory cytokines in the inflamed paw tissues such as tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein 1 (MCP1), interleukin-5 (IL-5), etc. detected by Luminex liquid chip. Collectively, the present study provides evidences for the marked anti-inflammatory effects of alloferon-1 which might represent new therapeutic options for the treatment of acute inflammatory diseases.
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Project description:PurposeEvaluate the relationship between muscle microstructure, diffusion time (Δ), and the diffusion tensor (DT) to identify the optimal Δ where changes in muscle fiber size may be detected.MethodsThe DT was simulated in models with histology informed geometry over a range of Δ with a stimulated echo DT imaging (DTI) sequence using the numerical simulation application DifSim. The difference in the DT at each Δ between healthy and injured skeletal muscle models was calculated, to identify the optimal Δ at which changes in muscle fiber size may be detected. The random permeable barrier model (RPBM) was used to estimate muscle microstructure from the simulated DT measurements, which were compared to the ground truth.ResultsAcross all models, fractional anisotropy provided greater contrast between injured and control models than diffusivity measurements. Compared to control models, in atrophic injury models, the greatest difference in the DT was found between 90 ms and 250 ms. In models with acute edema, the contrast between injured and control muscle increased with increasing diffusion time, although these models had smaller mean fiber areas. RPBM systematically underestimated fiber size but accurately estimated surface area-to-volume ratio of simulated models.ConclusionThese findings may better inform pulse sequence parameter selection when performing DTI experiments in vivo. If only a single diffusion experiment can be performed, the selected Δ should be ~170 ms to maximize the ability to discriminate between different injury models. Ideally several diffusion times between 90 ms and 500 ms should be sampled in order to maximize diffusion contrast, particularly when the disease process is unknown.
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Project description:BackgroundThe purpose of this study was to develop a DTI-based method to quantitatively assess fiber angles and changes therein in leg muscles in order to facilitate longitudinal studies on muscle fiber architectural adaptations in healthy subjects.MethodsThe upper legs of five volunteers were scanned twice on the same day. The right lower legs of five volunteers were scanned twice with the ankle in three positions, i.e. -15° dorsiflexion, 0° neutral position, and 30° plantarflexion. The MRI protocols consisted of a noise scan, a 3-point mDixon scan and a DTI scan. Fiber-angle color maps were generated for four muscles in the upper legs and two muscles in the lower leg. Voxel-wise fiber angles (θ) were calculated from the angle between the principal eigenvector of the diffusion tensor and a reference line defined between the origo and insertion points of each muscle. Bland-Altman analysis, intraclass correlation coefficient (ICC), coefficient of variation (CV%), minimal detectable change (MDC), standard error (SE) and Friedman test were used for assessing the feasibility of this method and in order to have an indication of the repeatability and the sensitivity.ResultsBland-Altman analysis showed good repeatability (CV%<10 and 0.7≤ICC≤0.9) with exception of the Tibialis Anterior (TA) muscle in dorsiflexion position(CV%: 12.2) and the Semitendinosus (ST) muscle (left leg) (CV%: 11.4). The best repeatability metrics were found for the SOL muscle in neutral position (CV%: 2.6). Changes in average θ in TA and SOL with ankle positions were observed in accordance with expected agonist and antagonist functions of both muscles. For example, for the anterior left compartment the change in fiber angle Δθ with respect to the neutral position Δθ = -1.6° ± 0.8° and 2.2° ± 2.8° (p = 0.008), for dorsiflexion and plantarflexion, respectively.ConclusionOur method facilitates fast inspection and quantification of muscle fiber angles in the lower and upper leg muscles in rest and detection of changes in lower-leg muscle fiber angles with varying ankle angles.
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Project description:PurposeTo optimize diffusion-relaxation MRI with tensor-valued diffusion encoding for precise estimation of compartment-specific fractions, diffusivities, and T2 values within a two-compartment model of white matter, and to explore the approach in vivo.MethodsSampling protocols featuring different b-values (b), b-tensor shapes (bΔ ), and echo times (TE) were optimized using Cramér-Rao lower bounds (CRLB). Whole-brain data were acquired in children, adults, and elderly with white matter lesions. Compartment fractions, diffusivities, and T2 values were estimated in a model featuring two microstructural compartments represented by a "stick" and a "zeppelin."ResultsPrecise parameter estimates were enabled by sampling protocols featuring seven or more "shells" with unique b/bΔ /TE-combinations. Acquisition times were approximately 15 minutes. In white matter of adults, the "stick" compartment had a fraction of approximately 0.5 and, compared with the "zeppelin" compartment, featured lower isotropic diffusivities (0.6 vs. 1.3 μm2 /ms) but higher T2 values (85 vs. 65 ms). Children featured lower "stick" fractions (0.4). White matter lesions exhibited high "zeppelin" isotropic diffusivities (1.7 μm2 /ms) and T2 values (150 ms).ConclusionsDiffusion-relaxation MRI with tensor-valued diffusion encoding expands the set of microstructure parameters that can be precisely estimated and therefore increases their specificity to biological quantities.
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Project description:Diffusion-tensor MRI fiber tractography has been used to reconstruct skeletal muscle architecture, but remains a specialized technique using custom-written data processing routines. In this work, we describe the public release of a software toolbox having the following design objectives: accomplish the pre-processing tasks of file input, image registration, denoising, and diffusion-tensor calculation; allow muscle-specific methods for defining seed points; make fiber-tract architectural measurements referenced to tendinous structures; visualize fiber tracts and other muscle structures of interest; analyze the goodness of outcomes; and provide a programming structure that allows the addition of new capabilities in future versions. The proper function of the code was verified using simulated datasets. The toolbox capabilities for characterizing human muscle structure in vivo were demonstrated in a case study. These capabilities included measurements of muscle morphology; contractile and non-contractile tissue volumes; fiber-tract length, pennation angle, curvature; and the physiological cross-sectional area,. The free public release of this software is a first step in creating of a community of users who use these tools in studies of muscle physiology and biomechanics. Users may further contribute to code development. Along with simulated and actual datasets for benchmarking, these tools will further create mechanisms for enhancing scientific rigor and developing and validating new code features. Planned future developments include additional options for image pre-processing, development of a graphical user interface, analysis of architectural patterns during muscle contraction, and integration of functional imaging data.
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Project description:This communication reports gelation of lambda-carrageenan, for the first time, in the presence of trivalent iron ions. Kappa-, iota- and lambda-carrageenans are sulfated polysaccharides used extensively in food, pharmaceutical and medical applications. Kappa- and iota-carrageenans show gelation in the presence of mono- and di-valent ions, but lambda-carrageenan yields only viscous solutions. Our results show that gelation in lambda-carrageenan indeed is possible, but with trivalent ions. X-ray fiber diffraction patterns of iron (III)-lambda-carrageenan are characteristic of highly oriented and polycrystalline fibers containing well resolved Bragg reflections. The elastic modulus (G') of the product is far greater than the loss modulus (G") indicating the thermal stability of lambda-carrageenan in the presence of iron (III) ions. This novel finding has potential to expand lambda-carrageenan's current utility beyond a viscosifying agent.
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Project description:The flavonoid izalpinin was isolated from the aerial parts of Chromolaena leivensis. Its structural determination was carried out using MS and NMR spectroscopic techniques (1H, 13C). This compound was evaluated for its anti-inflammatory effect in a rat model on λ-carrageenan-induced plantar edema. Paw inflammation was measured at one-hour intervals for seven hours following the administration of λ-carrageenan. Serum creatine kinase (CK) levels were evaluated, obtaining statistically significant results with the treatments at doses of 10 mg/kg (* p < 0.01) and 20 mg/kg (** p < 0.005). The anti-inflammatory effect of the compound was evaluated by using plethysmography, and the results showed significant differences at the three concentrations (10 mg/kg, 20 mg/kg, 40 mg/kg) in the first and third hours after treatment. * p < 0.05; ** p < 0.001; **** p < 0.0001 vs. the negative control group treated with vehicle (DMSO). Lastly, molecular docking analyses reveal that izalpinin has a strong binding affinity with five target proteins involved in the inflammatory process. The analysis using molecular dynamics allowed demonstrating that the ligand-protein complexes present acceptable stability, with RMSD values within the allowed range.
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