Patterns of Intersecting Fiber Arrays Revealed in Whole Muscle with Generalized Q-Space Imaging

Abstract

The multiscale attributes of mammalian muscle confer significant challenges for structural imaging in vivo. To achieve this, we employed a magnetic resonance method, termed "generalized Q-space imaging", that considers the effect of spatially distributed diffusion-weighted magnetic field gradients and diffusion sensitivities on the morphology of Q-space. This approach results in a subvoxel scaled probability distribution function whose shape correlates with local fiber orientation. The principal fiber populations identified within these probability distribution functions can then be associated by streamline methods to create multivoxel tractlike constructs that depict the macroscale orientation of myofiber arrays. We performed a simulation of Q-space input parameters, including magnetic field gradient strength and direction, diffusion sensitivity, and diffusional sampling to determine the optimal achievable fiber angle separation in the minimum scan time. We applied this approach to resolve intravoxel crossing myofiber arrays in the setting of the human tongue, an organ with anatomic complexity based on the presence of hierarchical arrays of intersecting myocytes. Using parameters defined by simulation, we imaged at 3T the fanlike configuration of the human genioglossus and the laterally positioned merging fibers of the styloglossus, inferior longitudinalis, chondroglossus, and verticalis. Comparative scans of the excised mouse tongue at 7T demonstrated similar midline and lateral crossing fiber patterns, whereas histological analysis confirmed the presence and distribution of these myofiber arrays at the microscopic scale. Our results demonstrate a magnetic resonance method for acquiring and displaying diffusional data that defines highly ordered myofiber patterns in architecturally complex tissue. Such patterns suggest inherent multiscale fiber organization and provide a basis for structure-function analyses in vivo and in model tissues.

Crosshatch nanofiber networks of tunable interfiber spacing induce plasticity in cell migration and cytoskeletal response

“…The immediate environment surrounding a cell offers a variety of biophysical cues of confinement, rigidity, topography (isotropic and anisotropic), and porosity (79). Here, we have explored how in the context of in vivo crosshatch network of fibrous environments found in dermis (11), basement membrane (15), muscular hydrostats (37), and the loose connective tissue (17), different levels of interfiber spacing can result in different morphologies and associated migration dynamics. Firstly, we observed that, at a very high interfiber spacing (wide: ;54 3 54 mm), cells form symmetric kite shapes and have reduced migration rates and persistence due to the formation of significantly large FACs.…”

“…To investigate cell migration in a 3-dimensional (3D) environment, cells are embedded in a 2.5-or 3D gel system, and gels with built-in anisotropy recapitulate persistent migration (30)(31)(32)(33)(34). The given complexity and the interconnectivity of ECM biophysical parameters (stiffness, fiber size and alignment, pore size, and architecture) (34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)) make it exceedingly difficult to elucidate the role of individual parameters in persistent cell migration. Thus, it is not surprising that, in a recent commentary, it was noted that there are generally no accepted methods to crossvalidate in vitro findings and to compare them with in vivo behavior (5).…”

Alterations in Multi‐Scale Cardiac Architecture in Association With Phosphorylation of Myosin Binding Protein‐C

“…The theory and methods associated with the use of GQI for imaging myoarchitecture in humans (in vivo) and rodents (ex vivo) were previously described . Restricted nuclear magnetic resonance diffusion can be used to resolve anisotropy at the voxel scale, based largely on the influence of impediments to random translational motion of protons .…”

“…Previous work has demonstrated that the transmural transition of LV fiber helix angles measured with DW‐MRI emulate the findings of Streeter et al., and that these transmural patterns were disrupted post‐MYBPC3 ablation . Generalized Q‐space imaging (GQI) is a novel form of DW‐MRI, developed to resolve architectural details in muscular and neural structures with enhanced subvoxel angular resolution . Building on the template of cardiac architectural patterns, GQI (further described in Figure S1) was employed to determine the relationship between constitutive MYBPC3 phospho‐regulation and myoarchitecture.…”

Crossing muscle fibers of the human tongue resolved in vivo using constrained spherical deconvolution

“…This excessively long scan time makes DSI unsuitable for a clinical setting. Another diffusion model, generalized q‐space imaging (GQI), also has the ability to discern between crossing muscle fibers in the murine tongue using a similar HARDI scheme and scan time as CSD. However, the typical array of transverse, vertical, and longitudinal fibers could only be detected in the murine model and not in the in vivo human case.…”