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Inversion-recovery MR elastography of the human brain for improved stiffness quantification near fluid-solid boundaries

2021, Lilaj, Ledia, Herthum, Helge, Meyer, Tom, Shahryari, Mehrgan, Bertalan, Gergely, Caiazzo, Alfonso, Braun, Jürgen, Fischer, Thomas, Hirsch, Sebastian, Sack, Ingolf

Purpose: In vivo MR elastography (MRE) holds promise as a neuroimaging marker. In cerebral MRE, shear waves are introduced into the brain, which also stimulate vibrations in adjacent CSF, resulting in blurring and biased stiffness values near brain surfaces. We here propose inversion-recovery MRE (IR-MRE) to suppress CSF signal and improve stiffness quantification in brain surface areas. Methods: Inversion-recovery MRE was demonstrated in agar-based phantoms with solid-fluid interfaces and 11 healthy volunteers using 31.25-Hz harmonic vibrations. It was performed by standard single-shot, spin-echo EPI MRE following 2800-ms IR preparation. Wave fields were acquired in 10 axial slices and analyzed for shear wave speed (SWS) as a surrogate marker of tissue stiffness by wavenumber-based multicomponent inversion. Results: Phantom SWS values near fluid interfaces were 7.5 ± 3.0% higher in IR-MRE than MRE (P =.01). In the brain, IR-MRE SNR was 17% lower than in MRE, without influencing parenchymal SWS (MRE: 1.38 ± 0.02 m/s; IR-MRE: 1.39 ± 0.03 m/s; P =.18). The IR-MRE tissue–CSF interfaces appeared sharper, showing 10% higher SWS near brain surfaces (MRE: 1.01 ± 0.03 m/s; IR-MRE: 1.11 ± 0.01 m/s; P <.001) and 39% smaller ventricle sizes than MRE (P <.001). Conclusions: Our results show that brain MRE is affected by fluid oscillations that can be suppressed by IR-MRE, which improves the depiction of anatomy in stiffness maps and the quantification of stiffness values in brain surface areas. Moreover, we measured similar stiffness values in brain parenchyma with and without fluid suppression, which indicates that shear wavelengths in solid and fluid compartments are identical, consistent with the theory of biphasic poroelastic media. © 2021 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine

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Vitronectin-based hydrogels recapitulate neuroblastoma growth conditions

2022, Monferrer, Ezequiel, Dobre, Oana, Trujillo, Sara, González Oliva, Mariana Azevedo, Trubert-Paneli, Alexandre, Acevedo-León, Delia, Noguera, Rosa, Salmeron-Sanchez, Manuel

The tumor microenvironment plays an important role in cancer development and the use of 3D in vitro systems that decouple different elements of this microenvironment is critical for the study of cancer progression. In neuroblastoma (NB), vitronectin (VN), an extracellular matrix protein, has been linked to poor prognosis and appears as a promising therapeutic target. Here, we developed hydrogels that incorporate VN into 3D polyethylene glycol (PEG) hydrogel networks to recapitulate the native NB microenvironment. The stiffness of the VN/PEG hydrogels was modulated to be comparable to the in vivo values reported for NB tissue samples. We used SK-N-BE (2) NB cells to demonstrate that PEGylated VN promotes cell adhesion as the native protein does. Furthermore, the PEGylation of VN allows its crosslinking into the hydrogel network, providing VN retention within the hydrogels that support viable cells in 3D. Confocal imaging and ELISA assays indicate that cells secrete VN also in the hydrogels and continue to reorganize their 3D environment. Overall, the 3D VN-based PEG hydrogels recapitulate the complexity of the native tumor extracellular matrix, showing that VN-cell interaction plays a key role in NB aggressiveness, and that VN could potentially be targeted in preclinical drug studies performed on the presented hydrogels.

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The role of winding pattern on filament wound composite cylinders under radial compression

2020, Lisbôa, Tales V., Almeida Jr, José Humberto S., Dalibor, Ingo H., Spickenheuer, Axel, Marczak, Rogério J., Amico, Sandro C.

Filament wound (FW) structures present a geometric characteristic in their helical layers: the winding pattern. The pattern, however, is usually disregarded in conventional experimental or numerical approaches even though it can affect the behavior of FW structures, and most studies that account for the pattern are only theoretical. This study aims at deepening the understanding of pattern effects via a comprehensive experimental campaign focusing on composites cylinders under radial compression. Ten winding patterns were considered, from 1 to 10 units along the circumferential direction. Strength, stiffness, absorbed energy and failure mechanisms were evaluated. The results show that the pattern may have a strong influence on both maximum bearing load and absorbed energy, whereas stiffness is less affected.

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T cell stiffness is enhanced upon formation of immunological synapse

2021, Jung, Philipp, Zhou, Xiangda, Iden, Sandra, Bischoff, Markus, Qu, Bin

T cells are activated by target cells via an intimate contact, termed immunological synapse (IS). Cellular mechanical properties, especially stiffness, are essential to regulate cell functions. However, T cell stiffness at a subcellular level at the IS still remains largely elusive. In this work, we established an atomic force microscopy (AFM)-based elasticity mapping method on whole T cells to obtain an overview of the stiffness with a resolution of ~60 nm. Using primary human CD4+ T cells, we show that when T cells form IS with stimulating antibody-coated surfaces, the lamellipodia are stiffer than the cell body. Upon IS formation, T cell stiffness is enhanced both at the lamellipodia and on the cell body. Chelation of intracellular Ca2+ abolishes IS-induced stiffening at the lamellipodia but has no influence on cell-body-stiffening, suggesting different regulatory mechanisms of IS-induced stiffening at the lamellipodia and the cell body.