The Extracellular Matrix as a Target for Biophysical and Molecular Magnetic Resonance Imaging

Schellenberger, Angela Ariza de; Bergs, Judith; Sack, Ingolf; Taupitz, Matthias

doi:10.1007/978-3-319-65924-4_6

Cited by 7 publications

(7 citation statements)

References 184 publications

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“…Our MR elastography study also aligns with several established concepts in tissue mechanics. The elastic properties of tissues are defined by the mechanical characteristics of their cells and their surrounding ECM, yet tissue macroscopic viscoelastic properties are not greatly affected by differences in cell morphology and density, but are largely governed by their ECM composition (43). Herein, histologically-confirmed regions of tissue damage (necrosis) were associated with markedly reduced elasticity and viscosity visualized in vivo.…”

Section: Discussionmentioning

confidence: 99%

Investigating the Contribution of Collagen to the Tumor Biomechanical Phenotype with Noninvasive Magnetic Resonance Elastography

et al. 2019

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Increased stiffness in the extracellular matrix (ECM) contributes to tumor progression and metastasis. Therefore, stromal modulating therapies and accompanying biomarkers are being developed to target ECM stiffness. Magnetic resonance (MR) elastography can noninvasively and quantitatively map the viscoelastic properties of tumors in vivo and thus has clear clinical applications. Herein, we used MR elastography, coupled with computational histopathology, to interrogate the contribution of collagen to the tumor biomechanical phenotype and to evaluate its sensitivity to collagenase-induced stromal modulation. Elasticity (G d) and viscosity (G l) were significantly greater for orthotopic BT-474 (G d ¼ 5.9 AE 0.2 kPa, G l ¼ 4.7 AE 0.2 kPa, n ¼ 7) and luc-MDA-MB-231-LM2-4 (G d ¼ 7.9 AE 0.4 kPa, G l ¼ 6.0 AE 0.2 kPa, n ¼ 6) breast cancer xenografts, and luc-PANC1 (G d ¼ 6.9 AE 0.3 kPa, G l ¼ 6.2 AE 0.2 kPa, n ¼ 7) pancreatic cancer xenografts, compared with tumors associated with the nervous system, including GTML/Trp53 KI/KI medulloblastoma (G d ¼ 3.5 AE 0.2 kPa, G l ¼ 2.3 AE 0.2 kPa, n ¼ 7), orthotopic luc-D-212-MG (G d ¼ 3.5 AE 0.2 kPa, G l ¼ 2.3 AE 0.2 kPa, n ¼ 7), luc-RG2 (G d ¼ 3.5 AE 0.2 kPa, G l ¼ 2.3 AE 0.2 kPa, n ¼ 5), and luc-U-87-MG (G d ¼ 3.5 AE 0.2 kPa, G l ¼ 2.3 AE 0.2 kPa, n ¼ 8) glioblastoma xenografts, intracranially propagated luc-MDA-MB-231-LM2-4 (G d ¼ 3.7 AE 0.2 kPa, G l ¼ 2.2 AE 0.1 kPa, n ¼ 7) breast cancer xenografts, and Th-MYCN neuroblastomas (G d ¼ 3.5 AE 0.2 kPa, G l ¼ 2.3 AE 0.2 kPa, n ¼ 5). Positive correlations between both elasticity (r ¼ 0.72, P < 0.0001) and viscosity (r ¼ 0.78, P < 0.0001) were determined with collagen fraction, but not with cellular or vascular density. Treatment with collagenase significantly reduced G d (P ¼ 0.002) and G l (P ¼ 0.0006) in orthotopic breast tumors. Texture analysis of extracted images of picrosirius red staining revealed significant negative correlations of entropy with G d (r ¼ À0.69, P < 0.0001) and G l (r ¼ À0.76, P < 0.0001), and positive correlations of fractal dimension with G d (r ¼ 0.75, P < 0.0001) and G l (r ¼ 0.78, P < 0.0001). MR elastography can thus provide sensitive imaging biomarkers of tumor collagen deposition and its therapeutic modulation. Significance: MR elastography enables noninvasive detection of tumor stiffness and will aid in the development of ECM-targeting therapies.

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Section: Discussionmentioning

confidence: 99%

Investigating the Contribution of Collagen to the Tumor Biomechanical Phenotype with Noninvasive Magnetic Resonance Elastography

et al. 2019

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“…[19,115] An overexpression of GAGs will decrease flu-idity, and conversely, chain cleavage or depletion of GAGs will cause an increase. [115][116][117] As a result, a change in brain fluidity in either direction indicates disrupted homeostasis as a pathologic change. [23] With respect to our brain data shown above, an abundance of GAGs was found in glioblastoma (GB) compared to meningioma (MEN) in a histopathological analysis.…”

Section: Tumor Microenvironment and Extracellular Matrixmentioning

confidence: 99%

Changes in Tissue Fluidity Predict Tumor Aggressiveness In Vivo

Sauer¹,

Grosser

Shahryari

et al. 2023

Advanced Science

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Cancer progression is caused by genetic changes and associated with various alterations in cell properties, which also affect a tumor's mechanical state. While an increased stiffness has been well known for long for solid tumors, it has limited prognostic power. It is hypothesized that cancer progression is accompanied by tissue fluidization, where portions of the tissue can change position across different length scales. Supported by tabletop magnetic resonance elastography (MRE) on stroma mimicking collagen gels and microscopic analysis of live cells inside patient derived tumor explants, an overview is provided of how cancer associated mechanisms, including cellular unjamming, proliferation, microenvironment composition, and remodeling can alter a tissue's fluidity and stiffness. In vivo, state‐of‐the‐art multifrequency MRE can distinguish tumors from their surrounding host tissue by their rheological fingerprints. Most importantly, a meta‐analysis on the currently available clinical studies is conducted and universal trends are identified. The results and conclusions are condensed into a gedankenexperiment about how a tumor can grow and eventually metastasize into its environment from a physics perspective to deduce corresponding mechanical properties. Based on stiffness, fluidity, spatial heterogeneity, and texture of the tumor front a roadmap for a prognosis of a tumor's aggressiveness and metastatic potential is presented.

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“…For long-term levitation culture potential of our setup, efforts to reduce the concentration of gadobutrol will be important, as long-term effects of paramagnetic agents on cells are still unclear. Gadobutrol cannot naturally enter into the cells (Mohammadi et al, 2014), however, when the cells are cultured long time to form their own ECM, its effect is unclear so the system will also need additional research in terms of cell health that can be affected by various processes such as transchelation (de Schellenberger et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Magnetic levitation assisted biofabrication, culture, and manipulation of 3D cellular structures using a ring magnet based setup

Anıl-İnevi

Delikoyun

Meşe

et al. 2021

Biotech & Bioengineering

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Diamagnetic levitation is an emerging technology for remote manipulation of cells in cell and tissue level applications. Low-cost magnetic levitation configurations using permanent magnets are commonly composed of a culture chamber physically sandwiched between two block magnets that limit working volume and applicability. This work describes a single ring magnet-based magnetic levitation system to eliminate physical limitations for biofabrication. Developed configuration utilizes sample culture volume for construct size manipulation and long-term maintenance. Furthermore, our configuration enables convenient transfer of liquid or solid phases during the levitation. Before biofabrication, we first calibrated/ the platform for levitation with polymeric beads, considering the single cell density range of viable cells. By taking advantage of magnetic focusing and cellular self-assembly, millimeter-sized 3D structures were formed and maintained in the system allowing easy and on-site intervention in cell culture with an open operational space. We demonstrated that the levitation protocol could be adapted for levitation of various cell types (i.e., stem cell, adipocyte and cancer cell) representing cells of different densities by modifying the paramagnetic ion concentration that could be also reduced by manipulating the density of the medium. This technique allowed the manipulation and merging of separately formed 3D biological units, as well as the hybrid biofabrication with biopolymers. In conclusion, we believe that this platform will serve as an important tool in broad fields such as bottom-up tissue engineering, drug discovery and developmental biology.

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The Extracellular Matrix as a Target for Biophysical and Molecular Magnetic Resonance Imaging

Cited by 7 publications

References 184 publications

Investigating the Contribution of Collagen to the Tumor Biomechanical Phenotype with Noninvasive Magnetic Resonance Elastography

Investigating the Contribution of Collagen to the Tumor Biomechanical Phenotype with Noninvasive Magnetic Resonance Elastography

Changes in Tissue Fluidity Predict Tumor Aggressiveness In Vivo

Magnetic levitation assisted biofabrication, culture, and manipulation of 3D cellular structures using a ring magnet based setup

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