Decreased tissue stiffness in glioblastoma by MR elastography is associated with increased cerebral blood flow

Svensson, Siri Fløgstad; Fuster–Garcia, Elies; Latysheva, Anna; Fraser-Green, Jorunn; Nordhøy, Wibeke; Darwish, Omar; Hovden, Ivar Thokle; Holm, Sverre; Vik-Mo, Einar O.; Sinkus, Ralph; Emblem, Kyrre E.

doi:10.1016/j.ejrad.2021.110136

Cited by 21 publications

(22 citation statements)

References 27 publications

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“…In addition, our study showed the applicability of the clinically applied ultrasound shear wave elastography to monitor the effects of the mechanotherapeutic agent on tumor stiffness and also to predict the therapeutic outcome of nanomedicine, immunotherapy and the combination of the two, similar to our previous findings 22 . Furthermore, apart from ultrasound, magnetic resonance elastography can quantify tumor stiffness with a focus on brain tumors 48 . Therefore, we propose that tumor stiffness measured with established imaging techniques should be considered as an immune-predictor and should be further investigated as potential biomarkers of response to nanoand immuno-therapies and for monitoring the efficacy of mechanotherapeutic treatments.…”

Section: Discussionmentioning

confidence: 99%

Polymeric micelles effectively reprogram the tumor microenvironment to potentiate nano-immunotherapy in mouse breast cancer models

et al. 2022

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Nano-immunotherapy improves breast cancer outcomes but not all patients respond and none are cured. To improve efficacy, research focuses on drugs that reprogram cancer-associated fibroblasts (CAFs) to improve therapeutic delivery and immunostimulation. These drugs, however, have a narrow therapeutic window and cause adverse effects. Developing strategies that increase CAF-reprogramming while limiting adverse effects is urgent. Here, taking advantage of the CAF-reprogramming capabilities of tranilast, we developed tranilast-loaded micelles. Strikingly, a 100-fold reduced dose of tranilast-micelles induces superior reprogramming compared to free drug owing to enhanced intratumoral accumulation and cancer-associated fibroblast uptake. Combination of tranilast-micelles and epirubicin-micelles or Doxil with immunotherapy increases T-cell infiltration, resulting in cures and immunological memory in mice bearing immunotherapy-resistant breast cancer. Furthermore, shear wave elastography (SWE) is able to monitor reduced tumor stiffness caused by tranilast-micelles and predict response to nano-immunotherapy. Micellar encapsulation is a promising strategy for TME-reprogramming and SWE is a potential biomarker of response.

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Section: Discussionmentioning

confidence: 99%

Polymeric micelles effectively reprogram the tumor microenvironment to potentiate nano-immunotherapy in mouse breast cancer models

et al. 2022

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“…For the host tissue, elastography data of a healthy subject were used because the clinical patient scans did not cover the entire brain, only 4.65 cm, covering the tumor. Because the patients differ from healthy subjects in terms of MRE values [ 59 ], more accurate results would have been obtained if the specific patient’s elastography of the host tissue was used. In addition, patients’ MRE values were obtained at one time point during tumor development and, thus, in the model, the elastic properties were assumed constant during tumor progression.…”

Section: Discussionmentioning

confidence: 99%

“…MR imaging was performed on a 3T clinical MRI scanner (Ingenia, Philips Medical Systems, Best, The Netherlands) using a 32-channel head coil. Anatomical T1-weighted, T2-weighted and fluid attenuated inversion recovery (FLAIR) images, as well as DTI MRIs and MRE data, were acquired for five patients, using imaging parameters as in [ 59 ], also shown in Table S2 . The MRE was performed using a gravitational transducer [ 60 ] attached on the side of the head, inducing shear waves of 50 Hz into the brain.…”

Section: Methodsmentioning

confidence: 99%

Inducing Biomechanical Heterogeneity in Brain Tumor Modeling by MR Elastography: Effects on Tumor Growth, Vascular Density and Delivery of Therapeutics

Harkos

Svensson

Emblem

et al. 2022

Cancers

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The purpose of this study is to develop a methodology that incorporates a more accurate assessment of tissue mechanical properties compared to current mathematical modeling by use of biomechanical data from magnetic resonance elastography. The elastography data were derived from five glioblastoma patients and a healthy subject and used in a model that simulates tumor growth, vascular changes due to mechanical stresses and delivery of therapeutic agents. The model investigates the effect of tumor-specific biomechanical properties on tumor anisotropic growth, vascular density heterogeneity and chemotherapy delivery. The results showed that including elastography data provides a more realistic distribution of the mechanical stresses in the tumor and induces anisotropic tumor growth. Solid stress distribution differs among patients, which, in turn, induces a distinct functional vascular density distribution—owing to the compression of tumor vessels—and intratumoral drug distribution for each patient. In conclusion, incorporating elastography data results in a more accurate calculation of intratumoral mechanical stresses and enables a better mathematical description of subsequent events, such as the heterogeneous development of the tumor vasculature and intrapatient variations in tumor perfusion and delivery of drugs.

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“…84 Svenson et al have shown that abnormal tissue properties were present in regions that appeared normal of conventional MRI. 85 Three studies have investigated the use of MRE in the characterization of glioma, and all found glioblastomas to be softer than gliomas of lower grades. [81][82][83] In a piliot study studying various intracranial tumors, primary brain tumors and cerebral metastases were not distinguishable in terms of jG*j and φ.…”

Section: Mr Elastographymentioning

confidence: 99%

AdvancedMRTechniques for Preoperative Glioma Characterization: Part 2

Hangel

Schmitz-Abecassis

Sollmann

et al. 2023

Magnetic Resonance Imaging

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Decreased tissue stiffness in glioblastoma by MR elastography is associated with increased cerebral blood flow

Cited by 21 publications

References 27 publications

Polymeric micelles effectively reprogram the tumor microenvironment to potentiate nano-immunotherapy in mouse breast cancer models

Polymeric micelles effectively reprogram the tumor microenvironment to potentiate nano-immunotherapy in mouse breast cancer models

Inducing Biomechanical Heterogeneity in Brain Tumor Modeling by MR Elastography: Effects on Tumor Growth, Vascular Density and Delivery of Therapeutics

AdvancedMRTechniques for Preoperative Glioma Characterization: Part 2

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