Tumour biomechanical response to the vascular disrupting agent ZD6126 in vivo assessed by magnetic resonance elastography

Li, J.; Jamin, Yann; Boult, Jessica K.R.; Cummings, Craig; Waterton, John C.; Ulloa, Jose L.; Sinkus, Ralph; Bamber, Jeffrey C.; Robinson, Simon P.

doi:10.1038/bjc.2014.76

Cited by 49 publications

(50 citation statements)

References 29 publications

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“…In a more recent study, it has been observed that malignant liver tumors are mainly characterized by increased viscosity [128]. Small animal studies have shown that MR elastography is useful for assessing the early tumor response to vascular disrupting agents and to chemotherapy [129][130][131]. Further human trials are needed to clarify the role of multi-frequency MR elastography in characterizing liver tumors and assessing their response to treatment.…”

Section: Diffuse Liver Diseasesmentioning

confidence: 99%

New imaging techniques for liver diseases

Beers

Daire

Garteiser

2015

Journal of Hepatology

111

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Newly developed or advanced methods of ultrasonography and MR imaging provide combined anatomical and quantitative functional information about diffuse and focal liver diseases. Ultrasound elastography has a central role for staging liver fibrosis and an increasing role in grading portal hypertension; dynamic contrast-enhanced ultrasonography may improve tumor characterization. In clinical practice, MR imaging examinations currently include diffusion-weighted and dynamic MR imaging, enhanced with extracellular or hepatobiliary contrast agents. Moreover, quantitative parameters obtained with diffusion-weighted MR imaging, dynamic contrast-enhanced MR imaging and MR elastography have the potential to characterize further diffuse and focal liver diseases, by adding information about tissue cellularity, perfusion, hepatocyte transport function and visco-elasticity. The multiparametric capability of ultrasonography and more markedly of MR imaging gives the opportunity for high diagnostic performance by combining imaging biomarkers. However, image acquisition and post-processing methods should be further standardized and validated in multicenter trials.

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Section: Diffuse Liver Diseasesmentioning

confidence: 99%

New imaging techniques for liver diseases

Beers

Daire

Garteiser

2015

Journal of Hepatology

111

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“…Histological analysis showed decreased levels of cellular proliferation in chemotherapy treated tumors. Another preclinical study by Li et al [20] evaluated MRE derived stiffness in human colorectal carcinoma cells, which were implanted subcutaneously in the flanks of genetically modified mice. MRE was performed before and 24h after treatment with either the vascular disrupting agent ZD6126 (N-acetylcolchinol-O-phosphate) or vehicle control.…”

Section: Discussionmentioning

confidence: 99%

“…These results suggest that change in TS may antecede actual cell death as indicated by histology, and that decreasing cellularity may contribute to the change in tissue mechanical properties [20]. This would potentially allow us to use stiffness as a biomarker of treatment response and also to longitudinally monitor treatment response throughout the course of therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the performance of MRE as marker of tumor response was evaluated in two animal studies following chemotherapy. In these studies, reduction in tumor stiffness (TS) was associated with histologically proven central necrosis [20] and decreased cellular proliferation and moderate induction of apoptosis [21]. This suggests that changes in tumor mechanical properties, as changes in interstitial pressures, cellularity, and extracellular components, visualized by MRE may provide early evidence of therapeutic response.…”

Section: Introductionmentioning

confidence: 99%

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Value of tumor stiffness measured with MR elastography for assessment of response of hepatocellular carcinoma to locoregional therapy

et al. 2017

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Purpose To correlate tumor stiffness (TS) measured with MR elastography (MRE) with degree of tumor enhancement and necrosis on contrast-enhanced T1-weighted imaging (CE-T1WI) in hepatocellular carcinomas (HCC) treated with 90Yttrium radioembolization (RE) or transarterial chemoembolization plus radiofrequency ablation (TACE/RFA). Material and Methods This retrospective study was IRB-approved and the requirement for informed consent was waived. 52 patients (M/F 38/14, mean age 67 y) with HCC who underwent RE (n=22) or TACE/RFA (n=30) and 11 controls (M/F 6/5, mean age 64 y) with newly diagnosed untreated HCC were included. The MRI protocol included a 2D MRE sequence. TS and LS (liver stiffness) were measured on stiffness maps. Degree of tumor necrosis was assessed on subtraction images by two observers, and tumor enhancement ratios (ER) were calculated on CE-T1WI by one observer. Results 63 HCCs (mean size 3.2 ± 1.6 cm) were evaluated. TS was significantly lower in treated vs. untreated tumors (3.9 ± 1.8 vs. 6.9 ± 3.4 kPa, p=0.006) and also compared to LS (5.3 ± 2.2 kPa, p=0.002). There were significant correlations between TS and each of enhancement ratios (r=0.514, p=0.0001), and percentage of necrosis (r= -0.540, p=0.0001). The observed correlations were stronger in patients treated with RE (TS vs. ER, r=0.636, TS vs. necrosis, r= -0.711, both p=0.0001). Percentage of necrosis and T1-signal in native T1WI were significant independent predictors of TS (p=0.0001 and 0.001, respectively). Conclusion TS measured with MRE shows a significant correlation with tumor enhancement and necrosis, especially in HCCs treated with RE.

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“…27 Investigations of therapy-induced changes in tumor stiffness have continued in the preclinical setting, where Li et al found a significant decrease in bulk stiffness as assessed by magnetic resonance (MR) elastography 24 h after administration of a vascular disrupting agent in a murine model of breast cancer. 28 Interestingly, elasticity was seen to exhibit significant changes at this early imaging time point while another quantitative imaging biomarker, the apparent diffusion coefficient from diffusion-weighted MR imaging, did not. Pepin et al have also used MR elastography to assess therapy-induced changes in tumor stiffness and have shown a significant decrease in stiffness in response to cytotoxic therapy in a murine lymphoma xenograft model.…”

Section: Introductionmentioning

confidence: 92%

Assessing the accuracy and reproducibility of modality independent elastography in a murine model of breast cancer

et al. 2015

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Abstract. Cancer progression has been linked to mechanics. Therefore, there has been recent interest in developing noninvasive imaging tools for cancer assessment that are sensitive to changes in tissue mechanical properties. We have developed one such method, modality independent elastography (MIE), that estimates the relative elastic properties of tissue by fitting anatomical image volumes acquired before and after the application of compression to biomechanical models. The aim of this study was to assess the accuracy and reproducibility of the method using phantoms and a murine breast cancer model. Magnetic resonance imaging data were acquired, and the MIE method was used to estimate relative volumetric stiffness. Accuracy was assessed using phantom data by comparing to gold-standard mechanical testing of elasticity ratios. Validation error was <12%. Reproducibility analysis was performed on animal data, and within-subject coefficients of variation ranged from 2 to 13% at the bulk level and 32% at the voxel level. To our knowledge, this is the first study to assess the reproducibility of an elasticity imaging metric in a preclinical cancer model. Our results suggest that the MIE method can reproducibly generate accurate estimates of the relative mechanical stiffness and provide guidance on the degree of change needed in order to declare biological changes rather than experimental error in future therapeutic studies.

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Tumour biomechanical response to the vascular disrupting agent ZD6126 in vivo assessed by magnetic resonance elastography

Cited by 49 publications

References 29 publications

New imaging techniques for liver diseases

New imaging techniques for liver diseases

Value of tumor stiffness measured with MR elastography for assessment of response of hepatocellular carcinoma to locoregional therapy

Assessing the accuracy and reproducibility of modality independent elastography in a murine model of breast cancer

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