Feasibility and utility of MRI and dynamic 18F-FDG-PET in an orthotopic organoid-based patient-derived mouse model of endometrial cancer

Espedal, Heidi; Berg, Hege Fredriksen; Fonnes, Tina; Fasmer, Kristine Eldevik; Krakstad, Camilla; Haldorsen, Ingfrid Salvesen

doi:10.1186/s12967-021-03086-9

Cited by 9 publications

(5 citation statements)

References 41 publications

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“…In the past, the traditional MRI technique could compare the signal of myometrium with the signal of endometrium and analyze. However, the accuracy of overall clinical judgment was not satisfactory [8,9]. Therefore, with the continuous maturity and progress of MRI technology, the use of enhanced methods can improve the clinical diagnostic efficacy.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the diagnostic efficacy of DWI and DCE-MRI in depth of myometrial invasion, cervical invasion and FIGO staging in patients with endometrial cancer

2024

EJGO

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This study aims to compare the diagnostic efficacy of DWI (Diffusion Weighted Imaging) and DCE-MRI (Dynamic Contrast Enhancement-Magnetic Resonance Imaging) in the depth of myometrial invasion, cervical invasion and FIGO (Federation International of Gynecology and Obstetrics) staging in patients with endometrial cancer. 128 patients were selected for preoperative diagnosis with DWI and DCE-MRI techniques. The diagnostic efficacy of the two diagnostic methods on the depth of myometrial invasion, cervical invasion and FIGO staging was compared. Receiver operating characteristic curves were plotted for the two diagnostic methods to further compare the differences between the two diagnostic methods. The accuracy, sensitivity, positive predictive value and negative predictive value of DWI were conspicuously higher than that of DCE-MRI in the diagnosis of depth of myometrial invasion and cervical invasion (p < 0.05). ROC (Receiver Operating Characteristic Curve) analysis demonstrated that the diagnostic effect of DWI was better than that of DCE-MRI in the diagnosis of depth of myometrial invasion and cervical invasion, and the difference in the area under the curve between the two diagnostic methods was statistically significant (p < 0.05). In terms of FIGO staging diagnosis, the accuracy of DWI was 86.72%, which was higher than 65.63% of DCE-MRI (χ 2 = 15.689, p < 0.001). For patients with endometrial cancer, preoperative depth of myometrial invasion, cervical invasion and FIGO staging have critical guiding significance for clinical diagnosis and treatment. Compared with DCE-MRI, DWI has better diagnostic efficacy for depth of myometrial invasion, cervical invasion and FIGO staging, which is worthy of clinical application. Keywords DWI; DCE-MRI; Endometrial cancer; Depth of myometrial invasion; Cervical invasion; FIGO stagingHow to cite this article: Cheng Zhou, Gang Wang, Cheng Che. Comparison of the diagnostic efficacy of DWI and DCE-MRI in depth of myometrial invasion, cervical invasion and FIGO staging in patients with endometrial cancer. European

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Section: Discussionmentioning

confidence: 99%

Comparison of the diagnostic efficacy of DWI and DCE-MRI in depth of myometrial invasion, cervical invasion and FIGO staging in patients with endometrial cancer

2024

EJGO

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“…The T2w images were acquired coronally with TE/TR 25/2500 ms, 5 averages, 160x160 matrix, 32x32 mm field of view, 1 mm slice thickness and 0.2x0.2 mm resolution. Choice of MRI sequence was based on previous finding ( 24 ), showcasing T2w-imaging as a robust MRI method for tumor visualization and tumor delineation in orthotopic endometrial cancer models. We did not include any T1-weighted sequences due to intravenous contrast agent toxicity in mice, especially considering the significant number of imaging time points in the study.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, an organoid-based patient-derived xenograft mouse models (O-PDX) that recapitulate the histopathology- and genetic profiles of the donor tumor tissue has been developed ( 23 ). Furthermore, clinically relevant imaging methods including preclinical MRI to quantify tumor progression and assess treatment response in these models as been established ( 24 ). The development of non-invasive tools for early detection of treatment response is essential for rapid adaptation of treatment strategies in non-responding endometrial cancer patients.…”

Section: Introductionmentioning

confidence: 99%

MRI radiomics captures early treatment response in patient-derived organoid endometrial cancer mouse models

Espedal,

Fasmer,

Berg

et al. 2024

Front. Oncol.

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BackgroundRadiomics can capture microscale information in medical images beyond what is visible to the naked human eye. Using a clinically relevant mouse model for endometrial cancer, the objective of this study was to develop and validate a radiomic signature (RS) predicting response to standard chemotherapy.MethodsMice orthotopically implanted with a patient-derived grade 3 endometrioid endometrial cancer organoid model (O-PDX) were allocated to chemotherapy (combined paclitaxel/carboplatin, n=11) or saline/control (n=13). During tumor progression, the mice underwent weekly T2-weighted (T2w) magnetic resonance imaging (MRI). Segmentation of primary tumor volume (vMRI) allowed extraction of radiomic features from whole-volume tumor masks. A radiomic model for predicting treatment response was derived employing least absolute shrinkage and selection operator (LASSO) statistics at endpoint images in the orthotopic O-PDX (RS_O), and subsequently applied on the earlier study timepoints (RS_O at baseline, and week 1-3). For external validation, the radiomic model was tested in a separate T2w-MRI dataset on segmented whole-volume subcutaneous tumors (RS_S) from the same O-PDX model, imaged at three timepoints (baseline, day 3 and day 10/endpoint) after start of chemotherapy (n=8 tumors) or saline/control (n=8 tumors).ResultsThe RS_O yielded rapidly increasing area under the receiver operating characteristic (ROC) curves (AUCs) for predicting treatment response from baseline until endpoint; AUC=0.38 (baseline); 0.80 (week 1), 0.85 (week 2), 0.96 (week 3) and 1.0 (endpoint). In comparison, vMRI yielded AUCs of 0.37 (baseline); 0.69 (w1); 0.83 (week 2); 0.92 (week 3) and 0.97 (endpoint). When tested in the external validation dataset, RS_S yielded high accuracy for predicting treatment response at day10/endpoint (AUC=0.85) and tended to yield higher AUC than vMRI (AUC=0.78, p=0.18). Neither RS_S nor vMRI predicted response at day 3 in the external validation set (AUC=0.56 for both).ConclusionsWe have developed and validated a radiomic signature that was able to capture chemotherapeutic treatment response both in an O-PDX and in a subcutaneous endometrial cancer mouse model. This study supports the promising role of preclinical imaging including radiomic tumor profiling to assess early treatment response in endometrial cancer models.

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“…Furthermore, rate constants were calculated for K1, k2, k3, and macro parameters MRGlu and Flux derived. The image derived input function (idIF) was segmented from the inferior vena cava as it provides a robust estimation of the idIF ( 28 ) with special regard to the spill-in contamination from neighboring tissue when using the heart ( 29 ).…”

Section: Methodsmentioning

confidence: 99%

4-nitroquinoline 1-oxide-induced oral epithelial lesions exhibit time- and stage-dependent changes in the tumor immune microenvironment

Sellæg,

Schwienbacher,

Kranz

et al. 2024

Front. Oncol.

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Oral tongue squamous cell carcinoma (OTSCC) is the most common cancer of the oral cavity and is associated with high morbidity due to local invasion and lymph node metastasis. Tumor infiltrating lymphocytes (TILs) are associated with good prognosis in oral cancer patients and dictate response to treatment. Ectopic sites for immune activation in tumors, known as tertiary lymphoid structures (TLS), and tumor-associated high-endothelial venules (TA-HEVs), which are specialized lymphocyte recruiting vessels, are associated with a favorable prognosis in OSCC. Why only some tumors support the development of TLS and HEVs is poorly understood. In the current study we explored the infiltration of lymphocyte subsets and the development of TLS and HEVs in oral epithelial lesions using the 4-nitroquinoline 1-oxide (4NQO)-induced mouse model of oral carcinogenesis. We found that the immune response to 4NQO-induced oral epithelial lesions was dominated by T cell subsets. The number of T cells (CD4+, FoxP3+, and CD8+), B cells (B220+) and PNAd+ HEVs increased from the earliest to the latest endpoints. All the immune markers increased with the severity of the dysplasia, while the number of HEVs and B cells further increased in SCCs. HEVs were present already in early-stage lesions, while TLS did not develop at any timepoint. This suggests that the 4NQO model is applicable to study the dynamics of the tumor immune microenvironment at early phases of oral cancer development, including the regulation of TA-HEVs in OTSCC.

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Feasibility and utility of MRI and dynamic 18F-FDG-PET in an orthotopic organoid-based patient-derived mouse model of endometrial cancer

Cited by 9 publications

References 41 publications

Comparison of the diagnostic efficacy of DWI and DCE-MRI in depth of myometrial invasion, cervical invasion and FIGO staging in patients with endometrial cancer

Comparison of the diagnostic efficacy of DWI and DCE-MRI in depth of myometrial invasion, cervical invasion and FIGO staging in patients with endometrial cancer

MRI radiomics captures early treatment response in patient-derived organoid endometrial cancer mouse models

4-nitroquinoline 1-oxide-induced oral epithelial lesions exhibit time- and stage-dependent changes in the tumor immune microenvironment

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