**4. Discussion**

#### **4.1 Endometrial cancer characteristics of DCE-MRI**

Currently, staging of uterine lesions is often determined based on the findings of multiphase enhanced MRI in clinic, however, the selection of the enhanced phases is controversial【8】. DCE-MRI is a dynamic MR technology, focusing on the enhancement behaviors at different time points and reflecting the characteristics of tumor blood supply【9】 . Therefore, the tumor blood vessels can be quantified to a certain extent, which makes it possible to study the microvascular characteristics non-invasively.

It has been reported【5】that a mild thin-like enhancement can be observed in the thin layer of tissue between endometrium and myometrium in the early phase of DCE-MRI, which is called subendometrial enhancement (SEE). Similarly, because of the difference in blood supply between tumor and myometrial tissue, the signal enhancement in tumors is significantly lower than that in normal tissue, which leads to increased contrast between tumor and myometrium. Until to the delayed phase, the tumor enhancement is increasing, but the intensity in tumor is still lower than that in myometrium. The maximum signal difference between tumor and myometrium can be observed at certain time, at which the tumor size and margin can be seen clearly and accurate estimation of the invasion depth to myometrium can be made. In the present study, all 24 endometrial tumors were enhanced on DCE-MRI. The enhancement degree in 17 tumors was lower than that in the normal tissue in the early phase, which was consistent with the literature. The remaining 7 tumors showed significantly stronger enhancement than the normal tissues, and of the tumors, 3 were poorly differentiated adenocarcinoma, 1 was clear cell carcinoma, and 1 was serous carcinoma. These results suggest that the enhancement degree may be associated with the degree of malignancy as more abundant blood supply in higher malignant tumors. Only 1 tumor showed decreased contrast enhancement in the delayed phase, which was inconsistent with the report in the literature. The maximum signal intensity in the delayed phase was lower in the tumors than in the adjacent normal tissue, but the signal intensity difference between tumors and normal tissues was higher in the delayed phase than in the early phase, consistent with the previous reports【10-11】, indicating that the delayed phase (300 s) was more favorable to delineate the lesions on DCE-MRI.

#### **4.2 Quantitative evaluation of enhancement and TIC curves**

Enhanced patterns of tumors reflect the trend of enhancement, however there is no quantitative criterion for the enhancement evaluation. In recent years, many investigators measured the degree of the lesion enhancement with ARSI%, MRSI%, SER%, and other indicators, in addition to the detection sensitivity, noise, etc. These indicators reflect the degree of tumor angiogenesis and the status of blood supply. ARSI% reflects the relative degree of enhancement in the early phase, MRSI% reflects the maximum degree of enhancement, and SER% reflects the relative degree of enhancement in the delayed phase.

Our study showed that the mean value of ARSI% was significantly higher in poorly differentiated tumors than in well differentiated tumors, which was consistent with the findings by Yamashit et al.【12】who showed that the poorer the tumor differentiation was, the richer blood supply in the early phase there was. They also showed that ARSI% could be used to evaluate the prognosis to a certain extent. Bronow et al. found【1】 that the metastasis probabilities in the pelvic and para-aortic lymph nodes were 2.5% and 1.2%, respectively, if the tumor limited in the endometrium, while those probabilities were 46.4% and 28.5%, respectively, if tumors had deep myometrial invasion. Therefore, precise evaluation of the depth of myometrial invasion is critical for the clinical treatment selection and prognosis prediction. In our study, the ARSI% in deep myometrial invasion group was higher than in the no/superficial myometrial invasion group. The mean value of SER% in postmenopausal group was higher than in non-menopausal group, which may be due to the reasons of uterine atrophy, increased fiber content, and a larger extracellular space in postmenopausal women. Patients diagnosed with cervical involvement should expand the scope of operation, or take surgery after the radiotherapy. Seki et al.【5】 used DCE sequences in the detection of cervical involvement and they showed diagnostic accuracy of 95%, higher than 85% obtained on T2WI. Our study showed that the mean value of ARSI% in cervical involvement group was higher than in the unaffected group, but the difference was not significant. Further study is necessary in a large sample of tumors.

Regarding the TIC curves of the 24 endometrial cancers, 18 (18/24) were types I and II with an early peak and16 (16/24) were types I and III with ARSI% ≥ 60% and an early enhancement. All these endometrial cancers were those with rich blood supply.

In short, the signal enhancement of endometrial cancers in different phases of DCE-MRI can be quantitatively measured, which reflects the status of the tumor's blood supply, and indirectly provides information on their biology. The data in the early and delayed phases of DCE-MRI could provide more relevant information for prognosis prediction and tumor stage determination.

#### **5. References**

74 Cancer of the Uterine Endometrium – Advances and Controversies

Currently, staging of uterine lesions is often determined based on the findings of multiphase enhanced MRI in clinic, however, the selection of the enhanced phases is controversial【8】. DCE-MRI is a dynamic MR technology, focusing on the enhancement behaviors at different time points and reflecting the characteristics of tumor blood

It has been reported【5】that a mild thin-like enhancement can be observed in the thin layer of tissue between endometrium and myometrium in the early phase of DCE-MRI, which is called subendometrial enhancement (SEE). Similarly, because of the difference in blood supply between tumor and myometrial tissue, the signal enhancement in tumors is significantly lower than that in normal tissue, which leads to increased contrast between tumor and myometrium. Until to the delayed phase, the tumor enhancement is increasing, but the intensity in tumor is still lower than that in myometrium. The maximum signal difference between tumor and myometrium can be observed at certain time, at which the tumor size and margin can be seen clearly and accurate estimation of the invasion depth to myometrium can be made. In the present study, all 24 endometrial tumors were enhanced on DCE-MRI. The enhancement degree in 17 tumors was lower than that in the normal tissue in the early phase, which was consistent with the literature. The remaining 7 tumors showed significantly stronger enhancement than the normal tissues, and of the tumors, 3 were poorly differentiated adenocarcinoma, 1 was clear cell carcinoma, and 1 was serous carcinoma. These results suggest that the enhancement degree may be associated with the degree of malignancy as more abundant blood supply in higher malignant tumors. Only 1 tumor showed decreased contrast enhancement in the delayed phase, which was inconsistent with the report in the literature. The maximum signal intensity in the delayed phase was lower in the tumors than in the adjacent normal tissue, but the signal intensity difference between tumors and normal tissues was higher in the delayed phase than in the early phase, consistent with the previous reports【10-11】, indicating that the delayed phase

Enhanced patterns of tumors reflect the trend of enhancement, however there is no quantitative criterion for the enhancement evaluation. In recent years, many investigators measured the degree of the lesion enhancement with ARSI%, MRSI%, SER%, and other indicators, in addition to the detection sensitivity, noise, etc. These indicators reflect the degree of tumor angiogenesis and the status of blood supply. ARSI% reflects the relative degree of enhancement in the early phase, MRSI% reflects the maximum degree of enhancement, and SER% reflects the relative degree of enhancement in the delayed phase. Our study showed that the mean value of ARSI% was significantly higher in poorly differentiated tumors than in well differentiated tumors, which was consistent with the findings by Yamashit et al.【12】who showed that the poorer the tumor differentiation was, the richer blood supply in the early phase there was. They also showed that ARSI% could be

probabilities in the pelvic and para-aortic lymph nodes were 2.5% and 1.2%, respectively, if

that the metastasis

makes it possible to study the microvascular characteristics non-invasively.

(300 s) was more favorable to delineate the lesions on DCE-MRI.

**4.2 Quantitative evaluation of enhancement and TIC curves** 

used to evaluate the prognosis to a certain extent. Bronow et al. found【1】

. Therefore, the tumor blood vessels can be quantified to a certain extent, which

**4. Discussion** 

supply【9】

**4.1 Endometrial cancer characteristics of DCE-MRI** 

