Yong-Lan He1, Yuan Li1, Cheng-Yu Lin1, Ya-Fei Qi1, Xiaoqi Wang2, Hai-Long Zhou1, Hua-Dan Xue1, and Zheng-Yu Jin1
1Peking Union Medical College Hospital, Beijing, China, 2Philips Healthcare China, Beijing, China
Synopsis
This study demonstrates the first attempt of 3D TSE APTw MR imaging for endometrial carcinoma with excellent inter-observer measurement agreement. APT values on 22 type I endometrial carcinoma lesions were moderately positively correlated with Ki-67 labelling index (r = 0.583, p=0.004). APT values of Ki-67 low-proliferation group were significantly lower than high-proliferation group (p=0.016) with AUC 0.768. However, no correlation was found between IVIM-derived parameters and Ki-67 labeling index (Dt, p=0.717; D* p=0.151; f, p=0.153).
INTRODUCTION
Endometrial
carcinoma (EC) is the most prevalent gynecologic malignancy in developed
countries, with increasing incidence and mortality.1 Identifying
reliable imaging and histopathological markers to improve diagnostic accuracy
and prognosis is important in therapy strategy. 2 The Ki-67
proliferation index reflects the status of the proliferative activity in tumor
tissue and is used to predict the clinical recurrence and outcomes of
endometrial carcinoma. 3 Intravoxel incoherent motion (IVIM) imaging
could reflect EC with distinctive perfusion and diffusion characteristics, depending
on tumor vascularity and cellularity.4 Amide Proton Transfer (APT)
MR imaging is a new contrast-agent-free MRI technique that addresses the need
for a more confident diagnosis in oncology.5 In 2018, Yukihisa et al
reported the first use of 2-Dimensional APTw imaging on endometrial carcinoma,
APT signal intensity was positively correlated with the histologic grades of
EEA.6 The purpose of our study was to evaluate the feasibility of
3-Dimensional (3D) APTw and IVIM imaging for type I endometrial carcinoma
diagnosis, and the correlation with Ki-67 labelling index.METHODS
This prospective
study was approved by the institutional review board and informed consent were obtained.
Between January 2018 and December 2018, 54 consecutive patients suspected of
endometrial lesions underwent APTw and IVIM (b values 0, 10, 20, 50, 100, 200,
400 and 800) imaging on a 3T MR scanner (Ingenia 3.0T CX; Philips Healthcare,
Best, the Netherlands) equipped with dual radiofrequency (RF) transmission
subsystem. 3D turbo spin echo (TSE) sequence was used to acquire APT images,
and the APT values were calculated based on asymmetry of z-spectrum, in which saturation
RF’s with duration of 2s were applied at ±3.5 ppm with water frequency set at 0 ppm. B0 field maps, generated
by the build-in mDIXION TSE sequence, were used for APT calculation correction.
The diffusion images for IVIM were acquired with EPI sequence and with fat
saturation pulses applied. Least square fitting algorithm was used to calculate
the bi-exponential parameters (Dt, D*, f) for IVIM. Images were independently
measured by two radiologists on 22 postoperative pathological confirmed of type
I endometrial carcinoma lesions with Ki-67 labelling index as well as
IVIM-derived parameters. Inter-observer inter-class correlation coefficient
(ICC) was computed. Student's t-test and Mann-Whitney U test were used to
compare the differences of APT values and IVIM-derived parameters between
different histological grades and Ki-67 proliferation groups. Receiver
operating characteristic analysis was performed to computationally determine
the feasible threshold value, sensitivity and specificity. Pearson’s
correlation analysis was performed between the APT values, IVIM-derived
parameters and Ki-67 labeling index.RESULTS
The APT values (in
unit of percentage) and Dt, D*, f of all type I endometrial carcinoma were 2.865
± 0.129, 0.677 ± 0.027 x 10-3mm2/s, 31.801 ± 11.492 x 10-3mm2/s,
0.179 ± 0.050 with inter-observer ICC 0.996 (95%CI 0.989-0.998), 0.850 (95%CI
0.611-0.942), 0.956 (95%CI 0.885-0.983), 0.995 (95%CI 0.988-0.998) respectively.
APT values of Ki-67 low-proliferation group (<30%, n=8) were 2.466 ± 0.191,
significantly lower than high-proliferation group (>30%, n=14) with APT
values of 3.093 ± 0.142 (p=0.016) (Figure 1, 2). Area under the curve was
0.768. The feasible threshold value was determined as 2.595 with a sensitivity
of 92.9% and specificity of 75%. The APT values of type I endometrial carcinoma
were moderately positively correlated with Ki- 67 labeling index (r = 0.583,
p=0.004). There were no significant difference of Dt (p=0.843), D* (p=0.262), f
(p=0.553) between low-proliferation group and high-proliferation group. No
correlation was found between IVIM-derived parameters and Ki-67 labeling index
(Dt, p=0.717; D* p=0.151; f, p=0.153).DISCUSSION
The present study
demonstrates the first attempt of 3D TSE APTw MR imaging for endometrial
carcinoma with excellent inter-observer measurement agreement. Our study
revealed that the APT values were positively correlated with Ki-67 labelling
index, which is consistent with the results of APTw imaging of brain tumors
including gliomas and meningioma.7,8 Compared with the previous 2D
APT sequence,6 3D spin-echo APT sequence on uterus allowed to cover
the whole volume of the tumor during scanning and select the precise slice
showing the maximum area during the measuring. In this study, the saturation RF
pulses of the APT sequence was maintained for two seconds by interleaving two
RF transmitters, and the resulting APTw signal value corresponds to this
particular B1 setting (labelling time and strength).CONCLUSION
3D TSE APTw imaging is feasible in type I
endometrial carcinoma. APT values positively moderately correlates with Ki-67
proliferation status. However, no correlation was found between IVIM-derived
parameters and Ki-67 labeling index.Acknowledgements
NONEReferences
1. Ferlay J,
Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide:
sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359-386.
2. Murali R, Delair DF, Bean SM, et al. Evolving
Roles of Histologic Evaluation and Molecular/Genomic Profiling in the
Management of Endometrial Cancer. J Natl Compr Canc Netw. 2018;16(2):201-209.
3. Gulseren V, Kocaer M, Ozdemir IA, et al. Do
estrogen, progesterone, P53 and Ki67 receptor ratios determined from curettage
materials in endometrioid-type endometrial carcinoma predict lymph node
metastasis? Curr Probl Cancer. 2019;10.1016.
4. Liu J, Wan Y, Wang Z, et al. Perfusion and
diffusion characteristics of endometrial malignancy based on intravoxel
incoherent motion MRI at 3.0 T: comparison with normal endometrium. Acta Radiol. 2016;57(9):1140-1148.
5. Kamimura K, Nakajo M, Yoneyama T, et al. Amide
proton transfer imaging of tumors: theory, clinical applications, pitfalls, and
future directions. Jpn J Radiol. 2019;37(2):109-116.
6. Takayama Y,
Nishie A, Togao O, et al. Amide Proton Transfer MR Imaging of Endometrioid
Endometrial Adenocarcinoma: Association with Histologic Grade. Radiology. 2018;286(3):909-917.
7. Suh CH, Park JE, Jung SC, et al. Amide proton
transfer-weighted MRI in distinguishing high- and low-grade gliomas: a
systematic review and meta-analysis. Neuroradiology. 2019;61(5):525-534.
8. Yu H, Wen X, Wu
P, et al. Can amide proton transfer-weighted imaging differentiate tumor grade
and predict Ki-67 proliferation status of meningioma? Eur Radiol. 2019;29(10):5298-5306.