The differential diagnosis between the ACTH-producing pituitary adenoma and ectopic ACTH syndrome accompanies with non-functioning pituitary adenoma is problematic in clinical work¹. Thus, It is critical that provide some discriminative evidences between ACTH-producing and pure non-functional pituitary adenoma from the underlying pathophysiology of such diseases. Some kinetic curve-derived quantitative index of dynamic contrast enhancement MRI (DCE-MRI) has been used to assess the pituitary adenoma according to its hormone secretion. However, few studies involved the ACTH-producing pituitary adenoma . Besides, quantitative characterization of tumor’s heterogeneity often ignored. Taken together, this study aims to explore the whole-tumor parameters based on the three-time point (3TP) method of DCE-MRI, which is took the heterogeneity of tumors into account, to quantitatively distinguish the ACTH-producing pituitary adenoma. The local institutional review board approved this study and all the written informed consents were obtained. Subjects: 10 non-functioning and 5 ACTH-producing pituitary adenoma patients with complete endocrine examine and DCE-MRI images were recruited. Among them, 12 were confirmed by the pathology and 3 non-functioning adenomas were diagnosed allied with clinical manifestation. All MRI examinations were performed on GE-HDxt 3.0T scanner with 8-channel head coil. The dynamic T1-weighted fast spin-echo sequence (TR=360ms, TE=minimum, slice thickness=2mm with no gap, FOV=20mm×20mm, matrix=256×160, NEX=2) with the injection of gadolinium (1.0 mmol/kg) was performed coronally. 6-9 slice locations were acquired every 20-23 s. Image analysis: Firstly, according to its enhancement time-signal curve (TIC), each voxel within 3D tumor was grouped to one in three types by a preset threshold of ±10%: washout (type1, < -10%), plateau (type2, -10%~10%) and persistently enhancement (type3, >10%) (see Figure 1A); the volume percentage of each type was then calculated. Second, the enhancement ratios ER1=[S(T2)- S(T1)]/S(T1)×100% and ER2=[S(T3)- S(T2)]/S(T2)×100% were respectively calculated to characterize the rate of change during the early and delay enhancement phase. The parameters were analyzed by Mann-Whitney U test. A p<0.05 was considered to indicate a statistically significant difference. No statistical differences were found between the non-functioning and ACTH-producing group in terms of age, sex and tumor size (Table 1). Significant difference was only found in volume percentage of the type1 ( p=0.027). From the examples of two groups, there was obviously difference in the blue area of scatter plots (Figure 1B, 1C). Taken the wash-in and wash-out phases into consideration, the wash-in phase had no ability to identify these two tumors, but compared with non-functioning group, the ER2 of the type 1 in wash-out phase showed significantly higher in ACTH-producing pituitary adenoma (p=0.049) (Table 2). The functional vascularity of non-functioning pituitary adenoma is different from that of ACTH-producing pituitary adenoma³. Both the expression of vascular endothelial growth factor (VEGF) and the tumor angiogenesis in non-functioning are higher than those in ACTH-producing group^4,5.Most previous studies always focused on the 2D quantification at slice with maximal tumor diameter, rather than 3D whole tumor and thus underestimated the heterogeneity of tumors. Based on the characteristics of whole-tumor, our result indicates that there was no difference between two groups in terms of quantity of the supply artery. As result of highly expressed VEGF in the ACTH-producing pituitary adenoma, the contrast agent washes out more quickly in delay phase, suggesting the increase of vascular permeability, so the descending slope of ACTH-producing adenoma is greater. This may be a more reliable approach to differentiate the two types of pituitary adenomas.The 3TP method of DCE-MRI based on the whole-tumor can help to identify the ACTH-producing from the non-functioning pituitary adenoma, especially in the ectopic ACTH syndrome accompanied with non-functioning pituitary adenoma.