A waiver of consent for retrospective analysis of imaging data was granted by the local institutional review board because of the anonymous nature of this study. Thirty-five consecutive female patients (mean age, 48.4 years; age range, 41–67 years) with clinical symptoms of cervical cancer (e.g vaginal bleeding, abnormal discharge or pelvic pain) were presented to our department between March 2016 and September 2017. Our diagnostic protocol for patients suspected with cervix cancer included both cervical biopsy and MRI examination. Among the 35 consecutive patients, biopsies of 24 patients revealed the presence of cervix cancer cells, while cancer cells were not found in the biopsies of 11 subjects. For these 11 subjects with negative biopsies, their MRI examinations also did not reveal any suspicious mass or lesion, and therefore, their MRI data were considered as part of the normal tissue dataset. However, MRI data of one subject with negative biopsy and one patient with positive biopsy were excluded because of significant motion artifacts. Furthermore, 3 patients with positive biopsy were excluded because no obvious mass or lesion could be identified on MRI (i.e lesions could be too small) and a region-of-interest (ROI) for cancer cannot be identified on the MR images. Consequently, only MRI data of 20 patients with positive biopsy and 10 subjects with negative biopsy were processed in this study. Twenty ROIs for cervical cancer were obtained from the 20 patients with positive biopsy (i.e one ROI for each patient). Only 10 ROIs for normal-appearing tissue can be identified among the 20 patients with positive biopsy (because some tumors were too extensive and obscured the outline of normal-appearing tissue), while another 10 ROIs for normal tissue were obtained from the 10 subjects with negative biopsy (one ROI for each subject). Cervix cancer was clinically staged according to the International Federation of Gynecology and Obstetrics classifications. The 20 patients with positive biopsy were classified into stage Ib (n=8), IIa (n=6) and IIb (n=6). All patients were confirmed histopathologically and hysterectomy was performed for patients with cervix cancer.

MR imaging was performed on a 3.0 T scanner (Discovery™ MR750w, General Electric, USA) using an 8-channel torso phased-array coil. Routine clinical MRI sequences included a transverse fast spin-echo T1-weighted sequence (repetition time/echo time = 550~700/7~10 ms; field of view = 320 × 320 mm; matrix size = 512 × 512; slice thickness = 5.0 mm; intersection gap = 6 mm), and a short time inversion recovery (STIR) T2-weighted sequence (repetition time/echo time = 3000~4000/70~80 ms; field of view = 256~320 × 256~320 mm; matrix size = 512 × 512; slice thickness = 5.0 mm; intersection gap = 6~7 mm). Late contrast-enhanced T1-weighted (repetition time/echo time = 4/2 ms, flip angle = 13°, field of view = 280 × 280 mm, matrix size 512 × 512, slice thickness = 3 mm) images were acquired in the sagittal plane about 5 min after contrast administration.

Before administration of contrast agent, diffusion-weighted imaging (DWI) was performed using a single-shot spin-echo echo-planar imaging sequence in the axial plane with the following parameters: repetition time/echo time = 2400/74 ms, field of view = 360 × 360 mm, matrix size = 256 × 256 mm, number of slices = 10, slice thickness = 5.0 mm, intersection gap = 5 mm, number of averages=3. DWI data was acquired as trace-weighted images using 3 orthogonal-direction diffusion gradients, with parallel imaging (ASSET, acceleration factor = 2) to reduce possible imaging artifacts due to movement and eddy-currents. We acquired 6 b-values as follows: 0, 30, 100, 200, 400, 1000 s/mm2. These b-values were selected based on considerations for the prudent use of imaging time and the minimal requirements for estimation of IVIM parameters (i.e at least 2 b-values more than 200 s/mm2 for estimation of D, and at least 2 b-values less than 100 s/mm2 to adequately depict the initial rapid decrease). The total scan time for DWI was approximately 2.36 min. These aspects of the relative dominance of D and D* on opposite extremes of b-values is also related to the assumption of negligible water exchange between blood and tissue in the IVIM model (see Discussion on limitations of standard Gaussian and non-Gaussian IVIM).

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