Gadodiamide

Patients underwent MRI examinations on a 3.0 T MRI system (SIGNA^TM Premier, GE Healthcare, Milwaukee, WI, USA) equipped with a 48-channel head-neck coil. Synthetic MRI was performed by using an axial MDME sequence with the following parameters: TR =4,214 ms, TE1 =21 ms, TE2 =108 ms, FOV =24×18 cm², matrix =320×256, slice thickness =5 mm, spacing =1 mm, slice =20, echo train length =16, bandwidth =22.73 kHz, number of excitations =1, scan time =3 min 39 s. After the first MDME scan, a standard dose of 0.1 mmol/kg contrast agent (Gadodiamide, GE Healthcare, Ireland) was injected at a rate of 4.0 mL/s and then flushed with 20 mL of saline, and the contrast-enhanced MDME acquisition was performed closely after the injection. The scanning parameters of MDME pre- and post-contrast injection were identical.

Scanning was performed using a Siemens 1.5T MRI imaging device (Siemens AG, Munich, Germany). Examination position: The patient was prone on the examination bed with the head entering the scanner first. The upper arms were extended forward to allow the breasts to naturally hang inside the breast coil. Scanning area: The scanning area included both breasts and the axillary region.
Parameters for plain scanning: Row axial fast spin echo (FSE) T1-weighted (repetition time [TR] 600 ms, time to echo [TE] 13 ms, field of view [FOV] 340 mm $\times$ 340 mm), axial T2-weighted (T2W) trim sequence (TR 4,000 ms, TE 61 ms, FOV 340 mm $\times$ 340 mm) and FSE fat-suppressed T2W in the sagittal plane of the affected side (TR 3,500 ms, TE 61 ms, FOV 180 mm $\times$ 180 mm, slice thickness 5 mm, interslice spacing 0.5 mm). The DWI was acquired using the spin echo-echo planar imaging sequence, with a $b$ -value of 0 and 1,000 s/mm².
Parameters for DCE scanning: A high-pressure injector was used to inject gadodiamide (GE HealthCare) at a flow rate of 2.5 ml/s through the elbow vein at a dose of 0.2 ml/kg body weight, followed by an equal amount of normal saline at the same rate. A T1-Flash-3D sequence was performed without a slice gap (TR 4.67 ms, TE 1.66 ms, slice thickness 1.2 mm, FOV 340 mm $\times$ 340 mm). Seven subsequent continuous scans were performed with a duration of 1 min each.

In total, 1 × 10⁶ cells were seeded in 6-well plates overnight and treated with either 1.25 mM Gd-EOB-DTPA (Bayer Pharma, Berlin, Germany) or 1.25 mM gadodiamide (GE Healthcare, Waukesha, WI, USA) for 4 h. Some groups were also treated with 100 μM rifampicin, a competitive inhibitor of OATP1B3. Cells were trypsinized and then washed 3 times with PBS. After the cells were centrifuged at 1200 rpm for 5 min in 0.2 ml tubes at 4°C, they were detected with a clinical 3T-MR system (Signa Excite; GE Healthcare). The cells were centrifuged and placed in a water tank made inhouse. The tank was then placed in an 8-channel head coil. Two-dimensional T1-weighted fast spin–echo pulse sequences were used (TR/TE = 550/13 ms). The slice thickness was 1.0 mm, with a 0.5 mm gap, and the field of view was 14 × 10 cm. Moreover, the matrix size was 288 × 192. The total scan time was 4 min and 5 s at the number of excitations of 2. The images were then analyzed at an Advantage 4.2 workstation provided by GE Healthcare. The images were then analyzed with ImageJ software (NIH) (23 (link)).