Intera

We performed MR imaging experiment of MnO nanocubes solution with a 3.0 T clinical MRI scanner with a micro-47 surface coil (Intera; Philips Medical Systems, Best, the Netherlands). The R1 relaxivity of various concentrations of MnO nanocubes was measured by the Carr–Purcell–Meiboom–Gill (CPMG) sequence at room temperature with the following parameters: echo time (TE) = 60 ms, repetition time (TR) = 4000 ms, slice thickness = 2.0 mm, number of acquisitions = 1, and point resolution = 234 × 234 μm². The relaxivity values of R1 were calculated by a series of T1 values, when plotted as 1/T1 versus [Mn]. The relaxivity coefficient (mM⁻¹ s⁻¹) was equal to the ratio of R1 (1/T1, s⁻¹) and the nanoparticle concentration. In vitro/in vivo MRI experiments were performed using a 3.0 T clinical MRI instrument equipped with a micro-47 surface coil (Intera; Philips Medical Systems, Best, Netherlands). To acquire cellular T1-weighted MR images, following parameters were adopted: resolution = 234 × 234 mm, section thickness = 3.0 mm, TE = 18 ms, TR = 625 ms, and number of acquisitions = 2. For T1-weighted MR images of the nude mice, the following parameters were adopted: resolution = 234 × 234 mm, section thickness = 2.0 mm, TE = 60 ms, TR = 4000 ms, and number of acquisitions = 1.

All scans were conducted for clinical indications. The MRI acquisitions were performed on diverse scanners from referring institutions (n = 37; 1.0, 1.5, 3.0 T; (1) Siemens MRI models: Avanto, Espree, Aera, Verio, Essenza (Siemens, Erlangen, Germany), (2) Toshiba Titan (Toshiba, Tokio, Japan) and (3) Philips MRI models: Panorama, Intera, Achieva, Ingenia (Philips Healthcare, Best, The Netherlands) and on local scanners from the University Hospital of Cologne [n = 19, Philips models: Achieva, Ingenia, Intera; 1.5 and 3.0 T (Philips Healthcare, Best, The Netherlands)]. MRI scan parameters are given in Supplementary Table S1. At the University Hospital of Cologne, for T1CE MR images patients were injected intravenously with gadolinium (Dotarem; Guerbet, Roissy, France: 0.5 mmol/ml, i.e. 1 ml = 279.32 mg gadoteric acid = 78.6 mg gadolinium) with a concentration of 0.1 mmol/kg body weight. The contrast medium applications in the referring institutions were not standardised.

We performed the MR imaging experiment of a PEGylated MN solution with a 1.5 T clinical MRI instrument with a micro47 surface coil (Intera; Philips Medical Systems, Best, the Netherlands). The T2 weights of various concentrations of PEGylated MN solution were measured by the Carr–Purcell–Meiboom–Gill (CPMG) sequence at room temperature with the following parameters: TR = 10 s, 32 echoes with a 12-ms even echo space, number of acquisitions = 1, point resolution of 156 × 156 mm, and section thickness of 0.6 mm. The relaxivity coefficient (mM⁻¹ s⁻¹) was equal to the ratio of R2 (1/T2, S⁻¹) to the PEGylated MN concentration. In addition, in vivo MR imaging experiments were performed with a 3 T clinical MRI instrument with a micro-47 surface coil (Intera; Philips Medical Systems, Best, the Netherlands). The T2 weights of a nude mouse injected with PEGylated MNs were measured by the CPMG sequence at room temperature with the following parameters: TR = 10 s, 32 echoes with a 12-ms even echo space, number of acquisitions = 1, point resolution of 156 × 156 mm, and section thickness of 0.6 mm. For the T2-weighted MR imaging of the nude mouse model, we adopted the following parameters: resolution of 234 × 234 mm, section thickness of 2.0 mm, TE = 60 ms, TR = 4000 ms, and number of acquisitions = 1.