Animal experiments

All animal studies were approved by the State Office of Health and Social Affairs Berlin (LAGESO/A0409/12) and were carried out in accordance with institutional and federal animal care guidelines. Overall, 16 in vivo examinations were carried out on 8 healthy male Sprague Dawley rats (Charles River Laboratories, Sulzfeld, Germany), 7 weeks old and had an average body weight of 259 ± 19 g. Prior to MPI scan, rats were anesthetized in an anaesthetic induction chamber with 5% isoflurane and maintained in 1–2% isoflurane during MPI acquisitions. Each rat was imaged twice, once with MCP 3 and once with Resovist. The order of MNP type administration was random. Identical doses of MCP 3 and Resovist were successively administered intravenously (Fig. 6) with sufficient time between the examinations for clearance of the MNP from the blood (at least 1 h), when no signal modulation was detected prior to the MPI scans, as seen in raw data on the baseline signal (Fig. 5). The concentrations of the stock solutions were 145.5 mmol Fe/l for MCP 3 and 500 mmol Fe/l for Resovist, and the final administered doses were 0.025, 0.5, and 0.1 mmol Fe/kg of bodyweight. Final concentrations were prepared by diluting stock solutions with 7.5% mannitol. MPI acquisition, duration 2–5 min, started approximately 1 min before injection.

Preclinical MPI scanner (a) and diagram of experimental workflow (b). (a) Preclinical MPI scanner (MPI 25/20 FF, Bruker BioSpin) in a copper-shielded cabinet to suppress interferences from external electromagnetic fields. (b) Diagram of experimental workflow. First, background MPI signal is acquired, followed by IV injection of one of the MNP and MPI scanning for several minutes. After 1 h (no signals from MNP detectable in blood vessels), the second tracer, was injected intravenously. The order of MNP type administration was random.