In vitro skin penetration measurement with contrast-enhanced MRI at 7 Tesla

Methods: Penetration studies according to OECD guidelines [1] were performed using skin samples taken from porcine ear. For enhancing the transport of the contrast agent into the skin a submicron emulsion containing 1mmol/ml Gadolinium (Gadobutrol, Gadovist, Schering, Germany) was used. The experiments were performed using the Franz-Diffusion-Cell setup, a standard device for in vitro penetration studies. The penetration was done for 6h respectively 24h followed by deep-freezing of the skin samples. In vitro MRI was performed on a 7T small animal scanner (Clinscan, Bruker, Ettlingen, Germany). A Bruker mouse head phased array coil (2x2) was used for imaging the skin samples. High resolution (55 x 55 x 400μm) T1-weighted TSEsequences (TR: 600ms, TE: 11ms, FA: 120°) were used for imaging the skin and assessing contrast agent penetration with and without background inversion. TIR-sequences (TR: 5000ms, TE: 14ms, 200 x 200 x 500μm) with 5 Inversion times (100, 250, 500, 750 and 1000ms) were used for measuring T1-Relaxation and contrast media quantification. T1Relaxivity and concentration of Gadobutrol were measured with TIR-Sequences as well. Measurement setup additionally consists of one untreated skin sample and one measurement phantom containing 0.01mmol/ml Gadobutrol as references. T1 was calculated ROI-based in the different skin layers. One ROI was drawn for each of epidermis (0.1–0.2 mm deep), outer dermis (0.6 – 0.7 mm deep) and inner dermis (0.9 – 1.0 mm deep).