Preliminary study for non-invasive magnetic resonance imaging and spectroscopy of the eye: A novel technique for monitoring pharmacokinetics of ocular drug delivery

Introduction Conventional pharmacokinetic methods for studying ocular drug delivery are invasive and cannot be conveniently applied to humans. The development of non-invasive techniques in monitoring pharmacokinetics of ocular drug delivery is of vital importance. Purpose The aim of this study was to develop a novel clinical technique that permits monitoring of in vivo intravitreal drug pharmacokinetics based on both Hydrogen Magnetic Resonance Spectroscopy (H-MRS) and/or quantitative Magnetic Resonance Imaging (qMRI) methodologies. Materials and methods Advanced qMRI and H-MRS were performed using a high resolution clinical MRI eye protocol based on T1w and T2w 3D-sequences as well as a standard single voxel. H-MRS protocol utilizing a clinical 1.5T whole-body scanner enforced with a specially designed small coil apparatus for signal detection. H-MRS single voxel dimensions were (1.5 × 1.5 × 1.5 cm 3 ). In vitro and ex vivo experiments were performed using pig eyes as reference standards and Flurbiprofen (a non-steroidal anti-inflammatory ocular drug) in concentrations 0.04 M–2 mM. All measurements performed at a fixed temperature of 37 °C utilizing an in-house developed temperature monitor/controller device. Results High resolution qMRI images and MRS spectra of the vitreous with and without the presence of ocular drugs at different concentrations were obtained. Characteristic H-MRS peaks on 1.5 and 7 ppm were observed on both Flurbiprofen concentrations. Differences on the relative NMR signal measurements were obtained using various Flurbiprofen concentrations. Characteristic water H-MRS peak on 4.7 ppm was observed in vitreous samples proved a valuable means for the assessment of pharmacokinetics on ocular drug delivery. Conclusion A clinical protocol of H-MRS and/or qMRI will become feasible with the development of a rapid, inexpensive, and automated technique that could be easily integrated on any conventional clinical MRI examination.