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

• Published in: Physica medica 2016-09, Vol.32, p.249-249
• Main Authors: Tsiapa, Irene, Boursianis, Themistoklis, Kalaitzakis, Georgios, Nikiforaki, Katerina, Papadaki, Efrosini, Bontzos, George, Karantanas, Apostolos H, Tsilimbaris, Miltiadis K, Maris, Thomas G
• Format: Article
• Language: English
• Subjects: Radiology
• ISSN: 1120-1797; 1724-191X
• DOI: 10.1016/j.ejmp.2016.07.530

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 cm3 ). 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.