7.1 T MRI and T2 mapping of the human and porcine vitreous body post mortem

Abstract

Numerous literature reports describe the liquefaction of the vitreous body with increasing age. It must be expected that this process also influences drug distribution and elimination following intravitreal application of active pharmaceutical ingredients (APIs). To better understand the impact and extent of the liquefaction a magnetic resonance imaging (MRI) study was performed examining human donor eyes post mortem. For comparison, eyes of juvenile pigs were also examined representing a fully gelled vitreous. 7.1Tesla ultra-high field MRI and T2 mapping of the vitreous body were used in this study since it must be expected that age-induced degradation processes and structural changes of the vitreous gel to a liquid state will result in changes of the T2 relaxation time of water proton spins. The vitreous bodies were imaged in 12 axial slices and within each image the T2 relaxation times of water proton spins were determined. It was found that T2 relaxation time increased with increasing age of the donor. Whilst the mean T2 relaxation time (±standard deviation) of water proton spins within the central vitreous body of a juvenile porcine eye was 210.1 ± 31.1 ms, the mean T2 relaxation time within the central vitreous body of the 88-year-old and therefore oldest human donor was 528.0 ± 79.3 ms. Within the vitreous body of a single donor, the T2 relaxation time increased from the anterior to the posterior segment, for example in the vitreous body of the oldest human donor from 388.0 ± 31.1 ms on average in the anterior to 631.7 ± 42.8 ms in the posterior segment, indicating an increase in intravitreal liquefaction respectively inhomogeneity from anterior to posterior regions. Additionally, physicochemical parameters were determined yielding averages of 7.54 ± 0.34 for pH, 1.33629 ± 0.00044 for refractive index, 368.99 ± 26.87 mosmol/kg for osmolality, 97.56 ± 0.43% for drying mass loss and 0.73 ± 0.18 mg/mL for total protein content. The aging process and the liquefaction of the vitreous body are expected to affect the pharmacokinetic profile of intravitreally injected APIs, which is of high relevance to drug release from intravitreal drug delivery systems and the therapeutic concept in the treatment of posterior segment diseases. Our data indicate that such processes are not reflected in animal models. Since there is still a need for valid pharmacokinetic data, invitro test systems for the characterization of intraocular drug delivery systems have to be improved according to the current state of knowledge about the vitreous structure and intravitreal transport phenomena.

Keywords: Intravitreal drug application; Magnetic resonance imaging; T2 relaxation time; Vitreous body; Vitreous liquefaction.