MRI in ocular drug delivery

Abstract

Conventional pharmacokinetic methods for studying ocular drug delivery are invasive and cannot be conveniently applied to humans. The advancement of MRI technology has provided new opportunities in ocular drug-delivery research. MRI provides a means to non-invasively and continuously monitor ocular drug-delivery systems with a contrast agent or compound labeled with a contrast agent. It is a useful technique in pharmacokinetic studies, evaluation of drug-delivery methods, and drug-delivery device testing. Although the current status of the technology presents some major challenges to pharmaceutical research using MRI, it has a lot of potential. In the past decade, MRI has been used to examine ocular drug delivery via the subconjunctival route, intravitreal injection, intrascleral injection to the suprachoroidal space, episcleral and intravitreal implants, periocular injections, and ocular iontophoresis. In this review, the advantages and limitations of MRI in the study of ocular drug delivery are discussed. Different MR contrast agents and MRI techniques for ocular drug-delivery research are compared. Ocular drug-delivery studies using MRI are reviewed.

Figure 1

(a) Examples of drug-delivery methods studied using MRI: A, intrascleral infusion or injection into the suprachoroidal space; B, subconjunctival injection; C, intravitreal injection; D, transscleral iontophoresis; E, episcleral implant; F, intravitreal implant; G, transcorneal iontophoresis. (b) Representative MR images of ocular drug delivery in rabbits: A, intrascleral infusion; B, subconjunctival injection; C, intravitreal injection; D, ocular iontophoresis; E, episcleral implant; F, intravitreal implant. The arrows indicate the sites of drug delivery or the drug-delivery systems. Images are obtained from previous studies at 1.5, 3, or 4.7 T (53,73,108,109,112).

Figure 2

(a) Relationships between relaxation rates and contrast agent concentration. In this example, data for Mn²⁺ in saline at 1.5 T are used. Lines: solid, T₁; dashed, T₂. (b) Relationships between the signal intensity normalized by S_o (i.e. S/S_o) and the concentration of contrast agent Mn²⁺. Lines: thick solid, TR 400 ms, TE 12 ms; thin solid, TR 1200 ms, TE 12 ms; thick dashed, TR 400 ms, TE, 6 ms.

Figure 3

Distribution of Mn²⁺ in the eye after 20 min of 3 mA transscleral iontophoresis applied on the sclera next to the limbus: (a), from left to right, control and at 1, 2, 3, and 11 h after iontophoresis application; (b) model simulation result of a finite element method using Comsol (Burlington, MA, USA) mimicking the 3 h MRI data. The MRI scans were performed with a 3 T Siemens clinical scanner.

Figure 4

MR images of rabbit eyes at (a) 0.47 mm × 0.47 mm × 2 mm resolution and (b) 0.3 mm × 0.3 mm × 1 mm resolution. The MRI scans were performed with 1.5 T GE clinical and 3 T Siemens clinical scanners with scan times of ∼1.5 and 20 min for (a) and (b), respectively. MR images obtained in an ocular delivery study conducted with the 3 T Siemens clinical scanner (c) with motion artifacts in the phase-encoding direction and (d) without motion artifacts.

Figure 5

Effects of partial-volume averaging in MRI ocular drug-delivery study.