Prognostic MRI biomarkers of treatment efficacy for retinopathy

Abstract

There is a pressing need for retina-specific imaging biomarkers that robustly measure early (subclinical) changes in physiology, are linked to the histopathology responsible for vision loss, and, importantly, predict treatment efficacy. This review focuses on the following four MRI markers that we have developed and applied in preclinical and clinical settings: preretinal vitreous oxygen level (a steady-state biomarker of inner retinal oxygen tension); leakage of contrast agent into the vitreous (a steady-state biomarker of blood-retinal barrier permeability surface area product); change in preretinal vitreous oxygen tension during a hyperoxic provocation (a functional biomarker of vascular autoregulation); and retinal uptake of systemically administered manganese during a visual task (a functional biomarker of intraretinal ion regulation). We conclude that functional biomarkers are most promising for prognostic evaluation of treatment efficacy earlier in the course of retinopathy than is currently possible.

Molecular imaging in the eye

“…Prognostic MRI biomarkers of treatment efficacy for retinopathy have been established, such as: (1) preretinal vitreous oxygen level (a steady-state biomarker of inner retinal oxygen tension); (2) change in preretinal vitreous oxygen tension during a hyperoxic provocation (a functional biomarker of vascular autoregulation); (3) leakage of contrast agent into the vitreous (a steady-state biomarker of blood–retinal barrier (BRB) permeability surface area product); and (4) retinal uptake of systemically administered manganese Mn 2+ during a visual task (a functional biomarker of intraretinal ion regulation) 30. These four areas are now described in more detail.…”

“…ΔPO 2 as measured with fMRI can therefore be a clinically relevant prognostic biomarker of the development of vascular pathology and drug treatment efficacy 33. Alternative methods using the BOLD-MRI technique are being developed to provide information about the perfusion/oxygenation index, but these have yet to demonstrate their ability to distinguish between inner and outer retinal signal intensity changes associated with oxygenation 29 30…”

“…Ionic control is also important in the cell cycle and in neuronal development. Cellular ion demand has been used as an index of viability in proliferating cells 30. High-resolution ME-MRI data allow accurate measurement of the thickness of different retinal layers, which can be clearly distinguished from the choroid.…”

“…After systemic injection of MnCl 2 , paramagnetic manganese (Mn 2+ ), an MRI contrast agent and ion analogue, readily accumulates intracellularly as a function of membrane integrity and cellular activation, and is removed relatively slowly (figure 4). Therefore, ME-MRI is ideally suited for determining how small changes in ion activity and retinal thickness are spatially and temporally linked to progression of retinopathy, ocular injury and glaucoma 29 30. Other studies have investigated intravitreally administered Mn 2+ to highlight the optic nerve and examine its transport 34…”

Measuring the Effect of Pars Plana Vitrectomy on Vitreous Oxygenation Using Magnetic Resonance Imaging

“…[34][35][36][37] Berkowitz et al provided proof of principle that MRI could provide a noninvasive, indirect measurement of pO 2 in the eye. 35 The technique is able to rapidly capture images, and provide precise measurement of T 1 , without the image artifacts that would usually result from ocular movements and the blink reflex.…”