Most retinal imaging has been performed using optical techniques. This paper reviews alternative retinal imaging methods based on magnetic resonance imaging (MRI) performed with spatial resolution sufficient to resolve multiple well-defined retinal layers. The development of these MRI technologies to study retinal anatomy, physiology (blood flow, blood volume, and oxygenation) and function, and their applications to study normal retinas, retinal degeneration and diabetic retinopathy in animal models are discussed. While the spatiotemporal resolution of MRI is poorer than optical imaging techniques, MRI is unhampered by media opacity and can thus image all retinal and pararetinal structures, and has the potential to provide multiple unique clinically relevant data in a single setting and could thus complement existing retinal imaging techniques. In turn, the highly structured retina with well-defined layers serves as an excellent model to advance emerging highresolution anatomic, physiologic and functional MRI technologies.
KeywordsChoroid; retinal blood flow; BOLD; fMRI; diffusion-weighted MRI; high resolution imaging; retinal diseases; manganese-enhanced MRI (MEMRI)
1) RETINAL ANATOMY AND PHYSIOLOGY
Anatomical layersThe retina consists of multiple well-defined layers (1-3). Starting from the vitreous boundary, they include the ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), and photoreceptor inner and outer segments (IS+OS) (Figure 1, rat retina). The plexiform layers are synaptic links between adjacent nuclear cell layers.
Vascular layersThe retina is nourished by two separate blood supplies, namely, the retinal and choroidal circulations (1,4,5). The retinal vessels exist within the GCL, INL, IPL and OPL. The *Correspondence: Timothy Q Duong, PhD, Yerkes Imaging Center, Emory University, 954 Gatewood Road NE, Atlanta, Georgia 30329.
NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript choroidal vessels do not exist within the neural retina, but rather are located posterior to the photoreceptor layer, sandwiched between the retinal pigment epithelium and sclera. Thus, the outer nuclear layer and the inner and outer segments, are avascular, relying on diffusion predominantly from the choroidal circulation for oxygen delivery (1,4,5). In fact, oxygen tension in the middle of the retina is close to zero under normal physiologic conditions (6-8) likely due to the high oxidative demands of the photoreceptors and their dependence on diffusive oxygen transport (1,4,5). The total retinal thickness across multiple mammalian species, excluding the choroid, has been reported to be approximately 217 µm (2,3) and the choroidal thickness, which is less well documented, has been reported to be 25-45 µm (9) based on histology in rats.While both vasculatures are required for proper retinal function, blood flow is regulated differently in the retinal and choroidal vessels. Basal choroidal blood flow is many ...