Layer‐specific anatomical, physiological and functional MRI of the retina

Abstract

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 ...

MR Imaging of Papilledema and Visual Pathways: Effects of Increased Intracranial Pressure and Pathophysiologic Mechanisms

“…Retinal fMRI is still in the early stages of development and is currently performed only in animal models, still well below the resolution of optical imaging techniques. [47][48][49] These animal experiments have already shown promise in imaging the activity of the retina in response to visual stimuli 50 and can distinguish the 2 retinal layers supplied by the retinal and choroidal arteries with differing responses to hypercapnia and hyperoxia. 51 fMRI has been shown to detect retinal damage by evaluating decreased basal blood flow in rats.…”

Prognostic MRI biomarkers of treatment efficacy for retinopathy

“…If the spatial resolution is somewhat less than 10 pixels across the retina, then changes in oxygenation and/or retinal and choroidal perfusion, such as during a hyperoxic provocation, can produce variations in signal or in-flow artifacts, making interpretation of intraretinal signal intensities uncertain (11,14). Alternatively, different groups are currently investigating arterial spin labeling methods that measure some combination of retinal and choroidal perfusion more directly (97,98,15). It is not yet clear whether these methods will be able to unambiguously resolve retinal circulatory from choroidal contributions.…”

High-Resolution 3D MR Microangiography of the Rat Ocular Circulation

“…Image analysis was performed by using custom-written programs (Matlab; MathWorks, Natick, Mass) (2,11,12). Blood volume (BV) index was calculated as the change in transverse relaxivity (DR2*) between images obtained before and after MION administration (13).…”