Blood flow and anatomical MRI in a mouse model of retinitis pigmentosa

Abstract

This study tested the sensitivity of an arterial spin labeling MRI method to image changes in retinal and choroidal blood flow (BF) and anatomical thickness of the retina in the rd10 mouse model of retinitis pigmentosa. High-resolution (42 × 42 μm) MRI was performed on rd10 mice and age-matched controls at 25, 35, and 60 days of age (n = 6 each group) on a 7-T scanner. Anatomical MRI was acquired, and quantitative BF was imaged using arterial spin labeling MRI with a separate cardiac labeling coil. Histology was obtained to confirm thickness changes in the retina. In control mice, the retinal and choroidal vascular layers were quantitatively resolved. In rd10 mice, retinal BF decreased progressively over time, while choroidal BF was unchanged. The rd10 retina became progressively thinner at later time points compared with age-matched controls by anatomical MRI and histology (P < 0.01). BF and anatomical MRI were capable of detecting decreased BF and thickness in the rd10 mouse retina. Because BF is tightly coupled to metabolic function, BF MRI has the potential to noninvasively assess retinal diseases in which metabolism and function are perturbed and to evaluate novel treatments, complementing existing retinal imaging techniques.

Figure 1

Histology from control and rd10 mouse retinas obtained at 40x magnification. The numbered arrows correspond to the proposed anatomical MRI layers (see Figure 2). GCL – ganglion cell and nerve fiber layers, IPL – inner plexiform layer, INL – inner nuclear layer, OPL – outer plexiform layer, ONL – outer nuclear layer, IS – inner segment, OS – outer segment.

Figure 2

Anatomical images at 42×42×400μm from a single (A) control and (B) rd10 mouse at P60. (C) The group average anatomical profiles for control mice at P25, P35, and P60 (n=6 at each age) and for rd10 mice at P25, P35, and P60 (n=6 at each age). The choroid peaks from all profiles were aligned together. Four layers were present in the control retina, including the choroid (labeled 1-4 in red below the profiles). Two layers were present in the rd10 retina, including the choroid (labeled 3-4 in blue above the profiles). Layer 3 likely corresponds to different anatomical layers in the control and rd10 retina. Error bars are SD. The green arrows indicate the choroid (layer 4). The black arrowheads indicate the vitreous-retina edge. The white boxes indicate the two 273μm wide regions from where the profiles were obtained. To avoid blurring in the group average profiles a 1D spatial transformation, including translation and scaling, was performed so that the 4 (or 2) labeled maxima and minima from each animal were aligned to all other animals in the group. Profiles were normalized by their maximum and minimum values before calculation of mean and SD.

Figure 3

Group-averaged normalized thicknesses of the neural retina from (A) histology and (B) anatomical MRI (sum of MRI layers 1, 2, and 3) at 42×42×400μm from control and rd10 mice at P25, P35, and P60. (C) Group-averaged absolute thicknesses of the choroid from anatomical MRI (MRI layer 4). Error bars represent SD. *p<0.01 compared to age-matched control mice, **p<1E-6 compared to age-matched control mice. From MRI, P35 and P60 rd10 mice also had significantly thinner retinas compared to P25 rd10 mice, p<0.01. From histology, P60 rd10 mice had significantly thinner retinas compared to P25 and P35 rd10 mice, p<0.01, and P35 rd10 mice had thinner retinas compared to P25 rd10 mice, p<0.05.

Figure 4

Blood flow images at 42×42×400μm from control and rd10 mice at P25, P35, and P60. The arrows indicate chBF and the white arrowhead indicates rBF.

Figure 5

Group average BF (top) and anatomical (bottom) profiles from control and rd10 mice at (A) P25, (B) P35, and (C) P60 (n=6 control and 6 rd10 at each age). The anatomical profiles come from the EPI images that the BF profiles were calculated from (and not from the bSSFP images) and were not intensity normalized. Error bars represent SD. The solid vertical lines indicate the approximate location of rBF in controls, and the dashed vertical lines indicate rBF in rd10 mice.

Figure 6

Group average (A) retinal and (B) choroidal BF in control and rd10 mice at P25, P35, and P60. Error bars represent SD. *p<0.05.