MRI of retinal and choroidal blood flow with laminar resolution

Abstract

The retina is nourished by two distinct circulations: the retinal vessels within the inner retina and the choroidal vessels behind the neural retina. The outer nuclear layer and the inner and outer segments of the photoreceptors in between are avascular. The aim of this study was to determine whether arterial spin labeling MRI could provide sufficient resolution to differentiate between quantitative retinal blood flow (rBF) and choroidal blood flow (chBF), and whether this technique is sufficiently sensitive to detect vascular-specific blood flow (BF) changes modulated by anesthetics. Arterial spin labeling MRI was performed at 42 × 42 × 400 µm(3) in the mouse retina at 7 T, and was used to investigate the effects of isoflurane and ketamine/xylazine anesthesia on rBF and chBF. MRI yielded unambiguous differentiation of rBF, chBF and the avascular layer in between. Under isoflurane, chBF was 7.7 ± 2.1 mL/g/min and rBF was 1.3 ± 0.44 mL/g/min (mean ± SD, n = 7, p < 0.01). Under ketamine/xylazine anesthesia in the same animals, chBF was 4.3 ± 1.9 mL/g/min and rBF was 0.88 ± 0.22 mL/g/min (p < 0.01). Under ketamine/xylazine anesthesia, rBF was lower by 29% (P < 0.01) and chBF by 42% (P < 0.01) relative to isoflurane. This study demonstrates, for the first time, the quantitative imaging of rBF and chBF in vivo, providing a new method to study basal values and alterations of rBF and chBF.

Figure 1

(A) Layer-specific blood flow image from a mouse under 1.1% isoflurane. (B) Blood flow acquired in a dead mouse in the same setting (same animal). Scale bar indicates blood flow values from 0 to 7 mL/g/min. (C) Blood flow profiles from the images in (A) and (B). chBF, choroidal blood flow; rBF, retinal blood flow.

Figure 2

Blood flow images in a mouse under 1.1% isoflurane (A) and ketamine/xylazine (100 mg/kg–10 mg/kg) (B). Scale bar indicates blood flow values from 0 to 7 mL/g/min. (C) Group-average blood flow profiles across the retinal thickness under either isoflurane or ketamine/xylazine from the same animals (n = 4, error bars show standard deviation).