The coupling of blood flow, oxygenation, and metabolism in the brain has been well described.
36 –38 There is also evidence of such coupling in the retina. For example, flickering light increases retinal and optic nerve head blood flow
39 and respiratory challenges with oxygen or carbogen modulate ocular blood flow and retinal oxygenation.
40 Visual stimulation also modulates optical absorption and scattering as detected by intrinsic optical imaging.
4 Gas inhalation challenge
24 and visually evoked
32 retinal BOLD fMRI responses in animal models have been also reported recently. Our BOLD fMRI findings in the unanesthetized human retina are in general agreement with previous studies showing strong vascular coupling in the retina.
Oxygen inhalation is expected to increase arteriole, capillary, and venous oxygen saturation and thus increase the BOLD signal relative to air inhalation, as has been well demonstrated in the brain.
36 –38 Oxygen inhalation has been reported to increase BOLD signals in the gray matter of the brain by 3.3% at 3 T,
41 3.41% at 1.5 T,
42 and 1.7% at 1.5 T.
43 Note that BOLD signals are dependent on field strength, with higher field strength generally yielding larger changes. Blood flow through the choroid is high, and the arteriovenous oxygen difference in the choroid
44 is small compared with that in the brain. Thus, one might expect a small hyperoxia-induced BOLD increase. In contrast, the group-averaged BOLD increase in the retina-choroid during oxygen challenge was 5.2 ± 1.4%, generally larger than those in the brain with good contrast-to-noise ratios. This is likely because the choroid has a high vascular density, and thus larger percent changes. In addition, it is worth pointing out that hyperoxia has a vasoconstrictive effect on the retinal vessels but not on choroidal vessels, and hyperoxia is known to markedly decrease retinal blood flow by 30–60% relative to air inhalation,
9,45 compared with a 10% reduction in brain blood flow under hyperoxia.
46 Such vasoconstriction would tend to counteract the BOLD signal increase from elevated oxygen tension by hyperoxia per se. The net effect observed in our study is a positive BOLD increase, suggesting that the increased oxygen delivery per se from oxygen inhalation dominates. The results herein are consistent with a BOLD fMRI study of oxygen challenge reported in the rat retina, which also detected positive BOLD signal changes.
24 Laminar-specific BOLD and blood-flow measurements would help further explore these unique vascular responses in the retina and would have important applications.
Similarly, carbogen inhalation is expected to increase arteriole, capillary, and venous oxygen saturation and thus increase BOLD signal relative to air inhalation as has been well demonstrated in the brain.
36,37 With the vasodilatory effect of 5% CO
2 in carbogen, BOLD responses are expected to be larger than for oxygen inhalation. Carbogen inhalation has been reported to increase BOLD signals in the gray matter of the brain by 3.6%,
43 and 6% at 1.5 T
47 and 6.8% at 2 T
48 , which changes were indeed larger than those with oxygen inhalation in the brain described above. In the retina-choroid, the group-averaged BOLD percent changes to carbogen challenge was 5.2 ± 1.3%, not statistically different from BOLD changes to oxygen challenge, contrary to predictions based on brain data. There are three possible explanations. First, although 5% CO
2 has significant vasodilatory effect on retinal vessels, it has little or no vasodilatory effect on choroid vessels,
44,49,50 and the choroid is expected to dominate the BOLD responses because of its high vascular density.
44,51 Second, the BOLD signal may have been near saturation with room air, and further vasodilation of the retinal vessels with carbogen and the small arteriovenous oxygen difference in the choroid would not further increase BOLD responses. Third, BOLD fMRI may not have sufficient sensitivity to detect the small BOLD differences between oxygen and carbogen inhalation, although this is unlikely if the magnitude of the changes is similar to those in the brain. The next logical step is to explore laminar-specific BOLD and blood-flow fMRI to address these and other questions and to further explore the unique hemodynamic and its regulation in the retina.
Some regional differences in BOLD fMRI responses in the retina were observed. The BOLD percent change was lower in region 3 (which included the optic nerve head) and higher in region 2 (which included the fovea). A possible explanation could be the sensitivity of the BOLD signals arising from different vessel types
37 and that the BOLD responses in the large veins of the optic nerve head were small, compared with those in smaller vessels (capillaries and venules) in the fovea—that is, capillaries and venules were more deoxygenated compared with large veins under baseline. These regional differences, however, need to be interpreted with caution because of significant PVE, SNR limitation, and small sample size. Further studies are needed to investigate regional differences at higher spatial resolution.