Hyperspectral Image Analysis for Oxygen Saturation Automated Localization of the Eye

ONH structures over a range of IOP are consistent with early studies that showed that the NFL could become ischemic during very low perfusion pressure, while the regions of the anterior ONH underlying the NFL could be protected from ischemia.

4.5. Experiment Four

4.5.1. Methods and Materials

All methods and materials are the same as in the previous experiment except for theoretical development of oxygen diffusion out of the RA.

We hypothesized that the decrease of O2Sat in RA caused by the increase in IOP can be explained by oxygen diffusion out of the RA alone. Consider a cylindrical RA 0.2 mm in diameter (d), a wall thickness of 0.03 mm (w),82 surrounded by tissue with oxygen tension (PO2) that is in equilibrium with venous PO2 (see Fig. 4.24). Intaglietta et al.83 have shown that tissue regions between arterioles and venules have essentially uniform tissue PO2. Under normal IOP, some oxygen in the RA blood diffuses through the arterial wall. Two cases were assumed. In the first case, RA and RV were assumed to be separated by arterial wall thickness. The RA and RV are parallel each other for about 5 mm on the optic disk and the tissue underneath the optic disk surface. Thus, oxygen can diffuse from the artery to the tissue through a 0.03 mm layer that is 0.2 mm by 5 mm. For the vessels considered, the wall thickness is several times smaller than the vessel diameter, and the PO2 gradient is approximately constant across the wall. The arterial

Fig. 4.24. Schematic diagram of the RA diffusion model. Reprinted with permission from Beach, J.M., Ning, J., Khoobehi, B., and Rice, D.A. A simple model of oxygen diffusion out of the retinal artery. In: Manns, F., Soderberg, P.G., and Ho, A. (eds.), Ophthalmic Technologies XIX, Proc of SPIE. 7163, 71630S. ©2009 SPIE.

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oxygen partial pressure (PAO2) was assumed to be 100 mmHg, venous oxygen partial pressure (PVO2) 50 mmHg, oxygen diffusion coefficient (DO2) 2.4 × 10−3 mm2/s,84 oxygen solubility (α) 0.0284 µl/ml/mmHg,85 and all parameters were at body temperature and 1 atm pressure. A list of glossary and symbols is in the Appendix.

Figure 4.24 is a schematic diagram of the RA diffusion model. According to Fick’s law, the flux of oxygen across the arterial vessel

wall for P = (PAO2 − PVO2) per unit, area can be calculated as:

(4.14)

Total flux of oxygen across the arterial wall

(Q1(O2)) = F(O2) × area

= 1.14 × 10−4 µl/mm2/s × (0.2 mm × π × 5 mm)

Under normal IOP, we assume that retinal arterial blood flow is well mixed and in a steady state, and red cell velocity (V) is 9.28 mm/s.4 Blood flow and oxygen consumption are assumed to be distributed homogeneously. The amount of oxygen flowing in blood along the artery (Q(O2)) is the product of oxygen concentration ([O2]) and blood flow (Q), which is the product of blood velocity and the area of the artery (Aartery). In the discussion that follows, volumetric flow rate Q is the variable of significance, but we pose it as V · A because both V and A are more readily determined by optical methods. One gram of hemoglobin combines with 1.34 ml of oxygen, and 100 ml of blood contains 15 g of hemoglobin, thus carrying

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4.5.2. Results

Mean percentage O2Sat of the RAs was 78.9% at IOP of 10 mmHg, with no significant change when IOP was raised to 30 mmHg. O2Sat decreased to 74.1% at 45 mmHg (P = 0.01), and further decreased to 51.5% (P < 0.0001) at 55 mmHg IOP. From the modeling, the highest percentage of oxygen that can be lost visa diffusion through the arterial wall is 1.27% when retinal arterial blood velocity is normal. When IOP was raised to 55 mmHg, perfusion pressure (pressure difference between mean arterial blood pressure and IOP) decreased.73 We have assumed that the retinal arterial blood velocity drops to 1.0 mm/s at 55 mmHg. Substituting this value into the equations above, the percentage of oxygen that can be lost via diffusion through the arterial wall at most is about 38%. To have a drop of 35.7% in retinal arterial O2Sat, the model predicts that retinal arterial blood velocity needs to be less than 0.33 mm/s.

4.5.3. Discussion

Figure 4.25 shows that oxygen diffusion from the RA increased as the blood velocity was decreased by the elevation of IOP. There was not much difference in percentage O2Sat when IOP was raised from 10 to 30 mmHg; however, when IOP was raised to 45 mmHg, percentage O2Sat began to decrease and decreased significantly at an IOP of 55 mmHg. This nonlinear relationship between IOP and percentage O2Sat is consistent with the model predictions for oxygen diffusion in Fig. 4.5. This result was not expected; thus, we developed the model to interpret the data.

In the two studies of Khoobehi et al.33 and Beach et al.,73 IOP of 10– 15 mmHg was considered normal in anesthetized cynomolgus monkeys. Morita86 reported a diastolic pressure of 55 ± 11 mmHg and a systolic pressure of 102±18 mmHg (mean arterial blood pressure is about 70.67 mmHg) in 15 normal male cynomolgus monkeys under general anesthesia. The blood flow in the ONH is usually calculated as perfusion pressure divided by the resistance to flow. Practically, perfusion pressure in the optic disc is equal to mean arterial blood pressure in the ONH vessels minus IOP.5 For the HSI data acquisition in this study, the animals were deeply anesthetized, which decreased the mean blood pressure to the range of 50–60 mmHg. Thus, at an IOP of 55 or 60 mmHg, perfusion pressure in the ONH is low,

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Hyperspectral Image Analysis for Oxygen Saturation Automated Localization of the Eye

Fig. 4.25. Maximum percentage of oxygen that may diffuse out of the retinal arteries as RA blood velocity decreases from 9.28 mm/s to 0.33 mm/s. Reprinted with permission from Beach, J.M., Ning, J., Khoobehi, B., and Rice, D.A. A simple model of oxygen diffusion out of the retinal artery. In: Manns, F., Soderberg, P.G., and Ho, A. (eds.), Ophthalmic Technologies XIX, Proc of SPIE. 7163, 71630S. ©2009 SPIE.

and ONH blood flow could be significantly reduced or completely stopped, which may contribute to the significant diffusion of oxygen out of RA. However, experimental verification is needed.

What other factors may decrease O2Sat along the RA when the IOP is at 55 mmHg? It may be that the decrease in perfusion pressure at high IOP reduces the RA blood flow sufficiently to lower O2Sat. It is unlikely that significant changes in tissue oxygen consumption occur between normal and high IOP. The red blood cell and the arterial wall consume oxygen. A review by Tsai et al.87 concluded that the vascular wall has a high rate of oxygen consumption, positioning an oxygen sink between blood and tissue regulating oxygen release. A fixed rate of oxygen consumption that is maintained during significant reductions in the blood flow could also result in lowering the artery saturation through diffusion.

Our results show that diffusion of oxygen from retinal arteries could cause the observed RA O2Sat decrease during high IOP. Further investigation is needed to evaluate blood flow changes over the range of IOP studied.

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