Whole-globe biomechanics using high-field MRI

Abstract

The eye is a complex structure composed of several interconnected tissues acting together, across the whole globe, to resist deformation due to intraocular pressure (IOP). However, most work in the ocular biomechanics field only examines the response to IOP over smaller regions of the eye. We used high-field MRI to measure IOP induced ocular displacements and deformations over the whole globe. Seven sheep eyes were obtained from a local abattoir and imaged within 48 h using MRI at multiple levels of IOP. IOP was controlled with a gravity perfusion system and a cannula inserted into the anterior chamber. T2-weighted imaging was performed to the eyes serially at 0 mmHg, 10 mmHg, 20 mmHg and 40 mmHg of IOP using a 9.4 T MRI scanner. Manual morphometry was conducted using 3D visualization software to quantify IOP-induced effects at the globe scale (e.g. axial length and equatorial diameters) or optic nerve head scale (e.g. canal diameter, peripapillary sclera bowing). Measurement sensitivity analysis was conducted to determine measurement precision. High-field MRI revealed an outward bowing of the posterior sclera and anterior bulging of the cornea due to IOP elevation. Increments in IOP from 10 to 40 mmHg caused measurable increases in axial length in 6 of 7 eyes of 7.9 ± 5.7% (mean ± SD). Changes in equatorial diameter were minimal, 0.4 ± 1.2% between 10 and 40 mmHg, and in all cases less than the measurement sensitivity. The effects were nonlinear, with larger deformations at normal IOPs (10-20 mmHg) than at elevated IOPs (20-40 mmHg). IOP also caused measurable increases in the nasal-temporal scleral canal diameter of 13.4 ± 9.7% between 0 and 20 mmHg, but not in the superior-inferior diameter. This study demonstrates that high-field MRI can be used to visualize and measure simultaneously the effects of IOP over the whole globe, including the effects on axial length and equatorial diameter, posterior sclera displacement and bowing, and even changes in scleral canal diameter. The fact that the equatorial diameter did not change with IOP, in agreement with previous studies, indicates that a fixed boundary condition is a reasonable assumption for half globe inflation tests and computational models. Our results demonstrate the potential of high-field MRI to contribute to understanding ocular biomechanics, and specifically of the effects of IOP in large animal models.

Keywords: Biomechanics; Glaucoma; High-field MRI; IOP; Lamina cribrosa; Optic nerve head.

Figure 1

Geometric parameters measured by high-field MRI in this study. A. On the global scale, cup-to-cornea distance (an approximation of axial length), equatorial diameter, and whole globe perimeter length, were measured. B. At the local level of the optic nerve head, the lengths of the scleral canal diameters were calculated. Canal dimensions were measured from coronal views of the optic nerve head.

Figure 2

An example of sub-pixel measurement using non-linear interpolation. A–B. Simulated low resolution images of two circles with a 0.1 mm difference in radius. Although, the images are similar, there are subtle differences in the gradient on the edge of the circle. C–D. A cubic polynomial was fit to the gradient of the image and edge contours were detected using two different thresholds, a loose threshold (Red) and a tight threshold (Blue). The radius calculated for each case depended upon the chosen threshold; however, the difference between two measurements made using the same threshold was accurate to 0.01 mm. Note that here we do not mean the difference between the measurements, which is 0.1 mm, but the accuracy of the difference, which is 0.01 mm. This is well below the pixel edge length of 0.5 mm. E. The difference between the actual radius and measured radius for each threshold was consistent as the actual radius was varied from 4 to 6 mm. Thus, while there is uncertainty in the absolute measurements which may be attributable to the choice of threshold, a consistent threshold will allow for accurate calculation of differences in size.

Figure 3

Representative high-field MRI images of a sheep eye at controlled IOPs of 0, 10, 20 and 40 mmHg. Visually, an increase in axial length and globe cross-sectional area can be observed. The eye is oriented such that the nasal-temporal axis is vertical.

Figure 4

Differences between an eye at 10 and 40 mmHg. The 10 mmHg image is colored in red and the 40 mmHg image is colored in green. At 40 mmHg the iris, cornea, and anterior sclera move anteriorly as indicated by the green regions noted on the figure. The posterior sclera bulges posteriorly at 40 mmHg as indicated by the red region corresponding to the 10 mmHg condition indicated on the figure.

Figure 5

Changes in globe perimeter. A. The peripheries of a globe are shown at different pressures. Delineations were registered along the globe equator. Delineation at the optic nerve head was done at the anterior lamina cribrosa surface. Clear corneal and posterior scleral bulging are observed at high pressures. Large changes are seen between 10 and 20 mmHg but not between 0 and 10 mmHg or between 20 and 40 mmHg. Delineations shown on the original images appear in Supplementary Figure 1B. Globe perimeter increases non-linearly with increasing IOP, consistent with the nonlinear mechanical properties of ocular tissues.

Figure 6

Globe-level deformations of the eye. A. Axial length measurement sensitivity was computed by marking same images in triplicate. Differences between markings were small and mean standard deviation across all eyes and pressures was 94 μm. B. Axial length changes exceeded two times the average standard deviation from the sensitivity analysis in six of the seven eyes. Length changes were non-linear, with large deformations occurring between 10 and 20 mmHg and smaller changes between 20 and 40 mmHg. C. Equatorial diameter measurement sensitivity was also calculated and the average standard deviation across all eyes and pressures was 178 μm. D. No measureable changes in equatorial diameter, as defined by a change greater than twice the average standard deviation of the measurement sensitivity test, were observed. All colors correspond to same eyes across the four charts. Dashed lines represent measurements taken from images with best in-plane resolution in the sagittal plane and solid lines represent images with best in-plane resolution in the axial plane. Axial length was not measured at 0 mmHg as the cornea bowed inward at this sub-physiologic pressure.

Figure 7

Delineations of the posterior sclera and optic nerve head demonstrate scleral bowing and canal expansion with increasing IOP. To notice more clearly the outward bowing of the sclera and widening of the canal, the outlines were registered to one another in the peripheral sclera (notice the point where all lines cross) A. In one eye a non-linear deformation pattern was observed. Between 0 and 10 mmHg, little change was seen in the posterior sclera as the globe returned to its physiological shape. Between 10 and 20 mmHg the peripapillary sclera bowed outward and the lamina began to cup. Between 20 and 40 mmHg the sclera underwent only a small displacement, but noticeable deformation was seen in the canal and lamina surface. The delineations for this eye are shown on the original images in Supplementary Figure 2B. In a second eye, the deformation pattern was much more linear with moderate scleral bowing observed at each pressure change and little deformation of the lamina cribrosa surface. The delineations for this eye are shown on the original images in Supplementary Figure 3.

Figure 8

Detailed view of axial cross sections through the optic nerve head and peripapillary sclera showing outward bowing of the sclera with increased IOP. Straight lines connecting the most distal sclera in the images are overlaid to help notice the deformations. Note also the detail and substantial deformations of structures posterior to the sclera, typically hidden from OCT due to shadowing.

Figure 9

The scleral canal underwent measurable expansion due to IOP. A. Coronal views showing the scleral canal under 0, 10, 20 and 40 mmHg. The superior-inferior axis is shown top to bottom. B. Measurements of the canal diameters were marked in triplicate to determine measurement sensitivity and the average standard deviation of the triplicate measurements across all eyes, pressures, and axes was 30 μm. C. The nasal-temporal scleral canal diameter (solid lines) increased measurably due to IOP changes. The increase was greatest between IOPs of 10 and 20 mmHg. The superior-inferior canal diameter (dashed lines) only changed measurably in eye 2 (Green dashed line between 10 and 20 mmHg). In eye 2 we could not confidently identify a section at 0 mmHg that could be compared to the other pressures conditions and this condition was not considered in our measurements. Note that the resolution of this scan is higher in the nasal-temporal direction (left-right) than in the superior-inferior direction (top-bottom). Recall that sheep eyes have a scleral canal that is typically more elongated in the nasal-temporal direction than in the superior-inferior one.