MRI in vivo Assessment of Optic Nerve Degeneration in Experimental Glaucoma

Abstract

Purpose: : To assess diffusion tensor imaging (DTI) parameters as a biomarker for optic nerve (ON) degeneration in monkeys with chronically elevated IOP.

Methods: : Glaucoma was induced unilaterally in 8 cynomolgus monkeys by trabecular laser photocoagulation. Animals were scanned on a Siemens Trio 3T, 2 years post surgery. T1 weighted MPRAGE pulse sequence (TR/TE/TI/FA = 1.47/4.38/870/12) was used to obtain high resolution images (0.5x0.5x0.8 mm³) of the animals' whole heads. DTI scans were performed to assess integrity of the ON (TR/TE/TI=11.4s/118ms/2.2s; beta=0, 1000 s/mm², 30 sensitizing gradient directions, resolution 1.5x1.5x1.5 mm³). Axial and radial diffusivity; fractional anisotropy (FA), and apparent diffusion coefficient (ADC) were analyzed. Intraocular pressure (IOP) was measured in all 16 eyes. Comparative statistical analysis was performed between ON MRI parameters of normotensive and hypertensive eyes. Correlation between ON parameters and IOPs was also assessed.

Results: : In normotensive eyes, IOP was 15.0±1.7 mmHg and ON area was 6.4±0.8 mm². In contrast, IOP in hypertensive eyes was 34.1±6.6 mmHg and ON area was 4.5±4.7 mm² (p=0.027). ON cross sectional areas correlated with IOPs (Pearson's r=0.66, p=0.008). DTI diffusivity parameters in ON of normotensive eyes were 1.16±0.2 and 0.71±0.23 s/mm² for axial and radial diffusivity, respectively. In the ON of hypertensive eyes those parameters were 0.95±0.19 and 0.47±0.12 s/mm², respectively (axial p=0.034 and radial p=0.013). Fractional anisotropy was also lower in the ON of the hypertensive eye (0.35±0.09) when compared to the normotensive eye 0.45±0.07, (p=0.0167). The overall ADC in the ON of the hypertensive eye was larger (0.86±0.23 s/mm2) than in the normotensive eye (0.63±0.14 s/mm2, p=0.017). Pearson correlation coefficients between IOP and Axial and Radial diffusivity, FA and ADC were 0.58 (p=0.02), 0.71 (p=0.003), -0.59 (p=0.02) and 0.67 (p=0.006), respectively.

Conclusions: : This study shows that MRI can be used to study IOP-induced ON degeneration in vivo. Longitudinal studies will be required to determine the onset and rate of optic nerve degeneration to confirm the suitability of DTI to delineate surrogate markers for disease progression and address potential benefit of novel therapies to glaucoma patients.

Keywords: imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • optic nerve • intraocular pressure