Reduced Field-of-View Diffusion Tensor Imaging of the Optic Nerve in Retinitis Pigmentosa at 3T
Yanqiu Zhang1, Dapeng Shi1, Xirang Guo2, Meiyun Wang1, and Dandan Zheng3

1Radiology, Zhengzhou University People's Hospital (Henan Provincial People's Hospital), Zhengzhou, China, People's Republic of, 2Ophthalmology, Zhengzhou University People's Hospital (Henan Provincial People's Hospital), Zhengzhou, China, People's Republic of, 3GE Healthcare, MR Research China, Beijing, China, People's Republic of

Synopsis

DTI can provide in vivo information about the pathology of optic nerve (ON) disease, but the ability of DTI to evaluate alterations of ON in retinitis pigmentosa (RP) has not been explored so far. In this work, we demonstrate that reduced field-of-view DTI is very helpful for the diagnosis of optic neuropathy in patients with RP in vivo, which is very critical to connect radiology and ophthalmology together in RP.

BACKGROUND AND PURPOSE

DTI can provide in vivo information about the pathology of optic nerve (ON) disease,[1,2] but the ability of DTI to evaluate alterations of ON in retinitis pigmentosa (RP) has not been explored so far. Potential utility of rFOV-DTI in ON of RP would be novel, as routine MR imaging is usually not part of the algorithm for disease diagnosis or monitoring in patients with RP. Our aim was to investigate the potential diagnosis of reduced field-of-view DTI (rFOV-DTI) in optic neuropathy of RP at 3T.

MATERIALS AND METHODS

Thirty-eight patients (76 affected nerves) and thirty-five healthy controls (70 normal nerves) were enrolled in this study. Measures of visual field (VF) and visual acuity (VA) were performed on all subjects. In addition, MRI was performed using a rFOV-DTI sequence, which was used to determine fractional anisotropy (FA), mean diffusivity (MD), principal eigenvalue (λ//), and orthogonal eigenvalue (λ⊥) of ONs. The mean FA, MD, and eigenvalue maps (Figure 1) were obtained for quantitative analysis. Further analyses were performed to determine the correlation of FA, MD, λ//, λ⊥ of 76 affected ONs in patients with mean deviation of visual field (MDVF) and VA, respectively.

RESULTS

The mean MD, λ//, and λ⊥ in patient nerves were increased compared with control nerves (P<0.01), and the mean FA was reduced compared with control nerves (P<0.001)(Figure 2). There was a significant correlation of MDVF with FA (r=0.364, P=0.001), λ⊥ (r=-0.254, P=0.029)(Figure 3), but no correlation with MD, λ// (P>0.05). However, none of DTI measures were correlated to VA (P>0.05).

DISCUSSION

FA is the most widely used measurement of anisotropy in DTI to evaluate white matter tracts, and MD represents the mean diffusivity of water molecules in DTI. The reduced FA and increased MD in patient nerves compared to control nerves most probably reflect cell lysis, axonal disruption or loss, and demyelination of ONs caused by trans-synaptic degeneration[3-5] in RP. Furthermore, FA displayed significant correlations with VF, but no correlation with VA was seen in RP patients, indicating that the progression of optic neuropathy is related to VF instead of VA. The two types of photoreceptors (rods and cones) are both responsible for VF, but only cones concentrated in the fovea centralis are responsible for VA.[6] With progressive death of photoreceptor cells and following gradual loss of ganglion cells, corresponding VF defects develop and optic neuropathy advances in RP patients, but VA may not descend as the surviving cones concentrated in the fovea centralis can be of good function for a certain time.[7,8] Therefore, we could make a speculation that the progress of optic neuropathy in typical RP is more parallel to death of rods than loss of cones.

λ// and λ⊥, as the surrogates for the integrity of axon and myelin respectively, are common used to provide rich pathological information of ON disease.[9-11] In current study, both λ// and λ⊥ values of ONs in RP patients increased significantly compared with controls, and indicated that the pathology of optic neuropathy in RP is complex, with axon and myelin injury strongly linked. Although the pathogenesis of RP is absolutely different from glaucoma, their optic neuropathy, both of which are caused by the death of ganglion cells, may have a similar pathological process. In the optic neuropathy of glaucoma, demyelination in ONs is secondary to axonal loss.[12] Theoretically, axonal degeneration rather than demylination should be the underlying component in the optic neuropathy of RP patients as well. However, our study showed that there was a significant correlation of λ⊥ with VF, but no correlation of λ// with VF in RP patients. This might be expained by that the function of the remaining axon in RP patients would probably enhance, due to a protective compensation reaction of the body.[13] Thus, a lack correlation of λ// with VF was seen in our results.

CONCLUSIONS

The rFOV-DTI measurement of patient nerves provides in vivo information about pathology and may serve as a biomarker of axonal and myelin damage in optic neuropathy of RP. In addition, the potential diagnosis of rFOV-DTI in optic neuropathy of RP in vivo is critical to connect radiology and ophthalmology together in RP patients.

Acknowledgements

We thank Dr. Dandan Zheng, MRI Department of GE Healthcare, Beijing, China, for technical guidance and Dr. Ke Fan, Department of ophthalmology, Henan Provincial People's Hospital for clinical assistance. In addition, we are grateful to the staffs at the Center of Translation Medicine, Zhengzhou University People’s Hospital for their assistant to this project.This study is supported by the National Natural Science Foundation of China under Grant (No. 81271534, Zhengzhou, China).

References

[1]Wang MY, Qi PH, Shi DP. Diffusion tensor imaging of the optic nerve in subacute anterior ischemic optic neuropathy at 3 T. AJNR Am J Neuroradiol 2011;32:1188-94.

[2]Mei-Yun Wang, Ke Wu, Dapeng Shi, et al. Quantitative 3-T diffusion tensor imaging in detecting optic nerve degeneration in patients with glaucoma: association with retinal nerve fiber layer thickness and clinical severity. Neuroradiology 2013;55:493-8.

[3]Gartner S, Henkind P. Pathology of retinitis pigmentosa. Ophthalmology 1982;89:1425-32.

[4]Stone JL, Barlow WE, Humayun MS, et al. Morphometric analysis of macular photoreceptors and ganglion cells in retinas with retinitis pigmentosa. Arch Ophthalmol 1992;110:1634-9.

[5]Humayun MS, Prince M, de Juan E Jr. Morphometric analysis of the extramacular retina from postmortem eyes with retinitis pigmentosa. Invest Ophthalmol Vis Sci 1999;40:143-8.

[6]Naonori Ohno, Hideki Murai, Yukihisa Suzuki, et al. Alteration of the optic radiations using diffusion tensor MRI in patients with retinitis pigmentosa. Br J Ophthalmol 2015; 99:1051-4.

[7]John SK, Smith JE, Aguirre GD, et al. Loss of cone molecular markers in rhodopsin-mutant human retinas with retinitis pigmentosa. Mol Vis 2000;6:204-15.

[8]Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa. Lancet 2006;368:1795-809.

[9]Song SK, Sun SW, Ju WK, et al. Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia. Neuroimage 2003;20:1714-22.

[10]Xu J, Sun SW, Naismith RT, et al. Assessing optic nerve pathology with diffusion MRI: from mouse to human. NMR Biomed 2008;21:928-40.

[11]Michielse S1, Coupland N, Camicioli R, et al. Selective effects of aging on brain white matter microstructure: a diffusion tensor imaging tractography study. Neuroimage 2010;52:1190-201.

[12]Hui ES, Fu QL, So KF, et al. Diffusion tensor MR study of optic nerve degeneration in glaucoma. Conf Proc IEEE Eng Med Biol Soc 2007;2007:4312-5.

[13]Lin B, Peng EB. Retinal ganglion cells are resistant to photoreceptor loss in retinal degeneration. PLoS One 2013;8:e68084.

Figures

Figure 1: RFOV-DTI maps of the fractional anisotropy FA (A), mean diffusivity MD (B), principal eigenvalue (C) and orthogonal eigenvalue (D).

Figure 2: DTI parameters data of RP patients and controls. The values are mean± standard deviation (SD). *Significant difference between patient nerves and control nerves. R=right eye; L=left eye

Figure 3: Plot of fractional anisotropy (FA) and orthogonal eigenvalue λ⊥ versus mean deviation of visual field averaged across the pixels inside the regions of interest along the optic nerves of patients with RP, respectively.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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