In patients with retinal ganglion cell diseases, recent diffusion tensor imaging (DTI) studies have revealed structural abnormalities in visual white matter tracts such as the optic tract, and optic radiation. However, the microstructural origin of these diffusivity changes is unknown as DTI metrics involve multiple biological factors and do not correlate directly with specific microstructural properties. In contrast, recent quantitative T1 (qT1) mapping methods provide tissue property measurements relatively specific to myelin volume fractions in white matter. This study aims to improve our understanding of microstructural changes in visual white matter tracts following retinal ganglion cell damage in Leber's hereditary optic neuropathy (LHON) patients by combining DTI and qT1 measurements. We collected these measurements from seven LHON patients and twenty age-matched control subjects. For all individuals, we identified the optic tract and the optic radiation using probabilistic tractography, and evaluated diffusivity and qT1 profiles along them. Both diffusivity and qT1 measurements in the optic tract differed significantly between LHON patients and controls. In the optic radiation, these changes were observed in diffusivity but were not evident in qT1 measurements. This suggests that myelin loss may not explain trans-synaptic diffusivity changes in the optic radiation as a consequence of retinal ganglion cell disease.
Bibliographical noteFunding Information:
We thank Garikoitz Lerma-Usabiaga for suggestions in qT1 data collection, Kazuki Iijima in support of subject recruitment, Yusuke Sakai in support of data analysis, and Ariel Rokem for comments on an earlier version of the manuscript. This study was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI ( JP17H04684 , JP15J00412 to H.T.; JP17K18131 to S.O.; JP18K16939 to H.H.; JP19K09982 to Y.M), the Jikei University Research fund (to Y.M.) and Charitable Trust Fund for Ophthalmic Research in Commemoration of Santen Pharmaceutical's Founder (to Y.M. and H.H.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
© 2019 The Authors
- Leber's hereditary optic neuropathy
- Optic radiation
- Optic tract
- White matter