Measuring Connectivity in the Primary Visual Pathway in Human Albinism Using Diffusion Tensor Imaging and Tractography

Summary

This manuscript describes deterministic and probabilistic algorithms for white matter (WM) reconstruction, used to examine differences in optic radiation (OR) connectivity between albinism and controls. Although probabilistic tractography follows the true course of nerve fibers more closely, deterministic tractography was run to compare the reliability and reproducibility of both techniques.

Abstract

In albinism, the number of ipsilaterally projecting retinal ganglion cells (RGCs) is significantly reduced. The retina and optic chiasm have been proposed as candidate sites for misrouting. Since a correlation between the number of lateral geniculate nucleus (LGN) relay neurons and LGN size has been shown, and based on previously reported reductions in LGN volumes in human albinism, we suggest that fiber projections from LGN to the primary visual cortex (V1) are also reduced. Studying structural differences in the visual system of albinism can improve the understanding of the mechanism of misrouting and subsequent clinical applications. Diffusion data and tractography are useful for mapping the OR (optic radiation). This manuscript describes two algorithms for OR reconstruction in order to compare brain connectivity in albinism and controls.An MRI scanner with a 32-channel head coil was used to acquire structural scans. A T1-weighted 3D-MPRAGE sequence with 1 mm³ isotropic voxel size was used to generate high-resolution images for V1 segmentation. Multiple proton density (PD) weighted images were acquired coronally for right and left LGN localization. Diffusion tensor imaging (DTI) scans were acquired with 64 diffusion directions. Both deterministic and probabilistic tracking methods were run and compared, with LGN as the seed mask and V1 as the target mask. Though DTI provides relatively poor spatial resolution, and accurate delineation of OR may be challenging due to its low fiber density, tractography has been shown to be advantageous both in research and clinically. Tract based spatial statistics (TBSS) revealed areas of significantly reduced white matter integrity within the OR in patients with albinism compared to controls. Pairwise comparisons revealed a significant reduction in LGN to V1 connectivity in albinism compared to controls. Comparing both tracking algorithms revealed common findings, strengthening the reliability of the technique.

Introduction

Albinism is a genetic condition primarily characterized by overt hypopigmentation observed in affected individuals. It is caused by inherited mutations to genes involved in melanin synthesis¹. Albinism appears in two main forms: oculo-cutaneous albinism (OCA), an autosomal recessive trait presenting both ocular and cutaneous features; and ocular albinism (OA), an X-linked trait more prevalent in males and characterized primarily by the ocular symptoms². Melanin in the retinal pigment epithelium (RPE) is crucial for proper development of the central visual pathway. Its absence in albinism therefore results in visual impairments, including photopho....

Protocol

Ethics Statement: The current research study has been approved by the Human Participants Review Committee (HPRC) at York University, Toronto. All participants gave informed written consent.

1. Subject Preparation

Note: Eleven participants with OCA, aged 36 ± 4 years (6 females) were compared to ten age-matched controls, aged 32 ± 4 years (6 females). Participant history is recorded in Table 1.

1. Ask each participant to fill out and sign a consent form that lists MRI safety guidelines and imaging protocol.
2. For each participant, provide earplugs for the ears. Position participan....

Results

This section provides a summary of results obtained using two different algorithms of tractography, deterministic and probabilistic. LGN volumes in PD space in which masks were originally drawn, as well as in all other spaces used in this study, are recorded in Table 2, and LGN tracing is illustrated in Figure 4. The results reported here are based on runs that used a standard sphere as the LGN ROI. Standard LGN volume was 461 mm³

Discussion

Altered WM and, more specifically, decreased connectivity in albinism compared to controls were expected. Thus, the reduced FA in the right hemisphere of albinism compared to controls as well as the decreased connectivity in male patients with albinism reported here are in line with our prediction. Gender and hemisphere effects are not completely clear, although research on the healthy brain that suggests decreased WM complexity in the left hemisphere of males compared to females^30-31 could explain some of the.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Magnetom Tim Trio 3T MRI	Siemens (Erlangen, Germany)
FMRIB’s Software Library (FSL)			http://www.fmrib.ox.ac.uk/fsl/
FreeSurfer			http://surfer.nmr.mgh.harvard.edu
DSI Studio			http://dsi-studio.labsolver.org
SPSS