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

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 mm(3) 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.

Improving the Quantification of the Lateral Geniculate Nucleus in Magnetic Resonance Imaging Using a Novel 3D-Edge Enhancement Technique

“…Depending on whether no or all partial volume voxels are accounted for as part of LGN volume, the measured volume of the LGN would be between 110.6 and 262.1 mm 3 (or ∼2.4-fold), thus making the partial volume uncertainty the major source of the variability in the LGN volume measurements. For example, the range of human LGN volume measured in proton density MR images of 100-240 mm 3 (Bürgel et al, 1999) or 112-276 mm 3 (Grigorian et al, 2016) is in good agreement with our estimate of the range of LGN volume of 110.6-262.1 mm 3 . The partial volume uncertainty can generally be decreased by increasing image resolution (McKetton et al, 2015;Aldusary et al, 2019), but that often results in lower CNR and, therefore, a much noisier image.…”

“…The LGN volume measurements in our study were highly consistent between the raters, with the inter class correlation coefficients (ICCs) of 0.74 and 0.81, which are above the minimum value of ICC of 0.70 for reliable measurements (Cohen, 2001). As mentioned earlier, such high reproducibility rates among two raters for the LGN volume measurements from a low contrast and noisy 3D images, as part of routine imaging protocol, is comparable to images acquired on a 3T systems with multiple signal averaging of up to 30-40 using a proton density weighted sequence with a long acquisition time (Kelly et al, 2014;McKetton et al, 2014McKetton et al, , 2015Moro et al, 2015;Grigorian et al, 2016;Giraldo-Chica and Schneider, 2018;DeSimone and Schneider, 2019). However, the LGN volumes are hardly consistent between the previously reported studies (Table 4), ranging from 76 mm 3 (Li et al, 2012) to 267 mm 3 (Korsholm et al, 2007), with the average of the left and right LGN volumes of 149.6 ± 45.8 mm 3 (mean ± SD, n = 27).…”

“…Application of this post-processing algorithm on the native images acquired on a typical MRI system (3T Magnet) using a routine clinical protocol (e.g., 3D T1 weighted) dramatically improved the visualization of the LGN (see Figures 4 , 7 ). To achieve a similar contrast, previous studies have employed MR sequences not routinely used in a clinical setting, which required over one hour of acquisition time ( Kelly et al, 2014 ; McKetton et al, 2014 , 2015 ; Moro et al, 2015 ; Grigorian et al, 2016 ; Giraldo-Chica and Schneider, 2018 ; DeSimone and Schneider, 2019 ), focusing only on improving LGN visualization, as compared to a short 7-min sequence used as part of a routine clinical protocol (e.g., 3D MPRAGE).…”

“…The LGN volume has also been reported to be reduced in patients with one eye ( Moro et al, 2015 ; Wong et al, 2018 ), in patients with neuromyelitis optica spectrum disorders ( Papadopoulou et al, 2019a , b ), glaucoma ( Dai et al, 2011 ; Hernowo et al, 2011 ; Zhang Y.Q. et al, 2012 ; Chen et al, 2013 ; Lee et al, 2014 ; Wang et al, 2015 , 2016 ; Schmidt et al, 2018 ), albinism ( McKetton et al, 2014 ; Grigorian et al, 2016 ), patients with hemianopia ( Bridge et al, 2011 ), and patients with Parkinson’s disease ( Bohnen et al, 2019 ). The volume of the LGN has also been shown to be significantly affected by the normal aging process ( Li et al, 2012 ).…”

Aberrant visual pathway development in albinism: From retina to cortex

“…By quantifying the magnitude and principle direction of water diffusion within image voxels, DTI data can be used for reconstruction of principle white matter tracts, a technique referred to as tractography (Beaulieu, ). Grigorian et al used the technique to study the optic radiation and found that in albinism, fibres from lateral geniculate nucleus (LGN) to the primary visual cortex (V1) are reduced (Grigorian, McKetton, & Schneider, ).…”