Characterisation of metabolite concentration in the lateral geniculate nucleus and visual cortex of patients with different severity of glaucoma using magnetic resonance spectroscopy

Abstract

ABSTRACT Glaucoma is an ocular disease that results progressive damage of the retinal nerve fibre layer which result to irreversible visual deterioration. Glaucoma impact on the brain is not conclusive. Even the magnetic resonance spectroscopy (MRS) findings in the visual pathway areas shown incoherent findings. This study aimed to investigate and measure the concentration of metabolites in the lateral geniculate nucleus (LGN) and visual cortex (VC) of subjects with glaucoma using MRS. The MRS measurement using a single-voxel spectroscopy (SVS) was performed using 1.5 Tesla MRI, on healthy young adults, healthy older adults, mild glaucoma, and severe glaucoma. A standardised volume of interest of 13mm x 13mm x 13mm was placed in the region of LGN and VC. Five metabolites were extracted and quantified from raw spectra using the AMARES (Advanced Method for Accurate, Robust, and Efficient Spectral Fitting) method within the Java-based magnetic resonance user interface (jMRUI). The quantification process yields amplitudes in arbitrary units of N-acetyl aspartate (NAA), glutamate-glutamine (Glx), creatine (Cr), choline (Cho), and Myo-Inositol (mI). Two consecutive scans were performed on each LGN and VC from both brain hemispheres of young healthy adults. The repeatability of MRS measurement in the LGN and VC were analysed. The LGN and VC of young healthy subjects and healthy elderly subjects were scanned. The metabolites were compared between groups. The metabolites in the LGN of healthy elderly subjects, participants with mild glaucoma and severe glaucoma were compared. The metabolites in the VC of healthy elderly subjects, participants with mild glaucoma and severe glaucoma were compared. The metabolites concentration in the LGN and VC showed no significant differences between consecutive scan (p>0.05). Analysis showed good agreement and small variability between the consecutive MRS measurements (bias in LGN: -0.46 to 1.17; bias in VC: -0.61 to -0.22). Healthy older adults have lower levels of NAA and higher levels of Glx, Cr, and Cho in the LGN compared to healthy young adults (p<0.05). In the VC, healthy older adults have higher levels of Cr, Cho and mI compared to healthy young adults (p<0.05). Severe glaucoma group has higher level of NAA (65.03±14.66; Tukey HSD, p=0.03) and lower level of Cho (14.09±5.07; Games-Howell, p=0.016) in the LGN compared to healthy group. Glx (604.93±93.55; Games-Howell, p=0.031) level in the VC was lower in severe glaucoma compared to healthy group while Cho/Cr (0.030±0.06; Tukey HSD, p=0.031) level in the VC was lower in severe glaucoma group compared to mild glaucoma group. The single voxel MRS using 1.5 Tesla MRI is repeatable in determining metabolites concentration in the LGN and VC. Age affects the NAA, Glx, Cr and Cho concentrations in the LGN, and Cr, Cho and mI concentrations in the VC. Metabolites analysis should consider aging into factor. Glaucoma may cause shift in the NAA and Cho concentration amplitudes and ratio in the LGN. Glaucoma may cause shift in the Glx and Cho/Cr concentration amplitudes and ratio in the VC. Further research in this area may help elucidate the underlying mechanisms of glaucoma and potentially aid in the development of novel diagnostic or therapeutic approaches.