In vivo demonstration of globotriaosylceramide brain accumulation in Fabry Disease using MR Relaxometry

Neuroradiology. 2024 Sep;66(9):1593-1601. doi: 10.1007/s00234-024-03380-5. Epub 2024 May 21.

Abstract

Purpose: How to measure brain globotriaosylceramide (Gb3) accumulation in Fabry Disease (FD) patients in-vivo is still an open challenge. The objective of this study is to provide a quantitative, non-invasive demonstration of this phenomenon using quantitative MRI (qMRI).

Methods: In this retrospective, monocentric cross-sectional study conducted from November 2015 to July 2018, FD patients and healthy controls (HC) underwent an MRI scan with a relaxometry protocol to compute longitudinal relaxation rate (R1) maps to evaluate gray (GM) and white matter (WM) lipid accumulation. In a subgroup of 22 FD patients, clinical (FAbry STabilization indEX -FASTEX- score) and biochemical (residual α-galactosidase activity) variables were correlated with MRI data. Quantitative maps were analyzed at both global ("bulk" analysis) and regional ("voxel-wise" analysis) levels.

Results: Data were obtained from 42 FD patients (mean age = 42.4 ± 12.9, M/F = 16/26) and 49 HC (mean age = 42.3 ± 16.3, M/F = 28/21). Compared to HC, FD patients showed a widespread increase in R1 values encompassing both GM (pFWE = 0.02) and WM (pFWE = 0.02) structures. While no correlations were found between increased R1 values and FASTEX score, a significant negative correlation emerged between residual enzymatic activity levels and R1 values in GM (r = -0.57, p = 0.008) and WM (r = -0.49, p = 0.03).

Conclusions: We demonstrated the feasibility and clinical relevance of non-invasively assessing cerebral Gb3 accumulation in FD using MRI. R1 mapping might be used as an in-vivo quantitative neuroimaging biomarker in FD patients.

Keywords: Brain; Fabry Disease; Magnetic Resonance Imaging; Relaxometry.

MeSH terms

  • Adult
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Case-Control Studies
  • Cross-Sectional Studies
  • Fabry Disease* / diagnostic imaging
  • Fabry Disease* / metabolism
  • Female
  • Humans
  • Magnetic Resonance Imaging* / methods
  • Male
  • Middle Aged
  • Retrospective Studies
  • Trihexosylceramides* / metabolism
  • White Matter / diagnostic imaging
  • White Matter / metabolism

Substances

  • Trihexosylceramides
  • globotriaosylceramide