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

Giuseppe Pontillo; Mario Tranfa; Alessandra Scaravilli; Serena Monti; Ivana Capuano; Eleonora Riccio; Manuela Rizzo; Arturo Brunetti; Giuseppe Palma; Antonio Pisani; Sirio Cocozza

doi:10.1007/s00234-024-03380-5

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

Neuroradiology. 2024 May 21. doi: 10.1007/s00234-024-03380-5. Online ahead of print.

Authors

Affiliations

¹ Department of Advanced Biomedical Sciences, University of Naples "Federico II", Via Pansini 5, 80131, Naples, Italy.
² Institute of Biostructure and Bioimaging, National Research Council, Naples, Italy.
³ Department of Public Health, University of Naples "Federico II", Naples, Italy.
⁴ Institute for Biomedical Research and Innovation, National Research Council, Palermo, Italy.
⁵ Institute of Nanotechnology, National Research Council, Lecce, Italy.
⁶ Department of Advanced Biomedical Sciences, University of Naples "Federico II", Via Pansini 5, 80131, Naples, Italy. sirio.cocozza@unina.it.

PMID: 38771548
DOI: 10.1007/s00234-024-03380-5

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 (p_FWE = 0.02) and WM (p_FWE = 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.