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

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Applied Bio Materials Pub Date : 2024-09-01 Epub Date: 2024-05-21 DOI:10.1007/s00234-024-03380-5

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

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引用次数: 0

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.

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利用核磁共振弛豫测量法在法布里病患者脑内展示球形糖基甘油酰胺的积累。

目的：如何测量法布里病（Fabry Disease，FD）患者体内脑内球糖基甘油三酯（globotriaosylceramide，Gb3）的积累仍是一项挑战。本研究的目的是利用定量核磁共振成像（qMRI）对这一现象进行定量、无创的展示：在这项于 2015 年 11 月至 2018 年 7 月进行的回顾性单中心横断面研究中，FD 患者和健康对照组（HC）接受了采用弛豫测量方案的 MRI 扫描，计算纵向弛豫率（R1）图，以评估灰质（GM）和白质（WM）脂质堆积。在 22 例 FD 患者亚组中，临床（FABry STabilization indEX -FASTEX- 评分）和生化（残留的 α-半乳糖苷酶活性）变量与 MRI 数据相关。在全球（"整体 "分析）和区域（"体素 "分析）层面对定量图进行了分析：数据来自 42 名 FD 患者（平均年龄 = 42.4 ± 12.9，男/女 = 16/26）和 49 名 HC 患者（平均年龄 = 42.3 ± 16.3，男/女 = 28/21）。与 HC 相比，FD 患者的 R1 值广泛增加，包括 GM（pFWE = 0.02）和 WM（pFWE = 0.02）结构。虽然未发现 R1 值增加与 FASTEX 评分之间存在相关性，但残余酶活性水平与 GM（r = -0.57，p = 0.008）和 WM（r = -0.49，p = 0.03）中的 R1 值之间存在显著负相关：我们证明了利用磁共振成像无创评估 FD 大脑 Gb3 积累的可行性和临床相关性。R1图谱可作为FD患者体内定量神经影像生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464