Quantitative MRI Biomarkers for Early Muscle Involvement in Late Onset Pompe Disease

Area of Science:

• Neurology
• Medical Imaging
• Biomarkers

Background:

• Early detection of muscle involvement is crucial for timely treatment in late-onset Pompe disease (LOPD).
• Quantitative muscle MRI (qMRI) shows promise for assessing subclinical muscle changes in LOPD.
• LOPD diagnosis and management require sensitive tools to monitor disease progression and treatment efficacy.

Purpose of the Study:

• To evaluate the utility of quantitative muscle MRI (qMRI) parameters, including fat fraction (FF) and water T2 (wT2), in detecting and quantifying muscle involvement in LOPD patients.
• To assess the correlation between qMRI findings and clinical, functional, and respiratory outcomes in early-stage and symptomatic LOPD.
• To identify specific qMRI metrics, such as the adductor magnus (AM)/rectus femoris (RF) FF ratio, that can discriminate between disease stages and healthy controls.

Main Methods:

• A multicenter prospective study involving 33 LOPD patients (early-stage and symptomatic) and 34 controls.
• Acquisition of thigh MRIs at 3T using T1-weighted and STIR sequences for FF and wT2 calculations.
• Analysis of FF and wT2 in 11 thigh regions, evaluation of the AM/RF FF ratio, and calculation of a wT2 involvement score (WIS).

Main Results:

• Thigh FF strongly correlated with clinical disease severity scales (ρ up to 0.86).
• The adductor magnus (AM) FF (AUC: 0.96) and AM/RF FF ratio (AUC: 0.94) effectively discriminated LOPD stages.
• Symptomatic LOPD patients exhibited higher wT2 involvement scores (WIS) compared to early-stage patients and controls.

Conclusions:

• Thigh FF is a robust biomarker for LOPD disease severity.
• AM FF and the age-independent AM/RF FF ratio are sensitive to early structural muscle changes in LOPD.
• qMRI parameters, including FF and WIS, show potential for guiding optimal therapy initiation timing in LOPD upon longitudinal validation.