Quantitative MRI Assessment Using Variable Echo Time Imaging of Peripheral Nerve Injury in ATTRv Amyloidosis Patients

Background and Purpose: Early detection of peripheral nerve damage in patients with hereditary transthyretin amyloidosis (ATTRv) has become essential for the prompt initiation of effective, recently approved therapies. In our study, we propose a new variable echo time (vTE) MRI sequence as a non-invasive method to detect nerve injury in ATTRv patients and to establish a novel potential imaging marker of neuropathy that correlates with disease severity and abnormal results of NCS. Methods: In this cohort study, twenty patients with clinically confirmed ATTRv polyneuropathy (PNP) and twenty-one healthy volunteers underwent 3 T MRI. vTE was performed on the right thigh to include the proximal tract of the sciatic nerve. The cross-sectional area of the whole sciatic nerve, inner epineurium, and endoneurial fascicles was segmented, and the corresponding pseudo-T2* was extrapolated from the two acquired echoes of the vTE. Results: Significantly higher fascicles pT2* (p = < 0.001), total cross-sectional area (CSA: p = 0.017) and fascicular area (p = < 0.001) were found in the ATTRv group compared to healthy controls. Fascicles pT2* also correlated with previously validated clinical outcome measures such as Polyneuropathy Disability Scoring System (PND score p = < 0. 001), Neuropathy Impairment Score (NIS p = 0.030) and NIS items related to the lower limbs, and with nerve conduction parameters, demonstrating the ability to discriminate ATTRv patients with different degrees of PNP from HC. Conclusion: In conclusion, the vTE sequence provides novel and reliable imaging markers capable of detecting early nerve microstructural changes related to disease onset and severity.