MRI susceptibility map weighted imaging (SMWI) as a neurodegeneration biomarker in the prodromal to overt alpha-synucleinopathy continuum

Background and objective Nigrostriatal dopaminergic degeneration is commonly assessed using dopamine transporter (DaT) SPECT. Iron sensitive MRI is a promising technique to assess substantia nigra, yet few studies explored its application in the prodromal stage of alpha-synucleinopathies. Here, we used susceptibility map weighted imaging (SMWI) to assess the swallow tail sign, a radiological marker for substantia nigra integrity, to detect neurodegeneration across the alpha-synucleinopathy continuum. Methods 3T-MRI was performed on 115 subjects: 27 overt alpha-synucleinopathies, 34 prodromal alpha-synucleinopathies, 28 Alzheimer's disease and 26 healthy controls. SMWI was obtained with 3D multi-echo gradient-echo imaging. The presence/absence of the swallow tail sign was visually evaluated on SMWI by two neuroradiologists, blinded to the diagnosis. Swallow tail sign's visual assessment was compared across groups to investigate its sensitivity and specificity in identifying alpha-synucleinopathies. Additionally, we compared the SMWI visual analysis sign with both substantia nigra quantitative susceptibility mapping (QSM) and DaT-SPECT. Results The two radiologists' inter-rater agreement was substantial (kappa = 0.8). Visual analysis showed good sensitivity (0.85) and specificity (0.82) in identifying patients with alpha-synucleinopathies. When the subjects were grouped based on DaT-SPECT results, sensitivity increased (0.92), while specificity decreased (0.74). Visual scoring was associated with quantitative substantia nigra MRI assessment obtained with QSM (p < 0.001). Lastly, subjects with the swallow tail sign rated as absent showed significantly lower (p = 0.019) uptake at DaT-SPECT (-1.857 +/- 1.343) compared to those with the swallow tail sign rated as present (-0.385 +/- 1.850). Conclusions Visual analysis of SMWI swallow tail sign represents a new and reliable approach for evaluating substantia nigra neurodegeneration across the alpha-synucleinopathy continuum.