Role of Dual-Phase 18F FP-CIT PET for Subtyping of Multiple System Atrophy

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder with heterogeneous subtypes, including cerebellar (MSA-C) and parkinsonian (MSA-P). Dual-tracer PET imaging using 18F FDG and dopamine transporter (DAT) scans provides pathophysiologic insight but poses limitations in cost and resources. Dual-phase 18F FP-CIT PET offers an alternative by capturing perfusion-like and DAT signals in a single scan.

To evaluate the diagnostic and phenotypic utility of dual-phase 18F FP-CIT PET in early-stage MSA.

We retrospectively studied 39 patients with clinically established MSA who underwent dual-phase 18F FP-CIT PET within 2 years of symptom onset. Early-phase (0-10 min) images assessed perfusion-like uptake, and delayed-phase (90 min) images measured DAT uptake. PET patterns were visually classified as normal, presynaptic, or trans-synaptic based on DAT and putamen perfusion in the early phase, and compared across clinical subtypes, putaminal 3T MRI findings (DWI and SWI), and clinical severity. In addition, regional SUVR was compared across MSA subtypes and clinical severity.

Striatal PET patterns differed by subtype (P<0.001): Trans-synaptic pattern was predominant in MSA-P, while normal and presynaptic patterns were more common in MSA-C. MRI abnormalities in the putamen were present in all patients with abnormal putamen on early PET, but also in 58% of patients with normal PET. Early- and delayed-phase striatal SUVRs correlated inversely with UPDRS part III scores (P<0.001). Asymmetry of cerebellar perfusion on early PET was significantly elevated in MSA-C compared with MSA-P (P<0.001). Levodopa responsiveness was most frequent in patients with trans-synaptic PET patterns.

Dual-phase 18F FP-CIT PET provides a single-session approach for capturing both perfusion and DAT status, enabling subtype classification and disease severity assessment in early MSA. Putaminal abnormality on early FP-CIT PET might be less sensitive than MRI, and asymmetric cerebellar perfusion could be a useful marker for differential diagnosis of ataxia.