Identification of Metabolic Progression and Subtypes in Progressive Supranuclear Palsy by PET Molecular Imaging

Overview

Journal Eur J Nucl Med Mol Imaging

Specialties Biophysics
Nuclear Medicine
Radiology

Date 2024 Oct 22

PMID 39438298

Authors

Haotian Wang

Bo Wang

Yi Liao

Jiaqi Niu

Miao Chen

Xinhui Chen

Xiaofeng Dou

Congcong Yu

Yan Zhong

Jing Wang

Nan Jin

Yixin Kang

Hong Zhang

Mei Tian

Wei Luo

Affiliations

Soon will be listed here.

Abstract

Introduction: Progressive supranuclear palsy (PSP) is a neurodegenerative disorder with diverse clinical presentations that are linked to tau pathology. Recently, Subtype and Stage Inference (SuStaIn) algorithm, an innovative data-driven method, has been developed to model both the spatial-temporal progression and subtypes of disease. This study explores PSP progression using F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging and the SuStaIn algorithm to identify PSP metabolic progression subtypes and understand disease mechanisms.

Methods: The study included 72 PSP patients and 70 controls, with an additional 24 PSP patients enrolled as a test set, undergoing FDG-PET, dopamine transporter (DAT) PET, and neuropsychological assessments. The SuStaIn algorithm was employed to analyze the FDG-PET data, identifying progression subtypes and sequences.

Results: Two PSP subtypes were identified: the cortical subtype with early prefrontal hypometabolism and the brainstem subtype with initial midbrain alterations. The cortical subtype displayed greater cognitive impairment and DAT reduction than the brainstem subtype. The test set demonstrates the robustness and reproducibility of the findings. Pathway analysis indicated that disruptions in dopaminergic cortico-basal ganglia pathways are crucial for elucidating the mechanisms of cognitive and behavioral impairment in PSP, leading to the two metabolic progression subtypes.

Conclusion: This study identified two spatiotemporal progression subtypes of PSP based on FDG-PET imaging, revealing significant differences in metabolic patterns, striatal dopaminergic uptake, and clinical profiles, particularly cognitive impairments. The findings highlight the crucial role of dopaminergic cortico-basal ganglia pathways in PSP pathophysiology, especially in the cortical subtype, providing insights into PSP heterogeneity and potential avenues for personalized treatments.

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