Early Diagnosis of Murine Sepsis-Associated Encephalopathy Using Dynamic PET/CT Imaging and Multiparametric MRI

Abstract

Purpose: Early diagnosis of sepsis-associated encephalopathy (SAE) is essential for the treatment and prognosis of septic patients. Static PET and MRI have shown promise for early diagnosis, while pharmacokinetic parameters from dynamic PET may provide better quantification for SAE. This study aims to compare the performance of dynamic 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]F-FDG) PET and multiparametric MRI in early imaging SAE with a view to providing guidance for the early diagnosis of SAE.

Procedures: Dynamic [¹⁸F]F-FDG-PET/CT scans and multiparametric MRI were performed in SAE mice induced by LPS. Standardized uptake value (SUV) was measured in static scan images and [¹⁸F]F-FDG pharmacokinetic parameters were analyzed with two-tissue compartment model and Patlak plot. MRI relative signal intensity (rT1) derived from T1-weighted images (pre and post contrast) and 4 parameters originating from diffusion-weighted data were measured.

Results: Both SUV and dephosphorylation rate constant (k₄) increased in SAE model as early as 6 h post sepsis induction, while k₄ increased with the relative value (SAE/normal) significantly stronger than that of SUV. Moreover, the net influx constant (K_i) showed significant decrease in SAE as early as 6 h compared with normal mice. Increased signal intensity was identified in T1-weighted contrast enhanced images and rT1 value increased at 12 h post induction. Diffusion tensor imaging (DTI) revealed fractional anisotropy (FA) decreased at 12 h and 24 h in external capsule (ec) and declined axial diffusivity (AD) was shown in white matter at 24 h.

Conclusions: The dynamic PET (k₄) was more sensitive than static PET (SUV) for early diagnosis of SAE and declined K_i was firstly found in murine SAE, which indicated the advantage of dynamic PET/CT in early detection and differential diagnosis of SAE. While MRI has a higher soft tissue resolution than PET/CT and can classify more subtle brain areas, the comprehensive utilization of the two modalities is helpful for managing SAE.

Keywords: Dynamic PET/CT; Multiparametric magnetic resonance imaging; Sepsis; Sepsis-associated encephalopathy; [18F]F-FDG.