Assessment of myelin content using [11C]PIB PET-MR images of the cervical spinal cord in patients with different multiple sclerosis phenotypes and healthy volunteers

Author(s)

Leticia Zorante de Lucena

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
• Defense date: 2024-06-25

Examining board members

Daniele de Paula Faria; Suely Kazue Nagahashi Marie; Milena Sales Pitombeira; Marcelo Tatit Sapienza

• Advisor: Daniele de Paula Faria

Abstract

Introduction: Multiple sclerosis (MS) is a neurodegenerative disease of the central nervous system (CNS), characterized by a clinical course divided into Progressive MS (PMS) and Relapsing-Remitting MS (RRMS). The diagnosis and progression evaluation of MS are based on functional parameters, laboratory tests, and Magnetic Resonance Imaging (MRI). Studies of the spinal cord using Positron Emission Tomography (PET) imaging are necessary since up to 90% of patients with MS have spinal cord lesions, with the cervical region being particularly relevant due to increased lesion burden and severity of atrophy. These factors are associated with motor function changes in both upper and lower limbs. PET imaging and MRI acquired in a PET-MR hybrid equipment can provide new insights in understanding the heterogeneous behavior of the disease in the cervical spinal cord of affected individuals. Objectives: The aim of this study was to evaluate myelin content in the cervical spinal cord of patients with MS and healthy volunteers (HV) through hybrid PET-MR images and correlate the imaging data with clinical findings of these individuals. Methods: [11C]PIB (Pittsburgh Compound B) PET images and T1 weighted MRI of 49 participants with MS and 19 HV were used for drawing the volumes of interest (VOIs) in PMOD 4.1 Software. Each VOI was delimited based on anatomical level of C1-C2, C3 and C4 vertebrae. The [11C]PIB Standardized Uptake Value (SUV), Standardized Uptake Value ratio with muscle (SUVr) and volume (cm³) were determined. The p<0.05 was considered significative. Results: The uptake of [11C]PIB (SUV) and varied significantly among the RRMS and PMS groups at C1-C2 (p=0.014) and C3 (p=0.011), and SUVr at C1-C2 (p =0.020), C3 (p=0.023) and C4 (p=0.032). A significant smaller volume (cm³) of PMS compared to HV was obtained at C1-C4 (p=0.031). In the MS group, a moderate inverse correlation between [11C]PIB (SUV and SUVr) and Expanded Disability Status Scale (EDSS) at C1-C2 (r=-0.479; p<0.001) and (r=-0.427; p=0.003); C3 (r=-0.470; p<0.001) and (r=-0.454; p=0.002); and at C4 (r=-0.393; p=0.007) and (r=-0.386; p=0.008), respectively; between SUV, 9 Hole-peg-test (9HPT) and Timed 25 Foot Walk (25FW) at C1-C2 (r=-0.333; p=0.025) and (r=-0.355; p=0.016); C3 (p=-0.389; p=0.008) and (r=-0.319; p=0.030); and C4 (only for 25 FW; r=-0.309; p=0.037), respectively ; and between SUVr and 25FW at C1-C2 (r=-0.311; p=0.035) and C3 (r=-0.331; p=0.025) was observed. In the RRMS phenotype, a moderate inverse correlation between SUV and EDSS was observed at C1-C2 (r=-0.483; p=0.011), C3 (r=-0.440; p=0.022) e C4 (r=-0.420; p=0.029). For the PMS phenotype, a moderate inverse correlation between Volume and EDSS was obtained at C1-C2 (r=-0.503; p=0.040). Conclusion: The study findings show correlation between reduced [11C]PIB uptake and volume with increased functional disability. They suggest a complementary role between morphological information from MRI and physiological information from PET images in studying different MS phenotypes (AU)

• FAPESP's process: 21/00293-4 - Evaluation of neuroinflammation and myelin content using PET / MRI images of cervical spinal cord of patients with Multiple Sclerosis and healthy volunteers
• Grantee: Leticia Zorante de Lucena
• Support Opportunities: Scholarships in Brazil - Master