Microstructural Integrity of MS Lesions Phenotyped by TSPO-PET: A Multimodal Imaging Study
Seppä, Susanna (2025-09-25)
Microstructural Integrity of MS Lesions Phenotyped by TSPO-PET: A Multimodal Imaging Study
(25.09.2025)
Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty.
suljettu
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe20251107105881
https://urn.fi/URN:NBN:fi-fe20251107105881
Tiivistelmä
Background: Chronic T1-hypointense lesions in multiple sclerosis (MS) can be phenotyped with translocator protein (TSPO) positron emission tomography (PET) based on microglial activity. However, the microstructural properties of TSPO-high lesions and their relationship to disability remain unclear.
Aim: To investigate the microstructural integrity of chronic T1-hypointense lesions and their association with disability using diffusion tensor imaging (DTI) and TSPO PET.
Methods: 110 MS patients (82 relapsing–remitting, 28 progressive) and 16 healthy controls underwent DTI-MRI and [11C]PK11195 TSPO-PET. Lesions were classified as rim-active, overall-active, or inactive based on TSPO uptake patterns. DTI metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), were measured in lesion cores and in the 0–2 mm, 2–4 mm, and 4–6 mm perilesional zones. Disability was assessed by the Expanded Disability Status Scale (EDSS) at the time of imaging.
Results: Across 2241 lesions, 53% were overall-active, 32% inactive, and 15% rim-active based on TSPO-binding characteristics. Rim-active lesions showed the highest FA (0.296) and lowest MD (1.040), AD (1.366), and RD (0.872) in the lesion core, whereas inactive lesions showed the lowest FA (0.278) and highest MD (1.138), AD (1.493), and RD (0.961). These patterns were consistent across perilesional zones, with rim-active lesions generally exhibiting the highest FA and lowest diffusivity values. Rim-active and overall-active lesion counts and volumes correlated positively with EDSS (ρ = 0.32–0.45, all p < 0.005), while a higher proportion of inactive lesions correlated negatively with EDSS (ρ = –0.28, p = 0.003). Lesional DTI metrics were not associated with EDSS, whereas TSPO uptake and abnormal DTI in normal-appearing white matter (NAWM) showed strong correlations with disability.
Conclusions: The TSPO-PET-based phenotypes of chronic lesions associate with distinct DTI-MRI patterns. Rim-active lesions had the highest FA and lowest MD, AD and RD values, reflecting restricted diffusion and the smallest water content, potentially linked to the dense clustering of microglia and macrophages around these lesions. TSPO-high chronic lesions and NAWM showed a stronger association with disability compared to lesion-level DTI measures, highlighting the better sensitivity of PET to clinically relevant lesional pathology.
Aim: To investigate the microstructural integrity of chronic T1-hypointense lesions and their association with disability using diffusion tensor imaging (DTI) and TSPO PET.
Methods: 110 MS patients (82 relapsing–remitting, 28 progressive) and 16 healthy controls underwent DTI-MRI and [11C]PK11195 TSPO-PET. Lesions were classified as rim-active, overall-active, or inactive based on TSPO uptake patterns. DTI metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), were measured in lesion cores and in the 0–2 mm, 2–4 mm, and 4–6 mm perilesional zones. Disability was assessed by the Expanded Disability Status Scale (EDSS) at the time of imaging.
Results: Across 2241 lesions, 53% were overall-active, 32% inactive, and 15% rim-active based on TSPO-binding characteristics. Rim-active lesions showed the highest FA (0.296) and lowest MD (1.040), AD (1.366), and RD (0.872) in the lesion core, whereas inactive lesions showed the lowest FA (0.278) and highest MD (1.138), AD (1.493), and RD (0.961). These patterns were consistent across perilesional zones, with rim-active lesions generally exhibiting the highest FA and lowest diffusivity values. Rim-active and overall-active lesion counts and volumes correlated positively with EDSS (ρ = 0.32–0.45, all p < 0.005), while a higher proportion of inactive lesions correlated negatively with EDSS (ρ = –0.28, p = 0.003). Lesional DTI metrics were not associated with EDSS, whereas TSPO uptake and abnormal DTI in normal-appearing white matter (NAWM) showed strong correlations with disability.
Conclusions: The TSPO-PET-based phenotypes of chronic lesions associate with distinct DTI-MRI patterns. Rim-active lesions had the highest FA and lowest MD, AD and RD values, reflecting restricted diffusion and the smallest water content, potentially linked to the dense clustering of microglia and macrophages around these lesions. TSPO-high chronic lesions and NAWM showed a stronger association with disability compared to lesion-level DTI measures, highlighting the better sensitivity of PET to clinically relevant lesional pathology.