P2X -receptor binding in new-onset and secondary progressive MS - a [C]SMW139 PET study.

Background: PET imaging of activated microglia has improved our understanding of the pathology behind disability progression in MS, and pro-inflammatory microglia at 'smoldering' lesion rims have been implicated as drivers of disability progression. The P2X R is upregulated in the cellular membranes of activated microglia. A single-tissue dual-input model was applied to quantify P2X R binding in the normal appearing white matter, perilesional areas and thalamus among progressive MS patients, healthy controls and newly diagnosed relapsing MS patients.

Prolonged viral pneumonia and high mortality in COVID-19 patients on anti-CD20 monoclonal antibody therapy.

Purpose: In clinical practice, we observed an apparent overrepresentation of COVID-19 patients on anti-CD20 monoclonal antibody therapy. The aim of this study was to characterize the clinical picture of COVID-19 in these patients.

Methods: All adult patients from Turku University Hospital, Turku, Finland, with COVID-19 diagnosis and/or positive SARS-CoV-2 PCR test result up to March 2023, and with anti-CD20 therapy within 12 months before COVID-19 were included.

TSPO-Detectable Chronic Active Lesions Predict Disease Progression in Multiple Sclerosis.

Background And Objectives: In the multiple sclerosis (MS) brain, chronic active lesions can be detected using MRI- and PET-based methods. In this study, we investigated whether the frequency of TSPO-PET-detectable chronic active lesions associates with disease progression measured using the Expanded Disability Status Scale (EDSS) at 5-year follow-up.

Methods: Chronic lesion-associated innate immune cell activation was evaluated using TSPO-PET in 82 patients with MS.

Association of serum neurofilament light with microglial activation in multiple sclerosis.

Background: Translocator protein (TSPO)-PET and neurofilament light (NfL) both report on brain pathology, but their potential association has not yet been studied in multiple sclerosis (MS) in vivo. We aimed to evaluate the association between serum NfL (sNfL) and TSPO-PET-measurable microglial activation in the brain of patients with MS.

Methods: Microglial activation was detected using PET and the TSPO-binding radioligand [C]PK11195.

PET-measurable innate immune cell activation reduction in chronic active lesions in PPMS brain after rituximab treatment: a case report.

Objectives: To evaluate the effects of rituximab treatment on innate immune cell activation in primary progressive multiple sclerosis (PPMS).

Methods: A 48-year-old woman with PPMS was started on rituximab shortly after diagnosis. [C]PK11195 PET imaging was employed to assess innate immune cell activation with special interest in the white matter around chronic lesions.

Innate Immune Cell-Related Pathology in the Thalamus Signals a Risk for Disability Progression in Multiple Sclerosis.

Background And Objectives: Our aim was to investigate whether 18-kDa translocator protein (TSPO) radioligand binding in gray matter (GM) predicts later disability progression in multiple sclerosis (MS).

Methods: In this prospective imaging study, innate immune cells were investigated in the MS patient brain using PET imaging. The distribution volume ratio (DVR) of the TSPO-binding radioligand [C]PK11195 was determined in 5 GM regions: thalamus, caudate, putamen, pallidum, and cortical GM.

Association between microglial activation and serum kynurenine pathway metabolites in multiple sclerosis patients.

Background: Microglial activation associates with MS progression but it is unclear what drives their persistent pro-inflammatory state. Metabolites of the kynurenine pathway (KP), the main metabolism route of tryptophan, can influence the function of brain innate immune cells.

Objective: To investigate whether tryptophan metabolites in blood associate with TSPO-PET measurable microglial activation in MS brain.

Phenotyping of multiple sclerosis lesions according to innate immune cell activation using 18 kDa translocator protein-PET.

Chronic active lesions are promotors of neurodegeneration and disease progression in multiple sclerosis. They harbour a dense rim of activated innate immune cells at the lesion edge, which promotes lesion growth and thereby induces damage. Conventional MRI is of limited help in identifying the chronic active lesions, so alternative imaging modalities are needed.

Whole Brain Adiabatic T and Relaxation Along a Fictitious Field Imaging in Healthy Volunteers and Patients With Multiple Sclerosis: Initial Findings.

Background: In preclinical models of multiple sclerosis (MS), both adiabatic T (T ) and relaxation along a fictitious field (RAFF) imaging have demonstrated potential to noninvasively characterize MS.

Purpose: To evaluate the feasibility of whole brain T and RAFF imaging in healthy volunteers and patients with MS.

Study Type: Single institutional clinical trial.

Increased serum glial fibrillary acidic protein associates with microstructural white matter damage in multiple sclerosis: GFAP and DTI.

Background: Astrocytes and microglial cells are now recognized as active players in contributing to the diffuse neuroaxonal damage associated with disease progression of multiple sclerosis (MS). The serum level of glial fibrillary acidic protein (GFAP), a biomarker for astrocytic activation, is increased in MS and associates with disease progression and disability. Similarly, diffusion tensor imaging (DTI) parameters for microstructural changes in brain, including demyelination and axonal loss, associate with disability.

Fingolimod treatment reverses signs of diffuse white matter damage in multiple sclerosis: A pilot study.

Background: In multiple sclerosis (MS) diffuse normal appearing white matter (NAWM) damage may drive chronic worsening independent of relapse activity. Diffusion tensor imaging (DTI) is a nonconventional MRI technique that can be used to assess microstructural alterations in myelin and axons. The aim of our study was to investigate the effect of six months fingolimod treatment on the integrity of entire and segmented NAWM in patients with relapsing-remitting multiple sclerosis (RRMS).

High serum neurofilament associates with diffuse white matter damage in MS.

Objective: To evaluate to which extent serum neurofilament light chain (NfL) increase is related to diffusion tensor imaging-MRI measurable diffuse normal-appearing white matter (NAWM) damage in MS.

Methods: Seventy-nine patients with MS and 10 healthy controls underwent MRI including diffusion tensor sequences and serum NfL determination by single molecule array (Simoa). Fractional anisotropy and mean, axial, and radial diffusivities were calculated within the whole and segmented (frontal, parietal, temporal, occipital, cingulate, and deep) NAWM.

Brain TSPO-PET predicts later disease progression independent of relapses in multiple sclerosis.

Overactivation of microglia is associated with most neurodegenerative diseases. In this study we examined whether PET-measurable innate immune cell activation predicts multiple sclerosis disease progression. Activation of microglia/macrophages was measured using the 18-kDa translocator protein (TSPO)-binding radioligand 11C-PK11195 and PET imaging in 69 patients with multiple sclerosis and 18 age- and sex-matched healthy controls.

Insights into disseminated MS brain pathology with multimodal diffusion tensor and PET imaging.

Objective: To evaluate in vivo the co-occurrence of microglial activation and microstructural white matter (WM) damage in the MS brain and to examine their association with clinical disability.

Methods: 18-kDa translocator protein (TSPO) brain PET imaging was performed for evaluation of microglial activation by using the radioligand [C](R)-PK11195. TSPO binding was evaluated as the distribution volume ratio (DVR) from dynamic PET images.

Rituximab in the treatment of multiple sclerosis in the Hospital District of Southwest Finland.

Background: There are already numerous B-cell depleting monoclonal anti-CD20 antibodies which have been used to reduce the inflammatory burden associated with multiple sclerosis (MS). We describe here our experience of treating MS-patients with B-cell depleting rituximab.

Patients And Methods: All MS-patients (n = 72) who had received rituximab treatment for at least six months by January 2019 were identified from the patient charts at the Turku University Hospital.

Effects of age, BMI and sex on the glial cell marker TSPO - a multicentre [C]PBR28 HRRT PET study.

Purpose: The purpose of this study was to investigate the effects of ageing, sex and body mass index (BMI) on translocator protein (TSPO) availability in healthy subjects using positron emission tomography (PET) and the radioligand [C]PBR28.

Methods: [C]PBR28 data from 140 healthy volunteers (72 males and 68 females; N = 78 with HAB and N = 62 MAB genotype; age range 19-80 years; BMI range 17.6-36.

Natalizumab treatment reduces microglial activation in the white matter of the MS brain.

Objective: To evaluate whether natalizumab treatment reduces microglial activation in MS.

Methods: We measured microglial activation using the 18-kDa translocator protein (TSPO)-binding radioligand [C]PK11195 and PET imaging in 10 patients with MS before and after 1 year treatment with natalizumab. Microglial activation was evaluated as the distribution volume ratio (DVR) of the specifically bound radioligand in brain white and gray matter regions of interest.

Microglial activation, white matter tract damage, and disability in MS.

Objective: To investigate the relationship of in vivo microglial activation to clinical and MRI parameters in MS.

Methods: Patients with secondary progressive MS (n = 10) or relapsing-remitting MS (n = 10) and age-matched healthy controls (n = 17) were studied. Microglial activation was measured using PET and radioligand [C]()-PK11195.

Evaluation of the Effect of Fingolimod Treatment on Microglial Activation Using Serial PET Imaging in Multiple Sclerosis.

Traditionally, multiple sclerosis (MS) has been considered a white matter disease with focal inflammatory lesions. It is, however, becoming clear that significant pathology, such as microglial activation, also takes place outside the plaque areas, that is, in areas of normal-appearing white matter (NAWM) and gray matter (GM). Microglial activation can be detected in vivo using 18-kDa translocator protein (TSPO)-binding radioligands and PET.