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This comprehensive review aims to explore imaging outcome measures targeting compartmentalized inflammation in Phase 2 clinical trials for multiple sclerosis (MS). The traditional primary imaging outcomes used in Phase 2 MS trials, new or enhancing white matter lesions on MRI, target the effects of peripheral inflammation, but the widespread inflammation behind a mostly closed blood-brain barrier is not captured. This review discusses several emerging imaging technologies that could be used as surrogate markers of compartmentalized inflammation, targeting chronic active lesions, meningeal inflammation, and innate immune activation within the normal-appearing white matter and gray matter. The integration of specific imaging outcomes into Phase 2 trials can provide a more accurate assessment of treatment efficacy, ultimately contributing to the development of more effective therapies for MS. [ABSTRACT FROM AUTHOR]

Background: 11C-PBR28 positron emission tomography (PET), targeting the translocator protein, and paramagnetic rim lesions (PRL) have emerged as promising imaging markers of MS chronic inflammation. No consensus on which is the optimal marker exists. Objectives: To investigate the ability of 11C-PBR28 PET and PRL assessment to identify chronic inflammation in white matter (WM) MS lesions and their relation to neurological impairment. Methods: Based on 11C-PBR28 uptake, brain WM lesions from 30 MS patients were classified as PET active or inactive. The PRL presence was assessed on 7T phase reconstructions, T1/T2 ratio was calculated to measure WM microstructural integrity. Results: Less than half (44%) of non-PRL WM lesions were active on 11C-PBR28 imaging either throughout the lesion (whole active) or at its periphery. PET peripherally active lesions and PRL did not differ in T1/T2 ratio and 11C-PBR28 uptake. A positive correlation was observed between PRL and active PET lesion count. Whole active PET lesion volume was the strongest predictor (β = 0.97, p < 0.001) of increased Expanded Disability Status Scale scores. Conclusion: 11C-PBR28 imaging reveals more active WM lesions than 7T PRL assessment. Although PRL and PET active lesion counts are related, neurological disability is better explained by PET whole active lesion volume. [ABSTRACT FROM AUTHOR]

The given text is an index of authors who presented at the ACTRIMS Forum 2024. It is organized alphabetically by author's last name and includes page numbers where their work can be found in the Multiple Sclerosis Journal. The index covers a range of topics related to multiple sclerosis. Library patrons conducting research on specific topics may find this index helpful in locating relevant information within the journal. [Extracted from the article]

Background: Thalamic volume loss is known to be associated with clinical and cognitive disability in progressive multiple sclerosis (PMS). Objective: To investigate the treatment effect of ibudilast on thalamic atrophy more than 96 weeks in the phase 2 trial in progressive(MS Secondary and Primary Progressive Ibudilast NeuroNEXT Trial in Multiple Sclerosis [SPRINT-MS]). Methods: A total of 231 participants were randomized to either ibudilast (n = 114) or placebo (n = 117). Thalamic volume change was computed using Bayesian Sequence Adaptive Multimodal Segmentation tool (SAMseg) incorporating T1, fluid-attenuated inversion recovery (FLAIR), and fractional anisotropy maps and analyzed with a mixed-effects repeated-measures model. Results: There was no significant difference in thalamic volumes between treatment groups. On exploratory analysis, participants with primary progressive multiple sclerosis (PPMS) on placebo had a 0.004% greater rate of thalamic atrophy than PPMS participants on ibudilast (p = 0.058, 95% confidence interval (CI) = −0.008 to <0.001). Greater reductions in thalamic volumes at more than 96 weeks were associated with worsening multiple sclerosis functional composite (MSFC-4) scores (p = 0.002) and worsening performance on the symbol digit modality test (SDMT) (p < 0.001). Conclusion: In a phase 2 trial evaluating ibudilast in PMS, no treatment effect was demonstrated in preventing thalamic atrophy. Participants with PPMS exhibited a treatment effect that trended toward significance. Longitudinal changes in thalamic volume were related to worsening of physical and cognitive disability, highlighting this outcome's clinical importance. [ABSTRACT FROM AUTHOR]

Background: A growing body of evidence has shed light on the role of the hemostatic pathway and its components in the pathogenesis of multiple sclerosis (MS), particularly in enhancing and sustaining neuroinflammation. Objective: To review the clinical, experimental, and neuroimaging evidence supporting the role of different components of the hemostatic pathway in the pathogenesis of neuroinflammation in MS and discuss their translational potential as disease biomarkers and therapeutic targets. Methods: A literature search for most relevant articles from 1956 to 2020 was conducted in PubMed and Scopus. Results: Hemostasis components appear to be involved in different key events of neuroinflammation in MS including mononuclear cell diapedesis, microglia activation, and neuronal damage. Conclusion: The findings on the interplay between hemostatic and thrombotic molecular pathways in the pathogenesis of neuroinflammation in MS open new opportunities for developing novel biomarkers for disease monitoring and prognosis, as well as novel therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Dramatic improvements in visualization of cortical (especially subpial) multiple sclerosis (MS) lesions allow assessment of impact on clinical course. Objective: Characterize cortical lesions by 7 tesla (T) T2*-/T1-weighted magnetic resonance imaging (MRI); determine relationship with other MS pathology and contribution to disability. Methods: Sixty-four adults with MS (45 relapsing–remitting/19 progressive) underwent 3 T brain/spine MRI, 7 T brain MRI, and clinical testing. Results: Cortical lesions were found in 94% (progressive: median 56/range 2–203; relapsing–remitting: 15/0–168; p = 0.004). Lesion distribution across 50 cortical regions was nonuniform (p = 0.006), with highest lesion burden in supplementary motor cortex and highest prevalence in superior frontal gyrus. Leukocortical and white matter lesion volumes were strongly correlated (r = 0.58, p < 0.0001), while subpial and white matter lesion volumes were moderately correlated (r = 0.30, p = 0.002). Leukocortical (p = 0.02) but not subpial lesions (p = 0.40) were correlated with paramagnetic rim lesions; both were correlated with spinal cord lesions (p = 0.01). Cortical lesion volumes (total and subtypes) were correlated with expanded disability status scale, 25-foot timed walk, nine-hole peg test, and symbol digit modality test scores. Conclusion: Cortical lesions are highly prevalent and are associated with disability and progressive disease. Subpial lesion burden is not strongly correlated with white matter lesions, suggesting differences in inflammation and repair mechanisms. [ABSTRACT FROM AUTHOR]

B P453 b Chognot, C. P724 Choi, J. P350 Chomyk, A. B 175 b , P391 Chou, S. B P133 b Chouteau, R. P968 Chretien, N. P391 Christie, E. 175, P391 Christodoulou, C. P353, P985 Chu, L. B P078 b Chu, R. P441, P539 Chua, S. P148 Chun, J. B P712 b , P716 Chung, K.K. P456 Chung, Y.H. 064 Bjørnerud, A. P437 Bjornevik, K. 056, B P378 b Bjørnevik, K. P138 Black, L. P149 Blackburn, K. P987 Blagitko-Dorfs, N. P791 Blagotinsek Osep, A. P698 Blanchard, O. P057 Blanche, J. P541 Blanchette, F. P281 Blanck, R. P640 Blanco, Y. P463, P549, P647, P653, P800 Blandford, S.N. [Extracted from the article]

Background: Neuroinflammation with microglia activation is thought to be closely related to cortical multiple sclerosis (MS) lesion pathogenesis. Objective: Using 11C-PBR28 and 7 Tesla (7T) imaging, we assessed in 9 relapsing–remitting multiple sclerosis (RRMS) and 10 secondary progressive multiple sclerosis (SPMS) patients the following: (1) microglia activation in lesioned and normal-appearing cortex, (2) cortical lesion inflammatory profiles, and (3) the relationship between neuroinflammation and cortical integrity. Methods: Mean 11C-PBR28 uptake was measured in focal cortical lesions, cortical areas with 7T quantitative T2* (q-T2*) abnormalities, and normal-appearing cortex. The relative difference in cortical 11C-PBR28 uptake between patients and 14 controls was used to classify cortical lesions as either active or inactive. Disease burden was investigated according to cortical lesion inflammatory profiles. The relation between q-T2* and 11C-PBR28 uptake along the cortex was assessed. Results: 11C-PBR28 uptake was abnormally high in cortical lesions in RRMS and SPMS; in SPMS, tracer uptake was significantly increased also in normal-appearing cortex. 11C-PBR28 uptake and q-T2* correlated positively in many cortical areas, negatively in some regions. Patients with high cortical lesion inflammation had worse clinical outcome and higher intracortical lesion burden than patients with low inflammation. Conclusion: 11C-PBR28 and 7T imaging reveal distinct profiles of cortical inflammation in MS, which are related to disease burden. [ABSTRACT FROM AUTHOR]

Background: Activated microglia, which can be detected in vivo by 11C-PBR28 positron emission tomography (PET), represent a main component of MS pathology in the brain. Their role in the cerebellum is still unexplored, although cerebellar involvement in MS is frequent and accounts for disability progression. Objectives: We aimed at characterizing cerebellar neuroinflammation in MS patients compared to healthy subjects by combining 11C-PBR28 MRI-Positron Emission Tomography (MR-PET) with 7 Tesla (T) MRI and assessing its relationship with brain neuroinflammation and clinical outcome measures. Methods: Twenty-eight MS patients and 16 healthy controls underwent 11C-PBR28 MR-PET to measure microglia activation in normal appearing cerebellum and lesions segmented from 7 T scans. Patients were evaluated using the Expanded Disability Status Scale and Symbol Digit Modalities Test. 11C-PBR28 binding was assessed in regions of interest using 60–90 minutes standardized uptake values normalized by a pseudo-reference region in the brain normal appearing white matter. Multilinear regression was used to compare tracer uptake in MS and healthy controls and assess correlations with clinical scores. Results: In all cerebellar regions examined, MS patients showed abnormally increased tracer uptake, which correlated with cognitive and neurological disability. Conclusion: Neuroinflammation is widespread in the cerebellum of patients with MS and related to neurological disability and cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: Thalamic degeneration impacts multiple sclerosis (MS) prognosis. Objective: To investigate heterogeneous thalamic pathology, its correlation with white matter (WM), cortical lesions and thickness, and as function of distance from cerebrospinal fluid (CSF). Methods: In 41 MS subjects and 17 controls, using 3 and 7 T imaging, we tested for (1) differences in thalamic volume and quantitative T2* (q-T2*) (2) globally and (3) within concentric bands originating from the CSF/thalamus interface; (4) the relation between thalamic, cortical, and WM metrics; and (5) the contribution of magnetic resonance imaging (MRI) metrics to clinical scores. We also assessed MS thalamic lesion distribution as a function of distance from CSF. Results: Thalamic lesions were mainly located next to the ventricles. Thalamic volume was decreased in MS versus controls (p < 10−2); global q-T2* was longer in secondary progressive multiple sclerosis (SPMS) only (p < 10−2), indicating myelin and/or iron loss. Thalamic atrophy and longer q-T2* correlated with WM lesion volume (p < 0.01). In relapsing-remitting MS, q-T2* thalamic abnormalities were located next to the WM (p < 0.01 (uncorrected), p = 0.09 (corrected)), while they were homogeneously distributed in SPMS. Cortical MRI metrics were the strongest predictors of clinical outcome. Conclusion: Heterogeneous pathological processes affect the thalamus in MS. While focal lesions are likely mainly driven by CSF-mediated factors, overall thalamic degeneration develops in association with WM lesions. [ABSTRACT FROM AUTHOR]

The article offers information on the role of the positron emission tomography in pathogenesis of multiple sclerosis. Topics discussed include information on the substantial advances in the understanding of multiple sclerosis pathophysiology; discussions on the use of the radiotracers for imaging the tissue concentration of different types of molecules in multiple sclerosis; and the information on the limitations to the pharmacokinetics of radioligands.

An author index for the 2016 issue of the journal is presented.

The article offers information on the cortical pathology in multiple sclerosis (MS). It focuses on disentangling the individual contributions of different immune cells and soluble mediators. It states that pathology are microglia, the resident macrophages of the central nervous system (CNS). It states that activated microglia are found in active and chronic cortical MS lesions.

An author index for the 2015 issue of ''Multiple Sclerosis Journal" is presented.

The article offers information on the challenging goals in multiple sclerosis (MS) research. Topics discussed include information on the role of the neuropathological components in the pathophysiology of the disease; discussions on the advanced quantitative magnetic resonance imaging techniques for detecting microstructural changes affecting both lesions and normalappearing tissues in patients with MS.

The article offers information on multiple sclerosis (MS) pathology characterized by demyelination of white and gray matter. It mentions that demyelinating white matter lesions (WMLs) and gray matter lesions (GMLs) depict the type of pathology with the origin, or sequential stages in the development of a single type of MS. It focuses on the low number of infiltrating leukocytes in GMLs.

The article reports on prevention of multiple sclerosis with extensive infiltration of leukocytes into the central nervous system (CNS) and the activation of CNS-intrinsic microglia. Topics discussed include prevention of neurodegeneration; use of inflammatory processes for the treatment of CNS; and use of magnetic resonance imaging for the detection of the same.