Assessment of a 6-arylaminobenzamide lead derivative as a potential core scaffold for S1P positron emission tomography radiotracer development.

Sphingosine-1-phosphate-5 receptors (S1P) are predominantly expressed in oligodendrocytes and as a result have been proposed as an important target in Multiple Sclerosis (MS). Selective S1P radiotracers could enable in vivo positron emission tomography (PET) imaging of oligodendrocytes activity. Here we report the synthesis, radiolabelling and first preclinical evaluation of the pharmacokinetics and binding properties of a lead 6-arylaminobenzamide derivative, 6-(mesitylamino)-2-methoxy-3-methylbenzamide (also named as TEFM180), as a potential core scaffold for development of novel S1P PET radiotracers.

Perioperative research into memory (PRiMe), part 2: Adult burns intensive care patients show altered structure and function of the default mode network.

Background: Long-term cognitive impairment (LTCI) is experienced by up to two thirds of patients discharged from burns intensive care units (BICUs), however little is known about its neurobiological basis. This study investigated if patients previously admitted to BICU showed structural and functional MRI changes of the Default Mode Network (DMN).

Methods: Fifteen patients previously admitted to BICU with a significant burns injury, and 15 matched volunteers, underwent structural and functional MRI scans.

Investigating the brain's neurochemical profile at midlife in relation to dementia risk factors.

Changes in the brain's physiology in Alzheimer's disease are thought to occur early in the disease's trajectory. In this study our aim was to investigate the brain's neurochemical profile in a midlife cohort in relation to risk factors for future dementia using single voxel proton magnetic resonance spectroscopy. Participants in the multi-site PREVENT-Dementia study (age range 40-59 year old) underwent 3T magnetic resonance spectroscopy with the spectroscopy voxel placed in the posterior cingulate/precuneus region.

Brain connectivity changes underlying depression and fatigue in relapsing-remitting multiple sclerosis: A systematic review.

Multiple Sclerosis (MS) is an autoimmune disease affecting the central nervous system, characterised by neuroinflammation and neurodegeneration. Fatigue and depression are common, debilitating, and intertwined symptoms in people with relapsing-remitting MS (pwRRMS). An increased understanding of brain changes and mechanisms underlying fatigue and depression in RRMS could lead to more effective interventions and enhancement of quality of life.

Quantitative T brain mapping in early relapsing-remitting multiple sclerosis: longitudinal changes, lesion heterogeneity and disability.

Objectives: To quantify brain microstructural changes in recently diagnosed relapsing-remitting multiple sclerosis (RRMS) using longitudinal T measures, and determine their associations with clinical disability.

Methods: Seventy-nine people with recently diagnosed (< 6 months) RRMS were recruited from a single-centre cohort sub-study, and underwent baseline and 1-year brain MRI, including variable flip angle T mapping. Median T was measured in white matter lesions (WML), normal-appearing white matter (NAWM), cortical/deep grey matter (GM), thalami, basal ganglia and medial temporal regions.

Characterisation of the neonatal brain using myelin-sensitive magnetisation transfer imaging.

A cardinal feature of the encephalopathy of prematurity is dysmaturation of developing white matter and subsequent hypomyelination. Magnetisation transfer imaging (MTI) offers surrogate markers for myelination, including magnetisation transfer ratio (MTR) and magnetisation transfer saturation (MTsat). Using data from 105 neonates, we characterise MTR and MTsat in the developing brain and investigate how these markers are affected by gestational age at scan and preterm birth.

Patterns of brain atrophy in recently-diagnosed relapsing-remitting multiple sclerosis.

Recurrent neuroinflammation in relapsing-remitting MS (RRMS) is thought to lead to neurodegeneration, resulting in progressive disability. Repeated magnetic resonance imaging (MRI) of the brain provides non-invasive measures of atrophy over time, a key marker of neurodegeneration. This study investigates regional neurodegeneration of the brain in recently-diagnosed RRMS using volumetry and voxel-based morphometry (VBM).

Rationale and design of the brain magnetic resonance imaging protocol for FutureMS: a longitudinal multi-centre study of newly diagnosed patients with relapsing-remitting multiple sclerosis in Scotland.

Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease. MS prevalence varies geographically and is notably high in Scotland. Disease trajectory varies significantly between individuals and the causes for this are largely unclear.

Network analysis characterizes key associations between subjective fatigue and specific depressive symptoms in early relapsing-remitting multiple sclerosis.

Background: Fatigue is common and disabling in multiple sclerosis (MS), yet its mechanisms are poorly understood. In particular, overlap in measures of fatigue and depression complicates interpretation. We applied a multivariate network approach to quantify relationships between fatigue and other variables in early MS.

Protocol for the Tessa Jowell BRAIN MATRIX Platform Study.

Introduction: Gliomas are the most common primary tumour of the central nervous system (CNS), with an estimated annual incidence of 6.6 per 100 000 individuals in the USA and around 14 deaths per day from brain tumours in the UK. The genomic and biological landscape of brain tumours has been increasingly defined and, since 2016, the WHO classification of tumours of the CNS incorporates molecular data, along with morphology, to define tumour subtypes more accurately.

EANO - EURACAN - SNO Guidelines on circumscribed astrocytic gliomas, glioneuronal, and neuronal tumors.

In the new WHO 2021 Classification of CNS Tumors the chapter "Circumscribed astrocytic gliomas, glioneuronal and neuronal tumors" encompasses several different rare tumor entities, which occur more frequently in children, adolescents, and young adults. The Task Force has reviewed the evidence of diagnostic and therapeutic interventions, which is low particularly for adult patients, and draw recommendations accordingly. Tumor diagnosis, based on WHO 2021, is primarily performed using conventional histological techniques; however, a molecular workup is important for differential diagnosis, in particular, DNA methylation profiling for the definitive classification of histologically unresolved cases.

FutureMS cohort profile: a Scottish multicentre inception cohort study of relapsing-remitting multiple sclerosis.

Purpose: Multiple sclerosis (MS) is an immune-mediated, neuroinflammatory disease of the central nervous system and in industrialised countries is the most common cause of progressive neurological disability in working age persons. While treatable, there is substantial interindividual heterogeneity in disease activity and response to treatment. Currently, the ability to predict at diagnosis who will have a benign, intermediate or aggressive disease course is very limited.

Logistic Regression-Based Model Is More Efficient Than U-Net Model for Reliable Whole Brain Magnetic Resonance Imaging Segmentation.

Objectives: Automated whole brain segmentation from magnetic resonance images is of great interest for the development of clinically relevant volumetric markers for various neurological diseases. Although deep learning methods have demonstrated remarkable potential in this area, they may perform poorly in nonoptimal conditions, such as limited training data availability. Manual whole brain segmentation is an incredibly tedious process, so minimizing the data set size required for training segmentation algorithms may be of wide interest.

MRI-derived g-ratio and lesion severity in newly diagnosed multiple sclerosis.

Myelin loss is associated with axonal damage in established multiple sclerosis. This relationship is challenging to study in early disease. Here, we ask whether myelin loss is associated with axonal damage at diagnosis by combining non-invasive neuroimaging and blood biomarkers.

Rim lesions are demonstrated in early relapsing-remitting multiple sclerosis using 3 T-based susceptibility-weighted imaging in a multi-institutional setting.

Purpose: Rim lesions, characterised by a paramagnetic rim on susceptibility-based MRI, have been suggested to reflect chronic inflammatory demyelination in multiple sclerosis (MS) patients. Here, we assess, through susceptibility-weighted imaging (SWI), the prevalence, longitudinal volume evolution and clinical associations of rim lesions in subjects with early relapsing-remitting MS (RRMS).

Methods: Subjects (n = 44) with recently diagnosed RRMS underwent 3 T MRI at baseline (M0) and 1 year (M12) as part of a multi-centre study.

Resting-state brain connectivity in healthy young and middle-aged adults at risk of progressive Alzheimer's disease.

Functional brain connectivity of the resting-state networks has gained recent attention as a possible biomarker of Alzheimer's Disease (AD). In this paper, we review the literature of functional connectivity differences in young adults and middle-aged cognitively intact individuals with non-modifiable risk factors of AD (n = 17). We focus on three main intrinsic resting-state networks: The Default Mode network, Executive network, and the Salience network.

Application of the ATN classification scheme in a population without dementia: Findings from the EPAD cohort.

Background: We classified non-demented European Prevention of Alzheimer's Dementia (EPAD) participants through the amyloid/tau/neurodegeneration (ATN) scheme and assessed their neuropsychological and imaging profiles.

Materials And Methods: From 1500 EPAD participants, 312 were excluded. Cerebrospinal fluid cut-offs of 1000 pg/mL for amyloid beta (Aß)1-42 and 27 pg/mL for p-tau181 were validated using Gaussian mixture models.

A Position Statement on the Utility of Interval Imaging in Standard of Care Brain Tumour Management: Defining the Evidence Gap and Opportunities for Future Research.

Objectiv E: To summarise current evidence for the utility of interval imaging in monitoring disease in adult brain tumours, and to develop a position for future evidence gathering while incorporating the application of data science and health economics.

Methods: Experts in 'interval imaging' (imaging at pre-planned time-points to assess tumour status); data science; health economics, trial management of adult brain tumours, and patient representatives convened in London, UK. The current evidence on the use of interval imaging for monitoring brain tumours was reviewed.

Identification of occult cerebral microbleeds in adults with immune thrombocytopenia.

Management of symptoms and prevention of life-threatening hemorrhage in immune thrombocytopenia (ITP) must be balanced against adverse effects of therapies. Because current treatment guidelines based on platelet count are confounded by variable bleeding phenotypes, there is a need to identify new objective markers of disease severity for treatment stratification. In this cross-sectional prospective study of 49 patients with ITP and nadir platelet counts <30 × 109/L and 18 aged-matched healthy controls, we used susceptibility-weighted magnetic resonance imaging to detect cerebral microbleeds (CMBs) as a marker of occult hemorrhage.