Combination protein biomarkers predict multiple sclerosis diagnosis and outcomes.

Establishing biomarkers to predict multiple sclerosis diagnosis and prognosis has been challenging using a single biomarker approach. We hypothesised that a combination of biomarkers would increase the accuracy of prediction models to differentiate multiple sclerosis from other neurological disorders and enhance prognostication for people with multiple sclerosis. We measured 24 fluid biomarkers in the blood and cerebrospinal fluid of 77 people with multiple sclerosis and 80 people with other neurological disorders, using ELISA or Single Molecule Array assays. Primary outcomes were multiple sclerosis versus any other diagnosis, time to first relapse, and time to disability milestone (Expanded Disability Status Scale 6), adjusted for age and sex. Multivariate prediction models were calculated using the area under the curve value for diagnostic prediction, and concordance statistics (the percentage of each pair of events that are correctly ordered in time for each of the Cox regression models) for prognostic predictions. Predictions using combinations of biomarkers were considerably better than single biomarker predictions. The combination of cerebrospinal fluid [chitinase-3-like-1 + TNF-receptor-1 + CD27] and serum [osteopontin + MCP-1] had an area under the curve of 0.97 for diagnosis of multiple sclerosis, compared to the best discriminative single marker in blood (osteopontin: area under the curve 0.84) and in cerebrospinal fluid (chitinase-3-like-1 area under the curve 0.84). Prediction for time to next relapse was optimal with a combination of cerebrospinal fluid[vitamin D binding protein + Factor I + C1inhibitor] + serum[Factor B + Interleukin-4 + C1inhibitor] (concordance 0.80), and time to Expanded Disability Status Scale 6 with cerebrospinal fluid [C9 + Neurofilament-light] + serum[chitinase-3-like-1 + CCL27 + vitamin D binding protein + C1inhibitor] (concordance 0.98). A combination of fluid biomarkers has a higher accuracy to differentiate multiple sclerosis from other neurological disorders and significantly improved the prediction of the development of sustained disability in multiple sclerosis. Serum models rivalled those of cerebrospinal fluid, holding promise for a non-invasive approach. The utility of our biomarker models can only be established by robust validation in different and varied cohorts.

Real-world persistence of multiple sclerosis disease-modifying therapies.

BACKGROUND AND PURPOSE: Treatment persistence is the continuation of therapy over time. It reflects a combination of treatment efficacy and tolerability. We aimed to describe real-world rates of persistence on disease-modifying therapies (DMTs) for people with multiple sclerosis (pwMS) and reasons for DMT discontinuation. METHODS: Treatment data on 4366 consecutive people with relapse-onset multiple sclerosis (MS) were pooled from 13 UK specialist centres during 2021. Inclusion criteria were exposure to at least one MS DMT and a complete history of DMT prescribing. PwMS in blinded clinical trials were excluded. Data collected included sex, age at MS onset, age at DMT initiation, DMT treatment dates, and reasons for stopping or switching DMT. For pwMS who had received immune reconstituting therapies (cladribine/alemtuzumab), discontinuation date was defined as starting an alternative DMT. Kaplan-Meier survival analyses were used to express DMT persistence. RESULTS: In 6997 treatment events (1.6 per person with MS), median time spent on any single maintenance DMT was 4.3 years (95% confidence interval = 4.1-4.5 years). The commonest overall reasons for DMT discontinuation were adverse events (35.0%) and lack of efficacy (30.3%). After 10 years, 20% of people treated with alemtuzumab had received another subsequent DMT, compared to 82% of people treated with interferon or glatiramer acetate. CONCLUSIONS: Immune reconstituting DMTs may have the highest potential to offer a single treatment for relapsing MS. Comparative data on DMT persistence and reasons for discontinuation are valuable to inform treatment decisions and in personalizing treatment in MS.

COVID-19 Vaccine Response in People with Multiple Sclerosis.

OBJECTIVE: The purpose of this study was to investigate the effect of disease modifying therapies on immune response to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines in people with multiple sclerosis (MS). METHODS: Four hundred seventy-three people with MS provided one or more dried blood spot samples. Information about coronavirus disease 2019 (COVID-19) and vaccine history, medical, and drug history were extracted from questionnaires and medical records. Dried blood spots were eluted and tested for antibodies to SARS-CoV-2. Antibody titers were partitioned into tertiles with people on no disease modifying therapy as a reference. We calculated the odds ratio of seroconversion (univariate logistic regression) and compared quantitative vaccine response (Kruskal Wallis) following the SARS-CoV-2 vaccine according to disease modifying therapy. We used regression modeling to explore the effect of vaccine timing, treatment duration, age, vaccine type, and lymphocyte count on vaccine response. RESULTS: Compared to no disease modifying therapy, the use of anti-CD20 monoclonal antibodies (odds ratio = 0.03, 95% confidence interval [CI] = 0.01-0.06, p < 0.001) and fingolimod (odds ratio = 0.04; 95% CI = 0.01-0.12) were associated with lower seroconversion following the SARS-CoV-2 vaccine. All other drugs did not differ significantly from the untreated cohort. Both time since last anti-CD20 treatment and total time on treatment were significantly associated with the response to the vaccination. The vaccine type significantly predicted seroconversion, but not in those on anti-CD20 medications. Preliminary data on cellular T-cell immunity showed 40% of seronegative subjects had measurable anti-SARS-CoV-2 T cell responses. INTERPRETATION: Some disease modifying therapies convey risk of attenuated serological response to SARS-CoV-2 vaccination in people with MS. We provide recommendations for the practical management of this patient group. ANN NEUROL 20219999:n/a-n/a.

Metabolic activity diffusion imaging (MADI): II. Noninvasive, high-resolution human brain mapping of sodium pump flux and cell metrics.

We introduce a new 1 H2 O magnetic resonance approach: metabolic activity diffusion imaging (MADI). Numerical diffusion-weighted imaging decay simulations characterized by the mean cellular water efflux (unidirectional) rate constant (kio ), mean cell volume (V), and cell number density (ρ) are produced from Monte Carlo random walks in virtual stochastically sized/shaped cell ensembles. Because of active steady-state trans-membrane water cycling (AWC), kio reflects the cytolemmal Na+ , K+ ATPase (NKA) homeostatic cellular metabolic rate (c MRNKA ). A digital 3D "library" contains thousands of simulated single diffusion-encoded (SDE) decays. Library entries match well with disparate, animal, and human experimental SDE decays. The V and ρ values are consistent with estimates from pertinent in vitro cytometric and ex vivo histopathological literature: in vivo V and ρ values were previously unavailable. The library allows noniterative pixel-by-pixel experimental SDE decay library matchings that can be used to advantage. They yield proof-of-concept MADI parametric mappings of the awake, resting human brain. These reflect the tissue morphology seen in conventional MRI. While V is larger in gray matter (GM) than in white matter (WM), the reverse is true for ρ. Many brain structures have kio values too large for current, invasive methods. For example, the median WM kio is 22s-1 ; likely reflecting mostly exchange within myelin. The kio •V product map displays brain tissue c MRNKA variation. The GM activity correlates, quantitatively and qualitatively, with the analogous resting-state brain 18 FDG-PET tissue glucose consumption rate (t MRglucose ) map; but noninvasively, with higher spatial resolution, and no pharmacokinetic requirement. The cortex, thalamus, putamen, and caudate exhibit elevated metabolic activity. MADI accuracy and precision are assessed. The results are contextualized with literature overall homeostatic brain glucose consumption and ATP production/consumption measures. The MADI/PET results suggest different GM and WM metabolic pathways. Preliminary human prostate results are also presented.

Risk of COVID-19 in people with multiple sclerosis who are seronegative following vaccination.

BACKGROUND: People with multiple sclerosis (pwMS) treated with certain disease-modifying therapies (DMTs) have attenuated IgG response following COVID-19 vaccination; however, the clinical consequences remain unclear. OBJECTIVE: To report COVID-19 rates in pwMS according to vaccine serology. METHODS: PwMS with available (1) serology 2-12 weeks following COVID-19 vaccine 2 and/or vaccine 3 and (2) clinical data on COVID-19 infection/hospitalisation were included. Logistic regression was performed to examine whether seroconversion following vaccination predicted risk of subsequent COVID-19 infection after adjusting for potential confounders. Rates of severe COVID-19 (requiring hospitalisation) were also calculated. RESULTS: A total of 647 pwMS were included (mean age 48 years, 500 (77%) female, median Expanded Disability Status Scale (EDSS) 3.5% and 524 (81%) exposed to DMT at the time of vaccine 1). Overall, 472 out of 588 (73%) were seropositive after vaccines 1 and 2 and 222 out of 305 (73%) after vaccine 3. Seronegative status after vaccine 2 was associated with significantly higher odds of subsequent COVID-19 infection (odds ratio (OR): 2.35, 95% confidence interval (CI): 1.34-4.12, p = 0.0029), whereas seronegative status after vaccine 3 was not (OR: 1.05, 95% CI: 0.57-1.91). Five people (0.8%) experienced severe COVID-19, all of whom were seronegative after most recent vaccination. CONCLUSION: Attenuated humoral response to initial COVID-19 vaccination predicts increased risk of COVID-19 in pwMS, but overall low rates of severe COVID-19 were seen.

Persistent Paternalism: The Instantiation of Gendered Attributions in the System Response to Girls.

Prior research suggests that the juvenile legal system does too little to address the sources and underlying reasons for girls' court referrals. Drawing on attribution theories, the current study examined perspectives that characterize the response of the system to girls' behaviors. Data from this study were derived from a multimethod, qualitative study on system-involved girls. We find that court actors hold gendered attributions of girls' delinquency, in turn informing their decision-making about how to treat and sanction girls. Paternalism remains a persistent feature in how the system locates, defines, and responds to girls through varying gendered attributions. The findings lend further support to attribution perspectives that suggest implicit gender-biases influence court actor decision-making, exacerbating the challenges girls face in and out of the juvenile legal system. By extension, this study offers concrete policy and practice implications for systems change and improving its response to girls.

Family-based Intervention for Legal System-involved Girls: A Mixed Methods Evaluation.

The increased proportion of juvenile court-involved girls has spurred interest to implement and evaluate services to reduce girls' system involvement. The purpose of this study was to examine the effectiveness of a family-based intervention by using a dominant sequential mixed methods evaluation approach. First, we examined quantitative data using a quasi-experimental design to determine whether the family-based intervention reduced recidivism among court-involved girls. Propensity score matching (PSM) was used to construct statistically equivalent groups to compare one-year recidivism outcomes for girls who received the court-run family-based intervention (n = 181) to a group of girls on probation who did not receive the intervention (n = 803). Qualitative interviews (n = 39) were conducted to contextualize the quantitative findings and highlighted the circumstances that family-focused interventions for court-involved girls. Girls who received the program had slightly lower recidivism rates following the intervention. The qualitative findings contextualized the quasi-experimental results by providing an explanation as to the girls' family circumstances and insights into the mechanisms of the intervention. Results highlighted the importance of family-focused interventions for juvenile justice-involved girls. These findings have practical and policy implications for the use interventions-beyond the individual level-with adjudicated girls and offer suggestions for ways to improve their effectiveness using a community psychology lens. In addition, this paper includes a discussion of evaluating of juvenile court programming from a community psychology perspective including strengths, challenges, and considerations for future work in this area.

Human Trafficking Cases Presenting within Child Advocacy Centers.

Although human trafficking of minors is an increasing concern within the United States, very little information is known about how trafficking cases are processed within child advocacy centers (CACs). The current study addresses this gap in the literature by providing descriptive information about victims, service referrals, and prosecutorial outcomes for human trafficking cases presenting at CACs across a Midwestern state. The data originates from a state-wide study focused on understanding the scope of human trafficking cases. Specifically, the dataset includes 210 youth presenting at CACs over a three-year period of time. In this sample, the typical human trafficking case involved sex trafficking of a self-identified white female victim, with an offender known to the victim. Most child survivors passing through CACs were referred to medical and mental health services, although these service referrals did not greatly differ across at-risk versus substantiated trafficking cases. Overall, the findings suggest that CACs are uniquely positioned to encounter human trafficking cases and provide needed services to trafficking survivors. Finally, recommendations are provided for CACs regarding the intake and identification of trafficking cases more broadly.

A Meta-Analysis of Program Characteristics for Youth with Disruptive Behavior Problems: The Moderating Role of Program Format and Youth Gender.

There is high variability in efficacy for interventions for youth with disruptive behavior problems (DBP). Despite evidence of the unique correlates and critical consequences of girls' DBP, there is a dearth of research examining treatment efficacy for girls. This meta-analysis of 167 unique effect sizes from 29 studies (28,483 youth, 50% female; median age: 14) suggests that existing treatments have a medium positive effect on DBP (g = .33). For both boys and girls, the most effective interventions included (a) multimodal or group format, (b) cognitive skills or family systems interventions, and (c) length-intensive programs for (d) younger children. Boys demonstrated significantly greater treatment gains from group format interventions compared to girls, which is particularly important given that the group program format was the most prevalent format for boys and girls, with 14 studies involving 10,433 youth encompassing this category. This is the first meta-analysis to examine the effect of program characteristics in a sample of programs selected to be specifically inclusive of girls. Given that girls are underrepresented in intervention research on DBP, findings are discussed in terms of gender-responsive considerations and elucidating how key aspects of program structure can support more effective intervention outcomes for youth.

Victim or Prostitute? The Classification of Commercial Sex Events Involving Minors in the National Incident-Based Reporting System.

Sex trafficking is recognized as a national problem that inflicts serious harm on its victims, yet, legislative responses to trafficking vary depending on jurisdiction. Federal legislation considers youths who engage in commercial sex acts as trafficking victims. States, however, vary in the evidence required to prove a juvenile is a victim of sex trafficking, as opposed to an offender of prostitution. Using four years of data from the National Incident-Based Reporting System, we compared details of commercial sex incidents involving youths who were identified as trafficking victims or arrested as prostitutes. Beyond legislative differences, comparisons between cases are discussed to illuminate how state law enforcement officials legally classify these events involving adolescents (i.e., as victims or prostitutes). Further, we consider the policy implications of the findings.

Estimating the Prevalence of Human Trafficking in Ohio, 2014-2016.

Objectives. To develop statewide estimates of known victims and individuals at risk of human trafficking in Ohio.Methods. We collected information from 12 state and local sources including child welfare, legal services, and law enforcement data. We collected the data from agency records dating 2013 to 2018. However, the majority of data were from calendar years 2014, 2015, and 2016 (roughly 95% across individual and aggregate sources). We used probabilistic matching to estimate victim and at-risk cases-accounting for duplicates.Results. According to available data, there were 1032 known victims during the study time frame. We identified approximately 4209 at-risk individuals based on youths presenting with common risk factors for trafficking victimization.Conclusions. Estimating the prevalence of human trafficking is an important public health research priority. As the first "cataloging" of existing record systems in Ohio to our knowledge, this study provided a comprehensive overview of the number of victims and the type of information that is available in the state. This study highlights the importance of moving toward the use of epidemiological approaches to measure the prevalence of human trafficking.

Clinical Outcomes in Children With Orbital Cellulitis and Radiographic Globe Tenting.

PURPOSE: Axial displacement of the globe with tenting centered on the optic nerve-globe junction is a predictor of visual loss in adults. The purpose of this study was to determine the visual outcomes of children with orbital cellulitis and globe tenting. METHODS: The records of 46 consecutive children with orbital cellulitis at a single tertiary children's hospital were reviewed retrospectively. Initial and final visual acuities were available for 34 of 46 patients (74%). Globe tenting was defined by an angle of 130° or less at the optic nerve-globe junction as derived from sagittal CT or MRI. Visual acuities of 4 children with globe tenting (mean age, 10.3 ± 3.3 years) were compared with those of 30 children without globe tenting (mean age, 10.8 ± 3.5 years). Final logarithm of the minimum angle of resolution visual acuities were analyzed. RESULTS: The mean posterior globe angle was 124.5° ± 8.0° in patients with globe tenting, compared with 145.6° ± 7.4° in the affected eye of the patients without globe tenting (p = 0.002). Final visual acuity was logarithm of the minimum angle of resolution = 0 following treatment in patients with globe tenting and logarithm of the minimum angle of resolution = 0.02 in patients without tenting (p = 0.70). DISCUSSION: We propose that the increased elastic compliance of the optic nerve sheath and sclera in children may contribute to better visual outcomes. CONCLUSIONS: Pediatric orbital cellulitis with globe tenting may not lead to devastating vision loss as previously seen in adults.

Outbreak of syphilis in men who have sex with men living in rural North Wales (UK) associated with the use of social media.

OBJECTIVES: To describe an outbreak of infectious syphilis in rural North Wales and the control measures implemented. METHODS: Following reports of an increase of syphilis in North Wales, a multidisciplinary Outbreak Control Team (OCT) was established. A multilevel prevention and control response was initiated, including: active case surveillance, partner notification and treatment, sexual network analysis, awareness raising with professionals and affected communities, point-of-care syphilis testing at a sauna and a health promotion campaign targeting users of men who have sex with men (MSM) social network mobile phone applications (apps). RESULTS: Four cases of infectious syphilis were diagnosed in clinics in North Wales per 100 000 population in 2013 compared with a mean of one case per 100 000 in the preceding decade. Diagnosed cases peaked in January 2014, declining in the first half of 2014. Initial cases were clustered in the westerly rural counties of North Wales and were predominantly white men, self-reporting as MSM (median age: 34 years, range: 17-61). Point-of-care testing at a sauna did not identity further new infections, suggesting that the cluster was relatively focused and had probably been detected early. The use of apps to find sexual partners was a feature of the network affected. A health promotion campaign, initiated by the OCT, targeting men using MSM apps reached 92% of the 755 men messaged. CONCLUSIONS: The outbreak was successfully controlled. However, it is difficult to determine which of the interventions implemented were most effective. Future outbreaks should be used as an opportunity to evaluate interventions using apps.

Extensive gray matter volume reduction in treatment-resistant schizophrenia.

BACKGROUND: Approximately one-third of people with schizophrenia are treatment-resistant and some do not achieve remission with clozapine, the gold-standard antipsychotic medication for treatment-resistant schizophrenia. This study compared global and regional brain volumes between treatment-respondent and treatment-resistant patients with schizophrenia, including a group of patients who were clozapine-resistant. METHODS: T1-weighted brain MRIs were obtained on a 3T scanner in 20 controls and 52 people with schizophrenia who were selected based on their symptomatic responses to antipsychotic medication: 18 responded well to first-line atypical antipsychotics (FLR), 19 were treatment-resistant but responsive to clozapine monotherapy (TR), and 15 were ultra-treatment-resistant and did not respond to clozapine (UTR). Treatment groups were matched for disease duration and current psychopathology. SIENAX and FSL-VBM were used to investigate differences in the global brain, gray matter (GM), white matter, ventricular cerebrospinal fluid volumes, and regional GM volumes. RESULTS: GM volume was significantly reduced in the TR and UTR groups compared with controls and the FLR group (p < 0.05). GM volume was significantly reduced in TR patients compared with FLRs in the superior, middle, and inferior temporal gyri, pre- and post-central gyri, middle and superior frontal gyri, right supramarginal gyrus, and right lateral occipital cortex. UTR patients showed reduced GM compared with FLRs in their right parietal operculum and left cerebellum. No significant volume differences were observed between TR and UTR groups. CONCLUSIONS: These differences are unlikely to be solely due to medication effects, and reduced GM volume in treatment-resistant schizophrenia may represent an accelerated disease course or a different underlying pathology.

Glutamatergic neurometabolites in clozapine-responsive and -resistant schizophrenia.

BACKGROUND: According to the current schizophrenia treatment guidelines, 3 levels of responsiveness to antipsychotic medication exist: those who respond to first-line antipsychotics, those with treatment-resistant schizophrenia who respond to clozapine, and those with clozapine-resistant or ultra-treatment resistant schizophrenia. Proton magnetic resonance spectroscopy studies indicate that antipsychotic medication decreases glutamate or total glutamate + glutamine in the brains of patients with schizophrenia and may represent a biomarker of treatment response; however, the 3 levels of treatment responsiveness have not been evaluated. METHODS: Proton magnetic resonance spectroscopy spectra were acquired at 3 Tesla from patients taking a second generation non-clozapine antipsychotic (first-line responders), patients with treatment-resistant schizophrenia taking clozapine, patients with ultra-treatment resistant schizophrenia taking a combination of antipsychotics, and healthy comparison subjects. RESULTS: Group differences in cerebrospinal fluid-corrected total glutamate + glutamine levels scaled to creatine were detected in the dorsolateral prefrontal cortex [df(3,48); F = 3.07, P = .04, partial η(2) = 0.16] and the putamen [df(3,32); F = 2.93, P = .05, partial η(2) = 0.22]. The first-line responder group had higher dorsolateral prefrontal cortex total glutamate + glutamine levels scaled to creatine than those with ultra-treatment resistant schizophrenia [mean difference = 0.25, standard error = 0.09, P = .04, family-wise error-corrected]. Those with treatment-resistant schizophrenia had higher total glutamate + glutamine levels scaled to creatine in the putamen than the first-line responders (mean difference = 0.31, standard error = 0.12, P = .05, family-wise error-corrected) and those with ultra-treatment-resistant schizophrenia (mean difference = 0.39, standard error = 0.12, P = .02, family-wise error-corrected). CONCLUSIONS: Total glutamate + glutamine levels scaled to creatine in the putamen may represent a marker of response to clozapine. Future studies should investigate glutamatergic anomalies prior to clozapine initiation and following successful treatment.

Protective role of p450 epoxyeicosanoids in subarachnoid hemorrhage.

BACKGROUND: Patients recovering from aneurysmal subarachnoid hemorrhage (SAH) are at risk for developing delayed cerebral ischemia (DCI). Experimental and human studies implicate the vasoconstrictor P450 eicosanoid 20-hydroxyeicosatetraenoic acid (20-HETE) in the pathogenesis of DCI. To date, no studies have evaluated the role of vasodilator epoxyeicosatrienoic acids (EETs) in DCI. METHODS: Using mass spectrometry, we measured P450 eicosanoids in cerebrospinal fluid (CSF) from 34 SAH patients from 1 to 14 days after admission. CSF eicosanoid levels were compared in patients who experienced DCI versus those who did not. We then studied the effect of EETs in a model of SAH using mice lacking the enzyme soluble epoxide hydrolase (sEH), which catabolizes EETs into their inactive diol. To assess changes in vessel morphology and cortical perfusion in the mouse brain, we used optical microangiography, a non-invasive coherence-based imaging technique. RESULTS: Along with increases in 20-HETE, we found that CSF levels of 14,15-EET were elevated in SAH patients compared to control CSF, and levels were significantly higher in patients who experienced DCI compared to those who did not. Mice lacking sEH had elevated 14,15-EET and were protected from the delayed decrease in microvascular cortical perfusion after SAH, compared to wild type mice. CONCLUSIONS: Our findings suggest that P450 eicosanoids play an important role in the pathogenesis of DCI. While 20-HETE may contribute to the development of DCI, 14,15-EET may afford protection against DCI. Strategies to enhance 14,15-EET, including sEH inhibition, should be considered as part of a comprehensive approach to prevent DCI.

A qualitative natural history study of ME/CFS in the community.

In previous qualitative research on Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS), researchers have focused on the experiences of patients with ME/CFS in tertiary care samples. This qualitative study examined the natural history of people with ME/CFS (n = 19) from a community-based sample. Findings highlighted multilayered themes involving the illness experience and the physical construction of ME/CFS. In addition, this study further illuminated unique subthemes regarding community response and treatment, which have implications for understanding the progression of ME/CFS as well as experiences of those within patient networks. There is a need for more longitudinal qualitative research on epidemiological samples of patients with ME/CFS.

Screening Offenders: The Exploration of a Youth Level of Service/Case Management Inventory: (YLS/CMI) Brief Screener.

Although structured assessments have helped standardize juvenile court processes by systematically measuring risk for recidivism, it has been argued that some assessments lack the ability to perform as a brief screener. This study explored the potential for the original 42-item Youth Level of Service/Case Management Inventory (YLS/CMI) risk assessment to perform as a brief screener for a sample of first-time juvenile offenders in a mid-western, industrialized county. Results indicated that the original and shortened version of the YLS/CMI significantly predicted two-year recidivism for male and female offenders. Implications for situationally targeted forms of risk assessment are discussed.

ADvanced IMage Algebra (ADIMA): a novel method for depicting multiple sclerosis lesion heterogeneity, as demonstrated by quantitative MRI.

BACKGROUND: There are modest correlations between multiple sclerosis (MS) disability and white matter lesion (WML) volumes, as measured by T2-weighted (T2w) magnetic resonance imaging (MRI) scans (T2-WML). This may partly reflect pathological heterogeneity in WMLs, which is not apparent on T2w scans. OBJECTIVE: To determine if ADvanced IMage Algebra (ADIMA), a novel MRI post-processing method, can reveal WML heterogeneity from proton-density weighted (PDw) and T2w images. METHODS: We obtained conventional PDw and T2w images from 10 patients with relapsing-remitting MS (RRMS) and ADIMA images were calculated from these. We classified all WML into bright (ADIMA-b) and dark (ADIMA-d) sub-regions, which were segmented. We obtained conventional T2-WML and T1-WML volumes for comparison, as well as the following quantitative magnetic resonance parameters: magnetisation transfer ratio (MTR), T1 and T2. Also, we assessed the reproducibility of the segmentation for ADIMA-b, ADIMA-d and T2-WML. RESULTS: Our study's ADIMA-derived volumes correlated with conventional lesion volumes (p < 0.05). ADIMA-b exhibited higher T1 and T2, and lower MTR than the T2-WML (p < 0.001). Despite the similarity in T1 values between ADIMA-b and T1-WML, these regions were only partly overlapping with each other. ADIMA-d exhibited quantitative characteristics similar to T2-WML; however, they were only partly overlapping. Mean intra- and inter-observer coefficients of variation for ADIMA-b, ADIMA-d and T2-WML volumes were all < 6 % and < 10 %, respectively. CONCLUSION: ADIMA enabled the simple classification of WML into two groups having different quantitative magnetic resonance properties, which can be reproducibly distinguished.