ObjectivesTo investigate whether blood–brain barrier (BBB) permeability is disrupted in normal appearing white matter in MS patients, when compared to healthy controls and whether it is correlated with MS clinical characteristics.MethodsDynamic contrast-enhanced MRI was used to measure BBB permeability in 27 patients with MS and compared to 24 matched healthy controls.ResultsPermeability measured as Ktrans was significantly higher in periventricular normal appearing white matter (NAWM) and thalamic gray matter in MS patients when compared to healthy controls, with periventricular NAWM showing the most pronounced difference. Recent relapse coincided with significantly higher permeability in periventricular NAWM, thalamic gray matter, and MS lesions. Immunomodulatory treatment and recent relapse were significant predictors of permeability in MS lesions and periventricular NAWM. Our results suggest that after an MS relapse permeability gradually decreases, possibly an effect of immunomodulatory treatment.ConclusionsOur results emphasize the importance of BBB pathology in MS, which we find to be most prominent in the periventricular NAWM, an area prone to development of MS lesions. Both the facts that recent relapse appears to cause widespread BBB disruption and that immunomodulatory treatment seems to attenuate this effect indicate that BBB permeability is intricately linked to the presence of MS relapse activity. This may reveal further insights into the pathophysiology of MS.

See Naismith and Cross (doi:) for a scientific commentary on this article. Optic neuritis is highly associated with development of multiple sclerosis. Cramer et al. show that MRI measures of blood-brain barrier permeability improve prediction of conversion to multiple sclerosis within 2 years, compared to T2-lesion count alone. Permeability measures also correlate with CSF biomarkers of cellular trafficking and blood-brain barrier breakdown.

CBV measurements using DCE-MRI may predict the status of contrast enhancing lesions and give results very similar to FDG-PET with regards to differentiation between tumor recurrence and radiation necrosis.

Segmentation of the CST into three regions supports the hypothesis of a 'dying back' mechanism in ALS and suggests that ADC is a more sensitive measure than FA to detect pathological changes in ALS.

BackgroundMagnetic Resonance Imaging (MRI) methods were evaluated as a tool for the study of experimental meningitis. The identification and characterisation of pathophysiological parameters that vary during the course of the disease could be used as markers for future studies of new treatment strategies.MethodsRats infected intracisternally with S. pneumoniae (n = 29) or saline (n = 13) were randomized for imaging at 6, 12, 24, 30, 36, 42 or 48 hours after infection. T1W, T2W, quantitative diffusion, and post contrast T1W images were acquired at 4.7 T. Dynamic MRI (dMRI) was used to evaluate blood-brain-barrier (BBB) permeability and to obtain a measure of cerebral and muscle perfusion. Clinical- and motor scores, bacterial counts in CSF and blood, and WBC counts in CSF were measured.ResultsMR images and dMRI revealed the development of a highly significant increase in BBB permeability (P < 0.002) and ventricle size (P < 0.0001) among infected rats. Clinical disease severity was closely related to ventricle expansion (P = 0.024).Changes in brain water distribution, assessed by ADC, and categorization of brain 'perfusion' by cortex ΔSI(bolus) were subject to increased inter-rat variation as the disease progressed, but without overall differences compared to uninfected rats (P > 0.05). Areas of well-'perfused' muscle decreased with the progression of infection indicative of septicaemia (P = 0.05).ConclusionThe evolution of bacterial meningitis was successfully followed in-vivo with MRI. Increasing BBB-breakdown and ventricle size was observed in rats with meningitis whereas changes in brain water distribution were heterogeneous. MRI will be a valuable technique for future studies aiming at evaluating or optimizing adjunctive treatments

In this study of the acute phase of optic neuritis, the degree of optic nerve head edema depended upon the extent of the optic nerve lesion, but not on its location. This suggests that factors other than inflammation, such as compromised venous drainage, vascular leakage, impaired axonal transport, and other mechanisms, are involved in the development of optic nerve head edema in optic neuritis.

Analyses revealed no differences between controls and patients with TS in gray or white matter. Possible discrepancies between cohorts and methods may play a role in the different findings in other studies. Further studies investigating well-defined cohorts with TS analyzing both gray and white matter in the same cohort may add additional information to the pathophysiology of TS.

ObjectiveTo investigate whether blood–brain barrier (BBB) permeability, as measured by dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI), can provide early detection of suboptimal treatment response in relapsing–remitting multiple sclerosis (RRMS).MethodsThirty‐five RRMS patients starting on fingolimod or natalizumab, drugs with a common effect of decreasing lymphocyte influx into the central nervous system, were scanned with DCE‐MRI at 3T prior to treatment and at 3 and 6 months posttreatment. We calculated the influx constant Ki, a measure of BBB permeability, using the Patlak model. Suboptimal treatment response was defined as loss of no evidence of disease activity (NEDA) status after 2 years of treatment.ResultsSubjects with loss of NEDA status at 2 years had a 51% higher mean Ki in normal‐appearing white matter (NAWM) measured after 6 months of treatment, compared to subjects with maintained NEDA status (mean difference = 0.06ml/100g/min, 95% confidence interval [CI] = 0.02–0.09, p = 0.002). Ki in NAWM at 6 months was a good predictor of loss of NEDA status at 2 years (area under the curve = 0.84, 95% CI = 0.70–0.99, p = 0.003), and a value above 0.136ml/100/g/min yielded an odds ratio of 12.4 for suboptimal treatment response at 2 years, with a sensitivity of 73% and a specificity of 82%.InterpretationOur results suggest that BBB permeability as measured by DCE‐MRI reliably predicts suboptimal treatment response and is a surrogate marker of the state of health of the BBB. We find a predictive threshold for disease activity, which is remarkably identical in clinically isolated syndrome as previously reported and established RRMS as investigated here. Ann Neurol 2018;83:902–914