Methodology for Simultaneous Analysis of Photocatalytic deNO_x Products

The ISO standard 22197-1:2016 used for the evaluation of the photocatalytic nitric oxide removal has a main drawback, which allows only the decrease of nitric oxide to be determined specifically. The remaining amount, expressed as “NO2”, is considered as a sum of HNO3, HONO NO2, and other nitrogen-containing species, which can be potentially formed during the photocatalytic reaction. Therefore, we developed a new methodology combining our custom-made analyzers, which can accurately determine the true NO2 and HONO species, with the conventional NO one. Their function was validated via a photocatalytic experiment in which 100 ppbv of either NO or NO2 dispersed in air passed over (3 L min−1) an Aeroxide© TiO2 P25 surface. The gas-phase analysis was complemented with the spectrophotometric determination of nitrates (NO3−) and/or nitrites (NO2−) deposited on the P25 layer. Importantly, an almost perfect mass balance (94%) of the photocatalytic NOx abatement was achieved. The use of custom-made analyzers enables to obtain (i) no interference, (ii) high sensitivity, (iii) good linearity in the relevant concentration range, (iv) rapid response, and (v) long-term stability. Therefore, our approach enables to reveal the reaction complexity and is highly recommended for the photocatalytic NOx testing

Natalizumab Induces Changes of Cerebrospinal Fluid Measures in Multiple Sclerosis

Background: There is a lack of knowledge about the evolution of cerebrospinal fluid (CSF) markers in multiple sclerosis (MS) patients undergoing natalizumab treatment. Aim: We aimed to evaluate the effect of natalizumab on basic inflammatory CSF and MRI measures. Methods: Together, 411 patients were screened for eligibility and 93 subjects with ≥2 CSF examinations ≤6 months before and ≥12 months after natalizumab initiation were recruited. The effect of natalizumab on CSF as well as clinical and paraclinical measures was analyzed using adjusted mixed models. Results: Natalizumab induced a decrease in CSF leukocytes (p −15), CSF protein (p = 0.00007), the albumin quotient (p = 0.007), the IgG quotient (p = 6 × 10−15), the IgM quotient (p = 0.0002), the IgG index (p = 0.0004), the IgM index (p = 0.003) and the number of CSF-restricted oligoclonal bands (OCBs) (p = 0.0005). CSF-restricted OCBs positivity dropped from 94.6% to 86% but 26 patients (28%) had an increased number of OCBs at the follow-up. The baseline to follow-up EDSS and T2-LV were stable; a decrease in the relapse rate was consistent with a decrease in the CSF inflammatory markers and previous knowledge about the effectiveness of natalizumab. The average annualized brain volume loss during the follow-up was −0.50% (IQR = −0.96, −0.16) and was predicted by the baseline IgM index (B = −0.37; p = 0.003). Conclusions: Natalizumab is associated with a reduction of basic CSF inflammatory measures supporting its strong anti-inflammatory properties. The IgM index at the baseline predicted future brain volume loss during the course of natalizumab treatment

Neurological software tool for reliable atrophy measurement (NeuroSTREAM) of the lateral ventricles on clinical-quality T2-FLAIR MRI scans in multiple sclerosis

Background: There is a need for a brain volume measure applicable to the clinical routine scans. Nearly every multiple sclerosis (MS) protocol includes low-resolution 2D T2-FLAIR imaging. Objectives: To develop and validate cross-sectional and longitudinal brain atrophy measures on clinical-quality T2-FLAIR images in MS patients. Methods: A real-world dataset from 109 MS patients from 62 MRI scanners was used to develop a lateral ventricular volume (LVV) algorithm with a longitudinal Jacobian-based extension, called NeuroSTREAM. Gold-standard LVV was calculated on high-resolution T1 1mm, while NeuroSTREAM LVV was obtained on low-resolution T2-FLAIR 3mm thick images. Scan-rescan reliability was assessed in 5 subjects. The variability of LVV measurement at different field strengths was tested in 76 healthy controls and 125 MS patients who obtained both 1.5T and 3T scans in 72hours. Clinical validation of algorithm was performed in 176 MS patients who obtained serial yearly MRI 1.5T scans for 10years. Results: Correlation between gold-standard high-resolution T1 LVV and low-resolution T2-FLAIR LVV was r=0.99, p<0.001 and the scan-rescan coefficient of variation was 0.84%. Correlation between low-resolution T2-FLAIR LVV on 1.5T and 3T was r=0.99, p<0.001 and the scan-rescan coefficient of variation was 2.69% cross-sectionally and 2.08% via Jacobian integration. NeuroSTREAM showed comparable effect size (d=0.39–0.71) in separating MS patients with and without confirmed disability progression, compared to SIENA and VIENA. Conclusions: Brain atrophy measurement on clinical quality T2-FLAIR scans is feasible, accurate, reliable, and relates to clinical outcomes. Keywords: Brain atrophy, Ventricular volume, Automated measurement, Multiple sclerosi

MRI correlates of disability progression in patients with CIS over 48 months

Background: Gray matter (GM) and white matter (WM) pathology has an important role in disease progression of multiple sclerosis (MS). Objectives: To investigate the association between the development of GM and WM pathology and clinical disease progression in patients with clinically isolated syndrome (CIS). Methods: This prospective, observational, 48-month follow-up study examined 210 CIS patients treated with 30 µg of intramuscular interferon beta-1a once a week. MRI and clinical assessments were performed at baseline, 6, 12, 24, 36 and 48 months. Associations between clinical worsening [24-weeks sustained disability progression (SDP) and occurrence of a second clinical attack] and longitudinal changes in lesion accumulation and brain atrophy progression were investigated by a mixed-effect model analysis after correction for multiple comparisons. Results: SDP was observed in 32 (15.2%) CIS patients, while 146 (69.5%) were stable and 32 (15.2%) showed sustained disability improvement. 112 CIS patients (53.3%) developed clinically definite MS (CDMS). CIS patients who developed SDP showed increased lateral ventricle volume (p < .001), and decreased GM (p = .011) and cortical (p = .001) volumes compared to patients who remained stable or improved in disability. Converters to CDMS showed an increased rate of accumulation of number of new/enlarging T2 lesions (p < .001), decreased whole brain (p = .007) and increased lateral ventricle (p = .025) volumes. Conclusions: Development of GM pathology and LVV enlargement are associated with SDP. Conversion to CDMS in patients with CIS over 48 months is dependent on the accumulation of new lesions, LVV enlargement and whole brain atrophy progression

Volumetric MRI Markers and Predictors of Disease Activity in Early Multiple Sclerosis: A Longitudinal Cohort Study

<div><h3>Objectives</h3><p>To compare clinical and MRI parameters between patients with clinically isolated syndrome and those converting to clinically definite multiple sclerosis within 2 years, to identify volumetric MRI predictors of this conversion and to assess effect of early relapses.</p> <h3>Methods</h3><p>The SET study comprised 220 patients with clinically isolated syndrome treated with interferon beta (mean age, 29 years; Expanded Disability Status Scale, 1.5). Three patients with missing data were excluded from the analysis. Physical disability, time to clinically definite multiple sclerosis and volumetric MRI data were recorded for 2 years.</p> <h3>Results</h3><p>Patients reaching clinically definite multiple sclerosis showed impaired recovery of neurological function, faster decrease in corpus callosum cross-sectional area, higher T2 lesion volume and more contrast-enhancing lesions. Six-month decrease in corpus callosum cross-sectional area (≥1%) and baseline T2 lesion volume (≥5 cm³) predicted clinically definite multiple sclerosis within 2 years (hazard ratios 2.5 and 1.8, respectively). Of 22 patients fulfilling both predictive criteria, 83% reached clinically definite multiple sclerosis (hazard ratio 6.5). More relapses were associated with poorer recovery of neurological function and accelerated brain atrophy.</p> <h3>Conclusions</h3><p>Neurological impairment is more permanent, brain atrophy is accelerated and focal inflammatory activity is greater in patients converting to clinically definite multiple sclerosis. Six-month corpus callosum atrophy and baseline T2 lesion volume jointly help predict individual risk of clinically definite multiple sclerosis. Early relapses contribute to permanent damage of the central nervous system.</p> </div

Gray matter atrophy patterns in multiple sclerosis: A 10-year source-based morphometry study

Objectives: To investigate spatial patterns of gray matter (GM) atrophy and their association with disability progression in patients with early relapsing-remitting multiple sclerosis (MS) in a longitudinal setting. Methods: Brain MRI and clinical neurological assessments were obtained in 152 MS patients at baseline and after 10years of follow-up. Patients were classified into those with confirmed disability progression (CDP) (n=85) and those without CDP (n=67) at the end of the study. An optimized, longitudinal source-based morphometry (SBM) pipeline, which utilizes independent component analysis, was used to identify eight spatial patterns of common GM volume co-variation in a data-driven manner. GM volume at baseline and rates of change were compared between patients with CDP and those without CDP. Results: The identified patterns generally included structurally or functionally related GM regions. No significant differences were detected at baseline GM volume between the sub-groups. Over the follow-up, patients with CDP experienced a significantly greater rate of GM atrophy within two of the eight patterns, after correction for multiple comparisons (corrected p-values of 0.001 and 0.007). The patterns of GM atrophy associated with the development of CDP included areas involved in motor functioning and cognitive domains such as learning and memory. Conclusion: SBM analysis offers a novel way to study the temporal evolution of regional GM atrophy. Over 10years of follow-up, disability progression in MS is related to GM atrophy in areas associated with motor and cognitive functioning. Keywords: Multiple sclerosis, Disability, MRI, Atrophy, Gray matte

Effect of relapses on disability change and volumetric MRI parameters at 2 years of CIS.

<p>Patients were categorised by the number of relapses during the 2-year follow-up period (0: n = 125, 1: n = 30, 2: n = 35, 3: n = 16, 4+: n = 11). Least-squares regression lines (dashed) and statistically significant p-values are shown. EDSS, Expanded Disability Status Scale; Gd+, gadolinium positive; MSFC, Multiple Sclerosis Functional Composite; T2LV, T2 lesion volume.</p

Relative risk of conversion to CDMS predicted by decrease in CC area at 6 months of CIS.

*<p>reference for the odds ratio estimates.</p><p>CC, corpus callosum; CDMS, clinically definite multiple sclerosis.</p

Disability and volumetric MRI parameters in patients with CIS and in those converting to CDMS.

<p>Dashed lines delineate 95% confidence intervals. Statistically significant p-values are shown. CIS, clinically isolated syndrome; CDMS, clinically definite multiple sclerosis; EDSS, Expanded Disability Status Scale; Gd+, gadolinium positive; MSFC, Multiple Sclerosis Functional Composite.</p