Advancing renewable fuel integration: A comprehensive response surface methodology approach for internal combustion engine performance and emissions optimization.

In the realm of internal combustion engines, there is a growing utilization of alternative renewable fuels as substitutes for traditional diesel and gasoline. This surge in demand is driven by the imperative to diminish fuel consumption and adhere to stringent regulations concerning engine emissions. Sole reliance on experimental analysis is inadequate to effectively address combustion, performance, and emission issues in engines. Consequently, the integration of engine modelling, grounded in machine learning methodologies and statistical data through the response surface method (RSM), has become increasingly significant for enhanced analytical outcomes. This study aims to explore the contemporary applications of RSM in assessing the feasibility of a wide range of renewable alternative fuels for internal combustion engines. Initially, the study outlines the fundamental principles and procedural steps of RSM, offering readers an introduction to this multifaceted statistical technique. Subsequently, the study delves into a comprehensive examination of the recent applications of alternative renewable fuels, focusing on their impact on combustion, performance, and emissions in the domain of internal combustion engines. Furthermore, the study sheds light on the advantages and limitations of employing RSM, and discusses the potential of combining RSM with other modelling techniques to optimise results. The overarching objective is to provide a thorough insight into the role and efficacy of RSM in the evaluation of renewable alternative fuels, thereby contributing to the ongoing discourse in the field of internal combustion engines.

Influence of PODE1 additive into ethanol-gasoline blends (E10) on fuel properties and phase stability.

Polyoxymethylene dimethyl ethers (PODEn, n = 1-8) as an oxygenated fuel are a promising alternative fuel with a high oxygen concentration, a low C:H ratio, and no C-C bonds in their chemical structure. This could lead to smoke-free combustion. In this study, we chose to focus on PODE1 because of its lower cetane number, which makes it more suitable for use in spark ignition (SI) engines. However, its lower boiling point and octane number remain challenges. A low boiling point may lead to high vapour pressure and require storage and handling comparable to gaseous fuels. We investigated the effect of adding PODE1 to gasoline-ethanol blends (E10) on fuel properties, including distillation curve, octane number, phase stability, C/O/H ratio, heat of combustion, kinematic viscosity, and density. Our results showed that the blended fuels of E10 and PODE1 are stable up to 10 % PODE1, and there was no phase separation. Additionally, up to 10 % PODE1 additive had no significant side effect on the fuel properties of E10, particularly boiling point and octane number. Thus, work offers creative points by proposing a new candidate for additive fuel to gasoline-ethanol blends, which contributes to reducing the soot emission of GDI engines.

Heat Transfer Enhancement by Hybrid Nano Additives-Graphene Nanoplatelets/Cellulose Nanocrystal for the Automobile Cooling System (Radiator).

A radiator is used to remove a portion of the heat generated by a vehicle engine. It is challenging to efficiently maintain the heat transfer in an automotive cooling system even though both internal and external systems need enough time to keep pace with catching up with evolving engine technology advancements. The effectiveness of a unique hybrid's heat transfer nanofluid was investigated in this study. The hybrid nanofluid was mainly composed of graphene nanoplatelets (GnP), and cellulose nanocrystals (CNC) nanoparticles suspended in a 40:60 ratio of distilled water and ethylene glycol. A counterflow radiator equipped with a test rig setup was used to evaluate the hybrid nano fluid's thermal performance. According to the findings, the proposed GNP/CNC hybrid nanofluid performs better in relation to improving the efficiency of heat transfer of a vehicle radiator. The suggested hybrid nanofluid enhanced convective heat transfer coefficient by 51.91%, overall heat transfer coefficient by 46.72%, and pressure drop by 34.06% with respect to distilled water base fluid. Additionally, the radiator could reach a better CHTC with 0.01% hybrid nanofluid in the optimized radiator tube by the size reduction assessment using computational fluid analysis. In addition to downsizing the radiator tube and increasing cooling capacity over typical coolants, the radiator takes up less space and helps to lower the weight of a vehicle engine. As a result, the suggested unique hybrid graphene nanoplatelets/cellulose nanocrystal-based nanofluids perform better in heat transfer enhancement in automobiles.

Fused Deposition Modelling of Polymer Composite: A Progress.

Additive manufacturing (AM) highlights developing complex and efficient parts for various uses. Fused deposition modelling (FDM) is the most frequent fabrication procedure used to make polymer products. Although it is widely used, due to its low characteristics, such as weak mechanical properties and poor surface, the types of polymer material that may be produced are limited, affecting the structural applications of FDM. Therefore, the FDM process utilises the polymer composition to produce a better physical product. The review's objective is to systematically document all critical information on FDMed-polymer composite processing, specifically for part fabrication. The review covers the published works on the FDMed-polymer composite from 2011 to 2021 based on our systematic literature review of more than 150 high-impact related research articles. The base and filler material used, and the process parameters including layer height, nozzle temperature, bed temperature, and screw type are also discussed in this review. FDM is utilised in various biomedical, automotive, and other manufacturing industries. This study is expected to be one of the essential pit-stops for future related works in the FDMed-polymeric composite study.

A comprehensive review on fused deposition modelling of polylactic acid.

Fused Deposition Modelling (FDM) is one of the additive manufacturing (AM) techniques that have emerged as the most feasible and prevalent approach for generating functional parts due to its ability to produce neat and intricate parts. FDM mainly utilises one of the widely used polymers, polylactic acid, also known as polylactide (PLA). It is an aliphatic polyester material and biocompatible thermoplastic, with the best design prospects due to its eco-friendly properties; when PLA degrades, it breaks down into water and carbon dioxide, neither of which are hazardous to the environment. However, PLA has its limitations of poor mechanical properties. Therefore, a filler reinforcement may enhance the characteristics of PLA and produce higher-quality FDM-printed parts. The processing parameters also play a significant role in the final result of the printed parts. This review aims to study and discover the properties of PLA and the optimum processing parameters. This review covers PLA in FDM, encompassing its mechanical properties, processing parameters, characterisation, and applications. A comprehensive description of FDM processing parameters is outlined as it plays a vital role in determining the quality of a printed product. In addition, PLA polymer is highly desirable for various field industrial applications such as in a medical, automobile, and electronic, given its excellent thermoplastic and biodegradability properties.

Ultrasonication an intensifying tool for preparation of stable nanofluids and study the time influence on distinct properties of graphene nanofluids - A systematic overview.

Optimum ultrasonication time will lead to the better performance for heat transfer in addition to preparation methods and thermal properties of the nanofluids. Nano particles are dispersed in base fluids like water (water-based fluids), glycols (glycol base fluids) &oils at different mass or volume fraction by using different preparation techniques. Significant preparation technique can enhance the stability, effects various parameters & thermo-physical properties of fluids. Agglomeration of the dispersed nano particles will lead to declined thermal performance, thermal conductivity, and viscosity. For better dispersion and breaking down the clusters, Ultrasonication method is the highly influential approach. Sonication hour is unique for different nano fluids depending on their response to several considerations. In this review, systematic investigations showing effect on various physical and thermal properties based on ultrasonication/ sonication time are illustrated. In this analysis it is found that increased power or time of ideal sonication increases the dispersion, leading to higher stable fluids, decreased particle size, higher thermal conductivity, and lower viscosity values. Employing the ultrasonic probe is substantially more effective than ultrasonic bath devices. Low ultrasonication power and time provides best outcome. Various sonication time periods by various research are summarized with respect to the different thermophysical properties. This is first review explaining sonication period influence on thermophysical properties of graphene nanofluids.

Disability Improvement Is Associated with Less Brain Atrophy Development in Multiple Sclerosis.

BACKGROUND AND PURPOSE: It is unknown whether deceleration of brain atrophy is associated with disability improvement in patients with MS. Our aim was to investigate whether patients with MS with disability improvement develop less brain atrophy compared with those who progress in disability or remain stable. MATERIALS AND METHODS: We followed 980 patients with MS for a mean of 4.8 ± 2.4 years. Subjects were divided into 3 groups: progress in disability (n = 241, 24.6%), disability improvement (n = 101, 10.3%), and stable (n = 638, 65.1%) at follow-up. Disability improvement and progress in disability were defined on the basis of the Expanded Disability Status Scale score change using standardized guidelines. Stable was defined as nonoccurrence of progress in disability or disability improvement. Normalized whole-brain volume was calculated using SIENAX on 3D T1WI, whereas the lateral ventricle was measured using NeuroSTREAM on 2D-T2-FLAIR images. The percentage brain volume change and percentage lateral ventricle volume change were calculated using SIENA and NeuroSTREAM, respectively. Differences among groups were investigated using ANCOVA, adjusted for age at first MR imaging, race, T2 lesion volume, and corresponding baseline structural volume and the Expanded Disability Status Scale. RESULTS: At first MR imaging, there were no differences among progress in disability, disability improvement, and the stable groups in whole-brain volume (P = .71) or lateral ventricle volume (P = .74). During follow-up, patients with disability improvement had the lowest annualized percentage lateral ventricle volume change (1.6% ± 2.7%) followed by patients who were stable (2.1% ± 3.7%) and had progress in disability (4.1% ± 5.5%), respectively (P < .001). The annualized percentage brain volume change values were -0.7% ± 0.7% for disability improvement, -0.8% ± 0.7% for stable, and -1.1% ± 1.1% for progress in disability (P = .001). CONCLUSIONS: Patients with MS who improve in their clinical disability develop less brain atrophy across time compared with those who progress.

Thermal Performance of Hybrid-Inspired Coolant for Radiator Application.

Due to the increasing demand in industrial application, nanofluids have attracted the considerable attention of researchers in recent decades. The addition of nanocellulose (CNC) with water (W) and ethylene glycol (EG) to a coolant for a radiator application exhibits beneficial properties to improve the efficiency of the radiator. The focus of the present work was to investigate the performance of mono or hybrid metal oxide such as Al2O3 and TiO2 with or without plant base-extracted CNC with varying concentrations as a better heat transfer nanofluid in comparison to distilled water as a radiator coolant. The CNC is dispersed in the base fluid of EG and W with a 60:40 ratio. The highest absorption peak was noticed at 0.9% volume concentration of TiO2, Al2O3, CNC, Al2O3/TiO2, and Al2O3/CNC nanofluids which indicates a better stability of the nanofluids' suspension. Better thermal conductivity improvement was observed for the Al2O3 nanofluids in all mono nanofluids followed by the CNC and TiO2 nanofluids, respectively. The thermal conductivity of the Al2O3/CNC hybrid nanofluids with 0.9% volume concentration was found to be superior than that of the Al2O3/TiO2 hybrid nanofluids. Al2O3/CNC hybrid nanofluid dominates over other mono and hybrid nanofluids in terms of viscosity at all volume concentrations. CNC nanofluids (all volume concentrations) exhibited the highest specific heat capacity than other mono nanofluids. Additionally, in both hybrid nanofluids, Al2O3/CNC showed the lowest specific heat capacity. The optimized volume concentration from the statistical analytical tool was found to be 0.5%. The experimental results show that the heat transfer coefficient, convective heat transfer, Reynolds number and the Nusselt number have a proportional relationship with the volumetric flow rate. Hybrid nanofluids exhibit better thermal conductivity than mono nanofluids. For instance, a better thermal conductivity improvement was shown by the mono Al2O3 nanofluids than the CNC and TiO2 nanofluids. On the other hand, superior thermal conductivity was observed for the Al2O3/CNC hybrid nanofluids compared to the other mono and hybrid ones (Al2O3/TiO2).

Plasma levels of protein C pathway proteins and brain magnetic resonance imaging volumes in multiple sclerosis.

BACKGROUND AND PURPOSE: The involvement of protein C (PC) pathway components in multiple sclerosis (MS) has scarcely been explored. The aim was to investigate their levels in relation to clinical and neurodegenerative magnetic resonance imaging (MRI) outcomes in patients. METHODS: In all, 138 MS patients and 42 healthy individuals were studied. PC, protein S (PS) and soluble endothelial protein C receptor (sEPCR) were evaluated by multiplex assays and enzyme-linked immunosorbent assay. Regression analyses between 3 T MRI outcomes and PC pathway components were performed. ancova was used to compare MRI volumes based on protein level quartiles. Partial correlation was assessed amongst levels of PC pathway components and hemostasis protein levels, including soluble thrombomodulin (sTM), heparin cofactor II (HCII), plasminogen activator inhibitor 1 (PAI-1) and factor XII (FXII). The variation of PC concentration across four time points was evaluated in 32 additional MS patients. RESULTS: There was an association between PC concentration, mainly reflecting the zymogen PC, and MRI measures for volumes of total gray matter (GM) (P = 0.003), thalamus (P = 0.007), cortex (P = 0.008), deep GM (P = 0.009) and whole brain (P = 0.026). Patients in the highest PC level quartile were characterized by the lowest GM volumes. Correlations of PC-HCII, PC-FXII and sEPCR-sTM values were detectable in MS patients, whilst PC-PS and PS-PAI-1 correlations were present in healthy individuals only. CONCLUSIONS: Protein C plasma concentrations might be associated with neurodegenerative MRI outcomes in MS. Several differences in correlation amongst protein plasma levels suggest dysregulation of PC pathway components in MS patients. The stability of PC concentration over time supports a PC investigation in relation to GM atrophy in MS.

A Serial 10-Year Follow-Up Study of Atrophied Brain Lesion Volume and Disability Progression in Patients with Relapsing-Remitting MS.

BACKGROUND AND PURPOSE: Disappearance of T2 lesions into CSF spaces is frequently observed in patients with MS. Our aim was to investigate temporal changes of cumulative atrophied brain T2 lesion volume and 10-year confirmed disability progression. MATERIALS AND METHODS: We studied 176 patients with relapsing-remitting MS who underwent MR imaging at baseline, 6 months, and then yearly for 10 years. Occurrence of new/enlarging T2 lesions, changes in T2 lesion volume, and whole-brain, cortical and ventricle volumes were assessed yearly between baseline and 10 years. Atrophied T2 lesion volume was calculated by combining baseline lesion masks with follow-up CSF partial volume maps. Ten-year confirmed disability progression was confirmed after 48 weeks. ANCOVA detected MR imaging outcome differences in stable (n = 76) and confirmed disability progression (n = 100) groups at different time points; hierarchic regression determined the unique additive variance explained by atrophied T2 lesion volume regarding the association with confirmed disability progression, in addition to other MR imaging metrics. Cox regression investigated the association of early MR imaging outcome changes and time to development of confirmed disability progression. RESULTS: The separation of stable-versus-confirmed disability progression groups became significant even in the first 6 months for atrophied T2 lesion volume (140% difference, Cohen d = 0.54, P = .004) and remained significant across all time points (P ≤ .007). The hierarchic model, including all other MR imaging outcomes during 10 years predicting confirmed disability progression, improved significantly after adding atrophied T2 lesion volume (R 2 = 0.27, R 2 change 0.11, P = .009). In Cox regression, atrophied T2 lesion volume in 0-6 months (hazard ratio = 4.23, P = .04) and 0-12 months (hazard ratio = 2.41, P = .022) was the only significant MR imaging predictor of time to confirmed disability progression. CONCLUSIONS: Atrophied T2 lesion volume is a robust and early marker of disability progression in relapsing-remitting MS.

Leptomeningeal Contrast Enhancement Is Related to Focal Cortical Thinning in Relapsing-Remitting Multiple Sclerosis: A Cross-Sectional MRI Study.

BACKGROUND AND PURPOSE: Leptomeningeal inflammation is associated with the development of global cortical gray matter atrophy in multiple sclerosis. However, its association with localized loss of tissue remains unclear. The purpose of this study was to evaluate the relationship between leptomeningeal contrast enhancement, a putative marker of leptomeningeal inflammation, and focal cortical thinning in MS. MATERIALS AND METHODS: Forty-three patients with relapsing-remitting MS and 15 with secondary-progressive MS were imaged on a 3T scanner. Cortical reconstruction was performed with FreeSurfer. Leptomeningeal contrast-enhancement foci were visually identified on 3D-FLAIR postcontrast images and confirmed using subtraction imaging. Leptomeningeal contrast-enhancement foci were mapped onto the cortex, and ROIs were obtained by dilating along the surface multiple times (n = 5, 10, 15, 20, 25, 30, 35, 40). Resulting ROIs were then mapped onto the homologous region of the contralateral hemisphere. Paired t tests compared the thickness of the cortex surrounding individual leptomeningeal contrast-enhancement foci and the corresponding contralateral region. Results were corrected for the false discovery rate. RESULTS: Differences between ipsilateral and contralateral ROIs progressively decreased with larger ROIs, but no significant effects were detected when considering the entire MS sample. In patients with relapsing-remitting MS only, significantly reduced cortical thickness was found for 5 dilations (-8.53%, corrected P = .04) and 10 dilations (-5.20%, corrected P = .044). CONCLUSIONS: Focal leptomeningeal contrast enhancement is associated with reduced thickness of the surrounding cortex in patients with relapsing-remitting MS, but not in those with secondary-progressive MS. Our results suggest that pathology associated with the presence of leptomeningeal contrast-enhancement foci has a stronger, localized effect on cortical tissue loss earlier in the disease.

Hypertension and heart disease are associated with development of brain atrophy in multiple sclerosis: a 5-year longitudinal study.

BACKGROUND: Cardiovascular diseases (CVDs) are more frequent in multiple sclerosis (MS) patients when compared to controls. In particular, CVDs are linked with higher accumulation of lesions and advanced brain atrophy. OBJECTIVE: To investigate whether CVDs contribute to accelerated lesion accumulation and brain atrophy over 5 years in patients with MS. METHODS: 194 MS patients and 43 controls without neurologic disease were followed for 5 years. Full physical, neurological evaluation, and structured questionnaire investigating CVD and risk factors (hypertension, hyperlipidemia, heart disease, smoking, diabetes, obesity/overweight) were collected using interview-based questionnaire and further cross-reference with electronic medical records. Lesion and brain atrophy outcomes were assessed with 3T MRI. ANCOVA adjusted for age, gender, and disease duration were used accordingly. False discovery rate correction was performed using Benjamini-Hochberg correction. RESULTS: Patients with diagnosis of heart disease showed higher white matter and whole brain volume loss compared to those without (-4.2% vs. -0.7%, P = 0.01 and -3.4% vs. -1.6%, P = 0.01, respectively). The percentage lateral ventricle volume change in MS patients with hypertension was higher compared to non-hypertensive patients (24.5% vs. 14.1%, P = 0.05). Hyperlipidemia, smoking, and obesity/overweight were not associated with progression of MRI-derived outcomes. CVDs did not contribute to larger lesion volume accrual over the 5-year period. The presence of CVDs was not associated with MRI-derived changes in the controls. CONCLUSIONS: Hypertension and heart disease contribute to advanced brain atrophy in MS patients. CVDs did not contribute to additional lesion accrual. CVD comorbidities in MS patients may contribute to neurodegenerative tissue injury that can be detected with brain MRI.

Brain Atrophy Is Associated with Disability Progression in Patients with MS followed in a Clinical Routine.

BACKGROUND AND PURPOSE: The assessment of brain atrophy in a clinical routine is not performed routinely in multiple sclerosis. Our aim was to determine the feasibility of brain atrophy measurement and its association with disability progression in patients with MS followed in a clinical routine for 5 years. MATERIALS AND METHODS: A total of 1815 subjects, 1514 with MS and 137 with clinically isolated syndrome and 164 healthy individuals, were collected retrospectively. Of 11,794 MR imaging brain scans included in the analysis, 8423 MRIs were performed on a 3T, and 3371 MRIs, on a 1.5T scanner. All patients underwent 3D T1WI and T2-FLAIR examinations at all time points of the study. Whole-brain volume changes were measured by percentage brain volume change/normalized brain volume change using SIENA/SIENAX on 3D T1WI and percentage lateral ventricle volume change using NeuroSTREAM on T2-FLAIR. RESULTS: Percentage brain volume change failed in 36.7% of the subjects; percentage normalized brain volume change, in 19.2%; and percentage lateral ventricle volume change, in 3.3% because of protocol changes, poor scan quality, artifacts, and anatomic variations. Annualized brain volume changes were significantly different between those with MS and healthy individuals for percentage brain volume change (P < .001), percentage normalized brain volume change (P = .002), and percentage lateral ventricle volume change (P = .01). In patients with MS, mixed-effects model analysis showed that disability progression was associated with a 21.9% annualized decrease in percentage brain volume change (P < .001) and normalized brain volume (P = .002) and a 33% increase in lateral ventricle volume (P = .004). CONCLUSIONS: All brain volume measures differentiated MS and healthy individuals and were associated with disability progression, but the lateral ventricle volume assessment was the most feasible.

Impact of Focal White Matter Damage on Localized Subcortical Gray Matter Atrophy in Multiple Sclerosis: A 5-Year Study.

BACKGROUND AND PURPOSE: It is unclear to what extent subcortical gray matter atrophy is a primary process as opposed to a result of focal white matter damage. Correlations between WM damage and atrophy of subcortical gray matter have been observed but may be partly attributable to indirect relationships between co-occurring processes arising from a common cause. Our aim was to cross-sectionally and longitudinally characterize the unique impact of focal WM damage on the atrophy of connected subcortical gray matter regions, beyond what is explainable by global disease progression. MATERIALS AND METHODS: One hundred seventy-six individuals with MS and 47 healthy controls underwent MR imaging at baseline and 5 years later. Atrophy and lesion-based disruption of connected WM tracts were evaluated for 14 subcortical gray matter regions. Hierarchic regressions were applied, predicting regional atrophy from focal WM disruption, controlling for age, sex, disease duration, whole-brain volume, and T2-lesion volume. RESULTS: When we controlled for whole-brain volume and T2-lesion volume, WM tract disruption explained little additional variance of subcortical gray matter atrophy and was a significant predictor for only 3 of 14 regions cross-sectionally (ΔR2 = 0.004) and 5 regions longitudinally (ΔR2 = 0.016). WM tract disruption was a significant predictor for even fewer regions when correcting for multiple comparisons. CONCLUSIONS: WM tract disruption accounts for a small percentage of atrophy in connected subcortical gray matter when controlling for overall disease burden and is not the primary driver in most cases.

Hemostasis biomarkers in multiple sclerosis.

BACKGROUND AND PURPOSE: The aim was to investigate the plasma levels of hemostasis components in multiple sclerosis (MS) and their association with clinical and magnetic resonance imaging (MRI) outcomes. METHODS: In all, 138 MS patients [85 with relapsing-remitting MS (RR-MS) and 53 with progressive MS (P-MS) with a mean age of 54 years; 72.5% female; median Expanded Disability Status Scale 3.5; mean disease duration 21 years] and 42 age- and sex-matched healthy individuals (HI) were studied. All subjects were examined with 3 T MRI and clinical examinations. Plasma levels of hemostasis factors [procoagulant, factor XII (FXII)] and inhibitors [tissue factor pathway inhibitor (TFPI), thrombomodulin, heparin cofactor II, a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13) and plasminogen activator inhibitor 1 (PAI-1)] were evaluated by magnetic Luminex assays and enzyme-linked immunosorbent assay. Associations between hemostasis plasma levels and clinical and MRI outcomes were assessed. RESULTS: Lower ADAMTS13 levels were found in MS patients compared to HI (P = 0.008) and in MS patients presenting with cerebral microbleeds compared to those without (P = 0.034). Higher PAI-1 levels were found in MS patients compared to HI (P = 0.02). TFPI levels were higher in the P-MS subgroup compared to RR-MS patients (P = 0.011) and compared to HI (P = 0.002). No significant associations between hemostasis plasma levels and clinical or MRI outcomes were found. CONCLUSIONS: Decreased ADAMTS13, particularly in MS patients with cerebral microbleeds, which deserves further investigation, and increased PAI-1 and TFPI levels were observed in MS patients, which deserves further investigation. No relationship between hemostasis plasma levels and measures of disease severity was detected.

Evaluation of Leptomeningeal Contrast Enhancement Using Pre-and Postcontrast Subtraction 3D-FLAIR Imaging in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Leptomeningeal contrast enhancement is found in patients with multiple sclerosis, though reported rates have varied. The use of 3D-fluid-attenuated inversion recovery pre- and postcontrast subtraction imaging may more accurately determine the frequency of leptomeningeal contrast enhancement. The purpose of this study was to investigate the frequency of leptomeningeal contrast enhancement using the pre- and postcontrast subtraction approach and to evaluate 3 different methods of assessing the presence of leptomeningeal contrast enhancement. MATERIALS AND METHODS: We enrolled 258 consecutive patients with MS (212 with relapsing-remitting MS, 32 with secondary-progressive MS, and 14 with clinically isolated syndrome) who underwent both pre- and 10-minute postcontrast 3D-FLAIR sequences after a single dose of gadolinium injection on 3T MR imaging. The analysis included leptomeningeal contrast-enhancement evaluation on 3D-FLAIR postcontrast images in native space (method A), on pre- and postcontrast 3D-FLAIR images in native space (method B), and on pre-/postcontrast 3D-FLAIR coregistered and subtracted images (method C, used as the criterion standard). RESULTS: In total, 51 (19.7%) patients with MS showed the presence of leptomeningeal contrast enhancement using method A; 39 (15.1%), using method B; and 39 (15.1%), using method C (P = .002). Compared with method C as the criterion standard, method A showed 89.8% sensitivity and 92.7% specificity, while method B showed 84.6% sensitivity and 97.3% specificity (P < .001) at the patient level. Reproducibility was the highest using method C (κ agreement, r = 088, P < .001). The mean time to analyze the 3D-FLAIR images was significantly lower with method C compared with methods A and B (P < .001). CONCLUSIONS: 3D-FLAIR postcontrast imaging offers a sensitive method for detecting leptomeningeal contrast enhancement in patients with MS. However, the use of subtraction imaging helped avoid false-positive cases, decreased reading time, and increased the accuracy of leptomeningeal contrast-enhancement foci detection in a clinical routine.

Effect of natalizumab on brain atrophy and disability progression in multiple sclerosis patients over 5 years.

BACKGROUND AND PURPOSE: The long-term benefit of natalizumab on brain atrophy progression in multiple sclerosis (MS) patients is unknown. Our aim was to investigate its effect over 5 years. METHODS: This prospective study included 60 relapsing MS patients who started natalizumab treatment in years 2006-2007. RESULTS: At the 5-year follow-up, 20 patients discontinued natalizumab after an average of 29.5 cycles, 27 continued natalizumab treatment with some periods of honeymoon (average of 38.4 infusions) and 13 never stopped natalizumab (average of 60.6 infusions). In multiple linear regression analysis, adjusted for age, sex and baseline magnetic resonance imaging (MRI) status, the number of natalizumab infusions was associated with decrease of relapse rate (adjusted P = 0.037), but no association was found with the progression of disability, accumulation of lesion burden or brain volume loss. However, only one (8%) patient in the continuous monthly group experienced disability progression compared to 10 (37%) in the non-continuous and seven (35%) in the discontinuation natalizumab groups. At the follow-up, two patients had died [one from a fatal case of progressive multifocal leukoencephalopathy (PML) and one from a car accident] and 15 patients were lost to follow-up. There was another case of non-fatal PML over the follow-up. CONCLUSIONS: In line with previous reports, MS patients with longer and continuous use of natalizumab had fewer relapses and remained stable in their disability status. No difference in lesion burden accumulation or brain atrophy development was found in relation to the duration of natalizumab use. PML occurred in 2.5% of patients in this small sample cohort. Given the increased risk of PML and uncertain benefit of prolonged natalizumab use on clinical and MRI outcomes of disease progression found in this study, a careful risk-benefit therapeutic assessment is mandatory.

Early magnetic resonance imaging predictors of clinical progression after 48 months in clinically isolated syndrome patients treated with intramuscular interferon ß-1a.

BACKGROUND AND PURPOSE: Our aim was to identify early imaging surrogate markers of clinical progression in patients after the first demyelinating event suggestive of multiple sclerosis treated with weekly intramuscular interferon ß-1a. In a prospective observational study, the predictive role of baseline and 6-month changes in magnetic resonance imaging outcomes was investigated with respect to relapse activity and development of confirmed disability progression in patients after 48 months. METHODS: This study examined 210 patients. Multivariate Cox proportional hazard models were used to analyse predictors of relapse activity and confirmed disability progression after 48 months. RESULTS: Greater T2 lesion volume [hazard ratio (HR) 1.81; P = 0.005] and the presence of contrast-enhancing lesions (HR 2.13; P < 0.001) at baseline were significantly associated with increased cumulative risk of a second clinical attack over 48 months. A greater decrease of the corpus callosum volume (HR 2.74; P = 0.001) and greater lateral ventricle volume enlargement (HR 2.43; P = 0.002) at 6 months relative to baseline were associated with increased cumulative risk of a second clinical attack between months 6 and 48. In addition, increased risk of confirmed disability progression over 48 months in patients with greater lateral ventricle volume enlargement between baseline and 6 months (HR 4.70; P = 0.001) was detected. CONCLUSIONS: A greater T2 lesion volume, the presence of contrast-enhancing lesions at baseline, decrease of corpus callosum volume and lateral ventricle volume enlargement over the first 6 months in patients after the first demyelinating event treated with weekly intramuscular interferon ß-1a may assist in identification of patients with the highest risk of a second clinical attack and progression of disability.

Subcortical deep gray matter pathology in patients with multiple sclerosis is associated with white matter lesion burden and atrophy but not with cortical atrophy: a diffusion tensor MRI study.

BACKGROUND AND PURPOSE: The association between subcortical deep gray matter, white matter, and cortical pathology is not well understood in MS. The aim of this study was to use DTI to investigate the subcortical deep gray matter alterations and their relationship with lesion burden, white matter, and cortical atrophy in patients with MS and healthy control patients. MATERIALS AND METHODS: A total of 210 patients with relapsing-remitting MS, 75 patients with progressive MS, and 110 healthy control patients were included in the study. DTI metrics in whole brain, normal-appearing white matter, normal-appearing gray matter, and subcortical deep gray matter structures were compared. The association between DTI metrics of the subcortical deep gray matter structures with lesion burden, normalized white matter volume, and normalized cortical volume was investigated. RESULTS: DTI measures were significantly different in whole brain, normal-appearing white matter, and normal-appearing gray matter among the groups (P < .01). Significant differences in DTI diffusivity of total subcortical deep gray matter, caudate, thalamus, and hippocampus (P < .001) were found. DTI diffusivity of total subcortical deep gray matter was significantly associated with normalized white matter volume (P < .001) and normalized cortical volume (P = .033) in healthy control patients. In both relapsing and progressive MS groups, the DTI subcortical deep gray matter measures were associated with the lesion burden and with normalized white matter volume (P < .001), but not with normalized cortical volume. CONCLUSIONS: These findings suggest that subcortical deep gray matter abnormalities are associated with white matter lesion burden and atrophy, whereas cortical atrophy is not associated with microstructural alterations of subcortical deep gray matter structures in patients with MS.

Prevalence of radiologically isolated syndrome and white matter signal abnormalities in healthy relatives of patients with multiple sclerosis.

BACKGROUND AND PURPOSE: The exact prevalence of WM signal abnormalities in healthy relatives of MS patients and their impact on disease development has not been fully elucidated. The purpose of this study was to compare WM signal abnormality characteristics and the prevalence of radiologically isolated syndrome in healthy control subjects selected randomly from the population with the healthy relatives of patients with MS. MATERIALS AND METHODS: Healthy control subjects (n = 150) underwent physical and 3T MR imaging examinations. Healthy control subjects were classified as non-familial healthy control subjects (n = 82) if they had no family history of MS or as healthy relatives of patients with MS (n = 68) if they had ≥1 relative affected with MS. The presence of radiologically isolated syndrome was evaluated according to the Okuda criteria; dissemination in space on MR imaging and fulfillment of radiologically isolated syndrome criteria were also evaluated according to Swanton criteria. RESULTS: There was a significantly higher total volume of WM signal abnormality in the healthy relatives of patients with MS compared with the non-familial healthy control subjects (P = .024 for signal abnormality ≥3 mm in size and P = .025 for all sizes). Periventricular localization and the number of lesions in all groups (P = .034 and P = .043) were significantly higher in the healthy relatives of patients with MS; 8.8% of the healthy relatives of patients with MS and 4.9% of non-familial healthy control subjects showed ≥9 WM signal abnormalities; 2.9% of subjects in the healthy relatives of patients with MS group and 2.4% of non-familial healthy control subjects fulfilled radiologically isolated syndrome according to the Okuda criteria, whereas 10.3% and 3.7% of subjects fulfilled radiologically isolated syndrome according to the Swanton criteria. In the healthy relatives of patients with MS, smoking was associated with the presence of WM signal abnormalities, whereas obesity was related to the presence of ≥9 WM signal abnormalities and to fulfillment of radiologically isolated syndrome according to the Swanton criteria. CONCLUSIONS: The frequency of WM signal abnormalities and radiologically isolated syndrome is higher in the healthy relatives of patients with multiple sclerosis patients compared with non-familial healthy control subjects.