Advances in Magnetic Resonance Imaging in Multiple Sclerosis

Multiple sclerosis is the second most common cause of disability in young adults. Conventional imaging so far failed to explain the extent of clinical disability even by careful examination of white matter lesion volume and their topographical distribution. The increasing availability of ultra-high field imaging allowed the improvement in understanding the dynamic lesional and extralesional pathology in different stages of the disease and their potential contribution to clinical and cognitive disability. The contribution of cortical lesions of different subtypes, the degree of microstructural damage in those lesions has been examined. This is in addition to the influence of white matter lesions and spinal cord pathology on the degree of disability in multiple sclerosis. Prognostic factors influencing long-term disability in patients with multiple sclerosis have also been a subject of interest for many years, particularly their significance in early decision-making with regard to disease-modifying treatment choice and early initiation. The frequency of iron rims in white matter lesions has been linked to increased disease severity in multiple sclerosis. Iron rim lesions’ potential evolution to slowly expanding lesions as well as the long-term prognostic impact of such lesions on the degree of clinical disability has also been examined in this chapter

Cortical imaging as seen at ultrahigh field MRI

Multiple Sclerosis (MS) has long been considered as White matter (WM) disease. The last decade, the significance of cortical lesions (CL) and their contribution to MS pathology has been intensely investigated. They have been shown to play a major role in physical and cognitive impairment in MS patients. CL detection has proven to be challenging, mainly due to poor contrast between cortical lesion and surrounding normal grey matter (GM) tissue. Various magnetic resonance imaging (MRI) sequences have been used to improve cortical lesion detection in MS patients. In recent years, Double inversion recovery (DIR), Phase sensitive inversion recovery (PSIR) and 7 Tesla T2* have been found to improve CL detection. Magnetization Transfer Imaging (MTI) has the advantage over conventional imaging as it reflects tissue myelin content. In this thesis, I present our studies using MTI at 7 Tesla to study cortical pathology in MS. 1) For a pilot study aiming to validate the use of magnetization transfer ratio (MTR) to detect cortical lesions, We examined the sensitivity of MTR to detect cortical lesions in comparison with 3 T DIR, 7 T PSIR, and 7 T T2* in 18 MS patients and 9 healthy controls. 2) A further 42 patients (11 clinically isolated syndrome (CIS), 11 relapsing remitting MS (RRMS), 10 primary progressive MS (PPMS), and 10 secondary progressive MS (SPMS)) and 8 healthy controls were scanned at baseline, 23 of these patients had a follow up scan at 12 months. MTR at 7 Tesla has increased sensitivity to detect cortical lesions compared to 3T DIR, 7T PSIR and 7T T2*. CL myelin content as measured by the mean MTR lesional values were the lowest in SPMS patients in comparison with the rest of MS phenotypes. CL mean MTR values, more than volume was associated with the degree of physical and cognitive disability in MS patients. When MTR was studied in a longitudinal study, we have seen more changes in average MTR of cortical lesions in SPMS and CIS patients compared to RRMS and PPMS patients

Cortical imaging as seen at ultrahigh field MRI

Multiple Sclerosis (MS) has long been considered as White matter (WM) disease. The last decade, the significance of cortical lesions (CL) and their contribution to MS pathology has been intensely investigated. They have been shown to play a major role in physical and cognitive impairment in MS patients. CL detection has proven to be challenging, mainly due to poor contrast between cortical lesion and surrounding normal grey matter (GM) tissue. Various magnetic resonance imaging (MRI) sequences have been used to improve cortical lesion detection in MS patients. In recent years, Double inversion recovery (DIR), Phase sensitive inversion recovery (PSIR) and 7 Tesla T2* have been found to improve CL detection. Magnetization Transfer Imaging (MTI) has the advantage over conventional imaging as it reflects tissue myelin content. In this thesis, I present our studies using MTI at 7 Tesla to study cortical pathology in MS. 1) For a pilot study aiming to validate the use of magnetization transfer ratio (MTR) to detect cortical lesions, We examined the sensitivity of MTR to detect cortical lesions in comparison with 3 T DIR, 7 T PSIR, and 7 T T2* in 18 MS patients and 9 healthy controls. 2) A further 42 patients (11 clinically isolated syndrome (CIS), 11 relapsing remitting MS (RRMS), 10 primary progressive MS (PPMS), and 10 secondary progressive MS (SPMS)) and 8 healthy controls were scanned at baseline, 23 of these patients had a follow up scan at 12 months. MTR at 7 Tesla has increased sensitivity to detect cortical lesions compared to 3T DIR, 7T PSIR and 7T T2*. CL myelin content as measured by the mean MTR lesional values were the lowest in SPMS patients in comparison with the rest of MS phenotypes. CL mean MTR values, more than volume was associated with the degree of physical and cognitive disability in MS patients. When MTR was studied in a longitudinal study, we have seen more changes in average MTR of cortical lesions in SPMS and CIS patients compared to RRMS and PPMS patients

Imaging gray matter with concomitant null point imaging from the phase sensitive inversion recovery sequence

Purpose To present an improved three-dimensional (3D) interleaved phase sensitive inversion recovery (PSIR) sequence including a concomitantly acquired new contrast, null point imaging (NPI), to help detect and classify abnormalities in cortical gray matter. Methods The 3D gradient echo PSIR images were acquired at 0.6 mm isotropic resolution on 11 multiple sclerosis (MS) patients and 9 controls subjects using a 7 Tesla (T) MRI scanner, and 2 MS patients at 3T. Cortical abnormalities were delineated on the NPI/PSIR data and later classified according to position in the cortex. Results The NPI helped detect cortical lesions within the cortical ribbon with increased, positive contrast compared with the PSIR. It also provided improved intrinsic delineation of the ribbon, increasing confidence in classifying the lesions' locations. Conclusion The proposed PSIR facilitates the classification of cortical lesions by providing two T1-weighted 3D datasets with isotropic resolution, including the NPI showing cortical lesions with clear delineation of the gray/white matter boundary and minimal partial volume effects. Magn Reson Med 76:1512–1516, 2016. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

Longitudinal clinical study of patients with iron rim lesions in multiple sclerosis

Background: Iron rims (IRs) surrounding white matter lesions (WMLs) are suggested to predict a more severe disease course. Only small longitudinal cohorts of patients with and without iron rim lesions (IRLs) have been reported so far. Objective: To assess whether the presence and number of IRLs in patients with clinically isolated syndrome (CIS) and multiple sclerosis (MS) are associated with long-term disability or progressive disease. Methods: Ninety-one CIS/MS patients were recruited between 2008 and 2013 and scanned with 7 T magnetic resonance imaging (MRI). Expanded Disability Status Scale (EDSS) was used to calculate Age-related Multiple Sclerosis Severity Score (ARMSS) at the time of scan and at the latest clinical follow-up after 9 years. WMLs were assessed for the presence of IRL using Susceptibility weighted imaging (SWI)-filtered phase images. Results: In all, 132 IRLs were detected in 42 patients (46%); 9% of WMLs had IRs; 54% of the cohort had no rims, 30% had 1–3 rims and 16% had ⩾4. Patients with IRL had a higher EDSS and ARMSS. Presence of IRL was also a predictor of long-term disability, especially in patients with ⩾4 IRLs. IRLs have a greater impact on disability compared to the WML number and volume. Conclusion: The presence and number of perilesional IR on MRI hold prognostic value for long-term clinical disability in MS

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Imaging gray matter with concomitant null point imaging from the phase sensitive inversion recovery sequence

Purpose To present an improved three-dimensional (3D) interleaved phase sensitive inversion recovery (PSIR) sequence including a concomitantly acquired new contrast, null point imaging (NPI), to help detect and classify abnormalities in cortical gray matter. Methods The 3D gradient echo PSIR images were acquired at 0.6 mm isotropic resolution on 11 multiple sclerosis (MS) patients and 9 controls subjects using a 7 Tesla (T) MRI scanner, and 2 MS patients at 3T. Cortical abnormalities were delineated on the NPI/PSIR data and later classified according to position in the cortex. Results The NPI helped detect cortical lesions within the cortical ribbon with increased, positive contrast compared with the PSIR. It also provided improved intrinsic delineation of the ribbon, increasing confidence in classifying the lesions' locations. Conclusion The proposed PSIR facilitates the classification of cortical lesions by providing two T1-weighted 3D datasets with isotropic resolution, including the NPI showing cortical lesions with clear delineation of the gray/white matter boundary and minimal partial volume effects. Magn Reson Med 76:1512–1516, 2016. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

Imaging central veins in brain lesions with 3-T T2*-weighted magnetic resonance imaging differentiates multiple sclerosis from microangiopathic brain lesions

Background: White matter lesions are frequently detected using brain magnetic resonance imaging (MRI) performed for various indications. Most are microangiopathic, but demyelination, including multiple sclerosis (MS), is an important cause; conventional MRI cannot always distinguish between these pathologies. The proportion of lesions with a central vein on 7-T T2*-weighted MRI prospectively distinguishes demyelination from microangiopathic lesions. Objective: To test whether 3-T T2*-weighted MRI can differentiate MS from microangiopathic brain lesions. Methods: A total of 40 patients were studied. Initially, a test cohort of 10 patients with MS and 10 patients with microangiopathic white matter lesions underwent 3-T T2*-weighted brain MRI. Anonymised scans were analysed blind to clinical data, and simple diagnostic rules were devised. These rules were applied to a validation cohort of 20 patients (13 with MS and 7 with microangiopathic lesions) by a blinded observer. Results: Within the test cohort, all patients with MS had central veins visible in &gt;45% of brain lesions, while the rest had central veins visible in &lt;45% of lesions. By applying diagnostic rules to the validation cohort, all remaining patients were correctly categorised. Conclusion: 3-T T2*-weighted brain MRI distinguishes perivenous MS lesions from microangiopathic lesions. Clinical application of this technique could supplement existing diagnostic algorithms. </jats:sec