Cognitive dysfunction is common in multiple sclerosis (MS). However, the relationship between white matter (WM) damage and cognition remains insufficiently clear. This study investigates the extent and severity of WM diffusion abnormalities in MS patients and relations with cognition. Diffusion tensor imaging scans were obtained in 131 MS patients (88 women, 6 years postdiagnosis) and 49 age-matched controls (29 women). Patient groups were equal in terms of disease duration, disability, and WM lesion volume. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were compared between groups. Post hoc analyses calculated the spatial extent and severity of diffusion abnormalities to relate these to cognitive performance. In controls, 31% of WM voxels showed higher FA in men; therefore, all patient analyses were within-sex. The extent of diffusion changes was higher in male patients than in female patients for all parameters (FA: 24% in women, 53% in men), as was the severity of changes (FA: Z = -0.18 in women, Z = -0.41 in men). Especially the extent of FA abnormalities was strongly related to cognitive performance in all patients (r = -0.42, P < 0.0001). Regionally, thalamic decreases in FA were especially correlated with cognitive performance. Cognitively impaired patients showed greater extent and severity on all diffusion parameters compared to cognitively preserved patients. The WM of male patients was both more extensively and also more severely affected than that of female patients. The extent of WM FA changes, especially in the thalamus, was associated with cognitive performance in this cohort of early MS patients.

Classically multiple sclerosis (MS) has been regarded as an auto‐immune disease of the white matter in the central nervous system leading to severe disability over the course of several decades. Current therapeutic strategies in MS are mostly based on either immune suppression or immune modulation. Although effective in decreasing relapse frequency and severity as well as delaying disease progression, MS pathology ensues nonetheless. In the last decade it became evident that gray matter pathology plays an important role in disease progression and helps explaining certain aspects of MS‐related disability such as cognitive decline. Conventional MRI outcome measures commonly used in clinical trials are sufficient to demonstrate an anti‐inflammatory drug‐effect but lack pathological specificity and are poor to moderate predictors of disability. In this article, we review new insights in gray matter pathology and functional reorganization in MS and how these novel fields in MS research may validate and establish new MRI outcome measures, aid in the development of new therapeutic strategies for neuroprotection and neurorepair, and may lead to development of novel predictive measures of disability and disease progression in MS. J. Magn. Reson. Imaging 2012; 36:1–19. © 2012 Wiley Periodicals, Inc.

Background: Rapid and accurate detection of SARS-CoV-2 infected individuals is crucial for taking timely measures and minimizing the risk of further SARS-CoV-2 spread. We aimed to assess the accuracy of exhaled breath analysis by electronic nose (eNose) for the discrimination between individuals with and without a SARS-CoV-2 infection. Methods: This was a prospective real-world study of individuals presenting to public test facility for SARS-CoV-2 detection by molecular amplification tests (TMA or RT-PCR). After sampling of a combined throat/nasopharyngeal swab, breath profiles were obtained using a cloud-connected eNose. Data-analysis involved advanced signal processing and statistics based on independent t-tests followed by linear discriminant and ROC analysis. Data from the training set were tested in a validation, a replication and an asymptomatic set. Findings: For the analysis 4510 individuals were available. In the training set (35 individuals with; 869 without SARS-CoV-2), the eNose sensors were combined into a composite biomarker with a ROC-AUC of 0.947 (CI:0.928-0.967). These results were confirmed in the validation set (0.957; CI:0.942-0.971, n=904) and externally validated in the replication set (0.937; CI:0.926-0.947, n=1948) and the asymptomatic set (0.909; CI:0.879-0.938, n=754). Selecting a cut-off value of 0.30 in the training set resulted in a sensitivity/specificity of 100/78, >99/84, 98/82% in the validation, replication and asymptomatic set, respectively. Interpretation: eNose represents a quick and non-invasive method to reliably rule out SARS-CoV-2 infection in public health test facilities and can be used as a screening test to define who needs an additional confirmation test. Funding: Ministry of Health, Welfare and Sport

Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, clinicians have been struggling with the optimal diagnostic approach of suspected patients. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) testing of respiratory samples is generally being considered as the reference standard for establishing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection [1]. However, RT-PCR results take hours to become available and, although highly specific, sensitivity is moderate [2-4]. This could result in delayed and suboptimal clinical decision making. Several reports have suggested a potential role for chest computed tomography (CT) in patients with suspected COVID-19 [5-10]. Major advantages of CT are that it provides immediate results and can identify alternative diagnoses for respiratory symptoms. CT may show signs suspicious or typical of COVID-19 in patients with a negative RT-PCR result, ensuring that the patient remains isolated. On the other hand, a negative CT result in combination with a negative RT-PCR result may exclude COVID-19 with a higher level of certainty, in which case patient de-isolation can be considered, and additional diagnostic work-up can be initiated. In this study, we evaluated the added value of chest CT over RT-PCR testing alone. Consecutive patients with suspected COVID-19 who presented to the emergency department of our university hospital (Academic Medical Center, Amsterdam University Medical Centers, the Netherlands) from 16 March to 16 April 2020 were retrospectively assessed for inclusion. Patients with suspected COVID-19 were those with 1) fever, 2) cough or dyspnoea, or 3) other signs suggestive of COVID-19 (e.g. gastro-intestinal symptoms). Patients were included if they were 18 years or older, required hospital admission, and underwent both chest CT and RT-PCR testing for SARS-CoV-2 infection upon admission. In our hospital, performing both these tests is standard practice for patients with suspected COVID-19 requiring admission. We excluded patients who already had a prior positive RT-PCR result. Data were extracted from patient records by one author (D.A. Korevaar, R.S. Kootte or L.P. Smits). A non-enhanced low-dose chest CT scan was obtained from all patients (Somatom Force, Siemens Healthineers, Forchheim, Germany). CT images were read as part of standard clinical practice by attending radiologists, with varying degrees of experience. To improve uniformity, an informal second read was performed in some cases by a dedicated acute radiologist, and disagreements were solved by consensus. The radiological probability of pulmonary manifestations of COVID-19 was reported based on the "CO-RADS classification", a standardised reporting system for patients with suspected COVID-19, ranging from 1 (very unlikely) to 5 (very likely) [11, 12]. In this study, CO-RADS scores of 1-2 were considered as negative, scores of 4-5 were positive, and a score of 3 was indeterminate. CT readers were not blinded to clinical information, but RT-PCR results ...