Growing evidence links COVID-19 with acute and long-term neurological dysfunction. However, the pathophysiological mechanisms resulting in central nervous system involvement remain unclear, posing both diagnostic and therapeutic challenges. Here we show outcomes of a cross-sectional clinical study (NCT04472013) including clinical and imaging data and corresponding multidimensional characterization of immune mediators in the cerebrospinal fluid (CSF) and plasma of patients belonging to different Neuro-COVID severity classes. The most prominent signs of severe Neuro-COVID are blood-brain barrier (BBB) impairment, elevated microglia activation markers and a polyclonal B cell response targeting self-antigens and non-self-antigens. COVID-19 patients show decreased regional brain volumes associating with specific CSF parameters, however, COVID-19 patients characterized by plasma cytokine storm are presenting with a non-inflammatory CSF profile. Post-acute COVID-19 syndrome strongly associates with a distinctive set of CSF and plasma mediators. Collectively, we identify several potentially actionable targets to prevent or intervene with the neurological consequences of SARS-CoV-2 infection.

Objectives: Ischemic stroke is a leading cause of mortality and acquired disability worldwide and thus plays an enormous health-economic role. Imaging of choice is computed-tomographic (CT) or magnetic resonance imaging (MRI), especially diffusion-weighted (DW) sequences. However, MR imaging is associated with high costs and therefore has a limited availability leading to low-field-MRI techniques increasingly coming into focus. Thus, the aim of our study was to assess the potential of stroke imaging with low-field MRI. Material and Methods: A scanner comparison was performed including 27 patients (17 stroke cohort, 10 control group). For each patient, a brain scan was performed first with a 1.5T scanner and afterwards with a 0.55T scanner. Scan protocols were as identical as possible and optimized. Data analysis was performed in three steps: All DWI/ADC (apparent diffusion coefficient) and FLAIR (fluid attenuated inversion recovery) sequences underwent Likert rating with respect to image impression, resolution, noise, contrast, and diagnostic quality and were evaluated by two radiologists regarding number and localization of DWI and FLAIR lesions in a blinded fashion. Then segmentation of lesion volumes was performed by two other radiologists on DWI/ADC and FLAIR. Results: DWI/ADC lesions could be diagnosed with the same reliability by the most experienced reader in the 0.55T and 1.5T sequences (specificity 100% and sensitivity 92.9%, respectively). False positive findings did not occur. Detection of number/location of FLAIR lesions was mostly equivalent between 0.55T and 1.5T sequences. No significant difference (p = 0.789–0.104) for FLAIR resolution and contrast was observed regarding Likert scaling. For DWI/ADC noise, the 0.55T sequences were significantly superior (p < 0.026). Otherwise, the 1.5T sequences were significantly superior (p < 0.029). There was no significant difference in infarct volume and volume of infarct demarcation between the 0.55T and 1.5T sequences, when detectable. Conclusions: Low-field MRI stroke imaging at 0.55T may not be inferior to scanners with higher field strengths and thus has great potential as a low-cost alternative in future stroke diagnostics. However, there are limitations in the detection of very small infarcts. Further technical developments with follow-up studies must show whether this problem can be solved.

Levels of activated complement proteins in the CSF are increased in people with multiple sclerosis (MS) and are associated with clinical disease severity. In this study, we determined whether complement activation profiles track with quantitative MRI metrics and liquid biomarkers indicative of disease activity and progression. Complement components and activation products (Factor H and I, C1q, C3, C4, C5, Ba, Bb, C3a, C4a, C5a, and sC5b-9) and liquid biomarkers (neurofilament light chain, glial fibrillary acidic protein [GFAP], CXCL-13, CXCL-9, and IL-12b) were quantified in the CSF of 112 patients with clinically isolated syndromes and 127 patients with MS; longitudinal MRIs according to a standardized protocol of the Swiss MS cohort were assessed. We used multivariable models to analyze associations of the 12 complement parameters as individual independent variables and longitudinal brain volumes, T2-weighted (T2w) lesion volumes, contrast-enhancing (CELs) and paramagnetic rim lesions (PRLs), and molecular biomarkers as dependent variables, respectively. Strongest associations with accelerated brain atrophy were found for C4a: doubling of C4a CSF levels was associated with an additional brain volume loss of -0.24% (95% CI -0.31% to -0.16%; p < 0.0001) per year, followed by Ba and C3a (-0.22% [-0.29% to -0.15%]) and -0.13% ([-0.21 to -0.06]; both p < 0.001). Doubling of C3a, Ba, and C4a levels correlated with 2.2- (1.6-3.0; p < 0.0001), 2.0- (1.3-3.1; p = 0.0038), and 1.8-fold (1.2-2.6; p = 0.0029) increased longitudinal T2w lesion volumes; C3a and Ba were associated with 2.5- (1.4-4.6; p = 0.0022) and 3.3-fold (1.5-7.2; p = 0.0024) higher odds for CELs and 2.6- (1.7-4.0; p < 0.0001) and 2.3-fold (1.3-4.3; p = 0.006) increased PRL incidence rates. C1q, C3a, and C4a were associated with higher GFAP levels, and CXCL-13, CXCL-9, and IL-12b analyses showed consistent patterns with strongest associations for C1q, followed by Ba, C3a, and C4a. Intrathecal complement activation is consistently associated with MRI metrics and liquid biomarkers indicative for MS disease activity and progression. Our results demonstrate that aberrant complement activation is strongly associated with structural brain damage in MS. Therapeutic targeting of the complement system might limit disability accumulation due to MS.

BACKGROUND AND PURPOSE: While the use of cervical spine CT in trauma settings has increased, the balance between image quality and dose reduction remains a concern. The purpose of our study was to compare the image quality of CT of the cervical spine of cadaveric specimens at different radiation dose levels. MATERIALS AND METHODS: The cervical spine of 4 human cadavers (mean body mass index; 30.5 ± 5.2 kg/m²; range, 24–36 kg/m²) was examined using different reference tube current–time products (45, 75, 105, 135, 150, 165, 195, 275, 355 mAs) and a tube voltage of 120 kV(peak). Data were reconstructed with filtered back-projection and iterative reconstruction. Qualitative image noise and morphologic characteristics of bony structures were quantified on a Likert scale. Quantitative image noise was measured. Statistics included analysis of variance and the Tukey test. RESULTS: Compared with filtered back-projection, iterative reconstruction provided significantly lower qualitative (mean noise score: iterative reconstruction = 2.10/filtered back-projection = 2.18; P = .003) and quantitative (mean SD of Hounsfield units in air: iterative reconstruction = 30.2/filtered back-projection = 51.8; P < .001) image noise. Image noise increased as the radiation dose decreased. Qualitative image noise at levels C1–4 was rated as either “no noise” or as “acceptable noise.” Any shoulder position was at level C5 and caused more artifacts at lower levels. When we analyzed all spinal levels, scores for morphologic characteristics revealed no significant differences between 105 and 355 mAs (P = .555), but they were worse in scans at 75 mAs (P = .025). CONCLUSIONS: Clinically acceptable image quality of cervical spine CTs for evaluation of bony structures of cadaveric specimens with different body habitus can be achieved with a reference mAs of 105 at 120 kVp with iterative reconstruction. Pull-down of shoulders during acquisition could improve image quality but may not be feasible in trauma patients with unknown injuries.

To investigate if there is an association between atherosclerosis and depression by using as imaging biomarker the carotid intima media thickness (cIMT), a surrogate marker for atherosclerosis. PubMed/Medline, Embase and Cochrane databases were comprehensively searched to identify studies investigating the association between cIMT and depression. The results were pooled using a random-effects statistical model, appropriate for the expected high heterogeneity. Sensitivity and subgroup analyses were conducted where data was available. Overall, 22 and 13 studies met inclusion criteria for the qualitative and the quantitative synthesis, respectively, with a total of 4466 patients and 21,635 control participants. Results showed that cIMT is significantly higher in the depression, compared to the control groups with an overall mean difference of 0.07 mm (95% CI 0.04-0.10, p < 0.01). Subgroup analysis showed that diabetes could present as a confounding factor in patients with depression and an increased cIMT. This study confirms a significantly increased cIMT in patients with depression, compared with controls and suggests a possible bidirectional link between atherosclerosis and depression. An early screening of cardiovascular disease in individuals suffering with depression should be considered.

Purpose: Accurate detection of cerebral microbleeds (CMBs) on susceptibility-weighted (SWI) magnetic resonance imaging (MRI) is crucial for the characterization of many neurological diseases. Low-field MRI offers greater access at lower costs and lower infrastructural requirements, but also reduced susceptibility artifacts. We therefore evaluated the diagnostic performance for the detection of CMBs of a whole-body low-field MRI in a prospective cohort of suspected stroke patients compared to an established 1.5 T MRI. Methods: A prospective scanner comparison was performed including 27 patients, of whom 3 patients were excluded because the time interval was >1 h between acquisition of the 1.5 T and 0.55 T MRI. All SWI sequences were assessed for the presence, number, and localization of CMBs by two neuroradiologists and additionally underwent a Likert rating with respect to image impression, resolution, noise, contrast, and diagnostic quality. Results: A total of 24 patients with a mean age of 74 years were included (11 female). Both readers detected the same number and localization of microbleeds in all 24 datasets (sensitivity and specificity 100%; interreader reliability ϰ = 1), with CMBs only being observed in 12 patients. Likert ratings of the sequences at both field strengths regarding overall image quality and diagnostic quality did not reveal significant differences between the 0.55 T and 1.5 T sequences (p = 0.942; p = 0.672). For resolution and contrast, the 0.55 T sequences were even significantly superior (p < 0.0001; p < 0.0003), whereas the 1.5 T sequences were significantly superior (p < 0.0001) regarding noise. Conclusion: Low-field MRI at 0.55 T may have similar accuracy as 1.5 T scanners for the detection of microbleeds and thus may have great potential as a resource-efficient alternative in the near future.