Studio dell'emodinamica cerebrale in pazienti affetti da sclerosi multipla: ottimizzazione del protocollo di acquisizione e del processo di quantificazione

Questo lavoro ha avuto lo scopo di caratterizzare l'emodinamica cerebrale in pazienti affetti da sclerosi multipla a partire dalla definizione di un protocollo di acquisizione ottimizzato per questo tipo di indagini per poi proseguire nella quantificazione della perfusione cerebrale e nella sua analisi. é stato quindi definito, testato e validato un protocollo di acquisizione Dynamic Susceptibility Contrast (DSC-MRI), che è entrato a far parte della sequenza di esami standard che viene effettuata nei soggetti affetti da sclerosi multipla. In seguito si è adattato e migliorato un software preesistente per la quantificazione dei parametri emodinamici per il protocollo DSC-MRI. Inoltre si è messo a punto un metodo per l'analisi delle lesioni corticali tra soggetti diversi, confrontandole con l'andamento nelle zone apparentemente normali della materia grigia. é stato quindi possibile individuare una diminuzione significativa del flusso e del volume ematico (CBF e CBV) ed un aumento significativo del tempo medio di transito (MTT)ope

Dynamic Characterization of the Eiffel Tower

Abstract The Eiffel tower is the most visited monument in the world. Millions of visitors have taken millions of pictures of it over the last century but apparently a dynamic picture (that is a dynamic characterization) does not exist or is not publicly available. In this paper we show the amount of information that can be extracted from a few recordings of ambient tremor collected on the tower and on the surrounding subsoil with a single pocket seismometer in a few minutes, during a leisure visit. We also propose a numerical model for the tower, capable to fit the observed data. This is interesting because the mass and stiffness distribution of the tower is unique and does not follow any modern construction rule. The dynamic model of the tower would also be important if Paris were a high seismic hazard town, which is not. According to our model, the tower could withstand peak ground accelerations >100% larger than the values prescribed by current seismic hazard estimates. Regarding the wind, Eiffel could only study its effects from a static planar point of view, while the model allowed us to follow a 3D approach and to assess the expected displacements under different loads. Last, the dynamic model of the tower is also important to better design the future interventions and to monitor the ageing of the structure

The use of the central vein sign in the diagnosis of multiple sclerosis: a systematic review and meta-analysis

Background: The central vein sign (CVS) is a radiological feature proposed as a multiple sclerosis (MS) imaging biomarker able to accurately differentiate MS from other white matter diseases of the central nervous system. In this work, we evaluated the pooled proportion of the CVS in brain MS lesions and to estimate the diagnostic performance of CVS to perform a diagnosis of MS and propose an optimal cut-off value. Methods: A systematic search was performed on publicly available databases (PUBMED/MEDLINE and Web of Science) up to 24 August 2020. Analysis of the proportion of white matter MS lesions with a central vein was performed using bivariate random-effect models. A meta-regression analysis was performed and the impact of using particular sequences (such as 3D echo-planar imaging) and post-processing techniques (such as FLAIR*) was investigated. Pooled sensibility and specificity were estimated using bivariate models and meta-regression was performed to address heterogeneity. Inclusion and publication bias were assessed using asymmetry tests and a funnel plot. A hierarchical summary receiver operating curve (HSROC) was used to estimate the summary accuracy in diagnostic performance. The Youden index was employed to estimate the optimal cut-off value using individual patient data. Results: The pooled proportion of lesions showing a CVS in the MS population was 73%. The use of the CVS showed a remarkable diagnostic performance in MS cases, providing a pooled specificity of 92% and a sensitivity of 95%. The optimal cut-off value obtained from the individual patient data pooled together was 40% with excellent accuracy calculated by the area under the ROC (0.946). The 3D-EPI sequences showed both a higher pooled proportion compared to other sequences and explained heterogeneity in the meta-regression analysis of diagnostic performances. The 1.5 Tesla (T) scanners showed a lower (58%) proportion of MS lesions with a CVS compared to both 3T (74%) and 7T (82%). Conclusions: The meta-analysis we have performed shows that the use of the CVS in differentiating MS from other mimicking diseases is encouraged; moreover, the use of dedicated sequences such as 3D-EPI and the high MRI field is beneficial

Refining Rates of Active Crustal Deformation in the Upper Plate of Subduction Zones, Implied by Geological and Geodetic Data: The E-Dipping West Crati Fault, Southern Italy

We investigate crustal deformation within the upper plate of the Ionian Subduction Zone (ISZ) at different time scales by (i) refining geodetic rates of crustal extension from continuous Global Navigation Satellite System (GNSS) measurements and (ii) mapping sequence of Late Quaternary raised marine terraces tectonically deformed by the West Crati normal fault, in northern Calabria. This region experienced damaging earthquakes in 1184 (M 6.75) and 1854 (M 6.3), possibly on the E-dipping West Crati fault (WCF) which, however, is not unanimously considered to be a seismogenic source. We report geodetic measurements of extension and strain rates across the strike of the E dipping WCF and throughout the northern Calabria obtained by using velocities from 18 permanent GNSS stations with a series length longer than 4.5 years. These results suggest that crustal extension may be seismically accommodated in this region by a few normal faults. Furthermore, by applying a synchronous correlation approach, we refine the chronology of understudied tectonically deformed palaeoshorelines mapped on the footwall and along the strike of the WCF, facilitating calculation of the associated fault-controlled uplift rates. Raised Late Quaternary palaeoshorelines are preserved on the footwall of the WCF indicating that “regional” uplift, likely related to the deformation associated either with the subduction or mantle upwelling processes, is affected by local footwall uplift. We show that GIS-based elevations of Late Quaternary palaeoshorelines, as well as temporally constant uplift rates, vary along the strike of the WCF, implying normal faulting activity through time. This suggests that (i) the fault slip rate governing seismic hazard has also been constant over the Late Quaternary, over multiple earthquake cycles, and (ii) our geodetically derived fault throw rate for the WCF is likely a more than reasonable value to be used over longer time scales for an improved seismic hazard assessment. Overall, we emphasize the importance of mapping crustal deformation within the upper plate above subduction zones to avoid unreliable interpretations relating to the mechanism controlling regional uplift

A wide field-of-view, modular, high-density diffuse optical tomography system for minimally constrained three-dimensional functional neuroimaging

The ability to produce high-quality images of human brain function in any environment and during unconstrained movement of the subject has long been a goal of neuroimaging research. Diffuse optical tomography, which uses the intensity of back-scattered near-infrared light from multiple source-detector pairs to image changes in haemoglobin concentrations in the brain, is uniquely placed to achieve this goal. Here, we describe a new generation of modular, fibre-less, high-density diffuse optical tomography technology that provides exceptional sensitivity, a large dynamic range, a field-of-view sufficient to cover approximately one-third of the adult scalp, and also incorporates dedicated motion sensing into each module. Using in-vivo measures, we demonstrate a noise-equivalent power of 318 fW, and an effective dynamic range of 142 dB. We describe the application of this system to a novel somatomotor neuroimaging paradigm that involves subjects walking and texting on a smartphone. Our results demonstrate that wearable high-density diffuse optical tomography permits three-dimensional imaging of the human brain function during overt movement of the subject; images of somatomotor cortical activation can be obtained while subjects move in a relatively unconstrained manner, and these images are in good agreement with those obtained while the subjects remain stationary. The scalable nature of the technology we described here paves the way for the routine acquisition of high-quality, three-dimensional, whole-cortex diffuse optical tomography images of cerebral haemodynamics, both inside and outside of the laboratory environment, which has profound implications for neuroscience

Case Report: A Peculiar Case of Inflammatory Colitis After SARS-CoV-2 Infection

open14noWe report a case of inflammatory colitis after SARS-CoV-2 infection in a patient with no additional co-morbidity who died within three weeks of hospitalization. As it is becoming increasingly clear that SARS-CoV-2 infection can cause immunological alterations, we investigated the expression of the inhibitory checkpoint PD-1 and its ligand PD-L1 to explore the potential role of this axis in the break of self-tolerance. The presence of the SARS-CoV-2 virus in colon tissue was demonstrated by qRT-PCR and immunohistochemical localization of the nucleocapsid protein. Expression of lymphocyte markers, PD-1, and PD-L1 in colon tissue was investigated by IHC. SARSCoV- 2-immunoreactive cells were detected both in the ulcerated and non-ulcerated mucosal areas. Compared to healthy tissue, where PD-1 is weakly expressed and PD-L1 is absent, PD-1 and PD-L1 expression appears in the inflamed mucosal tissue, as expected, but was mainly confined to non-ulcerative areas. At the same time, these markers were virtually undetectable in areas of mucosal ulceration. Our data show an alteration of the PD-1/PD-L1 axis and suggest a link between SARS-CoV-2 infection and an aberrant autoinflammatory response due to concomitant breakdown of the PD-1/ PD-L1 interaction leading to early death of the patient.openRutigliani, Mariangela; Bozzo, Matteo; Barberis, Andrea; Greppi, Marco; Anelli, Emanuela; Castellaro, Luca; Bonsignore, Alessandro; Azzinnaro, Antonio; Pesce, Silvia; Filauro, Marco; Rollandi, Gian Andrea; Castagnola, Patrizio; Candiani, Simona; Marcenaro, EmanuelaRutigliani, Mariangela; Bozzo, Matteo; Barberis, Andrea; Greppi, Marco; Anelli, Emanuela; Castellaro, Luca; Bonsignore, Alessandro; Azzinnaro, Antonio; Pesce, Silvia; Filauro, Marco; Rollandi, Gian Andrea; Castagnola, Patrizio; Candiani, Simona; Marcenaro, Emanuel

The prognostic value of white-matter selective double inversion recovery mri sequence in multiple sclerosis: an exploratory study

Using a white-matter selective double inversion recovery sequence (WM-DIR) that suppresses both grey matter (GM) and cerebrospinal fluid (CSF) signals, some white matter (WM) lesions appear surrounded by a dark rim. These dark rim lesions (DRLs) seem to be specific for multiple sclerosis (MS). They could be of great usefulness in clinical practice, proving to increase the MRI diagnostic criteria specificity. The aims of this study are the identification of DRLs on 1.5 T MRI, the exploration of the relationship between DRLs and disease course, the characterization of DRLs with respect to perilesional normal-appearing WM using magnetization transfer imaging, and the investigation of possible differences in the underlying tissue properties by assessing WM-DIR images obtained at 3.0 T MRI. DRLs are frequent in primary progressive MS (PPMS) patients. Amongst relapsing-remitting MS (RRMS) patients, DRLs are associated with a high risk of the disease worsening and secondary progressive MS (SPMS) conversion after 15 years. The mean magnetization transfer ratio (MTR) of DRLs is significantly different from the lesion without the dark rim, suggesting that DRLs correspond to more destructive lesions

CSF TNF and osteopontin levels correlate with the response to dimethyl fumarate in early multiple sclerosis

Background: Disease activity in the first years after a diagnosis of relapsing-remitting multiple sclerosis (RRMS) is a negative prognostic factor for long-term disability. Markers of both clinical and radiological responses to disease-modifying therapies (DMTs) are advocated. Objective: The objective of this study is to estimate the value of cerebrospinal fluid (CSF) inflammatory markers at the time of diagnosis in predicting the disease activity in treatment-naïve multiple sclerosis (MS) patients exposed to dimethyl fumarate (DMF). Methods: In total, 48 RRMS patients (31 females/17 males) treated with DMF after the diagnosis were included in this 2-year longitudinal study. All patients underwent a CSF examination, regular clinical and 3T magnetic resonance imaging (MRI) scans that included the assessment of white matter (WM) lesions, cortical lesions (CLs) and global cortical thickness. CSF levels of 10 pro-inflammatory markers - CXCL13 [chemokine (C-X-C motif) ligand 13 or B lymphocyte chemoattractant], CXCL12 (stromal cell-derived factor or C-X-C motif chemokine 12), tumour necrosis factor (TNF), APRIL (a proliferation-inducing ligand, or tumour necrosis factor ligand superfamily member 13), LIGHT (tumour necrosis factor ligand superfamily member 14 or tumour necrosis factor superfamily member 14), interferon (IFN) gamma, interleukin 12 (IL-12), osteopontin, sCD163 [soluble-CD163 (cluster of differentiation 163)] and Chitinase3-like1 - were assessed using immune-assay multiplex techniques. The combined three-domain status of 'no evidence of disease activity' (NEDA-3) was defined by no relapses, no disability worsening and no MRI activity, including CLs. Results: Twenty patients (42%) reached the NEDA-3 status; patients with disease activity showed higher CSF TNF (p = 0.009), osteopontin (p = 0.005), CXCL12 (p = 0.037), CXCL13 (p = 0.040) and IFN gamma levels (p = 0.019) compared with NEDA-3 patients. After applying a random forest approach, TNF and osteopontin revealed the most important variables associated with the NEDA-3 status. Six molecules that emerged at the random forest approach were added in a multivariate regression model with demographic, clinical and MRI measures of WM and grey matter damage as independent variables. TNF levels confirmed to be associated with the absence of disease activity: odds ratio (OR) = 0.25, CI% = 0.04-0.77. Conclusion: CSF inflammatory markers may provide prognostic information in predicting disease activity in the first years after DMF initiation. CSF TNF levels are a possible candidate in predicting treatment response, in addition to clinical, demographic and MRI variables

Iron homeostasis, complement, and coagulation cascade as CSF signature of cortical lesions in early multiple sclerosis

OBJECTIVE: Intrathecal inflammation, compartmentalized in cerebrospinal fluid (CSF) and in meningeal infiltrates, has fundamental role in inflammation, demyelination, and neuronal injury in cerebral cortex in multiple sclerosis (MS). Since the exact link between intrathecal inflammation and mechanisms of cortical pathology remains unknown, we aimed to investigate a detailed proteomic CSF profiling which is able to reflect cortical damage in early MS. METHODS: We combined new proteomic method, TRIDENT, CSF analysis, and advanced 3T magnetic resonance imaging (MRI), in 64 MS patients at the time of diagnosis and 26 controls with other neurological disorders. MS patients were stratified according to cortical lesion (CL) load. RESULTS: We identified 227 proteins differently expressed between the patients with high and low CL load. These were mainly related to complement and coagulation cascade as well as to iron homeostasis pathway (30 and 6% of all identified proteins, respectively). Accordingly, in the CSF of MS patients with high CL load at diagnosis, significantly higher levels of sCD163 (P < 0.0001), free hemoglobin (Hb) (P < 0.05), haptoglobin (P < 0.0001), and fibrinogen (P < 0.01) were detected. By contrast, CSF levels of sCD14 were significantly (P < 0.05) higher in MS patients with low CL load. Furthermore, CSF levels of sCD163 positively correlated (P < 0.01) with CSF levels of neurofilament, fibrinogen, and B cell-related molecules, such as CXCL13, CXCL12, IL10, and BAFF. INTERPRETATION: Intrathecal dysregulation of iron homeostasis and coagulation pathway as well as B-cell and monocyte activity are strictly correlated with cortical damage at early disease stages