Multiple sclerosis lesions in motor tracts from brain to cervical cord: spatial distribution and correlation with disability.

Despite important efforts to solve the clinico-radiological paradox, correlation between lesion load and physical disability in patients with multiple sclerosis remains modest. One hypothesis could be that lesion location in corticospinal tracts plays a key role in explaining motor impairment. In this study, we describe the distribution of lesions along the corticospinal tracts from the cortex to the cervical spinal cord in patients with various disease phenotypes and disability status. We also assess the link between lesion load and location within corticospinal tracts, and disability at baseline and 2-year follow-up. We retrospectively included 290 patients (22 clinically isolated syndrome, 198 relapsing remitting, 39 secondary progressive, 31 primary progressive multiple sclerosis) from eight sites. Lesions were segmented on both brain (T2-FLAIR or T2-weighted) and cervical (axial T2- or T2*-weighted) MRI scans. Data were processed using an automated and publicly available pipeline. Brain, brainstem and spinal cord portions of the corticospinal tracts were identified using probabilistic atlases to measure the lesion volume fraction. Lesion frequency maps were produced for each phenotype and disability scores assessed with Expanded Disability Status Scale score and pyramidal functional system score. Results show that lesions were not homogeneously distributed along the corticospinal tracts, with the highest lesion frequency in the corona radiata and between C2 and C4 vertebral levels. The lesion volume fraction in the corticospinal tracts was higher in secondary and primary progressive patients (mean = 3.6 ± 2.7% and 2.9 ± 2.4%), compared to relapsing-remitting patients (1.6 ± 2.1%, both P < 0.0001). Voxel-wise analyses confirmed that lesion frequency was higher in progressive compared to relapsing-remitting patients, with significant bilateral clusters in the spinal cord corticospinal tracts (P < 0.01). The baseline Expanded Disability Status Scale score was associated with lesion volume fraction within the brain (r = 0.31, P < 0.0001), brainstem (r = 0.45, P < 0.0001) and spinal cord (r = 0.57, P < 0.0001) corticospinal tracts. The spinal cord corticospinal tracts lesion volume fraction remained the strongest factor in the multiple linear regression model, independently from cord atrophy. Baseline spinal cord corticospinal tracts lesion volume fraction was also associated with disability progression at 2-year follow-up (P = 0.003). Our results suggest a cumulative effect of lesions within the corticospinal tracts along the brain, brainstem and spinal cord portions to explain physical disability in multiple sclerosis patients, with a predominant impact of intramedullary lesions.

Fast and accurate localization of multiple RF markers for tracking in MRI-guided interventions.

OBJECT: A new method for 3D localization of N fiducial markers from 1D projections is presented and analysed. It applies to semi-active markers and active markers using a single receiver channel. MATERIALS AND METHODS: The novel algorithm computes candidate points using peaks in three optimally selected projections and removes fictitious points by verifying detected peaks in additional projections. Computational complexity was significantly reduced by avoiding cluster analysis, while higher accuracy was achieved by using optimal projections and by applying Gaussian interpolation in peak detection. Computational time, accuracy and robustness were analysed through Monte Carlo simulations and experiments. The method was employed in a prototype MRI guided prostate biopsy system and used in preclinical experiments. RESULTS: The computational time for 6 markers was better than 2 ms, an improvement of up to 100 times, compared to the method by Flask et al. (J Magn Reson Imaging 14(5):617-627, 2001). Experimental maximum localization error was lower than 0.3 mm; standard deviation was 0.06 mm. Targeting error was about 1 mm. Tracking update rate was about 10 Hz. CONCLUSION: The proposed method is particularly suitable in systems requiring any of the following: high frame rate, tracking of three or more markers, data filtering or interleaving.

SARS-CoV2 Infection and Comorbidity in Inmates: A Study of Central Italy.

BACKGROUND AND OBJECTIVE: The presence of multiple chronic diseases is associated with an increase in mortality when related to COVID-19 infection. THE AIMS OF OUR STUDY WERE: (i) to evaluate the association between the severity of the COVID-19 disease, defined as symptomatic hospitalized in prison or symptomatic hospitalized out of prison, and the presence of one or more comorbidities in two prisons in central Italy: L'Aquila and Sulmona; (ii) to describe the profiles of inmates using multiple correspondence analysis (MCA). METHODS: A database was created including age, gender and clinical variables. The database containing anonymized data was password-protected. The Kruskal-Wallis test was used to evaluate a possible association between diseases and the severity of COVID-19 stratified by age groups. We used MCA to describe a possible characteristic profile of inmates. RESULTS: Our results show that in the 25-50-year-old age group (COVID-19-negative) in the L'Aquila prison, 19/62 (30.65%) were without comorbidity, 17/62 (27.42%) had 1-2 comorbidities and only 3.23% had >2 diseases. It is interesting to note that in the elderly group, the frequency of 1-2 or >2 pathologies was higher than in the younger group, and only 3/51 (5.88%) inmates did not have comorbidities and were COVID-19 negative (p = 0.008). The MCA identified the following profiles: the prison of L'Aquila showed a group of women over 60 with diabetes, cardiovascular and orthopedic problems, and hospitalized for COVID-19; the Sulmona prison presented a group of males over 60 with diabetes, cardiovascular, respiratory, urological, gastrointestinal and orthopedic problems, and hospitalized or symptomatic due to COVID-19. CONCLUSIONS: our study has demonstrated and confirmed that advanced age and the presence of concomitant pathologies have played a significant role in the severity of the disease: symptomatic hospitalized in the prison; symptomatic hospitalized out of the prison.

The Burden of Modifiable Cardiovascular Risk Factors in a Population of Central Italy: A Pilot Study.

BACKGROUND: By the mid-20th century, cardiovascular disease (CVD) had become an important cause of mortality and morbidity in developed countries. The aim was to set up a pilot study to screen citizens aged 45-59 in order to identify modifiable risk factors (RFs). METHODS: Our study was conducted from February 2019 to February 2020 on citizens of a population of central Italy, aged 45-59, contacted by letter. The variables evaluated were lipid profile, glycemia, anthropometric parameters, lifestyle and utility of screening. RESULTS: It is important to underline that from the comparison with Italian national data, our results showed that blood pressure and lipid profile had better values. On the contrary, there were some alarm bells: a high percentage (57%) of smokers (63.9 in men and 37.1 in women), a sedentary lifestyle (24.5%), and a significantly higher waist circumference than the reference cut-offs for both men and women. The organization of the screening was considered excellent by 56.3% of women and 48.4% of men, and good by 37.5% of women and 46.5% of men. CONCLUSIONS: Our study provides a picture to stakeholders of the state of the health of citizens in the area under study, in the immediate pre-pandemic period; however, it is important to underline that their state of health may be modified after the pandemic period. Furthermore, cardiovascular (CV) screening was perceived by the citizens to be important for health care.

A Clinically-Compatible Workflow for Computer-Aided Assessment of Brain Disease Activity in Multiple Sclerosis Patients.

Over the last 10 years, the number of approved disease modifying drugs acting on the focal inflammatory process in Multiple Sclerosis (MS) has increased from 3 to 10. This wide choice offers the opportunity of a personalized medicine with the objective of no clinical and radiological activity for each patient. This new paradigm requires the optimization of the detection of new FLAIR lesions on longitudinal MRI. In this paper, we describe a complete workflow-that we developed, implemented, deployed, and evaluated-to facilitate the monitoring of new FLAIR lesions on longitudinal MRI of MS patients. This workflow has been designed to be usable by both hospital and private neurologists and radiologists in France. It consists of three main components: (i) a software component that allows for automated and secured anonymization and transfer of MRI data from the clinical Picture Archive and Communication System (PACS) to a processing server (and vice-versa); (ii) a fully automated segmentation core that enables detection of focal longitudinal changes in patients from T1-weighted, T2-weighted and FLAIR brain MRI scans, and (iii) a dedicated web viewer that provides an intuitive visualization of new lesions to radiologists and neurologists. We first present these different components. Then, we evaluate the workflow on 54 pairs of longitudinal MRI scans that were analyzed by 3 experts (1 neuroradiologist, 1 radiologist, and 1 neurologist) with and without the proposed workflow. We show that our workflow provided a valuable aid to clinicians in detecting new MS lesions both in terms of accuracy (mean number of detected lesions per patient and per expert 1.8 without the workflow vs. 2.3 with the workflow, p = 5.10-4) and of time dedicated by the experts (mean time difference 2'45″, p = 10-4). This increase in the number of detected lesions has implications in the classification of MS patients as stable or active, even for the most experienced neuroradiologist (mean sensitivity was 0.74 without the workflow and 0.90 with the workflow, p-value for no difference = 0.003). It therefore has potential consequences on the therapeutic management of MS patients.

Unsupervised Domain Adaptation With Optimal Transport in Multi-Site Segmentation of Multiple Sclerosis Lesions From MRI Data.

Automatic segmentation of Multiple Sclerosis (MS) lesions from Magnetic Resonance Imaging (MRI) images is essential for clinical assessment and treatment planning of MS. Recent years have seen an increasing use of Convolutional Neural Networks (CNNs) for this task. Although these methods provide accurate segmentation, their applicability in clinical settings remains limited due to a reproducibility issue across different image domains. MS images can have highly variable characteristics across patients, MRI scanners and imaging protocols; retraining a supervised model with data from each new domain is not a feasible solution because it requires manual annotation from expert radiologists. In this work, we explore an unsupervised solution to the problem of domain shift. We present a framework, Seg-JDOT, which adapts a deep model so that samples from a source domain and samples from a target domain sharing similar representations will be similarly segmented. We evaluated the framework on a multi-site dataset, MICCAI 2016, and showed that the adaptation toward a target site can bring remarkable improvements in a model performance over standard training.

Point-Cloud Method for Automated 3D Coronary Tree Reconstruction From Multiple Non-Simultaneous Angiographic Projections.

X-ray angiography is the most commonly used imaging modality for the detection of coronary stenoses due to its high spatial and temporal resolution of lumen contour and its utility to guide coronary interventions in real time. However, the high inter- and intra-observer variability in interpreting the geometry of 3D vascular structure based on multiple 2D image projections is a limitation in the accurate determination of lesion severity. This could be addressed by the 3D reconstruction of the coronary arterial (CA) tree. The automated reconstruction of 3D CA tree from 2D projections is challenging due to the existence of several imaging artifacts, such as vessel overlap, foreshortening, and most importantly respiratory and cardiac motion. Along with these artifacts, the acquisition geometry introduces the possibility of generating false vessel segments in the reconstruction. Our approach aims to reduce the motion artifacts in angiographic projections by developing a new method for rigid and non-rigid motion correction. A novel point-cloud based approach is subsequently introduced for reconstruction of 3D vessel centerlines by iteratively minimizing the reconstruction error. The performance of the proposed 3D reconstruction is evaluated using angiographic projections from 45 patients, producing average reprojection errors of 0.092 ±0.055 mm and 0.910 ±0.352 mm for 3D centerlines reconstruction, when co-registered with the parent vessels on projection planes that were/were not used to derive the 3D reconstruction, respectively. A comparison of the reconstructed 3D lumen surface with optical coherence tomography (OCT) measurements has been performed, showing no statistically significant difference in the luminal cross-sections reconstructed with our method, compared to OCT.

T2 mapping MRI technique quantifies carotid plaque lipid, and its depletion after statin initiation, following acute myocardial infarction.

BACKGROUND & AIMS: A recently-validated, highly-sensitive T2 mapping magnetic resonance (MRI) technique accurately quantifies carotid plaque lipid. The aims of this study were to determine: (i) the extent of carotid plaque lipid in patients with acute coronary syndromes (ACS); (ii) the effects of initiation of high-intensity statin on plaque lipid content and (iii) whether plaque lipid content is related to standard or 'functional' blood lipid measurements. METHODS: Statin naïve subjects presenting with ACS underwent carotid artery MRI at 3 T scanner to quantify plaque lipid. Patients were subsequently commenced on high dose statin as part of clinical care and underwent a second MRI after three months. Plaque composition was measured using objective semi-automated techniques. RESULTS: 23 out of 24 patients had measurable lipid. Three months after statin initiation there was a significant reduction in carotid lipid percentage [from 10.3% (7.2-14.2) to 7.4% (5.4-10.0), p = 0.002] and a significant increase in fibrous percentage [from 83.3% ±â€¯6.6-85.5% ±â€¯4.8, p = 0.039]. None of the studied functional blood biomarkers were related to either baseline carotid plaque lipid content or its propensity to change with statin treatment. CONCLUSIONS: T2-mapping demonstrated depleted carotid plaque lipid following the initiation of high-intensity statin treatment. Standard or 'functional' blood biomarkers were dissociated from plaque lipid content or changes with treatment. These findings further reinforce the importance of disease characterisation over risk factor assessment. Subject to clinical trial findings, quantification of plaque lipid may provide the basis for an approach to identify patients suitable for intensive lipid reduction regimes.

3D reconstruction of coronary arteries from 2D angiographic projections using non-uniform rational basis splines (NURBS) for accurate modelling of coronary stenoses.

OBJECTIVE: Assessment of coronary stenosis severity is crucial in clinical practice. This study proposes a novel method to generate 3D models of stenotic coronary arteries, directly from 2D coronary images, and suitable for immediate assessment of the stenosis severity. METHODS: From multiple 2D X-ray coronary arteriogram projections, 2D vessels were extracted. A 3D centreline was reconstructed as intersection of surfaces from corresponding branches. Next, 3D luminal contours were generated in a two-step process: first, a Non-Uniform Rational B-Spline (NURBS) circular contour was designed and, second, its control points were adjusted to interpolate computed 3D boundary points. Finally, a 3D surface was generated as an interpolation across the control points of the contours and used in the analysis of the severity of a lesion. To evaluate the method, we compared 3D reconstructed lesions with Optical Coherence Tomography (OCT), an invasive imaging modality that enables high-resolution endoluminal visualization of lesion anatomy. RESULTS: Validation was performed on routine clinical data. Analysis of paired cross-sectional area discrepancies indicated that the proposed method more closely represented OCT contours than conventional approaches in luminal surface reconstruction, with overall root-mean-square errors ranging from 0.213mm2 to 1.013mm2, and maximum error of 1.837mm2. Comparison of volume reduction due to a lesion with corresponding FFR measurement suggests that the method may help in estimating the physiological significance of a lesion. CONCLUSION: The algorithm accurately reconstructed 3D models of lesioned arteries and enabled quantitative assessment of stenoses. The proposed method has the potential to allow immediate analysis of the stenoses in clinical practice, thereby providing incremental diagnostic and prognostic information to guide treatments in real time and without the need for invasive techniques.

Quantification of carotid plaque lipid content with magnetic resonance T2 mapping in patients undergoing carotid endarterectomy.

BACKGROUND AND PURPOSE: Techniques to stratify subgroups of patients with asymptomatic carotid artery disease are urgently needed to guide decisions on optimal treatment. Reliance on estimates of % luminal stenosis has not been effective, perhaps because that approach entirely disregards potentially important information on the pathological process in the wall of the artery. METHODS: Since plaque lipid is a key determinant of plaque behaviour we used a newly validated, high-sensitivity T2-mapping MR technique for a systematic survey of the quantity and distribution of plaque lipid in patients undergoing endarterectomy. Lipid percentage was quantified in 50 carotid endarterectomy patients. Lipid distribution was tested, using two imaging indices (contribution of the largest lipid deposit towards total lipid (LLD %) and a newly-developed LAI 'lipid aggregation index'). RESULTS: The bifurcation contained maximal lipid volume. Lipid percentage was higher in symptomatic vs. asymptomatic patients with degree of stenosis (DS ≥ 50%) and in the total cohort (P = 0.013 and P = 0.005, respectively). Both LLD % and LAI was higher in symptomatic patients (P = 0.028 and P = 0.018, respectively), suggesting that for a given plaque lipid volume, coalesced deposits were more likely to be associated with symptomatic events. There was no correlation between plaque volume or lipid content and degree of luminal stenosis measured on ultrasound duplex (r = -0.09, P = 0.53 and r = -0.05, P = 0.75), respectively. However, there was a strong correlation in lipid between left and right carotid arteries (r = 0.5, P <0.0001, respectively). CONCLUSIONS: Plaque lipid content and distribution is associated with symptomatic status of the carotid plaque. Importantly, plaque lipid content was not related to the degree of luminal stenosis assessed by ultrasound. Determination of plaque lipid content may prove useful for stratification of asymptomatic patients, including selection of optimal invasive treatments.

Quantification of Lipid-Rich Core in Carotid Atherosclerosis Using Magnetic Resonance T2 Mapping: Relation to Clinical Presentation.

OBJECTIVES: The aim of this study was to: 1) provide tissue validation of quantitative T2 mapping to measure plaque lipid content; and 2) investigate whether this technique could discern differences in plaque characteristics between symptom-related and non-symptom-related carotid plaques. BACKGROUND: Noninvasive plaque lipid quantification is appealing both for stratification in treatment selection and as a possible predictor of future plaque rupture. However, current cardiovascular magnetic resonance (CMR) methods are insensitive, require a coalesced mass of lipid core, and rely on multicontrast acquisition with contrast media and extensive post-processing. METHODS: Patients scheduled for carotid endarterectomy were recruited for 3-T carotid CMR before surgery. Lipid area was derived from segmented T2 maps and compared directly to plaque lipid defined by histology. RESULTS: Lipid area (%) on T2 mapping and histology showed excellent correlation, both by individual slices (R = 0.85, p < 0.001) and plaque average (R = 0.83, p < 0.001). Lipid area (%) on T2 maps was significantly higher in symptomatic compared with asymptomatic plaques (31.5 ± 3.7% vs. 15.8 ± 3.1%; p = 0.005) despite similar degrees of carotid stenosis and only modest difference in plaque volume (128.0 ± 6.0 mm3 symptomatic vs. 105.6 ± 9.4 mm3 asymptomatic; p = 0.04). Receiver-operating characteristic analysis showed that T2 mapping has a good ability to discriminate between symptomatic and asymptomatic plaques with 67% sensitivity and 91% specificity (area under the curve: 0.79; p = 0.012). CONCLUSIONS: CMR T2 mapping distinguishes different plaque components and accurately quantifies plaque lipid content noninvasively. Compared with asymptomatic plaques, greater lipid content was found in symptomatic plaques despite similar degree of luminal stenosis and only modest difference in plaque volumes. This new technique may find a role in determining optimum treatment (e.g., providing an indication for intensive lipid lowering or by informing decisions of stents vs. surgery).

Urban air pollution monitoring and correlation properties between fixed-site stations.

The rich regional air-monitoring network of the Emilia-Romagna region of Italy has been used to quantify the spatial variability of the main pollutants within urban environments and to analyze the correlations between stations. The spatial variability of the concentrations of the majority of pollutants within the city was very high, making it difficult to differentiate and characterize the urban environments and to apply legal limits with uniform criteria. On the other hand, the correlations between the fixed-site monitoring stations were high enough for their data to be retained generally very appropriately for controlling temporal trends. Starting from the high correlation level, a procedure was proposed and tested to derive pollution levels, using short-term measurements, such as passive samplers and mobile-station data. The importance of long-term statistics in urban air pollution mapping was emphasized. Treatment of missing data in time series and quality assurance were indicated as possible fields for applications for the correlation properties.