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Background and objective: This article uses three different probabilistic convolutional architectures applied to ultrasound image analysis for grading Fatty Liver Content (FLC) in Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) patients. Steatosis is a new silent epidemic and its accurate measurement is an impelling clinical need, not only for hepatologists, but also for experts in metabolic and cardiovascular diseases. This paper aims to provide a robust comparison between different uncertainty quantification strategies to identify advantages and drawbacks in a real clinical setting. Methods: We used a classical Convolutional Neural Network, a Monte Carlo Dropout, and a Bayesian Convolutional Neural Network with the goal of not only comparing the goodness of the predictions, but also to have access to an evaluation of the uncertainty associated with the outputs. Results: We found that even if the prediction based on a single ultrasound view is reliable (relative RMSE [5.93%-12.04%]), networks based on two ultrasound views outperform them (relative RMSE [5.35%-5.87%]). In addition, the results show that the introduction of a “not confident” category contributes to increase the percentage of correctly predicted cases and to decrease the percentage of mispredicted cases, especially for semi-intrusive methods. Conclusions: The possibility of having access to information about the confidence with which the network produces its outputs is a great advantage, both from the point of view of physicians who want to use neural networks as computer-aided diagnosis, and for developers who want to limit overfitting and obtain information about dataset problems in terms of out-of-distribution detection.

Background: The study of medium and small-size arteries might be useful in the characterization of vascular adaptation, remodeling and wall ultrastructure modifications occurring with aging and in the presence of cardiovascular risk factors. However, to date, these districts have not been extensively explored non-invasively, due to limited spatial resolution power of standard ultrasound (US) machines. Methods: High-frequency US examination by Vevo MD (FUJIFILM, VisualSonics, Toronto, Canada) was performed in 5 healthy volunteers (2 men, mean age: 26.4±3.3 years). Images were obtained at the carotid, brachial and radial artery level, using the 48 MHz (for carotid and brachial) and 70 MHz (for radial) US probes. Mean diameter, relative distension and intima-media thickness (IMT) were obtained using edge detection and contour tracking techniques. Texture analysis was performed on carotid, brachial and radial US images. Contrast, correlation, energy and homogeneity were evaluated from the grey-level co-occurrence matrix calculated on the pixels belonging to the IMT. Results: IMT and relative distension, as well as texture analysis, could be successfully assessed in all the arterial districts evaluated. Correspondent results are reported in Table 1. Conclusions: The multidistrict assessment of wall ultrastructure and mechanics in medium- and small-size arteries is highly feasible in healthy individuals. This kind of analysis might provide novel insight on the development of vascular alterations in previously neglected arterial districts, as well as their clinical significance. Carotid artery Brachial Artery Radial Artery Mean Diameter (mm) 5.9±0.74 3.22±0.65 2.03±0.24 IMT (mm) 0.42±0.05 0.14±0.02 0.12±0.01 Relative distension (%) 10.6±1.8 4±1.7 7.4±2.5 Contrast 0.05±0.008 0.04±0.01 0.05±0.01 Correlation 0.99±0.001 0.99±0.003 0.99±0.001 Energy 0.19±0.05 0.33±0.17 0.23±0.07 Homogeneity 0.97±0.004 0.97±0.005 0.97±0.005

Objective: Cardiovascular complications, mainly caused by an accelerated atherosclerosis, are one of the leading causes of death and disability in patients with systemic autoimmune diseases. Endothelial dysfunction is considered the earliest and reversible step of atherogenesis. Aim of the present study is to investigate endothelial function (EF) in patients with systemic lupus erythematosus (SLE), undifferentiated connective tissue diseases (UCTD) and correlate the results with clinical and laboratory variables. Methods: EF was assessed on the peripheral microcirculation by the perfused forearm technique that can estimate both endothelium- dependent and endothelium- independent vasodilatation. The same evaluation has been repeated in two patients after the administration of 20 mg of 6-metilprednisolone. Results: Twenty-three female patients with SLE or UCTD, with a follow up of at least 1 year have been studied and compared with 8 healthy controls matched for epidemiological variables and traditional risk factors for cardiovascular disease. A significant reduction both in endothelium dependent than endothelium independent vasodilatation was observed in both patients groups compared with controls. In addition, UCTD patients demonstrated a significant reduction in the nitric oxide pathway compared with controls and SLE patients. Finally, steroid administration induced an improvement of vascular reactivity. Conclusions: Despite the well documented side effects of chronic corticosteroid therapy, our data might suggest a role for antinflammatory and immunosuppressive therapy in the prevention of premature atherosclerosis in patients with systemic autoimmune diseases.

Aim: To evaluate vascular function and structure in subjects with mild cognitive impairment (MCI). Methods: 58 MCI and 22 controls (age 74±5vs75±4years, men 45vs59% p=ns) were recruited. Endothelial function in the brachial artery (BA) was studied by flow-mediated dilation (FMD) and response to glyceryl trinitrate, (GTN), while large artery stiffness was measured as carotid-femoral pulse wave velocity (PWV). Results: MCI and controls had a similar prevalence of established CV disease (14vs13%,p=ns) and traditional CV risk factors (hypertension 50vs54%, diabetes 13vs5%, dyslipidemia 28vs48%, smoking 4vs9%, p=ns for all). MCI showed higher blood pressure (BP) values than controls (pulse pressure 70±16vs62±12mmHg, mean BP 97±9vs91±8 mmHg, p

In recent years, great attention has been placed on local carotid elasticity. Carotid pulse wave velocity (cPWV) can be considered a surrogate marker for carotid stiffness evaluation. Aim of this study was to compare four different techniques for carotid stiffness assessment. Ten young healthy subjects (34.7±6.9 years, 40% males, BMI 21.6±2.2 kg/m2) were enrolled. For each volunteer, four different carotid stiffness measurements were obtained: i) ultrasound carotid stiffness (CS) values were estimated from US diameter and tonometric pulse pressure measurements combined by Bramwhell-Hill equation ii) cPWVloop values were calculated from US simultaneous measurements of diameter and flow velocity using the lnD-V loop slope iii) cPWVMRI values were obtained from velocity-encoded MRI images using QA method iv) cPWVAcc values were achieved by means of a new accelerometric system which consists in two percutaneous accelerometers placed 2.4 cm apart on the subject’s neck; PWV is calculated dividing the distance between the sensors for the time delay between the signals. Table 1 shows the results of the comparisons between CS (5.39±0.76 m/s), cPWVMRI (5.81±0.77 m/s), cPWVloop (4.18±0.96 m/s) and cPWVAcc (5.12±1.25 m/s) values. All the comparisons exhibit satisfying correlations. The only non-significative bias is shown by the comparison between CS values and cPWVAcc ones while the comparison between CS measurements and cPWVloop evaluations provides the lowest standard deviation of the difference. In conclusion, this preliminary study suggests that attention should be placed when using different methods of carotid stiffness assessment, especially in case of comparison between values obtained with different methods. Mean Difference ± SD of difference (m/s) R2 CS vs cPWVloop 1.29±0.42 0.81 CS vs cPWVMRI −0.51±0.54 0.55 CS vs cPWVAcc 0.27±0.75 0.67 cPWVloop vs cPWVMRI −1.77±0.56 0.71 cPWVloop vs cPWVAcc −1.16±0.57 0.66 cPWVMRI vs cPWVAcc −0.92±0.99 0.39

Background: Systemic Lupus Erithematosus (SLE) is associated with increased cardiovascular risk and early vascular aging. The aim of the study was to evaluate aortic and carotid stiffness, central blood pressure (BP) and wave reflection in women with SLE, in order to identify whether different vascular districts are similarly influenced by disease duration, activity and organ damage. Methods: Medical and pharmacological history were collected. Disease activity and organ damage were evaluated by ECLAM e SLICC/ACR-DI scores, respectively. Pulse Wave Velocity (PWV) and Augmentation Index (AI) were acquired by applanation tonometry, whereas carotid intima-media thickness (IMT) and stiffness were obtained by an automated image analysis system. Results: 46 SLE women were enrolled (age 41±10years, BP 116±16/76±9 mmHg). Mean disease duration was 17±9years, ECLAM 0,9±1, SLICC 0,9±1,5. PWV(7,4±1,5 m/s) was related to age (r=0.52, p

Accumulating evidence suggests that dental treatment is associated with systemic inflammation. We aimed to preliminarily study the impact of third molar removal on biomarkers of inflammation and oxidative stress. Ten consecutive subjects underwent the removal of third molars under local anaesthesia and provided blood samples before and 1, 7 and 60 days following therapy assessed for high-sensitivity serum concentrations of C-Reactive Protein (CRP), fibrinogen, white cell counts and a number of measures of oxidative stress (MDA, LOOH and FRAP). One week inflammatory response ensued with acute increases after 24 h of CRP (P

The continuous monitoring of arterial stiffness during pharmacological and dynamic stress is an intriguing and partially unexplored topic. In this work we present a new method for the continuous assessment of the aortic-to-carotid pulse transit time (PTT), which is inversely proportional to the pulse wave velocity (PWV), the gold-standard for arterial stiffness evaluation. The measurement is based on two cutaneous MEMS accelerometers: the first accelerometer is placed on the chest in mid-sternal precordial region and detects the heart vibrations; the second accelerometer is positioned on the neck and detects the carotid vibrations. The time corresponding to the closure of the aortic valve is found automatically on both the accelerometer signals and the PTT is computed as the difference between the two times. We tested our system by monitoring the pulse pressure transit time variation of 8 healthy volunteers during sublingual GTN administration (25μg). The mean maximal percent variation of the PTT after GTN was 3.84±1.69% (range 1.86–6.48%), that is in accordance with the literature where Wilkinson et al. (2002) showed a reduction of the PWV after GTN administration. In conclusion, we propose a new method which is able to the evaluate the variation of the true central PTT during pharmacological and dynamic stress. With this approach, only the proximal tract of the arterial bed (aorta-to-carotid) is considered: muscular arteries, whose contribution in the evaluation of arterial elasticity is usually poor, are excluded.

Brachial artery flow-mediated dilation (FMD) is the most widely used technique for assessing endothelial function in humans. FMD is reduced in the presence of cardiovascular risk factors and diseases and it is an independent predictor of events. However, its major limitation is the relatively low reproducibility. One of the main challenge is to maintain a stable scan plane during examinations, especially when the forearm cuff is inflated/deflated. The aim of this study was to evaluate the FMD reproducibility when resting diameter is calculated as the mean value measured from 8th to 9th minute after reactive hyperemia, when the vasodilation is concluded (BAS_POST), and to compare the results with those obtained with a standard assessment of resting diameter over 1minute before cuff inflation (BAS_PRE). Thirty healthy subjects (age 25–45 years) underwent two FMD examinations 30minutes apart. FMD to 5minutes forearm ischemia was assessed by one trained operator using a clamp to hold the ultrasound probe in the same position and calculated as maximum percentage increase in diameter with respect to BAS_PRE and BAS_POST, by a real-time automatic edge-detection system (FMD Studio, Institute of Clinical Physiology, Pisa, Italy). FMD% variability was assessed as intra-session coefficients of variation (CV). Diameter was 3.56+0.66mm in BAS_PRE and 3.57+0.66mm in the BAS_POST. FMD% was 7.4+3.8% with BAS_PRE and 7.1+3.7% with BAS_POST. CV of FMD% was 15.61+10.9% in BAS PRE and 9.22+5.93% with BAS_POST calculation. These results suggest that FMD% calculated with BAS_POST can ensure a more reproducible measure of conduit artery endothelial function.

Objectives: To evaluate the effect of recombinant human TSH (rhTSH) on endothelial function, aortic and carotid stiffness, and wave reflection in a population living in the Chernobyl area at the time of 1986 blast, treated with thyroidectomy for thyroid cancer. Methods: 23 subjects (age 26±3 years, 10 men) underwent evaluations at baseline and after rhTSH administration, 0.9mg daily on 2 consecutive days. A real time contour tracking algorithm was applied to B-mode scans for assessing brachial artery endothelium-dependent (flow-mediated dilation, FMD), and -independent dilation (glycerol trinitrate, GTN, 25 μg sublingual) and carotid stiffness (CS) by Bramwell-Hill equation. Carotid blood pressure (BP) waveform, augmentation index (AIx), and carotid-femoral PWV were assessed by applanation tonometry. Results: RhTSH decreased diastolic BP (from 79±11 to 72±9 mmHg, p

Both endothelial dysfunction and arterial stiffness are considered as independent predictors of cardiovascular mortality, but their interrelationship has been poorly explored. Therefore we evaluated the relationship between endothelial function and pulse wave velocity (PWV) in essential hypertensive patients with (DM+) or without (DM-) diabetes mellitus, on chronic pharmacological treatment. 51 DM+ patients and 51 DM- patients matched for age, gender and BP were included. Applanation tonometry (Sphygmocor®) was used to determine aortic (carotid to femoral) PWV. Brachial artery endothelium-dependent flow-mediated dilation (FMD), and endothelium-independent dilation by 25 μg sublingual glycerol trinitrate (GTN) were assessed by high resolution ultrasound and computerized edge detection system. In DM+ PWV was higher (9.9±1.8 vs 8.4±1.4m/s, p=0.0001) and FMD was lower (3.1±1.7 vs 6.3±3.5, p