Comparative Assessment of Physiological Responses to Emotional Elicitation by Auditory and Visual Stimuli.

The study of emotions through the analysis of the induced physiological responses gained increasing interest in the past decades. Emotion-related studies usually employ films or video clips, but these stimuli do not give the possibility to properly separate and assess the emotional content provided by sight or hearing in terms of physiological responses. In this study we have devised an experimental protocol to elicit emotions by using, separately and jointly, pictures and sounds from the widely used International Affective Pictures System and International Affective Digital Sounds databases. We processed galvanic skin response, electrocardiogram, blood volume pulse, pupillary signal and electroencephalogram from 21 subjects to extract both autonomic and central nervous system indices to assess physiological responses in relation to three types of stimulation: auditory, visual, and auditory/visual. Results show a higher galvanic skin response to sounds compared to images. Electrocardiogram and blood volume pulse show different trends between auditory and visual stimuli. The electroencephalographic signal reveals a greater attention paid by the subjects when listening to sounds compared to watching images. In conclusion, these results suggest that emotional responses increase during auditory stimulation at both central and peripheral levels, demonstrating the importance of sounds for emotion recognition experiments and also opening the possibility toward the extension of auditory stimuli in other fields of psychophysiology. Clinical and Translational Impact Statement- These findings corroborate auditory stimuli's importance in eliciting emotions, supporting their use in studying affective responses, e.g., mood disorder diagnosis, human-machine interaction, and emotional perception in pathology.

Deep learning-based algorithm for postoperative glioblastoma MRI segmentation: a promising new tool for tumor burden assessment.

OBJECTIVE: Clinical and surgical decisions for glioblastoma patients depend on a tumor imaging-based evaluation. Artificial Intelligence (AI) can be applied to magnetic resonance imaging (MRI) assessment to support clinical practice, surgery planning and prognostic predictions. In a real-world context, the current obstacles for AI are low-quality imaging and postoperative reliability. The aim of this study is to train an automatic algorithm for glioblastoma segmentation on a clinical MRI dataset and to obtain reliable results both pre- and post-operatively. METHODS: The dataset used for this study comprises 237 (71 preoperative and 166 postoperative) MRIs from 71 patients affected by a histologically confirmed Grade IV Glioma. The implemented U-Net architecture was trained by transfer learning to perform the segmentation task on postoperative MRIs. The training was carried out first on BraTS2021 dataset for preoperative segmentation. Performance is evaluated using DICE score (DS) and Hausdorff 95% (H95). RESULTS: In preoperative scenario, overall DS is 91.09 (± 0.60) and H95 is 8.35 (± 1.12), considering tumor core, enhancing tumor and whole tumor (ET and edema). In postoperative context, overall DS is 72.31 (± 2.88) and H95 is 23.43 (± 7.24), considering resection cavity (RC), gross tumor volume (GTV) and whole tumor (WT). Remarkably, the RC segmentation obtained a mean DS of 63.52 (± 8.90) in postoperative MRIs. CONCLUSIONS: The performances achieved by the algorithm are consistent with previous literature for both pre-operative and post-operative glioblastoma's MRI evaluation. Through the proposed algorithm, it is possible to reduce the impact of low-quality images and missing sequences.

Application of an OCT-based 3D reconstruction framework to the hemodynamic assessment of an ulcerated coronary artery plaque.

The rupture of a vulnerable plaque, known as ulceration, is the most common cause of myocardial infarction. It can be recognized by angiographic features, such as prolonged intraluminal filling and delayed clearance of the contrast liquid. The diagnosis of such an event is an open challenge due to the limited angiographic resolution and acquisition frequency. The treatment of ulcerated plaques is an open discussion, due to the high heterogeneity and the lack of evidences that support particular strategies. Therefore, the therapeutic decision should follow a detailed investigation with angiography and intravascular imaging, such as optical coherence tomography (OCT), to locate the lesion, besides its geometric features and the lumen occlusion severity. The aim of this study is the application of a framework for the in-silico analysis of the disrupted hemodynamics due to an ulcerated lesion. The study employed a validated OCT-based reconstruction methodology and computational fluid dynamics (CFD) simulations for the computation of local hemodynamic quantities, such as wall shear stress. The reported findings, such as disrupted pre-operative flow conditions, proved the applicability of the developed framework for CFD analyses on complicated patient-specific anatomies that feature ulcerated plaques. The prediction of lesion expansion and the clinical decision making can benefit from a reliable computation of wall shear stress distributions that result from the peculiar anatomy of the lesion. The application of intravascular OCT imaging, high fidelity 3D reconstructions and CFD simulations might guide the treatment of such pathology.

Assessment of spatial heterogeneity of ventricular repolarization after multi-channel blocker drugs in healthy subjects.

BACKGROUND AND OBJECTIVES: In contrast to potassium channel blockers, drugs affecting multiple channels seem to reduce torsadogenic risks. However, their effect on spatial heterogeneity of ventricular repolarization (SHVR) is still matter of investigation. Aim of this work is to assess the effect of four drugs blocking the human ether-à-go-go-related gene (hERG) potassium channel, alone or in combination with other ionic channel blocks, on SHVR, as estimated by the V-index on short triplicate 10 s ECG. METHODS: The V-index is an estimate of the standard deviation of the repolarization times of the myocytes across the entire myocardium, obtained from multi-lead surface electrocardiograms. Twenty-two healthy subjects received a pure hERG potassium channel blocker (dofetilide) and 3 other drugs with additional varying degrees of sodium and calcium (L-type) channel block (quinidine, ranolazine, and verapamil), as well as placebo. A one-way repeated-measures Friedman test was performed to compare the V-index over time. RESULTS: Computer simulations and Bland-Altman analysis supported the reliability of the estimates of V-index on triplicate 10 s ECG. Ranolazine, verapamil and placebo did not affect the V-index. On the contrary, after quinidine and dofetilide administration, an increase of V-index from predose to its peak value was observed (ΔΔV-index values were 19 ms and 27 ms, respectively, p < 0.05). CONCLUSIONS: High torsadogenic drugs (dofetilide and quinidine) affected significantly the SHVR, as quantified by the V-index. The metric has therefore a potential in assessing drug arrhythmogenicity.

Assessment of the effect of intensity standardization on the reliability of T1-weighted MRI radiomic features: experiment on a virtual phantom.

The effect of time of repetition (TR) and time of echo (TE) on radiomic features was evaluated using a virtual phantom. Forty-two T1-weighted MRI images of the same virtual phantom were simulated with TR and TE in a range used in clinical practice. Fifty-eight radiomic features were considered for this analysis. Features were extracted from 3 different regions of interest (ROIs) from the original images and from images that underwent intensity standardization (linear intensity standardization, Z-score standardization and histogram matching). Intraclass correlation coefficient (ICC) was used to assess the reliability of the radiomic features and a threshold of 0.75 was used to discriminate features with good or bad reliability. The coefficient of determination R2 was used to quantify correlation between features and image acquisition parameters. The majority of radiomic features (76%) had good reliability (ICC>0.75) and 66% of the features were uncorrelated with TR and TE (R2<; 0.5). Intensity standardization (in particular histogram matching) significantly reduced the correlation. Intensity standardization also increased the reliability of FOS features, but histogram matching significantly reduced the reliability of GLCM features.

A Stimulus-Response Processing Framework for Pupil Dynamics Assessment during Iso-Luminant Stimuli.

Pupil size is governed by the synergic action of the Autonomic Nervous System. Pupil Diameter (PD) is primarily influenced by the light level and it is responsive to variations of global luminance level. However, recent studies have shown that there is also a high-level interpretation which could modulate this physiological response. In this paper, we develop an ad-hoc protocol based on iso-luminant stimuli and validate its effectiveness for the analysis of high-level modulation of pupil response. A visual illusion was reproduced from literature and adapted in two different colors. Prior to the response analysis, a reconstruction of the missing data due to blinks and other artifacts were reconstructed by using a recently developed signal reconstruction algorithm (Iterative - Single Spectrum Analysis: I-SSA); then both time and frequency domain parameters were extracted from the PD signal. Results indicate that there are peculiarly different responses to iso-luminant stimuli with different image structures and dominating colors, thus indicating a possible high-level processing mechanism. Our results pave the way for future evaluation of comatose or generic unconscious state based on non-contact pupil dynamics assessment.

Assessment of Stability and Discrimination Capacity of Radiomic Features on Apparent Diffusion Coefficient Images.

The objectives of the study are to develop a new way to assess stability and discrimination capacity of radiomic features without the need of test-retest or multiple delineations and to use information obtained to perform a preliminary feature selection. Apparent diffusion coefficient (ADC) maps were computed from diffusion-weighted magnetic resonance images (DW-MRI) of two groups of patients: 18 with soft tissue sarcomas (STS) and 18 with oropharyngeal cancers (OPC). Sixty-nine radiomic features were computed, using three different histogram discretizations (16, 32, and 64 bins). Geometrical transformations (translations) of increasing entity were applied to the regions of interest (ROIs), and the intra-class correlation coefficient (ICC) was used to compare the features computed on the original and modified ROIs. The distribution of ICC values for minimal and maximal entity translations (ICC10 and ICC100, respectively) was used to adjust thresholds of ICC (ICCmin and ICCmax) used to discriminate between good, unstable (ICC10 < ICCmin), and non-discriminative features (ICC100 > ICCmax). Fifty-four and 59 radiomic features passed the stability-based selection for all the three histogram discretizations for the OPC and STS datasets, respectively. The excluded features were similar across the different histogram discretizations (Jaccard's index 0.77 ± 0.13 and 0.9 ± 0.1 for OPC and STS, respectively) but different between datasets (Jaccard's index 0.19 ± 0.02). The results suggest that the observed radiomic features are mainly stable and discriminative, but the stability depends on the region of the body under observation. The method provides a way to assess stability without the need of test-retest or multiple delineations.

Stability assessment of first order statistics features computed on ADC maps in soft-tissue sarcoma.

Radiomics extracts a large number of features from medical images to perform a quantitative characterization. Aim of this study was to assess radiomic features stability and relevance. Apparent diffusion coefficient (ADC) maps were computed from diffusion-weighted magnetic resonance images (DW-MRI) of 18 patients diagnosed with soft-tissue sarcomas (STSs). Thirty-seven intensity-based features were computed on the regions of interest (ROIs). First, ROIs of the images were subjected to translations and rotations in specific ranges. The 37 features computed on the original and transformed ROIs were compared in terms of percentage of variations. The intra-class correlation coefficient (ICC) was computed. To be accepted, a feature should satisfy the following conditions: the ICC after a minimum entity transformation is > 0.6 and the ICC after a maximum entity translation is <; 0.4. In total, 31 features out of 37 were accepted by the algorithm. This stability analysis can be used as a first step in the features selection process.

Assessment of instantaneous cardiovascular dynamics from video plethysmography.

Although there is growing interest in estimating cardiovascular information using contactless video plethysmography (VP), an in-depth validation of time-varying, nonlinear dynamics of the related pulse rate variability is still missing. In this study we estimate the heartbeat through VP and standard ECG, and employ inhomogeneous point-process nonlinear models to assess instantaneous heart rate variability measures defined in the time, frequency, and bispectral domains. Experimental data were gathered from 60 young healthy subjects (age: 24±3 years) undergoing postural changes (rest-to-stand maneuver). Video recordings are processed using our recently proposed method based on zero-phase component analysis. Results show that, at a group level, there is an overall agreement between linear and nonlinear indices computed from ECG and VP during resting state conditions. However, significant differences are found, especially in the bispectral domain, when considering data gathered while standing. Although significant differences exist between cardiovascular estimates from VP and ECG, results can be considered very promising as instantaneous sympatho-vagal changes were correctly identified. More research is indeed needed to improve on the precise estimation of nonlinear sympatho-vagal interactions.

Non-invasive assessment of the effect of beta blockers and calcium channel blockers on the AV node during permanent atrial fibrillation.

AIM: We aimed at assessing changes in AV nodal properties during administration of the beta blockers metoprolol and carvedilol, and the calcium channel blockers diltiazem and verapamil from electrocardiographic data. METHODS: Parameters accounting for the functional refractory periods of the slow and fast pathways (aRPs and aRPf) were estimated using atrial fibrillatory rate (AFR) and ventricular response assessed from 15-min ECG segments recorded at baseline and on drug treatment from sixty patients with permanent AF. RESULTS: The results showed that AFR and HR were significantly reduced for all drugs, and that aRPs and aRPf were significantly prolonged in both pathways. The prolongation in aRP was significantly larger for the calcium channel blockers than for the beta blockers. CONCLUSIONS: The changes observed in the AV node parameters are in line with the results of previous electrophysiological studies performed in patients during sinus rhythm, therefore supporting the clinical value of the method.

Noninvasive Assessment of Atrioventricular Nodal Function: Effect of Rate-Control Drugs during Atrial Fibrillation.

BACKGROUND: During atrial fibrillation (AF), conventional electrophysiological techniques for assessment of refractory period or conduction velocity of the atrioventricular (AV) node cannot be used. We aimed at evaluating changes in AV nodal properties during administration of tecadenoson and esmolol using a novel ECG-based method. METHODS: Fourteen patients (age 58 ± 8 years, 10 men) with AF were randomly assigned to either 75 or 300 µg intravenous tecadenoson. After tecadenoson wash-out, patients received esmolol continuously (100 µg/kg per min for 10 mins, then 50 µg/kg per min for 50 mins). Atrial fibrillatory rate (AFR) and heart rate (HR) were assessed in 15-min segments. Using the novel method, we assessed the absolute refractory periods of the slow and fast pathways (aRPs and aRPf) of the AV node to produce an estimate of the functional refractory period. RESULTS: During esmolol infusion, AFR and HR were significantly decreased and the absolute refractory period was significantly prolonged in both pathways (aRPs: 387 ± 73 vs 409 ± 62 ms, P < 0.05; aRPf: 490 ± 80 vs 529 ± 58 ms, P < 0.05). During both tecadenoson doses, HR decreased significantly and AFR was unchanged. Both aRPs and aRPf were prolonged for a 75 µg dose (aRPs: 322 ± 97 vs 476 ± 75 ms, P < 0.05; aRPf: 456 ± 102 vs 512 ± 55 ms, P < 0.05) whereas a trend toward prolongation was observed for a 300 µg dose. CONCLUSIONS: The estimated parameters reflect expected changes in AV nodal properties, i.e., slower conduction through the AV node for tecadenoson and prolongation of the AV node refractory period for esmolol. Thus, the proposed approach may be used to assess drug effects on the AV node in AF patients.

Radiofrequency ablation of liver tumors: quantitative assessment of tumor coverage through CT image processing.

BACKGROUND: Radiofrequency ablation (RFA) is one of the most promising non-surgical treatments for hepatic tumors. The assessment of the therapeutic efficacy of RFA is usually obtained by visual comparison of pre- and post-treatment CT images, but no numerical quantification is performed. METHODS: In this work, a novel method aiming at providing a more objective tool for the evaluation of RFA coverage is described. Image registration and segmentation techniques were applied to enable the visualization of the tumor and the corresponding post-RFA necrosis in the same framework. In addition, a set of numerical indexes describing tumor/necrosis overlap and their mutual position were computed. RESULTS: After validation of segmentation step, the method was applied on a dataset composed by 10 tumors, suspected not to be completed treated. Numerical indexes showed that only two tumors were totally treated and the percentage of a residual tumor was in the range of 5.12%-35.92%. CONCLUSIONS: This work represents a first attempt to obtain a quantitative tool aimed to assess the accuracy of RFA treatment. The possibility to visualize the tumor and the correspondent post-RFA necrosis in the same framework and the definition of some synthetic numerical indexes could help clinicians in ameliorating RFA treatment.

Amplitude of Dominant T-Wave Alternans assessment on ECGs obtained from a biophysical model.

The Amplitude of Dominant T-Wave Alternans (ADTWA) is a recently introduced index which quantifies the presence of microvolt T Wave Alternans (TWA) on surface ECG recordings. In this paper we investigate the reliability of ADTWA and its robustness against broadband noise. At this regard, we generated synthetic 12-leads ECG recordings through a forward electrophysiological model and we added TWA, at different extent, by modulating the variation of the repolarization times of transmembrane action potentials across even and odd beats. Using a stochastic model, we derived an analytical relationship between the repolarization variation injected into the model and TWA at the surface, thus offering a strategy to evaluate lead sensitivity. In terms of robustness, the results of the simulations show that ADTWA correctly measured the amplitude of synthetic TWA with an average error of 3.3% ± 5.8% in absence of noise. When a 100 µV peak-to-peak broadband noise is present, its effects on estimation errors were kept limited by singular value decomposition on which ADTWA builds.

Dynamic assessment of spontaneous baroreflex sensitivity by means of time-frequency analysis using either RR or pulse interval variability.

In this study we propose a method to continuously assess the changes of spontaneous baroreflex sensitivity (BRS). Systolic arterial pressure and RR intervals are analyzed by time-frequency analysis to estimate their instantaneous powers as well as the time-course of their spectral coherence. The BRS estimated in classical frequency bands is compared to the BRS estimated in dynamic frequency bands centered on respiratory frequency. The possibility of obtaining reliable estimations of the BRS using the pulse interval from the pressure signal as a surrogate of the RR is considered. Results on a tilt table test database suggest that is possible to obtain reliable BRS estimates just from the analysis of the pressure signal, without the need of ECG recordings.

ITAC volume assessment through a Gaussian hidden Markov random field model-based algorithm.

In this paper, a semi-automatic segmentation method for volume assessment of Intestinal-type adenocarcinoma (ITAC) is presented and validated. The method is based on a Gaussian hidden Markov random field (GHMRF) model that represents an advanced version of a finite Gaussian mixture (FGM) model as it encodes spatial information through the mutual influences of neighboring sites. To fit the GHMRF model an expectation maximization (EM) algorithm is used. We applied the method to a magnetic resonance data sets (each of them composed by T1-weighted, Contrast Enhanced T1-weighted and T2-weighted images) for a total of 49 tumor-contained slices. We tested GHMRF performances with respect to FGM by both a numerical and a clinical evaluation. Results show that the proposed method has a higher accuracy in quantifying lesion area than FGM and it can be applied in the evaluation of tumor response to therapy.

Exercise testing for non-invasive assessment of atrial electrophysiological properties in patients with persistent atrial fibrillation.

AIMS: Experimental studies suggest that the autonomic nervous system modulates atrial refractoriness and conduction velocity in atrial fibrillation (AF). These modulatory effects are, however, difficult to assess in the clinical setting. This study sought to non-invasively characterize in patients with persistent AF, the influence of autonomic modulation induced by exercise on atrial fibrillatory rate as marker of atrial refractoriness and to identify clinical and electrocardiographic predictors of atrial rate response. METHODS AND RESULTS: In 24 patients (16 males, mean age 60 +/- 13 years) with persistent AF (16 +/- 25 months), continuous ECGs were recorded during bicycle exercise testing. Fibrillatory rate (in fibrillations per minute, fpm) was assessed at baseline and immediately after termination of exercise with spatiotemporal QRST cancellation and time-frequency analysis. Ventricular response was characterized by time-domain HRV indices. Exercise had no influence on mean fibrillatory rate (409 +/- 42 vs. 414 +/- 43 fpm, P = NS). Seven patients responded to exercise with an increase in fibrillatory rate (26 +/- 10 fpm, P < 0.001 and three with a decrease (-21 +/- 8 fpm, P < 0.001), while the remaining 14 patients did not show a response. Responders' HRV indices changed in response to exercise similarly to that of non-responders. Their baseline fibrillatory rate was, however, lower than that of non-responders (387 +/- 18 vs. 425 +/- 48 fpm, P = 0.028). No other clinical or echocardiographic variable was associated with fibrillatory rate response. Twelve weeks after cardioverson, responders were more likely to remain in sinus rhythm than non-responders (88 vs. 46 %, P = 0.04). CONCLUSIONS: Exercise-induced autonomic activation produces changes in atrial electrophysiological properties that can be detected by time-frequency analysis. Higher baseline fibrillatory rates are associated with an impaired atrial response to exercise that suggests advanced electrical remodelling and reduced sensitivity to autonomic stimuli.

Assessment of spatial organization in the atria during paroxysmal atrial fibrillation and adrenergic stimulation.

Non-linear parameters were computed to assess the extent of spatial organization in the atria in terms of coupling/synchronization between electrograms recorded in different atrial sites. Recordings of 9 patients suffering from paroxysmal atrial fibrillation were tested during four clinical experimental conditions: sinus rhythm and atrial fibrillation, both before and after isoproterenol infusion, a drug mimicking adrenergic activation. Two non-linear metrics were investigated: an index of non-linear association (NLA) and a synchronization (S) index based on the cross-conditional entropy. Results evidence the presence of reduced coupling after drug infusion in both sinus rhythm and atrial fibrillation. Moreover, passing from the NLA to the S index, the capability of the parameter to capture the subtle changes due to isoproterenol administration increased.

Assessment of the dynamics of atrial signals and local atrial period series during atrial fibrillation: effects of isoproterenol administration.

BACKGROUND: The autonomic nervous system (ANS) plays an important role in the genesis and maintenance of atrial fibrillation (AF), but quantification of its electrophysiologic effects is extremely complex and difficult. Aim of the study was to evaluate the capability of linear and non-linear indexes to capture the fine changing dynamics of atrial signals and local atrial period (LAP) series during adrenergic activation induced by isoproterenol (a sympathomimetic drug) infusion. METHODS: Nine patients with paroxysmal or persistent AF (aged 60 +/- 6) underwent electrophysiological study in which isoproterenol was administered to patients. Atrial electrograms were acquired during i) sinus rhythm (SR); ii) sinus rhythm during isoproterenol (SRISO) administration; iii) atrial fibrillation (AF) and iv) atrial fibrillation during isoproterenol (AFISO) administration. The level of organization between two electrograms was assessed by the synchronization index (S), whereas the degree of recurrence of a pattern in a signal was defined by the regularity index (R). In addition, the level of predictability (LP) and regularity of LAP series were computed. RESULTS: LAP series analysis shows a reduction of both LP and R index during isoproterenol infusion in SR and AF (RSR = 0.75 +/- 0.07 RSRISO = 0.69 +/- 0.10, p < 0.0001; RAF = 0.31 +/- 0.08 RAFISO = 0.26 +/- 0.09, p < 0.0001; LPSR = 99.99 +/- 0.001 LPSRISO = 99.97 +/- 0.03, p < 0.0001; LPAF = 69.46 +/- 21.55 LPAFISO = 55 +/- 24.75; p < 0.0001). Electrograms analysis shows R index reductions both in SR (RSR = 0.49 +/- 0.08 RSRISO = 0.46 +/- 0.09 p < 0.0001) and in AF (RAF = 0.29 +/- 0.09 RAFISO = 0.28 +/- 0.08 n.s.). CONCLUSIONS: The proposed parameters succeeded in discriminating the subtle changes due to isoproterenol infusion during both the rhythms especially when considering LAP series analysis. The reduced value of analyzed parameters after isoproterenol administration could reflect an important pro-arrhythmic influence of adrenergic activation on favoring maintenance of AF.