Non Invasive Tools for Early Detection of Autism Spectrum Disorders

Autism Spectrum Disorders (ASDs) describe a set of neurodevelopmental disorders. ASD represents a significant public health problem. Currently, ASDs are not diagnosed before the 2nd year of life but an early identification of ASDs would be crucial as interventions are much more effective than specific therapies starting in later childhood. To this aim, cheap an contact-less automatic approaches recently aroused great clinical interest. Among them, the cry and the movements of the newborn, both involving the central nervous system, are proposed as possible indicators of neurological disorders. This PhD work is a first step towards solving this challenging problem. An integrated system is presented enabling the recording of audio (crying) and video (movements) data of the newborn, their automatic analysis with innovative techniques for the extraction of clinically relevant parameters and their classification with data mining techniques. New robust algorithms were developed for the selection of the voiced parts of the cry signal, the estimation of acoustic parameters based on the wavelet transform and the analysis of the infant’s general movements (GMs) through a new body model for segmentation and 2D reconstruction. In addition to a thorough literature review this thesis presents the state of the art on these topics that shows that no studies exist concerning normative ranges for newborn infant cry in the first 6 months of life nor the correlation between cry and movements. Through the new automatic methods a population of control infants (“low-risk”, LR) was compared to a group of “high-risk” (HR) infants, i.e. siblings of children already diagnosed with ASD. A subset of LR infants clinically diagnosed as newborns with Typical Development (TD) and one affected by ASD were compared. The results show that the selected acoustic parameters allow good differentiation between the two groups. This result provides new perspectives both diagnostic and therapeutic.

Non invasive assessment of right ventricle in patients with operated tetralogy of Fallot

The objective of this study was to evaluate right ventricular function in patients with right ventricular volume overload in patients with (tetralogy of Fallot, and pulmonary atresia + VSD ) underwent corrective surgery; with echocardiography measure that can be easily applied; and to study the relationship between ProBNP and the contractile function of the right ventricle, dilated right atrium, and the consequences of pulmonary insufficiency . Methods: The study included 50 patients (50% males, mean age 30.64 ± 13.30 years) with prior cardiac surgical intervention of TDF (90%) or pulmonary atresia + VSD (10%). (49 pz) have performed a cardiac MRI and clinical evaluation, (47 pz) echocardiogram, (48 pz) ECG, (34 pz) a cardiopulmonary exercise testing, (29 pz) a dosage of ProBNP. Results: The S-wave velocity (p <0.0001), the TAPSE (p <0.0001) correlated significantly with RVEF estimated by cardiac MRI. The VO2 max was 27.93 ± 12.91 ml / kg / min, 15% of patients had VE/VCO2 The peak> 35. ProBNP correlated positively and significantly with the area of the right atrium (p = 0.0001), and negative and significant with VO2 max (p = 0.04). Those who have increased pulmonary insufficiency (PVR fraction> 30%) have a significantly increased RVED volume (p = 0.01), reduced VO2 max (p = 0.04), and lower ejection fraction of LV (p = 0.02) than the group of patients with PVR ≤ 30. Conclusion: The TAPSE and S-wave velocity are fundamental and may become the technique of choice for routine assessment of RV systolic function in adult patients with TOF. The monitoring of the Pro BNP is probably a choice, given the simplicity and their information that correlate with the test cardiopulmonary. In view of the ventricular-ventricular interaction, so measures to maintain or restore the functioning of the pulmonary valve could preserve biventricular function.

Electrothermal characterization and nonlinear modelling of GaN transistors for telecommunication circuit design

This thesis starts showing the main characteristics and application fields of the AlGaN/GaN HEMT technology, focusing on reliability aspects essentially due to the presence of low frequency dispersive phenomena which limit in several ways the microwave performance of this kind of devices. Based on an equivalent voltage approach, a new low frequency device model is presented where the dynamic nonlinearity of the trapping effect is taken into account for the first time allowing considerable improvements in the prediction of very important quantities for the design of power amplifier such as power added efficiency, dissipated power and internal device temperature. An innovative and low-cost measurement setup for the characterization of the device under low-frequency large-amplitude sinusoidal excitation is also presented. This setup allows the identification of the new low frequency model through suitable procedures explained in detail. In this thesis a new non-invasive empirical method for compact electrothermal modeling and thermal resistance extraction is also described. The new contribution of the proposed approach concerns the non linear dependence of the channel temperature on the dissipated power. This is very important for GaN devices since they are capable of operating at relatively high temperatures with high power densities and the dependence of the thermal resistance on the temperature is quite relevant. Finally a novel method for the device thermal simulation is investigated: based on the analytical solution of the tree-dimensional heat equation, a Visual Basic program has been developed to estimate, in real time, the temperature distribution on the hottest surface of planar multilayer structures. The developed solver is particularly useful for peak temperature estimation at the design stage when critical decisions about circuit design and packaging have to be made. It facilitates the layout optimization and reliability improvement, allowing the correct choice of the device geometry and configuration to achieve the best possible thermal performance.

Ground penetrating radar early-time technique for soil electromagnetic parameters estimation

In recent years, thanks to the technological advances, electromagnetic methods for non-invasive shallow subsurface characterization have been increasingly used in many areas of environmental and geoscience applications. Among all the geophysical electromagnetic methods, the Ground Penetrating Radar (GPR) has received unprecedented attention over the last few decades due to its capability to obtain, spatially and temporally, high-resolution electromagnetic parameter information thanks to its versatility, its handling, its non-invasive nature, its high resolving power, and its fast implementation. The main focus of this thesis is to perform a dielectric site characterization in an efficient and accurate way studying in-depth a physical phenomenon behind a recent developed GPR approach, the so-called early-time technique, which infers the electrical properties of the soil in the proximity of the antennas. In particular, the early-time approach is based on the amplitude analysis of the early-time portion of the GPR waveform using a fixed-offset ground-coupled antenna configuration where the separation between the transmitting and receiving antenna is on the order of the dominant pulse-wavelength. Amplitude information can be extracted from the early-time signal through complex trace analysis, computing the instantaneous-amplitude attributes over a selected time-duration of the early-time signal. Basically, if the acquired GPR signals are considered to represent the real part of a complex trace, and the imaginary part is the quadrature component obtained by applying a Hilbert transform to the GPR trace, the amplitude envelope is the absolute value of the resulting complex trace (also known as the instantaneous-amplitude). Analysing laboratory information, numerical simulations and natural field conditions, and summarising the overall results embodied in this thesis, it is possible to suggest the early-time GPR technique as an effective method to estimate physical properties of the soil in a fast and non-invasive way.

Foetal heart rate recording: analysis and comparison of different methodologies

Monitoring foetal health is a very important task in clinical practice to appropriately plan pregnancy management and delivery. In the third trimester of pregnancy, ultrasound cardiotocography is the most employed diagnostic technique: foetal heart rate and uterine contractions signals are simultaneously recorded and analysed in order to ascertain foetal health. Because ultrasound cardiotocography interpretation still lacks of complete reliability, new parameters and methods of interpretation, or alternative methodologies, are necessary to further support physicians’ decisions. To this aim, in this thesis, foetal phonocardiography and electrocardiography are considered as different techniques. Further, variability of foetal heart rate is thoroughly studied. Frequency components and their modifications can be analysed by applying a time-frequency approach, for a distinct understanding of the spectral components and their change over time related to foetal reactions to internal and external stimuli (such as uterine contractions). Such modifications of the power spectrum can be a sign of autonomic nervous system reactions and therefore represent additional, objective information about foetal reactivity and health. However, some limits of ultrasonic cardiotocography still remain, such as in long-term foetal surveillance, which is often recommendable mainly in risky pregnancies. In these cases, the fully non-invasive acoustic recording, foetal phonocardiography, through maternal abdomen, represents a valuable alternative to the ultrasonic cardiotocography. Unfortunately, the so recorded foetal heart sound signal is heavily loaded by noise, thus the determination of the foetal heart rate raises serious signal processing issues. A new algorithm for foetal heart rate estimation from foetal phonocardiographic recordings is presented in this thesis. Different filtering and enhancement techniques, to enhance the first foetal heart sounds, were applied, so that different signal processing techniques were implemented, evaluated and compared, by identifying the strategy characterized on average by the best results. In particular, phonocardiographic signals were recorded simultaneously to ultrasonic cardiotocographic signals in order to compare the two foetal heart rate series (the one estimated by the developed algorithm and the other provided by cardiotocographic device). The algorithm performances were tested on phonocardiographic signals recorded on pregnant women, showing reliable foetal heart rate signals, very close to the ultrasound cardiotocographic recordings, considered as reference. The algorithm was also tested by using a foetal phonocardiographic recording simulator developed and presented in this research thesis. The target was to provide a software for simulating recordings relative to different foetal conditions and recordings situations and to use it as a test tool for comparing and assessing different foetal heart rate extraction algorithms. Since there are few studies about foetal heart sounds time characteristics and frequency content and the available literature is poor and not rigorous in this area, a data collection pilot study was also conducted with the purpose of specifically characterising both foetal and maternal heart sounds. Finally, in this thesis, the use of foetal phonocardiographic and electrocardiographic methodology and their combination, are presented in order to detect foetal heart rate and other functioning anomalies. The developed methodologies, suitable for longer-term assessment, were able to detect heart beat events correctly, such as first and second heart sounds and QRS waves. The detection of such events provides reliable measures of foetal heart rate, potentially information about measurement of the systolic time intervals and foetus circulatory impedance.

Ruolo dell'elastometria pulsata monodimensionale ad ultrasuoni (fibroscan) nella stadiazione della fibrosi epatica in pazienti sottoposti a trapianto ortotopico di fegato con recidiva di epatite C

PREMESSA: La progressione della recidiva d’epatite C è accelerata nei pazienti sottoposti a trapianto di fegato e ciò ha portato alla necessità di sviluppare nuove e validate metodiche non invasive per la quantificazione e la misura della fibrosi epatica. SCOPI: Stabilire l’efficacia dell’elastometria epatica (Fibroscan®) e dei parametri sierici di fibrosi, attualmente disponibili nella pratica clinica, per predire il grado di fibrosi nei pazienti sottoposti a trapianto epatico. METODI: La correlazione fra fibrosi epatica, determinata mediante biopsia epatica ed esame istologico, e Fibroscan® o indici clinico-sierologici di fibrosi (Benlloch, Apri, Forns, Fibrotest and Doppler resistance index), è stata studiata in pazienti che avevano ricevuto un trapianto ortotopico di fegato con evidenza di recidiva d’epatite da HCV. Un totale di 36 pazienti, con la seguente classificazione istologica: fibrosi secondom METAVIR F1=24, F2=8, F3=3, F4=1, sono stati arruolati nella popolazione oggetto di studio. Un totale di 29 individui volontari sani sono serviti come controllo. Le differenze fra gli stadi di fibrosi sono state calcolate mediante analisi statistica non parametrica. Il miglior cut-off per la differenziazione di fibrosi significativa (F2-F4) è stato identificato mediante l’analisi delle curve ROC. RISULTATI: La rigidità epatica ha presentato valori di 4.4 KPa (2.7-6.9) nei controlli (mediane e ranges), con valori in tutti i soggeti <7.0 KPa; 7.75 KPa (4.2-28.0) negli F1; 16.95 KPa (10.2-31.6) negli F2; 21.10 KPa nell’unico paziente F4 cirrotico. Le differenze sono state statisticamente significative per i soggetti controllo versus F1 e F2 (p<0.0001) e per F1 versus F2 (p<0.0001). Un cut-off elastografico di 11.2 KPagarantisce 88% di Sensibilità, 90% di Specificità, 79% di PPV e 95% di NPV nel differenziare i soggetti F1 dagli F2-F4. Le AUROC, relativamente alla capacità di discriminare fra i differenti gradi di fibrosi, evidenziavano un netto vantaggio per il Fibroscan® rispetto ad ognuno degli indici non invasivi di fibrosi. CONCLUSIONI: L’elastometria epatica presenta una buona accuratezza diagnostica nell’identificare pazienti con fibrosi epatica di grado significativo, superiore a quella di tutti gli altri test non invasivi al momento disponibili nella clinica, nei pazienti portatori di trapianto epatico ortotopico da cadavere con recidiva di HCV.

Studio di biomateriali usati come scaffold per Tissue Engineering e loro caratterizzazione con tecniche spettroscopiche vibrazionali e di analisi termica

This research investigated someone of the main problems connected to the application of Tissue Engineering in the prosthetic field, in particular about the characterization of the scaffolding materials and biomimetic strategies adopted in order to promote the implant integration. The spectroscopic and thermal analysis techniques were usefully applied to characterize the chemico-physical properties of the materials such as – crystallinity; – relative composition in case of composite materials; – Structure and conformation of polymeric and peptidic chains; – mechanism and degradation rate; – Intramolecular and intermolecular interactions (hydrogen bonds, aliphatic interactions). This kind of information are of great importance in the comprehension of the interactions that scaffold undergoes when it is in contact with biological tissues; this information are fundamental to predict biodegradation mechanisms and to understand how chemico-physical properties change during the degradation process. In order to fully characterize biomaterials, this findings must be integrated by information relative to mechanical aspects and in vitro and in vivo behavior thanks to collaborations with biomedical engineers and biologists. This study was focussed on three different systems that correspond to three different strategies adopted in Tissue Engineering: biomimetic replica of fibrous 3-D structure of extracellular matrix (PCL-PLLA), incorporation of an apatitic phase similar to bone inorganic phase to promote biomineralization (PCL-HA), surface modification with synthetic oligopeptides that elicit the interaction with osteoblasts. The characterization of the PCL-PLLA composite underlined that the degradation started along PLLA fibres, which are more hydrophylic, and they serve as a guide for tissue regeneration. Moreover it was found that some cellular lines are more active in the colonization of the scaffold. In the PCL-HA composite, the weight ratio between the polymeric and the inorganic phase plays an essential role both in the degradation process and in the biomineralization of the material. The study of self-assembling peptides allowed to clarify the influence of primary structure on intermolecular and intermolecular interactions, that lead to the formation of the secondary structure and it was possible to find a new class of oligopeptides useful to functionalize materials surface. Among the analytical techniques used in this study, Raman vibrational spectroscopy played a major role, being non-destructive and non-invasive, two properties that make it suitable to degradation studies and to morphological characterization. Also micro-IR spectroscopy was useful in the comprehension of peptide structure on oxidized titanium: up to date this study was one of the first to employ this relatively new technique in the biomedical field.

Longterm peripheral baroreflex and chemoreflex function after bilateral eversion carotid endarterectomy

Introduction The “eversion” technique for carotid endarterectomy (e-CEA), that involves the transection of the internal carotid artery at the carotid bulb and its eversion over the atherosclerotic plaque, has been associated with an increased risk of postoperative hypertension possibly due to a direct iatrogenic damage to the carotid sinus fibers. The aim of this study is to assess the long-term effect of the e-CEA on arterial baroreflex and peripheral chemoreflex function in humans. Methods A retrospective review was conducted on a prospectively compiled computerized database of 3128 CEAs performed on 2617 patients at our Center between January 2001 and March 2006. During this period, a total of 292 patients who had bilateral carotid stenosis ≥70% at the time of the first admission underwent staged bilateral CEAs. Of these, 93 patients had staged bilateral e-CEAs, 126 staged bilateral s- CEAs and 73 had different procedures on each carotid. CEAs were performed with either the eversion or the standard technique with routine Dacron patching in all cases. The study inclusion criteria were bilateral CEA with the same technique on both sides and an uneventful postoperative course after both procedures. We decided to enroll patients submitted to bilateral e-CEA to eliminate the background noise from contralateral carotid sinus fibers. Exclusion criteria were: age >70 years, diabetes mellitus, chronic pulmonary disease, symptomatic ischemic cardiac disease or medical therapy with b-blockers, cardiac arrhythmia, permanent neurologic deficits or an abnormal preoperative cerebral CT scan, carotid restenosis and previous neck or chest surgery or irradiation. Young and aged-matched healthy subjects were also recruited as controls. Patients were assessed by the 4 standard cardiovascular reflex tests, including Lying-to-standing, Orthostatic hypotension, Deep breathing, and Valsalva Maneuver. Indirect autonomic parameters were assessed with a non-invasive approach based on spectral analysis of EKG RR interval, systolic arterial pressure, and respiration variability, performed with an ad hoc software. From the analysis of these parameters the software provides the estimates of spontaneous baroreflex sensitivity (BRS). The ventilatory response to hypoxia was assessed in patients and controls by means of classic rebreathing tests. Results A total of 29 patients (16 males, age 62.4±8.0 years) were enrolled. Overall, 13 patients had undergone bilateral e-CEA (44.8%) and 16 bilateral s-CEA (55.2%) with a mean interval between the procedures of 62±56 days. No patient showed signs or symptoms of autonomic dysfunction, including labile hypertension, tachycardia, palpitations, headache, inappropriate diaphoresis, pallor or flushing. The results of standard cardiovascular autonomic tests showed no evidence of autonomic dysfunction in any of the enrolled patients. At spectral analysis, a residual baroreflex performance was shown in both patient groups, though reduced, as expected, compared to young controls. Notably, baroreflex function was better maintained in e-CEA, compared to standard CEA. (BRS at rest: young controls 19.93 ± 2.45 msec/mmHg; age-matched controls 7.75 ± 1.24; e-CEA 13.85 ± 5.14; s-CEA 4.93 ± 1.15; ANOVA P=0.001; BRS at stand: young controls 7.83 ± 0.66; age-matched controls 3.71 ± 0.35; e-CEA 7.04 ± 1.99; s-CEA 3.57 ± 1.20; ANOVA P=0.001). In all subjects ventilation (VÝ E) and oximetry data fitted a linear regression model with r values > 0.8. Oneway analysis of variance showed a significantly higher slope both for ΔVE/ΔSaO2 in controls compared with both patient groups which were not different from each other (-1.37 ± 0.33 compared with -0.33±0.08 and -0.29 ±0.13 l/min/%SaO2, p<0.05, Fig.). Similar results were observed for and ΔVE/ΔPetO2 (-0.20 ± 0.1 versus -0.01 ± 0.0 and -0.07 ± 0.02 l/min/mmHg, p<0.05). A regression model using treatment, age, baseline FiCO2 and minimum SaO2 achieved showed only treatment as a significant factor in explaining the variance in minute ventilation (R2= 25%). Conclusions Overall, we demonstrated that bilateral e-CEA does not imply a carotid sinus denervation. As a result of some expected degree of iatrogenic damage, such performance was lower than that of controls. Interestingly though, baroreflex performance appeared better maintained in e-CEA than in s-CEA. This may be related to the changes in the elastic properties of the carotid sinus vascular wall, as the patch is more rigid than the endarterectomized carotid wall that remains in the e-CEA. These data confirmed the safety of CEA irrespective of the surgical technique and have relevant clinical implication in the assessment of the frequent hemodynamic disturbances associated with carotid angioplasty stenting.

A skin surface characterization system based on capacitive image analysis

During the last few years, several methods have been proposed in order to study and to evaluate characteristic properties of the human skin by using non-invasive approaches. Mostly, these methods cover aspects related to either dermatology, to analyze skin physiology and to evaluate the effectiveness of medical treatments in skin diseases, or dermocosmetics and cosmetic science to evaluate, for example, the effectiveness of anti-aging treatments. To these purposes a routine approach must be followed. Although very accurate and high resolution measurements can be achieved by using conventional methods, such as optical or mechanical profilometry for example, their use is quite limited primarily to the high cost of the instrumentation required, which in turn is usually cumbersome, highlighting some of the limitations for a routine based analysis. This thesis aims to investigate the feasibility of a noninvasive skin characterization system based on the analysis of capacitive images of the skin surface. The system relies on a CMOS portable capacitive device which gives 50 micron/pixel resolution capacitance map of the skin micro-relief. In order to extract characteristic features of the skin topography, image analysis techniques, such as watershed segmentation and wavelet analysis, have been used to detect the main structures of interest: wrinkles and plateau of the typical micro-relief pattern. In order to validate the method, the features extracted from a dataset of skin capacitive images acquired during dermatological examinations of a healthy group of volunteers have been compared with the age of the subjects involved, showing good correlation with the skin ageing effect. Detailed analysis of the output of the capacitive sensor compared with optical profilometry of silicone replica of the same skin area has revealed potentiality and some limitations of this technology. Also, applications to follow-up studies, as needed to objectively evaluate the effectiveness of treatments in a routine manner, are discussed.

Circoli collaterali porto-sistemici all'eco-color-Doppler addominale in pazienti con ipertensione portale cirrotica: correlazione con il gradiente porto-epatico e valore prognostico

Background. Abdominal porto-systemic collaterals (APSC) on Color-Doppler ultrasound are a frequent finding in portal hypertensive cirrhotic patients. In patients with cirrhosis, an HVPG ≥ 16mmHg has been shown to be associated with increased mortality in two studies. Non-invasive indicators of HVPG ≥ 16 mmHg might define a subgroup of high-risk patients, but data on this aspect are lacking. Aims. We aimed to investigate whether HVPG predicts mortality in patients with clinically significant portal hypertension, and if APSC may predict a severe portal hypertensive state (i.e. HVPG≥16mmHg) in patients with cirrhosis and untreated portal hypertension. Methods. We analysed paired HVPG and ultrasonographic data of 86 untreated portal hypertensive cirrhotic patients. On abdominal echo-color-Doppler data on presence, type and number of APSC were prospectively collected. HVPG was measured following published guidelines. Clinical, laboratory and endoscopic data were available in all cases. First decompensation of cirrhosis and liver-disease related mortality on follow-up (mean 28±20 months) were recorded. Results. 73% of patients had compensated cirrhosis, while 27% were decompensated. All patients had an HVPG≥10 mmHg (mean 17.8±5.1 mmHg). 58% of compensated patients and 82% of decompensated patients had an HVPG over 16 mmHg. 25% had no varices, 28% had small varices, and 47% had medium/large varices. HVPG was higher in patients with esophageal varices vs. patients without varices (19.0±4.8 vs. 14.1±4.2mmHg, p<0.0001), and correlated with Child-Pugh score (R=0.494,p=0.019). 36 (42%) patients had APSC were more frequent in decompensated patients (60% vs. 35%, p=0.03) and in patients with esophageal varices (52% vs. 9%,p=0.001). HVPG was higher in patients with APSC compared with those without PSC (19.9± 4.6 vs. 16.2± 4.9mmHg, p=0.001). The prevalence of APSC was higher in patients with HVPG≥16mmHg vs. those with HVPG<16mmHg (57% vs. 13%,p<0.0001). Decompensation was significantly more frequent in patients with HVPG≥16mmHg vs. HVPG<16mmHg (35.1% vs. 11.5%, p=0.02). On multivariate analysis only HVPG and bilirubin were independent predictors of first decompensation. 10 patients died during follow-up. All had an HVPG≥16 mmHg (26% vs. 0% in patients with HVPG <16mmHg,p=0.04). On multivariate analysis only MELD score and HVPG ≥16mmHg were independent predictors of mortality. In compensated patients the detection of APSC predicted an HVPG≥16mmHg with 92% specificity, 54% sensitivity, positive and negative likelihood ratio 7.03 and 0.50, which implies that the demonstration of APSC on ultrasound increased the probability of HVPG≥16mmHg from 58% to 91%. Conclusions. HVPG maintains an independent prognostic value in the subset of patients with cirrhosis and clinically significant portal hypertension. The presence of APSC is a specific indicator of severe portal hypertension in patients with cirrhosis. Detection of APSC on ultrasound allows the non-invasive identification of a subgroup of compensated patients with bad prognosis, avoiding the invasive measurement of HVPG.

Changes in tumor stiffness for early prediction of tumor response to sorafenib: a proof-of-concept study with elastosonography in an animal model of Hepatocellular Carcinoma (HCC)

Background and aims: Sorafenib is the reference therapy for advanced Hepatocellular Carcinoma (HCC). No method exists to predict in the very early period subsequent individual response. Starting from the clinical experience in humans that subcutaneous metastases may rapidly change consistency under sorafenib and that elastosonography a new ultrasound based technique allows assessment of tissue stiffness, we investigated the role of elastonography in the very early prediction of tumor response to sorafenib in a HCC animal model. Methods: HCC (Huh7 cells) subcutaneous xenografting in mice was utilized. Mice were randomized to vehicle or treatment with sorafenib when tumor size was 5-10 mm. Elastosonography (Mylab 70XVG, Esaote, Genova, Italy) of the whole tumor mass on a sagittal plane with a 10 MHz linear transducer was performed at different time points from treatment start (day 0, +2, +4, +7 and +14) until mice were sacrified (day +14), with the operator blind to treatment. In order to overcome variability in absolute elasticity measurement when assessing changes over time, values were expressed in arbitrary units as relative stiffness of the tumor tissue in comparison to the stiffness of a standard reference stand-off pad lying on the skin over the tumor. Results: Sor-treated mice showed a smaller tumor size increase at day +14 in comparison to vehicle-treated (tumor volume increase +192.76% vs +747.56%, p=0.06). Among Sor-treated tumors, 6 mice showed a better response to treatment than the other 4 (increase in volume +177% vs +553%, p=0.011). At day +2, median tumor elasticity increased in Sor-treated group (+6.69%, range –30.17-+58.51%), while decreased in the vehicle group (-3.19%, range –53.32-+37.94%) leading to a significant difference in absolute values (p=0.034). From this time point onward, elasticity decreased in both groups, with similar speed over time, not being statistically different anymore. In Sor-treated mice all 6 best responders at day 14 showed an increase in elasticity at day +2 (ranging from +3.30% to +58.51%) in comparison to baseline, whereas 3 of the 4 poorer responders showed a decrease. Interestingly, these 3 tumours showed elasticity values higher than responder tumours at day 0. Conclusions: Elastosonography appears a promising non-invasive new technique for the early prediction of HCC tumor response to sorafenib. Indeed, we proved that responder tumours are characterized by an early increase in elasticity. The possibility to distinguish a priori between responders and non responders based on the higher elasticity of the latter needs to be validated in ad-hoc experiments as well as a confirmation of our results in humans is warranted.