Detection and Grading of Prostate Cancer in Temporal Enhanced Ultrasound using Convolutional Neural Networks

Prostate cancer is the most common non-dermatological cancer amongst men in the developed world. The current definitive diagnosis is core needle biopsy guided by transrectal ultrasound. However, this method suffers from low sensitivity and specificity in detecting cancer. Recently, a new ultrasound based tissue typing approach has been proposed, known as temporal enhanced ultrasound (TeUS). In this approach, a set of temporal ultrasound frames is collected from a stationary tissue location without any intentional mechanical excitation. The main aim of this thesis is to implement a deep learning-based solution for prostate cancer detection and grading using TeUS data. In the proposed solution, convolutional neural networks are trained to extract high-level features from time domain TeUS data in temporally and spatially adjacent frames in nine in vivo prostatectomy cases. This approach avoids information loss due to feature extraction and also improves cancer detection rate. The output likelihoods of two TeUS arrangements are then combined to form our novel decision support system. This deep learning-based approach results in the area under the receiver operating characteristic curve (AUC) of 0.80 and 0.73 for prostate cancer detection and grading, respectively, in leave-one-patient-out cross-validation. Recently, multi-parametric magnetic resonance imaging (mp-MRI) has been utilized to improve detection rate of aggressive prostate cancer. In this thesis, for the first time, we present the fusion of mp-MRI and TeUS for characterization of prostate cancer to compensates the deficiencies of each image modalities and improve cancer detection rate. The results obtained using TeUS are fused with those attained using consolidated mp-MRI maps from multiple MR modalities and cancer delineations on those by multiple clinicians. The proposed fusion approach yields the AUC of 0.86 in prostate cancer detection. The outcomes of this thesis emphasize the viable potential of TeUS as a tissue typing method. Employing this ultrasound-based intervention, which is non-invasive and inexpensive, can be a valuable and practical addition to enhance the current prostate cancer detection.

Contrast-enhanced ultrasound of abdominal organs in cats

The primary aim of this thesis was the evaluation of the perfusion of normal organs in cats using contrast-enhanced ultrasound (CEUS), to serve as a reference for later clinical studies. Little is known of the use of CEUS in cats, especially regarding its safety and the effects of anesthesia on the procedure, thus, secondary aims here were to validate the quantitative analyzing method, to investigate the biological effects of CEUS on feline kidneys, and to assess the effect of anesthesia on splenic perfusion in cats undergoing CEUS. -- The studies were conducted on healthy, young, purpose-bred cats. CEUS of the liver, left kidney, spleen, pancreas, small intestine, and mesenteric lymph nodes was performed to characterize the normal perfusion of these organs on ten anesthetized, male cats. To validate the quantification method, the effects of placement and size of the region of interest (ROI) on perfusion parameters were investigated using CEUS: Three separate sets of ROIs were placed in the kidney cortex, varying in location, size, or depth. The biological effects of CEUS on feline kidneys were estimated by measuring urinary enzymatic activities, analyzing urinary specific gravity, pH, protein, creatinine, albumin, and sediment, and measuring plasma urea and creatinine concentrations before and after CEUS. Finally, the impact of anesthesia on contrast enhancement of the spleen was investigated by imaging cats with CEUS first awake and later under anesthesia on separate days. -- Typical perfusion patterns were found for each of the studied organs. The liver had a gradual and more heterogeneous perfusion pattern due to its dual blood flow and close proximity to the diaphragm. An obvious and statistically significant difference emerged in the perfusion between the kidney cortex and medulla. Enhancement in the spleen was very heterogeneous at the beginning of imaging, indicating focal dissimilarities in perfusion. No significant differences emerged in the perfusion parameters between the pancreas, small intestine, and mesenteric lymph nodes. -- The ROI placement and size were found to have an influence on the quantitative measurements of CEUS. Increasing the depth or the size of the ROI decreased the peak intensity value significantly, suggesting that where and how the ROI is placed does matter in quantitative analyses. --- A significant increase occurred in the urinary N-acetyl-β-D-glucosaminidase (NAG) to creatinine ratio after CEUS. No changes were noted in the serum biochemistry profile after CEUS, with the exception of a small decrease in blood urea concentration. The magnitude of the rise in the NAG/creatinine ratio was, however, less than the circadian variation reported earlier in healthy cats. Thus, the changes observed in the laboratory values after CEUS of the left kidney did not indicate any detrimental effects in kidneys. Heterogeneity of the spleen was observed to be less and time of first contrast appearance earlier in nonanesthetized cats than in anesthetized ones, suggesting that anesthesia increases heterogeneity of the feline spleen in CEUS. ---- In conclusion, the results suggest that CEUS can be used also in feline veterinary patients as an additional diagnostics aid. The perfusion patterns found in the imaged organs were typical and similar to those seen earlier in other species, with the exception of the heterogeneous perfusion pattern in the cat spleen. Differences in the perfusion between organs corresponded with physiology. Based on the results, estimation of focal perfusion defects of the spleen in cats should be performed with caution and after the disappearance of the initial heterogeneity, especially in anesthetized or sedated cats. Finally, these results indicate that CEUS can be used safely to analyze kidney perfusion also in cats. Future clinical studies are needed to evaluate the full potential of CEUS in feline medicine as a tool for diagnosing lesions in various organ systems.

THE ROLE OF ACOUSTIC CAVITATION IN ENHANCED ULTRASOUND-INDUCED HEATING IN A TISSUE-MIMICKING PHANTOM

A complete understanding of high-intensity focused ultrasound-induced temperature changes in tissue requires insight into all potential mechanisms for heat deposition. Applications of therapeutic ultrasound often utilize acoustic pressures capable of producing cavitation activity. Recognizing the ability of bubbles to transfer acoustic energy into heat generation, a study of the role bubbles play in tissue hyperthermia becomes necessary. These bubbles are typically less than 50μm. This dissertation examines the contribution of bubbles and their motion to an enhanced heating effect observed in a tissue-mimicking phantom. A series of experiments established a relationship between bubble activity and an enhanced temperature rise in the phantom by simultaneously measuring both the temperature change and acoustic emissions from bubbles. It was found that a strong correlation exists between the onset of the enhanced heating effect and observable cavitation activity. In addition, the likelihood of observing the enhanced heating effect was largely unaffected by the insonation duration for all but the shortest of insonation times, 0.1 seconds. Numerical simulations were used investigate the relative importance of two candidate mechanisms for heat deposition from bubbles as a means to quantify the number of bubbles required to produce the enhanced temperature rise. The energy deposition from viscous dissipation and the absorption of radiated sound from bubbles were considered as a function of the bubble size and the viscosity of the surrounding medium. Although both mechanisms were capable of producing the level of energy required for the enhanced heating effect, it was found that inertial cavitation, associated with high acoustic radiation and low viscous dissipation, coincided with the the nature of the cavitation best detected by the experimental system. The number of bubbles required to account for the enhanced heating effect was determined through the numerical study to be on the order of 150 or less.

Contrast enhanced ultrasound eases interpretation of an unclear renal tumor in addition to CT, MRI and histological findings--a case report in a young patient

Renal cancer represents accounts for approximately 3% of all adult malignancies with a rising incidence. Incidental diagnosis is mostly based upon ultrasound (US). US and Computed tomography (CT) are the standard imaging modalities for detecting renal cell cancer (RCC). Differentiation between malignant and benign renal tumors is of utmost importance. Contrast enhanced ultrasound (CUS) seems to be a promising new diagnostic option for diagnosis and preoperative treatment planning for patients with renal cancer. It is an additional examination to baseline ultrasound and CT. We report a case of a 37-year-old woman with a papillary renal cell cancer in which CUS helped to differentiate dignity of the tumor. CUS is an additional examination to baseline ultrasound and CT. It is a less invasive technique than contrast enhanced CT and shows even slight tumor blood flow. In addition it may allow a more rapid diagnosis, because of its bedside availability.

Contrast-enhanced ultrasound for myocardial perfusion imaging.

Ultrasound contrast agents are gas-filled microbubbles that enhance visualization of cardiac structures, function and blood flow during contrast-enhanced ultrasound (CEUS). An interesting cardiovascular application of CEUS is myocardial contrast echocardiography, which allows real-time myocardial perfusion imaging. The intraoperative use of this technically challenging imaging method is limited at present, although several studies have examined its clinical utility during cardiac surgery in the past. In the present review we provide general information on the basic principles of CEUS and discuss the methodology and technical aspects of myocardial perfusion imaging.

Evaluation of treatment response after chemoembolisation (TACE) in hepatocellular carcinoma using real time image fusion of contrast-enhanced ultrasound (CEUS) and computed tomography (CT)--preliminary results.

OBJECTIVE To evaluate treatment response of hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) with a new real-time imaging fusion technique of contrast-enhanced ultrasound (CEUS) with multi-slice detection computed tomography (CT) in comparison to conventional post-interventional follow-up. MATERIAL AND METHODS 40 patients with HCC (26 male, ages 46-81 years) were evaluated 24 hours after TACE using CEUS with ultrasound volume navigation and image fusion with CT compared to non-enhanced CT and follow-up contrast-enhanced CT after 6-8 weeks. Reduction of tumor vascularization to less than 25% was regarded as "successful" treatment, whereas reduction to levels >25% was considered as "partial" treatment response. Homogenous lipiodol retention was regarded as successful treatment in non-enhanced CT. RESULTS Post-interventional image fusion of CEUS with CT was feasible in all 40 patients. In 24 patients (24/40), post-interventional image fusion with CEUS revealed residual tumor vascularity, that was confirmed by contrast-enhanced CT 6-8 weeks later in 24/24 patients. In 16 patients (16/40), post-interventional image fusion with CEUS demonstrated successful treatment, but follow-up CT detected residual viable tumor (6/16). Non-enhanced CT did not identify any case of treatment failure. Image fusion with CEUS assessed treatment efficacy with a specificity of 100%, sensitivity of 80% and a positive predictive value of 1 (negative predictive value 0.63). CONCLUSIONS Image fusion of CEUS with CT allows a reliable, highly specific post-interventional evaluation of embolization response with good sensitivity without any further radiation exposure. It can detect residual viable tumor at early state, resulting in a close patient monitoring or re-therapy.

Contrast-enhanced ultrasound evaluation of the renal microcirculation response to terlipressin in hepato-renal syndrome: a preliminary report

BACKGROUND: Terlipressin improves renal function in some patients with type-1 hepato-renal syndrome (HRS). Renal contrast-enhanced ultrasound (CEUS), a novel imaging modality, may help to predict terlipressin responsiveness. OBJECTIVES: We used CEUS to estimate the effect of terlipressin on the renal cortical microcirculation in type-1 HRS. METHODS: We performed renal CEUS scans with destruction-replenishment sequences using Sonovue(®) (Bracco, Milano Italy) as a contrast agent at baseline and after the intravenous administration of 1 mg of terlipressin, in four patients with type-1 HRS. We analyzed video sequences offline using dedicated software. We derived a perfusion index (PI) at each time point for each patient. RESULTS: Patients 1 and 2 had severe presentation and were admitted to the intensive care unit. Both showed a marked increase in PI (+216% and + 567% of baseline) in response to terlipressin. Patients 3 and 4 had less severe presentations and had a decrease in PI (-53% and -20% of baseline) in response to terlipressin. Patients 1, 2, and 4, but not patient 3, responded to terlipressin therapy with a decrease in serum creatinine to <150 µmol/L. CONCLUSIONS: CEUS detected changes in renal cortical microcirculation in response to terlipressin and demonstrated heterogeneous microvascular responses to terlipressin. These initial proof-of-concept findings justify future investigations.

Use of VEGFR-2 targeted microbubbles (BR55, Bracco imaging) for the early ultrasound evaluation of response to antiangiogenic treatment in a xenograft model of hepatocarcinoma

Aim: To evaluate the early response to treatment to an antiangiogenetic drug (sorafenib) in a heterotopic murine model of hepatocellular carcinoma (HCC) using ultrasonographic molecular imaging. Material and Methods: the xenographt model was established injecting a suspension of HuH7 cells subcutaneously in 19 nude mice. When tumors reached a mean diameter of 5-10 mm, they were divided in two groups (treatment and vehicle). The treatment group received sorafenib (62 mg/kg) by daily oral gavage for 14 days. Molecular imaging was performed using contrast enhanced ultrasound (CEUS), by injecting into the mouse venous circulation a suspension of VEGFR-2 targeted microbubbles (BR55, kind gift of Bracco Swiss, Geneve, Switzerland). Video clips were acquired for 6 minutes, then microbubbles (MBs) were destroyed by a high mechanical index (MI) impulse, and another minute was recorded to evaluate residual circulating MBs. The US protocol was repeated at day 0,+2,+4,+7, and +14 from the beginning of treatment administration. Video clips were analyzed using a dedicated software (Sonotumor, Bracco Swiss) to quantify the signal of the contrast agent. Time/intensity curves were obtained and the difference of the mean MBs signal before and after high MI impulse (Differential Targeted Enhancement-dTE) was calculated. dTE represents a numeric value in arbitrary units proportional to the amount of bound MBs. At day +14 mice were euthanized and the tumors analyzed for VEGFR-2, pERK, and CD31 tissue levels using western blot analysis. Results: dTE values decreased from day 0 to day +14 both in treatment and vehicle groups, and they were statistically higher in vehicle group than in treatment group at day +2, at day +7, and at day +14. With respect to the degree of tumor volume increase, measured as growth percentage delta (GPD), treatment group was divided in two sub-groups, non-responders (GPD>350%), and responders (GPD<200%). In the same way vehicle group was divided in slow growth group (GPD<400%), and fast growth group (GPD>900%). dTE values at day 0 (immediately before treatment start) were higher in non-responders than in responders group, with statistical difference at day 2. While dTE values were higher in the fast growth group than in the slow growth group only at day 0. A significant positive correlation was found between VEGFR-2 tissue levels and dTE values, confirming that level of BR55 tissue enhancement reflects the amount of tissue VEGF receptor. Conclusions: the present findings show that, at least in murine experimental models, CEUS with BR55 is feasable and appears to be a useful tool in the prediction of tumor growth and response to sorafenib treatment in xenograft HCC.

Diagnostic efficacy of SonoVue, a second generation contrast agent, in the assessment of extracranial carotid or peripheral arteries using colour and spectral Doppler ultrasound: a multicentre study

The purpose of this study was to demonstrate the improvement in diagnostic quality and diagnostic accuracy of SonoVue microbubble contrast-enhanced ultrasound (CE-US) versus unenhanced ultrasound imaging during the investigation of extracranial carotid or peripheral arteries. 82 patients with suspected extracranial carotid or peripheral arterial disease received four SonoVue doses (0.3 ml, 0.6 ml, 1.2 ml and 2.4 ml) with Doppler ultrasound performed before and following each dose. Diagnostic quality of the CE-US examinations was evaluated off-site for duration of clinically useful contrast enhancement, artefact effects and percentage of examinations converted from non-diagnostic to diagnostic. Accuracy, sensitivity and specificity were assessed as agreement of CE-US diagnosis evaluated by an independent panel of experts with reference standard modality. The median duration of clinically useful signal enhancement significantly increased with increasing SonoVue doses (p< or =0.002). At the dose of 2.4 ml of SonoVue, diagnostic quality evaluated as number of inconclusive examinations significantly improved, falling from 40.7% at baseline down to 5.1%. Furthermore, SonoVue significantly (p<0.01) increased the accuracy, sensitivity and specificity of assessment of disease compared with baseline ultrasound. SonoVue increases the diagnostic quality of Doppler images and improves the accuracy of both spectral and colour Doppler examinations of extracranial carotid or peripheral arterial disease.

Evaluation of liver parenchyma and perfusion using dynamic contrast-enhanced computed tomography and contrast-enhanced ultrasonography in captive green iguanas (Iguana iguana) under general anesthesia.

BACKGROUND Contrast-enhanced diagnostic imaging techniques are considered useful in veterinary and human medicine to evaluate liver perfusion and focal hepatic lesions. Although hepatic diseases are a common occurrence in reptile medicine, there is no reference to the use of contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CECT) to evaluate the liver in lizards. Therefore, the aim of this study was to evaluate the pattern of change in echogenicity and attenuation of the liver in green iguanas (Iguana iguana) after administration of specific contrast media. RESULTS An increase in liver echogenicity and density was evident during CEUS and CECT, respectively. In CEUS, the mean ± SD (median; range) peak enhancement was 19.9% ± 7.5 (18.3; 11.7-34.6). Time to peak enhancement was 134.0 ± 125.1 (68.4; 59.6-364.5) seconds. During CECT, first visualization of the contrast medium was at 3.6 ± 0.5 (4; 3-4) seconds in the aorta, 10.7 ± 2.2 (10.5; 7-14) seconds in the hepatic arteries, and 15 ± 4.5 (14.5; 10-24) seconds in the liver parenchyma. Time to peak was 14.1 ± 3.4 (13; 11-21) and 31 ± 9.6 (29; 23-45) seconds in the aorta and the liver parenchyma, respectively. CONCLUSION CEUS and dynamic CECT are practical means to determine liver hemodynamics in green iguanas. Distribution of contrast medium in iguana differed from mammals. Specific reference ranges of hepatic perfusion for diagnostic evaluation of the liver in iguanas are necessary since the use of mammalian references may lead the clinician to formulate incorrect diagnostic suspicions.

Is ultrasound perfusion imaging capable of detecting mismatch? A proof-of-concept study in acute stroke patients.

In this study, we compared contrast-enhanced ultrasound perfusion imaging with magnetic resonance perfusion-weighted imaging or perfusion computed tomography for detecting normo-, hypo-, and nonperfused brain areas in acute middle cerebral artery stroke. We performed high mechanical index contrast-enhanced ultrasound perfusion imaging in 30 patients. Time-to-peak intensity of 10 ischemic regions of interests was compared to four standardized nonischemic regions of interests of the same patient. A time-to-peak >3 s (ultrasound perfusion imaging) or >4 s (perfusion computed tomography and magnetic resonance perfusion) defined hypoperfusion. In 16 patients, 98 of 160 ultrasound perfusion imaging regions of interests of the ischemic hemisphere were classified as normal, and 52 as hypoperfused or nonperfused. Ten regions of interests were excluded due to artifacts. There was a significant correlation of the ultrasound perfusion imaging and magnetic resonance perfusion or perfusion computed tomography (Pearson`s chi-squared test 79.119, p < 0.001) (OR 0.1065, 95% CI 0.06-0.18). No perfusion in ultrasound perfusion imaging (18 regions of interests) correlated highly with diffusion restriction on magnetic resonance imaging (Pearson's chi-squared test 42.307, p < 0.001). Analysis of receiver operating characteristics proved a high sensitivity of ultrasound perfusion imaging in the diagnosis of hypoperfused area under the curve, (AUC = 0.917; p < 0.001) and nonperfused (AUC = 0.830; p < 0.001) tissue in comparison with perfusion computed tomography and magnetic resonance perfusion. We present a proof of concept in determining normo-, hypo-, and nonperfused tissue in acute stroke by advanced contrast-enhanced ultrasound perfusion imaging.

Local nitric oxide synthase inhibition reduces skeletal muscle glucose uptake but not capillary blood flow during in situ muscle contraction in rats

OBJECTIVE: We have previously shown in humans that local infusion of a nitric oxide synthase (NOS) inhibitor into the femoral artery attenuates the increase in leg glucose uptake during exercise without influencing total leg blood flow. However, rodent studies examining the effect of NOS inhibition on contraction-stimulated skeletal muscle glucose uptake have yielded contradictory results. This study examined the effect of local infusion of an NOS inhibitor on skeletal muscle glucose uptake (2-deoxyglucose) and capillary blood flow (contrast-enhanced ultrasound) during in situ contractions in rats.

RESEARCH DESIGN AND METHODS: Male hooded Wistar rats were anesthetized and one hindleg electrically stimulated to contract (2 Hz, 0.1 ms) for 30 min while the other leg rested. After 10 min, the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (arterial concentration of 5 µmol/l) or saline was infused into the epigastric artery of the contracting leg.

RESULTS: Local NOS inhibition had no effect on blood pressure, heart rate, or muscle contraction force. Contractions increased (P < 0.05) skeletal muscle NOS activity, and this was prevented by L-NAME infusion. NOS inhibition caused a modest significant (P < 0.05) attenuation of the increase in femoral blood flow during contractions, but importantly there was no effect on capillary recruitment. NOS inhibition attenuated (P < 0.05) the increase in contraction-stimulated skeletal muscle glucose uptake by ~35%, without affecting AMP-activated protein kinase (AMPK) activation.

CONCLUSIONS: NOS inhibition attenuated increases in skeletal muscle glucose uptake during contraction without influencing capillary recruitment, suggesting that NO is critical for part of the normal increase in skeletal muscle fiber glucose uptake during contraction.

Aspetti diagnostici, strategie terapeutiche ed esito clinico dei tumori primitivi colangiocellulari insorti su cirrosi

Background: The recent increasing incidence of intrahepatic cholangiocellular carcinoma (ICC) in cirrhosis increased the problem of noninvasive differential diagnosis between ICC and hepatocellular carcinoma (HCC) in cirrhosis. In literature there isn’t data about treatment and prognosis of ICC in cirrhosis. Aim: To investigate the role of the different imaging techniques in the diagnosis of ICC in cirrhosis; to analyze treatments and prognosis with particular attention to factors associated with survival. Methods: The data of 30 cirrhotic patients with ICC were retrospectively collected; patients were referred to Liver Units (S.Orsola-Malpighi and S.Matteo Hospitals) between 2005 and 2011. The results of contrast-enhanced ultrasound (CEUS), computed tomography (CT) and magnetic resonance (MR) were evaluated; the enhancement pattern at different imaging techniques were analysed, with particular attention to misdiagnosis of HCC. We evaluated the different treatments and survival of the study group and then we performed the survival analysis of different clinico-pathologic factors. Results: Twenty-five patients underwent CEUS, 27 CT and 10 MR. In 3 cases (12%) CEUS misdiagnosed ICC for HCC, in 7 cases (26%) CT misdiagnosed ICC and in 1 case (10%) MR misdiagnosed ICC. Patient were followed for a mean of 30 months (range:4-86), with a mean survival of 30 months. Twenty-four out of 30 patients were treated with curative approach, while the other 6 underwent TACE (n=4), radioembolization (n=1) or systemic treatment with Gemcitabine (n=1). The univariate analysis revealed that CA19-9 levels, surveillance program and nodule size were significantly related with survival. By multivariate analysis only nodule size £ 40mm was significant (p=0,004). Conclusion: Diagnosis of ICC in cirrhosis remains difficult because there isn’t a typical enhancement pattern and in some cases it cannot be distinguished from HCC by the different imaging techniques. The study of survival related factors shows that nodule size ≤ 40mm is correlated with improved survival.

Aspetti Ultrasonografici in Corso di Sviluppo Placentare e Adattamento Cardiovascolare nella Cavalla Gravida: ecografia bidimensionale, ecocardiografia ed ecocontrastografia (CEUS)

In corso di gravidanza normale avvengono modificazioni emodinamiche centrali e periferiche volte a garantire le crescenti richieste nutritive dell'unità feto-placentare. L’ecografia con mezzo di contrasto (CEUS-Contrast Enhanced Ultrasonography) a base di microbolle offre una nuova opportunità di monitorare e quantificare la perfusione utero-placentare in condizioni normali e patologiche. L’ecocardiografia è stata ampiamente usata in medicina umana per valutare l’adattamento morfo-funzionale cardiaco materno durante la gravidanza. Gli scopi di questo lavoro prospettico sono stati di applicare, per la prima volta nella specie equina, un mezzo di contrasto di II generazione (Sonovue®), al fine quantificare la perfusione utero-placentare in corso di gravidanza normale, valutandone gli effetti sul benessere materno-fetale e di descrivere le modificazioni nei parametri ecocardiografici morfometrici e funzionali cardiaci, in particolare relativi alla funzione del ventricolo sinistro nel corso di una gravidanza fisiologica. Due fattrici sane di razza Trottatore sono state monitorate ecograficamente in maniera seriale durante l’intero corso della gravidanza, tramite esame bidimensionale, ecocontrastografia dell'unità utero-placentare, flussimetria Doppler delle arterie uterine, ecocardiografia materna in modalità bidimensionale, M-mode, Doppler e Tissue Doppler Imaging. I neonati sono stati clinicamente monitorati e gli invogli fetali esaminati. Il pattern di microperfusione utero-placentare è valutabile quali-quantitativamente tramite la CEUS e dimostra un’aumento del flusso a livello di microvascolarizzazione uterina con l'avanzare della gravidanza; non è stata rilevata la presenza di microbolle a livello di strutture fetali nè effetti dannosi sul benessere materno-fetale. In questo studio sono state osservate delle modificazioni cardiache materne in corso di gravidanza fisiologica, relative all'aumento della FC, del CO ed in particolare all'aumento delle dimensioni dell'atrio sinistro ed a modificazioni nelle onde di velocità di flusso e tissutali di riempimento del ventricolo sinistro.