Monica Ragucci

Internal jugular vein blood flow in multiple sclerosis patients and matched controls.

The aim of the study was to investigate the Internal Jugular Veins dynamics using contrast enhanced ultrasonography in Multiple Sclerosis patients, clinically isolated syndrome patients and healthy controls. Contrast enhanced ultrasonography imaging of the Internal Jugular Vein was performed in fifty-eight patients with Multiple Sclerosis, seven clinically isolated syndrome patients and in thirteen healthy controls. Time-intensity curves were quantified using a semi-automated method and compared with clinical disease outcomes. Wash-out parameters were calculated and six Time-intensity curves shapes were created. Significantly reduction of wash-out rate in Internal Jugular Veins was detected in Multiple Sclerosis patients compared to healthy controls [22.2% (2.7%–65.9%) vs. 33.4% (16.2%–76.8%); P<0.005]. Internal Jugular Vein enhancement was heterogeneous in patients with Multiple Sclerosis and consisted of slow wash-out Time-intensity curves shapes, compared with almost only one type of Time-intensity curves shape in control subjects that correspond to fast enhancement and fast wash-out. The vein wash-in parameters were similar in Multiple Sclerosis group compared with controls. A significant correlation was found between Internal Jugular Vein wash-out and level of disability (R = −0.402, p<0.05). Contrast enhanced ultrasonography of the Internal Jugular Vein with time intensity curve analysis revealed alterations of cerebral venous outflow in Multiple Sclerosis patients, however mechanisms that determine this condition remains unclear.

Uncommon pancreatic tumors and pseudotumors

Abstract A heterogeneous group of uncommon neoplastic and non-neoplastic pancreatic pathologies exists that can mimic pancreatic adenocarcinoma. These “imitators” are unique and may demonstrate characteristic clinical and imaging features. Imaging characteristics of some of these diverse lesions are not well described in the literature, and erroneous diagnoses of these entities as pancreatic carcinoma may be responsible for unnecessary surgeries. Knowledge of these selected pancreatic pathologies is essential to facilitate optimal patient management.

Renal Duplex Sonographic Evaluation of Type 2 Diabetic Patients

The purpose of this study was to evaluate the renal volume and intrarenal hemodynamics with duplex sonography in a group of diabetic patients with normal renal function in comparison to nondiabetic controls.

Head and Neck Veins of the Mouse. A Magnetic Resonance, Micro Computed Tomography and High Frequency Color Doppler Ultrasound Study

To characterize the anatomy of the venous outflow of the mouse brain using different imaging techniques. Ten C57/black male mice (age range: 7-8 weeks) were imaged with high-frequency Ultrasound, Magnetic Resonance Angiography and ex-vivo Microcomputed tomography of the head and neck. Under general anesthesia, Ultrasound of neck veins was performed with a 20MHz transducer; head and neck Magnetic Resonance Angiography data were collected on 9.4T or 7T scanners, and ex-vivo Microcomputed tomography angiography was obtained by filling the vessels with a radiopaque inert silicone rubber compound. All procedures were approved by the local ethical committee. The dorsal intracranial venous system is quite similar in mice and humans. Instead, the mouse Internal Jugular Veins are tiny vessels receiving the sigmoid sinuses and tributaries from cerebellum, occipital lobe and midbrain, while the majority of the cerebral blood, i.e. from the olfactory bulbs and fronto-parietal lobes, is apparently drained through skull base connections into the External Jugular Vein. Three main intra-extracranial anastomoses, absent in humans, are: 1) the petrosquamous sinus, draining into the posterior facial vein, 2) the veins of the olfactory bulb, draining into the superficial temporal vein through a foramen of the frontal bone 3) the cavernous sinus, draining in the External Jugular Vein through a foramen of the sphenoid bone. The anatomical structure of the mouse cranial venous outflow as depicted by Ultrasound, Microcomputed tomography and Magnetic Resonance Angiography is different from humans, with multiple connections between intra- and extra- cranial veins.

High Frequency Ultrasound for In Vivo Pregnancy Diagnosis and Staging of Placental and Fetal Development in Mice

Background Ultrasound is a valuable non-invasive tool used in obstetrics and gynecology to monitor the growth and well being of the human fetus. The laboratory mouse has recently emerged as an appropriate model for fetal and perinatal studies because morphogenetic processes in mice exhibit adequate homology to those in humans, and genetic manipulations are relatively simple to perform in mice. High-frequency ultrasound (HFUS) has recently become available for small animal preclinical imaging and can be used to study pregnancy and development in the mouse. The objective of the current study was to assess the main applications of HFUS in the evaluation of fetal growth and placental function and to better understand human congenital diseases. Methodology/Principal Findings On each gestational day, at least 5 dams were monitored with HFUS; a total of ∼200 embryos were examined. Because it is not possible to measure each variable for the entire duration of the pregnancy, the parameters were divided into three groups as a function of the time at which they were measured. Univariate analysis of the relationship between each measurement and the embryonic day was performed using Spearman’s rank correlation (Rs). Continuous linear regression was adopted for multivariate analysis of significant parameters. All statistical tests were two-sided, and a p value of 0.05 was considered statistically significant. Conclusions/Significance The study describes the main applications of HFUS to assess changes in phenotypic parameters in the developing CD1 mouse embryo and fetus during pregnancy and to evaluating physiological fetal and placental growth and the development of principal organs such as the heart, kidney, liver, brain and eyes in the embryonic mouse. A database of normal structural and functional parameters of mouse development will provide a useful tool for the better understanding of morphogenetic and cardiovascular anomalies in transgenic and mutant mouse models.

Repeatability, Reproducibility and Standardisation of a Laser Doppler Imaging Technique for the Evaluation of Normal Mouse Hindlimb Perfusion

Background Preclinical perfusion studies are useful for the improvement of diagnosis and therapy in dermatologic, cardiovascular and rheumatic human diseases. The Laser Doppler Perfusion Imaging (LDPI) technique has been used to evaluate superficial alterations of the skin microcirculation in surgically induced murine hindlimb ischemia. We assessed the reproducibility and the accuracy of LDPI acquisitions and identified several critical factors that could affect LDPI measurements in mice. Methods Twenty mice were analysed. Statistical standardisation and a repeatability and reproducibility analysis were performed on mouse perfusion signals with respect to differences in body temperature, the presence or absence of hair, the type of anaesthesia used for LDPI measurements and the position of the mouse body. Results We found excellent correlations among measurements made by the same operator (i.e., repeatability) under the same experimental conditions and by two different operators (i.e., reproducibility). A Bland-Altman analysis showed the absence of bias in repeatability (p = 0.29) or reproducibility (p = 0.89). The limits of agreement for repeatability were –0.357 and –0.033, and for reproducibility, they were –0.270 and 0.238. Significant differences in perfusion values were observed in different experimental groups. Conclusions Different experimental conditions must be considered as a starting point for the evaluation of new drugs and strategic therapies.

Visceral adiposity and subclinical atherosclerosis in healthy young men

Abstract Background: Atherosclerosis begins in childhood and develops silently for decades before clinical events such as myocardial infarction or stroke occur. Only few studies have evaluated the relationship between CVD risk factors and carotid artery Intimal Media Thickness (IMT) in young asymptomatic people. Aim: The aim of this study is to investigate risk factors for cardiovascular disease associated with higher Carotid Intimal Media Thickness (IMT) in healthy young subjects. Methods: A cohort of 106 healthy young men, mean age 21 ± 2 years (mean ± SD), BMI 24.4 ± 2.8 (kg/m2), on military duty, participated in this cross-sectional study. Waist circumference, carotid intima–media thickness (IMT), blood pressure, and plasma concentrations of relevant metabolic parameters were measured at fasting. Smoking and habitual dietary patterns were evaluated by a semiquantitative questionnaire. Results: The population was divided into two groups on the basis of IMT values: the lowest three quartiles versus the highest quartile (cut-off value = 0.7 mm). BMI, waist circumference, systolic (SBP), and diastolic (DBP) blood pressure were significantly higher in the group with higher IMT (p = 0.02). All other variables, including dietary parameters and smoking, were similar in the two groups. Data analysis showed that IMT values correlated positively with SBP (r = 0.22; p = 0.025), DBP (r = 0.27; p = 0.005), waist circumference (r = 0.29; p = 0.002), and fat mass (r = 0.24; p = 0.01), and negatively with kcal/kg of body weight (r = −0.220.22; p = 0.022) – an indirect marker of physical activity. Based on multiple regression analysis, waist circumference and DBP were the only variables independently associated with IMT (p = 0.029). Conclusions: In a non-selected sample of healthy young adult males, a larger waist circumference and a higher diastolic blood pressure – albeit within normal values – are the only parameters independently associated with higher IMT.

Does Second Reader Opinion Affect Patient Management in Pancreatic Ductal Adenocarcinoma

RATIONALE AND OBJECTIVES To determine the impact of second-opinion assessment on cancer staging and patient management in patients with pancreatic ductal adenocarcinoma. METHODS AND MATERIALS This retrospective study was approved by our institutional review board with a waiver of informed consent. Second-opinion reports between January 1, 2009 and December 31, 2013, alongside outside reports for 65 consecutive cases of biopsy-proven pancreatic adenocarcinomas, were presented in random order to two experienced abdominal surgeons who independently reviewed them blinded to the origin of the report, images of the examinations, and patient identifier. Each surgeon filled in a questionnaire for each report recommending cancer staging and patient management. Recommended patient management and staging were evaluated against reference standards (actual patient management at 6 months following second-opinion assessment, and pathology or other clinical and imaging reference standards at 6 months or longer, respectively) using Cohen kappa. RESULTS Cancer staging differed in 13% (9 of 65) of cases for surgeon 1 and in 18.4% (12 of 65) for surgeon 2. Patient management changed in 38.4% (25 of 65) of cases for surgeon 1 and in 20% (13 of 65) for surgeon 2. When compared to the pathologic staging gold standard, second opinion was correct in 85.7% (six of seven) of the time for both surgeons. Recommended patient management from second-opinion reports showed good agreement with the reference standard (weighted k = 0.6467 [0.4014-0.892] and weighted k = 0.6262 [0.3954-0.857] for surgeon 2). CONCLUSION Second-opinion review by subspecialized oncologic radiologists can impact patient care, specifically in terms of management decision.

High-Frequency Ultrasound for the Study of Early Mouse Embryonic Cardiovascular System.

An accurate diagnosis of congenital heart defects during fetal development is critical for interventional planning. Mice can be used to generate animal models with heart defects, and high-frequency ultrasound (HFUS) imaging enables in utero imaging of live mouse embryos. A wide range of physiological measurements is possible using Doppler-HFUS imaging; limitations of any single measurement warrant a multiparameter approach to characterize cardiovascular function. Doppler-HFUS was used to explore the embryonic (heart, aorta) and extraembryonic (umbilical blood flow) circulatory systems to create a database in normal mouse embryos between 9.5 and 16.5 days of gestation. Multivariate analyses were performed to explore correlations between gestational age and embryo echocardiographic parameters. Heart rate and peak velocity in the aorta were positively correlated with gestational time, whereas cardiac cycle length, isovolumetric relaxation time, myocardial performance index, and arterial deceleration time of the umbilical cord were negatively correlated with it. Doppler-HFUS facilitated detailed characterization of the embryonic mouse circulation and represents a useful tool for investigation of the early mouse embryonic cardiovascular system.

Optimization of tagged MRI for quantification of liver stiffness using computer simulated data

The heartbeat has been proposed as an intrinsic source of motion that can be used in combination with tagged Magnetic Resonance Imaging (MRI) to measure displacements induced in the liver as an index of liver stiffness. Optimizing a tagged MRI acquisition protocol in terms of sensitivity to these displacements, which are in the order of pixel size, is necessary to develop the method as a quantification tool for staging fibrosis. We reproduced a study of cardiac-induced strain in the liver at 3T and simulated tagged MR images with different grid tag patterns to evaluate the performance of the Harmonic Phase (HARP) image analysis method and its dependence on the parameters of tag spacing and grid angle. The Partial Volume Effect (PVE), T1 relaxation, and different levels of noise were taken into account. Four displacement fields of increasing intensity were created and applied to the tagged MR images of the liver. These fields simulated the deformation at different liver stiffnesses. An Error Index (EI) was calculated to evaluate the estimation accuracy for various parameter values. In the absence of noise, the estimation accuracy of the displacement fields increased as tag spacings decreased. EIs for each of the four displacement fields were lower at 0° and the local minima of the EI were found to correspond to multiples of pixel size. The accuracy of the estimation decreased for increasing levels of added noise; as the level increased, the improved estimation caused by decreasing the tag spacing tended to zero. The optimal tag spacing turned out to be a compromise between the smallest tag period that is a multiple of the pixel size and is achievable in a real acquisition and the tag spacing that guarantees an accurate liver displacement measure in the presence of realistic levels of noise.