Longitudinal changes of the femoral bone mineral density from first to third trimester of pregnancy: bone health assessment by means of non-ionizing REMS technology.

BACKGROUND: Throughout the pregnancy, there is a substantial transfer of calcium from the maternal skeleton to the fetus, which leads to a transient net reduction of the maternal bone mineral density. AIMS: To assess longitudinally the changes in the bone mineral density at the femoral neck between the first and third trimester of pregnancy in a cohort of healthy participants using Radiofrequency Echographic Multi Spectrometry (REMS) technology. METHODS: Prospective, cohort study conducted at the University hospital of Parma, Italy between July 2022 and February 2023. We recruited healthy participants with an uncomplicated singleton pregnancy before 14 completed weeks of gestation. All included participants were submitted to a sonographic examination of the femoral neck to assess the bone mineral density (and the corresponding Z-score values) using REMS at 11-13 and 36-38 weeks of pregnancy. The primary outcome was the change in the bone mineral density values at the maternal femoral neck between the first and third trimester of pregnancy. RESULTS: Over a period of 7 months, a total of 65 participants underwent bone mineral density measurement at the femoral neck at first and third trimester of the pregnancy using REMS. A significant reduction of the bone mineral density at the femoral neck (0.723 ± 0.069 vs 0.709 ± 0.069 g/cm2; p < 0.001) was noted with a mean bone mineral density change of - 1.9 ± 0.6% between the first and third trimester of pregnancy. At multivariable linear regression analysis, none of the demographic or clinical variables of the study population proved to be independently associated with the maternal bone mineral density changes at the femoral neck. CONCLUSIONS: Our study conducted on a cohort of healthy participants with uncomplicated pregnancy demonstrates that there is a significant reduction of bone mineral density at femoral neck from early to late gestation.

The success of vaginal birth by use of trans-labial ultrasound plus vaginal examination and vaginal examination only in pregnant women with labor induction: a comparative study.

BACKGROUND: Predicting the success of vaginal delivery is an important issue in preventing adverse maternal and neonatal outcomes. Thus, this study aimed to compare the success rate of vaginal birth by using trans-labial ultrasound and vaginal examination, and vaginal examination only in pregnant women with labor induction. METHODS: This was a comparative study including 392 eligible pregnant women with labor induction attending to a teaching hospital affiliated with Iran University of Medical Sciences from April to October 2018 in Tehran, Iran. Women were randomly assigned to two groups; the trans-labial ultrasound plus vaginal examination (group A), and the vaginal examination only (group B). Women were included in the study if they satisfied the following criteria: singleton pregnancy, 37 to 42 weeks of gestational age, fetal head presentation, a living fetus with no abnormalities, uncomplicated pregnancy, and no previous cesarean section or any uterine surgery. We used a partograph for both groups to assess the fetal head position and the fetal head station. In group 1, the Angle of Progression (AoP) and Rotation Angle (RA) were also assessed. Finally, the success and progression of vaginal delivery in two groups were compared by predicting the duration of delivery and mode of delivery. RESULTS: The findings showed that 8.68% of women in the trans-labial plus vaginal examination group delivered by cesarean section, while 6.13% in the vaginal examination only group delivered by cesarean section (P = 0.55). In women with cesarean section in positive fetal head stations, Angle of Progression (AoP) was significantly decreased ranging from 90 to 135 degrees compared to women who delivered vaginally (135-180 degrees; P <  0.001). In addition, the Rotation Angle (RA) was significantly decreased in women with cesarean section ranging from 0 to 30 degrees compared to women who delivered vaginally (60-90degrees; P <  0.001). Further analysis indicated that a higher risk of cesarean section was associated with vaginal examination only as compared to trans-labial ultrasound plus vaginal examination (HR: 8.65, P <  0.001). CONCLUSION: Angle of Progression (AoP) and Rotation Angle (RA) indexes might be useful parameters to predict labor progression and successful vaginal delivery among women undergoing labor induction.

Fragility Score: a REMS-based indicator for the prediction of incident fragility fractures at 5 years.

BACKGROUND: Accurate estimation of the imminent fragility fracture risk currently represents a challenging task. The novel Fragility Score (FS) parameter, obtained during a Radiofrequency Echographic Multi Spectrometry (REMS) scan of lumbar or femoral regions, has been developed for the non-ionizing estimation of skeletal fragility. AIMS: The aim of this study was to assess the performance of FS in the early identification of patients at risk for incident fragility fractures with respect to bone mineral density (BMD) measurements. METHODS: Data from 1989 Caucasians of both genders were analysed and the incidence of fractures was assessed during a follow-up period up to 5 years. The diagnostic performance of FS to discriminate between patients with and without incident fragility fracture in comparison to that of the BMD T-scores measured by both Dual X-ray Absorptiometry (DXA) and REMS was assessed through ROC analysis. RESULTS: Concerning the prediction of generic osteoporotic fractures, FS provided AUC = 0.811 for women and AUC = 0.780 for men, which resulted in AUC = 0.715 and AUC = 0.758, respectively, when adjusted for age and body mass index (BMI). For the prediction of hip fractures, the corresponding values were AUC = 0.780 for women and AUC = 0.809 for men, which became AUC = 0.735 and AUC = 0.758, respectively, after age- and BMI-adjustment. Overall, FS showed the highest prediction ability for any considered fracture type in both genders, resulting always being significantly higher than either T-scores, whose AUC values were in the range 0.472-0.709. CONCLUSION: FS displayed a superior performance in fracture prediction, representing a valuable diagnostic tool to accurately detect a short-term fracture risk.

Pulse-Echo Measurements of Bone Tissues. Techniques and Clinical Results at the Spine and Femur.

The aim of this chapter is to review the available pulse-echo approaches for the quantitative evaluation of bone health status, with a specific application to the assessment of possible osteoporosis presence and to the fracture risk prediction. Along with a review of the main in-vivo imaging approaches for skeletal robustness evaluation and fracture risk assessment, further understanding into Radiofrequency Echographic Multi Spectrometry (REMS), an ultrasound-based method measuring clinically relevant bone districts (i.e. lumbar vertebrae and proximal femur), is provided, and the further potentialities of this technology are discussed.Currently, the bone mineral density (BMD) provided by dual X-ray absorptiometry (DXA) is considered an established indicator for osteoporosis status assessment and fracture risk prediction, however, in order to obtain more accurate results, an additional step beyond BMD would be necessary, which means including data on bone quality for an improved evaluation of the disease and its consequences.REMS is a technology which allows both osteoporosis diagnosis, through the BMD estimation, and the prediction of fracture risk, through the computation of the Fragility Score; both measures are obtained by the automatic processing of unfiltered ultrasound signals acquired in correspondence of anatomical reference sites.

Human Hepatocarcinoma Cell Targeting by Glypican-3 Ligand Peptide Functionalized Silica Nanoparticles: Implications for Ultrasound Molecular Imaging.

Silica nanoparticles (SiNPs) are widely studied nanomaterials for their potential employment in advanced biomedical applications, such as selective molecular imaging and targeted drug delivery. SiNPs are generally low cost and highly biocompatible, can be easily functionalized with a wide variety of functional ligands, and have been demonstrated to be effective in enhancing ultrasound contrast at clinical diagnostic frequencies. Therefore, SiNPs might be used as contrast agents in echographic imaging. In this work, we have developed a SiNPs-based system for the in vitro molecular imaging of hepatocellular carcinoma cells that express high levels of glypican-3 protein (GPC-3) on their surface. In this regard, a novel GPC-3 targeting peptide was designed and conjugated to fluorescent silica nanoparticles. The physicochemical properties, acoustic behavior, and biocompatibility profile of the functionalized SiNPs were characterized; then binding and uptake of both naked and functionalized SiNPs were analyzed by laser scanning confocal microscopy and transmission electron microscopy in GPC-3 positive HepG2 cells, a human hepatocarcinoma cell line. The results obtained showed that GPC-3-functionalized fluorescent SiNPs significantly enhanced the ultrasound contrast and were effectively bound and taken up by HepG2 cells without affecting their viability.

New perspectives in echographic diagnosis of osteoporosis on hip and spine.

Currently, the accepted "gold standard" method for bone mineral density (BMD) measurement and osteoporosis diagnosis is dual-energy X-ray absorptiometry (DXA). However, actual DXA effectiveness is limited by several factors, including intrinsic accuracy uncertainties and possible errors in patient positioning and/or post-acquisition data analysis. DXA employment is also restricted by the typical issues related to ionizing radiation employment (high costs, need of dedicated structures and certified operators, unsuitability for population screenings). The only commercially-available alternative to DXA is represented by "quantitative ultrasound" (QUS) approaches, which are radiation-free, cheaper and portable, but they cannot be applied on the reference anatomical sites (lumbar spine and proximal femur). Therefore, their documented clinical usefulness is restricted to calcaneal applications on elderly patients (aged over 65 y), in combination with clinical risk factors and only for the identification of healthy subjects at low fracture risk. Literature-reported studies performed some QUS measurements on proximal femur, but their clinical translation is mostly hindered by intrinsic factors (e.g., device bulkiness). An innovative ultrasound methodology has been recently introduced, which performs a combined analysis of B-mode images and corresponding "raw" radiofrequency signals acquired during an echographic scan of the target reference anatomical site, providing two novel parameters: Osteoporosis Score and Fragility Score, indicative of BMD level and bone strength, respectively. This article will provide a brief review of the available systems for osteoporosis diagnosis in clinical routine contexts, followed by a synthesis of the most promising research results on the latest ultrasound developments for early osteoporosis diagnosis and fracture prevention.

[Translational perspectives in molecular imaging: methodological evolution and nanostructured materials]. / Prospettive traslazionali dell'imaging molecolare: evoluzione delle metodiche e materiali nanostrutturati.

Molecular imaging techniques play an increasingly important role in the deep understanding of pathologies. They represent a direct spotlight on the molecular correlates of diseases and can be used for assessing earlier the state of health and decide the treatment of each patient in a personalized way. This article will show the basis of several imaging techniques, and give examples on the application and development of molecular imaging tracers. Particular attention will be pointed on the use of nanostructured materials, that has a promising role in the finding of new tracers, on the use of novel methodological approaches (multimodality, theranostics, pretargeting) and on the possibility of translational applications.

Automatic measurement of head-perineum distance during intrapartum ultrasound: description of the technique and preliminary results.

OBJECTIVES: To evaluate the accuracy and reliability of a new ultrasound technique for the automatic assessment of the head-perineum distance (HPD) during childbirth. METHODS: HPD was measured on a total of 40 acquisition sessions in 30 laboring women both automatically by an innovative algorithm and manually by trained sonographers, assumed as gold standard. RESULTS: A significant correlation was found between manual and automatic measurements (Intra-CC = 0.994). High values of the coefficient of determination (r2=0.98) and low residual errors: RMSE = 2.01 mm (4.9%) were found. CONCLUSION: The automatic algorithm for the assessment of the HPD represents a reliable technique.

First assessment of bone mineral density in healthy pregnant women by means of Radiofrequency Echographic Multi Spectrometry (REMS) technology.

OBJECTIVE: The maternal bone structure is the largest calcium reserve for the fetus during pregnancy, and this is claimed to lead to a bone mineral density (BMD) reduction in pregnant women. The primary outcome of the present work was to assess the BMD in a group of healthy pregnant women. STUDY DESIGN: In this prospective case - control observational study, a non-consecutive group of pregnant women with uncomplicated pregnancy at or >37 weeks were enrolled at the unit of Obstetrics and Gynecology, University of Parma, from February to December 2020. The study subjects were submitted to a sonographic examination of the proximal femur with Radiofrequency Echographic Multi Spectrometry (REMS) technology to quantify the BMD of the femur. The BMD values obtained in the study group were compared with those of a control group of non-pregnant women matched for age, ethnicity and pre-pregnant body mass index (BMI). RESULTS: Overall, 78 pregnant women at 39.1 ±â€¯1.5 weeks were assessed. Compared with non-pregnant women, the femoral BMD values measured in pregnancy using REMS were significant lower (0.769 ±â€¯0.094 g/cm2 vs 0.831 ±â€¯0.101 g/cm2, p = 0.0001) with a mean BMD reduction of 8.1%. The femoral neck BMD presented a positive correlation with the pre-pregnant BMI (p = 0.0004) and a negative correlation with the maternal age (p < 0.0001). In addition, a lower femoral neck BMD in Caucasian ethnicity compared with non-Caucasian was noted (p < 0.0001). CONCLUSION: In this exploratory and proof of concept study, for the first time, a decreased BMD has been objectively demonstrated in pregnant compared with non-pregnant women by means of REMS technology. New studies are required to assess the longitudinal changes of maternal bone density throughout the pregnancy.

Full experimental modelling of a liver tissue mimicking phantom for medical ultrasound studies employing different hydrogels.

Tissue mimicking phantoms have been widely reported to be an important tool for development, optimisation and performance testing of ultrasound-based diagnostic techniques. In particular, modern applications of tissue mimicking phantoms often include characterisation of the nonlinear behaviour of experimental ultrasound contrast agents. In such cases, the tissue-mimicking materials should be chosen not only based on the values of their density, speed of sound and attenuation coefficient, but also considering their effect on the appearance of "native harmonics" due to nonlinear distortion of ultrasound signal during propagation. In a previous paper it was demonstrated that a cellulose-based hydrogel is suitable to simulate nonlinear acoustical behaviour of liver tissue for thicknesses up to 8 cm. In this paper we present the experimental characterisation of the nonlinear acoustical behaviour of a different polyethylene glycol diacrylate (PEGDA)-based hydrogel, in order to assess whether and how it can improve the performances and overcome some limitations of the cellulose-based hydrogel as liver tissue-mimicking material. Samples of pig liver tissue, cellulose-based hydrogel and PEGDA-based hydrogel were insonified in a through-transmission set-up, employing 2.25-MHz pulses with different mechanical index (MI) values. Second harmonic and first harmonic amplitudes were extracted from the spectra of received signals and their difference was then used to compare sample behaviours. Obtained results show how a new more accurate and combined experimental model of linear and nonlinear acoustical behaviour of liver tissue is feasible. In fact, a further confirmation of the cellulose-based hydrogel effectiveness to precisely simulate the liver tissue for penetration depths up to 8 cm was provided, and it was also shown that the employment of the PEGDA-based hydrogel can extend the range of useful tissue-mimicking material thicknesses up to 11 cm, moreover allowing a considerable improvement of the time stability and behaviour reliability of the corresponding manufactured phantoms.

Experimental investigations of nonlinearities and destruction mechanisms of an experimental phospholipid-based ultrasound contrast agent.

OBJECTIVES: We sought to characterize the acoustical behavior of the experimental ultrasound contrast agent BR14 by determining the acoustic pressure threshold above which nonlinear oscillation becomes significant and investigating microbubble destruction mechanisms. MATERIALS AND METHODS: We used a custom-designed in vitro setup to conduct broadband attenuation measurements at 3.5 MHz varying acoustic pressure (range, 50-190 kPa). We also performed granulometric analyses on contrast agent solutions to accurately measure microbubble size distribution and to evaluate insonification effects. RESULTS: Attenuation did not depend on acoustic pressure less than 100 kPa, indicating this pressure as the threshold for the appearance of microbubble nonlinear behavior. At the lowest excitation amplitude, attenuation increased during insonification, while, at higher excitation levels, the attenuation decreased over time, indicating microbubble destruction. The destruction rate changed with pressure amplitude suggesting different destruction mechanisms, as it was confirmed by granulometric analysis. CONCLUSIONS: Microbubbles showed a linear behavior until 100 kPa, whereas beyond this value significant nonlinearities occurred. Observed destruction phenomena seem to be mainly due to gas diffusion and bubble fragmentation mechanisms.

Major osteoporotic fragility fractures: Risk factor updates and societal impact.

Osteoporosis is a silent disease without any evidence of disease until a fracture occurs. Approximately 200 million people in the world are affected by osteoporosis and 8.9 million fractures occur each year worldwide. Fractures of the hip are a major public health burden, by means of both social cost and health condition of the elderly because these fractures are one of the main causes of morbidity, impairment, decreased quality of life and mortality in women and men. The aim of this review is to analyze the most important factors related to the enormous impact of osteoporotic fractures on population. Among the most common risk factors, low body mass index; history of fragility fracture, environmental risk, early menopause, smoking, lack of vitamin D, endocrine disorders (for example insulin-dependent diabetes mellitus), use of glucocorticoids, excessive alcohol intake, immobility and others represented the main clinical risk factors associated with augmented risk of fragility fracture. The increasing trend of osteoporosis is accompanied by an underutilization of the available preventive strategies and only a small number of patients at high fracture risk are recognized and successively referred for therapy. This report provides analytic evidences to assess the best practices in osteoporosis management and indications for the adoption of a correct healthcare strategy to significantly reduce the osteoporosis burden. Early diagnosis is the key to resize the impact of osteoporosis on healthcare system. In this context, attention must be focused on the identification of high fracture risk among osteoporotic patients. It is necessary to increase national awareness campaigns across countries in order to reduce the osteoporotic fractures incidence.

An Advanced Quantitative Echosound Methodology for Femoral Neck Densitometry.

The aim of this paper was to investigate the clinical feasibility and the accuracy in femoral neck densitometry of the Osteoporosis Score (O.S.), an ultrasound (US) parameter for osteoporosis diagnosis that has been recently introduced for lumbar spine applications. A total of 377 female patients (aged 61-70 y) underwent both a femoral dual X-ray absorptiometry (DXA) and an echographic scan of the proximal femur. Recruited patients were sub-divided into a reference database used for ultrasound spectral model construction and a study population for repeatability assessments and accuracy evaluations. Echographic images and radiofrequency signals were analyzed through a fully automatic algorithm that performed a series of combined spectral and statistical analyses, providing as a final output the O.S. value of the femoral neck. Assuming DXA as a gold standard reference, the accuracy of O.S.-based diagnoses resulted 94.7%, with k = 0.898 (p < 0.0001). Significant correlations were also found between O.S.-estimated bone mineral density and corresponding DXA values, with r(2) up to 0.79 and root mean square error = 5.9-7.4%. The reported accuracy levels, combined with the proven ease of use and very good measurement repeatability, provide the adopted method with a potential for clinical routine application in osteoporosis diagnosis.

Automatic Echographic Detection of Halloysite Clay Nanotubes in a Low Concentration Range.

Aim of this work was to investigate the automatic echographic detection of an experimental drug delivery agent, halloysite clay nanotubes (HNTs), by employing an innovative method based on advanced spectral analysis of the corresponding "raw" radiofrequency backscatter signals. Different HNT concentrations in a low range (5.5-66 × 1010 part/mL, equivalent to 0.25-3.00 mg/mL) were dispersed in custom-designed tissue-mimicking phantoms and imaged through a clinically-available echographic device at a conventional ultrasound diagnostic frequency (10 MHz). The most effective response (sensitivity = 60%, specificity = 95%), was found at a concentration of 33 × 1010 part/mL (1.5 mg/mL), representing a kind of best compromise between the need of enough particles to introduce detectable spectral modifications in the backscattered signal and the necessity to avoid the losses of spectral peculiarity associated to higher HNT concentrations. Based on theoretical considerations and quantitative comparisons with literature-available results, this concentration could also represent an optimal concentration level for the automatic echographic detection of different solid nanoparticles when employing a similar ultrasound frequency. Future dedicated studies will assess the actual clinical usefulness of the proposed approach and the potential of HNTs for effective theranostic applications.

A novel ultrasound methodology for estimating spine mineral density.

We investigated the possible clinical feasibility and accuracy of an innovative ultrasound (US) method for diagnosis of osteoporosis of the spine. A total of 342 female patients (aged 51-60 y) underwent spinal dual X-ray absorptiometry and abdominal echographic scanning of the lumbar spine. Recruited patients were subdivided into a reference database used for US spectral model construction and a study population for repeatability and accuracy evaluation. US images and radiofrequency signals were analyzed via a new fully automatic algorithm that performed a series of spectral and statistical analyses, providing a novel diagnostic parameter called the osteoporosis score (O.S.). If dual X-ray absorptiometry is assumed to be the gold standard reference, the accuracy of O.S.-based diagnoses was 91.1%, with k = 0.859 (p < 0.0001). Significant correlations were also found between O.S.-estimated bone mineral densities and corresponding dual X-ray absorptiometry values, with r(2) values up to 0.73 and a root mean square error of 6.3%-9.3%. The results obtained suggest that the proposed method has the potential for future routine application in US-based diagnosis of osteoporosis.

Echographic imaging of tumoral cells through novel nanosystems for image diagnosis.

Since the recognition of disease molecular basis, it has become clear that the keystone moments of medical practice, namely early diagnosis, appropriate therapeutic treatment and patient follow-up, must be approached at a molecular level. These objectives will be in the near future more effectively achievable thanks to the impressive developments in nanotechnologies and their applications to the biomedical field, starting-up the nanomedicine era. The continuous advances in the development of biocompatible smart nanomaterials, in particular, will be crucial in several aspects of medicine. In fact, the possibility of manufacturing nanoparticle contrast agents that can be selectively targeted to specific pathological cells has extended molecular imaging applications to non-ionizing techniques and, at the same time, has made reachable the perspective of combining highly accurate diagnoses and personalized therapies in a single theranostic intervention. Main developing applications of nanosized theranostic agents include targeted molecular imaging, controlled drug release, therapeutic monitoring, guidance of radiation-based treatments and surgical interventions. Here we will review the most recent findings in nanoparticles contrast agents and their applications in the field of cancer molecular imaging employing non-ionizing techniques and disease-specific contrast agents, with special focus on recent findings on those nanomaterials particularly promising for ultrasound molecular imaging and simultaneous treatment of cancer.

Magnetically-coated silica nanospheres for dual-mode imaging at low ultrasound frequency.

AIM: To experimentally investigate the acoustical behavior of different dual-mode nanosized contrast agents (NPCAs) for echographic medical imaging at low ultrasound (US) frequency. METHODS: We synthesized three different nanosized structures: (1) Pure silica nanospheres (SiNSs); (2) FePt-iron oxide (FePt-IO)-coated SiNSs; and (3) IO-coated SiNSs, employing three different diameter of SiNS-core (160, 330 and 660 nm). Tissue mimicking phantoms made of agarose gel solution containing 5 mg of different NPCAs in 2 mL-Eppendorf tubes, were insonified by a commercial echographic system at three different low US pulse values (2.5, 3.5 and 4.5 MHz). The raw radiofrequency signal, backscattered from each considered NPCA containing sample, has been processed in order to calculate the US average backscatter intensity and compare the acoustic behavior of the different NPCA types. RESULTS: The highest US contrast was exhibited by pure SiNSs; FePt-IO-coated SiNSs acoustical behavior followed a similar trend of pure SiNSs with a slight difference in terms of brightness values. The acoustic response of the examined NPCAs resulted function of both SiNS diameter and US frequency. Specifically, higher US frequencies determined higher value of the backscatter for a given SiNS diameter. Frequency-dependent enhancement was marked for pure SiNSs and became less remarkable for FePt-IO-coated SiNSs, whereas IO-coated SiNSs resulted almost unaffected by such frequency variations. Pure and FePt-IO-coated SiNSs evidenced an image backscatter increasing with the diameter up to 330 nm. Conversely, among the types of NPCA tested, IO-coated SiNSs showed the lowest acoustical response for each synthesized diameter and employed US frequency, although a diameter-dependent raising trend was evidenced. CONCLUSION: The US characterization of magnetically covered SiNS shows that FePt-IO, rather than IO, was the best magnetic coating for realizing NPCAs suitable for dual mode imaging of deep organs, combining US and magnetic resonance imaging.

Automatic evaluation of progression angle and fetal head station through intrapartum echographic monitoring.

Labor progression is routinely assessed through transvaginal digital inspections, meaning that the clinical decisions taken during the most delicate phase of pregnancy are subjective and scarcely supported by technological devices. In response to such inadequacies, we combined intrapartum echographic acquisitions with advanced tracking algorithms in a new method for noninvasive, quantitative, and automatic monitoring of labor. Aim of this work is the preliminary clinical validation and accuracy evaluation of our automatic algorithm in assessing progression angle (PA) and fetal head station (FHS). A cohort of 10 parturients underwent conventional labor management, with additional translabial echographic examinations after each uterine contraction. PA and FHS were evaluated by our automatic algorithm on the acquired images. Additionally, an experienced clinical sonographer, blinded regarding the algorithm results, quantified on the same acquisitions of the two parameters through manual contouring, which were considered as the standard reference in the evaluation of automatic algorithm and routine method accuracies. The automatic algorithm (mean error ± 2SD) provided a global accuracy of 0.9 ± 4.0 mm for FHS and 4° ± 9° for PA, which is far above the diagnostic ability shown by the routine method, and therefore it resulted in a reliable method for earlier identification of abnormal labor patterns in support of clinical decisions.

Screening and early diagnosis of osteoporosis through X-ray and ultrasound based techniques.

Effective prevention and management of osteoporosis would require suitable methods for population screenings and early diagnosis. Current clinically-available diagnostic methods are mainly based on the use of either X-rays or ultrasound (US). All X-ray based methods provide a measure of bone mineral density (BMD), but it has been demonstrated that other structural aspects of the bone are important in determining fracture risk, such as mechanical features and elastic properties, which cannot be assessed using densitometric techniques. Among the most commonly used techniques, dual X-ray absorptiometry (DXA) is considered the current "gold standard" for osteoporosis diagnosis and fracture risk prediction. Unfortunately, as other X-ray based techniques, DXA has specific limitations (e.g., use of ionizing radiation, large size of the equipment, high costs, limited availability) that hinder its application for population screenings and primary care diagnosis. This has resulted in an increasing interest in developing reliable pre-screening tools for osteoporosis such as quantitative ultrasound (QUS) scanners, which do not involve ionizing radiation exposure and represent a cheaper solution exploiting portable and widely available devices. Furthermore, the usefulness of QUS techniques in fracture risk prediction has been proven and, with the last developments, they are also becoming a more and more reliable approach for assessing bone quality. However, the US assessment of osteoporosis is currently used only as a pre-screening tool, requiring a subsequent diagnosis confirmation by means of a DXA evaluation. Here we illustrate the state of art in the early diagnosis of this "silent disease" and show up recent advances for its prevention and improved management through early diagnosis.

Sonographic markers for early diagnosis of fetal malformations.

Fetal malformations are very frequent in industrialized countries. Although advanced maternal age may affect pregnancy outcome adversely, 80%-90% of fetal malformations occur in the absence of a specific risk factor for parents. The only effective approach for prenatal screening is currently represented by an ultrasound scan. However, ultrasound methods present two important limitations: the substantial absence of quantitative parameters and the dependence on the sonographer experience. In recent years, together with the improvement in transducer technology, quantitative and objective sonographic markers highly predictive of fetal malformations have been developed. These markers can be detected at early gestation (11-14 wk) and generally are not pathological in themselves but have an increased incidence in abnormal fetuses. Thus, prenatal ultrasonography during the second trimester of gestation provides a "genetic sonogram", including, for instance, nuchal translucency, short humeral length, echogenic bowel, echogenic intracardiac focus and choroid plexus cyst, that is used to identify morphological features of fetal Down's syndrome with a potential sensitivity of more than 90%. Other specific and sensitive markers can be seen in the case of cardiac defects and skeletal anomalies. In the future, sonographic markers could limit even more the use of invasive and dangerous techniques of prenatal diagnosis (amniocentesis, etc.).