Ernesto Casciaro

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.

Fully Automatic Segmentations of Liver and Hepatic Tumors From 3-D Computed Tomography Abdominal Images: Comparative Evaluation of Two Automatic Methods

An adaptive initialization method was developed to produce fully automatic processing frameworks based on graph-cut and gradient flow active contour algorithms. This method was applied to abdominal Computed Tomography (CT) images for segmentation of liver tissue and hepatic tumors. Twenty-five anonymized datasets were randomly collected from several radiology centres without specific request on acquisition parameter settings nor patient clinical situation as inclusion criteria. Resulting automatic segmentations of liver tissue and tumors were compared to their reference standard delineations manually performed by a specialist. Segmentation accuracy has been assessed through the following evaluation framework: dice similarity coefficient (DSC), false negative ratio (FNR), false positive ratio (FPR) and processing time. Regarding liver surfaces, graph-cuts achieved a DSC of 95.49% ( FPR=2.35% and FNR=5.10%), while active contours reached a DSC of 96.17% (FPR=3.35% and FNR=3.87%). The analyzed datasets presented 52 tumors: graph-cut algorithm detected 48 tumors with a DSC of 88.65%, while active contour algorithm detected only 44 tumors with a DSC of 87.10%. In addition, in terms of time performances, less time was requested for graph-cut algorithm with respect to active contour one. The implemented initialization method allows fully automatic segmentation leading to superior overall performances of graph-cut algorithm in terms of accuracy and processing time. The initialization method here presented resulted suitable and reliable for two different segmentation techniques and could be further extended.

Harmonic Ultrasound Imaging of Nanosized Contrast Agents for Multimodal Molecular Diagnoses

The aim of the present work was to demonstrate the possibility of selective detection of nanoparticle contrast agents (NPCAs) on diagnostic echographic images by exploiting the second harmonic component they introduce in the spectra of corresponding ultrasound signals, as a consequence of nonlinear distortion during ultrasound propagation. We employed silica nanospheres (SiNSs) of variable diameter (160 nm, 330 nm, and 660 nm) dispersed in different volume concentrations (range 0.07-0.8%) in agarose gel samples that were automatically scanned through a digital ecograph using narrow-band ultrasound pulses at 6.6 MHz and variable mechanical index (MI range 0.2-0.6). In the first part of the study, the intensity peaks of four different spectral components of the backscattered signal were considered: fundamental (detected in correspondence of the incident ultrasound frequency), subharmonic (detected at half of the fundamental frequency), ultra harmonic (detected at 1.5 times the fundamental frequency), and second harmonic (detected at twice the fundamental frequency). Subsequently, based on the experimental results of the first part of the study and on our recently reported findings, the focus was moved to a detailed comparison between subharmonic and second harmonic trend, which were determined as a function of nanoparticle composition, sample concentration, and MI. The experiments were also repeated on different agarose samples, containing SiNSs covered by an outer shell of smaller magnetic nanoparticles, made of either iron oxide (IO) or FePt-IO nanocrystals. Obtained results show that this new ultrasound-based method for NPCA imaging has a detection sensitivity similar to that of our previously introduced subharmonic-based technique in the presence of 330-nm SiNSs, but performs significantly better in the detection of both the types of “dual mode” NPCAs. The fact that the reported detection method was optimized for identification of 330-nm SiNSs (a sort of “ideal” size for the development of novel tumor-targeting NPCAs) and that the magnetically coated particles are detectable also through magnetic resonance imaging makes the presented second harmonic ultrasound method a valuable solution for the introduction of new protocols for multimodal molecular diagnoses employing only nonionizing radiations.

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 detectability of optoacoustic signals from low-concentration PEG-coated gold nanorods

Purpose: To evaluate the diagnostic performance of gold nanorod (GNR)-enhanced optoacoustic imaging employing a conventional echographic device and to determine the most effective operative configuration in order to assure optoacoustic effectiveness, nanoparticle stability, and imaging procedure safety. Methods: The most suitable laser parameters were experimentally determined in order to assure nanoparticle stability during the optoacoustic imaging procedures. The selected configuration was then applied to a novel tissue-mimicking phantom, in which GNR solutions covering a wide range of low concentrations (25–200 pM) and different sample volumes (50–200 μL) were exposed to pulsed laser irradiation. GNR-emitted optoacoustic signals were acquired either by a couple of single-element ultrasound probes or by an echographic transducer. Off-line analysis included: (a) quantitative evaluation of the relationships between GNR concentration, sample volume, phantom geometry, and amplitude of optoacoustic signals propagating along different directions; (b) echographic detection of “optoacoustic spots,” analyzing their intensity, spatial distribution, and clinical exploitability. MTT measurements performed on two different cell lines were also used to quantify biocompatibility of the synthesized GNRs in the adopted doses. Results: Laser irradiation at 30 mJ/cm2 for 20 seconds resulted in the best compromise among the requirements of effectiveness, safety, and nanoparticle stability. Amplitude of GNR-emitted optoacoustic pulses was proportional to both sample volume and concentration along each considered propagation direction for all the tested boundary conditions, providing an experimental confirmation of isotropic optoacoustic emission. Average intensity of echographically detected spots showed similar behavior, emphasizing the presence of an “ideal” GNR concentration (100 pM) that optimized optoacoustic effectiveness. The tested GNRs also exhibited high biocompatibility over the entire considered concentration range. Conclusion: An optimal configuration for GNR-enhanced optoacoustic imaging was experimentally determined, demonstrating in particular its feasibility with a conventional echographic device. The proposed approach can be easily extended to quantitative performance evaluation of different contrast agents for optoacoustic imaging.

A quantitative and automatic echographic method for real-time localization of endovascular devices

Current imaging methods for catheter position monitoring during minimally invasive surgery do not provide an effective support to surgeons, often resulting in the choice of more invasive procedures. This study was conducted to demonstrate the feasibility of non-ionizing monitoring of endovascular devices through embedded quantitative ultrasound (QUS) methods, providing catheter self-localization with respect to selected anatomical structures. QUS-based algorithms for real-time automatic tracking of device position were developed and validated on in vitro and ex vivo phantoms. A trans-esophageal ultrasound probe was adapted to simulate an endovascular device equipped with an intravascular ultrasound probe. B-mode images were acquired and processed in real time by means of a new algorithm for accurate measurement of device position. After off-line verification, automatic position calculation was found to be correct in 96% and 94% of computed frames in the in vitro and ex vivo phantoms, respectively. The average errors of distance measurements (bias ± 2SD) in a 41-step 10-cm-long parabolic pathway were 0.76 ± 3.75 mm or 0.52 ± 3.20 mm, depending on algorithm implementations. Our results showed the effectiveness of QUS-based tracking algorithms for real-time automatic calculation and display of endovascular system position. The method, validated for the case of an endoclamp balloon catheter, can be easily extended to most endovascular surgical systems.

Advanced spectral analyses for real-time automatic echographic tissue-typing of simulated tumor masses at different compression stages

Prototypal software algorithms for advanced spectral analysis of echographic images were developed to perform automatic detection of simulated tumor masses at two different pathological stages. Previously published works documented the possibility of characterizing macroscopic variation of mechanical properties of tissues through elastographic techniques, using different imaging modalities, including ultrasound (US); however, the accuracy of US-based elastography remains affected by the variable manual modality of the applied compression and several attempts are under investigation to overcome this limitation. Quantitative US (QUS), such as Fourier- and wavelet-based analyses of the RF signal associated with the US images, has been developed to perform a microscopic-scale tissue-type imaging offering new solutions for operator-independent examinations. Because materials able to reproduce the harmonic behavior of human liver can be realized, in this study, tissue-mimicking structures were US imaged and the related RF signals were analyzed using wavelet transform through an in-house-developed algorithm for tissue characterization. The classification performance and reliability of the procedure were evaluated on two different tumor stiffnesses (40 and 130 kPa) and with two different applied compression levels (0 and 3.5 N). Our results demonstrated that spectral components associated with different levels of tissue stiffness within the medium exist and can be mapped onto the original US images independently of the applied compressive forces. This wavelet-based analysis was able to identify different tissue stiffness with satisfactory average sensitivity and specificity: respectively, 72.01% ± 1.70% and 81.28% ± 2.02%.

Effectiveness of Functionalized Nanosystems for Multimodal Molecular Sensing and Imaging in Medicine

Successful employment of multimodal molecular imaging for cancer targeting entails the development of safe nanoparticle contrast agents (NPCAs), detects at least by two nonionizing imaging techniques. This paper presents a quantitative assessment of the effectiveness of both pure silica nanospheres (SiNSs) and composite silica/superparamagnetic NPCAs as scatterers for low-frequency diagnostic ultrasound (US) (3 MHz) in very low range of concentrations (1.5–5 mg/mL). Iron oxide (IO) and FePt-IO nanocrystals are employed for SiNS magnetic coating. Different samples of NPCA-containing agarose gel are US imaged through a commercially available system and acquired data are processed through a dedicated prototypal platform to extract image backscatter information and perform evaluation of the image gray level. The pure silica NPCAs confirms recent reports for higher concentrations at higher frequencies. The FePt-IO-coated NPCAs show similar behavior, although with lower values of image backscatter, with a marked effectiveness peak for 330-nm SiNSs, particularly useful for tumor targeting purposes. Finally, the IO-coated SiNSs presented a marked lowering of US enhancement potential and a peak efficiency for a particle diameter of 660 nm. The extent of US backscatter reduction is found to be a function of the number of magnetic nanoparticles per mL of NPCA-containing gel and decreased with increasing NPCA concentrations. These results broadened our knowledge of dual-mode molecular imaging of deep tumors, employing US, and magnetic resonance techniques for the accurate, safe and early detection of cancer cells located in internal organs.

Multiparametric Evaluation of the Acoustic Behavior of Halloysite Nanotubes for Medical Echographic Image Enhancement

Halloysite nanotubes (HNTs) are nanomaterials composed of double layered aluminosilicate minerals characterized by a wide range of medical applications. Nonetheless, systematic investigations of their imaging potential are still poorly documented. This paper shows a parametric assessment of the effectiveness of HNTs as scatterers for safe ultrasound (US)-based molecular imaging. Quantitative evaluation of average signal enhancement produced by HNTs with varying set up configuration was performed. The influence of different levels of power (20%, 50%, and 80%) of the signal emitted by clinical equipment was determined, to assess the efficacy of different HNT concentrations (1.5, 3, and 5 mg/mL) at conventional ultrasonic frequencies (5.7-7 MHz), even in case of specific limitation regarding US mechanical interaction with target tissues. Different samples of HNT containing agarose gel were imaged through a commercially available echographic system and acquired data were processed through a dedicated prototypal platform to extract the average ultrasonic signal amplitude. The rate of signal enhancement achieved by different concentration values was quantified and the contribution of frequency increment was separately evaluated. Despite influencing the level of mechanical excitation on HNTs and tissues, our results demonstrated how increasing the power of the emitted signal negatively affected the measured backscatter. Conversely, noticeable improvements in signal backscatter could be achieved incrementing HNT concentration and the echographic frequency employed; specifically the signal enhancement over the used concentration range could be improved by averagely 20%, corresponding to 4.86 ± 0.80 (a.u.), when employing the higher value of echographic frequency.

A new automatic phase mask filter for high-resolution brain venography at 3 T: theoretical background and experimental validation.

To improve vessel contrast in high-resolution susceptibility-based brain venography, an automatic phase contrast enhancing procedure is proposed, based on a new phase mask filter suitable for maximizing contrast of venous MR signals. The effectiveness of the new approach was assessed both on digital phantoms and on acquired MR human brain images, and then compared with venographic results of phase masking methods in recent literature. The digital phantom consisted of a simulated MR dataset with given signal-to-noise ratios (SNRs), while real human data were collected by scanning healthy volunteers with a 3.0-T MR system and a 3D gradient echo pulse sequence. The new phase mask (NM) was more effective than the conventional mask (CM) both on the digital phantoms and on the acquired MR images. A quantitative comparison based on phantom venograms indicates how this phase enhancement can lead to a significant increase in the contrast-to-noise ratio (CNR) for all considered phase values as well as for all vessel sizes of clinical interest. Likewise, the in vivo brain venograms reveal a better depiction of the smallest venous vessels and the enhancement of many details undetectable in conventional venograms.