Correction of MHS Viscosimetric Constants upon Numerical Simulation of Temperature Induced Degradation Kinetic of Chitosan Solutions.

The Mark⁻Houwink⁻Sakurada (MHS) equation allows for estimation of rheological properties, if the molecular weight is known along with good understanding of the polymer conformation. The intrinsic viscosity of a polymer solution is related to the polymer molecular weight according to the MHS equation, where the value of the constants is related to the specific solvent and its concentration. However, MHS constants do not account for other characteristics of the polymeric solutions, i.e., Deacetilation Degree (DD) when the solute is chitosan. In this paper, the degradation of chitosan in different acidic environments by thermal treatment is addressed. In particular, two different solutions are investigated (used as solvent acetic or hydrochloric acid) with different concentrations used for the preparation of chitosan solutions. The samples were treated at different temperatures (4, 30, and 80 °C) and time points (3, 6 and 24 h). Rheological, Gel Permeation Chromatography (GPC), Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC) and Thermal Gravimetric Analyses (TGA) were performed in order to assess the degradation rate of the polymer backbones. Measured values of molecular weight have been integrated in the simulation of the batch degradation of chitosan solutions for evaluating MHS coefficients to be compared with their corresponding experimental values. Evaluating the relationship between the different parameters used in the preparation of chitosan solutions (e.g., temperature, time, acid type and concentration), and their contribution to the degradation of chitosan backbone, it is important to have a mathematical frame that could account for phenomena involved in polymer degradation that go beyond the solvent-solute combination. Therefore, the goal of the present work is to propose an integration of MHS coefficients for chitosan solutions that contemplate a deacetylation degree for chitosan systems or a more general substitution degree for polymers in which viscosity depends not only on molecular weight and solvent combinations.

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.

Flow pattern analysis in a highly stenotic patient-specific carotid bifurcation model using a turbulence model.

The aim of this study is to investigate the blood flow pattern in carotid bifurcation with a high degree of luminal stenosis, combining in vivo magnetic resonance imaging (MRI) and computational fluid dynamics (CFD). A newly developed two-equation transitional model was employed to evaluate wall shear stress (WSS) distribution and pressure drop across the stenosis, which are closely related to plaque vulnerability. A patient with an 80% left carotid stenosis was imaged using high resolution MRI, from which a patient-specific geometry was reconstructed and flow boundary conditions were acquired for CFD simulation. A transitional model was implemented to investigate the flow velocity and WSS distribution in the patient-specific model. The peak time-averaged WSS value of approximately 73 Pa was predicted by the transitional flow model, and the regions of high WSS occurred at the throat of the stenosis. High oscillatory shear index values up to 0.50 were present in a helical flow pattern from the outer wall of the internal carotid artery immediately after the throat. This study shows the potential suitability of a transitional turbulent flow model in capturing the flow phenomena in severely stenosed carotid arteries using patient-specific MRI data and provides the basis for further investigation of the links between haemodynamic variables and plaque vulnerability. It may be useful in the future for risk assessment of patients with carotid disease.

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.

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%.

Progress in atherosclerotic plaque imaging.

Cardiovascular diseases are the primary cause of mortality in the industrialized world, and arterial obstruction, triggered by rupture-prone atherosclerotic plaques, lead to myocardial infarction and cerebral stroke. Vulnerable plaques do not necessarily occur with flow-limiting stenosis, thus conventional luminographic assessment of the pathology fails to identify unstable lesions. In this review we discuss the currently available imaging modalities used to investigate morphological features and biological characteristics of the atherosclerotic plaque. The different imaging modalities such as ultrasound, magnetic resonance imaging, computed tomography, nuclear imaging and their intravascular applications are illustrated, highlighting their specific diagnostic potential. Clinically available and upcoming methodologies are also reviewed along with the related challenges in their clinical translation, concerning the specific invasiveness, accuracy and cost-effectiveness of these methods.

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/cm(2) 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.