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

Quantification of venous blood signal contribution to BOLD functional activation in the auditory cortex at 3 T

Most modern techniques for functional magnetic resonance imaging (fMRI) rely on blood-oxygen-level-dependent (BOLD) contrast as the basic principle for detecting neuronal activation. However, the measured BOLD effect depends on a transfer function related to neurophysiological changes accompanying electrical neural activation. The spatial accuracy and extension of the region of interest are determined by vascular effect, which introduces incertitude on real neuronal activation maps. Our efforts have been directed towards the development of a new methodology that is capable of combining morphological, vascular and functional information; obtaining new insight regarding foci of activation; and distinguishing the nature of activation on a pixel-by-pixel basis. Six healthy volunteers were studied in a parametric auditory functional experiment at 3 T; activation maps were overlaid on a high-resolution brain venography obtained through a novel technique. The BOLD signal intensities of vascular and nonvascular activated voxels were analyzed and compared: it was shown that nonvascular active voxels have lower values for signal peak (Pb10−7) and area (Pb10−8) with respect to vascular voxels. The analysis showed how venous blood influenced the measured BOLD signals, supplying a technique to filter possible venous artifacts that potentially can lead to misinterpretation of fMRI results. This methodology, although validated in the auditory cortex activation, maintains a general applicability to any cortical fMRI study, as the basic concepts on which it relies on are not limited to this cortical region. The results obtained in this study can represent the basis for new methodologies and tools that are capable of adding further characterization to the BOLD signal properties

A novel dual-frequency method for selective ultrasound imaging of targeted nanoparticles

Current methods for ultrasound (US) molecular imaging suffer the lack of image processing techniques specifically designed to identify the newer nanosized contrast agents (CAs). The available pulse sequences and signal analysis methods for US contrast detection, in fact, were developed for the older microbubble CAs, whose acoustic properties differ significantly from those of nanoparticles. This work illustrates the implementation and experimental testing of a new contrast detection scheme, tailored to enhance the contribution of solid nanosized CAs in echographic images. The proposed protocol, including a novel pulse sequence and a two-step image processing algorithm, was evaluated on a phantom consisting of silica nanospheres dispersed into an agarose gel matrix that was imaged through a conventional echographic transducer. Obtained results demonstrated the capability of selectively suppressing non-contrast echoes, without any loss in spatial resolution and maintaining the characteristics of real-time imaging, therefore showing very promising perspectives for clinical applications

Simulated Measurements of the Magnetic Behavior of New Dual-Mode Nanosized Contrast Agents

Aim of this work was to perform simulated measurements of the magnetic behavior of a novel class of bimodal nanosized contrast agents (CAs), made of a silica core covered by smaller superparamagnetic nanoparticles (NPs) and designed to be detected through both ultrasound and magnetic resonance imaging (MRI), in order to compare their performance in terms of MRI signal enhancement with that of the superparamagnetic NPs alone. The considered bimodal nanocomposites consisted of 330-nm silica nanospheres covered by either superparamagnetic iron oxide NPs or dumbbell-like FePt-IO nanocrystals. We simulated the MRI signal generated by each of the considered CAs during a brain venography in standard clinical conditions. Quantitative assessments of signal enhancement were carried out as a function of the main model parameters. The performed numerical simulations showed that the magnetic response of the novel nanocomposites was similar or better compared to that of the superparamagnetic NPs alone for echo times longer than 20 ms, leading to an easier detection of smaller vessels. Obtained results suggest that the bimodal NPs have an exciting potential for the development of innovative clinical protocols for multimodal imaging, combining quantitative measurements of cerebral blood flow and targeted molecular imaging of specific diseases

Experimental investigation and theoretical modelling of the nonlinear acoustical behaviour of a liver tissue and comparison with a tissue mimicking hydrogel

Native harmonics generated by nonlinear distortion of ultrasound during propagation in a medium may cause misinterpretations in spectral analysis when studying contrast agents. The aim of this paper is to quantitatively evaluate nonlinear propagation effects of diagnostic ultrasound pulses in biological tissues and to assess whether a cellulose-based hydrogel can be a suitable material for tissue mimicking purposes. Hydrogel and pig liver tissue samples of various thicknesses were insonified in a through-transmission set-up, employing 2.25-MHz pulses with different mechanical index (MI) values (range 0.06-0.60). Second harmonic and first harmonic amplitudes were extracted from spectra of received signals and their ratio was then used to compare hydrogel and liver behaviours. Resulting trends are very similar for sample thicknesses up to 8 cm and highlight a significant increase in nonlinearity for MI > 0.3, for both liver and hydrogel. A numerical procedure was also employed to calculate pressure distribution along the beam axis: these theoretical results showed a very good agreement with experimental data in the low pressure range, though failed in predicting the MI threshold. In conclusion, the hydrogel resulted to be a suitable material for manufacturing tissue mimicking phantoms, in particular to study contrast agent behaviour with a "low power approach

Gold Nanorod Coating Influence on Effectiveness and Safety in Photoacoustic Applications

Photoacoustic (PA) imaging is based on the detection of ultrasound signals emitted by physiological targets that underwent a pulsed laser irradiation. Gold nanoparticles are being currently studied by several research groups as potential molecular contrast agents for PA imaging. Aim of this paper was to test whether a highly biocompatible PEG (polyethylene glycol) coating can improve the stability of gold nanorods (GNRs) under laser irradiation and their effectiveness as contrast agents for PA imaging with respect to uncoated GNRs. Uncoated GNRs and PEG-coated GNRs were synthesized with the same size (48x7 nm) and very similar absorption spectra (main peak at 1055 nm). GNR stability was evaluated as a function of both laser fluence (range 40-100 mJ/cm2) and exposure duration (30-60 s), monitoring optical and morphological GNR changes. PA effectiveness was then tested using a custom-designed phantom which allowed laser irradiation of GNR solutions of variable concentration contained in a tissue-mimicking hydrogel and acquisition of the corresponding PA signals through a clinically-available ultrasound device. Obtained results showed that absorption spectrum of uncoated GNRs was significantly deteriorated after laser exposure already in the mildest adopted conditions (30-s exposure to 40-mJ/cm2 laser), while PEG-coated GNRs always resulted much more stable, with negligible peak intensity decrements in the mildest irradiation conditions. TEM analysis confirmed the higher morphological stability of PEG-coated GNRs, which also resulted more effective as PA contrast enhancers, since their PA signal intensity was always significantly higher than the corresponding value measured for uncoated GNRs

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

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