Or Perlman

Copper oxide nanoparticles as contrast agents for MRI and ultrasound dual-modality imaging

Multimodal medical imaging is gaining increased popularity in the clinic. This stems from the fact that data acquired from different physical phenomena may provide complementary information resulting in a more comprehensive picture of the pathological state. In this context, nano-sized contrast agents may augment the potential sensitivity of each imaging modality and allow targeted visualization of physiological points of interest (e.g. tumours). In this study, 7 nm copper oxide nanoparticles (CuO NPs) were synthesized and characterized. Then, in vitro and phantom specimens containing CuO NPs ranging from 2.4 to 320 μg · mL(-1) were scanned, using both 9.4 T MRI and through-transmission ultrasonic imaging. The results show that the CuO NPs induce shortening of the magnetic T1 relaxation time on the one hand, and increase the speed of sound and ultrasonic attenuation coefficient on the other. Moreover, these visible changes are NP concentration-dependent. The change in the physical properties resulted in a substantial increase in the contrast-to-noise ratio (3.4-6.8 in ultrasound and 1.2-19.3 in MRI). In conclusion, CuO NPs are excellent candidates for MRI-ultrasound dual imaging contrast agents. They offer radiation-free high spatial resolution scans by MRI, and cost-effective high temporal resolution scans by ultrasound.

Atrial Electrical Activity Detection Using Linear Combination of 12-Lead ECG Signals

ECG analysis is the method for cardiac arrhythmia diagnosis. During the diagnostic process many features should be taken into consideration, such as regularity and atrial activity. Since in some arrhythmias, the atrial electrical activity (AEA) waves are hidden in other waves, and a precise classification from surface ECG is inapplicable, a confirmation diagnosis is usually performed during an invasive procedure. In this paper, we study a “semiautomatic” method for AEA-waves detection using a linear combination of 12-lead ECG signals. This methods objective is to be applicable to a variety of arrhythmias with emphasis given to detect concealed AEA waves. It includes two variations--using maximum energy ratio and a synthetic AEA signal. In the former variation, an energy ratio-based cost function is created and maximized using the gradient ascent method. The latter variation adapted the linear combiner method, when applied on a synthetic signal, combined with surface ECG leads. A study was performed evaluating the AEA-waves detection from 63 patients (nine training, 54 validation) presenting eight arrhythmia types. Averaged sensitivity of 92.21% and averaged precision of 92.08% were achieved compared to the definite diagnosis. In conclusion, the presented method may lead to early and accurate detection of arrhythmias, which will result in a better oriented treatment.

Ultrasonic computed tomography imaging of iron oxide nanoparticles

Iron oxide nanoparticles (IONPs) are becoming increasingly used and intensively investigated in the field of medical imaging. They are currently FDA approved for magnetic resonance imaging (MRI), and it would be highly desirable to visualize them by ultrasound as well. Previous reports using the conventional ultrasound B-scan (pulse-echo) imaging technique have shown very limited detectability of these particles. The aim of this study is to explore the feasibility of imaging IONPs using the through-transmission ultrasound methodology and demonstrate their detectability using ultrasonic computed tomography (UCT). Commercially available IONPs were acoustically analysed to quantify their effect on the speed of sound (SOS) and acoustic attenuation as a function of concentration. Next, through-transmission projection and UCT imaging were performed on a breast mimicking phantom and on an ex vivo tissue model, to which IONPs were injected. Finally, an MRI scan was performed to verify that the same particles examined in the ultrasound experiment can be imaged by magnetic resonance, using the same clinically relevant concentrations. The results have shown a consistent concentration dependent speed of sound increase (1.86 [Formula: see text] rise per 100 µg · ml-1 IONPs). Imaging based on this property has shown a substantial contrast-to-noise ratio improvement (up to 5 fold, p  <  0.01). The SOS-related effect generated a well discernible image contrast and allowed the detection of the particles existence and location, in both raster-scan projection and UCT imaging. Conversely, no significant change in the acoustic attenuation coefficient was noted. Based on these findings, it is concluded that IONPs can be used as an effective SOS-based contrast agent, potentially useful for ultrasonic breast imaging. Furthermore, the particle offers the capacity of significantly enhancing diagnosis accuracy using multimodal MRI-ultrasound imaging capabilities.

Cardiac arrhythmia classification in 12-lead ECG using synthetic atrial activity signal

Analysis of the ECG signal is the prevalent method for diagnosing cardiac arrhythmia. In order to achieve a precise diagnosis, the physician must carefully examine the quantity, location, and relations between the ECG signal elements, with emphasis given to the atrial electrical activity (AEA) wave characteristics. Nevertheless, in some cases the AEA-waves are hidden in other waves, and in order to classify the correct arrhythmia an invasive procedure is performed. We propose a fully automated computer-based method for arrhythmia classification, based on our recently developed AEA detection algorithm, combined with two extracted rhythm-based features and a clinically oriented set of rules. Twenty-nine patients presenting atrioventricular nodal reentry tachycardia, atrioventricular reentry tachycardia, sinus tachycardia, atrial flutter, and sinus rhythm were studied. The arrhythmia classifier achieved 92.2% accuracy, 83.9% sensitivity, and 94.9% specificity.

Supraventricular Tachycardia Classification in the 12-Lead ECG Using Atrial Waves Detection and a Clinically Based Tree Scheme

Specific supraventricular tachycardia (SVT) classification using surface ECG is considered a challenging task, since the atrial electrical activity (AEA) waves, which are a crucial element for obtaining diagnosis, are frequently hidden. In this paper, we present a fully automated SVT classification method that embeds our recently developed hidden AEA detector in a clinically based tree scheme. The process begins with initial noise removal and QRS detection. Then, ventricular features are extracted. According to these features, an initial AEA-wave search window is defined and a single AEA-wave is detected. Using a synthetic Gaussian signal and a linear combination of 12-lead ECG signals, all AEA-waves are detected. In accord with the atrial and ventricular information found, classification to atrial fibrillation, atrial flutter, atrioventricular nodal reentry tachycardia, atrioventricular reentry tachycardia, or sinus rhythm is performed in the framework of a clinically oriented decision tree. A study was performed to evaluate the classification from 68 patients (26 were used for the classifiers design, 42 were used for its validation). Average sensitivity of 83.21% [95% confidence interval (CI): 79.33-86.49%], average specificity of 95.80% (95% CI: 94.73-96.67%), and average accuracy of 93.29% (95% CI: 92.13-94.28%) were achieved compared to the definite diagnosis. In conclusion, the presented method may serve as a valuable decision support tool, allowing accurate detection of SVTs using noninvasive means.

MRI and Ultrasound Imaging of Nanoparticles for Medical Diagnosis

Magnetic resonance imaging (MRI) and ultrasound (US) are two prominent medical imaging modalities. They are extensively and routinely used in various medical fields, such as cardiology, embryology, neurology, and oncology. In this chapter we describe the application of nanoparticles for MRI and US image enhancement. Moreover, the utilization of nano-scaled compounds for multimodal MRI-US imaging, allowing further increase of diagnosis certainty, is depicted.

Copper oxide loaded PLGA nanospheres: towards a multifunctional nanoscale platform for ultrasound-based imaging and therapy

Copper oxide nanoparticles (CuO-NPs) are increasingly becoming the subject of investigation exploring their potential use for diagnostic and therapeutic purposes. Recent work has demonstrated their anticancer potential, as well as contrast agent capabilities for magnetic resonance imaging (MRI) and through-transmission ultrasound. However, no capability of CuO-NPs has been demonstrated using conventional ultrasound systems, which, unlike the former, are widely deployed in the clinic. Furthermore, in spite of their potential as multifunctional nano-based materials for diagnosis and therapy, CuO-NPs have been delayed from further clinical application due to their inherent toxicity. Herein, we present the synthesis of a novel nanoscale system, composed of CuO-loaded PLGA nanospheres (CuO-PLGA-NS), and demonstrate its imaging detectability and augmented heating effect by therapeutic ultrasound. The CuO-PLGA-NS were prepared by a double emulsion (W/O/W) method with subsequent solvent evaporation. They were characterized as sphere-shaped, with size approximately 200 nm. Preliminary results showed that the viability of PANC-1, human pancreatic adenocarcinoma cells was not affected after 72 h exposure to CuO-PLGA-NS, implying that PLGA masks the toxic effects of CuO-NPs. A systematic ultrasound imaging evaluation of CuO-PLGA-NS, using a conventional system, was performed in vitro and ex vivo using poultry heart and liver, and also in vivo using mice, all yielding a significant contrast enhancement. In contrast to CuO-PLGA-NS, neither bare CuO-NPs nor blank PLGA-NS possess these unique advantageous ultrasonic properties. Furthermore, CuO-PLGA-NS accelerated ultrasound-induced temperature elevation by more than 4 °C within 2 min. The heating efficiency (cumulative equivalent minutes at 43 °C) was increased approximately six-fold, demonstrating the potential for improved ultrasound ablation. In conclusion, CuO-PLGA-NS constitute a versatile platform, potentially useful for combined imaging and therapeutic ultrasound-based procedures.

Target visualisation and microwave hyperthermia monitoring using nanoparticle-enhanced transmission ultrasound (NETUS)

Abstract Purpose: The aim of this study was to examine the feasibility of using nanoparticle-enhanced transmission ultrasound (NETUS) as an image-based monitoring modality for microwave hyperthermia treatment. Methods: A dedicated transmission ultrasound imaging system was used to obtain acoustic projections and ultrasound computed tomography images. Initially, speed-of-sound based images were used to non-invasively monitor temperature changes in in vitro and ex vivo specimens, induced by a microwave needle-type applicator. Next, the hyperthermia acceleration ability of two ultrasound nanoparticles based contrast agents (iron oxide and copper oxide) was examined and visualised. Finally, a two-step image guided microwave therapeutic procedure using NETUS was investigated in a realistic breast mimicking phantom. First, the pathology simulating region borders were detected. Then, a microwave-induced temperature elevation was non-invasively monitored. Results: The transmission ultrasound scanning system was able to detect temperature changes with a resolution of less than 0.5 °C, both in vitro and ex vivo. In accordance with previous studies, it was visually demonstrated that iron oxide nanoparticles expedite the heating process (p < 0.05). Copper oxide nanoparticles, however, did not alter the hyperthermia profile significantly. In the breast mimicking phantom, NETUS yielded accurate detection of the target region as well as thermal monitoring of the microwave heating procedure. Conclusions: NETUS can combine enhanced target visualisation with non-invasive thermometry and accelerated heating effect. Quantitative feedback, however, requires a tissue-specific calibration-curve. A proof of concept for microwave hyperthermia treatment monitoring using NETUS was established. The suggested methodology may potentially provide a non-invasive cost-effective means for monitoring thermal treatment of the breast.

Preliminary study of copper oxide nanoparticles acoustic and magnetic properties for medical imaging

The implementation of multimodal imaging in medicine is highly beneficial as different physical properties may provide complementary information, augmented detection ability, and diagnosis verification. Nanoparticles have been recently used as contrast agents for various imaging modalities. Their significant advantage over conventional large-scale contrast agents is the ability of detection at early stages of the disease, being less prone to obstacles on their path to the target region, and possible conjunction to therapeutics. Copper ions play essential role in human health. They are used as a cofactor for multiple key enzymes involved in various fundamental biochemistry processes. Extremely small size copper oxide nanoparticles (CuO-NPs) are readily soluble in water with high colloidal stability yielding high bioavailability. The goal of this study was to examine the magnetic and acoustic characteristics of CuO-NPs in order to evaluate their potential to serve as contrast imaging agent for both MRI and ultrasound. CuO-NPs 7nm in diameter were synthesized by hot solution method. The particles were scanned using a 9.4T MRI and demonstrated a concentration dependent T1 relaxation time shortening phenomenon. In addition, it was revealed that CuO-NPs can be detected using the ultrasonic B-scan imaging. Finally, speed of sound based ultrasonic computed tomography was applied and showed that CuO-NPs can be clearly imaged. In conclusion, the preliminary results obtained, positively indicate that CuO-NPs may be imaged by both MRI and ultrasound. The results motivate additional in-vivo studies, in which the clinical utility of fused images derived from both modalities for diagnosis improvement will be studied.