Nicole Di Lascio

Organosilicon phantom for photoacoustic imaging

Abstract. Photoacoustic imaging is an emerging technique. Although commercially available photoacoustic imaging systems currently exist, the technology is still in its infancy. Therefore, the design of stable phantoms is essential to achieve semiquantitative evaluation of the performance of a photoacoustic system and can help optimize the properties of contrast agents. We designed and developed a polydimethylsiloxane (PDMS) phantom with exceptionally fine geometry; the phantom was tested using photoacoustic experiments loaded with the standard indocyanine green dye and compared to an agar phantom pattern through polyethylene glycol-gold nanorods. The linearity of the photoacoustic signal with the nanoparticle number was assessed. The signal-to-noise ratio and contrast were employed as image quality parameters, and enhancements of up to 50 and up to 300%, respectively, were measured with the PDMS phantom with respect to the agar one. A tissue-mimicking (TM)-PDMS was prepared by adding TiO2 and India ink; photoacoustic tests were performed in order to compare the signal generated by the TM-PDMS and the biological tissue. The PDMS phantom can become a particularly promising tool in the field of photoacoustics for the evaluation of the performance of a PA system and as a model of the structure of vascularized soft tissues.

Carotid-Ventricular Coupling During Exercise A Pilot Study

To evaluate carotid elasticity and left ventricular elastance during a graded bicycle semisupine exercise test in patients with known or suspected coronary artery disease and compare them with a control group of healthy young volunteers.

Noninvasive Assessment of Carotid Pulse Pressure Values: An Accelerometric-Based Approach

Objective: Central pulse pressure (cPP) is increasingly investigated as possible independent predictor of cardiovascular risk and carotid pulse pressure (carPP) can be used as a surrogate of cPP. Despite its importance, carPP measurement remains challenging in clinical practice. The aim of this study was to introduce a new easier-to-use method for noninvasive carPP evaluation based on the use of a MEMS accelerometer. Methods: carPP values (carPP_acc) were obtained in 22 subjects (10 males, 47 ± 17 years, hypertension: 50%) postprocessing and double integrating the accelerometric signals. carPP_acc measurements were compared with tonometric assessments (carPP_ton), and ultrasound-derived measurements (carPP_US). Moreover, accelerometric carotid pressure waveforms (P_acc) were contrasted in terms of shape to those obtained by tonometry (P_ton) and ultrasound images elaboration (P_US), calculating the root mean square error (RMSE_ton, RMSE_US) and the regression coefficients (r_ton and r_US). Moreover, both the repeatability and reproducibility analyses were performed. Results: carPP_acc values (45.9 ± 10.6 mmHg) were significantly correlated with carPP_ton (47.5 ± 11.3 mmHg) and carPP_US (43.3 ± 8.4 mmHg) assessments (R = 0.94, p <; 0.0001 and R = 0.80, p <; 0.0001, respectively). The validity of the accelerometric approach was confirmed by morphological parameters (RMSE_ton = 5 ± 1.95 mmHg, RMSE_US = 5.5 ± 2.3 mmHg, r_ton = 0.94 ± 0.04, r_US = 0.93 ± 0.04). Coefficient of variation (CV) was equal to 6.2% for the repeatability analysis, while CV values for interoperator and intersession reproducibilities were 8.9% and 9.4%, respectively. Conclusion: The proposed approach, providing an easier and more available measurement, could represent a valid alternative to existing and used technique for carPP assessment.

Phantom studies with gold nanorods as contrast agents for photoacoustic imaging: novel and old approaches

Photoacoustic imaging is emerging as a bioimaging technique. The development of contrast agents extend the potential towards novel application. The design of stable phantoms is needed to achieve a semi-quantitative evaluation of the performance of contrast agents. The aim of this study was to investigate the PA signal generated from gold nanorods (GNRs) loaded in custom made phantoms. VevoLAZR (VisualSonics Inc., Toronto) was used with custom made agar phantom, with 5 parallel polyethylene tubes (with 0.58mm internal and 0.99mm external diameter), and a PDMS phantom, with six parallel channels with sizes from 50 μm to 500 μm, loaded with two different types of GNRs: PEGGNRs (53nm length and 11nm axial diameter, plasmon resonance at 840nm, 87nM (15mM Au equivalent)); and gold nanorods (NPZ) coated in a dense layer of hydrophilic polymers by Nanopartz Inc., Loveland, CO (41nm length and 10nm axial diameter, plasmon resonance at 808nm, 83 nM (14mM Au equivalent)). The absorption spectra acquired with the PA system and the spectrophotometer were compared. The reproducibility and stability of the PA signal were evaluated at different dilutions. The dynamic variation of the PA signal was evaluated as function of the number of the GNRs. The SNR and the contrast were measured across the range of concentrations studied. The custom made agar phantom demonstrated suitable for the characterization of PA contrast agents such as PEG-GNRs and NPZ. The PDMS phantom is promising in the field of photoacoustics, therefore future works will conducted exploiting its precise and controlled geometry.

Digital liver biopsy: Bio-imaging of fatty liver for translational and clinical research

The rapidly growing field of functional, molecular and structural bio-imaging is providing an extraordinary new opportunity to overcome the limits of invasive liver biopsy and introduce a “digital biopsy” for in vivo study of liver pathophysiology. To foster the application of bio-imaging in clinical and translational research, there is a need to standardize the methods of both acquisition and the storage of the bio-images of the liver. It can be hoped that the combination of digital, liquid and histologic liver biopsies will provide an innovative synergistic tri-dimensional approach to identifying new aetiologies, diagnostic and prognostic biomarkers and therapeutic targets for the optimization of personalized therapy of liver diseases and liver cancer. A group of experts of different disciplines (Special Interest Group for Personalized Hepatology of the Italian Association for the Study of the Liver, Institute for Biostructures and Bio-imaging of the National Research Council and Bio-banking and Biomolecular Resources Research Infrastructure) discussed criteria, methods and guidelines for facilitating the requisite application of data collection. This manuscript provides a multi-Author review of the issue with special focus on fatty liver.

Steato-Score: Non-Invasive Quantitative Assessment of Liver Fat by Ultrasound Imaging

Non-alcoholic fatty liver disease is becoming a global epidemic. The aim of this study was to develop a system for assessing liver fat content based on ultrasound images. Magnetic resonance spectroscopy measurements were obtained in 61 patients and the controlled attenuation parameter in 54. Ultrasound images were acquired for all 115 participants and used to calculate the hepatic/renal ratio, hepatic/portal vein ratio, attenuation rate, diaphragm visualization and portal vein wall visualization. The Steato-score was obtained by combining these five parameters. Magnetic resonance spectroscopy measurements were significantly correlated with hepatic/renal ratio, hepatic/portal vein ratio, attenuation rate, diaphragm visualization and portal vein wall visualization; Steato-score was dependent on hepatic/renal ratio, attenuation rate and diaphragm visualization. Area under the receiver operating characteristic curve was equal to 0.98, with 89% sensitivity and 94% specificity. Controlled attenuation parameter values were significantly correlated with hepatic/renal ratio, attenuation rate, diaphragm visualization and Steato-score; the area under the curve was 0.79. This system could be a valid alternative as a non-invasive, simple and inexpensive assessment of intrahepatic fat.

Novel organosilicon phantoms as testing material for photoacoustic imaging

The contrast in photoacoustic (PA) imaging depends on the mechanical and elastic properties of the tissue, as well as on his optical absorption and scatter properties. Thanks to these futures, this novel modality could offer additional specificity compared to conventional ultrasound techniques, being able to reveal the signal of absorbing materials and chomophores, e.g. endogenous molecules like haemoglobin or specific near infrared dyes or plasmonic contrast agents. The development of semi-quantitative protocols for the assessment of the contrast enhancement, is one of the key aspect of the ongoing research, that could open new routes to the use of PA imaging for a variety of applications in preclinical research of cancer and cardiovascular diseases. In this work, we designed and tested a tissue mimicking polydimethylsiloxane (PDMS) phantom for photoacoustic applications, with tailored biomechanical/optical and geometrical properties. In order to modulate the light fluence and penetration, that remains one of the major challenge for this technique, we added titanium dioxide and black ink, rendering the optical absorption and scattering coefficients similar to those of biological tissues. The PDMS phantom can become a particularly promising tool in the field of photoacoustics for the evaluation of the performance of a PA system and as a model of the structure of vascularized soft tissues.

Pattern of distribution and kinetics of accumulation of gold nanorods in mouse spleen

Gold nanorods (GNRs) offer a tunable optical absorption in the near infra-red wavelength region due to their plasmon resonance, which results in strong photoacoustic (PA) signal and make them suitable as contrast agent by means of PA imaging. The aim of this study was to examine the performance of synthesized polyethilene glicol (PEG)-GNRs as contrast agent for in vivo PA imaging and to evaluate their accumulation and distribution real time. Two-three month old FVB female mice were enrolled for the study, a bolus of 200μL of synthesized PEG-GNRs (53 nm length and 11 nm axial diameter, plasmon resonance at 840 nm, 1 mM Au concentration) solution was injected intravenously and detected with PA imaging. The accumulation of GNRs in the spleen was studied by means of the amplitude dynamic variation of the PA signal during time. GNRs contrast was clearly distinguished from endogenous background thanks to the nanoparticle spectroscopic specificity. Our results suggest that PA imaging could allow an efficient and noninvasive tool for in vivo detection of GNRs content and for the assessment of the kinetic parameters in target organs. The coregistration of μ-ultrasound and PA imaging is crucial for the real time evaluation of the GNRs distribution in different organs.

Effects of carotid pressure waveforms on the results of wave separation, wave intensity and reservoir pressure analysis

OBJECTIVE Recently great attention has been paid to innovative cardiovascular biomarkers obtained from wave separation (WS), wave intensity (WI) and reservoir-wave (RW) theories. All these approaches share a requirement for pressure information. The aim of this study was to evaluate differences in WS-, WI- and RW-derived parameters obtained achieving pressure waveforms in different ways. APPROACH Twenty-two individuals (49  ±  17 years, 59% males) were examined. Common carotid blood flow waveforms were obtained from pulsed-wave Doppler images. Carotid pressure waveforms were achieved in four different ways: (1) with applanation tonometry, used as a reference method; (2) linear scaling from an ultrasound (US)-derived diameter curve; (3) exponential scaling from a US-derived diameter curve; and (4) linear scaling from an accelerometric-derived diameter signal. For each case, the reflection magnitude (RM) and index (RI) were obtained from the WS. The amplitude of the first positive peak (W 1), of the second positive peak (W 2) and of the negative peak (W b) were calculated from the WI, while the maximum of the reservoir (maxPr) and the excess (maxPex) pressure were achieved from the RW. MAIN RESULTS According to the intra-class coefficient values, the agreement between the standard method and all the others was excellent for the RM (linear: 0.82; exponential: 0.83; accelerometric: 0.86), RI (linear: 0.84; exponential: 0.85; accelerometric: 0.87), maxPr (linear: 0.97; exponential: 0.96; accelerometric: 0.97) and maxPex (linear: 0.85; exponential: 0.87; accelerometric: 0.89), while only a fair/good level was reached for W 1 (linear: 0.67; exponential: 0.77; accelerometric: 0.52), W 2 (linear: 0.52; exponential: 0.69; accelerometric: 0.83) and W b (linear: 0.60; exponential: 0.44; accelerometric: 0.50). SIGNIFICANCE Measuring carotid pressure waveforms with different approaches does not influence the cardiovascular parameters obtained by WS and RW; those derived by WI are affected by the carotid pressure curve employed.

Acute Cardiovascular Adaptation to Strenuous Exercise: An Integrative Ultrasound Study: Acute Cardiovascular Adaptation to Strenuous Exercise

The aim of this study was to evaluate the acute effects of participation in an Ironman distance triathlon competition on arterial function by ultrasound, in relation to cardiac function and body water content.