Wave Intensity Analysis (WIA) can provide parameters representative of the interaction between the vascular network
and the heart. It has been already demonstrated that WIA-derived biomarkes have a quantitative physiological meaning.
Aim of this study was to develop an image process algorithm for performing non-invasive WIA in mice and correlate
commonly used cardiac function parameters with WIA-derived indexes.
Sixteen wild-type male mice (8 weeks-old) were imaged with high-resolution ultrasound (Vevo 2100). Abdominal aorta
and common carotid pulse wave velocities (PWVabd, PWVcar) were obtained processing B-Mode and PW-Doppler
images and employed to assess WIA. Amplitudes of the first (W1abd, W1car) and the second (W2abd, W2car) local maxima
and minimum (Wbabd,Wbcar) were evaluated; areas under the negative part of the curve were also calculated (NAabd,
NAcar). Cardiac output (CO), ejection fraction (EF) fractional shortening (FS) and stroke volume (SV) were estimated;
strain analysis provided strain and strain rate values for longitudinal, radial and circumferential directions (LS, LSR, RS,
RSR, CS, CSR). Isovolumetric relaxation time (IVRT) was calculated from mitral inflow PW-Doppler images; IVRT
values were normalized for cardiac cycle length.
W1abd was correlated with LS (R=0.65) and LSR (R=0.59), while W1car was correlated with CO (R=0.58), EF (R=0.72),
LS (R=0.65), LSR (R=0.89), CS (R=0.71), CSR (R=0.70). Both W2abd and W2car were not correlated with IVRT.
Carotid artery WIA-derived parameters are more representative of cardiac function than those obtained from the
abdominal aorta. The described US-based method can provide information about cardiac function and cardio-vascular
interaction simply studying a single vascular site.
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.
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.
KEYWORDS: Spleen, Gold, Absorption, Photoacoustic spectroscopy, Nanoparticles, In vivo imaging, Photoacoustic imaging, Plasmons, Real time imaging, Nanorods
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.
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.
Pulse wave velocity (PWV) is considered a surrogate marker of arterial stiffness and could be useful for characterizing cardiovascular disease progression even in mouse models. Aim of this study was to develop an image process algorithm for assessing arterial PWV in mice using ultrasound (US) images only and test it on the evaluation of age-associated differences in abdominal aorta PWV (aaPWV). US scans were obtained from six adult (7 months) and six old (19 months) wild type male mice (strain C57BL6) under gaseous anaesthesia. For each mouse, diameter and flow velocity instantaneous values were achieved from abdominal aorta B-mode and PW-Doppler images; all measurements were obtained using edge detection and contour tracking techniques. Single-beat mean diameter and velocity were calculated and time-aligned, providing the lnD-V loop. aaPWV values were obtained from the slope of the linear part of the loop (the early systolic phase), while relative distension (relD) measurements were calculated from the mean diameter signal. aaPWV values for young mice (3.5±0.52 m/s) were lower than those obtained for older ones (5.12±0.98 m/s) while relD measurements were higher in young (25%±7%) compared with older animals evaluations (15%±3%). All measurements were significantly different between the two groups (P<0.01 both). In conclusion, the proposed image processing technique well discriminate between age groups. Since it provides PWV assessment just from US images, it could represent a simply and useful system for vascular stiffness evaluation at any arterial site in the mouse, even in preclinical small animal models.
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