Ton van der Steen

Intravascular photoacoustic imaging of human coronary atherosclerosis.

We demonstrate intravascular photoacoustic imaging of human coronary atherosclerotic plaque. The data was obtained from two fresh human coronary arteries ex vivo, showing different stages of disease. A 1.25 mm diameter intravascular imaging catheter was built, comprising an angle-polished optical fiber adjacent to a 30 MHz ultrasound transducer. Specific photoacoustic imaging of lipid content, a key factor in vulnerable plaques that may lead to myocardial infarction, is achieved by spectroscopic imaging at different wavelengths between 1180 and 1230 nm. Simultaneous imaging with intravascular ultrasound was performed.

Plaque and shear stress distribution in human coronary bifurcations: a multislice computed tomography study

AIMS Early atherosclerosis is located in low wall shear-stress (WSS) regions, however plaques are also found in the high WSS sensing flow divider walls of coronary bifurcations. We assessed the plaque distribution and morphology near bifurcations non-invasively with 64-slice computed tomography in relation to the WSS distribution. METHODS AND RESULTS We inspected 65 cross-sections near coronary bifurcations for the presence of plaque. Cross-sections were divided into four equal parts, which we numbered according to expected levels of WSS, with part I the lowest WSS (outer wall) and increasing WSSs in part II (inner bend), III (outer bend) and IV (flow divider). Of the cross-sections 88% had plaque. Of all parts I, 72% contained plaque. This was 62%, 38% and 31% in parts II, III and IV. In cross-sections with only 1 or 2 parts inflicted, plaque was found in part I and/or II in 94%. In 93% of the cross-sections with the flow divider inflicted, parts I and/or II were also inflicted. Plaque was never found exclusively in the flow divider part IV. CONCLUSIONS We demonstrated that plaque is mostly present in low WSS regions, whereas plaque in high WSS regions is accompanied by plaque in adjacent low WSS regions. It is therefore plausible that plaque grows from the outer wall (low WSS) of the bifurcation towards the flow divider (high WSS).

First use in patients of a combined near infra-red spectroscopy and intra-vascular ultrasound catheter to identify composition and structure of coronary plaque

A 70 year-old diabetic female with a history of hyperlipidaemia treated with statin therapy underwent coronary angioplasty of her right coronary artery (RCA, Figure 1). Post-procedure the RCA was assessed using, for the first time, a combination intravascular ultrasound (IVUS) and near infrared spectroscopy (NIRS) catheter, which indicated that the proximal end of the stent was located in an area of lipid core plaque (Figure 2 and Video 1); a potential risk factor for stent thrombosis.1 Prospective studies are needed to assess the risk of ending a stent in a fibroatheroma, and to investigate the use of NIRS-IVUS to determine the optimal landing zone for a stent. In this manner, the co-localization of lipid core with structure may provide useful information that will enhance the safety of stenting and, with prospective studies, increase the ability to correctly identify plaque at risk of rupture.

In vivo findings of tissue characteristics using iMap™ IVUS and virtual histology™ IVUS

1017 Description Intravascular ultrasound (IVUS) with radiofrequency data analysis is a novel technology which allows identification of atherosclerotic plaque components. Todays, tissue characterisation can be achieved using two different IVUS systems: Virtual HistologyTM IVUS (VH, 20 MHz, phased-array transducer, 2.9 F Eagle EyeTM Gold, Volcano Therapeutics, Rancho Cordova, CA, USA), and iMapTM IVUS (iMap, 40 MHz, mechanical-type transducer, 3.2 F Atlantis, Boston Scientific Corporation, Natick, MA, USA). These two methodological approaches so far had not been compared in vivo. The purpose of this paper is to compare overall in vivo findings between these two IVUS radiofrequency based tissue characterisation systems.

Targeted microbubble mediated sonoporation of endothelial cells in vivo

Ultrasound contrast agents as drug-delivery systems are an emerging field. Recently, we reported that targeted microbubbles are able to sonoporate endothelial cells in vitro. In this study, we investigated whether targeted microbubbles can also induce sonoporation of endothelial cells in vivo, thereby making it possible to combine molecular imaging and drug delivery. Live chicken embryos were chosen as the in vivo model. αvß3-targeted microbubbles attached to the vessel wall of the chicken embryo were insonified at 1 MHz at 150 kPa (1 × 10 000 cycles) and at 200 kPa (1 × 1000 cycles) peak negative acoustic pressure. Sonoporation was studied by intravital microscopy using the model drug propidium iodide (PI). Endothelial cell PI uptake was observed in 48% of microbubble-vessel-wall complexes at 150 kPa (n = 140) and in 33% at 200 kPa (n = 140). Efficiency of PI uptake depended on the local targeted microbubble concentration and increased up to 80% for clusters of 10 to 16 targeted microbubbles. Ultrasound or targeted microbubbles alone did not induce PI uptake. This intravital microscopy study reveals that sonoporation can be visualized and induced in vivo using targeted microbubbles.

State of the art in ICUS quantitation

IntraCoronary UltraSound (ICUS) data are the basis of two-dimensional (2D) quantitative information and three-dimensional (3D) reconstruction. A method for semi-automatic 3D image quantification for volumetric study of series of echo slices has been developed. The semi-automatic contour detection method was tested in-vitro in tubular phantoms of known dimensions. Intra- and interobserver variability was evaluated in-vivo for area and volume measurements of diseased human coronary arteries.

Emerging technology update: Intravascular photoacoustic imaging of vulnerable atherosclerotic plaque

The identification of vulnerable atherosclerotic plaques in the coronary arteries is emerging as an important tool for guiding atherosclerosis diagnosis and interventions. Assessment of plaque vulnerability requires knowledge of both the structure and composition of the plaque. Intravascular photoacoustic (IVPA) imaging is able to show the morphology and composition of atherosclerotic plaque. With imminent improvements in IVPA imaging, it is becoming possible to assess human coronary artery disease in vivo. Although some challenges remain, IVPA imaging is on its way to being a powerful tool for visualising coronary atherosclerotic features that have been specifically associated with plaque vulnerability and clinical syndromes, and thus such imaging might become valuable for clinical risk assessment in the catheterisation laboratory.

Automated characterisation of lipid core plaques in vivo by quantitative optical coherence tomography tissue type imaging

AIMS Qualitative criteria for plaque tissue characterisation by OCT are well established, but quantitative methods lack systematic validation in vivo. High optical attenuation coefficient µt has been associated with unstable plaque features, such as lipid core. The purpose of this study was to validate optical coherence tomography (OCT) attenuation imaging for tissue characterisation in vivo, specifically to detect lipid core in coronary atherosclerotic plaques, and to evaluate quantitatively the ability of OCT attenuation imaging to differentiate thin-cap (TCFA) and thick-cap fibroatheroma (FA). METHODS AND RESULTS We prospectively enrolled 85 patients undergoing imaging of a native coronary segment by both OCT and near-infrared spectroscopy and intravascular ultrasound (NIRS-IVUS). Ninety-eight NIRS-positive 4 mm plaque segments were selected and matched to the OCT data. Two experienced OCT readers classified the plaque type using OCT criteria. A cap thickness of 65 μm was used to differentiate TCFA and FA. We computed an index of plaque attenuation (IPA) in the 4 mm blocks, and assessed the association of this index with plaque type. IPA differentiated between TCFA and FA (AUC=0.82 in ROC analysis; p<0.0001). LCBI was numerically, but not significantly, higher in TCFA compared to FA (p=0.097). CONCLUSIONS IPA is an unbiased reproducible measure of tissue optical properties. The fraction of pixels with attenuation coefficient ≥11 mm-1 can identify TCFA.

Liposome shedding from a vibrating microbubble on nanoseconds timescale

When ultrasound contrast agents microbubbles (MBs) are preloaded with liposomes, they can be applied as a potential drug delivery vehicle. The fate of the liposomes under ultrasound excitations is of prime interest for investigations, since it is an essential step in the application of drug delivery. Previous studies on regular lipid-shelled MBs have shown lipid shedding phenomena, accompanied by MB shrinkage under ultrasound excitations. Here we present a multi-modal study to optically characterize shedding behavior of liposome-loaded MBs (lps-MBs) based on high-speed fluorescence imaging. First, the dynamics of shedding were resolved by the Brandaris camera operating at up to 2 million frames per second (Mfps). Shedding of shell material was observed after few cycles of the excitation pulse. Second, a parametric study using a Photron camera running at 75 kfps indicates a significant influence of MB resonance on the shedding behavior. Third, the shedding behavior was investigated as a function of the MB oscillatory dynamics, facilitated by combination of the two fast cameras. We found a threshold of the relative amplitude of oscillations (35%) for the onset of lipids shedding. Overall, the shedding behavior from lps-MBs could well be controlled by the excitation pulse.

A single-cable PVDF transducer readout IC for intravascular photoacoustic imaging

This paper presents a custom-designed single-cable readout IC for the reception of the broadband photoacoustic (PA) signal in intravascular photoacoustic (IVPA) imaging. The readout IC is intended for direct integration behind a broadband polyvinylidene fluoride (PVDF) transducer in an IVPA catheter tip to match the impedance between the small PVDF element and the connecting cable. The capability of the readout IC to work with a single cable that combines the output signal and the power supply ensures the mechanical flexibility of the IVPA catheter. Electrical measurements show that the readout IC provides a flat frequency response from 1 MHz to 20 MHz with a 6 mA external current supply. The acoustical measurements involving the readout IC and the PVDF transducer demonstrate a 60 dB dynamic range, a sensitivity of 3.8 μV/Pa at 2.25 MHz, and a broad receiving bandwidth from 2 MHz to 15 MHz.