What have we learned from in vitro intravascular ultrasound?

In vitro studies have established that intravascular ultrasound is a reliable technique for accurate assessment of vascular anatomic structure and disease conditions before and after intervention. In addition, quantitative data from intravascular ultrasound studies correspond well with histologic findings, which serve as the gold standard. These in vitro studies permit the understanding and interpretation of ultrasound images obtained in vivo, although differences between the two settings should be taken into account. New ultrasound modalities currently being developed may enhance the diagnostic differentiation of plaque morphologic characteristics and facilitate on-line quantitative assessment of vessel structure

Spectroscopic photoacoustic imaging of radiofrequency ablation in the left atrium

Catheter-based radiofrequency ablation for atrial fibrillation has long-term success in 60-70% of cases. A better assessment of lesion quality, depth, and continuity could improve the procedure’s outcome. We investigate here photoacoustic contrast between ablated and healthy atrial-wall tissue in vitro in wavelengths spanning from 410 nm to 1000 nm. We studied single-and multi-wavelength imaging of ablation lesions and we demonstrate that a two-wavelength technique yields precise detection of lesions, achieving a diagnostic accuracy of 97%. We compare this with a best single-wavelength (640 nm) analysis that correctly identifies 82% of lesions. We discuss the origin of relevant spectroscopic features and perspectives for translation to clinical imaging

Characterization of plaque components with intravascular ultrasound elastography in human femoral and coronary arteries in vitro

BACKGROUND: The composition of plaque is a major determinant of coronary-related clinical syndromes. Intravascular ultrasound (IVUS) elastography has proven to be a technique capable of reflecting the mechanical properties of phantom material and the femoral arterial wall. The aim of this study was to investigate the capability of intravascular elastography to characterize different plaque components. METHODS AND RESULTS: Diseased human femoral (n=9) and coronary (n=4) arteries were studied in vitro. At each location (n=45), 2 IVUS images were acquired at different intraluminal pressures (80 and 100 mm Hg). With the use of cross-correlation analysis on the high-frequency (radiofrequency) ultrasound signal, the local strain in the tissue was determined. The strain was color-coded and plotted as an additional image to the IVUS echogram. The visualized segments were stained on the presence of collagen, smooth muscle cells, and macrophages. Matching of elastographic data and histology were performed with the use of the IVUS echogram. The cross sections were segmented in regions (n=125) that were based on the strain value on the elastogram. The dominant plaque types in these regions (fibrous, fibro-fatty, or fatty) were obtained from histology and correlated with the average strain and echo intensity. The strain for the 3 plaque types as determined by histology differed significantly (P=0.0002). This difference was mainly evident between fibrous and fatty tissue (P=0.0004). The plaque types did not reveal echo-intensity differences in the IVUS echogram (P=0.882). CONCLUSIONS: Different strain values are found between fibrous, fibro-fatty, and fatty plaque components, indicating the potential of intravascular elastography to distinguish different plaque morphologies

Model-based cap thickness and peak cap stress prediction for carotid MRI

A rupture-prone carotid plaque can potentially be identified by calculating the peak cap stress (PCS). For these calculations, plaque geometry from MRI is often used. Unfortunately, MRI is hampered by a low resolution, leading to an overestimation of cap thickness and an underestimation of PCS. We developed a model to reconstruct the cap based on plaque geometry to better predict cap thickness and PCS. We used histological stained plaques from 34 patients. These plaques were segmented and served as the ground truth. Sections of these plaques contained 93 necrotic cores with a cap thickness <0.62 mm which were used to generate a geometry-based model. The histological data was used to simulate in vivo MRI images, which were manually delineated by three experienced MRI readers. Caps below the MRI resolution (n = 31) were (digitally removed and) reconstructed according to the geometry-based model. Cap thickness and PCS were determined for the ground truth, readers, and reconstructed geometries. Cap thickness was 0.07 mm for the ground truth, 0.23 mm for the readers, and 0.12 mm for the reconstructed geometries. The model predicts cap thickness significantly better than the readers. PCS was 464 kPa for the ground truth, 262 kPa for the readers and 384 kPa for the reconstructed geometries. The model did not predict the PCS significantly better than the readers. The geometry-based model provided a significant improvement for cap thickness estimation and can potentially help in rupture-risk prediction, solely based on cap thickness. Estimation of PCS estimation did not improve, probably due to the complex shape of the plaques

Specific imaging of atherosclerotic plaque lipids with two-wavelength intravascular photoacoustics

The lipid content in plaques is an important marker for identifying atherosclerotic lesions and disease states. Intravascular photoacoustic (IVPA) imaging can be used to visualize lipids in the artery. In this study, we further investigated lipid detection in the 1.7-μm spectral range. By exploiting the relative difference between the IVPA signal strengths at 1718 and 1734 nm, we could successfully detect and differentiate between the plaque lipids and peri-adventitial fat in human coronary arteries ex vivo. Our study demonstrates that IVPA imaging can positively identify atherosclerotic plaques using only two wavelengths, which could enable rapid data acquisition in vivo

Fast and Accurate Pressure-Drop Prediction in Straightened Atherosclerotic Coronary Arteries

Atherosclerotic disease progression in coronary arteries is influenced by wall shear stress. To compute patient-specific wall shear stress, computational fluid dynamics (CFD) is required. In this study we propose a method for computing the pressure-drop in regions

Photoacoustic imaging of carotid artery atherosclerosis

We introduce a method for photoacoustic imaging of the carotid artery, tailored toward detection of lipidrich atherosclerotic lesions. A common human carotid artery was obtained at autopsy, embedded in a neck mimicking phantom and imaged with a multimodality imaging system using interstitial illumination. Light was delivered through a 1.25-mm-diameter optical probe that can be placed in the pharynx, allowing the carotid artery to be illuminated from within the body. Ultrasound imaging and photoacoustic signal detection is achieved by an external 8-MHz linear array coupled to an ultrasound imaging system. Spectroscopic analysis of photoacoustic images obtained in the wavelength range from 1130 to 1250 nm revealed plaque-specific lipid accumulation in the collagen structure of the artery wall. These spectroscopic findings were confirmed by histology

Temporal and spatial changes in wall shear stress during atherosclerotic plaque progression in mice

Wall shear stress (WSS) is involved in atherosclerotic plaque initiation, yet its role in plaque progression remains unclear. We aimed to study (i) the temporal and spatial changes in WSS over a growing plaque and (ii) the correlation between WSS and plaque composition, using animal-specific data in an atherosclerotic mouse model. Tapered casts were placed around the right common carotid arteries (RCCA) of ApoE−/− mice. At 5, 7 and 9 weeks after cast placement, RCCA geometry was reconstructed using contrast-enhanced micro-CT. Lumen narrowing was observed in all mice, indicating the progression of a lumen intruding plaque. Next, we determined the flow rate in the RCCA of each mouse using Doppler Ultrasound and computed WSS at all time points. Over time, as the plaque developed and further intruded into the lumen, absolute WSS significantly decreased. Finally at week 9, plaque composition was histologically characterized. The proximal part of the plaque was small and eccentric, exposed to relatively lower WSS. Close to the cast a larger and concentric plaque was present, exposed to relatively higher WSS. Lower WSS was significantly correlated to the accumulation of macrophages in the eccentric plaque. When pooling data of all animals, correlation between WSS and plaque composition was weak and no longer statistically significant. In conclusion, our data showed that in our mouse model absolute WSS strikingly decreased during disease progression, which was significantly correlated to plaque area and macrophage content. Besides, our study demonstrates the necessity to analyse individual animals and plaques when studying correlations between WSS and plaque composition