Frits Mastik

Arterial wall characteristics determined by intravascular ultrasound imaging: An in vitro study☆

The feasibility of assessing arterial wall configuration with an intravascular 40 MHz ultrasound imaging device was investigated in an in vitro study of 11 autopsy specimens of human arteries. The system consists of a single element transducer, rotated with a motor mounted on an 8F catheter tip. Cross sections obtained with ultrasound were matched with the corresponding histologic sections. The arterial specimens were histologically classified as of the muscular or elastic type. Muscular arteries interrogated with ultrasound presented with a hypoechoic media, coinciding with the smooth muscle cells. In contrast, the media of an elastic artery densely packed with elastin fibers was as echogenic as the intima and the adventitia. On the basis of the cross-sectional image, it was possible to determine the nature of the atherosclerotic plaque. The location and thickness of the lesion measured from the histologic sections correlated well with the data derived from the corresponding ultrasound images. This study indicates that characterization of the type of artery and detection of arterial wall disease are possible with use of an intravascular ultrasound imaging technique.

Effects of the direct lipoprotein-associated phospholipase A2 inhibitor darapladib on human coronary atherosclerotic plaque

Background— Lipoprotein-associated phospholipase A2 (Lp-PLA2) is expressed abundantly in the necrotic core of coronary lesions, and products of its enzymatic activity may contribute to inflammation and cell death, rendering plaque vulnerable to rupture. Methods and Results— This study compared the effects of 12 months of treatment with darapladib (an oral Lp-PLA2 inhibitor, 160 mg daily) or placebo on coronary atheroma deformability (intravascular ultrasound palpography) and plasma high-sensitivity C-reactive protein in 330 patients with angiographically documented coronary disease. Secondary end points included changes in necrotic core size (intravascular ultrasound radiofrequency), atheroma size (intravascular ultrasound gray scale), and blood biomarkers. Background therapy was comparable between groups, with no difference in low-density lipoprotein cholesterol at 12 months (placebo, 88±34 mg/dL; darapladib, 84±31 mg/dL; P=0.37). In contrast, Lp-PLA2 activity was inhibited by 59% with darapladib (P<0.001 versus placebo). After 12 months, there were no significant differences between groups in plaque deformability (P=0.22) or plasma high-sensitivity C-reactive protein (P=0.35). In the placebo-treated group, however, necrotic core volume increased significantly (4.5±17.9 mm3; P=0.009), whereas darapladib halted this increase (−0.5±13.9 mm3; P=0.71), resulting in a significant treatment difference of −5.2 mm3 (P=0.012). These intraplaque compositional changes occurred without a significant treatment difference in total atheroma volume (P=0.95). Conclusions— Despite adherence to a high level of standard-of-care treatment, the necrotic core continued to expand among patients receiving placebo. In contrast, Lp-PLA2 inhibition with darapladib prevented necrotic core expansion, a key determinant of plaque vulnerability. These findings suggest that Lp-PLA2 inhibition may represent a novel therapeutic approach.

Characterizing Vulnerable Plaque Features With Intravascular Elastography

Background—In vivo detection of vulnerable plaques is presently limited by a lack of diagnostic tools. Intravascular ultrasound elastography is a new technique based on intravascular ultrasound and has the potential to differentiate between different plaques phenotypes. However, the predictive value of intravascular elastography to detect vulnerable plaques had not been studied. Methods and Results—Postmortem coronary arteries were investigated with intravascular elastography and subsequently processed for histology. In histology, a vulnerable plaque was defined as a plaque consisting of a thin cap (<250 &mgr;m) with moderate to heavy macrophage infiltration and at least 40% of atheroma. In elastography, a vulnerable plaque was defined as a plaque with a high strain region at the surface with adjacent low strain regions. In 24 diseased coronary arteries, we studied 54 cross sections. In histology, 26 vulnerable plaques and 28 nonvulnerable plaques were found. Receiver operator characteristic analysis revealed a maximum predictive power for a strain value threshold of 1.26%. The area under the receiver operator characteristic curve was 0.85. The sensitivity was 88%, and the specificity was 89% to detect vulnerable plaques. Linear regression showed high correlation between the strain in caps and the amount of macrophages (P <0.006) and an inverse relation between the amount of smooth muscle cells and strain (P <0.0001). Plaques, which are declared vulnerable in elastography, have a thinner cap than nonvulnerable plaques (P <0.0001). Conclusions—Intravascular elastography has a high sensitivity and specificity to detect vulnerable plaques in vitro.

Identification of Atherosclerotic Plaque Components With Intravascular Ultrasound Elastography In Vivo A Yucatan Pig Study

Background—Intravascular ultrasound elastography assesses the local strain of the atherosclerotic vessel wall. In the present study, the potential to identify different plaque components in vivo was investigated. Methods and Results—Atherosclerotic external iliac and femoral arteries (n=24) of 6 Yucatan pigs were investigated. Before termination, elastographic data were acquired with a 20-MHz Visions catheter. Two frames acquired at end-diastole with a pressure differential of ≈4 mm Hg were acquired to obtain the elastograms. Before dissection, x-ray was used to identify the arterial segments that had been investigated by ultrasound. Specimens were stained for collagen, fat, and macrophages. Plaques were classified as absent, early fibrous lesion, early fatty lesion, or advanced fibrous plaque. The average strains in the plaque-free arterial wall (0.21%) and the early (0.24%) and advanced fibrous plaques (0.22%) were similar. Higher average strain values were observed in fatty lesions (0.46%) compared with fibrous plaques (P =0.007). After correction for confounding by lipid content, no additional differences in average strain were found between plaques with and without macrophages (P =0.966). Receiver operating characteristic analysis revealed a sensitivity and a specificity of 100% and 80%, respectively, to identify fatty plaques. The presence of a high-strain spot (strain >1%) has 92% sensitivity and 92% specificity to identify macrophages. Conclusions—To the best of our knowledge, this is the first time that intravascular ultrasound elastography has been validated in vivo. Fatty plaques have an increased mean strain value. High-strain spots are associated with the presence of macrophages.

Brandaris 128: A digital 25 million frames per second camera with 128 highly sensitive frames

A high-speed camera that combines a customized rotating mirror camera frame with charge coupled device (CCD) image detectors and is practically fully operated by computer control was constructed. High sensitivity CCDs are used so that image intensifiers, which would degrade image quality, are not necessary. Customized electronics and instruments were used to improve the flexibility and control precisely the image acquisition process. A full sequence of 128 consecutive image frames with 500×292 pixels each can be acquired at a maximum frame rate of 25 million frames/s. Full sequences can be repeated every 20 ms, and six full sequences can be stored on the in-camera memory buffer. A high-speed communication link to a computer allows each full sequence of about 20 Mbytes to be stored on a hard disk in less than 1 s. The sensitivity of the camera has an equivalent International Standards Organization number of 2500. Resolution was measured to be 36 lp/mm on the detector plane of the camera, while under a microscope a bar pattern of 400 nm spacing line pairs could be resolved. Some high-speed events recorded with this camera, dubbed Brandaris 128, are presented.

Contactless multiple wavelength photoplethysmographic imaging: a first step toward "SpO2 camera" technology.

We describe a route toward contactless imaging of arterial oxygen saturation (SpO2) distribution within tissue, based upon detection of a two-dimensional matrix of spatially resolved optical plethysmographic signals at different wavelengths. As a first step toward SpO2-imaging we built a monochrome CMOS-camera with apochromatic lens and 3λ-LED-ringlight (λ1 = 660 nm, λ2 = 810 nm, λ3 = 940 nm; 100 LEDs λ−1). We acquired movies at three wavelengths while simultaneously recording ECG and respiration for seven volunteers. We repeated this experiment for one volunteer at increased frame rate, additionally recording the pulse wave of a pulse oximeter. Movies were processed by dividing each image frame into discrete Regions of Interest (ROIs), averaging 10 × 10 raw pixels each. For each ROI, pulsatile variation over time was assigned to a matrix of ROI-pixel time traces with individual Fourier spectra. Photoplethysmograms correlated well with respiration reference traces at three wavelengths. Increased frame rates revealed weaker pulsations (main frequency components 0.95 and 1.9 Hz) superimposed upon respiration-correlated photoplethysmograms, which were heartbeat-related at three wavelengths. We acquired spatially resolved heartbeat-related photoplethysmograms at multiple wavelengths using a remote camera. This feasibility study shows potential for non-contact 2-D imaging reflection-mode pulse oximetry. Clinical devices, however, require further development.

Characterization of plaque components and vulnerability with intravascular ultrasound elastography

Intravascular ultrasound elastography is a method for measuring the local elastic properties using intravascular ultrasound (IVUS). The elastic properties of the different tissues within the atherosclerotic plaque are measured through the strain. Knowledge of these elastic properties is useful for guiding interventional procedures (balloon dilatation, ablation) and detection of the vulnerable plaque. In the last decade, several groups have applied elastography intravascularly with various levels of success. In this paper, the approaches of the different research groups will be discussed. The focus will be on our approach to the application of intravascular elastography. Elastograms were acquired in vitro and in vivo using the relative local displacements between IVUS images acquired at two levels of intravascular pressure with a 30 MHz mechanical or a 20 MHz array echo catheter. These displacements were estimated from the time shift between gated radiofrequency echo signals using cross-correlation algorithms with interpolation around the peak. Experiments on gel-based phantoms mimicking atherosclerotic vessels demonstrated the capability of elastography to identify soft and hard tissues independently of the echogenicity contrast. In vitro experiments on human arteries have demonstrated the potential of intravascular elastography to identify different plaque types based on their mechanical properties. These plaques could not be identified using the IVUS image alone. In vivo experiments revealed that reproducible elastograms could be obtained near end-diastole. Partial validation using the echogram was performed. Intravascular elastography provides information that is frequently unavailable or inconclusive from the IVUS image and which may therefore assist in the diagnosis and treatment of atherosclerotic disease.

Incidence of High-Strain Patterns in Human Coronary Arteries Assessment With Three-Dimensional Intravascular Palpography and Correlation With Clinical Presentation

Background—Rupture of thin-cap fibroatheromatous plaques is a major cause of acute myocardial infarction (AMI). Such plaques can be identified in vitro by 3D intravascular palpography with high sensitivity and specificity. We used this technique in patients undergoing percutaneous intervention to assess the incidence of mechanically deformable regions. We further explored the relation of such regions to clinical presentation and to C-reactive protein levels. Method and Results—Three-dimensional palpograms were derived from continuous intravascular ultrasound pullbacks. Patients (n= 55) were classified by clinical presentation as having stable angina, unstable angina, or AMI. In every patient, 1 coronary artery was scanned (culprit vessel in stable and unstable angina, nonculprit vessel in AMI), and the number of deformable plaques assessed. Stable angina patients had significantly fewer deformable plaques per vessel (0.6±0.6) than did unstable angina patients (P = 0.0019) (1.6±0.7) or AMI patients (P < 0.0001) (2.0±0.7). Levels of C-reactive protein were positively correlated with the number of mechanically deformable plaques (R2 = 0.65, P < 0.0001). Conclusions—Three-dimensional intravascular palpography detects strain patterns in human coronary arteries that represent the level of deformation in plaques. The number of highly deformable plaques is correlated with both clinical presentation and levels of C-reactive protein. Further studies will assess the potential role of the technique to identify patients at risk of future clinical events

Fully automatic luminal contour segmentation in intracoronary ultrasound imaging-a statistical approach

In this paper, a fully automatic method for luminal contour segmentation in intracoronary ultrasound imaging is introduced. Its principle is based on a contour with a priori properties that evolves according to the statistics of the ultrasound texture brightness, which is generally Rayleigh distributed. The main interest of the technique is its fully automatic character. This is insured by an initial contour that is not set by the user, like in classical snake-based algorithms, but estimated and, thus, adapted to each image. Its estimation combines two pieces of information extracted from the a posteriori probability function of the contour position: the function maximum location (or maximum a posteriori estimator) and the first zero-crossing of its derivative. Then, starting from the initial contour, a region of interest is automatically selected and the process iterated until the contour evolution can be ignored. In vivo coronary images from 15 patients, acquired with the 20-MHz central frequency Jomed Invision ultrasound scanner, were segmented with the developed method. Automatic contours were compared to those manually drawn by two physicians in terms of mean absolute difference. The results demonstrate that the error between automatic contours and the average of manual ones is of small amplitude, and only very slightly higher (0.099/spl plusmn/0.032 mm) than the interexpert error (0.097/spl plusmn/0.027 mm).

Strain distribution over plaques in human coronary arteries relates to shear stress

Once plaques intrude into the lumen, the shear stress they are exposed to alters with hitherto unknown consequences for plaque composition. We investigated the relationship between shear stress and strain, a marker for plaque composition, in human coronary arteries. We imaged 31 plaques in coronary arteries with angiography and intravascular ultrasound. Computational fluid dynamics was used to obtain shear stress. Palpography was applied to measure strain. Each plaque was divided into four regions: upstream, throat, shoulder, and downstream. Average shear stress and strain were determined in each region. Shear stress in the upstream, shoulder, throat, and downstream region was 2.55+/-0.89, 2.07+/-0.98, 2.32+/-1.11, and 0.67+/-0.35 Pa, respectively. Shear stress in the downstream region was significantly lower. Strain in the downstream region was also significantly lower than the values in the other regions (0.23+/-0.08% vs. 0.48+/-0.15%, 0.43+/-0.17%, and 0.47+/-0.12%, for the upstream, shoulder, and throat regions, respectively). Pooling all regions, dividing shear stress per plaque into tertiles, and computing average strain showed a positive correlation; for low, medium, and high shear stress, strain was 0.23+/-0.10%, 0.40+/-0.15%, and 0.60+/-0.18%, respectively. Low strain colocalizes with low shear stress downstream of plaques. Higher strain can be found in all other plaque regions, with the highest strain found in regions exposed to the highest shear stresses. This indicates that high shear stress might destabilize plaques, which could lead to plaque rupture.