Intravascular Palpography for Vulnerable Plaque Assessment

Palpography assesses the local mechanical properties of tissue using the deformation caused by the intraluminal pressure. The technique was validated in vitro using diseased human coronary and femoral arteries. Especially between fibrous and fatty tissue, a highly significant difference in strain (p = 0.0012) was found. Additionally, the predictive value to identify the vulnerable plaque was investigated. A high-strain region at the lumen vessel wall boundary has 88% sensitivity and 89% specificity for identifying these plaques. In vivo, the technique is validated in an atherosclerotic Yucatan minipig animal model. This study also revealed higher strain values in fatty than in fibrous plaques (p < 0.001). The presence of a high-strain region at the lumen-plaque interface has a high predictive value to identify macrophages. Patient studies revealed high strain values (1% to 2%) in noncalcified plaques. Calcified material showed low strain values (0% to 0.2%). With the development of three-dimensional palpography, identification of weak spots over the full length of a coronary artery becomes available. Patients with myocardial infarction or unstable angina have more high-strain spots in their coronary arteries than patients with stable angina. In conclusion, intravascular palpography is a unique tool to assess lesion composition and vulnerability. Three-dimensional palpography provides a technique that may develop into a clinically available tool for decision making to treat hemodynamically nonsignificant lesions by identifying vulnerable plaques. The clinical utility of this technique is yet to be determined, and more investigation is needed

信用金庫における中小企業金融の実証分析

博士（経済学）神戸大

The relative contributions of myocardial wall thickness and ischemia to ultrasonic myocardial integrated backscatter during experimental ischemia

Abstract The purpose of this study was to assess the empirical relationship between myocardial integrated backscatter (IB) and myocardial wall thickness (WT) in normal myocardium. A second object was to estimate the additional contribution to acute ischemic integrated backscatter levels given this relationship. Myocardial IB measurements and simultaneous myocardial WT measurements were made in 16 open-chested pigs with intact coronary circulation (normal myocardium) and 10 min after the flow in the left anterior descending coronary artery had been reduced to 20% of its baseline value (ischemic myocardium). Measurements were made 50 times during one cardiac cycle and averaged over 10 cardiac cycles. IB and WT measurements were normalized with respect to the nonischemic end-diastolic values. The relationship between IB and WT in normal myocardium was estimated in every individual pig by simple linear regression. Estimates of IB during ischemia were calculated on the basis of this relationship and the ischemic WT measurements. Differences of the estimator and the actual measurement made during ischemia depict the actual contribution of the state of acute ischemia, without the influence of WT. The slope of the relationship between IB and WT during normal myocardial contraction ranged from −0.16 to 0.03 dB/% (mean = −0.036 dB/%, SD = 0.06 dB/%). The additional contribution of ischemia ranged from −3.84 to 5.56 dB (mean = 0.31 dB, SD = 2.72 dB). It was concluded that the average contribution of ischemia to IB measurements is insignificant if the IB dependency on WT is removed from the data and that the higher level of ischemic IB measurements can be explained by the decrease in wall thickness during ischemia and not by the ischemia itself

Compressive 3D ultrasound imaging using a single sensor

Three-dimensional ultrasound is a powerful imaging technique, but it requires thousands of sensors and complex hardware. Very recently, the discovery of compressive sensing has shown that the signal structure can be exploited to reduce the burden posed by traditional sensing requirements. In this spirit, we have designed a simple ultrasound imaging device that can perform three-dimensional imaging using just a single ultrasound sensor. Our device makes a compressed measurement of the spatial ultrasound field using a plastic aperture mask placed in front of the ultrasound sensor. The aperture mask ensures that every pixel in the image is uniquely identifiable in the compressed measurement. We demonstrate that this device can successfully image two structured objects placed in water. The need for just one sensor instead of thousands paves the way for cheaper, faster, simpler, and smaller sensing devices and possible new clinical applications

Simultaneous Morphological and Flow Imaging Enabled by Megahertz Intravascular Doppler Optical Coherence Tomography

We demonstrate three-dimensional intravascular flow imaging compatible with routine clinical image acquisition workflow by means of megahertz (MHz) intravascular Doppler Optical Coherence Tomography (OCT). The OCT system relies on a 1.1 mm diameter motorized imaging catheter and a 1.5 MHz Fourier Domain Mode Locked (FDML) laser. Using a post processing method to compensate the drift of the FDML laser output, we can resolve the Doppler phase shift between two adjoining OCT A-line datasets. By interpretation of the velocity field as measured around the zero phase shift, the flow direction at specific angles can be qualitatively estimated. Imaging experiments were carried out in phantoms, micro channels, and swine coronary artery in vitro at a speed of 600 frames/s. The MHz wavelength sweep rate of the OCT system allows us to directly investigate flow velocity of up to 37.5 cm/s while computationally expensive phase-unwrapping has to be applied to measure such high speed using conventional OCT system. The MHz sweep rate also enables a volumetric Doppler imaging even with a fast pullback at 40 mm/s. We present the first simultaneously recorded 3D morphological images and Doppler flow profiles. Flow pattern estimation and three-dimensional structural reconstruction of entire coronary artery are achieved using a single OCT pullback dataset

Intravascular palpography for high-risk vulnerable plaque assessment.

Item does not contain fulltextBACKGROUND: The composition of an atherosclerotic plaque is considered more important than the degree of stenosis. An unstable lesion may rupture and cause an acute thrombotic reaction. Most of these lesions contain a large lipid pool covered by an inflamed thin fibrous cap. The stress in the cap increases with decreasing cap thickness and increasing macrophage infiltration. Intravascular ultrasound (IVUS) palpography might be an ideal technique to assess the mechanical properties of high-risk plaques. TECHNIQUE: Palpography assesses the local mechanical properties of tissue using its deformation caused by the intraluminal pressure. IN VITRO VALIDATION: The technique was validated in vitro using diseased human coronary and femoral arteries. Especially between fibrous and fatty tissue, a highly significant difference in strain (p = 0.0012) was found. Additionally, the predictive value to identify the vulnerable plaque was investigated. A high-strain region at the lumen-vessel wall boundary has an 88% sensitivity and 89% specificity for identifying such plaques. IN VIVO VALIDATION: In vivo, the technique was validated in an atherosclerotic Yucatan minipig animal model. This study also revealed higher strain values in fatty than fibrous plaques (p < 0.001). The presence of a high-strain region at the lumenplaque interface has a high predictive value to identify macrophages. PATIENT STUDIES: Patient studies revealed high-strain values (1-2%) in thin-cap fibrous atheroma. Calcified material showed low strain values (0-0.2%). With the development of three-dimensional (3-D) palpography, identification of highstrain spots over the full length of a coronary artery becomes available. CONCLUSION: Intravascular palpography is a unique tool to assess lesion composition and vulnerability. The development of 3-D palpography provides a technique that may develop into a clinical tool to identify the high-risk plaque

Opening of endothelial cell–cell contacts due to sonoporation

Ultrasound insonification of microbubbles can locally increase vascular permeability to enhance drug delivery. To control and optimize the therapeutic potential, we need to better understand the underlying biological mechanisms of the drug delivery pathways. The aim of this in vitro study was to elucidate the microbubble-endothelial cell interaction using the Brandaris 128 ultra-high-speed camera (up to 25 Mfps) coupled to a custom-built Nikon confocal microscope, to visualize both microbubble oscillation and the cellular response. Sonoporation and opening of cell-cell contacts by single αVβ3-targeted microbubbles (n = 152) was monitored up to 4 min after ultrasound insonification (2 MHz, 100–400 kPa, 10 cycles). Sonoporation occurred when microbubble excursion amplitudes exceeded 0.7 μm. Quantification of the influx of the fluorescent model drug propidium iodide upon sonoporation showed that the size of the created pore increased for larger microbubble excursion amplitudes. Microbubble-mediated opening of cell-cell contacts occurred as a cellular response upon sonoporation and did not correlate with the microbubble excursion amplitude itself. The initial integrity of the cell-cell contacts affected the susceptibly to drug delivery, since cell-cell contacts opened more often when cells were only partially attached to their neighbors (48%) than when fully attached (14%). The drug delivery outcomes were independent of nonlinear microbubble behavior, microbubble location, and cell size. In conclusion, by studying the microbubble–cell interaction at nanosecond and nanometer resolution the relationship between drug delivery pathways and their underlying mechanisms was further unraveled. These novel insights will aid the development of safe and efficient microbubble-mediated drug delivery