Interstudy reproducibility of the second generation, Fourier domain optical coherence tomography in patients with coronary artery disease and comparison with intravascular ultrasound: a study applying automated contour detection.

Recently, Fourier domain OCT (FD-OCT) has been introduced for clinical use. This approach allows in vivo, high resolution (15 micron) imaging with very fast data acquisition, however, it requires brief flushing of the lumen during imaging. The reproducibility of such fast data acquisition under intracoronary flush application is poorly understood. To assess the inter-study variability of FD-OCT and to compare lumen morphometry to the established invasive imaging method, IVUS. 18 consecutive patients with coronary artery disease scheduled for PCI were included. In each target vessel a FD-OCT pullback (MGH system, light source 1,310 nm, 105 fps, pullback speed 20 mm/s) was acquired during brief (3 s) injection of X-ray contrast (flow 3 ml/s) through the guiding catheter. A second pullback was repeated under the same conditions after re-introduction of the FD OCT catheter into the coronary artery. IVUS and OCT imaging was performed in random order. FD-OCT and IVUS pullback data were analyzed using a recently developed software employing semi automated lumen contour and stent strut detection algorithms. Corresponding ROI were matched based on anatomical landmarks such as side branches and/or stent edges. Inter-study variability is presented as the absolute difference between the two pullbacks. FD-OCT showed remarkably good reproducibility. Inter-study variability in native vessels (cohort A) was very low for mean and minimal luminal area (0.10 ± 0.38, 0.19 ± 0.57 mm(2), respectively). Likewise inter-study variability was very low in stented coronary segments (cohort B) for mean lumen, mean stent, minimal luminal and minimal stent area (0.06 ± 0.08, 0.07 ± 0.10, 0.04 ± 0.09, 0.04 ± 0.10 mm(2), respectively). Comparison to IVUS morphometry revealed no significant differences. The differences between both imaging methods, OCT and IVUS, were very low for mean lumen, mean stent, minimal luminal and minimal stent area (0.10 ± 0.45, 0.10 ± 0.36, 0.26 ± 0.54, 0.05 ± 0.47 mm(2), respectively). FD-OCT shows excellent reproducibility and very low inter-study variability in both, native and stented coronary segments. No significant differences in quantitative lumen morphometry were observed between FD-OCT and IVUS. Evaluating these results suggest that FD-OCT is a reliable imaging tool to apply in longitudinal coronary artery disease studies.

The diagnostic value of intracoronary optical coherence tomography.

Optical coherence tomography (OCT) is a novel light-based imaging modality for application in the coronary circulation. Compared to conventional intravascular ultrasound, OCT has a ten-fold higher image resolution. This advantage has seen OCT successfully applied in the assessment of atherosclerotic plaque, stent apposition, and tissue coverage, heralding a new era in intravascular coronary imaging. The present article discusses the diagnostic value of OCT, both in cardiovascular research as well as in potential clinical application.The unparalleled high image resolution and strong contrast between the coronary lumen and the vessel wall structure enable fast and reliable image interpretation. OCT makes it possible to visualize the presence of atherosclerotic plaque in order to characterize the structure and extent of coronary plaque and to quantify lumen dimensions, as well as the extent of lumen narrowing, in unprecedented detail. Based on optical properties, OCT is able to distinguish different tissue types, such as fibrous, lipid-rich, necrotic, or calcified tissue. Furthermore, OCT is able to cover the visualization of a variety of features of atherosclerotic plaques that have been associated with rapid lesion progression and clinical events, such as thin cap fibroatheroma, fibrous cap thickness, dense macrophage infiltration, and thrombus formation. These unique features allow the use of OCT to assess patients with acute coronary syndrome and to study the dynamic nature of coronary atherosclerosis in vivo and over time. This permits new insights into plaque progression, regression, and rupture, as well as the study of effects of therapies aimed at modulating these developments.Today's OCT technology allows high detail resolution as well as fast and safe clinical image acquisition. These unique features have established OCT as the gold standard for the assessment of coronary stents. This technique makes it possible to study stent expansion, peri-procedural vessel trauma, and the interaction of the stent with the vessel wall down to the level of individual stent struts, both acutely as well as in the long term, where it is has proven extremely sensitive to the detection of even minor amounts of tissue coverage. These qualities render OCT indispensable to addressing vexing clinical questions such as the relationship of drug-eluting stent deployment, vascular healing, the true time course of endothelial stent coverage, and late stent thrombosis. This may also better guide the optimal duration of dual anti-platelet therapy that currently remains unclear and relatively empirical.In the future, OCT might emerge, parallel to its undisputed position in research, as the tool of choice in all clinical scenarios where angiography is limited by its nature as a two-dimensional luminogram.

Combined optical coherence tomography and intravascular ultrasound radio frequency data analysis for plaque characterization. Classification accuracy of human coronary plaques in vitro.

This study was performed to characterize coronary plaque types by optical coherence tomography (OCT) and intravascular ultrasound (IVUS) radiofrequency (RF) data analysis, and to investigate the possibility of error reduction by combining these techniques. Intracoronary imaging methods have greatly enhanced the diagnostic capabilities for the detection of high-risk atherosclerotic plaques. IVUS RF data analysis and OCT are two techniques focusing on plaque morphology and composition. Regions of interest were selected and imaged with OCT and IVUS in 50 sections, from 14 human coronary arteries, sectioned post-mortem from 14 hearts of patients dying of non-cardiovascular causes. Plaques were classified based on IVUS RF data analysis (VH-IVUS(TM)), OCT and the combination of those. Histology was the benchmark. Imaging with both modalities and coregistered histology was successful in 36 sections. OCT correctly classified 24; VH-IVUS 25, and VH-IVUS/OCT combined, 27 out of 36 cross-sections. Systematic misclassifications in OCT were intimal thickening classified as fibroatheroma in 8 cross-sections. Misclassifications in VH-IVUS were mainly fibroatheroma as intimal thickening in 5 cross-sections. Typical image artifacts were found to affect the interpretation of OCT data, misclassifying intimal thickening as fibroatheroma or thin-cap fibroatheroma. Adding VH-IVUS to OCT reduced the error rate in this study.

Imaging atherosclerotic plaque composition with intracoronary optical coherence tomography.

Optical coherence tomography (OCT) allows highly accurate diagnosis of atherosclerotic plaques, including measurement of the thickness of fibrous caps, permitting an assessment of the risk of rupture. While the OCT image presents morphological information in highly resolved detail, it relies on interpretation by trained readers for the identification of tissue type. We developed a method for quantitative classification of atherosclerotic plaque constituents. The optical attenuation coefficient mu(t) distinguishes different tissue types: necrotic core and macrophage infiltration exhibit strong attenuation, mu(t)>/=10 mm(-1), while calcific and fibrous tissue have a lower mu(t) approximately 2-5 mm(-1). (Neth Heart J 2009;17:448-50.).

Dynamics of a random laser above threshold.

We have performed enhanced backscattering experiments in a high gain random laser, under circumstances where a stationary theory predicts the laser intensity to diverge. Above the laser threshold the observed backscatter cone changes only gradually, not showing any signs of the divergence. We present measurements and theory-generalized laser equations with a diffusive transport term for pump and laser light-to explain the observed behavior. The population dynamics prevent an indefinite growth of the intensity. Time dependence is essential for a theory of random lasers above the laser threshold.

Amplifying volume in scattering media.

We investigate the influence of the excitation spot diameter on the laser threshold of a scattering amplifying medium. Fluorescence spectra are recorded from a suspension of TiO(2) scatterers in Sulforhodamine B dye. The threshold pump intensity becomes larger by a factor of 70 if the excitation beam diameter gets close to the mean free path?. This increase is explained by use of a simple model describing diffusion out of the amplifying volume and is confirmed by a Monte Carlo simulation.

Physiological effects of short-term treatment with enalapril in hypertensive patients.

To assess the effects of enalapril eight hospitalized hypertensive patients on constant sodium intake were treated with incremental doses of this angiotensin converting enzyme blocking drug. After four days of placebo treatment enalapril was given in single daily doses, starting with 1.25 mg and increasing until blood pressure was adequately controlled. On the 1.25 mg dose, angiotensin II (AII) and blood pressure did not change significantly, despite a 50% reduction in converting enzyme activity. There were, however, significant increases in noradrenaline, renin and aldosterone. With high doses a more pronounced reduction in converting enzyme activity was found while AII, aldosterone and blood pressure all fell significantly. Renin levels rose, but noradrenaline and adrenaline were reduced. Orthostatic hypotension did not occur. With continued treatment renal vascular resistance decreased concurrently with enhanced natriuresis and a reduction in body weight. Plasma volume rose slightly. The data indicate that enalapril may lower blood pressure by converting enzyme inhibition, but sodium loss and a decrease in sympathetic activity are associated features.

Humoral and renal effects of MK-421 (enalapril) in hypertensive subjects.

To assess the effect of MK-421 (enalapril) we treated six hospitalized hypertensive patients receiving constant sodium intake with incremental doses of this new angiotensin-converting enzyme blocking drug. After a few days of placebo treatment, MK-421 was given in single daily doses, starting with 1.25 mg and increasing until blood pressure was adequately controlled. On the lowest dose, converting enzyme activity was reduced by 50%, but angiotensin II and blood pressure did not change significantly. There were, however, significant increases in noradrenaline, renin, and aldosterone. With higher doses there was a more pronounced reduction in converting enzyme activity, while angiotensin II, aldosterone, and blood pressure all fell significantly. Renin levels rose, but noradrenaline and adrenaline were reduced. Orthostatic hypotension was not observed. With continued treatment, renal vasodilatation and enhanced natriuresis occurred together with a 1.2 kg decrement in body weight. Concurrently plasma volume rose, but renal blood flow remained unchanged. The data indicate that MK-421 effectively lowers blood pressure, and it does so by converting enzyme inhibition; sodium loss and a decrease in sympathetic activity are associated features. Since plasma volume increased despite enhanced natriuresis, the drug may act both at the arteriolar and at the venular level.

Aldosterone response to antihypertensive treatment.

To investigate whether changes in aldosterone during antihypertensive treatment would be related to alterations in the renin-angiotensin system or to changes in sodium-fluid balance, 54 essential hypertensives were hospitalized. Sodium intake was restricted to 55 mmoles per day. Levels of renin, angiotensin II and aldosterone were measured before and after two weeks treatment with atenolol (n=15), prazosin (n=15), the converting enzyme inhibitor MK 421 (n=6), verapamil (n=9) and the vasodilator L 6150 (n=10). Daily sodium excretion was determined from 24 h urine collections. The results indicate that, when renin or angiotensin levels do not change, the aldosterone response depends on alterations in sodium balance. When the renin system is depressed, sodium loss may prevent a large drop in aldosterone levels. It is concluded that during antihypertensive treatment body sodium status in itself modifies aldosterone secretion, irrespective of the renin-angiotensin system.

Effect of sympathetic stimulation on inactive renin.

In the present study we investigated the effect of three manoeuvres known to be associated with enhanced sympathetic activity on plasma levels of active and inactive renin. To this end, active and trypsin-activatable renin were measured in blood drawn from 12 untreated essential hypertensive patients before, during and after any of the following tests: isometric exercise (handgrip), noise stimulation and 45 degrees head-up tilt. These studies were repeated after the patients had been treated with either atenolol (n = 6) or SL 77499 (n = 6), an alpha-1 adrenoceptor blocking agent for 10 days. The results indicate that active and inactive renin often change in an unpredictable way in response to sympathetic stimulation. There are, as yet, no conclusive explanations which describe the behaviour of both forms of renin during these manoeuvres.

Neurohumoral response to hospitalization in hypertensive patients.

1. To investigate whether reduced activity of pressor systems could explain the spontaneous drop in pressure upon hospitalization, 51 subjects with uncomplicated essential hypertension were admitted to hospital. Sodium intake was fixed at 55 mmol/day. 2. Blood samples for noradrenaline, adrenaline, active renin, angiotensin II and aldosterone were drawn on each morning of the first 3 days of hospitalization; blood pressure was measured at 2 h intervals and values were averaged for each day. 3. Subjects were divided in two groups depending on whether they became normotensive (group 1; n = 12) or remained hypertensive (group 2; n = 39). This distinction was thought to reflect mild and more severe hypertensive groups respectively. 4. Although both groups showed a comparable fall in blood pressure during hospitalization, noradrenaline levels fell more consistently in group 1, whereas adrenaline levels fell only in group 2. The components of the renin--angiotensin--aldosterone system rose, but more conspicuously in group 1. 5. It is concluded that withdrawal of sympathetic activity can only partly explain the hypotensive response to hospitalization. The renin--angiotensin system behaves only passively and appears to be counterproductive to alterations in blood pressure.

Renin secretion by the human kidney.

1. 20 subjects with uncomplicated essential hypertension were studied, 10 of whom were on propranolol treatment. Several blood samples for determination of total and active renin were drawn simultaneously from the renal artery and vein after angiographic studies. 2. In all patients renal blood flow was measured by Hippuran-clearance at the time of blood sampling. Intrarenal blood flow was assessed by xenon-washout. 3. The results indicate that under basal conditions renin is secreted mainly in the active form, although secretion of inactive renin does occur. During propranolol treatment there is a tendency for secretion of active renin to be reduced.