A porcine coronary stent model of increased neointima formation in the left anterior descending coronary artery.

BACKGROUND: Clinical trials suggest an increased frequency of restenosis after coronary intervention in left anterior descending (LAD) compared to the left circumflex or right coronary arteries. Experimental studies correlate stent-induced arterial injury and the extent of neointima formation. This study investigates whether the coronary artery affects the relationship between arterial injury and neointima hyperplasia in the porcine stent model. METHODS: Non-lipemic farm pigs underwent stent placement in the LAD (n = 26) and the right coronary artery (RCA; n = 30). Quantitative coronary angiography (QCA) was performed before and after stent placement, and at follow-up; quantitative histomorphometry and injury score were analyzed at 30-day follow-up. RESULTS: Initial procedure balloon/artery ratios (LAD 1.17 +/- 0.11 vs RCA 1.17 +/- 0.09, P = NS), and minimal stent lumen diameters (MLD; LAD 2.91 +/- 0.31 vs RCA: 2.93 +/- 0.28 mm, P = NS) were similar suggesting no difference in deployment technique. At follow-up there was more restenosis in the LAD (diameter stenosis: 55.0 +/- 26.4% vs 37.3 +/- 18.1%, and MLD: 1.24 +/- 0.78 mm vs. 1.71 +/- 0.57 mm, P < 0.05 for both comparisons). No differences were seen for injury score (1.09 +/- 0.51 vs 1.01 +/- 0.57; LAD vs RCA) or stent area (6.13 +/- 0.99 vs 6.55 +/- 1.42 mm2). Histomorphometry demonstrated smaller lumen area (2.15 +/- 0.94 vs 2.96 +/- 1.29 mm2) and thicker neointima (0.63 +/- 0.25 vs 0.51 +/- 0.17 mm; all P < 0.05) in the LAD. Multiple linear regression analysis identified the LAD as an independent predictive factor for increased neointima formation. CONCLUSIONS: These observations establish an animal model that is consistent with clinical experience showing that restenosis after stenting is more common in the LAD. The findings may be useful for understanding and developing systemic and local antirestenotic strategies.

Accuracy assessment of layer decomposition using simulated angiographic image sequences.

Layer decomposition is a promising method for obtaining accurate densitometric profiles of diseased coronary artery segments. This method decomposes coronary angiographic image sequences into moving densitometric layers undergoing translation, rotation, and scaling. In order to evaluate the accuracy of this technique, we have developed a technique for embedding realistic simulated moving stenotic arteries in real clinical coronary angiograms. We evaluate the accuracy of layer decomposition in two ways. First, we compute tracking errors as the distance between the true and estimated motion of a reference point in the arterial lesion. We find that noise-weighted phase correlation and layered background subtraction are superior to cross correlation and fixed mask subtraction, respectively. Second, we compute the correlation coefficient between the true vessel profile and the raw and processed images in the region of the stenosis. We find that layer decomposition significantly improves the correlation coefficient.

Usefulness of intracoronary brachytherapy for in-stent restenosis with a 188Re liquid-filled balloon.

The objective of this randomized pilot trial with 21 patients was to evaluate the effectiveness of a rhenium-188 liquid-filled balloon system to prevent recurrent restenosis after percutaneous transluminal coronary angioplasty for in-stent restenosis. A significant benefit from brachytherapy was seen at 6-month repeat angiography, as well as during the clinical follow-up of 12 months.

Simulating coronary arteries in x-ray angiograms.

Clinical validation of quantitative coronary angiography (QCA) algorithms is difficult due to the lack of a simple alternative method for accurately measuring in vivo vessel dimensions. We address this problem by embedding simulated coronary artery segments with known geometry in clinical angiograms. Our vessel model accounts for the profile of the vessel, x-ray attenuation in the original background, and noise in the imaging system. We have compared diameter measurements of our computer simulated arteries with measurements of an x-ray Telescopic-Shaped Phantom (XTSP) with the same diameters. The results show that for both uniform and anthropomorphic backgrounds there is good agreement in the measured diameters of XTSP compared to the simulated arteries (Pearson's correlation coefficient 0.99). In addition, the difference in accuracy and precision of the true diameter measures compared to the XTSP and simulated artery diameters was small (mean absolute error across all diameters was < or = 0.11 mm +/- 0.09 mm).

Regularization method for scatter-glare correction in fluoroscopic images.

Fluoroscopic images are degraded by scattering of x-rays from within the patient and by veiling glare in the image intensifier. Both of these degradations are well described by a response function applied to either the scatter-free or primary intensity. The response function is variable, with dependence on such factors as patient thickness and imaging geometry. We describe an automated regularization technique for obtaining response function parameters with a minimal loss of signal. This method requires a high-transmission structured reference object to be interposed between the x-ray source and the subject. We estimate the parameters by minimizing residual correlations between the reference object and the computed subject density after a scatter-glare correction. We use simulated images to evaluate our method for both ideal and clinically realistic conditions. We find that the residual root-mean-square (rms) error ideally decreases with an increasing number of independent pixels (N) as (1/N)1/2. In simulated 256x256 angiograms mean normalized rms errors were reduced from 40% to 11% in noise-free images, and from 41% to 17% in noisy images, with a similar improvement in densitometric vessel cross-section measurements. These results demonstrate the validity of the method for simulated images and characterize its expected performance on clinical images.

A new experimental determination of the dose calibrator setting for 188Re.

UNLABELLED: Accurate activity measurements of radionuclides using commercial dose calibrators requires that the correct dial setting (or calibration factor) be applied. The dose calibrator setting for the medical radionuclide 188Re (as 188ReO4-) has been determined experimentally using solution sources prepared and calibrated at the National Institute of Standards and Technology (NIST). METHODS: The specific activity of two sources (in units of MBq/g) in the standard 5-mL NIST ampoule and in a 5-mL SoloPak dose vial were calibrated using 4pibeta liquid scintillation counting with 3H-standard efficiency tracing and gamma-ray/bremmstrahlung counting in the NIST "4pi" gamma ionization chamber on gravimetrically related sources. RESULTS: The newly determined settings for the NIST Capintec CRC-12 dose calibrator are (631+/-4) x 10 and (621+/-3) x 10 for the respective ampoule and dose vial geometries with an expanded (at a presumed 95% confidence level) uncertainty of 0.4%-0.5% in the activity determination. The setting for the dose vial geometry was independently confirmed using a Capintec CRC-15R at Cedars-Sinai Medical Center using sources calibrated against a NIST standard. CONCLUSION: These new settings result in activity readings 28%-30% lower than those obtained using the previously recommended setting of 496 x 10. This discrepancy most likely results from underestimating the total radiation yield from 188Re decay when calculating the dose calibrator response. This study emphasizes the need for experimental determinations of dose calibrator settings in the geometry in which the measurements will be performed.

Why do anatomic backgrounds reduce lesion detectability?

RATIONALE AND OBJECTIVES: Developing metrics of medical image quality requires an understanding of how anatomic backgrounds reduce human visual detection performance. Visual psychophysics has shown that there are two distinct ways in which a complex background can degrade performance: (1) the presence of a deterministic high-contrast background, (2) variability in the background from location to location. The authors investigated how these two sources of performance degradation reduce human visual performance locating a lesion in anatomic backgrounds. METHODS: Human performance localizing a disk-shaped lesion in one of four locations (four alternative forced choice) was measured for three background conditions. In the first condition the background was a uniform gray. In the second condition (the repeated background condition) an anatomic background was sampled on each trial and used as a background for the four possible lesion locations. In the third condition (the different background condition) four different anatomic backgrounds were sampled on each trial and used for the four possible lesion locations. Test images consisted of computer simulated lesions mathematically projected on digital x-ray coronary angiograms. RESULTS: For five levels of lesion contrast, visual detection performance for two observers decreased significantly from the uniform background condition to the repeated background condition, and decreased even further for the different background condition. CONCLUSIONS: Study results show that both the presence of a deterministic high-contrast background and the background variations contribute to performance degradation of human visual detection of signals in anatomic backgrounds.

Characterization of a positron emitting V48 nitinol stent for intracoronary brachytherapy.

Percutaneous transluminal coronary angioplasty (PTCA) is currently one of the most common treatments for obstructive coronary artery disease. The long term success of the treatment, however, is severely limited by restenosis. Recently, different investigators have begun to study the possibility of radiation therapy in restenosis prevention and have shown promising results. However, an optimal radiation delivery device for delivering a highly localized radiation dose to the arterial medial layer while preserving the viability of the artery has yet to be established. In this article, we discuss the development of a unique mixed gamma/beta brachytherapy source capable of delivering high radiation dose to a 0.5 mm thick vessel wall by proton-beam activating an existing nickel titanium stent to produce vanadium-48. The dose distribution of the activated stent is determined by computer simulation using MCNP Monte Carlo code and is verified by radiochromic film measurement.

Role of knowledge in human visual temporal integration in spatiotemporal noise.

Previous studies have shown how human observers' knowledge about the signal's spatial frequency, spatial phase, and spatial locations affects human performance in detecting and identifying signals in spatial noise. These results have led to the idea that human observers can be modeled as suboptimal Bayesian observers that use a priori information to generate probabilities or likelihoods for hypothesis. This approach has also been applied more recently to object recognition. We investigate whether human observers have the ability to use information about the temporal profile of a temporally modulated signal in temporal information processing. We measure human performance in detecting a time-varying signal embedded in spatiotemporal (dynamic) noise with and without a cue that contains information about the temporal phase of the signal. Results show improvement in performance in the phase-cued condition, suggesting that human observers act as if they have the ability to use knowledge about the temporal shape of the signal when performing temporal information processing. Human performance is consistent with a suboptimal Bayesian observer and a newly proposed Max-Min observer. The results also suggest that models based solely on the integration of the early temporal filters in the human visual system and/or any further integration (e.g., probability summation), which do not make use of knowledge about the signals' temporal profile, are incomplete models of human visual detection in spatiotemporal noise.

Visual signal detection in structured backgrounds. I. Effect of number of possible spatial locations and signal contrast.

Several studies have investigated the effect of signal location uncertainty on the detectability of simple visual signals in uncorrelated Gaussian noise with a deterministic background. For this case, human performance in locating a signal in a forced-choice experiment has been successfully predicted for 2-1800 alternative locations with the use of signal detection theory and the usual assumption that the observer's internal response is Gaussian distributed. Gaussian uncorrelated noise is far from realistic medical image noise, which includes not only fluctuations in intensity of quantum origin but also other anatomical objects lying in the x-ray path (structured backgrounds). Our goal is to determine whether signal detection theory with the Gaussian assumption is adequate for the case of structured backgrounds, or whether other more complex models need to be developed to predict human performance as a function of the number of possible signal locations in structured backgrounds. We present experimental data suggesting that an assumed Gaussian internal response accurately predicts the decrease in observer performance as the number of alternative locations is increased. The one exception is a lower-than-predicted performance for the detection of low-contrast signals for two alternative locations. Performance as measured by the index of detectability d' is also found to be linear with signal contrast. Together these findings extend the applicability of signal detection theory with Gaussian internal response functions to the case of complex structured backgrounds.

Automatic correction of biplane projection imaging geometry.

A novel method is presented for correcting errors in measurements of biplane projection imaging geometry without prior identification of corresponding points in the two images. For imaged objects that project onto both images, a constraint equation is obtained that relates weighted integrals along corresponding epipolar lines. The integrals are computed to first order in the angular beamwidth, which is assumed to be small. Starting from measured or estimated values, geometrical parameters are computed iteratively in order to maximize the correlation between epipolar line integrals in the two images. Improvement in the computation of corresponding epipolar lines is demonstrated on images of a wire phantom. The root mean square distance of the epipolar lines from the corresponding reference points is improved from 15 pixel widths to less than 4 pixel widths (1.3 mm). Convergence is demonstrated on phantom images for individual parameter variations up to 70% in relative magnification, a relative shift of the imaging planes by 50 pixels, or a relative rotation of at least 35 degrees around either of two axes. Applicability to clinical images is demonstrated by using a biplane angiogram of a pig to align corresponding points determined from images of a Perspex cube acquired with the same geometry.

Digital angiographic impulse response analysis of myocardial perfusion: influence of heart rate and blood pressure changes on microcirculatory transit time measurement in the normal canine coronary circulation.

The study describes the effect of acute changes in aortic blood pressure and heart rate in the intact normal canine coronary circulation on digital angiographic measurements of the mean transit time of the microcirculation compartment and on direct flow meter measurement of resting and maximal hyperemic coronary blood flow. The mean transit time of the radiographic contrast material through the normal coronary circulation was calculated in 20 dogs by the impulse response analysis from serial digital coronary angiograms under systematically changed blood pressure and heart rate conditions. The mean aortic blood pressure (MAP) was controlled by the inflation of a balloon in the descending aorta (70-150 mmHg). The heart rate was altered by atrial pacing (90, 120, and 150/min). The mean transit times (T mu) of contrast material across the myocardial microcirculation which had been recently shown to correlate with coronary flow reserve (CFR) in stenosed arteries in the canine model were calculated under resting and hyperemic flow conditions from 428 selective coronary angiograms after a hand-injected contrast bolus, T mu was found to be heart rate independent. T mu-1 was linearly correlated with MAP (r = 0.7). There was no difference in T mu under resting and hyperemic flow conditions at comparable MAP. The corresponding distribution volume (V mu) of the microcirculation was calculated as the product of the mean transit time T mu and the measured coronary blood flow. Under resting flow conditions, V mu decreased with rising MAP. Furthermore, V mu increased with rising heart rate, V mu was constant during blood pressure or heart rate changes under hyperemic flow conditions. The data suggest that CFR whether by direct measurements of flow or by radiographic assessment of contrast material kinetics should be standardized with respect to hemodynamic conditions of heart rate and MAP.

Recent technical advances in digital coronary angiography.

Digital coronary angiography systems are widely available in interventional catheterization laboratories. Although quantitative coronary angiography is an important and widely used endpoint for research and clinical trials, the capabilities of digital imaging now available are underused in clinical practice, and potential capabilities have not yet been developed or practically implemented. This paper reviews recently published technical developments in digital angiography and fluoroscopy, including radiographic dose reduction methods that have minimal impact on image quality, image processing and display methods for improving image quality, new algorithms and validations for quantitative coronary angiography, and methods for obtaining images of and analyzing the complete three-dimensional coronary tree. These advancements may lead to reduced radiation exposure, improved image quality, better automated stenosis quantitation programs, and extraction of new and useful kinds of information from the coronary angiogram.

Digital angiographic assessment of the physiological changes to the regional microcirculation induced by successful coronary angioplasty.

BACKGROUND: Impulse response analysis of digital coronary angiographic images calculates a parameter known as the mean transit time of the microcirculation (Tmicro). This has been shown to accurately assess the regional microcirculatory response to proximal stenosis in relation to flow. Our goal was to apply impulse response analysis to patients undergoing successful angioplasty and to quantify the induced physiological changes with respect to quantitative angiographic measurements of stenosis dimensions. METHODS AND RESULTS: We studied 24 patients before and after successful single-vessel percutaneous transluminal coronary angioplasty (PTCA). Minimal luminal stenosis area was increased from 0.9 +/- 0.6 before PTCA to 4.1 +/- 1.3 mm2 after PTCA (P < .0001). In all patients this was accompanied by an increase in the inverse of Tmicro (Tmicro-1), from 8.5 +/- 3.0 to 26.5 +/- 9.0 min-1 (P < .0001) with a linear correlation between Tmicro-1 and minimal luminal stenosis area (r = .73; SEE = 7.74). Stenosis flow reserve, estimated by integration of stenosis dimensions, increased in all patients from 1.8 +/- 1.0 to 4.5 +/- 0.4 after PTCA (P < .01). A comparison of Tmicro-1 with stenosis flow reserve revealed a nonlinear relation. In 16 patients undergoing PTCA of the left anterior descending or circumflex artery, contrast injections into the left main stem allowed simultaneous measurements of Tmicro-1 in the adjacent, nonstenotic artery. Adjacent artery Tmicro-1 did not change after PTCA (25.8 +/- 6.2 compared with 25.6 +/- 6.8 min-1 before PTCA; P = NS); moreover, Tmicro-1 of the dilated artery measured after PTCA was equivalent to the nonstenotic adjacent artery, indicating normalization of microcirculatory responses. CONCLUSIONS: These data suggest that Tmicro-1 determined by digital angiographic impulse response analysis of a single contrast injection under resting flow conditions may be a practical method to assess the regional microcirculatory response to changes in stenosis severity effected by coronary angioplasty.

Improving detection of coronary morphological features from digital angiograms. Effect of stenosis-stabilized display.

BACKGROUND: We have developed a digital display method that stabilizes the motion of a stenosis in sequential frames of a coronary angiogram, allowing it to be scrutinized at high display frame rates. The purpose of this study was to determine whether this technique improves visual detection of low-contrast luminal morphological features. METHODS AND RESULTS: An observer detection study was conducted using computer-simulated arterial segments containing known target features, inserted into clinical digital coronary angiograms. Four observers performed a forced-choice detection of a simulated filling defect in each of 320 angiograms using the conventional and stenosis-stabilized dynamic displays (at 7.5, 15, and 32 frames per second) and a single-frame static display (total of 8960 detections). In a second simulated clinical task, three observers detected a bridging stenotic lumen in 600 angiograms using the two displays (3600 detections). In a third experiment, two angiographers rated the likelihood of intraluminal thrombus in 89 right coronary digital angiograms by consensus reading with both dynamic displays. Detectability of the simulated filling defect was similar for both dynamic display methods at 7.5 frames per second (averaging twice that for static images). As display rate was increased to 32 frames per second, detectability for the conventional display declined, whereas the stabilized display detectability increased for all observers (P < .05). On average, stabilization allowed detection of filling defects equivalent to a 71% increase in feature contrast. Response time for the conventional display averaged 12.9 +/- 4.7 seconds. For the stenosis-stabilized display, response time fell with increased frame rate (P < .05) to 4.9 +/- 1.2 seconds at 32 Hz, similar to the time for static images (4.6 +/- 0.8 seconds). The detectability of the bridging stenotic lumen was increased by 62% with the stabilization compared with conventional dynamic display (P < .00001). Consensus reading of coronary angiograms showed differences between the two dynamic display methods (kappa = 0.11) that may be explained by an improvement in observer uncertainty. A rating of definite for thrombus present or absent was more frequent with the stabilized display (39% versus 15%, P < .0001). CONCLUSIONS: These data suggest that stabilized display of coronary angiograms significantly increases detectability, reduces the time required for detection, and improves observer uncertainty for the presence of small luminal morphological features. The method of angiographic display may thus have an impact on clinical coronary angiographic interpretation.

Digital angiographic impulse response analysis of regional myocardial perfusion. Detection of autoregulatory changes in nonstenotic coronary arteries induced by collateral flow to adjacent stenotic arteries.

BACKGROUND: Our study compares the effect of acute proximal stenosis of a coronary artery supplying a myocardial perfusion bed with that of stenosis of an adjacent artery resulting in collateral flow diversion supplied by the same perfusion bed. These alterations in coronary physiology were quantified by digital angiographic impulse response analysis of contrast material mean transit time for the coronary microcirculation, Tmicro, and by flowmeter and microsphere assessment of flow and regional flow distribution. METHODS AND RESULTS: In 25 open-chest, anesthetized dogs, progressive circumflex artery stenosis led to a concordant decrease of circumflex artery resting and hyperemic flow, coronary flow reserve, and inverse angiographic mean transit time Tmicro-1 (P < .01). Progressive left anterior descending artery stenosis led to no or only minor changes of circumflex artery resting or hyperemic flow or flow reserve; only occlusion induced a significant decrease of coronary flow reserve (from 4.0 +/- 0.7 to 3.2 +/- 0.5, P < .05), whereas resting flow was increased by +8.6 +/- 5.9%. In contrast, circumflex artery Tmicro-1 diminished significantly with critical left anterior descending artery stenosis and occlusion (from 16.7 +/- 4.2 to 12.6 +/- 2.2 [P < .05] and 12.0 +/- 3.0 min-1 [P < .01], respectively). In 8 dogs, collateral flow induced by left anterior descending artery occlusion was quantified by microsphere injections. The decrease of circumflex artery Tmicro-1 correlated with the magnitude of collateral flow (r = .76) and was associated with the angiographic extent of collateral filling. CONCLUSIONS: Digital angiographic impulse response analysis is a sensitive method to detect the influence of proximal artery stenosis on an artery's myocardial perfusion bed as well as the changes induced by an adjacent artery stenosis inducing collateral flow diversion from the supplying myocardial perfusion zone.

Grading the angiographic extent of collateral filling. Comparison with coronary flow, collateral flow, and regional coronary flow distribution measurements.

Angiography frequently demonstrates a collateral circulation in severe coronary artery disease. An easily applicable method to quantify collateral flow might be a useful adjunct for the assessment of the hemodynamic effects of coronary artery disease. The purpose of this study was to validate a visual scaling of the extent of angiographic collateral filling by comparison with flowmeter- and microsphere-derived measurements of collateral flow. In 12 open-chest dogs, collaterals from the circumflex artery were angiographically visualized (n = 80) by creating acute critical left anterior descending artery occlusion. The extent of collateral filling was graded in four levels from 0 = no visible filling to 3 = complete epicardial filling. Collateral filling correlated with the change in flow of the collateral supplying circumflex artery (delta Q; r = 0.84) which was + 5.3 +/- 4.6% with grade 1, + 9.1 +/- 3.5% with grade 2 and + 14.6 +/- 4.7% with grade 3 (p < 0.01). In parallel, coronary flow reserve decreased from 4.1 +/- 0.8 with grade 0 to 2.9 +/- 0.2 with grade 3 (p < 0.01). Colored microspheres were injected subselectively into the circumflex artery of 9 dogs (45 injections). The ratio of microspheres counted in the collateralized myocardium of the left anterior descending artery to the total number injected increased from 0.6 +/- 0.9% for grade 0 to 17.1 +/- 2.8% with grade 3 (p < 0.01). Absolute collateral flow derived from the microsphere counts averaged 5.5 +/- 0.9 ml/min with grade 3 and closely correlated with collateral filling grade (r = 0.88). Semiquantitative grading of angiographic collateral filling in response to acute coronary occlusion in a canine model correlates with an increase in collateral source artery flow, absolute collateral flow and a decrease in source artery flow reserve. These data suggest that this scale might be a simple but useful adjunct tool to assess the hemodynamic significance of a collateral circulation.