Mixed integer evolution strategies for parameter optimization.

Evolution strategies (ESs) are powerful probabilistic search and optimization algorithms gleaned from biological evolution theory. They have been successfully applied to a wide range of real world applications. The modern ESs are mainly designed for solving continuous parameter optimization problems. Their ability to adapt the parameters of the multivariate normal distribution used for mutation during the optimization run makes them well suited for this domain. In this article we describe and study mixed integer evolution strategies (MIES), which are natural extensions of ES for mixed integer optimization problems. MIES can deal with parameter vectors consisting not only of continuous variables but also with nominal discrete and integer variables. Following the design principles of the canonical evolution strategies, they use specialized mutation operators tailored for the aforementioned mixed parameter classes. For each type of variable, the choice of mutation operators is governed by a natural metric for this variable type, maximal entropy, and symmetry considerations. All distributions used for mutation can be controlled in their shape by means of scaling parameters, allowing self-adaptation to be implemented. After introducing and motivating the conceptual design of the MIES, we study the optimality of the self-adaptation of step sizes and mutation rates on a generalized (weighted) sphere model. Moreover, we prove global convergence of the MIES on a very general class of problems. The remainder of the article is devoted to performance studies on artificial landscapes (barrier functions and mixed integer NK landscapes), and a case study in the optimization of medical image analysis systems. In addition, we show that with proper constraint handling techniques, MIES can also be applied to classical mixed integer nonlinear programming problems.

Integrated contour detection and pose estimation for fluoroscopic analysis of knee implants.

With fluoroscopic analysis of knee implant kinematics the implant contour must be detected in each image frame, followed by estimation of the implant pose. With a large number of possibly low-quality images, the contour detection is a time-consuming bottleneck. The present paper proposes an automated contour detection method, which is integrated in the pose estimation. In a phantom experiment the automated method was compared with a standard method, which uses manual selection of correct contour parts. Both methods demonstrated comparable precision, with a minor difference in the Y-position (0.08 mm versus 0.06 mm). The precision of each method was so small (below 0.2 mm and 0.3 degrees) that both are sufficiently accurate for clinical research purposes. The efficiency of both methods was assessed on six clinical datasets. With the automated method the observer spent 1.5 min per image, significantly less than 3.9 min with the standard method. A Bland-Altman analysis between the methods demonstrated no discernible trends in the relative femoral poses. The threefold increase in efficiency demonstrates that a pose estimation approach with integrated contour detection is more intuitive than a standard method. It eliminates most of the manual work in fluoroscopic analysis, with sufficient precision for clinical research purposes.

Neurological signs in relation to white matter hyperintensity volumes in memory clinic patients.

PURPOSE: To determine the frequency of neurological signs in a memory clinic population and to explore their associations with white matter hyperintensity (WMH). METHODS: We included patients with Alzheimer disease (AD; n = 210), vascular dementia (VaD; n = 34), mild cognitive impairment (MCI; n = 86) and subjective complaints (n = 153). The presence of extrapyramidal and unilateral signs was assessed from medical charts. On MRI, WMH volumes were extracted automatically. RESULTS: Extrapyramidal signs were found in 10% and unilateral signs in 12% of the patients. Age- and sex-adjusted extrapyramidal signs occurred more often in VaD compared to patients with subjective complaints. Unilateral signs were more prevalent in all groups compared to patients with subjective complaints. Two-way analysis of variance (ANOVA) with WMH as the dependent variable showed a main effect of diagnosis (p < 0.001), but not of extrapyramidal signs (p = 0.62). In contrast, 2-way ANOVA showed main effects of diagnosis (p < 0.001) and unilateral signs (p = 0.001). Furthermore, there was an interaction between these factors (p = 0.04); if unilateral signs were present, patients with subjective complaints and VaD showed more WMH, whereas there was no relation in AD and MCI. CONCLUSION: Extrapyramidal and unilateral signs are common in memory clinic patients, but are only modestly related to WMH.

Handling modular hip implants in model-based RSA: combined stem-head models.

Migration measurements of hip prostheses using marker-based Roentgen stereophotogrammetric analysis (RSA) require the attachment of markers to the prostheses. The model-based approach, which does not require these markers, is, however, less precise. One of the reasons may be the fact that the spherical head has not been modelled. Therefore, we added a 3D surface model of the spherical head and estimated the position and orientation of the combined stem-head model. The new method using a combined stem-head model was compared in a phantom study on five prostheses (of different types) and in a clinical study using double examinations of implanted hip prostheses, with two existing methods: a standard model-based approach and one using elementary geometrical shapes. The combined model showed the highest precision for the rotation about the longitudinal axis in the phantom experiments. With a standard deviation of 0.69 degrees it showed a significant improvement (p=0.02) over the model-based approach (0.96 degrees ) on the phantom data, but no improvement on the clinical data. Overall, the use of elementary geometrical shapes was worse with respect to the model-based approach, with a standard deviation of 1.02 degrees on the phantom data and 0.79 degrees on the clinical data. This decrease in precision was significant (p<0.01) on the clinical data. With relatively small differences in the other migration directions, these results demonstrate that the new method with a combined stem-head model can be a useful alternative to the standard model-based approach.

Image-based RSA: Roentgen stereophotogrammetric analysis based on 2D-3D image registration.

Image-based Roentgen stereophotogrammetric analysis (IBRSA) integrates 2D-3D image registration and conventional RSA. Instead of radiopaque RSA bone markers, IBRSA uses 3D CT data, from which digitally reconstructed radiographs (DRRs) are generated. Using 2D-3D image registration, the 3D pose of the CT is iteratively adjusted such that the generated DRRs resemble the 2D RSA images as closely as possible, according to an image matching metric. Effectively, by registering all 2D follow-up moments to the same 3D CT, the CT volume functions as common ground. In two experiments, using RSA and using a micromanipulator as gold standard, IBRSA has been validated on cadaveric and sawbone scapula radiographs, and good matching results have been achieved. The accuracy was: |mu |< 0.083 mm for translations and |mu| < 0.023 degrees for rotations. The precision sigma in x-, y-, and z-direction was 0.090, 0.077, and 0.220 mm for translations and 0.155 degrees , 0.243 degrees , and 0.074 degrees for rotations. Our results show that the accuracy and precision of in vitro IBRSA, performed under ideal laboratory conditions, are lower than in vitro standard RSA but higher than in vivo standard RSA. Because IBRSA does not require radiopaque markers, it adds functionality to the RSA method by opening new directions and possibilities for research, such as dynamic analyses using fluoroscopy on subjects without markers and computer navigation applications.

Time continuous detection of the left ventricular long axis and the mitral valve plane in 3-D echocardiography.

Automated segmentation approaches for the left ventricle (LV) in 3-D echocardiography (3DE) often rely on manual initialization. So far, little effort has been put into automating the initialization procedure to get to a fully automatic segmentation approach. We propose a fully automatic method for the detection of the LV long axis (LAX) and the mitral valve plane (MVP) over the full cardiac cycle, for the initialization of segmentation algorithms in 3DE. Our method exploits the cyclic motion of the LV and therefore detects salient structures in a time-continuous way. Probabilities to candidate LV center points are assigned through a Hough transform for circles. The LV LAX is detected by combining dynamic programming detections on these probabilities in 3-D and 2D + time to obtain a time continuous solution. Subsequently, the mitral valve plane is detected in a projection of the data on a plane through the previously detected LAX. The method easily adjusts to different acquisition routines and combines robustness with good accuracy and low computational costs. Automatic detection was evaluated using patient data acquired with the fast rotating ultrasound (FRU) transducer (n=11 patients) and with the Philips Sonos 7500 ultrasound system (Philips Medical Systems, Andover, MA, USA), with the X4 matrix transducer (n=14 patients). For the FRU-transducer data, the LAX was estimated with a distance error of 2.85+/-1.70 mm (mean+/-SD) and an angle of 5.25+/-3.17 degrees; the mitral valve plane was estimated with a distance of -1.54+/-4.31 mm. For the matrix data, these distances were 1.96+/-1.30 mm with an angle error of 5.95+/-2.11 and -1.66+/-5.27 mm for the mitral valve plane. These results confirm that the method is very suitable for automatic detection of the LV LAX and MVP. It provides a basis for further automatic exploration of the LV and could therefore serve as a replacement of manual initialization of 3-D segmentation approaches.

Clinical validation of an automated vessel-segmentation software of the extracranial-carotid arteries based on 3D-MRA: a prospective study.

OBJECTIVES: To determine the accuracy of automated vessel-segmentation software for vessel-diameter measurements based on three-dimensional contrast-enhanced magnetic resonance angiography (3D-MRA). METHOD: In 10 patients with high-grade carotid stenosis, automated measurements of both carotid arteries were obtained with 3D-MRA by two independent investigators and compared with manual measurements obtained by digital subtraction angiography (DSA) and 2D maximum-intensity projection (2D-MIP) based on MRA and duplex ultrasonography (US). In 42 patients undergoing carotid endarterectomy (CEA), intraoperative measurements (IOP) were compared with postoperative 3D-MRA and US. RESULTS: Mean interoperator variability was 8% for measurements by DSA and 11% by 2D-MIP, but there was no interoperator variability with the automated 3D-MRA analysis. Good correlations were found between DSA (standard of reference), manual 2D-MIP (rP=0.6) and automated 3D-MRA (rP=0.8). Excellent correlations were found between IOP, 3D-MRA (rP=0.93) and US (rP=0.83). CONCLUSION: Automated 3D-MRA-based vessel segmentation and quantification result in accurate measurements of extracerebral-vessel dimensions.

Accuracy and reproducibility of fast fractional flow reserve computation from invasive coronary angiography.

Fractional flow reserve (FFR) guided percutaneous coronary intervention (PCI) is associated with favourable outcome compared with revascularization based on angiographic stenosis severity alone. The feasibility of the new image-based quantitative flow ratio (QFR) assessed from 3D quantitative coronary angiography (QCA) and thrombolysis in myocardial infarction (TIMI) frame count using three different flow models has been reported recently. The aim of the current study was to assess the accuracy, and in particular, the reproducibility of these three QFR techniques when compared with invasive FFR. QFR was derived (1) from adenosine induced hyperaemic coronary angiography images (adenosine-flow QFR [aQFR]), (2) from non-hyperemic images (contrast-flow QFR [cQFR]) and (3) using a fixed empiric hyperaemic flow [fixed-flow QFR (fQFR)]. The three QFR values were calculated in 17 patients who prospectively underwent invasive FFR measurement in 20 vessels. Two independent observers performed the QFR analyses. Mean difference, standard deviation and 95% limits of agreement (LOA) between invasive FFR and aQFR, cQFR and fQFR for observer 1 were: 0.01 ± 0.04 (95% LOA: -0.07; 0.10), 0.01 ± 0.05 (95% LOA: -0.08; 0.10), 0.01 ± 0.04 (95% LOA: -0.06; 0.08) and for observer 2: 0.00 ± 0.03 (95% LOA: -0.06; 0.07), -0.01 ± 0.03 (95% LOA: -0.07; 0.05), 0.00 ± 0.03 (95% LOA: -0.06; 0.05). Values between the 2 observers were (to assess reproducibility) for aQFR: 0.01 ± 0.04 (95% LOA: -0.07; 0.09), for cQFR: 0.02 ± 0.04 (95% LOA: -0.06; 0.09) and for fQFR: 0.01 ± 0.05 (95% LOA: -0.07; 0.10). In a small number of patients we showed good accuracy of three QFR techniques (aQFR, cQFR and fQFR) to predict invasive FFR. Furthermore, good inter-observer agreement of the QFR values was observed between two independent observers.

Decreased coagulability has no clinically relevant effect on atherogenesis: observations in individuals with a hereditary bleeding tendency.

BACKGROUND: Hemostasis affects ischemic cardiovascular disease through its role in formation of occluding arterial thrombi. Several studies suggest that hemostasis also might play a role in atherogenesis. We investigated whether individuals with an inherited bleeding tendency are protected against development of atherosclerosis. METHODS AND RESULTS: A total of 76 individuals with an inherited bleeding tendency (hemophilia and von Willebrand disease) and 142 healthy controls were included in the present study. Early atherosclerotic vessel-wall changes were quantified by measurement of intima-media thickness in the carotid and femoral arteries by B-mode ultrasonography. To validate intima-media thickness measurements, measurements also were performed in 77 individuals with clinically proven atherosclerosis and in 34 healthy, age-matched controls. A large difference in intima-media thickness was found between individuals with proven atherosclerosis and healthy controls, in particular for the femoral artery (difference for carotid artery, 0.16 mm; femoral artery, 0.53 mm). Comparison between patients with a bleeding tendency and healthy controls showed only minimally reduced intima-media in femoral artery in individuals with a bleeding tendency (adjusted difference, -0.078 mm; 95% CI, -0.17 to 0.018 mm). Subgroup analysis revealed that in subjects with moderate to severe hemophilia, vessel walls were thinnest (adjusted difference, -0.10 mm; 95% CI, -0.27 to 0.061 mm). CONCLUSIONS: Hypocoagulability caused by hemophilia or von Willebrand disease has at most a limited effect on atherogenesis.

Patients with type 3 severe von Willebrand disease are not protected against atherosclerosis: results from a multicenter study in 47 patients.

BACKGROUND: The results of a number of studies in pigs and mice suggest that absence of von Willebrand factor (vWF) protects against the development of atherosclerosis. We studied whether patients with a complete deficiency of vWF (type 3 von Willebrand disease [vWD]) develop fewer atherosclerotic vessel wall changes than healthy controls. METHODS AND RESULTS: This study included 47 individuals with type 3 vWD and 84 healthy controls. Early atherosclerotic changes were assessed by measuring the thickness of the intima-media in the carotid and femoral arteries by B-mode ultrasonography. Advanced atherosclerotic changes were quantified by summing the maximal thickness of atherosclerotic plaques in the carotid and femoral arteries and were expressed as a plaque score. Established risk factors were determined to adjust for possible differences between the groups. We found no substantial difference in intima-media thickness between vWD patients and controls (adjusted difference for carotid artery 0.007 mm, 95% CI -0.022 to 0.036 mm; femoral artery 0.069 mm, 95% CI -0.056 to 0.19 mm). Similar proportions of patients and controls had atherosclerotic plaques (19% and 17%, respectively). No difference was found in the plaque score between groups (adjusted difference -0.22 mm, 95% CI -0.69 to 0.26). Among vWD patients, we found no effect of treatment with vWF concentrates on intima-media thickness or plaque score. CONCLUSIONS: The results of this study indicate that vWF does not play a substantial role in human atherogenesis.

Stent placement to prevent restenosis after angioplasty in small coronary arteries.

BACKGROUND: Lesions in small-diameter vessels (<3 mm) define a group with distinct clinical and morphological characteristics. There is an inverse relationship between vessel size and angiographic restenosis rate. This study assessed whether stents reduce angiographic restenosis in small coronary arteries compared with standard balloon angioplasty. METHODS AND RESULTS: We randomly assigned 351 symptomatic patients needing dilatation of 1 native coronary vessel between 2.3 and 2.9 mm in size to angioplasty alone (n=182) or stent implantation (n=169). The primary end point was angiographic restenosis at 6 months. Secondary end points included death, myocardial infarction, bypass surgery, and target vessel revascularization in hospital and at 6 months. There were no significant differences between groups in terms of major in-hospital complications. There was a trend toward fewer in-hospital events in the stent group (3% versus 7.1% in angioplasty group, P=0.076). Crossovers to stent occurred in 37 patients (20.3%). Repeat angiography at 6-month follow-up was performed in 85.3% of patients. Angiographic restenosis occurred in 28% of the stent group and 32.9% of the angioplasty group (P=0.36). Target vessel revascularization was required in 17.8% versus 20.3% of patients (P=0.54), respectively. CONCLUSIONS: Stenting and standard coronary angioplasty are associated with equal restenosis rate in small coronary arteries. With a lower in-hospital complication rate, stenting may be a superior strategy in small vessels.

A new approach for the quantification of complex lesion morphology: the gradient field transform; basic principles and validation results.

OBJECTIVES: This report describes the basic principles and the results from clinical evaluation studies of a new algorithm that has been designed specifically for the quantification of complex coronary lesions. BACKGROUND: Currently used edge detection algorithms in quantitative coronary arteriography, such as the minimum cost algorithm, are limited in the precise quantification of complex coronary lesions characterized by abruptly changing shapes of the obstruction. METHODS: The new algorithm, the gradient field transform, is not limited in its search directions and incorporates the directional information of the arterial boundaries. To evaluate its accuracy and precision, 11 tubular phantoms (sizes 0.6 to 5.0 mm), were analyzed. Second, angiographic images of 12 copper phantoms with U-shaped obstructions were analyzed by both the gradient field transform and the minimum cost algorithm. Third, 25 coronary artery segments with irregularly shaped obstructions were selected from 19 routinely acquired angiograms. RESULTS: The plexiglass phantom study demonstrated an accuracy and precision of -0.004 and 0.114 mm, respectively. The U-shaped copper phantoms showed that the gradient field transform performed very well for short, severe obstructions, whereas the minimum cost algorithm severely overestimated the minimal lumen diameter. From the coronary angiograms, the intraobserver variability in the minimal lumen diameter was found to be 0.14 mm for the gradient field transform and 0.20 mm for the minimum cost algorithm. CONCLUSIONS: The new gradient field transform eliminates the limitations of the currently used edge detection algorithms in quantitative coronary arteriography and is therefore particularly suitable for the quantification of complex coronary artery lesions.

Which cineangiographically assessed anatomic variable correlates best with functional measurements of stenosis severity? A comparison of quantitative analysis of the coronary cineangiogram with measured coronary flow reserve and exercise/redistribution thallium-201 scintigraphy.

The goal of this investigation was to establish which measured anatomic variable of stenotic coronary lesions correlates best with functional severity. Therefore, 38 patients with single vessel disease underwent coronary cineangiography and exercise/redistribution thallium-201 scintigraphy. The computer-based Cardiovascular Angiography Analysis System was used to determine the cross-sectional area at the site of obstruction (OA) and percent diameter stenosis (DS), and to calculate the pressure drop over the stenosis (PD) with use of fluid dynamic equations. Coronary flow reserve was measured radiographically. Myocardial perfusion defects on thallium scintigrams were analyzed quantitatively and by visual interpretation. The relations between coronary flow reserve (CFR) and the three anatomic variables were described by the following equations: 1) CFR = 4.6 - 0.053 DS, r = 0.82; SEE: 0.79, p less than 0.001. 2) CFR = 0.5 + 0.75 OA, r = 0.87; SEE: 0.68, p less than 0.001). 3 CFR = 3.6 - 1.5 log PD, r = 0.90; SEE: 0.62, p less than 0.001. The calculated pressure drop was highly predictive of the thallium scintigraphic results with a sensitivity of 94% and a specificity of 90%. The calculated pressure drop is a better anatomic variable for assessing the functional importance of a stenosis than is percent diameter stenosis or obstruction area. However, the 95% confidence limits of the relation between pressure drop and coronary flow reserve are wide, making the measurement of coronary flow reserve an indispensable addition to quantitative angiography, especially when determining the functional importance of moderately severe coronary artery lesions.

American College of Cardiology/European Society of Cardiolgoy International Study of Angiographic Data Compression Phase II: the effects of varying JPEG data compression levels on the quantitative assessment of the degree of stenosis in digital coronary angiography. Joint Photographic Experts Group.

OBJECTIVES: This report describes whether lossy Joint Photographic Experts Group (UPEG) image compression/decompression has an effect on the quantitative assessment of vessel sizes by state-of-the-art quantitative coronary arteriography (QCA). BACKGROUND: The Digital Imaging and Communications in Medicine (DICOM) digital exchange standard for angiocardiography prescribes that images must be stored loss free, thereby limiting JPEG compression to a maximum ratio of 2:1. For practical purposes it would be desirable to increase the compression ratio (CR), which would lead to lossy image compression. METHODS: A series of 48 obstructed coronary segments were compressed/decompressed at CR 1:1 (uncompressed), 6:1, 10:1 and 16:1 and analyzed blindly and in random order using the QCA-CMS analytical software. Similar catheter and vessel start- and end-points were used within each image quartet, respectively. All measurements were repeated after several weeks using newly selected start- and end-points. Three different sub-analyses were carried out: the intra-observer, fixed inter-compression and variable inter-compression analyses, with increasing potential error sources, respectively. RESULTS: The intra-observer analysis showed significant systematic and random errors in the calibration factor at JPEG CR 10:1. The fixed inter-compression analysis demonstrated systematic errors in the calibration factor and recalculated vessel parameter results at CR 16:1 and for the random errors at CR 10:1 and 16:1. The variable inter-compression analysis presented systematic and random errors in the calibration factor and recalculated parameter results at CR 10:1 and 16:1. Any negative effect at CR 6:1 was found only for the calibration factor of the variable inter-compression analysis, which did not show up in the final vessel measurements. CONCLUSIONS: Compression ratios of 10:1 and 16:1 affected the QCA results negatively and therefore should not be used in clinical research studies.

Quantitative assessment of regional left ventricular motion using endocardial landmarks.

In this study the hypothesis is tested that the motion pattern of small anatomic landmarks, recognizable at the left ventricular endocardial border in the contrast angiocardiogram, reflects the motion of the endocardial wall. To verify this, minute metal markers were inserted in the endocardium of eight pigs with a novel retrograde transvascular approach. Marker motion was subsequently recorded with roentgen cinematography and compared with the motion of the landmarks on the endocardial contours detected from the contrast ventriculogram with an automated contour detection system. Linear regression analysis of the directions of the systolic metal marker and endocardial landmark pathways yielded a correlation coefficient of 0.86 and a standard error of the estimate of 10.3 degrees. Landmark pathways were also measured in 23 normal human left ventriculograms. Normal left ventricular endocardial wall motion during systole, as observed in the 30 degrees right anterior oblique view, is characterized by a dominant inward transverse motion of the opposite anterior and inferoposterior walls and a descent of the base toward the apex. The apex itself is almost stationary. On the basis of these observations, a widely applicable model for the assessment of left ventricular wall motion is described in mathematical terms.

Change in diameter of coronary artery segments adjacent to stenosis after percutaneous transluminal coronary angioplasty: failure of percent diameter stenosis measurement to reflect morphologic changes induced by balloon dilation.

To determine the changes in stenotic and nonstenotic segments of a dilated coronary artery, detailed quantitative angiographic measurements were performed in 342 patients (398 lesions) immediately after angioplasty and at a predetermined follow-up time of 30, 60, 90 or 120 days after the dilation. Measurements of the stenotic segments were expressed as minimal luminal diameter, and the adjacent nonstenotic segments were expressed as interpolated reference diameter (both in millimeters). A follow-up rate of 86% was achieved. In the patients followed up at 30 and 60 days, there was no significant change in either the mean minimal luminal diameter or the mean reference diameter. However, at 90 and 120 days, there was significant deterioration in both the mean minimal luminal diameter (-0.37 and -0.42 mm, respectively) and the mean reference diameter (-0.17 and -0.26 mm, respectively), all of the changes being highly significant (p less than 0.00001). The reference diameter is involved in the dilation process and may be subject to the same restenosis process that takes place in initially stenotic segments. Percent diameter stenosis measurements, which are conventionally used to express the change in the severity of a stenosis after angioplasty, will tend to underestimate the change when there is a simultaneous reduction in the reference diameter.

Angiotensin-converting enzyme inhibitor therapy affects left ventricular mass in patients with ejection fraction > 40% after acute myocardial infarction.

OBJECTIVES: We tested the hypothesis that angiotensin-converting enzyme (ACE) inhibitor therapy decreases left ventricular (LV) mass in patients with a left ventricular ejection fraction (LVEF) > 40% and no evidence of heart failure after their first acute Q wave myocardial infarction (MI). BACKGROUND: Recently, ACE inhibitor therapy has been shown to have an early mortality benefit in unselected patients with acute MI, including patients without heart failure and a LVEF > 35%. However, the effects on LV mass and volume in this patient population have not been studied. METHODS: Thirty-five patients with a LVEF > 40% after their first acute Q wave MI were randomized to titrated oral ramipril (n = 20) or conventional therapy (control, n = 15). Magnetic resonance imaging (MRI) performed an average of 7 days and 3 months after MI provided LV volumes and mass from summated serial short-axis slices. RESULTS: Left ventricular end-diastolic volume index did not change in ramipril-treated patients (62 +/- 16 [SD] to 66 +/- 17 ml/m2) or in control patients (62 +/- 16 to 68 +/- 17 ml/m2), and stroke volume index increased significantly in both groups. However, LV mass index decreased in ramipril-treated patients (82 +/- 18 to 73 +/- 19 g/m2, p = 0.0002) but not in the control patients (77 +/- 15 to 79 +/- 23 g/m2). Systolic arterial pressure did not change in either group at 3-month follow-up. CONCLUSIONS: In patients with a LVEF > 40% after acute MI, ramipril decreased LV mass, and blood pressure and LV function were unchanged after 3 months of therapy. Whether the decrease in mass represents a sustained effect that is associated with a decrease in morbid events requires further investigation.

Predictors of coronary in-stent restenosis: importance of angiotensin-converting enzyme gene polymorphism and treatment with angiotensin-converting enzyme inhibitors.

OBJECTIVES: This study aimed to clarify the role of the angiotensin-converting enzyme (ACE) gene polymorphism in the development of in-stent restenosis. BACKGROUND: In-stent restenosis occurs after treatment of coronary artery stenosis in 12% to 32% of coronary interventions with stents. Experimental and clinical studies have suggested that the deletion/insertion (D/I) polymorphism of the ACE gene plays a role in this. METHODS: Quantitative coronary angiography before, immediately after and six months after stent implantation were compared in 369 patients, in whom D/I typing of the ACE gene was performed. RESULTS: At follow-up we found no differences between the three genotypes in minimal lumen diameter (homozygotes with two deletion alleles in the ACE gene [DD], 2.20 mm; heterozygotes with one deletion and one insertion allele in the ACE gene [DI], 2.19 mm; and homozygotes with two insertion alleles in the ACE gene [II], 2.25 mm). The corresponding diameter stenoses were: DD: 25%, DI: 27%, II: 27% (p = NS), and the frequency of restenosis (>50% diameter stenosis) was: DD: 15.7%, DI: 11.0% and II: 16.4% (p = NS). Logistic regression analysis identified diabetes (odds ratio [OR]: 3.0, 95% confidence interval [CI]: 1.0 to 8.7), lesion length (OR: 1.1, 95% CI: 1.01 to 1.30) and minimal lumen diameter immediately after the intervention (OR: 0.3, 95% CI: 0.14 to 0.85) as predictors of in-stent restenosis. In a post hoc analysis of patients treated versus those not treated with an ACE-inhibitor antagonist or an angiotensin receptor antagonist, we found an increased frequency of in-stent restenosis in the DD genotypes (40% vs. 12%, p = 0.006). CONCLUSIONS: The D/I polymorphism is not an independent predictor of coronary in-stent restenosis in general, but it may be of clinical importance in patients treated with ACE inhibitors or angiotensin receptor antagonists.

Optimizing the automatic segmentation of the left ventricle in magnetic resonance images.

Automatic segmentation of the left ventricular (LV) myocardial borders in cardiovascular MR (CMR) images allows a significant speed-up of the procedure of quantifying LV function, and improves its reproducibility. The automated boundary delineation is usually based on a set of parameters that define the algorithms. Since the automatic segmentation algorithms are usually sensitive to the image quality and frequently depend heavily on the acquisition protocol, optimizing the parameters of the algorithm for such different protocols may be necessary to obtain optimal results. In other words, using a default set of parameters may be far from optimal for different scanners or protocols. For the MASS-software, for example, this means that a total of 14 parameters need to be optimized. This optimization is a difficult and labor-intensive process. To be able to more consistently and rapidly tune the parameters, an automated optimization system would be extremely desirable. In this paper we propose such an approach, which is based on genetic algorithms (GAs). The GA is an unsupervised iterative tool that generates new sets of parameters and converges toward an optimal set. We implemented and compared two different types of the genetic algorithms: a simple GA (SGA) and a steady state GA (2SGA). The difference between these two algorithms lies in the characteristics of the generated populations: "nonoverlapping populations" and "overlapping populations," respectively "nonoverlapping" population means that the two populations are disjoint, and "overlapping" means that the best parameters found in the previous generation are included in the present population. The performance of both algorithms was evaluated on twenty routinely obtained short-axis examinations (eleven examinations acquired with a steady-state free precession pulse sequence, and nine examinations with a gradient echo pulse sequence). The optimal parameters obtained with the GAs were used for the LV myocardial border delineation. Finally, the automatically outlined contours were compared to the gold standard--manually drawn contours by experts. The result of the comparison was expressed as a degree of similarity after a processing time of less than 72 h to a 59.5% of degree of similarity for SGA and a 66.7% of degree of similarity for 2SGA. In conclusion, genetic algorithms are very suitable to automatically tune the parameters of a border detection algorithm. Based on our data, the 2SGA was more suitable than the SGA method. This approach can be generalized to other optimization problems in medical image processing.

A new type of model-based Roentgen stereophotogrammetric analysis for solving the occluded marker problem.

Roentgen stereophotogrammetric analysis (RSA) measures micromotion of an orthopaedic implant with respect to its surrounding bone. A problem in RSA is that the markers are sometimes overprojected by the implant itself. This study describes the so-called Marker Configuration Model-based RSA (MCM-based RSA) that is able to measure the pose of a rigid body in situations where less than three markers could be detected in both images of an RSA radiograph. MCM-based RSA is based on fitting a Marker Configuration model (MC-model) to the projection lines from the marker projection positions in the image to their corresponding Roentgen foci. An MC-model describes the positions of markers relative to each other and is obtained using conventional RSA. We used data from 15 double examinations of a clinical study of total knee prostheses and removed projections of the three tibial component markers, simulating occlusion of markers. The migration of the tibial component with respect to the bone, which should be zero, for the double examination is a measure of the accuracy of algorithm. With the new algorithm, it is possible to estimate the pose of a rigid body of which one or two markers are occluded in one of the images of the RSA radiograph with high accuracy as long as a proper MC-model of the markers in the rigid body is available. The new algorithm makes RSA more robust for occlusion of markers. This improves the results of clinical RSA studies because the number of lost RSA follow-up moments is reduced.