Determination of intima-media thickness of the carotid artery: influences of methods, proband and examination variables

AIM: Comparison of two different methods for the measurement of the common carotid artery intima-media thickness (IMT) regarding results and reproducibility, and investigation of the influence of the subjects' characteristics on the results. METHOD: 20 healthy subjects were studied (6 men, 14 women, mean age 27.4 +/- 4.4 years). B-Mode pictures were taken of the carotid arteries on both sides (longitudinal sections from ventral and lateral) and stored for measurement either in systole or in diastole. Maximum IMT was measured conventionally by manual setting of calipers (method 1), the mean IMT over a length of 1 cm was calculated from the area of the intima plus media by means of a computer (method 2). 10 subjects were studied twice for the evaluation of intra- and interobserver variability. RESULTS: Mean IMT was between 0.48 +/- 0.07 mm (method 1/observer 1) and 0.55 +/- 0.07 mm (method 2/observer 2). IMT values resulting from method 2 had a better correlation in repeated measurements (coefficient 0.84/0.93 for inter-/intraobserver comparison) than those resulting from method 1 (0.79/0.67). Age and height were significantly correlated with IMT (coefficients 0.53 and 0.52 for method 2), no correlation was found for body weight, BMI, sex or years of smoking. There was a significant inverse correlation between blood pressure and IMT (-0.21 to -0.32). CONCLUSION: In younger healthy subjects, the results of IMT measurement are influenced by age, height and actual blood pressure. The values resulting from both methods are comparable, whereas method 2 has a better reproducibility.     

Circulating cell adhesion molecules are correlated with ultrasound-based assessment of carotid atherosclerosis

Although cellular adhesion molecules (CAMs) are hypothesized to play an important role in atherogenesis, the relationship between CAMs and systemic atherosclerosis is uncertain. Among 92 outpatients (48 men; mean+/-SD age, 65+/-9 years), we evaluated the association of soluble vascular CAM-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1) with carotid intimal-medial thickness (IMT), an index of early atherosclerosis. All subjects underwent a 2-dimensional ultrasound examination of both carotid arteries at the distal common carotid arteries and bifurcation. sVCAM-1 and sICAM-1 levels measured by enzyme-linked immunosorbent assay were significantly correlated with mean IMT of the common carotid artery (r=0.34 and r=0.30, respectively; P<0.01) and carotid bifurcation (r=0.31 and r=0.26, respectively; P<0.05), whereas sVCAM-1 was also positively associated with maximal carotid IMT (r=0.35, P<0.01). Adjustment for age attenuated the association between sVCAM-1 and common (r=0.16, P=0.13) and bifurcation (r=0.18, P=0.07) carotid IMT but had minimal effect on the associations between sICAM-1 and carotid measurements (r=0.32, P<0.01; r=0.23, P<0.05; for common and bifurcation IMT, respectively). Age-adjusted sICAM-1 levels increased in a stepwise fashion across common carotid IMT tertiles (253+/-27 versus 275+/-24 versus 384+/-26 pg/mL for the lowest, intermediate, and highest IMT tertiles, respectively; P<0.01). A similar trend was also found between sVCAM-1 levels and common carotid IMT tertiles (625+/-60 versus 650+/-53 versus 714+/-58 pg/mL; P<0.15). These associations were minimally affected in analyses adjusting for hypertension, diabetes, smoking, low and high density lipoprotein cholesterol, lipoprotein(a), and homocysteine, or in a subgroup analysis limited to those with no prior history of atherothrombotic disease. These data demonstrate a positive association between serum CAMs with carotid IMT and further support the hypothesis that systemic inflammation may have a role in atherosclerotic lesion development.     

Comparison of the precision of two vertebral morphometry programs for the lunar EXPERT-XL imaging densitometer

Comparative precision tests of the vertebral height measurement function of the Aberdeen Vertebral Morphometry System (AVMS) software and Lunar EXPERT-XL software were undertaken using four vertebrae from the same lateral spine dual energy X-ray absorptiometry (DXA) image of the same subject (male, 67 years). Two of the vertebrae were abnormal and two were normal. Three observers inexperienced in morphometry and one experienced observer took part in the study. Repeatability was obtained from 10 sequential measurements of the posterior, middle and anterior heights at the same sitting by the same observer. Intraobserver reproducibility compared the means of one set of measurements for all vertebrae with another taken 1 week later. Interobserver reproducibility compared the means of one set of measurements for all vertebrae from an experienced and an inexperienced observer, and from two inexperienced observers. The AVMS software had significantly higher (p < 0.05) repeatability (mean coefficient of variability, CV = 3.5%) than the Lunar software (mean CV = 5%), significantly higher (p < 0.01) intraobserver reproducibility (mean CV = 4.6%) than the Lunar software (mean CV = 8.5%), and significantly higher (p < 0.05) interobserver reproducibility (mean CV = 4.7%) than the Lunar software (mean CV = 7.5%). In conclusion, the new AVMS method possessed higher precision when measuring both abnormal and normal vertebrae and when used by both experienced and inexperienced observers.     

Repeat consultations in pediatric hospital emergencies

OBJECTIVE: To assess the extent of early atherosclerotic changes of the carotid arteries in young patients with familial hypercholesterolaemia (FH) detected as increased intima-media thickness (IMT), and to determine the relations between IMT and some clinical and blood variables such as lipid and lipoprotein(a) (Lp(a)) concentration and haemostatic factors. DESIGN: The IMT of the carotid bifurcation, the proximal 1 cm of the internal carotid artery, and the distal 1 cm of the common carotid artery was determined in all subjects using B mode ultrasonography. Blood lipids, fasting glucose, and several haemostatic variables were also analysed. SUBJECTS: 28 patients with FH (12 males and 16 females aged 11 to 27 years, one homozygote, 27 heterozygotes) and 28 sex and age matched normolipidaemic healthy subjects. RESULTS: The mean carotid IMT (the average of six measurements of the maximum far wall IMT in the three carotid segments on each side) was significantly greater in patients with FH than in controls (mean (SD) 0.71 (0.15) v 0.49 (0.08) mm, P < 0.001). In all subjects, the mean IMT was significantly correlated with total cholesterol (r = 0.59), low density lipoprotein (LDL) cholesterol (r = 0.60), triglycerides (r = 0.27), and systolic blood pressure (r = 0.47). No correlation was found between the mean IMT and Lp(a), fibrinogen, tissue plasminogen activator, and plasminogen activator inhibitor 1. CONCLUSIONS: The majority of young patients with FH have a greater intima-media thickness of the carotid arteries than healthy subjects. Since the individual susceptibility of patients with FH to increased LDL cholesterol is different, B mode ultrasonography could provide a useful tool to identify those who are more likely to develop premature atherosclerotic disease.     

Nitric oxide and ocular blood flow in patients with IDDM

PURPOSE: Color Doppler imaging (CDI) is a relatively new technique that allows quantification of blood flow velocity in orbital and ocular vasculature. Despite the numerous clinical studies that have used CDI, repeatability of this technique and agreement between observers have not been documented. METHODS: The authors performed a prospective investigation of the repeatability and agreement between observers on ophthalmic artery blood flow velocity measurements in 35 patients (35 eyes). RESULTS: Results on the estimated error of measurement (variability between repeated readings on the same subject) indicate good repeatability of the measurements; in fact, the measurement variances were only 5.6% for the peak systolic velocity, 11.4% for the end diastolic velocity, and 6.2% for the mean envelope velocity. The statistical analysis of repeatability showed a very narrow 95% confidence interval for both observers. The measurement of agreement between the two observers demonstrated the existence of a good concordance of the measurements taken by each observer on each subject. CONCLUSIONS: Results suggest that CDI is a reliable tool for quantitative assessment of ophthalmic artery blood flow velocity.     

Systemic pressure-flow reactivity to norepinephrine in rabbits: impact of endotoxin and fluid loading

The clinical significance of the dolichoarteriopathies (kinking, coiling and tortuosity) of the extracranial carotid arteries, their prognosis and etiopathogenesis have not yet been clearly defined. The aim of this study was to evaluate, by echo-color-Doppler, atherosclerotic lesions of carotids in subjects with, compared to those without dolichoarteriopathies. A total of 1220 subjects (aged 25-89 years), 316 with and 904 without dolichoarteriopathies, were studied. Patients were divided into 325 subjects without cardiovascular risk factors and 895 subjects with cardiovascular risk factors (352 with arterial hypertension alone, 298 with arterial hypertension associated with other cardiovascular risk factors, 245 with hypercholesterolemia, diabetes, cigarette smoking, alone or associated). Moreover, the study was performed specifically in a subgroup of 352 subjects with arterial hypertension without other cardiovascular risk factors. Myointimal thickness, as a mean of 5 measurements at the level of the common carotid, 2-3 cm from the flow-divider and plaques as a focal thickness > or = 2 mm, classified on the basis of echogenic characteristics (hard, fibrous, mixed, soft, hemorrhagic) and seat (bifurcation, common, internal and external carotid) were evaluated. In 316 patients with dolichoarteriopathies, compared to 904 patients without dolichoarteriopathies there were no differences in myointimal thickening (NS), the prevalence of carotid plaques was lower (p = 0.004) and there was no difference (NS) regarding ultrasonic characteristics (more frequently hard and less frequently fibrous, mixed and soft) and localization of plaques (more frequently at the level of the common and bifurcation and less frequently at the level of the internal and external carotid). In subjects without cardiovascular risk factors, myointimal thickness and carotid plaques did not show any significant differences (NS) in the group with compared to the without dolichoarteriopathies. On the contrary, either in subjects with cardiovascular risk factors, or in the subgroup with hypertension alone, myointimal thickening was equally represented (NS), while carotids with plaques were significantly less frequent (p = 0.002; p = 0.01) in the group with, compared to that without dolichoarteriopathies. In conclusion, dolichoarteriopathies of the carotids do not seem to be a consequence of atherosclerotic lesions but in the presence of cardiovascular risk factors or hypertension alone they may even prevent plaque formation.     

Chlamydia trachomatis screening in the adolescent population

1. The reproducibility of measurements of the arterial wall thickness in both the carotid and femoral artery was investigated by means of high-resolution B-mode ultrasonography. For this purpose, subjects with normal and increased intima-media thickness were selected. Images were stored on an optical disk and were analysed with a semi-automatic software program by two readers. Individuals were scanned twice by two independent observers. 2. Measurements were performed of the far and near wall of the common carotid artery and bulbous in 30 healthy subjects and 19 patients known to have an increased intima-media thickness. Far-wall measurements were made of the internal carotid artery on both sides and common femoral artery on the right side only. 3. In healthy subjects the mean within-observer coefficient of variation was 1.8% and 3.0% for the far wall in the common carotid artery on the right side and left side, respectively. For the near wall the mean coefficient of variation of the common carotid artery was 2.8% on the right and 3.4% on the left side. The mean coefficient of variation was less than 4% for both far and near wall in the bulbous and far wall in the internal carotid artery. Even in patients with increased intima-media thickness the mean coefficient of variation of each segment was less than 4.5%. In the control subjects the between-observer coefficient of variation of the common carotid artery was 2.8% and 5.1% for the far wall on the right and left side, respectively, and 3.4% and 4.2% for the near wall on the right and left side. In healthy subjects a mean difference of 0.002 mm within observers was found in the right far-wall common carotid artery, with limits of agreement of -0.048 to 0.052 mm. The coefficient of repeatability was 0.050 mm. For patients with increased intima-media thickness the mean difference in this segment was -0.006 mm (-0.094 to 0.082) with a coefficient of repeatability of 0.088 mm. For the near wall in the common carotid artery and far and near wall in the bulbous and internal carotid artery the mean differences were larger, but were all below 0.1 mm. The differences and limits of agreements increased between observers. In patients the between-observer mean difference of the far wall of the common carotid artery was -0.055 mm (-0.255 to 0.145). For the common femoral artery of normal control subjects the within- and between-observer mean differences were 0.005 mm (-0.119 to 0.129) and 0.015 mm (-0.081 to 0.111), respectively. 4. In conclusion, the reproducibility of intima-media thickness measurements in the common carotid artery is reliable, even in patients with increased artery wall thickness. Also in other segments prone to atherosclerosis, such as the bulbous, internal carotid artery and common femoral artery, a good reproducibility was found. To obtain good reproducibility it is highly recommended to use the same ultrasonographer to scan patients in follow-up studies.     

Differences in near-wall shear rate in the carotid artery within subjects are associated with different intima-media thicknesses

In the common carotid artery, reflections originating from the periphery and the flow divider may affect the shape of the flow velocity profile and, hence, near-wall shear rate (WSR) differently just before the bifurcation (location B) than 20 to 30 mm farther upstream (location A). Recent developments in ultrasound technology allow the assessment of WSR and intima-media thickness (IMT) at the same site in the carotid artery in vivo. We therefore determined WSR at locations A and B and investigated whether the differences between both sites, if any, were associated with different IMTs and different mechanical properties of the arterial wall. The effect of age on the possible differences was assessed as well. The study was performed on presumably healthy volunteers (n=53). In all individuals, IMT was larger at location B than at location A. The relative difference in IMT between both locations was not affected by age. No significant differences in diameter and distension were found between locations. Near peak systolic and near mean WSR at the posterior wall (PWSRp and MWSRp, respectively) were significantly lower at location B than at location A. The relative differences in PWSRp and MWSRp between both locations within subjects were independent of age. The velocity profiles were more blunted at location A than at location B. PWSRp and MWSRp significantly decreased and IMT significantly increased with age at both locations. IMT was negatively correlated with PWSRP and MWSRP at location B, but this correlation was not significant at location A. In summary, in the common carotid artery, the lower WSR near the bifurcation, as compared with 20 to 30 mm upstream, is associated with a larger IMT than at the more proximal site. The relative difference between both locations within subjects is independent of age.     

Increased common carotid intima-media thickness. Adaptive response or a reflection of atherosclerosis? Findings from the Rotterdam Study

BACKGROUND AND PURPOSE: Carotid intima-media thickness (IMT) measurements are used widely to study atherosclerosis. Some have suggested that an increased IMT reflects a nonatherosclerotic adaptive response to changes in shear stress and tensile stress. This stems from the hypothesis that changes in shear stress and subsequently in lumen diameter are followed by changes in IMT to keep tensile stress constant. We studied the relation of common carotid IMT to common carotid end-diastolic lumen diameter and tensile stress, as approximated by mean arterial pressure (lumen diameter/IMT)]. METHODS: A cross-sectional analysis was performed with data obtained from the first 1715 participants in the Rotterdam Study, a population-based cohort study among 7983 subjects aged 55 years and over who underwent ultrasonographic examination of the carotid arteries. End-diastolic lumen diameter and IMT of the common carotid arteries were evaluated and quantified. RESULTS: With increasing IMT, inner and outer lumen diameters increased gradually, and beyond an IMT of 1.10 mm, the inner lumen diameter decreased. Tensile stress increased with increasing lumen diameter instead of being constant. The lumen-to-IMT ratio was constant across levels of mean arterial pressure. CONCLUSIONS: Our findings are compatible with the view that at lower degrees of IMT, the thickening appears to reflect an equilibrium state in which the effects of pressure and flow on the arteries are in balance, given a characteristic relation between shear stress and local transmural pressure. Beyond a certain level, IMT more likely may represent atherosclerosis. Regardless of whether common carotid IMT reflects local atherosclerosis, it may still serve as a graded marker for cardiovascular risk.     

Variance components analysis of carotid and femoral intima-media thickness measurements. REGRESS Study Group, Interuniversity Cardiology Institute of The Netherlands, Utrecht, The Netherlands. Regression Growth Evaluation Statin Study

B-mode ultrasound intima-media thickness (IMT) measurements of carotid and femoral arterial walls are used in atherosclerosis studies. In this study, the components contributing to IMT measurement variability in males with coronary artery disease were investigated by means of repeated B-mode ultrasound scans and repeated off-line video image analyses. For statistical analysis, a mixed-model analysis of variance was used. From sonographer data, it was shown that human subjects and their arterial wall segments contributed 75% of the total IMT measurement variability in this population. Inter-sonographer variance contributed 25%. The intra-sonographer variance was negligible (<1%). In off-line image analysis, variance components due to subjects and segments, inter-analyst variance, and residual fluctuation were 88%, < 1% and 11%, respectively. Intra-analyst variance was negligible (<1%). The major source of B-mode ultrasound IMT measurement variability finds its origin in subjects and their arterial walls. Although sonographers proved a lesser source of variability, in comparative studies they should enter a study well trained and should be randomly assigned to subjects. Follow-up examinations should preferably be done by the same sonographer. Off-line image analysis contributed little to IMT measurement variability.     

Laryngeal tumor volume measurements determined with CT: a study on intra- and interobserver variability

PURPOSE: To investigate the intra- and interobserver variability of computed tomography-based volume measurements of laryngeal tumors. METHODS AND MATERIALS: The volume of 13 laryngeal tumors was repeatedly measured by five independent observers in four different sessions, using the summation-of-areas technique. Mean tumor volume and its standard deviation were calculated for each tumor. Statistical analysis was done with analysis of variance, Spearman rank correlation, and linear regression. RESULTS: Both the effect of the observers (p < 0.0001) and the effect of the session (p < 0.01) on tumor volume was statistically significant. Interobserver variability was the most important component of total variability (89.3%). A significant rank correlation was found between mean volume and standard deviation (p < 0.01); the relationship between mean tumor volume and standard deviation can be described using linear regression [standard deviation = 0.28 volume + 0.35 (R = 0.79)]. CONCLUSION: Total variability in the computed tomography-based measurement of laryngeal tumor volume can be reduced by having the measurements done by a single trained observer.     

Detection of the phosphorylcholine epitope in streptococci, Haemophilus and pathogenic Neisseriae by immunoblotting

Intimal-medial thickness (IMT) of the extracranial carotid arteries measured by B-mode ultrasonography has been used as a marker of systemic and coronary atherosclerosis. Previous studies have indicated that maximum and mean carotid IMT are significantly correlated with the extent and severity of coronary artery disease (CAD), but the clinical usefulness of these markers is limited because they are neither specific nor sensitive enough to identify patients with or without significant CAD. The correlation of a new IMT marker, variance of IMT, with coronary risk factors and coronary atherosclerosis was investigated in 200 patients who underwent carotid ultrasonography and coronary angiography. IMT was measured in 16 sites of the extracranial carotid arteries for the calculation of mean, maximum and variance of IMT. Univariate analysis showed that these three indexes were significantly correlated with age, serum lipoprotein (a) and hypertension. However, age was correlated weakly with variance of IMT. There were significant gender differences in the mean and maximum IMT but not in the variance. There were also significant correlations of mean IMT with smoking, and maximum and variance of IMT with high-density lipoprotein. Multiple logistic regression analysis in 100 age and sex matched patients indicated that the only significant predictor for CAD in this subgroup was variance of IMT (odds ratio = 1.6). These results indicated that each risk factor causes different morphologic manifestations in the carotid atherosclerotic lesion. Variance of IMT, which represents the irregularity of carotid IMT, was correlated well with CAD and appears to be useful for assessing systemic and coronary atherosclerosis.     

Severe rhabdomyolysis with renal failure after intranasal cocaine use

Torsion of a long bone is the twist along its longitudinal axis; torsion of the radius is defined by the angle between the proximal and distal metaphyses in the transverse plane. Measurement of the radial torsion angle provides a means of detection and quantification of malrotation after a fracture. The purpose of the current study was to develop and standardize a technique for the measurement of torsion of the radius. Axial computerized tomographic images of thirty-nine pairs of dry cadaver specimens of normal radii, and an additional four pairs of radii with a unilateral deformity of the distal metaphysis that was consistent with a previous fracture, were studied and a measurement protocol was established. The radial torsion angle was measured by three independent observers on two separate occasions. Reproducibility of the technique was determined with use of the intraclass correlation coefficient to express both interobserver and intraobserver reliability. Consistency of measurements between observers and by the same observer was high, with intraclass correlation coefficients ranging from 0.87 to 0.94. The mean torsion angle for the eighty-two normal radii in the study was 32.6 degrees (95 per cent confidence interval of the mean, 30.3 to 34.9 degrees; range, 1.4 to 58.8 degrees). There were small variations in torsion angle between the two radii of each normal pair (mean side-to-side difference, 4.9 degrees; 95 per cent confidence interval of the mean, 3.5 to 6.3 degrees). The mean torsion angle of the four radii with a malunited fracture was 10.4 degrees (95 per cent confidence interval of the mean, 5.7 to 15.1 degrees), and the mean side-to-side difference in the pairs containing these radii was 24.1 degrees (95 per cent confidence interval of the mean, 8.5 to 39.6 degrees; p < 0.0001 compared with the normal radii).     

Towards cost-effective dialysis therapy in Europe: the need for a multidisciplinary approach

BACKGROUND AND PURPOSE: Although the reliability of the assessment of severe 70% to 99% carotid stenosis by carotid angiography has been proven excellent, this may not necessarily be the case for a more detailed classification of carotid stenoses by 10% categories. METHODS: Angiograms of the carotid arteries were assessed pairwise by three independent, experienced observers. The measurements of the degree of stenosis of both the carotid bifurcation and the internal carotid artery were made according to the European Carotid Surgery Trial method. Kappa statistics were used to assess the agreement beyond chance for severe (70% to 99%) carotid stenosis (kappa 1) and for 10% categories of carotid stenosis (kappa 2). The penalty scores were adjusted by weights for the relative difference in risk (RDR) of stroke in the ipsilateral carotid distribution between the 10% categories (kappa 3). An adjustment of the RDR method was made by assuming that only patients with a severe carotid stenosis would undergo surgery, and the penalty would be 0 if no disagreement would exist about the indication for surgery (kappa 4). An even further adjustment (kappa 5) was made by assuming that assessment of the rate of carotid stenosis by one or both observers would lead to different treatment recommendations in 50% of the cases, and accordingly the penalty for disagreement (RDR) was halved. RESULTS: One hundred twenty-one carotid bifurcations in 65 patients with a transient ischemic attack or nondisabling stroke were assessed. The intraclass correlation between the exact estimates of carotid stenosis was .90 (95% confidence interval, .85 to .92). The mean difference in stenosis between the two raters was 0.8% (95% confidence interval, -2.1% to 3.7%). kappa 1 to kappa 5 equaled 0.80, 0.40, 0.79, 0.91, and 0.92, respectively. CONCLUSIONS: Interobserver agreement for distinct 10% categories of angiographic carotid stenosis is moderate, but when realistic risk- and decision-based weights are used, agreement between experienced observers can be almost perfect.     

Regional distribution of 5alpha-reductase type 1 and type 2 mRNA along the human epididymis

BACKGROUND AND PURPOSE: In women, symptoms of coronary artery disease are delayed by 10 to 15 years in comparison with men, most likely because of the protective effect of ovarian hormones. This report compares the prevalence and degree of carotid atherosclerosis between 292 premenopausal women and 294 women at 5 to 8 years after menopause. METHODS: Scans were performed in the same laboratory over the same time period for both groups. Intima-media thickness (IMT) was averaged across the common, bulb, and internal carotids. The plaque index summarized degree of focal plaque based on the size and number of plaques throughout both carotid systems. RESULTS: Mean IMT was 0.69 mm for premenopausal women and 0.77 mm for postmenopausal women (P < 0.001). Prevalence of plaque was 25% among premenopausal women and 54% among postmenopausal women (P < 0.001). In both premenopausal and postmenopausal women, risk factors measured before menopause were associated with carotid atherosclerosis. Premenopausal risk factors independently associated with IMT were higher pulse pressure (P < 0.001), triglycerides (P = 0.002), body mass index (P < 0.001), and study group (a surrogate for both age and menopausal status; P < 0.001). Premenopausal risk factors independently associated with focal plaque were ever smoking (P = 0.002), higher pulse pressure (P = 0.028), higher LDL (P = 0.003), age at baseline (P = 0.050), and study group (P < 0.001). CONCLUSIONS: Subclinical carotid atherosclerosis can be observed in middle-aged women. Risk factors measured before menopause are clearly associated with subclinical disease measured both concurrently and at 5 to 8 years after menopause.     

Measurement of regional aortic compliance by MR imaging: a study of reproducibility

The reproducibility of MR imaging for the measurement of aortic compliance was studied in 47 healthy volunteers. Long and short term reproducibility and intraobserver variability were tested. The method was modified to improve image quality and short term reproducibility and intraobserver variability retested. For comparison, spin echo imaging was compared with cine gradient echo imaging. Initial long term reproducibility showed a mean difference (+/-SE) of 3% (+/- 7%) with 95% confidence interval (CI) for limits of agreement of +/- 69%. Short term reproducibility (7% +/- 6%, 95% CI +/- 46%) and intraobserver variability (1% +/- 2%, 95% CI +/- 31%) were better. After modification of the technique and optimization of image quality, both short term reproducibility and intraobserver variability improved (0% +/- 3%, 95% CI +/- 17% and 5% +/- 2%, 95% CI +/- 16% respectively). Aortic compliance can be measured using spin echo MR imaging with good reproducibility provided care is taken to obtain good quality images with high spatial resolution.     

Angiogenesis in breast cancer: a comparative study of the observer variability of methods for determining microvessel density

The purpose of this study was to evaluate the reliability of different methods for estimating neovascularization in breast cancer and to compare them in terms of observer variability. The microvessel endothelium was stained immunohistochemically by antibodies against CD34. The investigated methods included Chalkley counting, estimation of intratumoral microvessel density (MVD) by one hot-spot, MVD by the mean value of three hot-spots, and the highest value of MVD in three hot-spots. In addition, we applied stereology in the quantification of angiogenesis in the whole tumor section by random and systematically distributed sampling fields. Each of forty tumors was measured with all methods, twice by the same observer and once by another observer. Observer variation was analyzed by orthogonal regression, estimating the slope and intercepts with 95% confidence intervals (CI), and by analysis of agreement using difference plots. Intraobservationally, the methods had variations of the same magnitude (coefficient of variation [CV] approximately 20%). Interobservationally, the stereologic estimate of vessel profiles, Q(A), from the whole tumor section and the Chalkley counting method had the lowest variation (CV approximately 21%), with a small contribution by observers alone (CV 8% to 9%). Interobservationally, the MVD methods had considerable variation with a large contribution by observers alone (CV approximately 30%), which was lowest using the mean of three hot-spots. Correlation slope and 95% CI of Chalkley were 1.18 (0.95, 1.48), CV 20%; slope of MVD (mean) was 1.14 (0.91, 1.43), CV 31%; and slope of MVD (max) was 1.15 (0.92, 1.45), CV 36%. The slope of MVD on one hot-spot was 1.33 (1.08, 1.63); CV 38%. Additional measurements performed using a conference microscope, eliminating subjectivity in hot-spot selection and field sampling, optimized the reproducibility: slope was 1.02 (0.99, 1.04); CV of differences, 3.5%. On the other hand, reproducibility was not necessarily optimized by choosing the same hot-spot area, because variation in selecting a microscopic field could yield different counting numbers. The stereologic estimation of QA based on the whole tumor section had a high reproducibility, with low variation due to observers. The Chalkley and MVD methods had moderate reproducibility, and the Chalkley method had low variation due to observers alone. For all methods, the biologic variation among patients was the major contributor to the total variation. The Chalkley and MVD methods have been published to provide significant prognostic estimates in breast cancer, but the Chalkley method has less observer variation and may be superior from a methodologic point of view.     

Measurement of rib vertebral angle difference. Intraobserver error and interobserver variation

STUDY DESIGN: The rib vertebral angle difference was measured on 50 juvenile scoliosis radiographs. Three observers measured each radiograph independently and on three separate occasions to determine interobserver and intraobserver error. OBJECTIVE: To determine the interobserver and intraobserver error in measuring the rib vertebral angle difference. SUMMARY OF BACKGROUND DATA: The rib vertebral angle difference is a commonly used measurement, the reliability of which has not been tested rigorously. METHODS: Fifty standing radiographs of juvenile scoliosis were measured. All patients were Risser 0 at the time of measurement. All angles were measured by the method of Mehta using the same protractor and apical vertebra to avoid confounding variables. Three surgeons individually measured the 50 radiographs randomly and on three separate occasions. All markings were erased before remeasurement. RESULTS: The intraobserver error was determined to be 4.4 degrees. The interobserver error was 3.6 degrees. The interobserver accuracy was 6.2 degrees. CONCLUSIONS: The rib vertebral angle measurement is highly reproducible and is a valid measurement.     

Validation of new pulsed Doppler echocardiographic techniques for assessment of pulmonary hemodynamics

In preparation for a vasodilator study on chronic obstructive pulmonary disease (COPD), we investigated the reliability of recently described pulsed Doppler techniques for estimating pulmonary artery pressure (PAP) and cardiac output (CO). Our aims were to determine the following: (1) the imaging success rate for pulsed Doppler measurements; (2) the repeatability of the measurements, and interobserver and intraobserver variability; and (3) the accuracy of Doppler compared with catheter measurements. Doppler studies were attempted in 81 patients (cardiac disease [23], COPD [22], sleep apnea [32], and normal subjects [4]). Suitable images were obtained in 68 subjects (84 percent) and in 76 subjects (94 percent) for PAP and CO estimations, respectively. The lowest imaging success rates were in COPD patients (68 percent for PAP and 86 percent for CO estimation). Repeatability of the techniques was assessed in four cardiac patients and three healthy volunteers by performing four replicate studies in each subject over 1 h. Intrasubject coefficient of variation was < 10 percent for PAP and < 5 percent for CO. The intraobserver variability for Doppler estimation of systolic and mean PAP was 5.5 percent and 5.8 percent, respectively. The corresponding values for interobserver variability were 6.7 percent and 6.2 percent. Intraobserver and interobserver variability for "nongeometric" method of estimating CO was 5.1 percent and 5.9 percent, respectively. Agreement was good between catheter-measured and Doppler-estimated PAP in the 27 patients tested (cardiac [19] and COPD [8]) for both mean and systolic pressures (r = 0.96 and r = 0.97, respectively). The correlations between thermodilution and Doppler estimations of CO in eight COPD patients were 0.77 ("geometric" technique) and 0.97 ("nongeometric" technique). We conclude that pulsed Doppler techniques can be used to obtain accurate and reproducible quantitative information on pulmonary hemodynamics in a wide range of patients. Suitable Doppler images can be obtained in more than two thirds of COPD patients.     

Reproducibility of fat area measurements in young, non-obese subjects by computerized analysis of magnetic resonance images

OBJECTIVE: To assess reproducibility, expressed as both inter-observer variability and intra-observer variability, of fat area measurements on images obtained by magnetic resonance (MR); to compare variability between fat area measurements, calculated from a single image per body region and from the average fat area of three images, and to determine reproducibility of image acquisition at the abdominal level. SUBJECTS: Thirty young, non-obese subjects (reproducibility of image analysis) and nine young, non-obese subjects (reproducibility of image acquisition). METHODS: Three MR images at the level of the abdomen (in 30 subjects) and at the level of the hip and thigh (in 14 of them). Quantification of subcutaneous fat depots (abdomen, hip and thigh) and visceral fat depots using an image-analyzing computer program. Assessment of variability of image analysis for fat area measurements between two observers and within observers. Assessment of reproducibility of image acquisition at the abdominal level (in nine subjects). RESULTS: Subcutaneous fat areas in all body regions were quantified with coefficients of variation (CV) ranging from only 2.1%-4.9%. By contrast, visceral fat area measurements showed markedly higher CVs (range: 9.4%-17.6%). Moreover, relative variability was much larger in small visceral fat areas (CVs up to 25.6%). The majority of CVs, calculated for intra-observer variability and calculated from the average fat area measurements of three images, was lower than calculated for inter-observer variability and for one single image, respectively. In particular, for the visceral fat depot, this reduction in variability had practical consequences for the number of subjects required for a study. Variation of repeated image acquisition was in the same range as variation of repeated measurements on the same image. CONCLUSION: One image per body site is sufficient to obtain a reliable estimate of subcutaneous fat depots. For estimations of the visceral fat depot, the average area measurements of three images reduces variability and increases statistical power. The availability of one single experienced observer during a study adds to accuracy.