Berend C. Stoel

Evaluation of Registration Methods on Thoracic CT: The EMPIRE10 Challenge

EMPIRE10 (Evaluation of Methods for Pulmonary Image REgistration 2010) is a public platform for fair and meaningful comparison of registration algorithms which are applied to a database of intra patient thoracic CT image pairs. Evaluation of nonrigid registration techniques is a nontrivial task. This is compounded by the fact that researchers typically test only on their own data, which varies widely. For this reason, reliable assessment and comparison of different registration algorithms has been virtually impossible in the past. In this work we present the results of the launch phase of EMPIRE10, which comprised the comprehensive evaluation and comparison of 20 individual algorithms from leading academic and industrial research groups. All algorithms are applied to the same set of 30 thoracic CT pairs. Algorithm settings and parameters are chosen by researchers expert in the con figuration of their own method and the evaluation is independent, using the same criteria for all participants. All results are published on the EMPIRE10 website (http://empire10.isi.uu.nl). The challenge remains ongoing and open to new participants. Full results from 24 algorithms have been published at the time of writing. This paper details the organization of the challenge, the data and evaluation methods and the outcome of the initial launch with 20 algorithms. The gain in knowledge and future work are discussed.

Diastolic Dysfunction in Hypertensive Heart Disease Is Associated With Altered Myocardial Metabolism

BACKGROUND Hypertension is an important clinical problem and is often accompanied by left ventricular (LV) hypertrophy and dysfunction. Whether the myocardial high-energy phosphate (HEP) metabolism is altered in human hypertensive heart disease and whether this is associated with LV dysfunction is not known. METHODS AND RESULTS Eleven patients with hypertension and 13 age-matched healthy subjects were studied with magnetic resonance imaging at rest and with phosphorus-31 magnetic resonance spectroscopy at rest and during high-dose atropine-dobutamine stress. Hypertensive patients showed higher LV mass (98+/-28 g/m2) than healthy control subjects (73+/-13 g/m2, P<0.01). LV filling was impaired in patients, reflected by a decreased peak rate of wall thinning (PRWThn), E/A ratio, early peak filling rate, and early deceleration peak (all P<0. 05), whereas systolic function was still normal. The myocardial phosphocreatine (PCr)/ATP ratio determined in patients at rest (1. 20+/-0.18) and during stress (0.95+/-0.25) was lower than corresponding values obtained from healthy control subjects at rest (1.39+/-0.17, P<0.05) and during stress (1.16+/-0.18, P<0.05). The PCr/ATP ratio correlated significantly with PRWThn (r=-0.55, P<0.01), early deceleration peak (r=-0.56, P<0.01), and with the rate-pressure product (r=-0.53, P<0.001). CONCLUSIONS Myocardial HEP metabolism is altered in patients with hypertensive heart disease. In addition, there is an association between impaired LV diastolic function and altered myocardial HEP metabolism in humans. The level of myocardial PCr/ATP is most likely determined by the level of cardiac work load.

A new model-based RSA method validated using CAD models and models from reversed engineering

Roentgen stereophotogrammetric analysis (RSA) was developed to measure micromotion of an orthopaedic implant with respect to its surrounding bone. A disadvantage of conventional RSA is that it requires the implant to be marked with tantalum beads. This disadvantage can potentially be resolved with model-based RSA, whereby a 3D model of the implant is used for matching with the actual images and the assessment of position and rotation of the implant. In this study, a model-based RSA algorithm is presented and validated in phantom experiments. To investigate the influence of the accuracy of the implant models that were used for model-based RSA, we studied both computer aided design (CAD) models as well as models obtained by means of reversed engineering (RE) of the actual implant. The results demonstrate that the RE models provide more accurate results than the CAD models. If these RE models are derived from the very same implant, it is possible to achieve a maximum standard deviation of the error in the migration calculation of 0.06 mm for translations in x- and y-direction and 0.14 mm for the out of plane z-direction, respectively. For rotations about the y-axis, the standard deviation was about 0.1 degrees and for rotations about the x- and z-axis 0.05 degrees. Studies with clinical RSA-radiographs must prove that these results can also be reached in a clinical setting, making model-based RSA a possible alternative for marker-based RSA.

Intravenous augmentation treatment and lung density in severe α1 antitrypsin deficiency (RAPID): a randomised, double-blind, placebo-controlled trial.

BACKGROUND The efficacy of α1 proteinase inhibitor (A1PI) augmentation treatment for α1 antitrypsin deficiency has not been substantiated by a randomised, placebo-controlled trial. CT-measured lung density is a more sensitive measure of disease progression in α1 antitrypsin deficiency emphysema than spirometry is, so we aimed to assess the efficacy of augmentation treatment with this measure. METHODS The RAPID study was a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial of A1PI treatment in patients with α1 antitrypsin deficiency. We recruited eligible non-smokers (aged 18-65 years) in 28 international study centres in 13 countries if they had severe α1 antitrypsin deficiency (serum concentration <11 μM) with a forced expiratory volume in 1 s of 35-70% (predicted). We excluded patients if they had undergone, or were on the waiting list to undergo, lung transplantation, lobectomy, or lung volume-reduction surgery, or had selective IgA deficiency. We randomly assigned patients (1:1; done by Accovion) using a computerised pseudorandom number generator (block size of four) with centre stratification to receive A1PI intravenously 60 mg/kg per week or placebo for 24 months. All patients and study investigators (including those assessing outcomes) were unaware of treatment allocation throughout the study. Primary endpoints were CT lung density at total lung capacity (TLC) and functional residual capacity (FRC) combined, and the two separately, at 0, 3, 12, 21, and 24 months, analysed by modified intention to treat (patients needed at least one evaluable lung density measurement). This study is registered with ClinicalTrials.gov, number NCT00261833. A 2-year open-label extension study was also completed (NCT00670007). FINDINGS Between March 1, 2006, and Nov 3, 2010, we randomly allocated 93 (52%) patients A1PI and 87 (48%) placebo, analysing 92 in the A1PI group and 85 in the placebo group. The annual rate of lung density loss at TLC and FRC combined did not differ between groups (A1PI -1·50 g/L per year [SE 0·22]; placebo -2·12 g/L per year [0·24]; difference 0·62 g/L per year [95% CI -0·02 to 1·26], p=0·06). However, the annual rate of lung density loss at TLC alone was significantly less in patients in the A1PI group (-1·45 g/L per year [SE 0·23]) than in the placebo group (-2·19 g/L per year [0·25]; difference 0·74 g/L per year [95% CI 0·06-1·42], p=0·03), but was not at FRC alone (A1PI -1·54 g/L per year [0·24]; placebo -2·02 g/L per year [0·26]; difference 0·48 g/L per year [-0·22 to 1·18], p=0·18). Treatment-emergent adverse events were similar between groups, with 1298 occurring in 92 (99%) patients in the A1PI group and 1068 occuring in 86 (99%) in the placebo group. 71 severe treatment-emergent adverse events occurred in 25 (27%) patients in the A1PI group and 58 occurred in 27 (31%) in the placebo group. One treatment-emergent adverse event leading to withdrawal from the study occurred in one patient (1%) in the A1PI group and ten occurred in four (5%) in the placebo group. One death occurred in the A1PI group (respiratory failure) and three occurred in the placebo group (sepsis, pneumonia, and metastatic breast cancer). INTERPRETATION Measurement of lung density with CT at TLC alone provides evidence that purified A1PI augmentation slows progression of emphysema, a finding that could not be substantiated by lung density measurement at FRC alone or by the two measurements combined. These findings should prompt consideration of augmentation treatment to preserve lung parenchyma in individuals with emphysema secondary to severe α1 antitrypsin deficiency. FUNDING CSL Behring.

Validation of computed tomographic lung densitometry for monitoring emphysema in α1-antitrypsin deficiency

Background: Lung densitometry derived from computed tomographic images offers an opportunity to quantify emphysema non-invasively, but a pathological standard cannot be applied to validate its use in longitudinal monitoring studies. Consequently, forced expiratory volume in 1 second (FEV1) remains the standard against which new methods must be judged. We related progression of densitometry (15th percentile point and voxel index, threshold −950 Hounsfield units) to disease stage and FEV1 decline in two studies of subjects with α1-antitrypsin deficiency (PiZ). Methods: Consistency of progression, measured using densitometry and FEV1, was assessed in relation to disease stage in a 2 year study of 74 subjects grouped according to the FEV1 criteria employed in the GOLD guidelines. In the second study of a subgroup of subjects with extended data (n = 34), summary statistics were applied to measurements performed annually over 3 years and the rate of progression of densitometry was related to FEV1 decline. Results: The progression of percentile point was consistent across a wide spectrum of disease severity, but voxel index progression varied in association with disease stage (p = 0.004). In the second study, FEV1 decline correlated with progression of lung densitometry (percentile point: rS = 0.527, p = 0.001; voxel index: rS = −0.398, p = 0.012). Conclusions: 15th percentile point is a more consistent measure of lung density loss across a wide range of physiological impairment than voxel index. However, both methods are valid for use in longitudinal and interventional studies in which emphysema is the major outcome target.

Optimization and standardization of lung densitometry in the assessment of pulmonary emphysema.

Currently, lung densitometry for the assessment of pulmonary emphysema has been fully validated against pathology, pulmonary function, and health status, and it is therefore being applied in pharmacotherapeutic trials. Nevertheless, its application for the early detection of emphysema has not yet been introduced in daily clinical practice. The main reason for this is the fact that it is not yet regarded a fully optimized and standardized technique. In this work, an overview is given on the current status of different standardization aspects that play an important role in this, ie, image acquisition, choice of densitometric parameter and image processing. To address these issues, solutions have been sought from the literature and from original data from previous studies. Standardization and optimization of lung densitometry has reached a more advanced stage than has been reported so far. If normal values will become available, this technique will be feasible for clinical practice. As a result, standardization for the detection and assessment of other density-related lung diseases can be achieved in a shorter period of time.

Correlation between annual change in health status and computer tomography derived lung density in subjects with α1-antitrypsin deficiency

Background: There is increasing recognition that questionnaires of health status and lung density measurements are more sensitive tools for assessing progression of emphysema than forced expiratory volume in 1 second (FEV1) and transfer coefficient (Kco). A study was undertaken to investigate prospectively the correlation between annual change in health status and computer tomography (CT) derived lung density in subjects with α1-antitrypsin deficiency. Methods: Twenty two patients of mean (SD) age 40.7 (9.2) years with ZZ type α1-antitrypsin deficiency were investigated at baseline and 30 months later by FEV1 and Kco, St George Respiratory Questionnaire (SGRQ), and by a spiral CT scan of the chest. CT data of chest images were analysed using software designed for automated lung contour detection and lung density measurements. The density data were corrected for changes in inspiration levels. Results: Changes in lung density, expressed as 15th percentile point or relative area below –950 HU, correlated well with changes in health status (SGRQ total score): R = −0.56, p = 0.007 or R = 0.6, p  = 0.003. Neither changes in health status nor changes in lung density correlated significantly with changes in FEV1 or changes in Kco. Conclusions: The SGRQ total score (which is a global measure in COPD) and lung density (a specific measure of emphysema) are sensitive to deterioration in patients with α1-antitrypsin deficiency. This finding may facilitate future studies with new drugs specific for emphysema, a frequently occurring component of COPD.

Variability in Densitometric Assessment of Pulmonary Emphysema With Computed Tomography.

Objectives:The objectives of this study were to investigate whether computed tomography (CT) densitometry can be applied consistently in different centers; and to evaluate the reproducibility of densitometric quantification of emphysema by assessment of different sources of variation, ie, intersite, interscan and inter- and intraobserver variability, in comparison with intersubject variability. Materials and Methods:In 5 different hospitals, 119 patients with emphysema were scanned using standardized protocols. In each site, an observer performed a quantitative densitometric analysis (including blood recalibration) on the corresponding patient group (n = 23–25) and one observer analyzed the entire group of 119 patients. After several months, the latter observer analyzed all data for a second time. Subsequently, different sources of variation were assessed by variance component analysis with and without volume correction of the data. Results:Inter- and intraobserver variability marginally contributes to the total variability (<0.001%). The interscan variability was 0.02% of the total variation after application of volume correction. The intersite variability was 48% as a result of one deviating CT scanner. Air recalibration normalized deviating air densities in CT scanners. Within sites, the intersubject variability ranged between 93% and 99% based on the analysis of 2 subsequent CT scans of the patients. Conclusions:Almost all variability in the density measurement of emphysema originates from differences between scanners and from differences in severity of emphysema between patients. Lung densitometry with multislice CT scanners is a highly reproducible measurement, especially if corrected for lung volume, because this reduces interscan variability.

Repeatability of lung density measurements with low-dose computed tomography in subjects with α-1-antitrypsin deficiency - Associated emphysema

Stolk J, Dirksen A, van der Lugt A, et al. Repeatability of lung density measurements with low-dose computed tomography in subjects with &agr;-1-antitrypsin deficiency–associated emphysema. Invest Radiol 2001;36:648-651. rationale and objectives. Multislice computed tomography (MSCT) of the lungs provides a new opportunity for longitudinal assessment of lung densities because of shorter scan duration. The aim of the present study was to assess the intraindividual variation of lung densities measured by MSCT of patients with emphysema. methods.Ten patients with emphysema participated in a study in which MSCT was obtained on two occasions, approximately 2 weeks apart. Scanning parameters were 140 kV, 20 mAs, 4 × 2.5-mm collimation, and effective slice thickness of 2.5 mm. Lung density was measured as the 15th percentile point and the relative area below −910 Hounsfield units (HU) by using Pulmo-LKEB software. results.The mean difference of the 15th percentile point was −1.29 ± 3.2 HU, and that for the relative area below the −910-HU parameter was −1.02% ± 3.09%. Intraclass coefficients of variation were 0.96 (0.86–0.99) and 0.94 (0.8–0.98), respectively (95% confidence interval). conclusions.Lung density parameters of emphysema derived by MSCT provide an opportunity for analysis of the treatment effects of new drugs on the progression of emphysema.

Sources of error in lung densitometry with CT.

RATIONALE AND OBJECTIVES To determine and analyze the most important error sources in lung CT densitometry in vivo. METHODS The authors examined the influences of CT acquisition errors, physiologic changes, and image segmentation errors on lung densitometry. Among others, spatial dependency and long-term reproducibility of the density measurements of blood and air were examined over a period of 4 years in a group of 28 patients with pulmonary emphysema. These results were related to the measured lung densities in this group. RESULTS The density measurement of blood and air is strongly dependent on the position in the thorax. Despite full-scanner calibrations, x-ray tube replacement can induce a significant increase in measured blood density. CONCLUSIONS A change in a lung density parameter over time can actually be the result of tube replacement or changing blood density. A simple postprocessing technique can correct for these changes.