Fast and robust 3D ultrasound registration – Block and game theoretic matching

Real-time 3D US has potential for image guidance in minimally invasive liver interventions. However, motion caused by patient breathing makes it hard to visualize a localized area, and to maintain alignment with pre-operative information. In this work we develop a fast affine registration framework to compensate in real-time for liver motion/displacement due to breathing. The affine registration of two consecutive ultrasound volumes in time is performed using block-matching. For a set of evenly distributed points in one volume and their correspondences in the other volume, we propose a robust outlier rejection method to reject false matches. The inliers are then used to determine the affine transformation. The approach is evaluated on 13 4D ultrasound sequences acquired from 8 subjects. For 91 pairs of 3D ultrasound volumes selected from these sequences, a mean registration error of 1.8 mm is achieved. A graphics processing unit (GPU) implementation runs the 3D US registration at 8 Hz.     

Respiratory motion compensation by model-based catheter tracking during EP procedures

In many cases, radio-frequency catheter ablation of the pulmonary veins attached to the left atrium still involves fluoroscopic image guidance. Two-dimensional X-ray navigation may also take advantage of overlay images derived from static pre-operative 3D volumetric data to add anatomical details otherwise not visible under X-ray. Unfortunately, respiratory motion may impair the utility of static overlay images for catheter navigation. We developed a novel approach for image-based 3D motion estimation and compensation as a solution to this problem. It is based on 3D catheter tracking which, in turn, relies on 2D/3D registration. To this end, a bi-plane C-arm system is used to take X-ray images of a special circumferential mapping catheter from two directions. In the first step of the method, a 3D model of the device is reconstructed. Three-dimensional respiratory motion at the site of ablation is then estimated by tracking the reconstructed catheter model in 3D based on bi-plane fluoroscopy. Phantom data and clinical data were used to assess model-based catheter tracking. Our phantom experiments yielded an average 2D tracking error of 1.4 mm and an average 3D tracking error of 1.1 mm. Our evaluation of clinical data sets comprised 469 bi-plane fluoroscopy frames (938 monoplane fluoroscopy frames). We observed an average 2D tracking error of 1.0 ± 0.4 mm and an average 3D tracking error of 0.8 ± 0.5 mm. These results demonstrate that model-based motion-compensation based on 2D/3D registration is both feasible and accurate.     

A sensitivity analysis on 3D velocity reconstruction from multiple registered echo Doppler views

We present a new method for reconstructing a 3D + t velocity field from multiple 3D + t colour Doppler images. Our technique reconstructs 3D velocity vectors from registered multiple standard 3D colour Doppler views, each of which contains a 1D projection of the blood velocity. Reconstruction is based on a scalable patch-wise Least Mean Squares approach, and a continuous velocity field is achieved by using a B-spline grid.We carry out a sensitivity analysis of clinically relevant parameters which affect the accuracy of the reconstruction, including the impact of noise, view angles and registration errors, using simulated data. A realistic simulation framework is achieved by a novel noise model to represent variations in colour Doppler images based on multiscale additive Gaussian noise. Simulations show that, if the Target Registration Error <2.5 mm, view angles are >20° and the standard deviation of noise in the input data is <10 cm/s, the reconstructed velocity field presents visually plausible flow patterns and mean error in flow rate is approximately 10% compared to 2D + t Flow MRI. These results are verified by reconstructing 3D velocity on three healthy volunteers. The technique is applied to reconstruct 3D flow on three paediatric patients showing promising results for clinical application.     

Interventional 4D motion estimation and reconstruction of cardiac vasculature without motion periodicity assumption

Anatomical and functional information of cardiac vasculature is a key component in the field of interventional cardiology. With the technology of C-arm CT it is possible to reconstruct static intraprocedural 3D images from angiographic projection data. Current approaches attempt to add the temporal dimension (4D). In the assumption of periodic heart motion, ECG-gating techniques can be used. However, arrhythmic heart signals and slight breathing motion are degrading image quality frequently.To overcome those problems, we present a reconstruction method based on a 4D time-continuous B-spline motion field. The temporal component of the motion field is parameterized by the acquisition time and does not assume a periodic heart motion. The analytic dynamic FDK-reconstruction formula is used directly for the motion estimation and image reconstruction.In a physical phantom experiment two vessels of size 3.1 mm and 2.3 mm were reconstructed using the proposed method and an algorithm with periodicity assumption. For a periodic motion both methods obtained an error of 0.1 mm. For a non-periodic motion the proposed method was superior, obtaining an error of 0.3 mm/0.2 mm in comparison to 1.2 mm/1.0 mm for the algorithm with periodicity assumption. For a clinical test case of a left coronary artery it could be further shown that the method is capable to produce diameter measurements with an absolute error of 0.1 mm compared to state-of-the-art measurement tools from orthogonal coronary angiography. Further, it is shown for three different clinical cases (left/right coronary artery, coronary sinus) that the proposed method is able to handle a large variability of vascular structures and motion patterns. The complete algorithm is hardware-accelerated using the GPU requiring a computation time of less than 3 min for typical clinical scenarios.     

The angiotensin converting enzyme D allele is an independent risk factor for early onset coronary artery disease

ObjectiveThe role of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in early onset coronary artery disease age < 55 years (ECAD) is controversial. The aim of this study was to further evaluate the role of this ACE(I/D) gene polymorphism on the risk of premature CAD in patients from western Iran.MethodsThe ACE(I/D) genotypes were detected by PCR-RFLP in 323 individuals undergoing their first coronary angiography. Patients were placed into two groups: ECAD and late onset CAD age ≥ 55 years (LCAD).ResultsWe found a statistically significant association of the ACE D allele, as homozygous or ACE ID plus DD genotypes (ID + DD), only in the ECAD subjects OR = 1.35, p = 0.015, OR = 3.27, p = 0.014, and OR = 2.8, p = 0.013, respectively. In addition, there was a significant association after adjustment for the absence of history of diabetes, presence of normolipidemia and absence of history of blood pressure [OR 1.38, p = 0.017 and 2.35, p = 0.02]. Our results indicated that the ACE D allele is a risk factor for early onset of CAD even after correcting for conventional risk factors. The incidence of triple vessel disease was significantly higher in individuals carrying ACE(D/D) genotype in ECAD patients compared to those who carried ACE(I/I) genotype (OR 3.38; p = 0.019; 57.5% vs. 42.5%; p = 0.013).ConclusionThe presence of D allele of ACE can be important independent risk factor in the onset of CAD patients less than 55 years old in a west population of Iran. Larger collaborative studies are needed to confirm these results.     

Respiratory motion correction for image-guided cardiac interventions using 3-D echocardiography

In this paper, we investigate the use of 3-D echocardiography (echo) data for respiratory motion correction of roadmaps in image-guided cardiac interventions. This is made possible by tracking and calibrating the echo probe and registering it to the roadmap coordinate system. We compare two techniques. The first uses only echo–echo registration to predict a motion-correction transformation in roadmap coordinates. The second combines echo–echo registration with a model of the respiratory motion of the heart. Using experiments with cardiac MRI and 3-D echo data acquired from eight volunteers, we demonstrate that the second technique is more robust than the first, resulting in motion-correction transformations that were accurate to within 5 mm in 60% of cases, compared to 42% for the echo-only technique, based on subjective visual assessments. Objective validation showed that the model-based technique had an accuracy of 3.3 ± 1.1 mm, compared to 4.1 ± 2.2 mm for the echo only technique. The greater errors of the echo-only technique were mostly found away from the area of echo coverage. The model-based technique was more robust away from this area, and also has significant benefits in terms of computational cost.     

Automatic carotid artery distensibility measurements from CTA using nonrigid registration

The distensibility of a blood vessel is a marker of atherosclerotic disease. In this paper we investigate the feasibility of measuring carotid artery distensibility on 4D CTA, both manually and using a new automatic method. On 4D CTA datasets manual (n = 38) and automatic (n = 76) measurements of the carotid distensibility were performed. A subset (n = 10) of the manual annotations were repeated by a second observer. The interobserver variability was assessed using a Bland–Altman analysis and appeared to be too large to reliably measure the distensibility using manual annotation. We compared two versions of the automatic method: one using 3D registration and one using a 4D registration method. The latter resulted in a more smooth deformation over time. The automatic method was evaluated using a synthetic deformation and by investigating whether known relations with cardiovascular risk factors could be reproduced. The relation between distensibility and cardiovascular risk factors was tested with a Mann–Whitney U test. Automatic measurements revealed an association with hypertension whereas the manual measurements did not. This relation has been found by other studies too. We conclude that carotid artery distensibility measurements should be performed automatically and that the method described in this paper is suitable for that. All CTA datasets and related clinical data used in this study can be downloaded from our website (http://ctadist.bigr.nl).     

Effect of vitamin D on musculoskeletal pain and headache: A randomized,double-blind,placebo-controlled trial among adult ethnic minorities in Norway

Immigrants from South Asia, the Middle East, and Africa living in Northern Europe frequently have low vitamin D levels and more pain compared to the native Western population. The aim of this study was to examine whether daily vitamin D₃ (25 μg/d or 10 μg/d) supplementation for 16 weeks would improve musculoskeletal pain or headache compared to placebo. This randomized, double-blind, placebo-controlled, parallel-group trial recruited 251 participants aged 18 to 50 years, and 215 (86%) attended the follow-up visit. The pain measures were occurrence, anatomical localization, and degree of musculoskeletal pain, as measured by visual analogue scale (VAS) score during the past 2 weeks. Headache was measured with VAS and the Headache Impact Test (HIT-6) questionnaire. At baseline, females reported more pain sites (4.7) than males (3.4), and only 7% reported no pain in the past 2 weeks. During the past 4 weeks, 63% reported headache with a high mean HIT-6 score of 60 (SD 7). At follow-up, vitamin D level, measured as serum 25(OH)D₃, increased from 27 nmol/L to 52 nmol/L and from 27 nmol/L to 43 nmol/L in the 25-μg and 10-μg supplementation groups, respectively, whereas serum 25(OH)D₃ did not change in the placebo group. Pain scores and headache scores were improved at follow-up compared with baseline. The use of vitamin D supplements, however, showed no significant effect on the occurrence, anatomical localization, and degree of pain or headache compared to placebo.     

A method of 2D/3D registration of a statistical mouse atlas with a planar X-ray projection and an optical photo

The development of sophisticated and high throughput whole body small animal imaging technologies has created a need for improved image analysis and increased automation. The registration of a digital mouse atlas to individual images is a prerequisite for automated organ segmentation and uptake quantification. This paper presents a fully-automatic method for registering a statistical mouse atlas with individual subjects based on an anterior–posterior X-ray projection and a lateral optical photo of the mouse silhouette. The mouse atlas was trained as a statistical shape model based on 83 organ-segmented micro-CT images. For registration, a hierarchical approach is applied which first registers high contrast organs, and then estimates low contrast organs based on the registered high contrast organs. To register the high contrast organs, a 2D-registration-back-projection strategy is used that deforms the 3D atlas based on the 2D registrations of the atlas projections. For validation, this method was evaluated using 55 subjects of preclinical mouse studies. The results showed that this method can compensate for moderate variations of animal postures and organ anatomy. Two different metrics, the Dice coefficient and the average surface distance, were used to assess the registration accuracy of major organs. The Dice coefficients vary from 0.31 ± 0.16 for the spleen to 0.88 ± 0.03 for the whole body, and the average surface distance varies from 0.54 ± 0.06 mm for the lungs to 0.85 ± 0.10 mm for the skin. The method was compared with a direct 3D deformation optimization (without 2D-registration-back-projection) and a single-subject atlas registration (instead of using the statistical atlas). The comparison revealed that the 2D-registration-back-projection strategy significantly improved the registration accuracy, and the use of the statistical mouse atlas led to more plausible organ shapes than the single-subject atlas. This method was also tested with shoulder xenograft tumor-bearing mice, and the results showed that the registration accuracy of most organs was not significantly affected by the presence of shoulder tumors, except for the lungs and the spleen.     

Circulating sTWEAK improves the prediction of coronary artery disease

ObjectivesDecreased concentrations of circulating soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) were recently reported to be associated with atherosclerosis, but there are still no data concerning its predictive performance.Design and methodsThe current cross-sectional study investigates the potential of the novel atherosclerotic biomarker for the prediction of coronary artery disease (CAD). Serum sTWEAK was measured by ELISA in 76 CAD patients and 82 CAD-free subjects.ResultsSerum sTWEAK concentrations were significantly lower in the patients (534.5 ± 110.9 μg/L) than in the controls (688.1 ± 150.0 μg/L, p < 0.001), even after adjusting for different confounders (p < 0.001). The areas under ROC curves (AUC)s calculated for logistic regression models that included different known risk factors were significantly increased when sTWEAK was added to the corresponding model (p = 0.011–0.035).ConclusionsThe measurement of serum sTWEAK concentrations improves the prediction of CAD based on existing biomarkers.     

Personalising population-based respiratory motion models of the heart using neighbourhood approximation based on learnt anatomical features

Respiratory motion models have been proposed for the estimation and compensation of respiratory motion during image acquisition and image-guided interventions on organs in the chest and abdomen. However, such techniques are not commonly used in the clinic. Subject-specific motion models require a dynamic calibration scan that interrupts the clinical workflow and is often impractical to acquire, while population-based motion models are not as accurate as subject-specific motion models. To address this lack of accuracy, we propose a novel personalisation framework for population-based respiratory motion models and demonstrate its application to respiratory motion of the heart. The proposed method selects a subset of the population sample which is more likely to represent the cardiac respiratory motion of an unseen subject, thus providing a more accurate motion model. The selection is based only on anatomical features of the heart extracted from a static image. The features used are learnt using a neighbourhood approximation technique from a set of training datasets for which respiratory motion estimates are available. Results on a population sample of 28 adult healthy volunteers show average improvements in estimation accuracy of 20% compared to a standard population-based motion model, with an average value for the 50th and 95th quantiles of the estimation error of 1.6 mm and 4.7 mm respectively. Furthermore, the anatomical features of the heart most strongly correlated to respiratory motion are investigated for the first time, showing the features on the apex in proximity to the diaphragm and the rib cage, on the left ventricle and interventricular septum to be good predictors of the similarity in cardiac respiratory motion.     

Bundled postconditioning therapies improve hemodynamics and neurologic recovery after 17 min of untreated cardiac arrest

ObjectiveIschemic postconditioning (stutter CPR) and sevoflurane have been shown to mitigate the effects of reperfusion injury in cardiac tissue after 15 min of ventricular fibrillation (VF) cardiac arrest. Poloxamer 188 (P188) has also proven beneficial to neuronal and cardiac tissue during reperfusion injury in human and animal models. We hypothesized that the use of stutter CPR, sevoflurane, and P188 combined with standard advanced life support would improve post-resuscitation cardiac and neurologic function after prolonged VF arrest.MethodsFollowing 17 min of untreated VF, 20 pigs were randomized to Control treatment with active compression/decompression (ACD) CPR and impedance threshold device (ITD) (n = 8) or Bundle therapy with stutter ACD CPR + ITD + sevoflurane + P188 (n = 12). Epinephrine and post-resuscitation hypothermia were given in both groups per standard protocol. Animals that achieved return of spontaneous circulation (ROSC) were evaluated with echocardiography, biomarkers, and a blinded neurologic assessment with a cerebral performance category score.ResultsBundle therapy improved hemodynamics during resuscitation, reduced need for epinephrine and repeated defibrillation, reduced biomarkers of cardiac injury and end-organ dysfunction, and increased left ventricular ejection fraction compared to Controls. Bundle therapy also improved rates of ROSC (100% vs. 50%), freedom from major adverse events (50% vs. 0% at 48 h), and neurologic function (42% with mild or no neurologic deficit and 17% achieving normal function at 48 h).ConclusionsBundle therapy with a combination of stutter ACD CPR, ITD, sevoflurane, and P188 improved cardiac and neurologic function after 17 min of untreated cardiac arrest in pigs.All studies were performed with approval from the Institutional Animal Care Committee of the Minneapolis Medical Research Foundation (protocol #12-11).     

Association of angiotensin-converting enzyme polymorphism with coronary artery disease in Iranian patients with unipolar depression

ObjectivesMajor depressive disorder (MDD) is an increasingly recognized risk factor of coronary artery disease (CAD). The aim of this study was to assess the relationship between renin-angiotensin system (RAS) genetic polymorphisms and CAD in a sample of depressed Iranian patients.Design and methodsA total of 191 patients with a history of unipolar depression were enrolled in a case/control study. The presence of MDD was reconfirmed at study entry using DSM-IV criteria and CAD was diagnosed by coronary angiography. Genotyping of six RAS genes polymorphisms was performed by a modified PCR-RFLP method.ResultsDD genotype of ACE I/D was independently associated with the incidence of CAD in depressed patients (P = 0.011, OR = 9.41, 95% CI: 1.68–17.81). Moreover, serum creatinine (P = 0.033, OR = 11.91, 95%CI: 7.23–15.62) was an independent predictor of CAD among depressed individuals.ConclusionACE I/D polymorphism may play a major role in the development of CAD amongst Iranian depressed patients.     

The copeptin response after physical activity is not associated with cardiac biomarkers or asymptomatic coronary artery disease: The North Sea Race Endurance Exercise Study (NEEDED) 2013

BackgroundCopeptin concentrations increase both during acute coronary syndrome and following physical exercise. The relationship between copeptin increase following physical exercise and coronary artery disease (CAD) is uncertain. The aim of this study was to 1) describe the copeptin response following strenuous physical exercise, and 2) investigate the determinants of exercise induced copeptin concentrations, particularly in relation to cardiac biomarkers and CAD.MethodsSerum samples were collected from 97 recreational cyclists 24 h before, and immediately, 3 and 24 h after a 91-km bike race. Three subjects were subsequently diagnosed with significant asymptomatic CAD. Delta copeptin concentrations were correlated to patient characteristics and to biomarker concentrations.ResultsParticipants were 42.8 ± 9.6 years, and 76.3% were male. Copeptin concentrations increased to maximal levels immediately after the race and were normalized in > 90% after 3 h. A total of 53% and 39% exceeded the 95th and 99th percentile of the assay (10 and 19 pmol/L) respectively. In multivariate models, race time, serum sodium, creatinine and cortisol were significant predictors of copeptin levels. There was no correlation between changes in copeptin and changes in cardiac biomarkers (hs-cTnI, hs-cTnT and BNP). Copeptin concentrations were normal in the subjects with asymptomatic CAD.ConclusionsThe moderate, short-term, exercise induced copeptin increase observed in the present study was not related to hs-cTn or BNP levels. Copeptin was normal in three asymptomatic recreational athletes with significant CAD.     

Lower limb alignment and laxity measures before,during and after total knee arthroplasty: A prospective cohort study

BackgroundThis study compared knee alignment and laxity in patients before, during and after total knee arthroplasty, using methodologically similar procedures, with an aim to help inform pre-operative planning.MethodsEighteen male and 13 female patients were recruited, mean age 66 years (51–82) and mean body mass index of 33 (23–43). All were assessed pre- and postoperatively using a non-invasive infrared position capture system and all underwent total knee arthroplasty using a navigation system. Knee kinematic data were collected and comparisons made between preoperative clinical and intraoperative measurements for osteoarthritic knees, and between postoperative clinical and intraoperative measurements for prosthetic knees.FindingsThere was no difference in unstressed coronal mechanical femoral-tibial angles for either osteoarthritic or prosthetic knees. However, for sagittal alignment the knees were in greater extension intraoperatively (osteoarthritic 5.2° p < 0.001, prosthetic 7.2° p < 0.001). For osteoarthritic knees, both varus and valgus stress manoeuvres had greater angular displacements intraoperatively by a mean value of 1.5° for varus (p = 0.002) and 1.6° for valgus (p < 0.001). For prosthetic knees, only valgus angular displacement was greater intraoperatively (0.9°, p = 0.002).InterpretationSurgeons performing total knee arthroplasties should be aware of potential differences in alignment and laxity measured under different conditions to facilitate more accurate operative planning and follow-up.     

A subject-specific technique for respiratory motion correction in image-guided cardiac catheterisation procedures

We describe a system for respiratory motion correction of MRI-derived roadmaps for use in X-ray guided cardiac catheterisation procedures. The technique uses a subject-specific affine motion model that is quickly constructed from a short pre-procedure MRI scan. We test a dynamic MRI sequence that acquires a small number of high resolution slices, rather than a single low resolution volume. Additionally, we use prior knowledge of the nature of cardiac respiratory motion by constraining the model to use only the dominant modes of motion. During the procedure the motion of the diaphragm is tracked in X-ray fluoroscopy images, allowing the roadmap to be updated using the motion model. X-ray image acquisition is cardiac gated. Validation is performed on four volunteer datasets and three patient datasets. The accuracy of the model in 3D was within 5 mm in 97.6% of volunteer validations. For the patients, 2D accuracy was improved from 5 to 13 mm before applying the model to 2–4 mm afterwards. For the dynamic MRI sequence comparison, the highest errors were found when using the low resolution volume sequence with an unconstrained model.     

Circulating osteoprotegerin is increased in the metabolic syndrome and associates with subclinical atherosclerosis and coronary arterial calcification

ContextThe relationship between osteoprotegerin (OPG) a glycoprotein related to bone metabolism and the metabolic syndrome (MS) has not been established.ObjectiveThe aim of this study is to evaluate OPG concentration in patients with MS and its association with subclinical atherosclerosis and coronary arterial calcification (CAC).Materials/methodsThe study included 238 asymptomatic patients. MS was diagnosed according to the NCEP/ATPIII guidelines. OPG was measured by ELISA. All subjects underwent ultrasonography of the common carotid arteries to measure intima-media thickness (IMT) and evaluate the presence of atheroma plaques. In a subgroup (n = 39) CAC was quantified by ECG-triggered cardiac computed tomography. Adipose tissue was excised from 25 patients and OPG expression by RT-PCR and immunohistochemistry was studied.ResultsPatients with the MS (n = 60) had higher OPG than patients without (n = 178) (p < 0.05). OPG correlated with IMT (r = 0.2, p = 0.005) and patients with atheroma plaques had higher OPG (p = 0.008) and also those with coronary artery calcification (p < 0.05).OPG expression was confirmed in adipose tissue (n = 12) and the expression was significantly higher in patients with MS than in those without (p = 0.003).ConclusionsThis study shows that OPG may potentially be a biomarker for cardiovascular risk/damage in the MS and identifies adipose tissue as a potential source of OPG.     

The myeloperoxidase -463G/A polymorphism and coronary artery disease risk: A meta-analysis of 1938 cases and 1990 controls

ObjectivesGenetic polymorphism of human myeloperoxidase (MPO) -463G/A has been implicated to alter the risk of coronary artery disease (CAD), but the results are controversial. To improve the reliability of the conflicting results, we conducted a meta-analysis of studies relating the MPO -463G/A polymorphism with the risk of CAD.Design and methodsTwo investigators independently searched the MEDLINE, EMBASE and Cochrane Library up to June, 2012. Summary odds ratios (OR) and 95% confidence interval (CI) for the MPO -463G/A polymorphism and CAD risk were calculated, and potential sources of heterogeneity and publication bias were explored. Statistical analysis was performed with the software program of Stata 9.0.Results5 case–control studies were finally identified for analyses, involving 1938 cases with CAD and 1990 controls. We found that the MPO -463G/A polymorphism has no significant association with overall CAD risk (G/G vs A/A: OR = 0.595, 95%CI = 0.298–1.188, P = 0.141; G/G vs G/A + A/A: OR = 0.886, 95%CI = 0.779–1.008, P = 0.066; G/G + G/A vs A/A: OR = 0.611, 95%CI = 0.334–1.119, P = 0.111; OR = 0.886, 95%CI = 0.779–1.008, P = 0.066; G vs A: OR = 0.843, 95%CI = 0.675–1.053, P = 0.133). The heterogeneity test showed that there were significant differences between individual studies in additive, recessive and allelic genetic models (P = 0.008, P = 0.021, P = 0.019, respectively); further analyses revealed that age and sex possibly account for the heterogeneity.ConclusionsOur meta-analysis demonstrated the evidence that there was no significant association between the MPO -463G/A polymorphism and the risk of CAD; larger and well-designed multicenter studies are needed to confirm our results.