Application of L1-Norm Regularization to Epicardial Potential Solution of the Inverse Electrocardiography Problem

The electrocardiographic inverse problem of computing epicardial potentials from multi-electrode body-surface ECG measurements, is an ill-posed problem. Tikhonov regularization is commonly employed, which imposes penalty on the L2-norm of the potentials (zero-order) or their derivatives. Previous work has indicated superior results using L2-norm of the normal derivative of the solution (a first order regularization). However, L2-norm penalty function can cause considerable smoothing of the solution. Here, we use the L1-norm of the normal derivative of the potential as a penalty function. L1-norm solutions were compared to zero-order and first-order L2-norm Tikhonov solutions and to measured ‘gold standards’ in previous experiments with isolated canine hearts. Solutions with L1-norm penalty function (average relative error [RE] = 0.36) were more accurate than L2-norm (average RE = 0.62). In addition, the L1-norm method localized epicardial pacing sites with better accuracy (3.8 ± 1.5 mm) compared to L2-norm (9.2 ± 2.6 mm) during pacing in five pediatric patients with congenital heart disease. In a pediatric patient with Wolff–Parkinson–White syndrome, the L1-norm method also detected and localized two distinct areas of early activation around the mitral valve annulus, indicating the presence of two left-sided pathways which were not distinguished using L2 regularization.     

Accuracy of Quadratic Versus Linear Interpolation in Noninvasive Electrocardiographic Imaging (ECGI)

Electrocardiographic Imaging (ECGI) is a cardiac functional imaging modality, noninvasively reconstructing epicardial potentials, electrograms and isochrones (activation maps) from multi-channel body surface potential recordings. The procedure involves solving Laplace’s equation in the source-free volume conductor between torso and epicardial surfaces, using Boundary Element Method (BEM). Previously, linear interpolation (LI) on three-noded triangular surface elements was used in the BEM formulation. Here, we use quadratic interpolation (QI) for potentials over six-noded linear triangles. The performance of LI and QI in ECGI is evaluated through direct comparison with measured data from an isolated canine heart suspended in a human-torso-shaped electrolyte tank. QI enhances the accuracy and resolution of ECGI reconstructions for two different inverse methods, Tikhonov regularization and Generalized Minimal Residual (GMRes) method, with the QI-GMRes combination providing the highest accuracy and resolution. QI reduces the average relative error (RE) between reconstructed and measured epicardial potentials by 25%. It preserves the amplitude (average RE reduced by 48%) and morphology of electrograms better (average correlation coefficient for QI ∼ 0.97, LI ∼ 0.92). We also applied QI to ECGI reconstructions in human subjects during cardiac pacing, where QI locates ventricular pacing sites with higher accuracy (≤ 10 mm) than LI (≤ 18 mm).     

A Minimal Product Method and Its Application to Cortical Imaging

In order to reduce the spatial blurring effect due to the head volume conductor, cortical imaging technique (CIT) can be used to reconstruct the cortical potential distribution from the scalp potential measurement with enhanced spatial resolution. To overcome the ill-posed nature of the inverse problem, Tikhonov regularization (TIK) and truncated Singular Value Decomposition (TSVD) are commonly used by choosing the appropriate regularization parameter and truncation parameter, respectively. We have developed a minimal product method (MINP) to determine the regularization and truncation parameters. The present computer simulation and experimental results indicate that the MINP can be easily implemented in both TIK and TSVD with satisfactory performance, and suggest the potential applications of the MINP method in determining the corner of the L-curve.     

Identification of a chemotactic sensitivity in a coupled system

Email: renee.fister{at}murraystate.edu Corresponding author. Email: maeve.mccarthy{at}murraystate.edu Received on July 16, 2007. Revised on March 24, 2008. Accepted on June 7, 2008. Chemotaxis is the process by which cells behave in a way thatfollows the chemical gradient. Applications to bacteria growth,tissue inflammation and vascular tumours provide a focus onoptimization strategies. Experiments can characterize the formof possible chemotactic sensitivities. This paper addressesthe recovery of the chemotactic sensitivity from these experimentswhile allowing for non-linear dependence of the parameter onthe state variables. The existence of solutions to the forwardproblem is analysed. The identification of a chemotactic parameteris determined by inverse problem techniques. Tikhonov regularizationis investigated and appropriate convergence results are obtained.Numerical results of concentration-dependent chemotactic termsare explored.     

Application of the Method of Fundamental Solutions to Potential-based Inverse Electrocardiography

Potential-based inverse electrocardiography is a method for the noninvasive computation of epicardial potentials from measured body surface electrocardiographic data. From the computed epicardial potentials, epicardial electrograms and isochrones (activation sequences), as well as repolarization patterns can be constructed. We term this noninvasive procedure Electrocardiographic Imaging (ECGI). The method of choice for computing epicardial potentials has been the Boundary Element Method (BEM) which requires meshing the heart and torso surfaces and optimizing the mesh, a very time-consuming operation that requires manual editing. Moreover, it can introduce mesh-related artifacts in the reconstructed epicardial images. Here we introduce the application of a meshless method, the Method of Fundamental Solutions (MFS) to ECGI. This new approach that does not require meshing is evaluated on data from animal experiments and human studies, and compared to BEM. Results demonstrate similar accuracy, with the following advantages: 1. Elimination of meshing and manual mesh optimization processes, thereby enhancing automation and speeding the ECGI procedure. 2. Elimination of mesh-induced artifacts. 3. Elimination of complex singular integrals that must be carefully computed in BEM. 4. Simpler implementation. These properties of MFS enhance the practical application of ECGI as a clinical diagnostic tool.     

Direct Inference of the Spectra of Pericardial Potentials Using the Boundary-Element Method

New methods, based on Tikhonov regularization, were developed to infer the magnitude and phase of pericardial potentials directly. These methods were tested in an adult-male torso model using measured human epicardial potentials. With 1% noise added to body-surface potentials, regularization with an optimal parameter at each frequency from 1 to 100 Hz gave an average relative error (RE) in inferred spectral magnitudes of 0.44. Regularization with the composite–residual–smoothing–operator (CRESO) parameter increased the RE slightly to 0.47. With 10% additive noise, 10 mm overestimation of heart radius, and a 10 mm error in heart position, the average CRESO parameter from 1 to 100 Hz gave an average RE of 0.71. Performance was frequency dependent. The smallest REs occurred at low frequencies. With 1% noise, optimal regularization gave average REs of 0.20, 0.40, and 0.53 in the 1–15, 15–46, and 46–100 Hz bands, respectively. Direct inference of spectral magnitudes was more accurate than Fourier transformation of inferred time-domain waveforms. Results suggest that when heart size and location are not known, minimum REs in spectral estimates are found using an overestimated heart size and a regularization parameter which is the average value over the frequency band of interest. © 1999 Biomedical Engineering Society. PAC99: 8719Hh, 8719Nn, 0260Lj     

Noninvasive prenatal screening (NIPS) for fetal chromosome abnormalities in a general-risk population: An evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG)

PurposeThis workgroup aimed to develop an evidence-based clinical practice guideline for the use of noninvasive prenatal screening (NIPS) for pregnant individuals at general risk for fetal trisomy 21, trisomy 18, or trisomy 13 and to evaluate the utility of NIPS for other chromosomal disorders.MethodsThe NIPS Evidence-Based Guideline Work Group (n = 7) relied on the results from the recent American College of Medical Genetics and Genomics (ACMG) systematic review to form the evidentiary basis of this guideline. Workgroup members used the Grading of Recommendations Assessment, Development, and Evaluation Evidence to Decision framework to draft recommendations. The guideline underwent extensive internal and external peer review with a public comment period before approval by the ACMG Board of Directors.ResultsEvidence consistently demonstrated improved accuracy of NIPS compared with traditional screening methods for trisomies 21, 18, and 13 in singleton and twin gestations. Identification of rare autosomal trisomies and other microdeletion syndromes with NIPS is an emerging area of interest.ConclusionACMG strongly recommends NIPS over traditional screening methods for all pregnant patients with singleton and twin gestations for fetal trisomies 21, 18, and 13 and strongly recommends NIPS be offered to patients to screen for fetal sex chromosome aneuploidy.     

Noninvasive Electrical Imaging of the Heart: Theory and Model Development

The aim of this work is to begin quantifying the performance of a recently developed activation imaging algorithm of Huiskamp and Greensite [IEEE Trans. Biomed. Eng. 44:433–446]. We present here the modeling and computational issues associated with this process. First, we present a practical construction of the appropriate transfer matrix relating an activation sequence to body surface potentials from a general boundary value problem point of view. This approach makes explicit the role of different Green's functions and elucidates features (such as the anisotropic versus isotropic distinction) not readily apparent from alternative formulations. A new analytic solution is then developed to test the numerical implementation associated with the transfer matrix formulation presented here and convergence results for both potentials and normal currents are given. Next, details of the construction of a generic porcine model using a nontraditional data-fitting procedure are presented. The computational performance of this model is carefully examined to obtain a mesh of an appropriate resolution to use in inverse calculations. Finally, as a test of the entire approach, we illustrate the activation inverse procedure by reconstructing a known activation sequence from simulated data. For the example presented, which involved two ectopic focii with large amounts of Gaussian noise (100 V rms) present in the torso signals, the reconstructed activation sequence had a similarity index of 0.880 when compared to the input source. © 2001 Biomedical Engineering Society. PAC01: 8719Nn, 8719Hh, 8710+e, 0210Yn, 0230Sa     

闪光视觉诱发电位无创颅内压监测结合头颅CT的临床研究

目的:探讨闪光视觉诱发电位无创颅内压监测与头颅CT之间的相关性.方法:用无创颅内压监测仪对50例颅脑外伤患者进行动态颅内压监测,其中重型颅脑损伤者20例,中型23例,轻型7例;每次检测后行头颅CT检查并计分,分析其CT变化特征,并与颅内压值对照.结果:伤后同一时点,患者的颅内压和头颅CT计分比较,重型＞中型＞轻型(P＜0.05).中、重型颅脑损伤患者保守治疗组和手术治疗组的颅内压与头颅CT计分之间,组内比较具有相关性,计算相关系数分别为r=0.92和r--0.96,差异有统计学意义(P＜0.05).结论:闪光视觉诱发电位无创颅内压监测与头颅CT变化呈正相关,两者结合可以指导治疗并判断预后.     

反演法设计磁共振射频阵列线圈的研究

磁共振射频阵列线圈技术的出现进一步提高了磁共振成像的质量,但现有的阵列线圈无法凸显局部感兴趣区域(ROI)。为了满足术中磁共振发展的需求,研究反演法在磁共振射频阵列发射线圈设计与优化中的应用。首先根据临床需求确定ROI,设计目标函数,应用反演法计算阵列线圈的电流密度,采用正则化技术优化计算中出现的高病态问题,采用流函数技术求解线圈绕组。根据临床不同需求设计了3种ROI位置的阵列发射线圈,ROI内的磁场强度达到 0.957 4 A/m以上,与目标磁场强度的误差在5%以内,10 cm ROI内磁场均匀度达到5×10^-8以内,满足理论设计要求。实验结果表明,基于反演法设计的射频阵列发射线圈在ROI内的磁场分布符合理论要求,证明反演法在射频阵列发射线圈设计中的适用性。     

A Minimal Set of SNPs for the Noninvasive Prenatal Diagnosis of β‐Thalassaemia

β‐thalassaemia is one of the commonest autosomal recessive single‐gene disorders worldwide. Prenatal tests use invasive methods, posing a risk for the pregnancy itself. Development of a noninvasive prenatal diagnostic method is, therefore, of paramount importance. The aim of the present study is to identify high‐heterozygote informative single‐nucleotide polymorphisms (SNPs), suitable for the development of noninvasive prenatal diagnosis (NIPD) of β‐thalassaemia. SNP genotyping analysis was performed on 75 random samples from the Cypriot population for 140 SNPs across the β‐globin cluster. Shortlisted, highly heterozygous SNPs were then examined in 101 carrier families for their applicability in the noninvasive detection of paternally inherited alleles. Forty‐nine SNPs displayed more than 6% heterozygosity and were selected for NIPD analysis, revealing 72.28% of the carrier families eligible for qualitative SNP‐based NIPD, and 92% for quantitative detection. Moreover, inference of haplotypes showed predominant haplotypes and many subhaplotypes with sufficient prevalence for diagnostic exploitation. SNP‐based analyses are sensitive and specific for the detection of the paternally inherited allele in maternal plasma. This study provides proof of concept for this approach, highlighting its superiority to NIPD based on single markers and thus providing a blueprint for the general development of noninvasive prenatal diagnostic assays for β‐thalassaemia.     

Two Dimensional Inverse Imaging (2DII) of Current Sources in Magnetoencephalography

A new magnetoencephalographic (MEG) technique for imaging the cortical distribution of neuronal activity is described. An iterative algorithm is employed, which successively alters an initial estimate of cortical source structure until it corresponds to the measured magnetic field data. In this new technique, the continuum of electrical activity across the cortical surface is modeled as a dense grid of thousands of single equivalent current dipoles. MEG imaging of both compact and extended sources is facilitated by a wavelet-like transformation of the source space into a sequence of successively smaller composite source structures. Two of these composite source structures are combined during each iterative step to generate an improved estimate of the cortical source structure. Thus, inversion of the complete gain matrix corresponding to thousands of cortical sources is not performed. The technique requires only moderate PC based resources even for very large source grids. In contrast to minimum norm MEG imaging methods, this new algorithm is insensitive to random noise in the data. If available, prior knowledge of source structure from other imaging techniques, such as PET, MRI and fMRI, is easily incorporated as additional constraints on the source structure solution. Source images solutions corresponding to simulated data are presented. In addition, the technique is applied to source imaging of real MEG data incorporating cortical structure from volumetric MRI data. These results demonstrate the capability of our new technique for imaging combinations of compact and extended source structures.     

Minimal deviation mucinous adenocarcinoma ('adenoma malignum') of the uterine corpus

Primary mucinous adenocarcinomas of the uterine corpus are typically low grade and frequently associated with endometrial hyperplasia and/or ordinary endometrioid adenocarcinoma, but may appear as a heterogeneous group of neoplasms. A case is described of a 56-year-old postmenopausal woman who presented with mucinous vaginal discharge. Imaging demonstrated thickened myometrium due to adenomyosis. Serum CA19-9 levels were elevated to 486 U/mL. Microscopic examination of hysterectomy specimens indicated highly differentiated mucinous adenocarcinoma diffusely infiltrating the portion of adenomyosis of the corpus. In some areas endometrial glands of adenomyosis were replaced by benign-looking mucinous metaplasia. The uterine cervix showed no abnormalities. HIK1083 and MUC6 immunohistochemistry indicated a gastric phenotype of the tumor, as seen in cases of prototypical minimal deviation adenocarcinoma (MDA) of the cervix. In summary, mucinous endometrial adenocarcinoma rarely shows features similar to MDA of the cervix. This case provokes a discussion on diagnostic and management strategy, and histogenesis of mucinous neoplasm of the endometrium.     

Understanding attitudes and behaviors towards cell-free DNA-based noninvasive prenatal testing (NIPT): A survey of European health-care providers

Cell-free DNA-based noninvasive prenatal testing (cfDNA) is a relatively new screening tool that analyzes cfDNA circulating in maternal plasma to screen for aneuploidies. Since its introduction, cfDNA has been rapidly adopted by health care providers (HCPs). This rapid adoption, as well as progressive developments in the technology, requires professional societies to continuously update their guidelines to indicate the broadening scope both in terms of test indications and patient populations for whom it has become the appropriate primary test. CfDNA testing, initially applied to high-risk patients, is now largely considered an option for all patients. For HCPs, the rapid introduction of cfDNA into clinical practice has come with the requirement to stay up-to-date and accurately informed. We performed a survey to understand the current practices and views of European HCPs on the use of cfDNA. European HCPs were surveyed on several topics such as familiarity with cfDNA-based noninvasive prenatal testing (NIPT), current usage, patient counseling, test menu expansion, and future perspectives. The results of this survey demonstrate increasing usage and awareness of cfDNA-based NIPT in five European countries (UK, France, Germany, Spain and Italy). Major barriers to implementation include cost and a lack of physician education on NIPT.     

Evidence of a previously undescribed form of respiratory sinus arrhythmia (RSA) —the physiological manifestation of “cardiac aliasing”

Summary Within the fluctuations that occur in heart rate, there is a major component known as respiratory sinus arrhythmia (RSA), which up to now has been defined as heart rate variability which is synchronous with respiratory movements. We have now discovered that RSA synchronous to respiratory movements is only one example of RSA. If a special relationship exists between mean heart rate (f_HR) and mean frequency of breathing (f_B) such that f_B>1/2 f_HR, RSA can be observed in a frequency range which is lower than the frequency of breathing. The mathematical fundamentals of this physiological phenomenon are the same as those for the aliasing-effect in signal sampling.Therefore, we have called this phenomenon cardiac aliasing. We have been able to experimentally demonstrate this, up to now unknown, phenomenon in adult rabbits and dogs as well as in human neonates.     

Residual latency (delay at the neuromuscular junction): normative values and heritability in mice

In vertebrates there is a delay in impulse transmission at the neuromuscular junction termed residual latency (RL). RL is composed of synaptic delay proper plus delays due to reduced conduction velocities of fine nerve and muscle fibers. There have been few studies on RL and none under controlled conditions. RL has been determined for 485 HS mice and for 65 male inbred mice in five strains. All measurements were made on tails of awake mice 60–72 days old. The interval between the peak of the compound nerve action potential and the peak of the compound muscle action potential is defined as RL. In 400 HS males the mean (±SE) RL was 0.930±0.005 ms, with a range of 0.726 to 1.375 ms. Inbred means ranged from 0.714±0.024 ms for A/J to 0.0902±0.020 ms for DBA/1J. The inbred means differed very significantly among themselves (F=11.36, df=4, 60,P<0.0001). Nested ANOVA of RL by litter, family, and generation for the HS males and repeated-measures (test-retest) ANOVA for some HS males and inbreds permit estimation of environmental and genetic variances. Corrected for testing error, broad-sense heritability is estimated to be at least one-third and may be appreciably greater. RL may be of interest to behavioral geneticists because of its heritability and its reflection of certain types of CNS synaptic activity.This work was supported by the Natural Sciences and Engineering Research Council of Canada.