Spectropolarimetric fluctuations in a sunspot chromosphere.

The instrumental advances made in this new era of 4 m class solar telescopes with unmatched spectropolarimetric accuracy and sensitivity will enable the study of chromospheric magnetic fields and their dynamics with unprecedented detail. In this regard, spectropolarimetric diagnostics can provide invaluable insight into magneto-hydrodynamic (MHD) wave processes. MHD waves and, in particular, Alfvénic fluctuations associated with particular wave modes were recently recognized as important mechanisms not only for the heating of the outer layers of the Sun's atmosphere and the acceleration of the solar wind, but also for the elemental abundance anomaly observed in the corona of the Sun and other Sun-like stars (also known as first ionization potential) effect. Here, we take advantage of state-of-the-art and unique spectropolarimetric Interferometric BIdimensional Spectrometer observations to investigate the relation between intensity and circular polarization (CP) fluctuations in a sunspot chromosphere. Our results show a clear link between the intensity and CP fluctuations in a patch which corresponds to a narrow range of magnetic field inclinations. This suggests the presence of Alfvénic perturbations in the sunspot. This article is part of the Theo Murphy meeting issue 'High-resolution wave dynamics in the lower solar atmosphere'.

On-Disc Observations of Flux Rope Formation Prior to Its Eruption.

Coronal mass ejections (CMEs) are one of the primary manifestations of solar activity and can drive severe space weather effects. Therefore, it is vital to work towards being able to predict their occurrence. However, many aspects of CME formation and eruption remain unclear, including whether magnetic flux ropes are present before the onset of eruption and the key mechanisms that cause CMEs to occur. In this work, the pre-eruptive coronal configuration of an active region that produced an interplanetary CME with a clear magnetic flux rope structure at 1 AU is studied. A forward-S sigmoid appears in extreme-ultraviolet (EUV) data two hours before the onset of the eruption (SOL2012-06-14), which is interpreted as a signature of a right-handed flux rope that formed prior to the eruption. Flare ribbons and EUV dimmings are used to infer the locations of the flux rope footpoints. These locations, together with observations of the global magnetic flux distribution, indicate that an interaction between newly emerged magnetic flux and pre-existing sunspot field in the days prior to the eruption may have enabled the coronal flux rope to form via tether-cutting-like reconnection. Composition analysis suggests that the flux rope had a coronal plasma composition, supporting our interpretation that the flux rope formed via magnetic reconnection in the corona. Once formed, the flux rope remained stable for two hours before erupting as a CME. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11207-017-1093-4) contains supplementary material, which is available to authorized users.

Unsupervised delineation of stratum corneum using reflectance confocal microscopy and spectral clustering.

BACKGROUND: Measuring the thickness of the stratum corneum (SC) in vivo is often required in pharmacological, dermatological, and cosmetological studies. Reflectance confocal microscopy (RCM) offers a non-invasive imaging-based approach. However, RCM-based measurements currently rely on purely visual analysis of images, which is time-consuming and suffers from inter-user subjectivity. METHODS: We developed an unsupervised segmentation algorithm that can automatically delineate the SC layer in stacks of RCM images of human skin. We represent the unique textural appearance of SC layer using complex wavelet transform and distinguish it from deeper granular layers of skin using spectral clustering. Moreover, through localized processing in a matrix of small areas (called 'tiles'), we obtain lateral variation of SC thickness over the entire field of view. RESULTS: On a set of 15 RCM stacks of normal human skin, our method estimated SC thickness with a mean error of 5.4 ± 5.1 µm compared to the 'ground truth' segmentation obtained from a clinical expert. CONCLUSION: Our algorithm provides a non-invasive RCM imaging-based solution which is automated, rapid, objective, and repeatable.

Evaluation of five methods for the interpolation of bad leads in the solution of the inverse electrocardiography problem.

Objective.This study aims to assess the sensitivity of epicardial potential-based electrocardiographic imaging (ECGI) to the removal or interpolation of bad leads.Approach.We utilized experimental data from two distinct centers. Langendorff-perfused pig (n= 2) and dog (n= 2) hearts were suspended in a human torso-shaped tank and paced from the ventricles. Six different bad lead configurations were designed based on clinical experience. Five interpolation methods were applied to estimate the missing data. Zero-order Tikhonov regularization was used to solve the inverse problem for complete data, data with removed bad leads, and interpolated data. We assessed the quality of interpolated ECG signals and ECGI reconstructions using several metrics, comparing the performance of interpolation methods and the impact of bad lead removal versus interpolation on ECGI.Main results.The performance of ECG interpolation strongly correlated with ECGI reconstruction. The hybrid method exhibited the best performance among interpolation techniques, followed closely by the inverse-forward and Kriging methods. Bad leads located over high amplitude/high gradient areas on the torso significantly impacted ECGI reconstructions, even with minor interpolation errors. The choice between removing or interpolating bad leads depends on the location of missing leads and confidence in interpolation performance. If uncertainty exists, removing bad leads is the safer option, particularly when they are positioned in high amplitude/high gradient regions. In instances where interpolation is necessary, the inverse-forward and Kriging methods, which do not require training, are recommended.Significance.This study represents the first comprehensive evaluation of the advantages and drawbacks of interpolating versus removing bad leads in the context of ECGI, providing valuable insights into ECGI performance.

Characterizing the transient electrocardiographic signature of ischemic stress using Laplacian Eigenmaps for dimensionality reduction.

OBJECTIVE: Despite a long history of ECG-based monitoring of acute ischemia quantified by several widely used clinical markers, the diagnostic performance of these metrics is not yet satisfactory, motivating a data-driven approach to leverage underutilized information in the electrograms. This study introduces a novel metric for acute ischemia, created using a machine learning technique known as Laplacian eigenmaps (LE), and compares the diagnostic and temporal performance of the LE metric against traditional metrics. METHODS: The LE technique uses dimensionality reduction of simultaneously recorded time signals to map them into an abstract space in a manner that highlights the underlying signal behavior. To evaluate the performance of an electrogram-based LE metric compared to current standard approaches, we induced episodes of transient, acute ischemia in large animals and captured the electrocardiographic response using up to 600 electrodes within the intramural and epicardial domains. RESULTS: The LE metric generally detected ischemia earlier than all other approaches and with greater accuracy. Unlike other metrics derived from specific features of parts of the signals, the LE approach uses the entire signal and provides a data-driven strategy to identify features that reflect ischemia. CONCLUSION: The superior performance of the LE metric suggests there are underutilized features of electrograms that can be leveraged to detect the presence of acute myocardial ischemia earlier and more robustly than current methods. SIGNIFICANCE: The earlier detection capabilities of the LE metric on the epicardial surface provide compelling motivation to apply the same approach to ECGs recorded from the body surface.

Automated identification of neurons in 3D confocal datasets from zebrafish brainstem.

Many kinds of neuroscience data are being acquired regarding the dynamic behaviour and phenotypic diversity of nerve cells. But as the size, complexity and numbers of 3D neuroanatomical datasets grow ever larger, the need for automated detection and analysis of individual neurons takes on greater importance. We describe here a method that detects and identifies neurons within confocal image stacks acquired from the zebrafish brainstem. The first step is to create a template that incorporates the location of all known neurons within a population - in this case the population of reticulospinal cells. Once created, the template is used in conjunction with a sequence of algorithms to determine the 3D location and identity of all fluorescent neurons in each confocal dataset. After an image registration step, neurons are segmented within the confocal image stack and subsequently localized to specific locations within the brainstem template - in many instances identifying neurons as specific, individual reticulospinal cells. This image-processing sequence is fully automated except for the initial selection of three registration points on a maximum projection image. In analysing confocal image stacks that ranged considerably in image quality, we found that this method correctly identified on average approximately 80% of the neurons (if we assume that manual detection by experts constitutes 'ground truth'). Because this identification can be generated approximately 100 times faster than manual identification, it offers a considerable time savings for the investigation of zebrafish reticulospinal neurons. In addition to its cell identification function, this protocol might also be integrated with stereological techniques to enhance quantification of neurons in larger databases. Our focus has been on zebrafish brainstem systems, but the methods described should be applicable to diverse neural architectures including retina, hippocampus and cerebral cortex.

A STATISTICAL APPROACH TO INCORPORATE MULTIPLE ECG OR EEG RECORDINGS WITH ARTIFACTUAL VARIABILITY INTO INVERSE SOLUTIONS.

Inverse methods for localization and characterization of cardiac and brain sources from ECG and EEG signals are notoriously ill-conditioned and thus sensitive to SNR in the measurements. Multiple recordings of the same underlying phenomenon are often available, but are contaminated by unmodeled correlated noise such as heart motion from respiration or superposition of atrial activation or on-going EEG in the case of inter-ictal spikes or evoked response in EEG. We address here the open question of how best to incorporate these multiple recordings, comparing standard ensemble averaging, a multichannel non-linear spline-based average designed to be less sensitive to timing variations from motion or modulation, and a probalistic inverse incorporating a data-driven model of the noise correlation and using all recordings jointly. Results are tested on localizations of clincally recorded 120 lead ECGs during ventricular pacing.

COMBINED DELAY AND GRAPH EMBEDDING OF EPILEPTIC DISCHARGES IN EEG REVEALS COMPLEX AND RECURRENT NONLINEAR DYNAMICS.

The dynamical structure of the brain's electrical signals contains valuable information about its physiology. Here we combine techniques for nonlinear dynamical analysis and manifold identification to reveal complex and recurrent dynamics in interictal epileptiform discharges (IEDs). Our results suggest that recurrent IEDs exhibit some consistent dynamics, which may only last briefly, and so individual IED dynamics may need to be considered in order to understand their genesis. This could potentially serve to constrain the dynamics of the inverse source localization problem.

Transplantation of Y79 cells into rat eyes: an in vivo model of human retinoblastomas.

PURPOSE: To develop an in vivo model of human retinoblastoma by returning cultured Y79 retinoblastoma cells to the retinal environment of a widely available laboratory animal. In so doing, to study the survival, integration, and invasive characteristics expressed by tumoral cells grafted into an intraocular milieu from which these progenitor cells originated more than 20 years ago. METHODS: Using the retinal grafting method of Lazar and del Cerro, Y79 cells were injected under direct visualization into the subretinal space of Fischer 344 rats. The host rats included 36 animals that received daily injections of cyclosporin A and 4 that did not. All hosts were sacrificed 30 to 60 days after transplantation. RESULTS: Clinical examination showed vitreal invasion by masses of flocculent white material or the intravitreal formation of solid tumors. Histologic examination showed these formations to be outgrowths of grafted tumoral cells into the host retina and vitreal cavity. Highly anaplastic tumoral cells were also found lodged in subretinal and intraretinal locations. There were signs of continued and intense cell division within the grafts, with no indication of cell-mediated host reaction against the grafted cells. CONCLUSIONS: After intraretinal xenografting, human Y79 retinoblastoma cells retain a highly tumoral nature despite many years of in vitro propagation. When xenografted, these cells survive, grow, and express their malignancy within the retina of the common laboratory rat protected by a moderate immunosuppressive regimen. This partial immunosuppression is a requirement for the xenografts to prosper. This model offers a valuable opportunity to study in vivo the cellular and molecular biology of this and other human retinoblastomas, and it may facilitate the evaluation of antitumoral treatments.

Postprandial rest pain and claudication of the lower extremity: A case report.

Postprandial rest pain and claudication in the lower extremities may occur in arteriosclerotic aortic occlusion when mesenteric and systemic collateral pathways provide inadequate blood flow to the extremity. The symptoms occur as a result of vasodilation of the distal mesenteric vascular bed with a concomitant increase in mesenteric blood flow which leads to a decrease in mesenteric artery to extremity collateral blood flow. This normal physiologic phenomenon, increase in mesenteric blood flow, causes the extremity pain. Such symptoms indicate a quite significant decrease in blood flow to the extremity, and prompt surgical correction is indicated. Aortofemoral reconstruction yields total reflief of the symptom complex.

The use of expanded microporous polytetrafluoroethylene for limb salvage: a preliminary report.

Initial laboratory and clinical evaluations of a new prosthetic material, expanded microporous polytetrafluoroethylene (PTFE), for small vessel replacement is promising and encourages further clinical trial. Frequently the autogenous saphenous vein is not available for bypass procedures, and alternative arterial substitutes have not proved reliable for replacement of small vessels. In this study, 15 patients with impending loss of limb and no available saphenous vein underwent revascularization of the lower extremity with expanded microporous PTFE grafts. Thirteen of 15 patients now demonstrate viable extremities with a resulting over-all early patency and limb salvage rate of 87 percent for this series. Follow-up ranges from one to 8 months. Seven patients had diabetes mellitus and eight had atherosclerotic heart disease. Nine grafts crossed the knee joint. In all patients arterial runoff was poor. Six patients had previous femoropopliteal bypasses, five with autogenous veins and one with Dacron velour. Two patients had multiple previous operations that failed, first with autogenous vein and later with fabric grafts. The current limb salvage and patency rate of 87 percent in high-risk patients suggests that expanded PTFE may be the prosthesis of choice when an autogenous vein is not available and possibly an equally good substitute when the venous autograft is available.

Expanded polytetrafluoroethylene femoropopliteal grafts: forty-eight-month follow-up.

Ninety-eight expanded polytetrafluoroethylene (PTFE) grafts were used for femoropopliteal reconstruction in 81 patients. Forty-eight-month follow-up is now available for 20 grafts and 36-month follow-up is available for 51 grafts. Seventy-four percent of the patients were men. Thirty-one percent had diabetes mellitus, 38% had hypertension, 36% had atherosclerotic heart disease, 18% had prior myocardial infarction, 17% had a previous operation for aortoiliac disease, and 14% had a previous ipsilateral femoropopliteal bypass procedure. The indication for operation was claudication in 47%, rest pain in 20%, and ischemic pregangrene or gangrene in 32% of patients. Distal runoff was angiographically graded as good (76%) or poor (24%). Seventy-three grafts were anastomosed to the proximal or midpopliteal artery (above the knee); 25 grafts were anastomosed to the distal popliteal artery (below the knee). Graft occlusion was determined by the return of ischemic symptoms, disappearance of previously palpable pulses, or by angiographic or Doppler assessment. There were no operative deaths. Nonocclusive causes of graft loss were death (7), amputation (2), infection (2), and aneurysm (5). The overall cumulative patency rate calculated by the life-table method, according to the criterion of occlusion alone, was 75% at 6 months, 68% at 2 years, 58% at 3 years, and 48% at 4 years. Preoperative symptoms, the number of patent outflow vessels, popliteal anastomosis placed above or below the knee, or hypertension did not adversely affect graft patency. Diabetes mellitus was associated with significantly increased graft failure. The PTFE graft is an acceptable alternative for femoropopliteal reconstruction for the patient without a suitable autologous saphenous vein.

Expanded microporous polytetrafluoroethylene as a vascular substitute: a two year follow-up.

Since 1974, 131 femoropopliteal, distal popliteal, and tibial bypasses have been performed using expanded microporous polytetrafluoroethylene (PTFE). Forty patients were operated on for limb salvage, and 21 had had previous bypass procedures. The overall patency rate was 82%. Early occlusions possibly were related to technical error, but most probably were due to severity of disease and poor runoff. Late occlusions were related to progressive atherosclerosis in the proximal or distal arterial tree. A 75.7% cumulative patency rate was noted at 28 months. In man the PTFE prosthesis demonstrates a smooth intimal lining with fibroblastic ingrowth into the interstices of the graft. These results are considered to be excellent in this high-risk patient population. The patency rates achieved with PTFE are better than those accomplished with alternative conduits and approach the patency rates reported with autogenous saphenous vein. Expanded microporous polytetrafluoroethylene with its high patency, pliability, and tissue incorporation is an excellent arterial substitute. Only with continued use of this material and a more uniform patient selection can more equitable comparisons be made between expanded PTFE and the autogenous vein.

A comparison study of linear reconstruction techniques for diffuse optical tomographic imaging of absorption coefficient.

We compare, through simulations, the performance of four linear algorithms for diffuse optical tomographic reconstruction of the three-dimensional distribution of absorption coefficient within a highly scattering medium using the diffuse photon density wave approximation. The simulation geometry consisted of a coplanar array of sources and detectors at the boundary of a half-space medium. The forward solution matrix is both underdetermined, because we estimate many more absorption coefficient voxels than we have measurements, and ill-conditioned, due to the ill-posedness of the inverse problem. We compare two algebraic techniques, ART and SIRT, and two subspace techniques, the truncated SVD and CG algorithms. We compare three-dimensional reconstructions with two-dimensional reconstructions which assume all inhomogeneities are confined to a known horizontal slab, and we consider two 'object-based' error metrics in addition to mean square reconstruction error. We include a comparison using simulated data generated using a different FDFD method with the same inversion algorithms to indicate how our conclusions are affected in a somewhat more realistic scenario. Our results show that the subspace techniques are superior to the algebraic techniques in localization of inhomogeneities and estimation of their amplitude, that two-dimensional reconstructions are sensitive to underestimation of the object depth, and that an error measure based on a location parameter can be a useful complement to mean squared error.

Inverse electrocardiography by simultaneous imposition of multiple constraints.

We describe two new methods for the inverse problem of electrocardiography. Both employ regularization with multiple constraints, rather than the standard single-constraint regularization. In one method, multiple constraints on the spatial behavior of the solution are used simultaneously. In the other, spatial constraints are used simultaneously with constraints on the temporal behavior of the solution. The specific cases of two spatial constraints and one spatial and one temporal constraint are considered in detail. A new method, the L-Surface, is presented to guide the choice of the required pairs of regularization parameters. In the case when both spatial and temporal regularization are used simultaneously, there is an increased computational burden, and two methods are presented to compute solutions efficiently. The methods are verified by simulations using both dipole sources and measured canine epicardial data.

An efficient region of interest acquisition method for dynamic magnetic resonance imaging.

Motivated by work in the area of dynamic magnetic resonance imaging (MRI), we develop a new approach to the problem of reduced-order MRI acquisition. Efforts in this field have concentrated on the use of Fourier and singular value decomposition (SVD) methods to obtain low-order representations of an entire image plane. We augment this work to the case of imaging an arbitrarily-shaped region of interest (ROI) embedded within the full image. After developing a natural error metric for this problem, we show that determining the minimal order required to meet a prescribed error level is in general intractable, but can be solved under certain assumptions. We then develop an optimization approach to the related problem of minimizing the error for a given order. Finally, we demonstrate the utility of this approach and its advantages over existing Fourier and SVD methods on a number of MRI images.

TIME INVARIANT MULTI ELECTRODE AVERAGING FOR BIOMEDICAL SIGNALS.

One of the biggest challenges in averaging ECG or EEG signals is to overcome temporal misalignments and distortions, due to uncertain timing or complex non-stationary dynamics. Standard methods average individual leads over a collection of epochs on a time-sample by time-sample basis, even when multi-electrode signals are available. Here we propose a method that averages multi electrode recordings simultaneously by using spatial patterns and without relying on time or frequency.

MANIFOLD LEARNING FOR ANALYSIS OF LOW-ORDER NONLINEAR DYNAMICS IN HIGH-DIMENSIONAL ELECTROCARDIOGRAPHIC SIGNALS.

The dynamical structure of electrical recordings from the heart or torso surface is a valuable source of information about cardiac physiological behavior. In this paper, we use an existing data-driven technique for manifold identification to reveal electrophysiologically significant changes in the underlying dynamical structure of these signals. Our results suggest that this analysis tool characterizes and differentiates important parameters of cardiac bioelectric activity through their dynamic behavior, suggesting the potential to serve as an effective dynamic constraint in the context of inverse solutions.

Refractive errors and corrections for OCT images in an inflated lung phantom.

Visualization and correct assessment of alveolar volume via intact lung imaging is important to study and assess respiratory mechanics. Optical Coherence Tomography (OCT), a real-time imaging technique based on near-infrared interferometry, can image several layers of distal alveoli in intact, ex vivo lung tissue. However optical effects associated with heterogeneity of lung tissue, including the refraction caused by air-tissue interfaces along alveoli and duct walls, and changes in speed of light as it travels through the tissue, result in inaccurate measurement of alveolar volume. Experimentally such errors have been difficult to analyze because of lack of 'ground truth,' as the lung has a unique microstructure of liquid-coated thin walls surrounding relatively large airspaces, which is difficult to model with cellular foams. In addition, both lung and foams contain airspaces of highly irregular shape, further complicating quantitative measurement of optical artifacts and correction. To address this we have adapted the Bragg-Nye bubble raft, a crystalline two-dimensional arrangement of elements similar in geometry to alveoli (up to several hundred µm in diameter with thin walls) as an inflated lung phantom in order to understand, analyze and correct these errors. By applying exact optical ray tracing on OCT images of the bubble raft, the errors are predicted and corrected. The results are validated by imaging the bubble raft with OCT from one edge and with a charged coupled device (CCD) camera in transillumination from top, providing ground truth for the OCT.