Selective increase of cerebrospinal fluid IL-6 during experimental systemic inflammation in humans: association with depressive symptoms.

Systemic inflammation is accompanied by profound behavioral and mood changes that resemble symptoms of depression. Findings in animals suggest that pro-inflammatory cytokines released by activated immune cells in the periphery evoke these behavioral symptoms by driving inflammatory changes in the brain. However, experimental data in humans are lacking. Here we demonstrate in healthy male volunteers (10 endotoxin treated, 8 placebo treated) that intravenous administration of low-dose endotoxin (0.8 ng/kg body weight), a prototypical pathogen-associated molecular pattern that activates the innate immune system, not only induces a significant increase in peripheral blood cytokine concentrations (that is, tumor necrosis factor-α, interleukin (IL)-6, IL-10) but also results, with some latency, in a robust and selective increase of IL-6 in the cerebrospinal fluid (CSF). Moreover, we found a strong association between the endotoxin-induced increase of IL-6 in the CSF and the severity of mood impairment, with larger increases in CSF IL-6 concentration followed by a greater deterioration in mood. Taken together, these findings suggest that the appearance of depressive symptoms in inflammatory conditions might be primarily linked to an increase in central IL-6 concentration, identifying IL-6 as a potential therapeutic target in mood disorders.

Novel 3D ultrasound system for midline single-operator epidurals: a feasibility study on a porcine model.

BACKGROUND: We developed a real-time 3D ultrasound thick slice rendering technique and innovative Epiguide needle-guide as an adjunct to single-operator midline epidural needle insertions. Study goals were to determine feasibility of the technique in a porcine model and compare the visibility of standard and echogenic needles. METHODS: Thirty-four lumbar needle insertions were performed on six intact porcine spines ex vivo. Ultrasound scanning identified the insertion site and, using an Epiguide, the needle was guided into the epidural space through the ligamentum flavum in the midline plane, watched in real-time on the 3D ultrasound. Entry into the epidural space was judged by a loss-of-resistance technique. Needle visibility was rated by the anesthesiologist performing the technique using a 4-point scale; (0=cannot see, 1=poor, 2=satisfactory, 3=excellent), and later by an independent assessor viewing screenshots. The procedure was repeated at all lumbar levels using either the standard or echogenic needle. RESULTS: Successful loss-of-resistance to fluid was achieved in 76% of needle insertions; needle visibility with echogenic needles (94.2% rated satisfactory/excellent) was significantly better than with standard needles (29.4% satisfactory/excellent, P<0.0001). Successful loss-of-resistance was 93% when mean needle visibility was rated as 'excellent'. Inter-observer agreement between assessors was 'near-perfect' (weighted kappa=0.83). CONCLUSION: It is feasible to perform 3D ultrasound-guided real-time single-operator midline epidural insertions, in a porcine model. Echogenic needles were found to consistently improve needle visibility; and improved needle visibility tended to increase successful entry into epidural space.

Correction to "Automatic Quality Assessment of Echocardiograms Using Convolutional Neural Networks: Feasibility on the Apical Four-Chamber View".

In the above paper [1], the first footnote should have indicated the following information: A. H. Abdi and C. Luong are joint first authors.

A comparison of direct and iterative finite element inversion techniques in dynamic elastography.

As part of tissue elasticity imaging or elastography, an inverse problem needs to be solved to find the elasticity distribution from the measured displacements. The finite element method (FEM) is a common method for solving the inverse problem in dynamic elastography. This problem has been solved with both direct and iterative FEM schemes. Each of these methods has its own advantages and disadvantages which are examined in this paper. Choosing the data resolution and the excitation frequency are critical for achieving the best estimation of the tissue elasticity in FEM methods. In this paper we investigate the performance of both direct and iterative FEMs for different ranges of excitation frequency. A new form of iterative method is suggested here which requires a lower mesh density compared to the original form. Also two forms of the direct method are compared in this paper: one using the exact fit for derivatives calculation and the other using the least squares fit. We also perform a study on the spatial resolution of these methods using simulations. The comparison is also validated using a phantom experiment. The results suggest that the direct method with least squares fit is more robust to noise compared to other methods but has slightly lower resolution results. For example, for the homogenous region with 20 dB noise added to the data, the RMS error for the direct method with least squares fit is approximately half of the iterative method. It was observed that the ratio of voxel size to the wavelength should be within a specific range for the results to be reliable. For example for the direct method with least squares fit, for the case of 20 dB noise level, this ratio should be between 0.1 to 0.2. On balance, considering the much higher computational cost of the iterative method, the dependency of the iterative method on the initial guess, and the greater robustness of the direct method to noise, we suggest using the direct method with least squares fit for linear elasticity cases.

Direct vibro-elastography FEM inversion in Cartesian and cylindrical coordinate systems without the local homogeneity assumption.

To produce images of tissue elasticity, the vibro-elastography technique involves applying a steady-state multi-frequency vibration to tissue, estimating displacements from ultrasound echo data, and using the estimated displacements in an inverse elasticity problem with the shear modulus spatial distribution as the unknown. In order to fully solve the inverse problem, all three displacement components are required. However, using ultrasound, the axial component of the displacement is measured much more accurately than the other directions. Therefore, simplifying assumptions must be used in this case. Usually, the equations of motion are transformed into a Helmholtz equation by assuming tissue incompressibility and local homogeneity. The local homogeneity assumption causes significant imaging artifacts in areas of varying elasticity. In this paper, we remove the local homogeneity assumption. In particular we introduce a new finite element based direct inversion technique in which only the coupling terms in the equation of motion are ignored, so it can be used with only one component of the displacement. Both Cartesian and cylindrical coordinate systems are considered. The use of multi-frequency excitation also allows us to obtain multiple measurements and reduce artifacts in areas where the displacement of one frequency is close to zero. The proposed method was tested in simulations and experiments against a conventional approach in which the local homogeneity is used. The results show significant improvements in elasticity imaging with the new method compared to previous methods that assumes local homogeneity. For example in simulations, the contrast to noise ratio (CNR) for the region with spherical inclusion increases from an average value of 1.5-17 after using the proposed method instead of the local inversion with homogeneity assumption, and similarly in the prostate phantom experiment, the CNR improved from an average value of 1.6 to about 20.

Automatic registration of 3-D ultrasound images.

One of the most promising applications of 3-D ultrasound (US) lies in the visualisation and volume estimation of internal 3-D structures. Unfortunately, artifacts and speckle make automatic analysis of the 3-D data sets difficult. In this study, we investigated the use of 3-D spatial compounding to improve data quality, and found that precise registration is the key. A correlation-based registration technique was applied to 3-D ultrasound data sets acquired from in vivo examinations of a human gall bladder. We found that the registration technique performed well, and visualisation and segmentation of the compounded data were clearly improved. We also demonstrated that an automatic volume estimate made from the compounded data (13.0 mL) was comparable to a labour-intensive manual estimate (12.5 mL). In comparison, automatic estimates of uncompounded data are less accurate (ranging from 13.5 mL to 16.7 mL). The registration technique also has applications in intra- and interpatient comparative studies.

Rapid calibration for 3-D freehand ultrasound.

3-D freehand ultrasound is a new imaging technique that is rapidly finding clinical applications. A position-sensing device is attached to a conventional ultrasound probe so that, as B-scans are acquired, they can be labelled with their relative positions and orientations. This allows a 3-D data set to be constructed from the B-scans. A key requirement of all freehand imaging systems is calibration; that is, determining the position and orientation of the B-scan with respect to the position sensor. This is typically a lengthy and tedious process that may need repeating every time a sensor is mounted on a probe. This paper describes a new calibration technique that takes only a few minutes to perform and produces results that compare favourably (in terms of both accuracy and precision) with previously published alternatives.

Three-dimensional spatial compounding of ultrasound images.

One of the most promising applications of 3-D ultrasound lies in the visualization and volume estimation of internal 3-D structures. Unfortunately, the quality of the ultrasound data can be severely degraded by artefacts and speckle, making automatic analysis of the 3-D data sets very difficult. In this paper we investigate the use of 3-D spatial compounding to reduce speckle. We develop a new statistical theory to predict the improvement in signal-to-noise ratio with increased levels of compounding, and verify the predictions empirically. We also investigate how registration errors can affect automatic volume estimation of structures within the compounded 3-D data set. Having established the need to correct these errors, we present a novel reconstruction algorithm which uses landmarks to register each B-scan accurately as it is inserted into the voxel array. In a series of in vitro and in vivo trials, we demonstrate that 3-D spatial compounding is very effective for improving the signal-to-noise ratio, but correction of registration errors is essential.

A comparison of freehand three-dimensional ultrasound reconstruction techniques.

Three-dimensional freehand ultrasound imaging produces a set of irregularly spaced B-scans, which are typically reconstructed on a regular grid for visualization and data analysis. Most standard reconstruction algorithms are designed to minimize computational requirements and do not exploit the underlying shape of the data. We investigate whether an approximation with splines holds any promise as a better reconstruction method. A radial basis function approximation method is implemented and compared with three standard methods. While the radial basis approach is computationally expensive, it produces accurate reconstructions without the kind of visible artefacts common with the standard methods. The other potential advantages of radial basis functions, such as the direct computation of derivatives, make further investigation worthwhile.

Multimodal strategy for reduction of homologous transfusions in cranio-maxillofacial surgery.

The transfusion of homologous blood carries well-known risks that have prompted efforts to develop alternative techniques. Such measures are of particular interest to patients undergoing elective procedures. A total of 204 patients, out of 1470 patients who consecutively underwent major craniomaxillofacial procedures under general anesthesia over a two-year period, were enrolled in a prospective protocol to reduce homologous transfusion requirements when a blood loss in excess of 500 ml was anticipated. The data were compared with the results of a retrospective control group (n=2890) covering major procedures during the previous four years, when blood-saving measures were applied occasionally, but not based on a global strategy. Techniques for the reduction of homologous transfusions were acute normovolemic hemodilution, controlled moderate hypotension, cell saver and predeposit autologous blood. In addition, preoperative administration of human recombinant erythropoietin was introduced during the last year of the study. These techniques were applied individually or in combination, depending on contraindications specific for each technique, using invasive monitoring in order to maintain intraoperative hemodynamic stability. The goal of this study was to examine the extent to which homologous transfusions may be reduced with the systematic application of transfusion-sparing techniques. Of 204 patients qualifying for the transfusion-sparing protocol, 30 received homologous transfusions. In comparison to the control group, utilization of transfusion-sparing techniques had doubled. The overall reduction in the use of homologous transfusions was highly significant. When acute normovolemic hemodilution, controlled moderate hypotension and the cell saver were used in combination, a greater reduction in homologous transfusions was achieved than with the use of either a single modality or combination of any two. No transfusions were required in patients pretreated with erythropoietin.

Anesthesia in a patient with acute respiratory insufficiency due to relapsing polychondritis.

We report on a male patient with advanced relapsing polychondritis (RP), who was hospitalized for an ophthalmologic intervention. He had to undergo a tracheostomy with general anesthesia due to respiratory decompensation. RP is a rare systemic, inflammatory, and destructive disease of the cartilaginous structures leading to multiple functional disorders in the affected organs. Involvement of the tracheobronchial tract may cause severe respiratory problems and even life-threatening respiratory insufficiency. Treatment consists of corticoids, chemotherapy, antirheumatics, and surgical intervention. Anesthesiologic management requires careful preoperative evaluation of vital organ functions, in particular respiration, so that the anesthetic approach can be tailored to the individual needs of each patient.

Risk of recurarization during retransfusion of autologous blood withdrawn after injection of muscle relaxants: a comparison of rocuronium and mivacurium.

STUDY OBJECTIVES: In the context of acute normovolemic hemodilution (ANH) recurarization, defined as significant decrease of train-of-four ratio (TOFR) during retransfusion of autologous blood withdrawn after induction of anesthesia, has been described for vecuronium and atracurium. The present study for the first time examined this risk for rocuronium and mivacurium. DESIGN: Prospective, randomized, unblinded clinical study. SETTING: University Hospital in Zurich/Switzerland. PATIENTS: 20 ASA physical status I and II patients undergoing general anesthesia for major maxillofacial surgery. INTERVENTIONS: Anesthesia was induced and maintained with propofol and remifentanil, and rocuronium (0.9 mg kg(-1)) or mivacurium (0.25 mg kg(-1)) was given to facilitate intubation. Thereafter, ANH was started with the removal of 500 mL autologous blood and the subsequent replacement by the same amount of 6% hydroxyethyl starch. The withdrawn blood was stored at 4 degrees C until retransfusion at the end of surgery. MEASUREMENTS: To estimate the risk of recurarization during retransfusion, the degree of recurarization during retransfusion of the autologous blood was assessed mechanomyographically. Plasma levels of rocuronium and mivacurium in the patients' plasma and the autologous blood were determined after its removal and before retransfusion. MAIN RESULTS: The TOFR before retransfusion was 0.97 (range: 0.96 to 0.98) for rocuronium (n = 10) and 0.98 (range: 0.96 to 1.0) for mivacurium (n = 8); n.s. During retransfusion, a slight, but statistically significant reduction of TOFR occurred in one patient in each group. In the mivacurium group, this recurarization occurred 10 minutes after the start of retransfusion; in the rocuronium group, it occurred 20 minutes after retransfusion. The plasma levels of rocuronium and mivacurium in the autologous blood did not change during storage. The plasma concentration of mivacurium in the autologous blood after its removal was 420 +/- 142 microg/L; before retransfusion, it was 384 +/- 147 microg/L. The respective concentrations for rocuronium were 2930 +/- 516 microg/L and 2660 +/- 464 microg/L. CONCLUSIONS: Recurarization during retransfusion may occur with both neuromuscular blocking drugs, mivacurium and rocuronium, when these drugs were injected before the removal of the autologous blood.

Sparsity regularization in dynamic elastography.

We consider the inverse problem of continuum mechanics with the tissue deformation described by a mixed displacement-pressure finite element formulation. The mixed formulation is used to model nearly incompressible materials by simultaneously solving for both elasticity and pressure distributions. To improve numerical conditioning, a common solution to this problem is to use regularization to constrain the solutions of the inverse problem. We present a sparsity regularization technique that uses the discrete cosine transform to transform the elasticity and pressure fields to a sparse domain in which a smaller number of unknowns is required to represent the original field. We evaluate the approach by solving the dynamic elastography problem for synthetic data using such a mixed finite element technique, assuming time harmonic motion, and linear, isotropic and elastic behavior for the tissue. We compare our simulation results to those obtained using the more common Tikhonov regularization. We show that the sparsity regularization is less dependent on boundary conditions, less influenced by noise, requires no parameter tuning and is computationally faster. The algorithm has been tested on magnetic resonance elastography data captured from a CIRS elastography phantom with similar results as the simulation.

Viscoelastic parameter estimation based on spectral analysis.

This paper introduces a new technique for the robust estimation of relaxation-time distribution in tissue. The main novelty is in the use of the phase of transfer functions calculated from a time series of strain measurements at multiple locations. Computer simulations with simulated measurement noise demonstrate the feasibility of the approach. An experimental apparatus and software were developed to confirm the simulations. The setup can be used both as a rheometer to characterize the overall mechanical properties of a material or as a vibro-elastography imaging device using an ultrasound system. The algorithms were tested on tissue mimicking phantoms specifically developed to exhibit contrast in elasticity and relaxation time. The phantoms were constructed using a combination of gelatin and a polyvinyl alcohol sponge to produce the desired viscoelastic properties. The tissue parameters were estimated and the elasticity and relaxation time of the materials have been used as complementary features to distinguish different materials. The estimation results are consistent with the rheometry, verifying that the relaxation time can be used as a complementary feature to elasticity to delineate the mechanical properties of the phantom.

INTENSITY-BASED REGISTRATION OF PROSTATE BRACHYTHERAPY IMPLANTS AND ULTRASOUND.

PURPOSE: In prostate brachytherapy, determining the 3D location of the seeds relative to surrounding structures is necessary for calculating dosimetry. Ultrasound imaging provides the ability to visualize soft tissues, and implanted seeds can be reconstructed from C-arm fluoroscopy. Registration between these two complementary modalities would allow us to make immediate provisions for dosimetric deviation from the optimal implant plan. METHODS: We propose intensity-based registration between ultrasound and a reconstructed model of seeds from fluoroscopy. The ultrasound images are pre-processed with recursive thresholding and phase congruency. Then a 3D ultrasound volume is reconstructed and registered to the implant model using mutual information. RESULTS: A standard training phantom was implanted with 49 seeds. Average registration error between corresponding seeds relative to the ground truth is 0.09 mm. The effect of false positives in ultrasound was investigated by masking seeds from the fluoroscopy reconstructed model. The registration error remained below 0.5 mm at a rate of 30% false positives. CONCLUSION: Our method promises to be clinically adequate, where requirements for registration is 1.5 mm.

Evaluating different radiology workstation interaction techniques with radiologists and laypersons.

This paper presents a new methodology for evaluating radiology workstation interaction features, using lay subjects to perform a radiology look-alike task with artificial stimuli. We validated this methodology by evaluating two different workstation interaction techniques with two groups of subjects: laypersons and radiologists, using a set of artificial targets to simulate the reading of a diagnostic examination. Overall, the results from the two groups of subjects performing the same tasks were very similar. Both groups showed significantly faster response times using a new interaction technique, and the mouse clicks for both groups were very similar, showing that all the subjects mastered the style of interaction in a similar way. The errors made by both groups were comparable. These results show that it is possible to test new workstation interaction features using look-alike radiological tasks and inexperienced laypersons, and that the results do transfer to radiologists performing the same tasks.

[Life support for homeostasis in organ donors]. / Aufrechterhaltung der Homöostase beim Organspender.

The main goal of intensive care of potential organ donors includes the maintenance of the organs' function with respect to their integrity after transplantation. Profound disturbances of cardiovascular, respiratory and endocrinological function may lead to early organ loss. Therefore, comprehensive therapy is required from the onset of brain death. The major dysfunctions and therapeutic goals in organ donors are summarized on the basis of current literature and our own findings.

Clinical investigation of a new combined pulse oximetry and carbon dioxide tension sensor in adult anaesthesia.

OBJECTIVE: To test the accuracy of a new combined oxygen saturation and cutaneous carbon dioxide tension (SPO2-PCO2) sensor in a routine adult clinical environment. This probe provides a non-invasive and continuous monitoring of the arterial oxyhaemoglobin saturation, arterial carbon dioxide tension and pulse rate at the ear lobe. The sensor is intended to measure both relevant respiration/ventilation parameters in one single probe. METHODS: Ten adult patients were consecutively studied during general anaesthesia. During the first 5 min after sensor placement at the ear lobe, arterial blood samples were drawn each minute. Carbon dioxide tension and oxygen saturation measurements were obtained simultaneously at 1-min intervals. After this period, patients were hyper-, normo- and hypoventilated. After 15 min at each setting, the simultaneously obtained cutaneous and arterial carbon dioxide tension values were compared. RESULTS: A total of 80 comparisons between ear lobe SpO2-PCO2 measurement, finger clip pulse oximetry and arterial blood gas values were analysed. Three minutes after sensor placement, there were no significant differences between ear probe (cutaneous) and arterial carbon dioxide tensions (p = 0.367). Comparison of arterial with cutaneous carbon dioxide values demonstrated an excellent linear correlation (r2 = 0.92), and showed a standard error of estimate (SDEE) of 0.26 kPa (1.95 mmHg) only. The mean difference was -0.08 kPa (-0.60 mmHg) with a limits of agreement range of -0.38 kPa to +0.22 kPa (-2.85 mmHg to +1.65 mmHg). Concerning oxygen saturation measurements, the absolute SpO2 value deviated 1% or less from standard pulse oximetry. CONCLUSIONS: During general anaesthesia, postoperative recovery and critical care treatment, both monitoring of oxygenation and ventilation is important. Since pulse oximetry estimates only arterial oxygen saturation, periodic blood sampling is still necessary to determine the patient's arterial carbon dioxide status. We could demonstrate that the difference between cutaneous and arterial PCO2 was clinically unimportant, and therefore we conclude that the two methods of estimating the patient's carbon dioxide status may be used interchangeably. Our results demonstrated that 3 min after sensor placement, the new SpO2-PCO2 sensor prototype proved to be a reliable tool for continuous non-invasive monitoring of oxygenation and ventilation.

[Auditory evoked potentials in determining brain death]. / Akustisch evozierte Potentiale in der Entwicklung des Hirntodes.

Until now, in hypothermic patients, patients under barbiturate therapy etc. brain death can only unequivocally be determined by cerebral panangiography. We evaluated in 41 patients, whether panangiography can be substituted by recording of brain stem auditory evoked potentials in combination with cerebral perfusion scintigraphy. Our results demonstrate, that even if no potential except wave I can be recorded, a minimal intracranial perfusion may exist, so that by definition the patient is not dead. During the course of our investigations we found one patient, in whom disappeared auditory evoked potentials recovered. So we conclude, that the recording of auditory evoked potentials is only an adjunct in determination of brain death, not an objective method as is cerebral panangiography. But recording of auditory evoked potentials is helpful in excluding brain death in certain patients.

Intravenous versus oral iron supplementation for preoperative stimulation of hemoglobin synthesis using recombinant human erythropoietin.

To compare two modalities of iron supplementation for the preoperative stimulation of erythropoiesis using recombinant human erythropoietin (rhEPO), 12 adults in normal hemoglobin and iron status due for elective surgery were randomized to rhEPO 200 U/kg body weight subcutaneously twice weekly combined with either iron sucrose 200 mg intravenously twice weekly or iron sulfate 160 mg/day orally, for 3 weeks preoperatively. Efficacy was measured by the increases over baseline in hemoglobin, reticulocyte count, and ferritin determined 3 days before surgery; preoperative reticulocyte count and ferritin were significantly higher with intravenous iron, whereas the only significant intragroup increases in hemoglobin between time points also occurred in this group. Intravenous iron significantly boosts the hematopoietic response to rhEPO and prevents iatrogenic iron depletion in otherwise healthy candidates for elective surgery.