Challenges to the development of complex virtual reality surgical simulations.

Virtual reality simulation in surgical training has become more widely used and intensely investigated in an effort to develop safer, more efficient, measurable training processes. The development of virtual reality simulation of surgical procedures has begun, but well-described technical obstacles must be overcome to permit varied training in a clinically realistic computer-generated environment. These challenges include development of realistic surgical interfaces and physical objects within the computer-generated environment, modeling of realistic interactions between objects, rendering of the surgical field, and development of signal processing for complex events associated with surgery. Of these, the realistic modeling of tissue objects that are fully responsive to surgical manipulations is the most challenging. Threats to early success include relatively limited resources for development and procurement, as well as smaller potential for return on investment than in other simulation industries that face similar problems. Despite these difficulties, steady progress continues to be made in these areas. If executed properly, virtual reality offers inherent advantages over other training systems in creating a realistic surgical environment and facilitating measurement of surgeon performance. Once developed, complex new virtual reality training devices must be validated for their usefulness in formative training and assessment of skill to be established.

Virtual reality simulator training equals mechanical robotic training in improving robot-assisted basic suturing skills.

BACKGROUND: This study aimed to investigate the effect of a virtual reality simulator on the learning of basic robotic suturing skills. METHODS: Two randomized groups of students underwent a controlled training program. Both groups completed an identical test before and after training. The increase in the number of stitches placed during the pretest and posttest was used as an objective measure of the training effect. To evaluate the subjective feeling of understanding and mastering, the students indicated this on a visual analog scale. RESULTS: Both groups showed a significant increase in the number of stitches placed during the posttest, and an increase in subjective feeling of understanding and mastering. The increase did not differ between the groups, indicating that the virtual reality simulator equaled the mechanical trainer in training of robotic suturing technique. CONCLUSIONS: Training in basic robot-assisted suturing skills using a virtual reality simulator without additional training equaled training using a mechanical simulator.

Accuracy of acoustic rhinometry.

OBJECTIVES: The objective of this study was to evaluate the ability of acoustic rhinometry (AR) (Rhin2100, Rhinometrics, Lynge, Denmark) to accurately determine the dimensions (cross-sectional areas and volumes) of the curved and complex slit-like geometry of the nasal airway. MATERIALS AND METHODS: A plastic model representing the replicate of a decongested nasal airway was produced by stereolithographic techniques from a 3-D MRI-scan. The exact dimensions of this model was determined from a high resolution CT-scan. Dimensions perpendicular to the curved course of the acoustic pathway were compared with dimensions inferred from parallel sections. The impact of sound loss to the paranasal sinuses and the ability to detect posterior volume changes was tested in the same model. RESULTS: The error in volume determination was < 14% for the MCA and < 8% for the volumes, whereas the error reached 52% for dimensions calculated from parallel sections in the coronal plane. The influence of the simulated maxillary sinuses depend primarily on the size of the ostia and may represent an important source of error for posterior measurements, in particular after decongestion. CONCLUSIONS: The accuracy of acoustically derived dimensions of the 3-D model depend on the orientation of the planes used to calculate the dimensions of the model. Volume estimates based on the smallest cross-sectional areas in points along the acoustic pathway correlate well with acoustically derived volumes, whereas single cross-sectional areas are more susceptible to error. Sound leakage to patent sinus ostia reduce the accuracy of posterior measurements.

Digital trainer developed for robotic assisted cardiac surgery.

Robotic systems for cardiac surgery have been introduced in clinical trials to facilitate minimally invasive techniques. Widespread use of surgical robotics necessitates new training methods to improve skills and continue practicing as the robotic systems are frequently being upgraded. Today, robotic training is performed on expensive animal models. An integration of a digital trainer with the two present robotic systems applied in coronary artery bypass procedures on beating heart requires real time simulation of tissue mechanics, sutures, instruments and bleeding. However, it requires no extra haptic device, since the robotic master is the haptic apparatus itself. By developing new data structures and parametric geometry descriptions we have demonstrated the possibility of obtaining surgical simulation on a standard PC Linux system. This technology is beneficial when simulation is exploited over a network with limited bandwidth, especially when it comes to the handling of soft tissue dynamics.

A single nocturnal exposure to 2-7 millitesla static magnetic fields does not inhibit the excretion of 6-sulfatoxymelatonin in healthy young men.

The present study sought to evaluate possible acute effects on 6-sulfatoxymelatonin (aMT6s) excretion, a surrogate for melatonin levels in blood, in volunteers exposed to static magnetic fields with flux densities representative for workers in light metal reduction plants and operators of medical MRI in hospitals. Eleven healthy male volunteers (23-43 years) participated. Urine samples were collected for two consecutive 24 h periods from 22:00 hours day 1 (exposure day) through day 2 (day after exposure) and then for 24 h from 07:00 hours on day 7 (control day). On the day of exposure the subjects slept in the MRI room from 22:00 hours until 07:00 hours next morning, thus receiving a 9 h exposure to the magnetic field (2-7 mT). On the day after exposure and on the control day, they slept at home and otherwise performed their ordinary daily activities. Total daily urine production was collected in four parts: 22:00-07:00 hours, 07:00-11:00 hours, 11:00-18:00 hours, 18:00-22:00 hours, and the volume for each interval was measured and recorded. Samples were transferred to coded bottles and frozen for later RIA analysis of aMT6s. Pairs of values of mean hourly aMT6s excretion, both diurnal and for the four daily intervals, were compared using two-sided Wilcoxon signed ranks test. The day of exposure and the day after exposure were not significantly different from the control day, either for the total diurnal secretion or the interval data. In summary, the study shows no association between a single nocturnal exposure to a static magnetic field of strength 2-7 mT and excretion of aMT6s in urine.

A magnetic resonance imaging study of modifications to the infraclavicular brachial plexus block.

A previously described infraclavicular brachial plexus block may be modified by using a more lateral needle insertion point, while the patient abducts the arm 45 degrees or 90 degrees. In performing the modified block on patients abducting 45 degrees, we often had problems finding the cords of the brachial plexus. Therefore, we designed an anatomic study to describe the ability of the recommended needle direction to consistently reach the cords. Additionally, we assessed the risk of penetrating the pleura by the needle. Magnetic resonance images were obtained in 10 volunteers. From these images, a virtual reality model of each volunteer was created, allowing precise positioning of a simulated needle according to the modified block, without exposing the volunteers to actual needle placement. In both arm positions, the recommended needle angle of 45 degrees to the skin was too shallow to reach a defined target on the cords. Comparing the two arm positions, target precision and risk of contacting the pleura were more favorable with the greater arm abduction. We conclude that when the arm is abducted to 90 degrees, a 65 degrees -needle angle to the skin appears optimal for contacting the cords, still with a minimal risk of penetrating the pleura. However, this needs to be confirmed by a clinical study.

[Telemedicine collaboration between the Rikshospitalet and the Ulleval hospital]. / Telemedisinsk samarbeid mellom Rikshospitalet og Ullevål sykehus.

BACKGROUND: During the last two years the Intervention Centre at the Nation Hospital of Norway and Ullevål Hospital have pursued a research programme in telemedicine aimed at exploring the potential of inter-hospital collaboration. MATERIAL AND METHODS: Both hospitals established a communication network between operating rooms and lecture halls. Sound and video from minimally invasive surgical and radiology procedures were transmitted on a wide bandwidth ATM network (34 Mbits/s) to gain experience with the use of telemedicine for educational purposes and the treatment of patients. RESULTS: Evaluations of technical off-line and clinical line transmissions have given us helpful information about the potential of telemedicine and what it will take to utilise this potential. With the MPEG2 standard, a wide bandwidth network yields sufficient sound and image quality for educational and clinical collaboration. However, multimedia communication requires changes in the organisation to secure quality of service in relation to technical management and telemedical production. INTERPRETATION: Inter-hospital collaboration on telemedicine may be a resource in clinical practice, facilitating professional enhancements, particularly in surgery, radiology and internal medicine. Changes in the organisation are needed, but they are feasible.

[Image guided and robotic treatment--the advance of cybernetics in clinical medicine]. / Bildeveiledet og robotisert behandling--kybernetikkens inntog i klinisk medisin.

The introduction of advanced technology in hospitals has changed the treatment practice towards more image guided and minimal invasive procedures. Modern computer and communication technology opens up for robot aided and pre-programmed intervention. Several robotic systems are in clinical use today both in microsurgery and in major cardiac and orthopedic operations. As this trend develops, professions which are new in this context such as physicists, mathematicians and cybernetic engineers will be increasingly important in the treatment of patients.

Acoustic rhinometry: a study of transient and continuous noise techniques with nasal models.

The objective of this study is to compare the properties of two of the most frequently used acoustic rhinometers: the EcoVision (Hood Laboratories, USA) using the transient technique, and the Rhin2100 (RhinoMetrics, Denmark) using the continuous wide-band technique. In the wide-band rhinometer (Rhin2100), the transient analog signals of traditional rhinometers (EcoVision), are replaced by a digitally produced continuous wide-band noise signal. Tubular models and a plastic model produced by stereolithography (SLA), representing the true replicate of the nasal anatomy, were used to compare the accuracy of the two rhinometers. The effect of increasing angling (0-50 degrees) between the sound wave tube and the cavity was evaluated in a tubular model. The curves obtained with the two rhinometers showed close similarity, and the acoustically derived volumes correlated well with the volumes of tubular (% error < 4%) as well as the complex nasal model (% error < 10.5%). Both rhinometers underestimated the minimum cross-sectional area (MCA) of the complex nasal model (mean % error complex model: Rhin2100 = -7.6%, EcoVision = -13%). The effect of increasing the angle between the nose adapter and the tubular models was small for both rhinometers (CV < 3% for MCA and CV < 1% for volumes). The similar, and in general, high accuracy of the two rhinometers evaluated, particularly in the complicated geometry of the SLA model, is an indication of the reliability of both. The small effect of changing the angle between the nose adapter and the models was unexpected and very encouraging. Nevertheless, some minor differences in performance and capabilities of the two rhinometers might influence interpretation and comparison of results. Further comparisons in a clinical setting are under current investigation.

Magnetic resonance imaging demonstrates lack of precision in needle placement by the infraclavicular brachial plexus block described by Raj et al.

UNLABELLED: The infraclavicular brachial plexus block first described by Raj et al. was supposed to anesthetize all the main peripheral nerves of the brachial plexus without the risk of pneumothorax. However, in performing the block, we have had difficulties finding the nerves at the cord level. Therefore, we questioned whether the recommended needle direction (the "Raj line") guides the needle close enough to the cords. We therefore designed an anatomic study to answer this question and to assess the risks of entering the pleura and axillary vein. Ten volunteers were examined noninvasively in an open model magnetic resonance scanner. The Raj line deviated greatly from a defined location on the cords by a mean of 26 (range 14-39) mm, always caudad, and posterior to the target in nine cases. Further, the needle trajectory's shortest distance to the pleura was only 10 (0-27) mm, and in one case, it hit the pleura. Finally, the Raj line's distance to the axillary vein was also short, 11 (0-18) mm. We conclude that a modification of the method is necessary to guide the needle closer to the cords and further away from the pleura and the axillary vein. A more lateral needle insertion seems beneficial. IMPLICATIONS: Using a magnetic resonance scanner, the anatomical basis of Raj's infraclavicular method for brachial plexus blockade was examined in volunteers. The results show that the method should be modified to make it more precise and to provide less risk of complications.

[The intervention center at the Rikshospital. Experiences from the first year of activity]. / Intervensjonssenteret ved Rikshospitalet. Erfaringer fra ett års drift.

In order to co-ordinate and promote the development of new clinical applications by structuring collaboration and communication across traditional specialty boundaries, a first of its kind hospital department was opened at Rikshospitalet in June 1996. The Interventional Centre is a multidisciplinary centre for research and development, teaching and quality management of imaging-guided minimally invasive therapy, endoscopic surgery and interventional radiology. The department is a full fusion of state-of-the art operating theatre with an advanced radiology department and with fully up-to-date ultrasound and endoscopy facilities for integrated use in the treatment of the patient. The department is cross-disciplinary organised. A small staff of 14 persons are responsible for the day-to-day running of the centre. Specialists from other hospital departments work together with the centre's permanent staff to develop new procedures. During the first year, 19 research projects were started and a total of 510 procedures performed within the fields of Radiology, Neurosurgery, Gastroenterology, Cardiology, Cardiovascular surgery and Paediatric cardiology, and also within the fields of image processing and telecommunication.

Dual T cell receptor T cells have a decreased sensitivity to physiological ligands due to reduced density of each T cell receptor.

A considerable fraction of T cells express two distinct T cell receptors (TCR), mainly due to expression of two TCR alpha chains. It has been suggested that such dual-TCR cells could have a role in autoimmunity. However, as such cells express less of each TCR, they could be less sensitive to their physiological ligand, i.e. peptide plus major histocompatibility complex molecules (MHC). We tested this hypothesis in a transgenic TCR model in which most T cells express different amounts of the transgene-encoded TCR, due to expression of endogenous TCR alpha chains. Five Th1 clones derived from lambda2(315) immunoglobulin light chain-specific TCR-transgenic mice expressed different levels of the transgene-encoded TCR, ranging from approximately 10,000 to approximately 50,000 TCR per cell. Cytosolic Ca2+ mobilization in single T cells from these clones elicited by lambda2(315) peptide-pulsed, I-Ed-expressing antigen-presenting cells, correlated linearly with the relative transgene-encoded TCR expression. The peptide requirement for half-maximal T cell proliferation showed a similar correlation, with low TCR levels requiring higher peptide concentration. Corroborative evidence was obtained by deployment of short-term polyclonal CD4+ lines from TCR-transgenic mice. Such lines had reduced early (Ca2+ mobilization) and late (lymphokine and proliferation) responses, compared with T cell lines from recombination-deficient TCR-transgenic severe combined immunodeficiency mice (which express only a single transgene-encoded TCR). Taken together, the Ca2+ responses increase gradually with increasing TCR expression per cell, similar to the previously described analog Ca2+ signaling elicited by increasing amounts of peptide/MHC [Røtnes et al., Eur. J. Immunol. 1994. 24: 851]. Surprisingly small reductions in TCR expression per cell reduce T cell responsiveness. This suggests that dual-TCR T cells are immunologically less effective than single-TCR T cells.

Interferon-gamma modulates cytosolic free calcium in human neutrophilic granulocytes.

To investigate the role of cytosolic free calcium ([Ca2+]i in interferon-gamma (IFN-gamma) pre-activation (priming) of human neutrophilic granulocytes (PMN) we used three different fluorescence methods, i.e. digital imaging of single, adherent, Fura-2 loaded cells, flow cytometric measurements of single, non-adherent, Fluo-3 loaded cells, and spectrofluorometry of Indo-1 loaded PMN in suspension. IFN-gamma increased the [Ca2+]i level in single, adherent PMN during the second phase of the fMLP response. The bacterial peptide fMLP (N-formyl-L-methionyl-L-leucyl-L-phenylalanine) is a known stimulant of the calcium/inositol phosphate system. The [Ca2+]i increase was abolished in Ca(2+)-free test buffer. Furthermore, the baseline [Ca2+]i level was found to be slightly increased in IFN-gamma primed PMN as analysed with flow cytometry. On the other hand, these [Ca2+]i responses were not detectable with the other methods used. We suggest that IFN-gamma increases the plasma membrane permeability for calcium in PMN, and substantiate this by demonstrating compliance with a capacitative model for intracellular calcium regulation. Mathematical modeling also suggested that IFN-gamma primed human PMN may sequester 13% more Ca2+ than unprimed cells in fMLP-insensitive intracellular stores. Thus, the Ca2+ responses to IFN-gamma are modest and not easily detectable with some of the methods currently in use. They nevertheless explain why fMLP elicits brisker responses from PMN after IFN-gamma priming.

Quantitative analysis of cytosolic free calcium oscillations in neutrophils by mathematical modelling.

Mathematical models are often used to elucidate mechanisms behind cytosolic Ca2+ oscillations. We have evaluated the use of mathematical modelling to analyse and quantify Ca2+ signal patterns, in single, adherent human neutrophils (PMN) after stimulation by the bacterial peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP). The cells were loaded with Fura-2 and fluctuations in cytosolic Ca2+ recorded with a video based digital imaging system. A new indirect intracellular calibration method was introduced to avoid the uncertainty in obtaining an equilibrium between the extracellular and intracellular calcium concentrations. Two different approaches to mathematical modelling were used. First, we applied a sensitivity analysis with a two-pool model by assuming an optimal situation using reliable a priori estimates of all structural parameters (e.g. Hill coefficients and dissociation constants). We found that the a priori estimates of the other 5 more variable parameters must lie within the range of 25-400% of the postulated true parameter values to be reliable in a parameter estimation method. Small changes (less than 5%) in those variable parameter values induced very different types of signal patterns which may have some relevance in evaluating a possible functional significance to the oscillatory signals. Second, we employed a one-pool, non oscillatory model integrated with a power spectrum method as a tool to quantify the dose dependency between fMLP (1-1000 nM) and parameters describing the biphasic process of calcium signalling and parameters describing only the oscillatory components. We conclude that the frequency of the observed oscillations assembled around one characteristic frequency independent of fMLP concentration, and sinusoidal oscillations were observed most frequently in PMN stimulated to a moderate peak [Ca2+]i level.

Ca2+ mobilization in physiologically stimulated single T cells gradually increases with peptide concentration (analog signaling).

We have investigated Ca2+ mobilization in single T cells stimulated with their physiological ligand, i.e. antigenic peptide bound to major histocompatibility complex (MHC) molecules on antigen-presenting cells (APC). Fibroblasts expressing I-Ed class II molecules were pulsed with a peptide derived from the lambda 2(315) immunoglobulin light chain. Onto such antigen-pulsed fibroblasts were sedimented cloned Th1 cells loaded with Fura-2. Changes in cytosolic Ca2+ concentration in single T cells were continually monitored by use of an imaging system based on fluorometry. Ca2+ mobilization was both peptide-specific and MHC-restricted. Within seconds of the initial APC-T cell contact, a Ca2+ spike could be observed. The Ca2+ response gradually declined over a 25-min period, during which oscillations were noted. Various parameters characterizing the magnitude of the Ca2+ response (latency, increase rate, max and mean Ca2+ increase, frequency and period of oscillations) all correlated with the amount of peptide used for pulsing the fibroblasts. Thus, Ca2+ mobilization in single T cells appears not to be an all or none phenomenon. Rather, activation is incremental (analog signaling), the degree of Ca2+ mobilization probably being related to the number of stimulatory peptide-MHC complexes on the surface of the APC. The extent of calcium mobilization and lymphokine production (interleukin (IL)-2, IL-3, interferon-gamma) correlated, at least at the population level.

Dependence of hepatocytic autophagy on intracellularly sequestered calcium.

Autophagic sequestration of endogenous lactate dehydrogenase or electroinjected [3H]raffinose in isolated rat hepatocytes was strongly suppressed by the Ca2+ chelator EGTA, unless the cells had previously been electroloaded in the presence of high concentrations of Ca2+ (1.2 mM). The extracellular Ca2+ chelator bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA) and the intracellular Ca2+ chelator BAPTA/tetra(acetoxymethyl)-ester (BAPTA/AM) both inhibited autophagy to the same extent as did EGTA. Inhibitors of Ca(2+)-activated protein kinases (KN-62, H-7, W-7) had little or no effect on autophagy, indicating that the Ca2+ requirement of autophagy was not mediated by such kinases. Agents that elevate cytosolic Ca2+ by releasing Ca2+ from intracellular stores, like thapsigargin, 2,5-di-(tert-butyl)-1,4-benzohydroquinone (tBuBHQ) and the ionophores A23187 and ionomycin, inhibited autophagy strongly, implicating depletion of sequestered rather than of cytosolic intracellular Ca2+ as a common mechanism of inhibition. Lysosomal (propylamine-sensitive) protein degradation, known to be largely autophagy-dependent, was inhibited by thapsigargin and tBuBHQ. Thapsigargin had no effect on cellular ATP levels, but all agents tested (thapsigargin, tBuBHQ, ionophores) inhibited protein synthesis. Our results suggest that autophagy, like protein synthesis, is dependent on the presence of Ca2+ in some intracellular storage compartment.

Epidermal growth factor stimulates the prolactin synthesis and secretion in rat pituitary cells in culture (GH4C1 cells) by increasing the intracellular concentration of free calcium.

Epidermal growth factor (EGF) stimulated the prolactin (PRL) synthesis and release from the GH4C1 cells in a dose-dependent manner. The ED50 was between 10(-11) and 10(-10) mol/l. The maximal effect was obtained at 10(-9) mol/l EGF for the release, and 10(-8) mol/l EGF for the synthesis. EGF stimulated the release of PRL from cell perfusion columns after a lag period of about 30 s. The maximal secretion of PRL occurred about 60 s after the start of stimulation. The PRL secretion declined to basal levels within 2 min. The EGF-stimulated PRL release was additive to the secretion evoked by thyrotropin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP). An instantaneous increase in the intracellular concentration of free calcium, [Ca2+]i, of the GH4C1 cells was observed after the administration of EGF. EGF modified neither the basal nor the TRH-stimulated inositoltrisphosphate production in the GH4C1 cells, and EGF did not show any effect on the cyclic adenosine monophosphate production of these cells.

Thapsigargin reveals evidence for fMLP-insensitive calcium pools in human leukocytes.

To investigate the relationship between different intracellular Ca2+ pools, cytosolic free calcium ([Ca2+]i) was surveyed by means of a Fura-2 fluorescence ratio method on single isolated human leukocytes. Both monocytes and neutrophilic granulocytes (PMN) displayed long lasting spontaneous [Ca2+]i transient changes (1-2 min). In PMN stimulated with the bacterial peptide fMLP we observed transients with shorter duration (10-30 s) and smaller amplitude often superimposed on the long lasting transients. The time course of changes in [Ca2+]i was recorded in a large number (149) of single leukocytes prestimulated for 5 min with fMLP and then challenged with thapsigargin (a blocker of Ca2+ uptake in intracellular pools). Statistical analysis of [Ca2+]i responses revealed that fMLP-sensitive pools contributed to the long lasting [Ca2+]i transients seen in both leukocyte types. However, the existence of fMLP-insensitive calcium pools may explain the superimposed transients seen in PMN. Thapsigargin was also added together with EGTA (to impede contribution from extracellular Ca2+) to 198 fMLP prestimulated and 153 unstimulated PMN. Based on Ca2+ registrations in these cells and a mathematical model (supposing two separate first order responses) the amount of Ca2+ stored in the various pools and their release kinetics were estimated. The results indicate that fMLP-insensitive calcium pools exist in PMN but not in monocytes. Since the digital imaging technique also depicts cellular motility, an additional finding was that the leukocyte's ability to sequestrate the Ca2+ from the cytosol seemed important to locomotion.