Integrator for qualitative and quantitative unit activity.

A simple device constructed from inexpensive components enables spike activity to be integrated and displayed in a convenient scale (spikes/sec) on a pen recorder. An input voltage threshold detection circuit is employed to eliminate any random baseline noise from being integrated. A pulse output is provided to drive a counter or accumulator so that quantitative as well as qualitative results may be obtained. A monostable multivibrator is used to insure that the integrated output is a function of the frequency of spike activity and not the amplitude or pattern of the spikes. An output isolation and buffer stage is provided to eliminate any loading effect on the filter section and also provide a gain or scaling adjustment so that the integrator may be used with practically any pen recorder.     

Stereological Methods for Estimating the Myelin Sheaths of the Myelinated Fibers in White Matter

In the present study, efficient and unbiased stereological techniques to investigate the myelin sheaths of the myelinated fibers in rat white matter were established. In the present design, four tissue blocks were obtained from the entire white matter of rat brain in a uniform, random fashion. Isotropic, uniform random (IUR) sections were ensured by the use of the isector technique. One section with the thickness of 60 nm was cut from the center of each epon block. Eight to 10 fields of vision were randomly photographed under a transmission electron microscope. The total length of the myelinated fibers and the total volume of the myelin sheaths in the white matter were the products of the length density, volume density, and the volume of the white matter obtained with the Cavalieri principle. The mean areas of the myelinated fibers profiles and myelin sheaths were estimated with the point counting technique. The inner and outer perimeters of the myelin sheaths were estimated by the use of a line grid, and the thickness of the myelin sheaths was estimated by direct orthogonal measurements in uniform, random locations. The described methods will provide very useful tools for future quantitative studies of changes in the myelin sheaths of white matter in various experimental conditions and in various neurodegenerative diseases. Anat Rec, 2009. © 2009 Wiley‐Liss, Inc.     

Effects of enzymatic treatments on the biomechanical properties of screws made of bone

Nowadays, bone tissue employed to manufacture screws used as osteosynthesis material is obtained from organ donors. But in different medical fields there is an increasing need to use xenogenic grafts and implants, which still imply risks of transmission of some diseases and antigenicity. Two different autoclaving programs (A1, A2) and an alternative to reduce the antigenicity of screws made of xenogenic bone based on enzymatic treatment are analyzed from a biomechanical point of view. 128 screws made of bovine femur bone were employed. Some of them were partially demineralized with 0.6 N HCl, enzymatically digested with collagenase (specific) and pepsin (nonspecific) and then autoclaved. The specimens were subjected to tension, shear and screw torque tests and histologically evaluated. Compared to A1, A2 sterilization method (134 degrees C but higher vacuum and longer time) considerably reduced the mechanical strength of specimens. The enzymatic digestion, expected to reduce antigenicity, did not affect the screw superficial structure and would not modify the bone biomechanical properties per se, but maybe because of the association with autoclaving and partial demineralization.     

Mast cells in human lungs

Mast cells were stained deeply in human lung tissue with acidic toluidine blue to obtain maximum numbers possible in paraffin sections. One hundred high-power fields were counted per section, and mean and median values summarized as mast cells per mm2. Immersion-fixed samples of fresh lung tissue (not bronchi) were taken as controls from seven patients after surgery, and showed mean values of 44.7 mast cells per mm2 after formalin fixation, and 51.9 per mm2 after Carnoy's fixative. Mast cell heterogeneity may explain these differences, but so could random variation between counts. In two patients with extrinsic allergic alveolitis (hypersensitivity pneumonitis), fresh lung tissue from open lung biopsies showed raised values of 90.8 and 101.9 mast cells per mm2, matching the high mast cell counts reported in bronchopulmonary lavage fluid in the condition. Control post-mortem lung tissue from two patients dying of non-pulmonary diseases showed mean values of 26.1 and 50.6 mast cells per mm2. Post-mortem lung tissue from three patients dying of asthma showed very low mean values of 4.7, 5.7, and 5.9 mast cells per mm2. Low mast cell counts due to severe degranulation have been reported before in the bronchi in asthma deaths, but not, to our knowledge, in the lung parenchyma. This finding implies a wider area of mediator release, and helps to explain the severity of the acute attack, and the fatal outcome.     

Using total-variation regularization for intensity modulated radiation therapy inverse planning with field-specific numbers of segments

Currently, there are two types of treatment planning algorithms for intensity modulated radiation therapy (IMRT). The beamlet-based algorithm generates beamlet intensity maps with high complexity, resulting in large numbers of segments in the delivery after a leaf-sequencing algorithm is applied. The segment-based direct aperture optimization (DAO) algorithm includes the physical constraints of the deliverable apertures in the calculation, and achieves a conformal dose distribution using a small number of segments. However, the number of segments is pre-fixed in most of the DAO approaches, and the typical random search scheme in the optimization is computationally intensive. A regularization-based algorithm is proposed to overcome the drawbacks of the DAO method. Instead of smoothing the beamlet intensity maps as in many existing methods, we include a total-variation term in the optimization objective function to reduce the number of signal levels of the beam intensity maps. An aperture rectification algorithm is then applied to generate a significantly reduced number of deliverable apertures. As compared to the DAO algorithm, our method has an efficient form of quadratic optimization, with an additional advantage of optimizing field-specific numbers of segments based on the modulation complexity. The proposed approach is evaluated using two clinical cases. Under the condition that the clinical acceptance criteria of the treatment plan are satisfied, for the prostate patient, the total number of segments for five fields is reduced from 61 using the Eclipse planning system to 35 using the proposed algorithm; for the head and neck patient, the total number of segments for seven fields is reduced from 107 to 28. The head and neck result is also compared to that using an equal number of four segments for each field. The comparison shows that using field-specific numbers of segments achieves a much improved dose distribution.     

接骨板不同螺钉布局下骨愈合过程有限元分析

目的探究螺钉布局方式对骨愈合的影响,为相关的骨折治疗提供基础。方法采用有限元方法研究不同螺钉布局方式下骨愈合过程;采用骨折块应变理论(interfragmentary strain theory,IFS)模拟骨痂的生长变化过程;利用Python语言对ABAQUS进行二次开发,使得迭代过程中骨痂所划分的每个单元都根据IFS理论更新弹性模量,从而模拟骨折愈合过程。结果不同数量螺钉对骨愈合过程的影响小于不同接骨板工作长度对骨愈合过程的影响;稳定固定的前提下,接骨板工作长度一定时,螺钉数量变化对接骨板或螺钉的应力影响较小;接骨板工作长度不同,对接骨板及螺钉的应力影响较大,且工作长度变化对螺钉上应力变化的影响大于对接骨板的影响。结论相较于螺钉数量,对于接骨板工作的长度应着重考虑,应当遵循在保证内固定系统稳定的前提下,减少接骨板上的螺钉数量,并对接骨板工作长度的选择进行恰当的选择。     

Strain-gauge versus water plethysmography description of simplified systems and analysis of differences and accuracy

Recently developed water and strain-gauge plethysmographs are compared on the same forearm. They do not differ systematically in absolute blood-flow values at different steady-state levels, provided that the strain gauge is applied at the middle, muscular, part of the forearm. The accuracy of the water and strain-gauge plethysmograph is identical, and the two instruments closely follow random variations in blood flow. The water plethysmograph is a reliable integrator of blood flow in a segment of a limb, and the strain-gauge described here can be used as an adequate substitute, when placed in the middle of the limb segment examined. However, the results from the strain-gauge plethysmograph are dependent on the actual location of the strain gauge.     

Biomaterials in spinal fixation. An experimental animal study to improve the performance

Different pedicle screws were biomechanically and morphologically studied and compared through the use of an animal model to determine their efficacy and resistance in spinal fixation. The principal objective was to compare biomechanical and histomorphological aspects of HA-coated screws to uncoated ones. Fourty-eight cylindrical transpedicular self-tapping screws divided into three groups of sixteen each were employed; Group A: stainless steel screws; Group B: titanium screws; Group C: HA-coated titanium screws. The screws were implanted bilaterally and randomly into the L3, L4, and L5 pedicles of eight adult mongrel sheep. The final insertion torque was measured in all the implants. After one and four months, upon euthanization, four samples per group were extracted from the surrounding bone and the screw extraction torque was measured. The remaining samples were examined and processed for histological and histomorphological evaluations. No differences were observed at one month among the extraction torque of the three groups. After four months the only significance between insertion and extraction values was for the HA group, i.e. p=0.001. Comparing the extraction torque values of the three groups after four months of healing, the HA-coated group showed a greater than twofold increase (p<0.0005). No differences were observed at one month among the percentages of bone-implant contact in the three groups. After four months the percentage was significant only for the C group (p<0.0005). At four months a correlation was found between the morphological and the biomechanical data of group C (p<0.0005). The use of hydroxyapatite-coated screws could act as an effective method to improve the bone-implant interface, thus obtaining a strong fixation of the implant independently of the arthrodesis achieved with bone graft.     

Evaluation of the Effect of Varying MPEG-2 Compression Ratios on Digital Coronary Angiographic Assessment of Stenosis Severity

The purpose of this study is to evaluate the influence of MPEG-2 compression scheme on coronary angiography and to search the highest compression ratio at which no significant effect to accuracy of assessment of stenosis severity occurs. Forty-Four digital cine angiographies were used. Three cardiologists participated in a subjective study in which they read both uncompressed images and compressed images. Furthermore, an objective study was carried out to measure vessel stenosis ratio by using software. The influence of compression was evaluated by kappa statistics in case of subjective study and by both systematic error and random error in case of objective study. Kappa statistics between uncompressed image and compressed image at a ratio of 80:1 was significantly lower than that of other compression ratios such as 40:1. Similar results were obtained in objective evaluation. In this report, the authors provide the baseline for further studies on observer performance for motion images.     

Innovative approach in the development of computer assisted algorithm for spine pedicle screw placement

Pedicle screws are typically used for fusion, percutaneous fixation, and means of gripping a spinal segment. The screws act as a rigid and stable anchor points to bridge and connect with a rod as part of a construct. The foundation of the fusion is directly related to the placement of these screws. Malposition of pedicle screws causes intraoperative complications such as pedicle fractures and dural lesions and is a contributing factor to fusion failure. Computer assisted spine surgery (CASS) and patient-specific drill templates were developed to reduce this failure rate, but the trajectory of the screws remains a decision driven by anatomical landmarks often not easily defined. Current data shows the need of a robust and reliable technique that prevents screw misplacement. Furthermore, there is a need to enhance screw insertion guides to overcome the distortion of anatomical landmarks, which is viewed as a limiting factor by current techniques. The objective of this study is to develop a method and mathematical lemmas that are fundamental to the development of computer algorithms for pedicle screw placement. Using the proposed methodology, we show how we can generate automated optimal safe screw insertion trajectories based on the identification of a set of intrinsic parameters. The results, obtained from the validation of the proposed method on two full thoracic segments, are similar to previous morphological studies. The simplicity of the method, being pedicle arch based, is applicable to vertebrae where landmarks are either not well defined, altered or distorted.     

On the Use of Optical Flow Methods with Spin-Tagging Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is a versatile noninvasive tool for achieving full-field quantitative visualization of biomedical fluid flows. In this study, two MRI velocimetry techniques (spin tagging and phase contrast) are used to obtain velocity measurements in a Poiseuille flow for Reynolds numbers below 1000. Spin-tagging MRI velocimetry supplies the displacement of tagged grids of nuclear spins from which the velocity field can be inferred, while phase contrast MRI velocimetry directly provides velocity data for every pixel in the field of view. Although the phase contrast method is more accurate for this flow, this technique is more sensitive to errors from magnetic susceptibility gradients, higher order motions, and has limited dynamic range. Spin-tagging MRI velocimetry is a viable alternative if automatic methods for extracting velocity fields from the tags can be found. Optical flow, a technique originally developed for machine vision applications, is proposed here as a postprocessing step to obtain two-dimensional velocity fields from spin-tagging MRI images. Results with artificially generated grids demonstrate the robustness of the optical flow algorithm to noise and indicate that a 7%–10% average error can be expected from the optical flow calculations alone, independent of MRI image artifacts. Experiments on spin-tagging MRI images for a Re=230 Poiseuille flow gave an average error of 6.41%, which was consistent with the measurement error of the generated (synthetic) images with the same level of random noise superimposed. © 2001 Biomedical Engineering Society. PAC01: 8761-c, 8719Uv, 8757Ce     

三维重建腰椎椎弓根螺钉置入的精确性

背景：三维重建技术已经广泛应用于椎弓根螺钉置入前规划,但是就其预测参数的准确性目前尚未见直接的分析与报道。 目的：基于CT三维重建技术应用于临床,对腰椎椎弓根螺钉置入前指导作用的精确性作初步分析。 方法：在Mimics软件下,随机对30例行腰椎椎弓根螺钉内固定的患者共136个椎弓根行内固定前CT三维重建,并通过内固定前模拟模块预测钉长、直径、水平面角及矢状面角度并与内固定后实际数据进行统计学比较。 结果与结论：内固定前通过Mimics软件对腰椎行三维重建,设计最佳钉道并模拟置钉,预测椎弓根螺钉长、直径、水平面角及矢状面角度与通过C型臂及内固定中导航系统等方式置钉后实际数据的差异无显著性意义(P > 0.05),并且内固定后行CT扫描见置钉位置及长度均良好。说明通过Mimics软件对腰椎进行三维重建模拟置钉并制定置钉参数,能比较精确的指导内固定中实际置钉,提高椎弓根螺钉的置钉安全。     

Early or late monitoring of stimulation of ovulation for in-vitro fertilization? A methodological discussion of a randomized study

Two GnRH agonist long-stimulation protocols, in association with HMG, are compared on a random basis. Group A (n = 53) was monitored daily from the 6th day of stimulation, whereas monitoring in group B (n = 55) began on the 11th day of stimulation. There was no significant difference in the numbers of follicles which matured, the numbers of collected oocytes, the numbers of embryos obtained in vitro and the clinical pregnancy rate. But the power of such a study is very weak (6%). It would have been necessary to include greater than 1000 patients in each group to obtain a bioequivalence test. Such a study is unrealistic for a single centre and multicentric studies are very difficult to achieve because of practical difficulties. A pooled analysis is perhaps the methodological answer.     

Volumetric three-dimensional recognition of biological microorganisms using multivariate statistical method and digital holography

We present a new statistical approach to real-time sensing and recognition of microorganisms using digital holographic microscopy. We numerically produce many section images at different depths along a longitudinal direction from the single digital hologram of three-dimensional (3D) microorganisms in the Fresnel domain. For volumetric 3D recognition, the test pixel points are randomly selected from the section image; this procedure can be repeated with different specimens of the same microorganism. The multivariate joint density functions are calculated from the pixel values of each section image at the same random pixel points. The parameters of the statistical distributions are compared using maximum likelihood estimation and statistical inference algorithms. The performance of the proposed system is illustrated with preliminary experimental results.     

Magnetophosphenes: a quantitative analysis of thresholds

Low-frequency and transient magnetic fields of moderate flux densities are known to generate visual phenomena, so-called magnetophosphenes. In the present study, time-variable very low frequency (10–50 Hz) electromagnetic fields of moderate flux density (0–40 mT) were used to induce magnetophosphenes. The threshold values for these phosphenes were determined as a function of the frequency of the magnetic field both in normal subjects and colour defective ones. Maximum sensitivity occurred at a frequency of approximately 20–30 Hz, and with broad-spectrum light the threshold flux density was 10–12 mT. The threshola values were found to be dependent upon the intensity and the spectral distribution of the background light. Sensitivity decreased during dark adaptation. In certain respects deutans differed from subjects with normal colour vision. Possible mechanisms for generation of magnetophosphenes are discussed. The present magnetic threshold curves show a close resemblance to corresponding curves obtained by electric stimulation at various frequencies provided the electric thresholds are divided by the a.c. frequency. These problems are under current investigation in our laboratory. This is in full agreement with the assumption that the fluctuating magnetic field affects retinal neurons by inducing currents which polarise synaptic terminals.     

Immunohistochemical quantitation of oestrogen receptors and proliferative activity in oestrogen receptor positive breast cancer.

AIM--To evaluate the effect of the duration of formalin fixation and of tumour heterogeneity on quantitative estimates of oestrogen receptor content (oestrogen receptor index) and proliferative activity (MIB-1 index) in breast cancer. METHODS--Two monoclonal antibodies, MIB-1 and oestrogen receptor, were applied to formalin fixed, paraffin wax embedded tissue from 25 prospectively collected oestrogen receptor positive breast carcinomas, using a microwave antigen retrieval method. Tumour tissue was allocated systematically to different periods of fixation to ensure minimal intraspecimen variation. The percentages of MIB-1 positive and oestrogen receptor positive nuclei were estimated in fields of vision sampled systematically from the entire specimen and from the whole tumour area of one "representative" cross-section. RESULTS--No correlation was found between the oestrogen receptor and MIB-1 indices and the duration of formalin fixation. The estimated MIB-1 and oestrogen receptor indices in tissue sampled systematically from the entire tumour were closely correlated with estimates obtained in a "representative" section. The intra- and interobserver correlation of the MIB-1 index was good, although a slight systematical error at the second assessment of the intraobserver study was noted. CONCLUSION--Quantitative estimates of oestrogen receptor content and proliferative activity are not significantly influenced by the period of fixation in formalin, varying from less than four hours to more than 48 hours. The MIB-1 and the oestrogen receptor indices obtained in a "representative" section do not deviate significantly from average indices determined in tissue samples from the entire tumour. Finally, the estimation of MIB-1 index is reproducible, justifying its routine use.     

2-dimensional MEMS dielectrophoresis device for osteoblast cell stimulation

A fixed microelectrode device for cell stimulation has been designed and fabricated using micro-electro-mechanical systems (MEMS) technology. Dielectrophoretic forces obtained from non-uniform electric fields were used for manipulating and positioning osteoblasts. The experiments show that the osteoblasts experience positive dielectrophoresis (p-DEP) when suspended in iso-osmotic culture medium and exposed to AC fields at 5 MHz frequency. Negative dielectrophoresis (n-DEP) is obtained at 0.1 MHz. The viability of osteoblasts under dielectrophoresis has been investigated. The viability values for cells exposed to DEP are nearly three times higher than the control values, indicating that dielectrophoresis may have an anabolic effect on osteoblasts.     

The thalamo-cortical auditory receptive fields: regulation by the states of vigilance,learning and the neuromodulatory systems

The goal of this review is twofold. First, it aims to describe the dynamic regulation that constantly shapes the receptive fields (RFs) and maps in the thalamo-cortical sensory systems of undrugged animals. Second, it aims to discuss several important issues that remain unresolved at the intersection between behavioral neurosciences and sensory physiology. A first section presents the RF modulations observed when an undrugged animal spontaneously shifts from waking to slow-wave sleep or to paradoxical sleep (also called REM sleep). A second section shows that, in contrast with the general changes described in the first section, behavioral training can induce selective effects which favor the stimulus that has acquired significance during learning. A third section reviews the effects triggered by two major neuromodulators of the thalamo-cortical system--acetylcholine and noradrenaline--which are traditionally involved both in the switch of vigilance states and in learning experiences. The conclusion argues that because the receptive fields and maps of an awake animal are continuously modulated from minute to minute, learning-induced sensory plasticity can be viewed as a "crystallization" of the receptive fields and maps in one of the multiple possible states. Studying the interplays between neuromodulators can help understanding the neurobiological foundations of this dynamic regulation.     

Quantifying lip‐read‐induced suppression and facilitation of the auditory N1 and P2 reveals peak enhancements and delays

Lip‐read speech suppresses and speeds up the auditory N1 and P2 peaks, but these effects are not always observed or reported. Here, the robustness of lip‐read‐induced N1/P2 suppression and facilitation in phonetically congruent audiovisual speech was assessed by analyzing peak values that were taken from published plots and individual data. To determine whether adhering to the additive model of AV integration (i.e., A+V ≠ AV, or AV?V ≠ A) is critical for correct characterization of lip‐read‐induced effects on the N1 and P2, auditory data was compared to AV and to AV?V. On average, the N1 and P2 were consistently suppressed and sped up by lip‐read information, with no indication that AV integration effects were significantly modulated by whether or not V was subtracted from AV. To assess the possibility that variability in observed N1/P2 amplitudes and latencies may explain why N1/P2 suppression and facilitation are not always found, additional correlations between peak values and size of the AV integration effects were computed. These analyses showed that N1/P2 peak values correlated with the size of AV integration effects. However, it also became apparent that a portion of the AV integration effects was characterized by lip‐read‐induced peak enhancements and delays rather than suppressions and facilitations, which, for the individual data, seemed related to particularly small/early A‐only peaks and large/late AV(?V) peaks.