Automatic electrode scalar location assessment after cochlear implantation using a novel imaging software.

As of today, image-based assessment of cochlear implant electrode array location is not part of the clinical routine. Low resolution and contrast of computer tomography (CT) imaging, as well as electrode array artefacts, prevent visibility of intracochlear structures and result in low accuracy in determining location of the electrode array. Further, trauma assessment based on clinical-CT images requires a uniform image-based trauma scaling. Goal of this study was to evaluate the accuracy of a novel imaging software to detect electrode scalar location. Six cadaveric temporal bones were implanted with Advanced Bionics SlimJ and Mid-Scala electrode arrays. Clinical-CT scans were taken pre- and postoperatively. In addition, micro-CTs were taken post-operatively for validation. The electrode scalar location rating done by the software was compared to the rating of two experienced otosurgeons and the micro-CT images. A 3-step electrode scalar location grading scale (0 = electrode in scala tympani, 1 = interaction of electrode with basilar membrane/osseous spiral lamina, 2 = translocation of electrode into scala vestibuli) was introduced for the assessment. The software showed a high sensitivity of 100% and a specificity of 98.7% for rating the electrode location. The correlation between rating methods was strong (kappa > 0.890). The software gives a fast and reliable method of evaluating electrode scalar location for cone beam CT scans. The introduced electrode location grading scale was adapted for assessing clinical CT images.

Principal Component Regression on Motor Evoked Potential in Single-Pulse Transcranial Magnetic Stimulation.

Motor evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS) are commonly characterized only by their onset (latency) and size (amplitude) whereas other potentially important information in the MEPs is discarded. Hence, our aim was to examine the morphological information of MEPs using principal component regression (PCR) providing additional perception of MEPs. MEPs were recorded from the first dorsal interosseous muscle following navigated TMS focused at the primary motor cortex. The PCR holding of at least 96% of total variance of the MEP dataset was performed to parameterize MEPs into principal components (PCs), which were used with non-linear least square estimation to reconstruct original MEPs. The comparison between the original and reconstructed MEPs showed that PCs, which accounted for 96% of total variance, were able to characterize the MEP morphology, i.e., the PCR summarizes the repeated information in the MEP dataset into the PC set. In addition, PCR benefited the automated quantification of MEP features as it removed the random noise caused by the environmental interference and the inconsistency of neuronal pathways. Furthermore, we could determine the minimum number of trials required to reliably represent the whole dataset by estimating the partial information of those trials accounted for. Our results showed that this partial information exponentially increased with respect to the number of trials, and saturated within 20 MEPs holding approximately 90% of total variance of the dataset.

Poisson's ratio of bovine meniscus determined combining unconfined and confined compression.

Poisson's ratio has not been experimentally measured earlier for meniscus in compression. It is however an important intrinsic material property needed in biomechanical analysis and computational models. In this study, equilibrium Poisson's ratio of bovine meniscus (n = 6) was determined experimentally by combining stress-relaxation measurements in unconfined and confined compression geometries. The average Young's modulus, aggregate modulus and Poisson's ratio were 0.182 ±â€¯0.086 MPa, 0.252 ±â€¯0.089 MPa and 0.316 ±â€¯0.040, respectively. These moduli are consistent with previously determined values, but the Poisson's ratio is higher than determined earlier for meniscus in compression through biomechanical modelling analysis. This new experimentally determined Poisson's ratio value could be used in the analysis of biomechanical data as well as in computational finite element analysis when the Poisson's ratio is needed as an input for the analysis.

Menthol concentration in topical cold gel does not have significant effect on skin cooling.

BACKGROUND: Topical menthol gels are used in the treatment of various pain conditions. However, the effect of the menthol concentration to skin cooling or cooling sensation is not clear. We hypothesized that increasing menthol concentration enhances skin cooling and causes elevated cooling sensation. METHODS: Ten healthy male volunteers (age range 25-30 years) were recruited for this study. Application of three gels with different menthol concentrations (0.5%, 4.6% and 10.0%) was tested in random sequence on the left thigh of the subjects. Skin cooling was recorded with a digital infrared camera (FLIR Systems Inc., USA), and cooling sensation was measured with the visual analogue scale rating. RESULTS: All gels decreased skin temperature significantly (P < 0.05) at least for one hour. However, the variation in menthol concentration seemed not to have a significant effect on skin cooling. Subjects experienced that gel with 4.6% menthol concentration caused significantly stronger cooling effect than 0.5% and 10.0% gels. Gel application had no significant effect on skin temperature in surrounding skin areas. CONCLUSION: In contrast to our hypothesis, menthol concentration was not connected to skin cooling, while moderate menthol concentration of 4.6% may induce stronger cooling sensation compared to low (0.5%) or high (10.0%) concentration gels.

Repetition suppression in transcranial magnetic stimulation-induced motor-evoked potentials is modulated by cortical inhibition.

Transcranial magnetic stimulation (TMS) can be applied to modulate cortical phenomena. The modulation effect is dependent on the applied stimulation frequency. Repetition suppression (RS) has been demonstrated in the motor system using TMS with short suprathreshold 1-Hz stimulation trains repeated at long inter-train intervals. RS has been reported to occur in the resting motor-evoked potentials (MEPs) with respect to the first pulse in a train of stimuli. Although this RS in the motor system has been described in previous studies, the neuronal origin of the phenomenon is still poorly understood. The present study evaluated RS in three TMS-induced motor responses; resting and active MEPs as well as corticospinal silent periods (SPs) in order to clarify the mechanism behind TMS-induced RS. We studied 10 healthy right-handed subjects using trains of four stimuli with stimulation intensities of 120% of the resting motor threshold (rMT) and 120% of the silent period threshold for an SP duration of 30 ms (SPT30). Inter-trial interval was 20s, with a 1-s inter-stimulus interval within the trains. We confirmed that RS appears in resting MEPs (p < 0.001), whereas active MEPs did not exhibit RS (p > 0.792). SPs, on the contrary, lengthened (p < 0.001) indicating modulation of cortical inhibition. The effects of the two stimulation intensities exhibited a similar trend; however, the SPT30 evoked a more profound inhibitory effect compared to that achieved by rMT. Moreover, the resting MEP amplitudes and SP durations correlated (rho ⩽ -0.674, p < 0.001) and the pre-TMS EMG level did not differ between stimuli in resting MEPs (F = 0.0, p ⩾ 0.999). These results imply that the attenuation of response size seen in resting MEPs might originate from increasing activity of inhibitory GABAergic interneurons which relay the characteristics of SPs.

Characterization of site-specific biomechanical properties of human meniscus-Importance of collagen and fluid on mechanical nonlinearities.

Meniscus adapts to joint loads by depth- and site-specific variations in its composition and structure. However, site-specific mechanical characteristics of intact meniscus under compression are poorly known. In particular, mechanical nonlinearities caused by different meniscal constituents (collagen and fluid) are not known. In the current study, in situ indentation testing was conducted to determine site-specific elastic, viscoelastic and poroelastic properties of intact human menisci. Lateral and medial menisci (n=26) were harvested from the left knee joint of 13 human cadavers. Indentation tests, using stress-relaxation and dynamic (sinusoidal) loading protocols, were conducted for menisci at different sites (anterior, middle, posterior, n=78). Sample- and site-specific axisymmetric finite element models with fibril-reinforced poroelastic properties were fitted to the corresponding stress-relaxation curves to determine the mechanical parameters. Elastic moduli, especially the instantaneous and dynamic moduli, showed site-specific variation only in the medial meniscus (p<0.05 between the sites). The instantaneous and dynamic elastic moduli of the anterior horn were significantly (p<0.05) greater in the medial than lateral meniscus. The phase angle showed no statistically significant variation between the sites (p>0.05). The values for the strain-dependent fibril network modulus (nonlinear behaviour of collagen) were significantly different (p<0.05) between all sites in the medial menisci. Additionally, there was a significant difference (p<0.01) in the strain-dependent fibril network modulus between the lateral and medial anterior horns. The initial permeability was significantly different (p<0.05) in the medial meniscus only between the middle and posterior sites. For the strain-dependent permeability coefficient, only anterior and middle sites showed a significant difference (p<0.05) in the medial meniscus. This parameter demonstrated a significant difference (p<0.05) between lateral and medial menisci at the anterior horns. Our results reveal that under in situ indentation loading, medial meniscus shows more site-dependent variation in the mechanical properties as compared to lateral meniscus. In particular, anterior horn of medial meniscus was the stiffest and showed the most nonlinear mechanical behaviour. The nonlinearity was related to both collagen fibrils and fluid.

Thermal imaging in screening of joint inflammation and rheumatoid arthritis in children.

Potential of modern thermal imaging for screening and differentiation of joint inflammation has not been assessed in child and juvenile patient populations, typically demanding groups in diagnostics of musculoskeletal disorders. We hypothesize that thermal imaging can detect joint inflammation in patients with juvenile idiopathic arthritis or autoimmune disease with arthritis such as systemic lupus erythematosus. To evaluate the hypothesis, we studied 58 children exhibiting symptoms of joint inflammation. First, the patients' joints were examined along clinical procedure supplemented with ultrasound imaging when deemed necessary by the clinician. Second, thermal images were acquired from patients' knees and ankles. Results of thermal imaging were compared to clinical evaluations in knee and ankle. The temperatures were significantly (pmax = 0.044, pmean < 0.001) higher in inflamed ankle joints, but not in inflamed knee joints. No significant difference was found between the skin surface temperatures of medial and lateral aspects of ankle joints. In knee joints the mean temperatures of medial and lateral aspect differed significantly (p = 0.004). We have demonstrated that thermal imaging may have potential for detecting joint inflammation in ankle joints of children. For knee joints our results are inconclusive and further research is warranted.

The auditory-evoked arousal modulates motor cortex excitability.

Arousal enhances the readiness to process sensory information and respond to it. Rapid increment of arousal, referred to as arousal reaction or startle, increases the level of attention and the chance of survival. Arousal reaction is known to originate from the brainstem ascending reticular activating system and to modulate neuronal activity throughout the central nervous system. In the present study we investigated the effect of arousal on the central motor system by synchronizing transcranial magnetic stimulation (TMS) with acoustically evoked N100 potential. Because of the widespread cortical distribution of N100 to a sudden acoustic stimulus it is thought to be related to arousal reaction. Eight healthy subjects participated in this study. TMS was focused on the primary motor cortex utilizing neuronavigation. Trains of four identical loud tones repeated at 1-s intervals were delivered to the right ear and TMS was randomly placed after one tone in the train. The motor-evoked potentials (MEPs) were measured from the contralateral first dorsal interosseous muscle. The MEPs evoked by TMS timed at N100 after the first tone in train were significantly (p<.001) larger in comparison with the control stimulation without a preceding sound or stimulation placed after the N100, i.e., 120% of the N100 interstimulus interval. Also, the MEPs following the second tone were significantly weaker (p<.05) when compared with the MEPs following the first tone. Our findings suggest that acoustic arousal reaction facilitates, not only the activation of sensory cortices, but also simultaneously the central motor system.

Repetition suppression in the cortical motor and auditory systems resemble each other--a combined TMS and evoked potential study.

Repetition suppression (RS) in cortical sensory systems optimizes the size of neuronal ensemble reacting to repetitive stimuli such as sounds. Recently RS has also been demonstrated to occur with mental imaging of movement. We studied the existence of RS in the motor system using transcranial magnetic stimulation (TMS). Six healthy subjects participated in this study. TMS was focused on the primary motor cortex with neuronavigation and RS was studied by measuring the motor-evoked potentials from the contralateral first dorsal interosseous muscle. At the same time, we measured TMS-induced cortical responses using electroencephalography (EEG). For a comparison baseline, we evaluated RS by recording EEG responses to sounds with the same stimulation protocol as with TMS. Each stimulus train included four identical stimuli repeated at 1-s intervals, and the stimulation trains were repeated at 20-s intervals. The response amplitude was reduced significantly (p<.01) after the first stimulus in all stimulus trains. This suggests that RS may be a general mechanism for adaptation of neuronal population responses in the human cortex.

Novel parameters for evaluating severity of sleep disordered breathing and for supporting diagnosis of sleep apnea-hypopnea syndrome.

Sleep apnea-hypopnea syndrome (SAHS) is a complex public health problem causing increased risk of cardiovascular diseases. Traditionally, evaluation of the severity of the disease is based on Apnea-Hypopnea Index (AHI). It is defined as the average number of apnea and hypopnea events per hour during sleep. However, e.g. the total duration and the morphology of the recorded events are not considered when evaluating the severity of the disease. This is surprising, as increasing the length of apnea and hypopnea events will most likely lead to longer and deeper oxygen desaturation events. Obviously, this is physiologically more stressful and may have more severe health consequences than shorter and shallower desaturation events. Paradoxically, the lengthening of apnea and hypopnea events may even lead to a decrease in AHI and oxygen desaturation index (ODI). This raises the question of whether additional information is needed besides AHI and ODI for the evaluation of the severity of SAHS and its potential cardiovascular consequences. In the present paper, several novel parameters are introduced to bring additional information for evaluation of the severity of SAHS. Besides the number of events per hour, that AHI and ODI takes into account, the duration of the breathing cessations and the morphology of the oxygen desaturation events are considered as important factors that may influence the daytime fatigue and also the related cardiovascular problems. In this study diagnostic ambulatory polygraphy recordings of 19 male patients were retrospectively analysed. Importantly, the novel parameters showed significant variation amongst patients with similar AHI. For example, the correlation between AHI and the Obstruction severity-parameter was only moderate (r(2)=0.604, p<0.001). This suggests that patients with similar AHI may exhibit significantly different cardiovascular stress related to the disease. It is suggested that the present novel parameters might provide additional information over the currently used parameters and support the evaluation of the severity of SAHS.

Effect of superficial collagen patterns and fibrillation of femoral articular cartilage on knee joint mechanics-a 3D finite element analysis.

Collagen fibrils of articular cartilage have specific depth-dependent orientations and the fibrils bend in the cartilage surface to exhibit split-lines. Fibrillation of superficial collagen takes place in osteoarthritis. We aimed to investigate the effect of superficial collagen fibril patterns and collagen fibrillation of cartilage on stresses and strains within a knee joint. A 3D finite element model of a knee joint with cartilage and menisci was constructed based on magnetic resonance imaging. The fibril-reinforced poroviscoelastic material properties with depth-dependent collagen orientations and split-line patterns were included in the model. The effects of joint loading on stresses and strains in cartilage with various split-line patterns and medial collagen fibrillation were simulated under axial impact loading of 1000 N. In the model, the collagen fibrils resisted strains along the split-line directions. This increased also stresses along the split-lines. On the contrary, contact and pore pressures were not affected by split-line patterns. Simulated medial osteoarthritis increased tissue strains in both medial and lateral femoral condyles, and contact and pore pressures in the lateral femoral condyle. This study highlights the importance of the collagen fibril organization, especially that indicated by split-line patterns, for the weight-bearing properties of articular cartilage. Osteoarthritic changes of cartilage in the medial femoral condyle created a possible failure point in the lateral femoral condyle. This study provides further evidence on the importance of the collagen fibril organization for the optimal function of articular cartilage.

Structural parameters of normal and osteoporotic human trabecular bone are affected differently by microCT image resolution.

UNLABELLED: This study employed microCT to investigate whether image resolution affects bone structural parameters differently in healthy normal and osteoporotic trabecular bone. With increasing image voxel size, the originally detected differences between sample groups diminished. The results suggest that structural differences may not be reliably detected with clinical scanners. INTRODUCTION: Structural parameters of bone reflect its health status, but are highly dependent on the image resolution. We hypothesized that image resolution affects bone structural parameters differently in normal and osteoporotic trabecular bone. METHODS: Human trabecular bone samples from the iliac crest and the knee were analyzed (normal n = 11, osteoporotic n = 15) using a high-resolution microCT (14 or 18 µm voxel sizes). Images were re-sampled to voxel sizes 1-16 times larger than the original image and thresholded with global or local adaptive algorithms. Absolute and normalized values of each structural parameter were calculated, and the effect of decreasing image resolution was compared between the normal and osteoporotic samples. RESULTS: Normal and osteoporotic samples had different (p < 0.05) absolute bone volume fractions. However, the normalized values showed that the osteoporotic samples were more prone to errors (p < 0.05) with increased voxel size. The absolute values of trabecular number, trabecular separation, degree of anisotropy, and structure model index were different between the groups at the original voxel size (p < 0.05), but at voxel sizes between 60 and 110 µm, those differences were no longer significant. CONCLUSIONS: The results suggest that structural differences between osteoporotic and normal trabecular bone may not be reliably detected with clinical CT scanners providing image voxel sizes above 100 µm.

Alterations in structure and properties of collagen network of osteoarthritic and repaired cartilage modify knee joint stresses.

Organization of the collagen network is known to be different in healthy, osteoarthritic and repaired cartilage. The aim of the study was to investigate how the structure and properties of collagen network of cartilage modulate stresses in a knee joint with osteoarthritis or cartilage repair. Magnetic resonance imaging (MRI) at 1.5 T was conducted for a knee joint of a male subject. Articular cartilage and menisci in the knee joint were segmented, and a finite element mesh was constructed based on the two-dimensional section in sagittal projection. Then, the knee joint stresses were simulated under impact loads by implementing the structure and properties of healthy, osteoarthritic and repaired cartilage in the models. During the progression of osteoarthritis, characterized especially by the progressive increase in the collagen fibrillation from the superficial to the deeper layers, the stresses were reduced in the superficial zone of cartilage, while they were increased in and under menisci. Increased fibril network stiffness of repair tissue with randomly organized collagen fibril network reduced the peak stresses in the adjacent tissue and strains at the repair-adjacent cartilage interface. High collagen fibril strains were indicative of stress concentration areas in osteoarthritic and repaired cartilage. The collagen network orientation and stiffness controlled the stress distributions in healthy, osteoarthritic and repaired cartilage. The evaluation of articular cartilage function using clinical MRI and biomechanical modeling could enable noninvasive estimation of osteoarthritis progression and monitoring of cartilage repair. This study presents a step toward those goals.

Diffusion coefficients of articular cartilage for different CT and MRI contrast agents.

In contrast enhanced magnetic resonance imaging (MRI) and computed tomography (CT), the equilibrium distribution of anionic contrast agent is expected to reflect the fixed charged density (FCD) of articular cartilage. Diffusion is mainly responsible for the transport of contrast agents into cartilage. In osteoarthritis, cartilage composition changes at early stages of disease, and solute diffusion is most likely affected. Thus, investigation of contrast agent diffusion could enable new methods for imaging of cartilage composition. The aim of this study was to determine the diffusion coefficient of four contrast agents (ioxaglate, gadopentetate, iodide, gadodiamide) in bovine articular cartilage. The contrast agents were different in molecular size and charge. In peripheral quantitative CT experiments, penetration of contrast agent into the tissue was allowed either through the articular surface or through deep cartilage. To determine diffusion coefficients, a finite element model based on Fick's law was fitted to experimental data. Diffusion through articular surface was faster than through deep cartilage with every contrast agent. Iodide, being of atomic size, diffused into the cartilage significantly faster (q<0.05) than the other three contrast agents, for either transport direction. The diffusion coefficients of all clinical contrast agents (ioxaglate, gadopentetate and gadodiamide) were relatively low (142.8-253.7 µm(2)/s). In clinical diagnostics, such slow diffusion may not reach equilibrium and this jeopardizes the determination of FCD by standard methods. However, differences between diffusion through articular surface and deep cartilage, that are characterized by different tissue composition, suggest that diffusion coefficients may correlate with cartilage composition. Present method could therefore enable image-based assessment of cartilage composition by determination of diffusion coefficients within cartilage tissue.

Depth-wise progression of osteoarthritis in human articular cartilage: investigation of composition, structure and biomechanics.

OBJECTIVE: Osteoarthritis (OA) is characterized by the changes in structure and composition of articular cartilage. However, it is not fully known, what is the depth-wise change in two major components of the cartilage solid matrix, i.e., collagen and proteoglycans (PGs), during OA progression. Further, it is unknown how the depth-wise changes affect local tissue strains during compression. Our aim was to address these issues. METHODS: Data from the previous microscopic and biochemical measurements of the collagen content, distribution and orientation, PG content and distribution, water content and histological grade of normal and degenerated human patellar articular cartilage (n=73) were reanalyzed in a depth-wise manner. Using this information, a composition-based finite element (FE) model was used to estimate tissue function solely based on its composition and structure. RESULTS: The orientation angle of collagen fibrils in the superficial zone of cartilage was significantly less parallel to the surface (P<0.05) in samples with early degeneration than in healthy samples. Similarly, PG content was reduced in the superficial zone in early OA (P<0.05). However, collagen content decreased significantly only at the advanced stage of OA (P<0.05). The composition-based FE model showed that under a constant stress, local tissue strains increased as OA progressed. CONCLUSION: For the first time, depth-wise point-by-point statistical comparisons of structure and composition of human articular cartilage were conducted. The present results indicated that early OA is primarily characterized by the changes in collagen orientation and PG content in the superficial zone, while collagen content does not change until OA has progressed to its late stage. Our simulation results suggest that impact loads in OA joint could create a risk for tissue failure and cell death.

Maturation of collagen fibril network structure in tibial and femoral cartilage of rabbits.

OBJECTIVE: The structure and composition of articular cartilage change during development and growth, as well as in response to varying loading conditions. These changes modulate the functional properties of cartilage. We studied maturation-related changes in the collagen network organization of cartilage as a function of tissue depth. DESIGN: Articular cartilage from the tibial medial plateaus and femoral medial condyles of female New Zealand white rabbits was collected from six age-groups: 4 weeks (n=30), 6 weeks (n=30), 3 months (n=24), 6 months (n=24), 9 months (n=27) and 18 months (n=19). Collagen fibril orientation, parallelism (anisotropy) and optical retardation were analyzed with polarized light microscopy. Differences in the development of depth-wise collagen organization in consecutive age-groups and the two joint locations were compared statistically. RESULTS: The collagen fibril network of articular cartilage undergoes significant changes during maturation. The most prominent changes in collagen architecture, as assessed by orientation, parallelism and retardation were noticed between the ages of 4 and 6 weeks in tibial cartilage and between 6 weeks and 3 months in femoral cartilage, i.e., orientation became more perpendicular-to-surface, and parallelism and retardation increased with changes being most prominent in the deep zone. At the age of 6 weeks, tibial cartilage had a more perpendicular-to-surface orientation in the middle and deep zones than femoral cartilage (P<0.001) and higher parallelism throughout the tissue depth (P<0.001), while femoral cartilage exhibited more parallel-to-surface orientation (P<0.01) above the deep zone after maturation. Optical retardation of collagen was higher in tibial than in femoral cartilage at the ages of 4 and 6 weeks (P<0.001), while at older ages, retardation below the superficial zone in the femoral cartilage became higher than in the tibial cartilage. CONCLUSIONS: During maturation, there is a significant modulation of collagen organization in articular cartilage which occurs earlier in tibial than in femoral cartilage, and is most pronounced in the deep zone.

Biomechanical, biochemical and structural correlations in immature and mature rabbit articular cartilage.

OBJECTIVE: The structure and composition of articular cartilage change during development and growth. These changes lead to alterations in the mechanical properties of cartilage. In the present study, biomechanical, biochemical and structural relationships of articular cartilage during growth and maturation of rabbits are investigated. DESIGN: Articular cartilage specimens from the tibial medial plateaus and femoral medial condyles of female New Zealand white rabbits were collected from seven age-groups; 0 days (n=29), 11 days (n=30), 4 weeks (n=30), 6 weeks (n=30), 3 months (n=24), 6 months (n=24) and 18 months (n=19). The samples underwent mechanical testing under creep indentation. From the mechanical response, instantaneous and equilibrium moduli were determined. Biochemical analyses of tissue collagen, hydroxylysylpyridinoline (HP) and pentosidine (PEN) cross-links in full thickness cartilage samples were conducted. Proteoglycans were investigated depth-wise from the tissue sections by measuring the optical density of Safranin-O-stained samples. Furthermore, depth-wise collagen architecture of articular cartilage was analyzed with polarized light microscopy. Finite element analyses of the samples from different age-groups were conducted to reveal tensile and compressive properties of the fibril network and the matrix of articular cartilage, respectively. RESULTS: Tissue thickness decreased from approximately 3 to approximately 0.5mm until the age of 3 months, while the instantaneous modulus increased with age prior to peak at 4-6 weeks. A lower equilibrium modulus was observed before 3-month-age, after which the equilibrium modulus continued to increase. Collagen fibril orientation angle and parallelism index were inversely related to the instantaneous modulus, tensile fibril modulus and tissue thickness. Collagen content and cross-linking were positively related to the equilibrium compressive properties of the tissue. CONCLUSIONS: During maturation, significant modulation of tissue structure, composition and mechanical properties takes place. Importantly, the present study provides insight into the mechanical, chemical and structural interactions that lead to functional properties of mature articular cartilage.

Mechanical characterization of articular cartilage by combining magnetic resonance imaging and finite-element analysis: a potential functional imaging technique.

Magnetic resonance imaging (MRI) provides a method for non-invasive characterization of cartilage composition and structure. We aimed to see whether T(1) and T(2) relaxation times are related to proteoglycan (PG) and collagen-specific mechanical properties of articular cartilage. Specifically, we analyzed whether variations in the depthwise collagen orientation, as assessed by the laminae obtained from T(2) profiles, affect the mechanical characteristics of cartilage. After MRI and unconfined compression tests of human and bovine patellar cartilage samples, fibril-reinforced poroviscoelastic finite-element models (FEM), with depthwise collagen orientations implemented from quantitative T(2) maps (3 laminae for human, 3-7 laminae for bovine), were constructed to analyze the non-fibrillar matrix modulus (PG specific), fibril modulus (collagen specific) and permeability of the samples. In bovine cartilage, the non-fibrillar matrix modulus (R = -0.64, p < 0.05) as well as the initial permeability (R = 0.70, p < 0.05) correlated with T(1). In bovine cartilage, T(2) correlated positively with the initial fibril modulus (R = 0.62, p = 0.05). In human cartilage, the initial fibril modulus correlated negatively (R = -0.61, p < 0.05) with T(2). Based on the simulations, cartilage with a complex collagen architecture (5 or 7 laminae), leading to high bulk T(2) due to magic angle effects, provided higher compressive stiffness than tissue with a simple collagen architecture (3 laminae). Our results suggest that T(1) reflects PG-specific mechanical properties of cartilage. High T(2) is characteristic to soft cartilage with a classical collagen architecture. Contradictorily, high bulk T(2) can also be found in stiff cartilage with a multilaminar collagen fibril network. By emerging MRI and FEM, the present study establishes a step toward functional imaging of articular cartilage.

Efficient reduction of stimulus artefact in TMS-EEG by epithelial short-circuiting by mini-punctures.

OBJECTIVE: We aimed at comparing the effects of two different electrode-to-skin contact preparation techniques on the stimulus artefact induced by transcranial magnetic stimulation (TMS) in electroencephalography (EEG) signals. METHODS: Six healthy subjects participated in a combined navigated brain stimulation (NBS) and EEG study. Electrode contacts were first prepared in the standard way of rubbing the skin using a wooden stick with a cotton tip. The location of hand motor area and the motor threshold (MT) was determined for each subject. Then, the TMS-induced artefact was measured at 60%, 80%, 100% and 120% of the MT. Subsequently, the epithelium under the electrode contacts was electrically short-circuited by puncturing with custom-made needles and the stimulation sequences were replicated. The artefact was compared between the preparation techniques. RESULTS: The TMS-induced artefact was significantly reduced after puncturing. In addition, the size and duration of the artefact depended on the applied stimulation intensity. The reduction of the artefact was largest in electrodes at and close to the stimulation site. CONCLUSIONS: Mini-puncturing technique enables more accurate analysis of TMS-induced short-latency phenomena in EEG during NBS, and it may aid in the examination of the short distance neural connectivity beneath and close to the stimulation site. SIGNIFICANCE: This study describes a practical skin preparation method that significantly improves the utility of TMS-EEG method in studying short-latency cortical connectivity.

Chloroform mode of action: implications for cancer risk assessment.

Risk assessment methodology, particularly pertaining to potential human carcinogenic risks from exposures to environmental chemicals, is undergoing intense scrutiny from scientists, regulators, and legislators. The current practice of estimating human cancer risk is based almost exclusively on extrapolating the results of chronic, high-dose studies in rodents to estimate potential risk in humans. However, many scientists are questioning whether the logic used in this current risk assessment methodology is the best way to safeguard public health. A major tool of human cancer risk assessment is the linearized multistage (LMS) model. The LMS model has been identified as an aspect of risk assessment that could be improved. One way to facilitate this improvement is by developing a way to incorporate a carefully derived, more biologically relevant mechanism of action data on carcinogenesis. Recent data on chloroform indicate that the dose-response relationship for chloroform-induced tumors in rats and mice is nonlinear, based upon events secondary to cell necrosis and subsequent regeneration as the likely mode of action for the carcinogenic effects of chloroform. In light of these data, there is a sound scientific basis for removing some of the uncertainty that accompanies current cancer risk assessments of chloroform. The following points summarize the critical data: (1) a substantial body of data demonstrates a lack of direct in vivo or in vitro genotoxicity of chloroform; (2) chloroform induces liver and kidney tumors in long-term rodent cancer bioassays only at doses that induce frank toxicity at these target sites; (3) the chloroform doses required to produce tumors in susceptible species exceed the MTD, often by a considerable margin; (4) cytotoxicity and compensatory cell proliferation are associated with the chloroform doses required to induce liver or kidney tumors in susceptible rodent species; (5) there are no instances of chloroform-induced tumors that are not preceded by this pattern of dose-dependent toxic responses; (6) it is biologically plausible that cytolethality leads to chronically stimulated cell proliferation and related events such as inflammation and growth stimulation which act to initiate and promote the carcinogenic process; and (7) the consistently linked cellular events of cytolethality and subsequent cell proliferation, for which doses of no adverse effect have been clearly shown to exist, are one of the biological prerequisites for chloroform-induced tumors in animals. Based on these data, it is inappropriate to extrapolate cancer risk from high doses that produce necrosis and regenerative cell proliferation to low doses that do not with a model that presumes genotoxicity and a linear dose-response relationship. The weight of the scientific evidence concerning chloroform-induced tumors in rodents is consistent with and supports a cancer risk assessment methodology based on mode of action as the basis for establishing regulatory standards for this compound.