A general-purpose framework to simulate musculoskeletal system of human body: using a motion tracking approach*

Computation of muscle force patterns that produce specified movements of muscle-actuated dynamic models is an important and challenging problem. This problem is an undetermined one, and then a proper optimization is required to calculate muscle forces. The purpose of this paper is to develop a general model for calculating all muscle activation and force patterns in an arbitrary human body movement. For this aim, the equations of a multibody system forward dynamics, which is considered for skeletal system of the human body model, is derived using Lagrange–Euler formulation. Next, muscle contraction dynamics is added to this model and forward dynamics of an arbitrary musculoskeletal system is obtained. For optimization purpose, the obtained model is used in computed muscle control algorithm, and a closed-loop system for tracking desired motions is derived. Finally, a popular sport exercise, biceps curl, is simulated by using this algorithm and the validity of the obtained results is evaluated via EMG signals.     

Absolute quantitation of endogenous proteins with precision and accuracy using a capillary Western system

Precise and accurate quantification of protein expression levels in a complex biological setting is challenging. Here, we describe a method for absolute quantitation of endogenous proteins in cell lysates using an automated capillary immunoassay system, the size-based Simple Western system (recently developed by ProteinSimple). The method was able to accurately measure the absolute amounts of target proteins at picogram or sub-picogram levels per nanogram of cell lysates. The measurements were independent of the cell matrix or the cell lysis buffer and were not affected by different antibody affinities for their specific epitopes. We then applied this method to quantitate absolute levels of expression of protein kinase C (PKC) isoforms in LNCaP and U937 cells, two cell lines used extensively for probing the downstream biological responses to PKC targeted ligands. Our absolute quantitation confirmed the predominance of PKCδ in both cells, supporting the important functional role of this PKC isoform in these cell lines. The method described here provides an approach to accurately quantitate levels of protein expression and correlate protein level with function. In addition to enhanced accuracy relative to conventional Western analysis, it circumvents the distortions inherent in comparison with signal intensities from different antibodies with different affinities.     

Improving the precision and accuracy for estimating energy expenditure using the heart rate method

The "heart rate technique" is commonly used to estimate the rate of oxygen consumption (a proxy for energy expenditure) of free-ranging animals. However, a major limitation of this technique is that interindividual variability in the relationship between heart rate (f(H)) and rate of oxygen consumption (Vo2) generates large errors of estimation when the technique is applied to individual free-ranging animals. In this study, we present a new analysis technique that takes advantage of the observation that the f(H) or Vo2 relationships between individuals are frequently parallel and differ only in elevation. This technique offers superior accuracy and precision of Vo2 estimates, reducing the coefficient of variability from 18% to 9% for individual animals in an example application in macaroni penguins. This approach enables application of the heart rate technique to deduce the energetic strategies of individual animals.     

Assessing the diagnostic accuracy of a sequence of tests

We consider the assessment of the overall diagnostic accuracy of a sequence of tests (e.g. repeated screening tests). The complexity of diagnostic choices when two or more continuous tests are used in sequence is illustrated, and different approaches to reducing the dimensionality are presented and evaluated. For instance, in practice, when a single test is used repeatedly in routine screening, the same screening threshold is typically used at each screening visit. One possible alternative is to adjust the threshold at successive visits according to individual-specific characteristics. Such possibilities represent a particular slice of a receiver operating characteristic surface, corresponding to all possible combinations of test thresholds. We focus in the development and examples on the setting where an overall test is defined to be positive if any of the individual tests are positive ('believe the positive'). The ideas developed are illustrated by an example of application to screening for prostate cancer using prostate-specific antigen.     

Protein tracking and detection of protein motion using atomic force microscopy.

Height fluctuations over three different proteins, immunoglobulin G, urease, and microtubules, have been measured using an atomic force microscope (AFM) operating in fluid tapping mode. This was achieved by using a protein-tracking system, where the AFM tip was periodically repositioned above a single protein molecule (or structure) as thermal drifting occurred. Height (z-piezo signal) data were taken in 1 - or 2-s time slices with the tip over the molecule and compared to data taken on the support. The measured fluctuations were consistently higher when the tip was positioned over the protein, as opposed to the support the protein was adsorbed on. Similar measurements over patches of an amphiphile, where the noise was identical to that on the support, suggest that the noise increase is due to some intrinsic property of proteins and is not a result of different tip-sample interactions over soft samples. The orientation of the adsorbed proteins in these preliminary studies was not known; thus it was not possible to make correlations between the observed motion and specific protein structure or protein function beyond noting that the observed height fluctuations were greater for an antibody (anti-bovine IgG) and an enzyme (urease) than for microtubules.     

The use of sequential MR image sets for determining tibiofemoral motion: reliability of coordinate systems and accuracy of motion tracking algorithm

The use of magnetic resonance imaging has been proposed by many investigators for establishment of joint reference systems and kinematic tracking of musculoskeletal joints. In this study, the intraobserver and interobserver reliability of a strategy to establish anatomic reference systems using manually selected fiducial points were quantified for seven sets of MR images of the human knee joint. The standard error of the measurement of the intraobserver and interobserver errors were less than 2.6 degrees, and 1.2 mm for relative tibiofemoral orientation and displacement, respectively. An automated motion tracking algorithm was also validated with a controlled motion experiment in a cadaveric knee joint. The controlled displacements and rotations prescribed in our motion tracking validation were highly correlated to those predicted (Pearson's correlation = 0.99, RMS errors = 0.39 mm, 0.38 degree). Finally, the system for anatomic reference system definition and motion tracking was demonstrated with a set of MR images of in vivo passive flexion in the human knee.     

A model-based time-reversal of left ventricular motion improves cardiac motion analysis using tagged MRI data

Background  

Myocardial motion is an important observable for the assessment of heart condition. Accurate estimates of ventricular (LV) wall motion are required for quantifying myocardial deformation and assessing local tissue function and viability. Harmonic Phase (HARP) analysis was developed for measuring regional LV motion using tagged magnetic resonance imaging (tMRI) data. With current computer-aided postprocessing tools including HARP analysis, large motions experienced by myocardial tissue are, however, often intractable to measure. This paper addresses this issue and provides a solution to make such measurements possible.     

Validation of a single camera three-dimensional motion tracking system

The ability to analyze human movement is an essential tool of biomechanical analysis for both sport and clinical applications. Traditional 3D motion capture technology limits the feasibility of large scale data collections and therefore the ability to address clinical questions. Ideally, the measurement system/protocol should be non-invasive, mobile, generate nearly instantaneous feedback to the clinician and athlete, and be relatively inexpensive. The retro-grate reflector (RGR) is a new technology that allows for three-dimensional motion capture using a single camera. Previous studies have shown that orientation and position information recorded by the RGR system has high measurement precision and is strongly correlated with a traditional multi-camera system across a series of static poses. The technology has since been refined to record moving pose information from multiple RGR targets at sampling rates adequate for assessment of athletic movements. The purpose of this study was to compare motion data for a standard athletic movement recorded simultaneously with the RGR and multi-camera (Motion Analysis Eagle) systems. Nine subjects performed three single-leg land-and-cut maneuvers. Thigh and shank three-dimensional kinematics were collected with the RGR and Eagle camera systems simultaneously at 100 Hz. Results showed a strong agreement between the two systems in all three planes, which demonstrates the ability of the RGR system to record moving pose information from multiple RGR targets at a sampling rate adequate for assessment of human movement and supports the ability to use the RGR technology as a valid 3D motion capture system.     

A new method for motion capture of the scapula using an optoelectronic tracking device: a feasibility study

Optoelectronic tracking systems are rarely used in 3D studies examining shoulder movements including the scapula. Among the reasons is the important slippage of skin markers with respect to scapula. Methods using electromagnetic tracking devices are validated and frequently applied. Thus, the aim of this study was to develop a new method for in vivo optoelectronic scapular capture dealing with the accepted accuracy issues of validated methods.

Eleven arm positions in three anatomical planes were examined using five subjects in static mode. The method was based on local optimisation, and recalculation procedures were made using a set of five scapular surface markers.

The scapular rotations derived from the recalculation-based method yielded RMS errors comparable with the frequently used electromagnetic scapular methods (RMS up to 12.6° for 150° arm elevation). The results indicate that the present method can be used under careful considerations for 3D kinematical studies examining different shoulder movements.     

Comparison of intervertebral disc displacements measured under applied loading with MRI at 3.0 T and 9.4 T

The purpose of this study was to compare displacement behavior of cyclically loaded cadaveric human intervertebral discs as measured noninvasively on a clinical 3.0 T and a research 9.4 T MRI system. Intervertebral discs were cyclically compressed at physiologically relevant levels with the same MRI-compatible loading device in the clinical and research systems. Displacement-encoded imaging was synchronized to cyclic loading to measure displacements under applied loading with MRI (dualMRI). Displacements from the two systems were compared individually using linear regression and, across all specimens, using Bland–Altman analysis. In-plane displacement patterns measured at 3.0 T and 9.4 T were qualitatively comparable and well correlated. Bland–Altman analyses showed that over 90% of displacement values within the intervertebral disc regions of interest lay within the limits of agreement. Measurement of displacement using dualMRI using a 3.0 T clinical system is comparable to that of a 9.4 T research system. Additional refinements of software, technique implementation, and image processing have potential to improve agreement between different MRI systems. Despite differences in MRI systems in this initial implementation, this work demonstrates that dualMRI can be reliably implemented at multiple magnetic field strengths, permitting translation of dualMRI for a variety of applications in the study of tissue and biomaterial biomechanics.     

A bioinformatic filter for improved base-call accuracy and polymorphism detection using the Affymetrix GeneChip whole-genome resequencing platform

DNA resequencing arrays enable rapid acquisition of high-quality sequence data. This technology represents a promising platform for rapid high-resolution genotyping of microorganisms. Traditional array-based resequencing methods have relied on the use of specific PCR-amplified fragments from the query samples as hybridization targets. While this specificity in the target DNA population reduces the potential for artifacts caused by cross-hybridization, the subsampling of the query genome limits the sequence coverage that can be obtained and therefore reduces the technique's resolution as a genotyping method. We have developed and validated an Affymetrix Inc. GeneChip(R) array-based, whole-genome resequencing platform for Francisella tularensis, the causative agent of tularemia. A set of bioinformatic filters that targeted systematic base-calling errors caused by cross-hybridization between the whole-genome sample and the array probes and by deletions in the sample DNA relative to the chip reference sequence were developed. Our approach eliminated 91% of the false-positive single-nucleotide polymorphism calls identified in the SCHU S4 query sample, at the cost of 10.7% of the true positives, yielding a total base-calling accuracy of 99.992%.     

Estimation of accuracy of patient-specific musculoskeletal modelling: case study on a post polio residual paralysis subject

For patients with patterns ranging out of anthropometric standard values, patient-specific musculoskeletal modelling becomes crucial for clinical diagnosis and follow-up. However, patient-specific modelling using imaging techniques and motion capture systems is mainly subject to experimental errors. The aim of this study was to quantify these experimental errors when performing a patient-specific musculoskeletal model. CT scan data were used to personalise the geometrical model and its inertial properties for a post polio residual paralysis subject. After having performed a gait-based experimental protocol, kinematics data were measured using a VICON motion capture system with six infrared cameras. The musculoskeletal model was computed using a direct/inverse algorithm (LifeMod software). A first source of errors was identified in the segmentation procedure in relation to the calculation of personalised inertial parameters. The second source of errors was subject related, as it depended on the reproducibility of performing the same type of gait. The impact of kinematics, kinetics and muscle forces resulting from the musculoskeletal modelling was quantified using relative errors and the absolute root mean square error. Concerning the segmentation procedure, we found that the kinematics results were not sensitive to the errors (relative error < 1%). However, a strong influence was noted on the kinetics results (deviation up to 71%). Furthermore, the reproducibility error showed a significant influence (relative mean error varying from 5 to 30%). The present paper demonstrates that in patient-specific musculoskeletal modelling variations due to experimental errors derived from imaging techniques and motion capture need to be both identified and quantified. Therefore, the paper can be used as a guideline.     

Estimation of accuracy of patient-specific musculoskeletal modelling: case study on a post polio residual paralysis subject

For patients with patterns ranging out of anthropometric standard values, patient-specific musculoskeletal modelling becomes crucial for clinical diagnosis and follow-up. However, patient-specific modelling using imaging techniques and motion capture systems is mainly subject to experimental errors. The aim of this study was to quantify these experimental errors when performing a patient-specific musculoskeletal model. CT scan data were used to personalise the geometrical model and its inertial properties for a post polio residual paralysis subject. After having performed a gait-based experimental protocol, kinematics data were measured using a VICON motion capture system with six infrared cameras. The musculoskeletal model was computed using a direct/inverse algorithm (LifeMod software). A first source of errors was identified in the segmentation procedure in relation to the calculation of personalised inertial parameters. The second source of errors was subject related, as it depended on the reproducibility of performing the same type of gait. The impact of kinematics, kinetics and muscle forces resulting from the musculoskeletal modelling was quantified using relative errors and the absolute root mean square error. Concerning the segmentation procedure, we found that the kinematics results were not sensitive to the errors (relative error<1%). However, a strong influence was noted on the kinetics results (deviation up to 71%). Furthermore, the reproducibility error showed a significant influence (relative mean error varying from 5 to 30%). The present paper demonstrates that in patient-specific musculoskeletal modelling variations due to experimental errors derived from imaging techniques and motion capture need to be both identified and quantified. Therefore, the paper can be used as a guideline.     

血源性兔VX2肿瘤脑及脑膜转移瘤动物模型的建立及MRI检测

目的：研究MRI对血源性脑及脑膜转移瘤动物模型转移灶的检出效果。方法：18只新西兰大白兔随机分为3组,分别从左颈总动脉内接种VX2瘤细胞,A组：20％甘露醇注入5min后接种VX2瘤细胞：B组：20％甘露醇注入5min后,加入肝素再接种VX2瘤细胞;C组,对照组,单纯注入等量生理盐水。术后2周后行MRI检查。病理取材HE染色光镜下观察。结果：平扫：A组,1只（1／6）发现脑内结节并脑膜结节样增厚,T1WI为等信号,T2WI为稍高信号。B组,2只（2／6）为脑内多发结节,T1WI为等信号,TM为稍高信号。2只（2／6）脑膜结节样增厚。增强扫描：A组,2只（2／6）脑内见强化结节灶;直径在1．5mm-7．0mm之间。4K（4／6）脑膜线样增厚或结节样增厚强化。B组,6只（6／6）脑内见直径在1．5mm-5．0mm的高信号结节,其中5只为脑内多发结节灶;4只（4／6）脑膜线样或结节样增厚强化,左侧为主,其中2只（2／6）为双侧脑膜增厚。增强扫描A、B组问脑内病灶差异有统计学意义（Fisher’s确切概率值为0．04）。C组平扫及增强扫描均未见异常信号。结论：上述方法制成的动物模型可为医学影像学研究提供可靠的动物模型,加入肝素可提高瘤灶的形成几率,并证实血脑屏障对脑转移瘤的形成起重要作用。MRI增强检查是检出脑内及脑膜转移瘤的首选方法。     

Improved precision of QTL mapping using a nonlinear Bayesian method in a multi-breed population leads to greater accuracy of across-breed genomic predictions

Background

Genomic selection is increasingly widely practised, particularly in dairy cattle. However, the accuracy of current predictions using GBLUP (genomic best linear unbiased prediction) decays rapidly across generations, and also as selection candidates become less related to the reference population. This is likely caused by the effects of causative mutations being dispersed across many SNPs (single nucleotide polymorphisms) that span large genomic intervals. In this paper, we hypothesise that the use of a nonlinear method (BayesR), combined with a multi-breed (Holstein/Jersey) reference population will map causative mutations with more precision than GBLUP and this, in turn, will increase the accuracy of genomic predictions for selection candidates that are less related to the reference animals.

Results

BayesR improved the across-breed prediction accuracy for Australian Red dairy cattle for five milk yield and composition traits by an average of 7% over the GBLUP approach (Australian Red animals were not included in the reference population). Using the multi-breed reference population with BayesR improved accuracy of prediction in Australian Red cattle by 2 – 5% compared to using BayesR with a single breed reference population. Inclusion of 8478 Holstein and 3917 Jersey cows in the reference population improved accuracy of predictions for these breeds by 4 and 5%. However, predictions for Holstein and Jersey cattle were similar using within-breed and multi-breed reference populations. We propose that the improvement in across-breed prediction achieved by BayesR with the multi-breed reference population is due to more precise mapping of quantitative trait loci (QTL), which was demonstrated for several regions. New candidate genes with functional links to milk synthesis were identified using differential gene expression in the mammary gland.

Conclusions

QTL detection and genomic prediction are usually considered independently but persistence of genomic prediction accuracies across breeds requires accurate estimation of QTL effects. We show that accuracy of across-breed genomic predictions was higher with BayesR than with GBLUP and that BayesR mapped QTL more precisely. Further improvements of across-breed accuracy of genomic predictions and QTL mapping could be achieved by increasing the size of the reference population, including more breeds, and possibly by exploiting pleiotropic effects to improve mapping efficiency for QTL with small effects.

Electronic supplementary material

The online version of this article (doi:10.1186/s12711-014-0074-4) contains supplementary material, which is available to authorized users.     

The accuracy of measuring glenohumeral motion with a surface humeral cuff

Conclusions about normal and pathologic shoulder motion are frequently made from studies using skin surface markers, yet accuracy of such sensors representing humeral motion is not well known. Nineteen subjects were investigated with flock of birds electromagnetic sensors attached to transcortical pins placed into the scapula and humerus, and a thermoplastic cuff secured on the arm. Subjects completed two repetitions of raising and lowering the arm in the sagittal, scapular and coronal planes, as well as shoulder internal and external rotation with the elbow at the side and abducted to 90°. Humeral motion was recorded simultaneously from surface and bone fixed sensors. The average magnitude of error was calculated for the surface and bone fixed measurements throughout the range of motion. ANOVA tested for differences across angles of elevation, raising and lowering, and differences in body mass index. For all five motions tested, the plane of elevation rotation average absolute error ranged from 0-2°, while the humeral elevation rotation average error ranged from 0-4°. The axial rotation average absolute error was much greater, ranging from 5° during elevation motions to approaching 30° at maximum excursion of internal/external rotation motions. Average absolute error was greater in subjects with body mass index greater than 25. Surface sensors are an accurate way of measuring humeral elevation rotations and plane of elevation rotations. Conversely, there is a large amount of average error for axial rotations when using a humeral cuff to measure glenohumeral internal/external rotation as the primary motion.