Subject-specific Measurements Research Articles

Regional variation in lateral and medial gastrocnemius muscle fibre lengths obtained from diffusion tensor imaging.

Assessment of regional muscle architecture is primarily done through the study of animals, human cadavers, or using b-mode ultrasound imaging. However, there remain several limitations to how well such measurements represent in vivo human whole muscle architecture. In this study, we developed an approach using diffusion tensor imaging and magnetic resonance imaging to quantify muscle fibre lengths in different muscle regions along a muscle's length and width. We first tested the between-day reliability of regional measurements of fibre lengths in the medial (MG) and lateral gastrocnemius (LG) and found good reliability for these measurements (intraclass correlation coefficient [ICC]=0.79 and ICC=0.84, respectively). We then applied this approach to a group of 32 participants including males (n=18), females (n=14), young (24±4years) and older (70±2years) adults. We assessed the differences in regional muscle fibre lengths between different muscle regions and between individuals. Additionally, we compared regional muscle fibre lengths between sexes, age groups, and muscles. We found substantial variability in fibre lengths between different regions within the same muscle and between the MG and the LG across individuals. At the group level, we found no difference in mean muscle fibre length between males and females, nor between young and older adults, or between the MG and the LG. The high variability in muscle fibre lengths between different regions within the same muscle, possibly expands the functional versatility of the muscle for different task requirements. The high variability between individuals supports the use of subject-specific measurements of muscle fibre lengths when evaluating muscle function.

Subject-Specific Calculation of Left Atrial Appendage Blood-Borne Particle Residence Time Distribution in Atrial Fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia that leads to thrombus formation, mostly in the left atrial appendage (LAA). The current standard of stratifying stroke risk, based on the CHA2DS2-VASc score, does not consider LAA morphology, and the clinically accepted LAA morphology-based classification is highly subjective. The aim of this study was to determine whether LAA blood-borne particle residence time distribution and the proposed quantitative index of LAA 3D geometry can add independent information to the CHA2DS2-VASc score. Data were collected from 16 AF subjects. Subject-specific measurements included left atrial (LA) and LAA 3D geometry obtained by cardiac computed tomography, cardiac output, and heart rate. We quantified 3D LAA appearance in terms of a novel LAA appearance complexity index (LAA-ACI). We employed computational fluid dynamics analysis and a systems-based approach to quantify residence time distribution and associated calculated variable (LAA mean residence time, tm) in each subject. The LAA-ACI captured the subject-specific LAA 3D geometry in terms of a single number. LAA tm varied significantly within a given LAA morphology as defined by the current subjective method and it was not simply a reflection of LAA geometry/appearance. In addition, LAA-ACI and LAA tm varied significantly for a given CHA2DS2-VASc score, indicating that these two indices of stasis are not simply a reflection of the subjects' clinical status. We conclude that LAA-ACI and LAA tm add independent information to the CHA2DS2-VASc score about stasis risk and thereby can potentially enhance its ability to stratify stroke risk in AF patients.

252. Prediction of subject-specific SAR distribution in MSK MR exam at 7 T

Purpose we predict SAR during MRI exam using a 7 T 1H 298 MHz eight-channel degenerate birdcage coil1 combining SAR simulations with subject-specific measured (RF) B 1 + maps. Materials and Methods We simulated the coil1 in CST MW Suite, loaded by a model of human knee (Fig. 1, top). B 1 + was calculated in an axial slice crossing the patella. The maximum local SAR for an Axial “Zero” Time-of-Echo (ZTE) sequence “SILENT”2 was calculated. We acquired ∣ B 1 , map + ∣ maps of an adult (female) knee with a Bloch-Siegert sequence on 7 axial slices, centered on the same slice of the simulation, on a GE MR950 7T human system. For each slice a coefficient C, proportional to avg ( ∣ B 1 , map + ∣ ) / B 1 , nominal + , was used to scale the SAR simulated3. Results Fig. 1 shows: bottom left, simulated B 1 + magnitude; bottom center, local SAR for an input of 1 W per channel; bottom right, simulated B 1 , nominal + magnitude for a FA = 90° (length = 3.2 ms) sinc-pulse in the slice previously chosen. Fig. 2 shows the subject-specific measured ∣ B 1 , map + ∣ for a FA = 90° sinc-pulse. The predicted SAR obtained with scaled B 1 + maps are 0.50 W/kg (global) and 3.68 W/kg (maximum). Conclusions we obtained a good agreement between simulated and measured in vivo B 1 + maps, and we were able to calculate the distribution of SAR exposure, a safety MRI parameter not available in current exams, where only global SAR is provided, combining simulations and subject-specific measurements. Limits on global and local SAR (20 W/kg) were met for this sequence [1] , [2] , [3] .

Functional deficits may be explained by plantarflexor remodeling following Achilles tendon rupture repair: Preliminary findings

Achilles tendon ruptures are common injuries that often lead to long-term functional deficits. Despite the prevalence of these injuries, the mechanism responsible for limited function has not yet been established. Therefore, the purpose of this study was to present preliminary findings that support a hypothesis that skeletal muscle remodeling is the driving factor of poor outcomes in some patients. Biomechanical and ultrasonography assessments were performed on a patient that presented with poor functional outcomes 2.5 years after a surgically-repaired acute Achilles tendon rupture. Single-leg heel raise height was decreased by 75% in the affected limb (3.0 cm compared to 11.9 cm) while walking mechanics showed no deficits. Ultrasonography revealed that the affected medial gastrocnemius muscle was less thick and had shorter, more pennate fascicles compared to the unaffected limb. A simple computational model of a maximal-effort plantarflexion contraction was employed to test the implications of changes in muscle architecture on single-leg heel raise function. Subject-specific measurements of fascicle length and pennation were input into the model, which supported these architectural parameters as being drivers of heel raise function. These preliminary findings support the hypothesis that an Achilles tendon rupture elicits changes in skeletal muscle architecture, which reduces the amount of work and power the joint can generate. This multidisciplinary framework of biomechanical, imaging, and computational modeling provides a unique platform for studying the complex interactions between structure and function in patients recovering from Achilles tendon injuries.

In vivo bone 31 P relaxation times and their implications on mineral quantification.

The intersubject variations in bone phosphorus-31 (31 P) T1 and , as well as the implications on in vivo 31 P MRI-based bone mineral quantification, were investigated at 3T field strength. A technique that isolates the bone signal from the composite in vivo 31 P spectrum was first evaluated via simulation and experiments ex vivo and subsequently applied to measure the T1 of bone 31 P collectively with a spectroscopic saturation recovery sequence in a group of healthy subjects aged 26 to 76 years. was derived from the bone signal linewidth. The density of bone 31 P was derived for all subjects from 31 P zero TE images acquired in the same scan session using the measured relaxation times. Test-retest experiments were also performed to evaluate repeatability of this in vivo MRI-based bone mineral quantification protocol. The T1 obtained in vivo using the proposed spectral separation method combined with saturation recovery sequence is 38.4 ± 1.5 s for the subjects studied. Average 31 P density found was 6.40 ± 0.58 mol/L (corresponding to 1072 ± 98 mg/cm3 mineral density), in good agreement with an earlier study in specimens from donors of similar age range. Neither the relaxation times (P = 0.18 for T1 , P = 0.99 for ) nor 31 P density (P = 0.55) were found to correlate with subject age. Average coefficients of variation for the repeat study were 1.5%, 2.6%, and 4.4% for bone 31 P T1 , , and density, respectively. Neither 31 P T1 nor varies significantly in healthy adults across a 50-year age range, therefore obviating the need for subject-specific measurements.

Abstract 4530: A biophysical model for necrosis development in glioblastoma informed by subject-specific MRI measurements

Abstract Introduction We have previously developed the means to use quantitative magnetic resonance imaging (MRI) data to initialize a biophysical model (Model 1) of tumor growth which accurately predicts future tumor volume but fails to capture the development of low-cellularity (or necrotic) regions in a murine model of glioblastoma. In this work, we expand upon this biophysical model (Model 2) to characterize necrosis by relating tissue perfusion to cell death. We evaluate the accuracy of both models to in vivo measurements of tumor growth. Methods To evaluate this model, rats (n = 4) with C6 gliomas were imaged with dynamic contrast enhanced MRI (DCE-MRI) and diffusion-weighted MRI (DW-MRI) seven times over 10 days. DCE-MRI was used to identify tumor regions and estimate tissue perfusion (as estimated by the parameter Ktrans), while DW-MRI was used to estimate cell number. For both Models 1 and 2, parameters describing tumor proliferation, diffusion, and carrying capacity were optimized from the first three imaging time points. For Model 1, these parameters were then used in a forward evaluation of the model to predict future tumor growth at the later days. For Model 2, additional parameters describing cell death and sensitivity to Ktrans were estimated from the all timepoints and used to simulate tumor growth over the final four time points. Error was assessed between the model and observed tumor growth by calculating the percent error in tumor volume, percent error in voxel cell number, and the concordance correlation coefficient (CCC) over the final four days. Results No statistically significant differences for percent error in tumor volume were observed between Model 1 (6.49 ± 4.70%, mean and 95% confidence interval) and Model 2 (6.77 ± 4.77%). Model 1 had 12.0 ± 0.3% error in voxel cell number in low cellularity regions (where cellularity was between 60-80% of carrying capacity). Model 2, however, exhibited a statistically significant decrease (P < 0.05) in error at the voxel level (8.3 ± 0.2%) in the same low cellularity regions. No significant differences for percent error in voxel cell number were observed between the models at high cellularity regions (greater than 80% of carrying capacity). Model 2 had stronger agreement (CCC = 0.69) between the measured and model described cell number in low cellularity regions compared to model 1 (CCC = 0.57). Both model 1 and 2 had CCC > 0.90 in high cellularity regions. Conclusion Incorporating a model of cell death informed by tissue perfusion improves the overall tumor growth characterization by decreasing the error in predicted cell number at the voxel level in the low cellularity (or hypoxic) regions. The lack of a model for Ktrans in the current implementation, however, requires a posteriori measurements to update tissue perfusion. Further work is needed to develop a predictive model for the spatial-temporal evolution of Ktrans. Citation Format: David A. Hormuth, Thomas E. Yankeelov. A biophysical model for necrosis development in glioblastoma informed by subject-specific MRI measurements [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4530. doi:10.1158/1538-7445.AM2017-4530

A Multibody Knee Model Corroborates Subject-Specific Experimental Measurements of Low Ligament Forces and Kinematic Coupling During Passive Flexion.

A multibody model of the knee was developed and the predicted ligament forces and kinematics during passive flexion corroborated subject-specific measurements obtained from a human cadaveric knee that was tested using a robotic manipulator. The model incorporated a novel strategy to estimate the slack length of ligament fibers based on experimentally measured ligament forces at full extension and included multifiber representations for the cruciates. The model captured experimentally measured ligament forces (≤ 5.7 N root mean square (RMS) difference), coupled internal rotation (≤ 1.6 deg RMS difference), and coupled anterior translation (≤ 0.4 mm RMS difference) through 130 deg of passive flexion. This integrated framework of model and experiment improves our understanding of how passive structures, such as ligaments and articular geometries, interact to generate knee kinematics and ligament forces.

Evaluation of land-use regression models used to predict air quality concentrations in an urban area

Cohort studies designed to estimate human health effects of exposures to urban pollutants require accurate determination of ambient concentrations in order to minimize exposure misclassification errors. However, it is often difficult to collect concentration information at each study subject location. In the absence of complete subject-specific measurements, land-use regression (LUR) models have frequently been used for estimating individual levels of exposures to ambient air pollution. The LUR models, however, have several limitations mainly dealing with extensive monitoring data needs and challenges involved in their broader applicability to other locations. In contrast, air quality models can provide high-resolution source–concentration linkages for multiple pollutants, but require detailed emissions and meteorological information. In this study, first we predicted air quality concentrations of PM 2.5, NO x, and benzene in New Haven, CT using hybrid modeling techniques based on CMAQ and AERMOD model results. Next, we used these values as pseudo-observations to develop and evaluate the different LUR models built using alternative numbers of (training) sites (ranging from 25 to 285 locations out of the total 318 receptors). We then evaluated the fitted LUR models using various approaches, including: 1) internal “Leave-One-Out-Cross-Validation” (LOOCV) procedure within the “training” sites selected; and 2) “Hold-Out” evaluation procedure, where we set aside 33–293 tests sites as independent datasets for external model evaluation. LUR models appeared to perform well in the training datasets. However, when these LUR models were tested against independent hold out (test) datasets, their performance diminished considerably. Our results confirm the challenges facing the LUR community in attempting to fit empirical response surfaces to spatially- and temporally-varying pollution levels using LUR techniques that are site dependent. These results also illustrate the potential benefits of enhancing basic LUR models by utilizing air quality modeling tools or concepts in order to improve their reliability or transferability.

An Image-Based Approach to Obtaining Anthropometric Measurements for Inertia Modeling

This study aimed to develop and evaluate an image-based method of obtaining anthropometric measurements for accurate subject-specific inertia parameter determination using Yeadon's (1990) inertia model. Ninety-five anthropometric measurements were obtained directly from five athletic performers and indirectly from digitization of subject-specific whole-body still images. The direct and image-based measurements were used as input into Yeadon's (1990) inertia model. The overall absolute error in predicted whole-body mass achieved using the image-based approach (2.87%) compared well to that achieved using the direct measurements (2.10%). The inclusion of image-based anthropometric measurements obtained from extremity (hand and feet) images was not found to consistently improve model accuracy achieved using whole-body images only. The presented method provides a successful alternative to direct measurement for obtaining anthropometric measurements required for customized inertia modeling. The noninvasive image-based approach is benefited by the potential for obtaining subject-specific measurements from large samples of subjects and elite athletic performers for whom time-consuming data collections may be undesirable.

Non-invasive bone competence analysis by high-resolution pQCT: An in vitro reproducibility study on structural and mechanical properties at the human radius

Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength. Bone strength depends, among others, on bone density, bone geometry and its internal architecture. With the recent introduction of a new generation high-resolution 3D peripheral quantitative computed tomography (HR-pQCT) system, direct quantification of structural bone parameters has become feasible. Furthermore, it has recently been demonstrated that bone mechanical competence can be derived from HR-pQCT based micro-finite element modeling (μFE). However, reproducibility data for HR-pQCT-derived mechanical indices is not well-known. Therefore, the aim of this study was to quantify reproducibility of HR-pQCT-derived indices. We measured 14 distal formalin-fixed cadaveric forearms three times and analyzed three different regions for each measurement. For each region cortical and trabecular parameters were determined. Reproducibility was assessed with respect to precision error (PE) and intraclass correlation coefficient (ICC). Reproducibility values were found to be best in all three regions for the full bone compartment with an average PE of 0.79%, followed by the cortical compartment (PE = 1.19%) and the trabecular compartment with an average PE of 2.31%. The mechanical parameters showed similar reproducibility (PE = 0.48%–2.93% for bone strength and stiffness, respectively). ICC showed a very high reproducibility of subject-specific measurements, ranging from 0.982 to 1.000, allowing secure identification of individual donors ranging from healthy to severely osteoporotic subjects. From these in vitro results we conclude that HR-pQCT derived morphometric and mechanical parameters are highly reproducible such that differences in bone structure and strength can be detected with a reproducibility error smaller than 3%; hence, the technique has a high potential to become a tool for detecting bone quality and bone competence of individual subjects.

The Diabetic Foot Load Monitor: A Portable Device for Real-Time Subject-Specific Measurements of Deep Plantar Tissue Stresses During Gait

Abstract Elevated stresses in deep plantar tissue of diabetic neuropathic patients were associated with an increased risk for foot ulceration, but only interfacial foot pressures are currently measured to evaluate susceptibility to ulcers. The goals of this study were to develop a real-time patient-specific plantar tissue stress monitor based on the Hertz contact theory. The biomechanical model for stress calculations considers the heel and metatarsal head pads, where most ulcers occur. For calculating stress concentrations around the bone-pad interface, plantar tissue is idealized as elastic and incompressible semi-infinite bulk (with properties measured by indentation), which is penetrated by a rigid sphere with the bone’s radius of curvature (from X-ray). Hertz’s theory is used to solve the bone-pad mechanical interactions, after introducing correction coefficients to consider large deformations. Foot-shoe forces are measured to solve and display the principal compressive, tensile, and von Mises plantar tissue stresses in real time. Our system can be miniaturized in a handheld computer, allowing plantar stress monitoring in the patient’s natural environment. Small groups of healthy subjects (N=6) and diabetic patients (N=3) participated in an evaluation study in which the differences between free walking and treadmill walking were examined. We also compared gait on a flat surface to gait on an ascending/descending slope of 3.5deg and when ascending/descending stairs. Peak internal compression stress was about threefold greater than the interface pressure at the calcaneus region. Subjects who were inexperience in treadmill walking displayed high gait-cycle variability in the internal stresses as well as poor foot loading. There was no statistical difference between gait on a flat surface and gait when ascending/descending a slope. Internal stresses under the calcaneus during gait on a flat surface, however, were significantly higher than when ascending/descending stairs. We conclude that the present stress monitor is a promising tool for real-time patient-specific evaluation of deep tissue stresses, providing valuable information in the effort to protect diabetic patients from foot ulceration. Clinical studies are now underway to identify which stress parameters can distinguish between diabetic and normal subjects; these parameters may be used for establishing injury threshold criteria.

Automatic measurement of the labyrinth using image registration and a deformable inner ear atlas

Rationale and objectives This article presents a new method for measuring the shape of the cochlea, vestibule, semi-circular canals, and internal auditory canal using image registration and a deformable inner ear atlas. Materials and methods Computed tomography images of the inner ear are analyzed by placing them into a common orientation and then registering a digital atlas of the inner ear to the data set. The atlas is deformed from its original shape to match the shape of the inner ear in the computed tomography data set using inverse consistent elastic image registration. This process produces an individualized inner ear atlas containing subject-specific measurements and segmentations of the inner ear anatomy in the target computed tomography data set. The shape measurements include the volume and length of the cochlea, vestibule, semi-circular canals, and internal auditory canal; and the angles between the semi-circular canals. Results A simulated population of inner ear shapes were generated based on the shape of a real population of inner ear shapes and were used to characterize the measurement error of this method. The deformable atlas was used to measure the shape of the left and right inner ear of six individuals. Conclusion Measurement error for 15 of the 24 measurements of our simulated population had an average error of less than 1% and only one measurement had an average error greater than 2.54%. The deformable human inner ear atlas shows promise as a new method for automatically measuring the shape of the labyrinth.

PHARMACODYNAMIC ANALYSIS OF ANALGESIC CLINICAL TRIALS: NONLINEAR MIXED-EFFECTS LOGISTIC MODELS

In the development of an analgesic product, placebo-controlled clinical trials in patients with defined pain are used to study the dose-time-response relationship of the drug. In such trials, the response is usually an ordered categorical variable with longitudinal and subject-specific repeated measurements. The primary causal variables are time and analgesic concentration. The response may be informative right-hand censored because remedication with a known analgesic may be given if a patient has inadequate pain relief. Mixed-effects logistic models are used to estimate the probabilities of having certain pain relief or pain severity scores. A jackknife method is proposed to estimate the standard errors of parameter estimates. Posterior estimates of these probabilities, or of the scores themselves, allow the evaluation of efficacy for an analgesic. In this evaluation, therapeutic as well as statistical significance is assessed. Two case studies, one focusing on pain relief and the other on pain severity, are used to demonstrate the approach. The level of baseline pain appears to be a determinant of the pattern of response.