Publications
2017
The purpose of this study was to develop a novel magnetic resonance imaging (MRI)-based modeling technique for measuring intervertebral displacements. Here, we present the measurement bias and reliability of the developmental work using a porcine spine model. Porcine lumbar vertebral segments were fitted in a custom-built apparatus placed within an externally calibrated imaging volume of an open-MRI scanner. The apparatus allowed movement of the vertebrae through pre-assigned magnitudes of sagittal and coronal translation and rotation. The induced displacements were imaged with static (T1) and fast dynamic (2D HYCE S) pulse sequences. These images were imported into animation software, in which these images formed a background 'scene'. Three-dimensional models of vertebrae were created using static axial scans from the specimen and then transferred into the animation environment. In the animation environment, the user manually moved the models (rotoscoping) to perform model-to-'scene' matching to fit the models to their image silhouettes and assigned anatomical joint axes to the motion-segments. The animation protocol quantified the experimental translation and rotation displacements between the vertebral models. Accuracy of the technique was calculated as 'bias' using a linear mixed effects model, average percentage error and root mean square errors. Between-session reliability was examined by computing intra-class correlation coefficients (ICC) and the coefficient of variations (CV). For translation trials, a constant bias (β0) of 0.35 (±0.11) mm was detected for the 2D HYCE S sequence (p=0.01). The model did not demonstrate significant additional bias with each mm increase in experimental translation (β1Displacement=0.01mm; p=0.69). Using the T1 sequence for the same assessments did not significantly change the bias (p>0.05). ICC values for the T1 and 2D HYCE S pulse sequences were 0.98 and 0.97, respectively. For rotation trials, a constant bias (β0) of 0.62 (±0.12)° was detected for the 2D HYCE S sequence (p<0.01). The model also demonstrated an additional bias (β1Displacement) of 0.05° with each degree increase in the experimental rotation (p<0.01). Using T1 sequence for the same assessments did not significantly change the bias (p>0.05). ICC values for the T1 and 2D HYCE S pulse sequences were recorded 0.97 and 0.91, respectively. This novel quasi-static approach to quantifying intervertebral relationship demonstrates a reasonable degree of accuracy and reliability using the model-to-image matching technique with both static and dynamic sequences in a porcine model. Future work is required to explore multi-planar assessment of real-time spine motion and to examine the reliability of our approach in humans.
Thyroid hormones boost animals' basal metabolic rate and represent an important thermoregulatory pathway for mammals that face cold temperatures. Whereas the cold thermal pressures experienced by primates in seasonal habitats at high latitudes and elevations are often apparent, tropical habitats also display distinct wet and dry seasons with modest changes in thermal environment. We assessed seasonal and temperature-related changes in thyroid hormone levels for two primate species in disparate thermal environments, tropical mantled howlers (Alouatta palliata), and seasonally cold-habitat Japanese macaques (Macaca fuscata). We collected urine and feces from animals and used ELISA to quantify levels of the thyroid hormone triiodothyronine (fT3 ). For both species, fT3 levels were significantly higher during the cooler season (wet/winter), consistent with a thermoregulatory role. Likewise, both species displayed greater temperature deficits (i.e., the degree to which animals warm their body temperature relative to ambient) during the cooler season, indicating greater thermoregulatory pressures during this time. Independently of season, Japanese macaques displayed increasing fT3 levels with decreasing recently experienced maximum temperatures, but no relationship between fT3 and recently experienced minimum temperatures. Howlers increased fT3 levels as recently experienced minimum temperatures decreased, although demonstrated the opposite relationship with maximum temperatures. This may reflect natural thermal variation in howlers' habitat: wet seasons had cooler minimum and mean temperatures than the dry season, but similar maximum temperatures. Overall, our findings support the hypothesis that both tropical howlers and seasonally cold-habitat Japanese macaques utilize thyroid hormones as a mechanism to boost metabolism in response to thermoregulatory pressures. This implies that cool thermal pressures faced by tropical primates are sufficient to invoke an energetically costly and relatively longer-term thermoregulatory pathway. The well-established relationship between thyroid hormones and energetics suggests that the seasonal hormonal changes we observed could influence many commonly studied behaviors including food choice, range use, and activity patterns.
2016
Background
In recent years large bibliographic databases have made much of the published literature of biology available for searches. However, the capabilities of the search engines integrated into these databases for text-based bibliographic searches are limited. To enable searches that deliver the results expected by comparative anatomists, an underlying logical structure known as an ontology is required.Development and testing of the ontology
Here we present the Mammalian Feeding Muscle Ontology (MFMO), a multi-species ontology focused on anatomical structures that participate in feeding and other oral/pharyngeal behaviors. A unique feature of the MFMO is that a simple, computable, definition of each muscle, which includes its attachments and innervation, is true across mammals. This construction mirrors the logical foundation of comparative anatomy and permits searches using language familiar to biologists. Further, it provides a template for muscles that will be useful in extending any anatomy ontology. The MFMO is developed to support the Feeding Experiments End-User Database Project (FEED, https://feedexp.org/), a publicly-available, online repository for physiological data collected from in vivo studies of feeding (e.g., mastication, biting, swallowing) in mammals. Currently the MFMO is integrated into FEED and also into two literature-specific implementations of Textpresso, a text-mining system that facilitates powerful searches of a corpus of scientific publications. We evaluate the MFMO by asking questions that test the ability of the ontology to return appropriate answers (competency questions). We compare the results of queries of the MFMO to results from similar searches in PubMed and Google Scholar.Results and significance
Our tests demonstrate that the MFMO is competent to answer queries formed in the common language of comparative anatomy, but PubMed and Google Scholar are not. Overall, our results show that by incorporating anatomical ontologies into searches, an expanded and anatomically comprehensive set of results can be obtained. The broader scientific and publishing communities should consider taking up the challenge of semantically enabled search capabilities.BACKGROUND: Single or biplanar video radiography and Roentgen stereophotogrammetry (RSA) techniques used for the assessment of in-vivo joint kinematics involves application of ionizing radiation, which is a limitation for clinical research involving human subjects. To overcome this limitation, our long-term goal is to develop a magnetic resonance imaging (MRI)-only, three dimensional (3-D) modeling technique that permits dynamic imaging of joint motion in humans. Here, we present our initial findings, as well as reliability data, for an MRI-only protocol and modeling technique.
METHODS: We developed a morphology-based motion-analysis technique that uses MRI of custom-built solid-body objects to animate and quantify experimental displacements between them. The technique involved four major steps. First, the imaging volume was calibrated using a custom-built grid. Second, 3-D models were segmented from axial scans of two custom-built solid-body cubes. Third, these cubes were positioned at pre-determined relative displacements (translation and rotation) in the magnetic resonance coil and scanned with a T1 and a fast contrast-enhanced pulse sequences. The digital imaging and communications in medicine (DICOM) images were then processed for animation. The fourth step involved importing these processed images into an animation software, where they were displayed as background scenes. In the same step, 3-D models of the cubes were imported into the animation software, where the user manipulated the models to match their outlines in the scene (rotoscoping) and registered the models into an anatomical joint system. Measurements of displacements obtained from two different rotoscoping sessions were tested for reliability using coefficient of variations (CV), intraclass correlation coefficients (ICC), Bland-Altman plots, and Limits of Agreement analyses.
RESULTS: Between-session reliability was high for both the T1 and the contrast-enhanced sequences. Specifically, the average CVs for translation were 4.31 % and 5.26 % for the two pulse sequences, respectively, while the ICCs were 0.99 for both. For rotation measures, the CVs were 3.19 % and 2.44 % for the two pulse sequences with the ICCs being 0.98 and 0.97, respectively. A novel biplanar imaging approach also yielded high reliability with mean CVs of 2.66 % and 3.39 % for translation in the x- and z-planes, respectively, and ICCs of 0.97 in both planes.
CONCLUSIONS: This work provides basic proof-of-concept for a reliable marker-less non-ionizing-radiation-based quasi-dynamic motion quantification technique that can potentially be developed into a tool for real-time joint kinematics analysis.
2015
As a negative regulator of muscle size, myostatin (Mstn) impacts the force-production capabilities of skeletal muscles. In the masticatory system, measures of temporalis-stimulated bite forces in constitutive myostatin KOs suggest an absolute, but not relative, increase in jaw-muscle force. Here, we assess the phenotypic and physiologic impact of postnatal myostatin inhibition on bite mechanics using an inducible conditional KO mouse in which myostatin is inhibited with doxycycline (DOX). Given the increased control over the timing of gene inactivation in this model, it may be more clinically-relevant for developing interventions for age-associated changes in the musculoskeletal system. DOX was administered for 12 weeks starting at age 4 months, during which time food intake was monitored. Sex, age and strain-matched controls were given the same food without DOX. Bite forces were recorded just prior to euthanasia after which muscle and skeletal data were collected. Food intake did not differ between control or DOX animals within each sex. DOX males were significantly larger and had significantly larger masseters than controls, but DOX and control females did not differ. Although there was a tendency towards higher absolute bite forces in DOX animals, this was not significant, and bite forces normalized to masseter mass did not differ. Mechanical advantage for incisor biting increased in the DOX group due to longer masseter moment arms, likely due to a more anteriorly-placed masseter insertion. Despite only a moderate increase in bite force in DOX males and none in DOX females, the increase in masseter mass in males indicates a potentially positive impact on jaw muscles. Our data suggest a sexual dimorphism in the role of mstn, and as such investigations into the sex-specific outcomes is warranted.