bioRxiv Science⌕ Search

Biology subjects

Gold, G. E.

Publications and source records attributed to Gold, G. E..

3 recordsLinked to original sources

Contrast Solution Properties and Scan Parameters Influence the Apparent Diffusivity of Computed Tomography Contrast Agents in Articular Cartilage

The inability to detect early degenerative changes to the articular cartilage surface that commonly precede bulk osteoarthritic degradation is an obstacle to early disease detection for research or clinical diagnosis. Leveraging a known artifact that blurs tissue boundaries in clinical arthrograms, contrast agent diffusivity can be derived from computed tomography arthrography (CTa) scans. We combined experimental and computational approaches to study protocol variations that may alter the CTa-derived apparent diffusivity. In experimental studies on bovine cartilage explants, we examined how contrast agent dilution and transport direction (absorption vs. desorption) influence the apparent diffusivity of untreated and enzymatically digested cartilage. Using multiphysics simulations, we examined mechanisms underlying experimental observations and the effects of image resolution, scan interval and early scan termination. The apparent diffusivity during absorption decreased with increasing contrast agent concentration by an amount similar to the increase induced by tissue digestion. Models indicated that osmotically induced fluid efflux strongly contributed to the concentration effect. Simulated changes to spatial resolution, scan spacing and total scan time all influenced the apparent diffusivity, indicating the importance of consistent protocols. With careful control of imaging protocols and interpretations guided by transport models, CTa-derived diffusivity offers promise as a biomarker for early degenerative changes.

bioengineering↗

Non-ionic CT Contrast Solutions Rapidly Alter Bovine Cartilage and Meniscus Mechanics

ObjectiveTo evaluate effects of a common CT contrast agent (iohexol) on the mechanical behaviors of cartilage and meniscus. MethodsIndentation responses of juvenile bovine cartilage and meniscus were monitored following exposure to undiluted contrast agent (100% CA), 50% CA/water, 50% CA/Phosphate Buffered Saline (PBS) or PBS alone, and during re-equilibration in PBS. The normalized peak force [Formula], effective osmotic strain ({varepsilon}osm), and normalized effective contact modulus [Formula] were calculated for every cycle, with time constants determined for both exposure and recovery via mono- or biexponential fits to [Formula]. ResultsAll cartilage CA groups exhibited long-term increases in [Formula] following exposure, although the hyperosmolal 100% CA and 50% CA/PBS groups showed an initial transient decrease. Meniscus presented opposing trends, with decreasing [Formula] for all CA groups. Re-equilibration in PBS for 1hr after exposure to 100% CA did not produce recovery to baseline [Formula] in either tissue. The recovery time for meniscus was substantially longer than that of cartilage. [Formula] increased with CA exposure time for cartilage but decreased for meniscus, suggesting an increased effective stiffness for cartilage and decreased stiffness for meniscus. Long-term changes to{varepsilon} osm in both tissues were consistent with changes in [Formula]. ConclusionExposure to iohexol solutions affected joint tissues differentially, with increased cartilage stiffness, likely relating to competing hyperosmotic and hypotonic interactions with tissue fixed charges, and decreased meniscus stiffness, likely dominated by hyperosmolarity. These altered tissue mechanics could allow non-physiological deformation during ambulatory weight-bearing, resulting in an increased risk of tissue or cell damage.

bioengineering↗

pyKNEEr: An image analysis workflow for open and reproducible research on femoral knee cartilage

Transparent research in musculoskeletal imaging is fundamental to reliably investigate diseases such as knee osteoarthritis (OA), a chronic disease impairing femoral knee cartilage. To study cartilage degeneration, researchers have developed algorithms to segment femoral knee cartilage from magnetic resonance (MR) images and to measure cartilage morphology and relaxometry. The majority of these algorithms are not publicly available or require advanced programming skills to be compiled and run. However, to accelerate discoveries and findings, it is crucial to have open and reproducible workflows. We present pyKNEEr, a framework for open and reproducible research on femoral knee cartilage from MR images. pyKNEEr is written in python, uses Jupyter notebook as a user interface, and is available on GitHub with a GNU GPLv3 license. It is composed of three modules: 1) image preprocessing to standardize spatial and intensity characteristics, 2) femoral knee cartilage segmentation for intersubject, multimodal, and longitudinal acquisitions, and 3) analysis of cartilage morphology and relaxometry. Each module contains one or more Jupyter notebooks with narrative, code, visualizations, and dependencies to reproduce computational environments. pyKNEEr facilitates transparent image-based research of femoral knee cartilage because of its ease of installation and use, and its versatility for publication and sharing among researchers. Finally, due to its modular structure, pyKNEEr favors code extension and algorithm comparison. We tested our reproducible workflows with experiments that also constitute an example of transparent research with pyKNEEr. We provide links to executed notebooks and executable environments for immediate reproducibility of our findings.

bioengineering↗