The spine is comprised of repeating units of intervertebral discs and vertebral bodies. The disc is a complex tissue with unique subcomponents including the gelatinous nucleus pulposus (NP), which is surrounded by the annulus fibrosus (AF). Injury of the AF through annular tears leads to degenerative changes or herniation, where NP material extrudes out of the disc and impinges on the spinal nerves. Unfortunately, there are relatively few studies that have measured intradiscal deformations during loading, making it difficult to discern how stresses are distributed throughout the disc, and how changes in stress distribution may lead to tissue damage. Noninvasive imaging and texture correlation techniques used by PI Dr. Grace O?Connell have been used to track tissue displacements within intact human lumbar discs using magnetic resonance imaging. However, this approach was limited to only assessing static disc mechanics due to long image acquisition times (~20 minutes), a timeframe that is not representative of physiological dynamic loading (e.g., walking, bending, etc.). Dr. Craig Goergen (Co-PI) has extensive experience using high frequency ultrasound imaging to track three- dimensional tissue deformations of cardiovascular and musculoskeletal tissues over time (i.e., 4D deformations). Preliminary data has been collected to determine feasibility of measuring intradiscal strains under dynamic loading conditions. Thus, the goal of this proposal is to integrate advanced high-resolution ultrasound imaging and texture correlation to quantify intradiscal strain profiles in the intervertebral disc under dynamic loading conditions. In the first aim, we will develop a framework for measuring and modeling 4D deformations throughout the intervertebral disc by combining techniques developed in O?Connell and Goergen?s labs. We will measure internal AF strains during dynamic compression of healthy intact discs. Intradiscal strains will be used to validate a finite element model that will be capable of describing viscoelastic (time-dependent) behavior.
In Aim 2, we will evaluate the effect of tissue degradation through enzymatic digestion of glycosaminoglycans and the effect of annular fissures on AF strain distributions during dynamic compression. Throughout the proposal, bovine disc will be used to develop and validate the technique. Then, healthy to moderately degenerated human disc will be collected to validate the technique works with human discs. Successful completion of this proposal project will transform approaches for assessing intradiscal strains by extending previous advancements in ultrasound and biomechanics. Moreover, a validated mathematical model will be useful for the study of more complex dynamic loading and evaluating the effect of new NP treatment strategies on AF mechanics by improving our understanding of disc injury.

Public Health Relevance

The intervertebral disc is a complex organ with two distinct materials (the nucleus pulposus and annulus fibrosus) that act to absorb and distribute stresses placed on the spine during daily activities. Understanding the mechanical behavior of the intact disc and its subcomponents has been a significant challenge in the field, limiting researchers ability to understand mechanical changes with injury, degeneration, or with biological repair strategies. In this study, we will 1) develop a framework that combines advances in high-resolution ultrasound imaging with computational modeling, 2) measured internal AF strains that will be used to validate a computational model, and 3) predict joint-level mechanical behavior under complex loading modalities.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AR075127-02
Application #
10085626
Study Section
Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Washabaugh, Charles H
Project Start
2020-01-16
Project End
2021-12-31
Budget Start
2021-01-01
Budget End
2021-12-31
Support Year
2
Fiscal Year
2021
Total Cost
Indirect Cost
Name
University of California Berkeley
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94710