Off-Campus Portion of Noninvasive tools for assessing muscle structure and function

Project: Research project

Description

Project Summary
Pathological changes in muscle stiffness can result from disease, blunt trauma, overuse, or as secondary
complications from other injuries and treatments. Changes in muscle stiffness can lead to reduced mobility,
chronic pain, discoordination, and increased rate of injury. Consequently, many therapeutic interventions target
muscle or joint stiffness. While there is a long history of measuring joint stiffness, there are no validated
methods to directly quantify the intrinsic stiffness of individual muscles independently from the other factors
influencing the mechanics of a joint. This is a major obstacle to identifying, treating, and monitoring muscle
contributions to stiffness-related impairments. Our long-term goal is to improve treatments for musculoskeletal
disorders associated with changes to the intrinsic properties of muscle. The central hypothesis of this proposal
is that ultrasound elastography (USE), a relatively new imaging tool for the clinic, can be used to measure the
intrinsic stiffness of living muscles. Variants of this hypothesis have been widely assumed, but not directly
tested aside from the preliminary data we have provided. Our rationale is that providing an objective measure
of intrinsic muscle stiffness will clarify the role of muscle in stiffness-related impairments, and lead to a
personalized approach to treatment design and evaluation.
We will evaluate our central hypothesis with three aims. Aim 1 will determine the extent to which
elastography can measure the intrinsic stiffness of muscles during active contractions. This will be completed
in architecturally different muscles of the cat hind limb, where activation can be controlled precisely and direct
mechanical measures obtained for comparison. Parallel human experiments will assess feasibility in clinically
relevant settings, when muscle is activated by normal patterns of recruitment and rate modulation. Aim 2 will
determine if substantial passive forces alter the stiffness estimates obtained by USE. For clinical utility, USE
must provide accurate measures during the many conditions in which passive and active structures are
relevant. These experiments will be conducted only in cats, as direct measures of passive muscle force are
difficult to obtain in humans. Aim 3 will determine if USE can detect microstructural changes in muscle, which
are typically only accessible by invasive techniques such as biopsies. We have shown that magnetic
resonance elastography (MRE) is sensitive to changes in tissue structure at scales well below image
resolution. Here we will determine if USE, a more clinically viable technique, can have a similar sensitivity. This
will be evaluated by applying MRE and USE to imaging phantoms created using our ability to print biomaterials
with known properties in 3D, and to living muscles from cats and humans. This third aim will extend current
technologies to characterize muscle and its underlying microstructure more completely. Together, our results
could profoundly impact the way disease-related changes in muscle stiffness are quantified and lead to more
targeted interventions that alleviate impairments associated with changes to intrinsic muscle stiffness.
StatusActive
Effective start/end date9/7/168/31/21

Funding

  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (1R01AR071162-01 REVISED)

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Muscles
Elasticity Imaging Techniques
Cats
Joints
Wounds and Injuries
Imaging Phantoms
Therapeutics
Mechanics
Chronic Pain
Extremities
Biopsy