Development of diagnostic and prognostic ultrasound imaging biomarkers for plantar heel pain

Project Summary/Abstract

Myofascial pain remains an underdiagnosed contributor to a range of musculoskeletal pain conditions. The

lack of validated biomarkers limits the ability to objectively detect myofascial pain, probe underlying pain

mechanisms, and guide targeted treatments. This proposal will address this gap by quantifying the

biochemical, biomechanical, and structural properties of myofascial pain using advanced, quantitative imaging

techniques. As a model of myofascial pain, we have chosen plantar fasciitis, which affects 1 out of every 10

adults. Our long-term goal is to enhance musculoskeletal pain management by creating better tools for

detecting abnormal myofascial tissue that enable more individualized treatment.

The objective of the R61 phase is to use novel imaging techniques to develop a diagnostic biosignature to

objectively and accurately determine the location and severity of abnormal myofascial tissue. Our approach will

use a cross-sectional study design with 3 groups: plantar fasciitis (n=50), Achilles tendinopathy (n=25), and

pain-free controls (n=25) to test Specific Aim 1: Develop a diagnostic imaging biosignature of myofascial

tissue to differentiate individuals with plantar fasciitis from other foot pain without a myofascial

component (Achilles tendinopathy) and from matched pain-free controls.

The objective of the R33 phase is to use novel imaging techniques to develop a predictive biosignature to

identify individuals most likely to respond to DN, and a response biosignature to guide dosing or continued use

of DN for myofascial pain for individuals with plantar foot pain. Our approach will use a parallel-group, doubleblinded randomized controlled trial (RCT) design with imaging measured before, during (1 m.), and after

treatment (3 & 6 m.). Participants will be randomized to one of two groups: 1) DN + standard care, or 2) Sham

DN + standard care to test Specific Aim 2: Determine 2A) predictive (Independent variable: imaging

biosignature; Primary outcome: Pain Intensity) and 2B) response (Independent variable: DN vs. Sham DN;

Primary outcome: Imaging biosignature/biomarkers) imaging biosignatures in an RCT.

Exploratory Aim 3: Will develop composite biosignatures, that combine multiple imaging biomarkers

developed in Aims 1 or 2 with psychosocial factors, to enhance the diagnostic, predictive, or response

capability for myofascial pain.

Transition criteria. 1) Adequate recruitment with >90% of participants in each group enrolled; 2) Adequate

representation with neither sex exceeding 60% of the sample; 3) Minimal missing data ( 0.7 and FDRs < 0.1; 5-8) Submit

DSMP, Study Accrual and Retention Plan, Final sample size and statistical analysis informed by mock

recruitment, and R33 transition application, including implementation of an effective sham DN.