Systematic review of quantitative imaging biomarkers for neck and shoulder musculoskeletal disorders

Gold et al. BMC Musculoskeletal Disorders (2017) 18:395 DOI 10.1186/s12891-017-1694-y RESEARCH ARTICLE Open Access Systematic review of quantitative imaging biomarkers for neck and shoulder musculoskeletal disorders Judith E. Gold1,5*, David M. Hallman1, Fredrik Hellström1, Martin Björklund1,2, Albert G. Crenshaw1, Svend Erik Mathiassen1, Mary F. Barbe3 and Sayed Ali4 Abstract Background: This study systematically summarizes quantitative imaging biomarker research in non-traumatic neck and shoulder musculoskeletal disorders (MSDs). There were two research questions: 1) Are there quantitative imaging biomarkers associated with the presence of neck and shoulder MSDs?, 2) Are there quantitative imaging biomarkers associated with the severity of neck and shoulder MSDs? Methods: PubMed and SCOPUS were used for the literature search. One hundred and twenty-five studies met primary inclusion criteria. Data were extracted from 49 sufficient quality studies. Results: Most of the 125 studies were cross-sectional and utilized convenience samples of patients as both cases and controls. Only half controlled for potential confounders via exclusion or in the analysis. Approximately one-third reported response rates. In sufficient quality articles, 82% demonstrated at least one statistically significant association between the MSD(s) and biomarker(s) studied. The literature synthesis suggested that neck muscle size may be decreased in neck pain, and trapezius myalgia and neck/shoulder pain may be associated with reduced vascularity in the trapezius and reduced trapezius oxygen saturation at rest and in response to upper extremity tasks. Reduced vascularity in the supraspinatus tendon may also be a feature in rotator cuff tears. Five of eight studies showed an association between a quantitative imaging marker and MSD severity. Conclusions: Although research on quantitative imaging biomarkers is still in a nascent stage, some MSD biomarkers were identified. There are limitations in the articles examined, including possible selection bias and inattention to potentially confounding factors. Recommendations for future studies are provided. Keywords: MRI, MSD, Near-infrared spectroscopy, Pain, Ultrasound Background Soft tissue neck and shoulder musculoskeletal disorders (MSDs), namely, disorders of the muscles, tendons, ligaments, nerves, or blood vessels, are prevalent worldwide [1–4], are a common cause of work absence and disability [5], and impose a sizeable societal economic burden [1, 3, 4, 6–11]. Most options for screening, surveillance and diagnosis of proximal upper extremity MSDs depend on symptoms. * Correspondence: 1 Centre for Musculoskeletal Research, Department of Occupational and Public Health Sciences, University of Gävle, Gävle, Sweden 5 Gold Standard Research Consulting, 830 Montgomery Ave, Bryn Mawr, PA, USA Full list of author information is available at the end of the article Improved diagnostic and screening methods, especially objective techniques, are needed [12, 13]. A biomarker has been defined as “a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention”[14]. Quantitative medical imaging techniques are increasingly used in clinical practice and MSD research, and enable detection of potential MSD biomarkers, including functional and morphological changes. The Quantitative Imaging Biomarkers Alliance and the Terminology Working Group define a quantitative imaging biomarker as “an objective characteristic derived from an in vivo image measured on a ratio or interval scale as an indicator of normal biological © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Gold et al. BMC Musculoskeletal Disorders (2017) 18:395 processes, pathogenic processes or a response to a therapeutic intervention” [15]. Valid and reliable biomarkers could improve diagnosis and screening methods [16] and provide objective means to evaluate medical treatments and workplace interventions. Use of such biomarkers may also elucidate MSD pathomechanisms. Three biomarkers classes are conventionally described: exposure, effect (disease), and susceptibility [17]. Herein, we have reviewed biomarkers of effect, defined as “any change that is qualitatively or quantitatively predictive of health impairment or potential impairment…” [17]. Through measurement of biomarkers of effect, pathophysiological processes may be illuminated and used to stage MSD severity, such as early biomarkers that precede disease diagnosis versus late biomarkers in already diagnosed subjects. Previous biomarker reviews Prior reviews on this topic include a pioneering paper highlighting the potential for MSD biomarkers to detect subclinical disease and monitor MSD severity [18], and a later MSD review article [19] focused on biochemical markers. Neither paper mentioned medical imaging. Our recent systematic review also focused on biochemical biomarkers in MSDs [20]. To our knowledge, there have been no published reviews of quantitative imaging biomarkers in neck and shoulder MSDs. The purpose of this systematic review was to conduct a comprehensive assessment of quantitative imaging biomarkers in neck and shoulder MSDs. We aimed to answer the following two research questions: 1. Are there quantitative imaging biomarkers associated with the presence of neck and shoulder MSDs? 2. Are there quantitative imaging biomarkers associated with the severity of neck and shoulder MSDs? Methods Review team and process overview. Our review team consisted of eight researchers with expertise in musculoskeletal radiology and in epidemiologic, intervention and experimental studies, including studies on pathomechanisms within the field of work-related MSD research. The review process was as follows: 1) research questions were formulated; 2) principal concepts of the review were defined; 3) a search strategy and terms were developed (Additional file 1); 4) PubMed and Scopus databases were searched, with results pooled with articles identified from the authors’ files; 5) identified papers were screened based on pre-defined criteria (Additional files 1, 2 and 3) using a two-step procedure of primary (title and abstract) and secondary (quality) screens; 6) summary tables were created from sufficient quality papers; and 7) evidence was synthesized with respect to Pag (...truncated)