The idiopathic inflammatory myopathies (IIM), including dermatomyositis (DM), polymyositis (PM), and inclusion body myositis (IBM), are autoimmune diseases resulting in muscle inflammation, weakness, and pain. Laboratory and imaging (MRI) studies are typically performed, but are not always well correlated with disease severity;patient management must be based on subjective clinical findings. Therefore, the overall objective of this study is to develop and elucidate the pathological basis of a battery of MRI tests that will objectively and quantitatively track specific aspects of IIM. These tests will include typical structural images;intramuscular adipose quantification using Dixon imaging;assessment of muscle quality and architecture using diffusion-tensor MRI;assessment of inflammation using short-tau inversion recovery;quantification of perfusion using dynamic-contrast enhanced MRI;metabolic assessments during exercise using blood oxygenation-level dependent MRI and 31P MR spectroscopy.
In Aim 1, these tests will be applied to increasingly complex mouse models of IIM. First, we will study 1) control C57/Bl6 mice;2) mice overexpressing aquaporin-4, to increase membrane permeability;3) mice injected with lambda-carageenan, to cause edema;and 4) both conditions. Then, we will study treated and untreated mice with a transgenically induced form of PM, over time. Advanced, multi-dimensional image analysis approaches will be used to correlate all of or a subset of the MRI findings with quantitative histological measures of muscle damage.
In Aim 2, the MRI tests will be applied to 1) humans undergoing controlled muscle damage and 2) DM, PM, and IBM patients and age- and gender- matched control subjects. Multidimensional image analysis approaches will be employed in order to correlate imaging findings with patient self-report of disease severity and clinical findings. Overall, we expect that these studies will provide new tools and approaches for quantitative characterization of muscle structure and function in IIM. These tools will allow for improved clinical management of individual patients and allow for characterization of responses to proposed treatments in group studies. Moreover, these studies will provide new tools for assessing muscle function i neuromuscular disorders more generally.

Public Health Relevance

Inflammatory diseases of muscle cause pain, swelling, weakness, and reduced quality of life. Typical clinical tests do not always correspond to disease severity, however. In this study, we would like to develop new tools, based on non-invasive imaging methods, that will allow clinicians to describe muscle damage brought about inflammatory muscle disease in a more specific and quantitative fashion.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR057091-03
Application #
8099655
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Nuckolls, Glen H
Project Start
2009-08-05
Project End
2014-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
3
Fiscal Year
2011
Total Cost
$333,108
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
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