quantitative-magnetic-resonance-imaging-of-skeletal-muscle-disease

Quantitative Magnetic Resonance Imaging of Skeletal Muscle Disease

Quantitative magnetic resonance imaging (qMRI) describes the development and use of MRI to quantify physical, chemical, and/or biological properties of ...

Vanderbilt University

In this study we compared the effects of downhill or horizontal treadmill running on the magnetic resonance imaging (MRI) transverse relaxation time constant (T(2)) in mdx mice.

Changes in muscle T2 and tissue damage after downhill running in mdx mice.

Myopathies often display a common set of complex pathologies that include muscle weakness, inflammation, compromised membrane integrity, fat deposition, and fibrosis. Multi-parametric, quantitative, non-invasive imaging approaches may be able to resolve these individual pathological components. The goal of this study was to use multi-parametric MRI to investigate inflammation as an isolated pathological feature. Proton relaxation, diffusion tensor imaging (DTI), quantitative magnetization transfer (qMT-MRI), and dynamic contrast enhanced (DCE-MRI) parameters were calculated from data acquired in a single imaging session conducted 6-8 hours following the injection of λ-carrageenan, a local inflammatory agent. T2 increased in the inflamed muscle and transitioned to bi-exponential behavior. In diffusion measurements, all three eigenvalues and the apparent diffusion coefficient increased, but λ3 had the largest relative change. Analysis of the qMT data revealed that the T1 of the free pool and the observed T1 both increased in the inflamed tissue, while the ratio of exchanging spins in the solid pool to those in the free water pool (the pool size ratio) significantly decreased. DCE-MRI data also supported observations of an increase in extracellular volume. These findings enriched the understanding of the relation between multiple quantitative MRI parameters and an isolated inflammatory pathology, and may potentially be employed for other single or complex myopathy models.

Multi-parametric MRI characterization of inflammation in murine skeletal muscle.

Muscle diseases commonly have clinical presentations of inflammation, fat infiltration, fibrosis, and atrophy. However, the results of existing laboratory tests and clinical presentations are not well correlated. Advanced quantitative MRI techniques may allow the assessment of myo-pathological changes in a sensitive and objective manner. To progress towards this goal, an array of quantitative MRI protocols was implemented for human thigh muscles; their reproducibility was assessed; and the statistical relationships among parameters were determined. These quantitative methods included fat/water imaging, multiple spin-echo T2 imaging (with and without fat signal suppression, FS), selective inversion recovery for T1 and quantitative magnetization transfer (qMT) imaging (with and without FS), and diffusion tensor imaging. Data were acquired at 3.0 T from nine healthy subjects. To assess the repeatability of each method, the subjects were re-imaged an average of 35 days later. Pre-testing lifestyle restrictions were applied to standardize physiological conditions across scans. Strong between-day intra-class correlations were observed in all quantitative indices except for the macromolecular-to-free water pool size ratio (PSR) with FS, a metric derived from qMT data. Two-way analysis of variance revealed no significant between-day differences in the mean values for any parameter estimate. The repeatability was further assessed with Bland-Altman plots, and low repeatability coefficients were obtained for all parameters. Among-muscle differences in the quantitative MRI indices and inter-class correlations among the parameters were identified. There were inverse relationships between fractional anisotropy (FA) and the second eigenvalue, the third eigenvalue, and the standard deviation of the first eigenvector. The FA was positively related to the PSR, while the other diffusion indices were inversely related to the PSR. These findings support the use of these T1 , T2 , fat/water, and DTI protocols for characterizing skeletal muscle using MRI. Moreover, the data support the existence of a common biophysical mechanism, water content, as a source of variation in these parameters.

Multi-parametric MRI characterization of healthy human thigh muscles at 3.0 T - relaxation, magnetization transfer, fat/water, and diffusion tensor imaging.

Magnetic resonance imaging (MRI) was used to monitor changes in the transverse relaxation time constant (T2) in lower hindlimb muscles of mdx mice at different ages.

Age-related T2 changes in hindlimb muscles of mdx mice.

Neuromuscular diseases often exhibit a temporally varying, spatially heterogeneous, and multifaceted pathology. The goals of this chapter are to describe and evaluate the use of quantitative magnetic resonance imaging (MRI) methods to characterize muscle pathology. The following criteria are used for this evaluation: objective measurement of continuously distributed variables; clear and well-understood relationship to the pathology of interest; sensitivity to improvement or worsening of clinical status; and the measurement properties of accuracy and precision. Two major classes of MRI methods meet all of these criteria: (1) MRI methods for measuring muscle contractile volume or cross-sectional area by combining structural MRI and quantitative fat-water MRI; and (2) an MRI method for characterizing the edema caused by inflammation, the measurement of the transverse relaxation time constant (T2). These methods are evaluated with respect to the four criteria listed above and examples from neuromuscular disorders are provided. Finally, these methods are summarized and synthesized and recommendations for additional quantitative MRI developments are made.

Article	Year
Changes in muscle T2 and tissue damage after downhill running in mdx mice. Muscle & nerve\| PubMed ID: 21488051	2011
Multi-parametric MRI characterization of inflammation in murine skeletal muscle. NMR in biomedicine\| PubMed ID: 24777935	2014
Multi-parametric MRI characterization of healthy human thigh muscles at 3.0 T - relaxation, magnetization transfer, fat/water, and diffusion tensor imaging. NMR in biomedicine\| PubMed ID: 25066274	2014
Age-related T2 changes in hindlimb muscles of mdx mice. Muscle & nerve\| PubMed ID: 25846867	2016
Magnetic resonance imaging of skeletal muscle disease. Handbook of clinical neurology\| PubMed ID: 27430444	2016

Nathan D. Bryant

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