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

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

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.

Quantitative effects of inclusion of fat on muscle diffusion tensor MRI measurements.

PURPOSE: To determine the minimum water percentage in a muscle region of interest that would allow diffusion tensor (DT-) MRI data to reflect the diffusion properties of pure muscle accurately. MATERIALS AND METHODS: Proton density-weighted images with and without fat saturation were obtained at the mid-thigh in four subjects. Co-registered DT-MR images were used to calculate the diffusion tensor's eigenvalues and fractional anisotropy. RESULTS: The eigenvalues transitioned monotonically as a function of water signal percentage from values near to those expected for pure fat to those for pure muscle. Also, the fractional anisotropy transitioned monotonically from 0.50 (fat) to 0.20 (muscle). For water signal percentages >55%, none of the diffusion indices differed significantly from those for regions of >90% muscle. CONCLUSION: Accounting for the T1 and T2 values of muscle and fat and the pulse sequence properties, it is concluded that, as a conservative estimate, regions must contain at least 76% muscle tissue to reflect the diffusion properties of pure muscle accurately.

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 living systems. Neuromuscular diseases often exhibit a temporally varying, spatially heterogeneous, and multi-faceted pathology. The goal of this protocol is to characterize this pathology using qMRI methods. The MRI acquisition protocol begins with localizer images (used to locate the position of the body and tissue of interest within the MRI system), quality control measurements of relevant magnetic field distributions, and structural imaging for general anatomical characterization. The qMRI portion of the protocol includes measurements of the longitudinal and transverse relaxation time constants (T1 and T2, respectively). Also acquired are diffusion-tensor MRI data, in which water diffusivity is measured and used to infer pathological processes such as edema. Quantitative magnetization transfer imaging is used to characterize the relative tissue content of macromolecular and free water protons. Lastly, fat-water MRI methods are used to characterize fibro-adipose tissue replacement of muscle. In addition to describing the data acquisition and analysis procedures, this paper also discusses the potential problems associated with these methods, the analysis and interpretation of the data, MRI safety, and strategies for artifact reduction and protocol optimization.

A rapid approach for quantitative magnetization transfer imaging in thigh muscles using the pulsed saturation method.

Quantitative magnetization transfer (qMT) imaging in skeletal muscle may be confounded by intramuscular adipose components, low signal-to-noise ratios (SNRs), and voluntary and involuntary motion artifacts. Collectively, these issues could create bias and error in parameter fitting. In this study, technical considerations related to these factors were systematically investigated, and solutions were proposed. First, numerical simulations indicate that the presence of an additional fat component significantly underestimates the pool size ratio (F). Therefore, fat-signal suppression (or water-selective excitation) is recommended for qMT imaging of skeletal muscle. Second, to minimize the effect of motion and muscle contraction artifacts in datasets collected with a conventional 14-point sampling scheme, a rapid two-parameter model was adapted from previous studies in the brain and spinal cord. The consecutive pair of sampling points with highest accuracy and precision for estimating F was determined with numerical simulations. Its performance with respect to SNR and incorrect parameter assumptions was systematically evaluated. QMT data fitting was performed in healthy control subjects and polymyositis patients, using both the two- and five-parameter models. The experimental results were consistent with the predictions from the numerical simulations. These data support the use of the two-parameter modeling approach for qMT imaging of skeletal muscle as a means to reduce total imaging time and/or permit additional signal averaging.

Diffusion-weighted imaging of inflammatory myopathies: polymyositis and dermatomyositis.

Muscles of myositis patients examined with MRI demonstrate heterogeneous pathology ranging from unaffected muscle groups to severe inflammation, fat infiltration, and eventually, more serious fat replacement. The purpose of this investigation was to characterize myositic thigh muscles using diffusion-weighted imaging (DWI) and to examine fluid motion at various disease stages. We chose to characterize total fluid motion within the muscle using the model proposed by Le Bihan et al (6,7) in which the apparent diffusion coefficient (ADC), diffusion in the extra- and intracellular muscle compartments (D), perfusion in capillaries (pseudodiffusion) (D*), and volume fraction of capillary perfusion (f) are determined. Unaffected patient muscles have DWI coefficients equivalent to those of normal muscles. Inflamed muscles show elevated ADC and D values compared to normal muscles (P < 0.0005), and fat-infiltrated muscles have lower values than control muscles (P < 0.001). Inflamed muscles have lower f values than unaffected muscles (P < 0.009), suggesting decreased fractional volume of capillary perfusion. DWI provides quantitative data on molecular fluid motion in diseased muscles and affords the potential for longitudinal monitoring of myositic patients.

Imaging and skeletal muscle disease.

Imaging techniques have assumed increasing importance in the diagnostic approach to patients with muscle disease. These techniques include computed tomography, ultrasound, and magnetic resonance imaging (MRI). For most disorders of muscle, ultrasound and MRI are more useful than computed tomography. Advantages of ultrasound include accessibility at the bedside and lower cost. However, MRI remains the gold standard for detecting changes in muscle tissue. In some cases, MRI examinations can take the place of muscle biopsy for diagnosis. New advances in MRI include diffusion-weighted imaging, which permits assessment of fluid motion in muscles, and blood-oxygen-level-dependent imaging to evaluate tissue oxygenation.

Magnesium abnormalities of skeletal muscle in dermatomyositis and juvenile dermatomyositis.

OBJECTIVE: To characterize abnormalities in magnesium levels in the muscles of patients with dermatomyositis (DM) and juvenile dermatomyositis (JDM) and to evaluate the beneficial effects of prednisone and immunosuppressive therapy in elevating free magnesium (Mg(2+)) and ATP-bound magnesium (Mg-ATP). METHODS: The study groups consisted of 12 adult patients with DM and 10 juvenile patients with JDM. The 2 control groups were 11 normal adults and 6 healthy children. Levels of total ATP in the quadriceps muscles of the subjects were determined during rest, exercise, and recovery, using noninvasive P-31 magnetic resonance spectroscopy (MRS). Concentrations of the biologically active free Mg(2+) and the enzymatically active Mg-ATP complex were determined from the spectroscopy data by calculation of the chemical shifts of the beta-phosphate peak of ATP. RESULTS: Mg-ATP levels in DM and JDM myopathic muscles were at least 37% lower than those in normal muscles during rest, exercise, and recovery from exercise (P < 0.0005). Free Mg(2+) levels were normal in DM and JDM myopathic muscles at rest, but were significantly lower than control values during exercise and recovery (P < 0.029 and P < 0.005 for DM and JDM, respectively). Prednisone and immunosuppressive therapy partially reversed the magnesium abnormalities, as evidenced by elevation of the levels of Mg-ATP and free Mg(2+). CONCLUSION: Low levels of Mg-ATP and free Mg(2+) are concordant with weakness and fatigue observed in DM and JDM patients. Immunosuppressive therapy alleviates, in part, the magnesium deficits in the diseased muscles. Therefore, Mg-ATP and free Mg(2+) may play a significant role in the pathophysiology of these diseases.