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 Ͻ 0.0005), and fatinfiltrated muscles have lower values than control muscles (P Ͻ 0.001). Inflamed muscles have lower f values than unaffected muscles (P Ͻ 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.
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.
Objective. To evaluate the utility of magnetic resonance imaging (MRI) and P-31 magnetic resonance spectroscopy (MRS) in the longitudinal management of patients with dermatomyositis (DM).Methods. The study group consisted of 11 patients, including 3 children, all of whom had a clinical diagnosis of DM. A control group of 8 subjects was studied simultaneously. MRI included images as well as calculations of T1 and T2 relaxation times. The P-31 MRS protocol evaluated metabolic status (i.e., inorganic phosphate/phosphocreatine ratios and phosphocreatine and ATP levels) during rest, exercise, and recovery.Results. T2-weighted images of the thigh muscles showed inflammation even when serum creatine phosphokinase levels were in the normal range. Metabolic abnormalities, which were accentuated with exercise,
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 on 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 2nd eigenvalue, the 3rd eigenvalue, and the standard deviation of 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.
Objective. To investigate the use of magnetic resonance imaging (MRI) and P-31 magnetic resonance spectroscopy (MRS) in characterizing the metabolic and functional status of muscles in patients with amyopathic dermatomyositis (DM) and to compare the findings with those in patients with classic myopathic DM.Methods. Nine patients with amyopathic DM, 11 patients with myopathic DM, and 11 normal individuals were studied. MRI images of thigh muscles were obtained, and T1 and T2 relaxation times were calculated. Biochemical status was quantitated with P-31 MRS, by determining concentrations of phosphate metabolites during rest and exercise.Results. Patients with amyopathic DM showed no muscle inflammation, and MRS data obtained during rest were normal. During exercise at 25% and 50% maximum voluntary contractile force, the MRS data revealed significant differences between amyopathic DM patients and control subjects indicating inefficient metabolism. In contrast, muscles of patients with myopathic DM showed inflammation and metabolic abnormalities even during rest.Conclusion. Metabolic deficiencies in patients with amyopathic DM were unmasked by exercise, sug-
Vertical fluctuations of the terminal methyl groups of stearic acid acyl chains toward the surface of dimyristoylphosphatidylcholine (DMPC) bilayers have been investigated by using spin-label electron-electron double-resonance ( ELDOR ) methodology. Spin-label pairs consisting of two populations of stearic acid spin-labels were employed, each at 0.25 mol% concentration, where the nitroxides of the first population were 15N substituted and the nitroxides of the second contained 14N. Various combinations of labels with the nitroxide moieties located at carbons 5, 12, or 16 (C5, C12, C16) were used. ELDOR permits measurement of collision frequencies between the two constituents of the pair, for example, between 15N spin-labels at C5 and 14N labels at C16. Intramolecular contributions to the ELDOR effect including nitrogen nuclear relaxation are eliminated by the use of spin-label pairs. Above the main phase transition temperature, bimolecular collisions between C5 and C16 occur with about half the frequency of C16:C16 collisions. It is concluded that vertical fluctuations are very pronounced. A dependence of these fluctuations on temperature and pH has been observed. Lateral diffusion constants calculated from the bimolecular collision frequencies of C16:C16 pairs are 4.56 X 10(-8), 5.77 X 10(-8), and 8.09 X 10(-8) cm2/s at 27, 37, and 47 degrees C. These values are in good agreement with previous measurements of lipid diffusion in DMPC.
Myopathies often display a common set of complex pathologies that include muscle weakness, inflammation, compromised membrane integrity, fat deposition, and fibrosis. Multi-parametric, quantitative, noninvasive 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 to other single or complex myopathy models.
Objective. To investigate the metabolic and functional status of muscles of fibromyalgia (FM) patients, using P-31 magnetic resonance spectroscopy (MRS). Methods. Twelve patients with FM and 11 healthy subjects were studied. Clinical status was assessed by questionnaire. Biochemical status of muscle was evaluated with P-31 MRS by determining concentrations of inorganic phosphate (Pi), phosphocreatine (PCr), ATP, and phosphodiesters during rest and exercise. Functional status was evaluated from the PCr/Pi ratio, phosphorylation potential (PP), and total oxidative ca-Results. Patients with FM reported greater difficulty in performing activities of daily living as well as increased pain, fatigue, and weakness compared with controls. MRS measurements showed that patients had significantly lower than normal PCr and ATP levels (P < 0.004) and PCr/Pi ratios (P < 0.04) in the quadriceps muscles during rest. Values for PP and V, , , also were significantly reduced during rest and exercise. Conclusion. P-31 MRS provides objective evidence for metabolic abnormalities consistent with weakness and fatigue in patients with FM. Noninvasive P-31 MRS may be useful in assessing clinical status and evaluating the effectiveness of treatment regimens in FM. pacity (VInaJ. Fibromyalgia (FM) is a syndrome of unknown cause and poorly understood pathophysiology, with an estimated prevalence as high as 10% in one population study (1). Although levels of serum muscle enzymes and electromyography findings are normal in FM patients, histologic studies indicate the presence of abnormalities in the morphology of muscle fibers (2 3). These abnormalities include the presence of ragged red fibers (4) and swelling of capillary endothelial cells (5-7). Abnormal distribution of oxygenation in the trapezius muscle of FM patients as measured with an oxygen-sensitive electrode has been reported (S), and this finding is consistent with other observations reported by Bennett et al, who found that the blood flow in the exercising muscles of FM patients was significantly lower than in age-and sex-matched controls (9). Decreased levels of the high-energy phosphate compounds ATP and phos-phocreatine (PCr) have been observed in muscle biopsy samples from patients with FM (4). The technique of P-31 magnetic resonance ypec-troscopy (MRS) has been shown to be useful in the evaluation of a number of muscle diseases, including glycogen phosphorylase deficiency (lo), mitochondria1 myopathies (11,12) and dermatomyositis (DM) (13,14), Recent P-31 MRS studies in FM investigated both resting and exercising muscles by evaluation of PCr/ inorganic phosphate (PCr/Pi) ratios (15-19), but no defect was found. However, it is critical to determine the absolute levels of Pi, PCr, and ATP, since ratios of these compounds can be normal while the actual concentrations of compounds are reduced (20). In the present study, we used P-31 MRS to quantitate levels of Pi, PCr, and ATP and their relevant ratios in the muscles of clinically characterized FM patients (21). The metabolic ab...
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