Monitoring creatine and phosphocreatine by (13)C MR spectroscopic imaging during and after (13)C4 creatine loading: a feasibility study.

Creatine (Cr) supplementation to enhance muscle performance shows variable responses among individuals and different muscles. Direct monitoring of the supplied Cr in muscles would address these differences. In this feasibility study, we introduce in vivo 3D (13)C MR spectroscopic imaging (MRSI) of the leg with oral ingestion of (13)C4-creatine to observe simultaneously Cr and phosphocreatine (PCr) for assessing Cr uptake, turnover, and the ratio PCr over total Cr (TCr) in individual muscles. (13)C MRSI was performed of five muscles in the posterior thigh in seven subjects (two males and two females of ~20 years, one 82-year-old male, and two neuromuscular patients) with a (1)H/(13)C coil in a 3T MR system before, during and after intake of 15 % (13)C4-enriched Cr. Subjects ingested 20 g Cr/day for 4 days in four 5 g doses at equal time intervals. The PCr/TCr did not vary significantly during supplementation and was similar for all subjects and investigated muscles (average 0.71 ± 0.07), except for the adductor magnus (0.64 ± 0.03). The average Cr turnover rate, assessed in male muscles, was 2.1 ± 0.7 %/day. The linear uptake rates of Cr were variable between muscles, although not significantly different. This assessment was possible in all investigated muscles of young male volunteers, but less so in muscles of the other subjects due to lower signal-to-noise ratio. Improvements for future studies are discussed. In vivo (13)C MRSI after (13)C-Cr ingestion is demonstrated for longitudinal studies of Cr uptake, turnover, and PCr/TCr ratios of individual muscles in one exam.

Quantitative muscle ultrasound versus quantitative magnetic resonance imaging in facioscapulohumeral dystrophy.

INTRODUCTION: Ultrasound and magnetic resonance imaging (MRI) are non-invasive methods that can be performed repeatedly and without discomfort. In the assessment of neuromuscular disorders it is unknown if they provide complementary information. In this study we tested this for patients with facioscapulohumeral muscular dystrophy (FSHD). METHODS: We performed quantitative muscle ultrasound (QMUS) and quantitative MRI (QMRI) of the legs in 5 men with FSHD. RESULTS: The correlation between QMUS-determined z-scores and QMRI-determined muscle fraction and T1 signal intensity (SI) was very high. QMUS had a wider dynamic range than QMRI, whereas QMRI could detect inhomogeneous distribution of pathology over the length of the muscles. CONCLUSIONS: Both QMUS and QMRI are well suited for imaging muscular dystrophy. The wider dynamic range of QMUS can be advantageous in the follow-up of advanced disease stages, whereas QMRI seems preferable in pathologies such as FSHD that affect deep muscle layers and show inhomogeneous abnormality distributions.

Determining the role of sarcomeric proteins in facioscapulohumeral muscular dystrophy: a study protocol.

BACKGROUND: Although muscle weakness is a hallmark of facioscapulohumeral muscular dystrophy (FSHD), the molecular mechanisms that lead to weakness in FSHD remain largely unknown. Recent studies suggest aberrant expression of genes involved in skeletal muscle development and sarcomere contractility, and activation of pathways involved in sarcomeric protein degradation. This study will investigate the contribution of sarcomeric protein dysfunction to the pathogenesis of muscle weakness in FSHD. METHODS/DESIGN: Evaluation of sarcomeric function using skinned single muscle fiber contractile studies and protein analysis in muscle biopsies (quadriceps femoris and tibialis anterior) from patients with FSHD and age- and gender-matched healthy controls. Patients with other forms of muscular dystrophy and inflammatory myopathy will be included as disease controls to assess whether results are due to changes specific for FSHD, or a consequence of muscle disease in general. A total of 56 participants will be included. Extensive clinical parameters will be measured using MRI, quantitative muscle studies and physical activity assessments. DISCUSSION: This study is the first to extensively investigate muscle fiber physiology in FSHD following an earlier pilot study suggesting sarcomeric dysfunction in FSHD. The results obtained in this study will increase the understanding of the pathophysiology of muscle weakness in FSHD, and possibly identify novel targets for therapeutic intervention.

MRI-Guided Biopsy as a Tool for Diagnosis and Research of Muscle Disorders.

BACKGROUND: Sampling error is a common problem in muscle biopsies. MRI-guided biopsy allows verification of biopsy site during the procedure, which may reduce sampling error in patients with focal disease. OBJECTIVES: To describe the technique for MRI-guided muscle biopsy and discuss potential applications. METHODS: Axial MRI images were acquired to determine the target site for muscle biopsy. Needle trajectory was planned on 3D T1 weighted imaging and a MRI-guided biopsy of the vastus lateralis was performed in 13 FSHD patients. RESULTS: An adequate amount of muscle tissue was obtained in all participants, and MRI-guided biopsy succeeded in reaching focal target sites. However, symptomatic hematomas were observed in 2/13 patientsDiscussion:MRI-guided biopsy has a higher complication rate compared to traditional needle biopsy, most likely due to proximity to blood vessels in combination with the vacuum-assisted suction of the MRI-guided technique. We recommend that this technique is reserved for select diagnostic cases and research questions, with careful assessment of vasculature and reduced suction levels.

Distinct disease phases in muscles of facioscapulohumeral dystrophy patients identified by MR detected fat infiltration.

Facioscapulohumeral muscular dystrophy (FSHD) is an untreatable disease, characterized by asymmetric progressive weakness of skeletal muscle with fatty infiltration. Although the main genetic defect has been uncovered, the downstream mechanisms causing FSHD are not understood. The objective of this study was to determine natural disease state and progression in muscles of FSHD patients and to establish diagnostic biomarkers by quantitative MRI of fat infiltration and phosphorylated metabolites. MRI was performed at 3T with dedicated coils on legs of 41 patients (28 men/13 women, age 34-76 years), of which eleven were re-examined after four months of usual care. Muscular fat fraction was determined with multi spin-echo and T1 weighted MRI, edema by TIRM and phosphorylated metabolites by 3D (31)P MR spectroscopic imaging. Fat fractions were compared to clinical severity, muscle force, age, edema and phosphocreatine (PCr)/ATP. Longitudinal intramuscular fat fraction variation was analyzed by linear regression. Increased intramuscular fat correlated with age (p<0.05), FSHD severity score (p<0.0001), inversely with muscle strength (p<0.0001), and also occurred sub-clinically. Muscles were nearly dichotomously divided in those with high and with low fat fraction, with only 13% having an intermediate fat fraction. The intramuscular fat fraction along the muscle's length, increased from proximal to distal. This fat gradient was the steepest for intermediate fat infiltrated muscles (0.07±0.01/cm, p<0.001). Leg muscles in this intermediate phase showed a decreased PCr/ATP (p<0.05) and the fastest increase in fatty infiltration over time (0.18±0.15/year, p<0.001), which correlated with initial edema (p<0.01), if present. Thus, in the MR assessment of fat infiltration as biomarker for diseased muscles, the intramuscular fat distribution needs to be taken into account. Our results indicate that healthy individual leg muscles become diseased by entering a progressive phase with distal fat infiltration and altered energy metabolite levels. Fat replacement then relatively rapidly spreads over the whole muscle.

Mindfulness meditation associated with alterations in bottom-up processing: psychophysiological evidence for reduced reactivity.

Mental training by meditation has been related to changes in high-level cognitive functions that involve top-down processing. The aim of this study was to investigate whether the practice of meditation is also related to alterations in low-level, bottom-up processing. Therefore, intersensory facilitation (IF) effects in a group of mindfulness meditators (MM) were compared to IF effects in an age- and gender-matched control group. Smaller and even absent IF effects were found in the MM group, which suggests that changes in bottom-up processing are associated with MM. Furthermore, reduced interference of a visual warning stimulus with the IF effects was found, which suggests an improved allocation of attentional resources in mindfulness meditators, even across modalities.