In Vivo Reconstruction of Lumbar Erector Spinae Architecture Using Diffusion Tensor MRI.

STUDY DESIGN: Diffusion tensor magnetic resonance imaging (DT-MRI) reconstruction of lumbar erector spinae (ES) compared with cadaver dissection. OBJECTIVE: The aim of this study was to reconstruct the human lumbar ES from in vivo DT-MRI measurements and to compare the results with literature and cadaver dissection. SUMMARY OF BACKGROUND DATA: DT-MRI enables 3-dimensional in vivo reconstruction of muscle architecture. Insight in ES architecture may improve the understanding of low back function. Furthermore, DT-MRI reconstructions allow individualized biomechanical modeling, which may serve as a clinical tool in injury evaluation and in improvement of understanding of pathologies like scoliosis. MATERIALS AND METHODS: The lumbar spine of 1 healthy male volunteer was scanned using a 3.0 T clinical MRI scanner. MRI data acquisition consisted of 3 parts: (1) high-resolution T1-weighted turbo spin echo for anatomical reference; (2) DT-MRI measurements for fiber tractography; (3) dual echo gradient echo sequence for signal correction purposes. After processing, DT-MRI data were exported to a custom-built software program for fiber tractography. The resulting reconstructions were anatomically validated by comparison with cadaver dissection and literature. RESULTS: DT-MRI reconstruction of 4 parts of the lumbar ES (thoracic part of iliocostalis lumborum, lumbar part of iliocostalis lumborum, thoracic part of longissimus thoracis, and lumbar part of longissimus thoracis) adequately reflected its complex geometry. Some inaccuracies were found in reconstruction details. DT-MRI reconstructions were generally in agreement with anatomical descriptions from literature and with findings in a dissected cadaver specimen. CONCLUSIONS: DT-MRI enables anatomically valid reconstruction of ES architecture. However, for reliable reconstruction of the smallest fascicles and attachments a higher resolution or application of higher-order models is needed. Reconstructions can be used as input for estimation of muscle architecture parameters in individualized biomechanical modeling. Such models are promising as a tool in clinical evaluation and in research of low back pain mechanisms.

Steep increase in myonuclear domain size during infancy.

We investigated whether myonuclear number increases in proportion to the increase in fiber size during maturational growth of skeletal muscle. Thoraco-abdominal muscle tissue was obtained from twenty 6-day to 15-year-old boys and girls during cardiothoracic surgery. Cross-sections were stained by anti-laminin for the basal lamina and by DAPI to identify nuclei. Basal lamina was traced on digital images to measure the fiber cross-sectional area (FCSA). Nuclei located within the basal lamina were considered myonuclei if pax7-negative and satellite cell nuclei if pax7-positive. Samples of two children were excluded from analysis because of clear signs of hypoxia as shown by positive carbonic anhydrase IX staining. Linear regression showed that FCSA increased with age by 187 µm(2) ·per annum (R(2) = 0.90; P < 0.001). Satellite cell density showed a dramatic decrease in the first months of life, but this was not accompanied by an increase in myonuclei per muscle fiber cross-section. Till four years of age the number of myonuclei per muscle fiber cross-section remained relatively constant but increased thereafter. Myonuclear domain size showed a steep increase during infancy and reached adult values in the young adolescent phase.

Dynamic MRS and MRI of skeletal muscle function and biomechanics.

MR is a powerful technique for studying the biomechanical and functional properties of skeletal muscle in vivo in health and disease. This review focuses on 31P, 1H and 13C MR spectroscopy for assessment of the dynamics of muscle metabolism and on dynamic 1H MRI methods for non-invasive measurement of the biomechanical and functional properties of skeletal muscle. The information thus obtained ranges from the microscopic level of the metabolism of the myocyte to the macroscopic level of the contractile function of muscle complexes. The MR technology presented plays a vital role in achieving a better understanding of many basic aspects of muscle function, including the regulation of mitochondrial activity and the intricate interplay between muscle fiber organization and contractile function. In addition, these tools are increasingly being employed to establish novel diagnostic procedures as well as to monitor the effects of therapeutic and lifestyle interventions for muscle disorders that have an increasing impact in modern society.

Lysosomal dysfunction, cellular pathology and clinical symptoms: basic principles.

UNLABELLED: Between 40 and 50 lysosomal storage disorders are known at present. Fine details of the pathogenic process involved are in general not known. This overview highlights the basic principles of lysosomal pathogenesis and the clinical consequences of defective genes involved in lysosomal functions. The subject is discussed in the context of the possibility of prevention and reversal of cellular and organ damage by enzyme replacement therapy. Also presented is a mechanical model for the muscle pathology observed in Pompe disease. Direct mechanical effects of the non-contractile inclusions - glycogen-loaded lysosomes - seem to be a key factor in the loss of force during both early and late stages of the disease. CONCLUSION: Each lysosomal storage disorder and each patient with a given lysosomal disorder has unique molecular, pathological and clinical features. But, the order of pathological events is largely the same. Mutations in a gene cause lysosomal dysfunction which, in turn, results in cellular pathology affecting organ structure and function. Clinical symptoms are the ultimate manifestation. The reversibility of symptoms with enzyme replacement therapy will vary according to the disease, as well as the nature and stage of organ pathology.

Impaired performance of skeletal muscle in alpha-glucosidase knockout mice.

Glycogen storage disease type II (GSD II) is an inherited progressive muscle disease in which lack of functional acid alpha-glucosidase (AGLU) results in lysosomal accumulation of glycogen. We report on the impact of a null mutation of the acid alpha-glucosidase gene (AGLU(-/-)) in mice on the force production capabilities, contractile mass, oxidative capacity, energy status, morphology, and desmin content of skeletal muscle. Muscle function was assessed in halothane-anesthetized animals, using a recently designed murine isometric dynamometer. Maximal torque production during single tetanic contraction was 50% lower in the knockout mice than in wild type. Loss of developed torque was found to be disproportionate to the 20% loss in muscle mass. During a series of supramaximal contraction, fatigue, expressed as percentile decline of developed torque, did not differ between AGLU(-/-) mice and age-matched controls. Muscle oxidative capacity, energy status, and protein content (normalized to either dry or wet weight) were not changed in knockout mice compared to control. Alterations in muscle cell morphology were clearly visible. Desmin content was increased, whereas alpha-actinin was not. As the decline in muscle mass is insufficient to explain the degree in decline of mechanical performance, we hypothesize that the large clusters of noncontractile material present in the cytoplasm hamper longitudinal force transmission, and hence muscle contractile function. The increase in muscular desmin content is most likely reflecting adaptations to altered intracellular force transmission.

Short-term effects of forced eccentric contractions on collagen synthesis and degradation in rat skeletal muscle.

Acute downhill running has been shown to activate matrix metalloproteinase- (MMP-) 2 and to change type IV collagen concentration in some muscle types. In order to study the influence of more intense exercise on total collagen and type IV collagen concentrations, molecules regulating their synthesis and degradation were investigated after forced lengthening contractions in rat skeletal muscle. Tibialis anterior (TA) muscle of 24 male Wistar rats was subjected to 240 forced lengthening contractions. TA muscle was excised at consecutive time points (0 and 6 h, 2, 4, and 7 days) after stimulation. With immunohistochemistry, types I, III and IV collagen were located in the swollen, necrotic and regenerated fibres in a similar manner as in intact undamaged skeletal muscle fibre. An increase in the activity of prolyl 4-hydroxylase was indicative of an overall elevated collagen biosynthesis. No change was demonstrated in total collagen concentration, whereas type IV collagen concentration increased after exercise. MMP-2 and MMP-9, which are the proteins that degrade type IV collagen, elevated after exercise. In conclusion, the increase in type IV collagen concentration seems to be the result of an increase in both the synthesis and activation of degrading enzymes and their inhibitors during recovery after forced lengthening contractions.