Muscle fibre morphology and microarchitecture in cerebral palsy patients obtained by 3D synchrotron X-ray computed tomography

BACKGROUND Synchrotron X-ray computed tomography (SXCT) allows for three-dimensional imaging of objects at a very high resolution and in large field-of-view. PURPOSE The aim of this study was to use SXCT imaging for morphological analysis of muscle tissue, in order to investigate whether the analysis reveals complementary information to two-dimensional microscopy. METHODS Three-dimensional SXCT images of muscle biopsies were taken from participants with cerebral palsy and from healthy controls. We designed morphological measures from the two-dimensional slices and three-dimensional volumes of the images and measured the muscle fibre organization, which we term orientation consistency. RESULTS The muscle fibre cross-sectional areas were significantly larger in healthy participants than in participants with cerebral palsy when carrying out the analysis in three dimensions. However, a similar analysis carried out in two dimensions revealed no patient group difference. The present study also showed that three-dimensional orientation consistency was significantly larger for healthy participants than for participants with cerebral palsy. CONCLUSION Individuals with CP have smaller muscle fibres than healthy control individuals. We argue that morphometric measures of muscle fibres in two dimensions are generally trustworthy only if the fibres extend perpendicularly to the slice plane, and otherwise three-dimensional aspects should be considered. In addition, the muscle tissue of individuals with CP showed a decreased level of orientation consistency when compared to healthy control tissue. We suggest that the observed disorganization of the tissue may be induced by atrophy caused by physical inactivity and insufficient neural activation.

[1]  Paolo Crenna,et al.  Spasticity and `Spastic' Gait in Children with Cerebral palsy , 1998, Neuroscience & Biobehavioral Reviews.

[2]  Martin Bech,et al.  Injection of high dose botulinum-toxin A leads to impaired skeletal muscle function and damage of the fibrilar and non-fibrilar structures , 2017, Scientific Reports.

[3]  Zhenzhou Wang,et al.  Generalizing cell segmentation and quantification , 2017, BMC Bioinformatics.

[4]  P. Grimaud [Cerebral palsy]. , 1972, Pediatrie.

[5]  G. Margaritondo,et al.  Coherence-enhanced synchrotron radiology: simple theory and practical applications , 2002 .

[6]  Thomas Brox,et al.  Fully automated segmentation and morphometrical analysis of muscle fiber images , 2007, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[7]  Zhenzhou Wang,et al.  A semi-automatic method for robust and efficient identification of neighboring muscle cells , 2016, Pattern Recognit..

[8]  Glen Lichtwark,et al.  Muscle growth is reduced in 15‐month‐old children with cerebral palsy , 2016, Developmental medicine and child neurology.

[9]  Giorgio Margaritondo,et al.  Q&A: Why use synchrotron x-ray tomography for multi-scale connectome mapping? , 2017, BMC Biology.

[10]  Normand Boucher,et al.  Factors Related to Physical Activity in Adults with Cerebral Palsy May Differ for Walkers and Nonwalkers , 2010, American journal of physical medicine & rehabilitation.

[11]  Fujun Liu,et al.  Automated fiber-type-specific cross-sectional area assessment and myonuclei counting in skeletal muscle. , 2013, Journal of applied physiology.

[12]  A. Shortland,et al.  Could muscle deformity in children with spastic cerebral palsy be related to an impairment of muscle growth and altered adaptation? , 2012, Developmental medicine and child neurology.

[13]  Steven J Obst,et al.  Quantitative 3-D Ultrasound of the Medial Gastrocnemius Muscle in Children with Unilateral Spastic Cerebral Palsy. , 2017, Ultrasound in medicine & biology.

[14]  Martin Bech,et al.  Validation strategies for the interpretation of microstructure imaging using diffusion MRI , 2018, NeuroImage.

[15]  Adam P Shortland,et al.  The morphology of the medial gastrocnemius in typically developing children and children with spastic hemiplegic cerebral palsy. , 2007, Journal of electromyography and kinesiology : official journal of the International Society of Electrophysiological Kinesiology.

[16]  K. Murphy,et al.  The adult with cerebral palsy. , 2010, The Orthopedic clinics of North America.

[17]  T. Roose,et al.  Investigation of microvascular morphological measures for skeletal muscle tissue oxygenation by image-based modelling in three dimensions , 2017, Journal of The Royal Society Interface.

[18]  Jenny Ziviani,et al.  Characteristics associated with physical activity among independently ambulant children and adolescents with unilateral cerebral palsy , 2015, Developmental medicine and child neurology.

[19]  Amir Karniel,et al.  Duration and patterns of habitual physical activity in adolescents and young adults with cerebral palsy , 2014, Developmental medicine and child neurology.

[20]  Jens Bo Nielsen,et al.  Impaired muscle growth precedes development of increased stiffness of the triceps surae musculotendinous unit in children with cerebral palsy , 2018, Developmental medicine and child neurology.

[21]  Harald Köstler,et al.  Segmentation of Skeletal Muscle Fibres for Applications in Computational Skeletal Muscle Mechanics , 2011 .

[22]  J. Bigun,et al.  Optimal Orientation Detection of Linear Symmetry , 1987, ICCV 1987.

[23]  Koji Ohata,et al.  Measurement of Muscle Thickness as Quantitative Muscle Evaluation for Adults With Severe Cerebral Palsy , 2006, Physical Therapy.

[24]  Jens Bo Nielsen,et al.  Impaired gait function in adults with cerebral palsy is associated with reduced rapid force generation and increased passive stiffness , 2015, Clinical Neurophysiology.

[25]  R. Barrett,et al.  Medial gastrocnemius muscle fascicle active torque-length and Achilles tendon properties in young adults with spastic cerebral palsy. , 2012, Journal of biomechanics.

[26]  G F Clough,et al.  Phase contrast synchrotron radiation computed tomography of muscle spindles in the mouse soleus muscle , 2017, Journal of anatomy.

[27]  Xiaodong Wu,et al.  Optimal Surface Segmentation in Volumetric Images-A Graph-Theoretic Approach , 2006, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[28]  John M. Cowley,et al.  High-resolution transmission electron microscopy and associated techniques , 1988 .

[29]  R Scelsi,et al.  Automatic morphometric analysis of skeletal muscle fibers in the aging man , 1987, The Anatomical record.

[30]  Nicholas F Taylor,et al.  Differences in habitual physical activity levels of young people with cerebral palsy and their typically developing peers: a systematic review , 2013, Disability and rehabilitation.

[31]  Lin Yang,et al.  Automated image analysis of skeletal muscle fiber cross-sectional area. , 2013, Journal of applied physiology.