title: Intramuscular distribution of botulinum toxin--visualized by MRI.
abstract: OBJECTIVE
  A precise knowledge of the spread of botulinum toxin (BoNT) in muscle tissue is required to efficiently access endplate zones and increase BoNT's therapeutic efficacy. Here, we aimed to understand the spatiotemporal dynamics of BoNT distribution in skeletal muscle and its modulating factors, such as injected volume and exercise after injection.
  
  
  METHODS
  To visualize distribution in muscle tissue, sagittal, dynamic, balanced fast field echo (BFFE) MRI imaging was performed during injection of 1 ml BoNT/NaCl bolus in spastic biceps brachii muscles (SBB, n=4), and 1 ml NaCl in the right and 2 ml NaCl in the left healthy biceps brachii (HBB, n=6), with or without successive muscle exercise. The pattern of extracellular fluid distribution was evaluated by T2-weighted and diffusion tensor imaging (DTI) sequences.
  
  
  RESULTS
  BFFE indicated an immediate increase in hyperintensity, parallel to the muscle fibers, in the shape of a long (5.3±1.7 cm) and thin (0.52±1.3 cm) layer in HBB. The layer in SBB was shorter (3.25±0.6 cm, p=0.01) and tended to be thicker (0.74±2.9 cm, p=0.27). In HBB, an increase in volume (2 ml) resulted in an increase in thickness (0.95±0.2 cm, p=0.015), but a consistent length (5.67±1.3 cm, p=0.54). DTI visualized a change of diffusion, which exceeded the bolus region by approximately 0.5 cm. Redistribution occurred 10 min after injection and was more prominent in HBB, compared to SBB. Additional muscle activity did not alter the diffusion pattern or bolus distribution.
  
  
  CONCLUSIONS
  Injecting BoNT at different depths perpendicular to the direction of the muscle fiber might optimize the efficacy of BoNT treatment. Additional sites along muscle fibers should be considered in SBB.
authors.affiliation: Department of Neurology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. Electronic address: kirsten_elwischger@hotmail.com.
authors.forename: K
authors.initials: K
authors.lastname: Elwischger
authors.affiliation: Department of Radiology, Division of Neuroradiology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. Electronic address: gregor.kasprian@meduniwien.ac.at.
authors.forename: G
authors.initials: G
authors.lastname: Kasprian
authors.affiliation: Department of Radiology, Division of Neuroradiology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. Electronic address: michael.weber@meduniwien.ac.at.
authors.forename: M
authors.initials: M
authors.lastname: Weber
authors.affiliation: Center for Medical Physics and Biomedical Engineering, Centre of Excellence "High-Field Magnetic Resonance", Lazarettgasse 14, 1090 Vienna, Austria. Electronic address: martin.meyerspeer@meduniwien.ac.at.
authors.forename: M
authors.initials: M
authors.lastname: Meyerspeer
authors.affiliation: Department of Neurology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. Electronic address: christoph.linder@meduniwien.ac.at.
authors.forename: C
authors.initials: C
authors.lastname: Linder
authors.affiliation: Department of Neurology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. Electronic address: eduard.auff@meduniwien.ac.at.
authors.forename: E
authors.initials: E
authors.lastname: Auff
authors.affiliation: Department of Radiology, Division of Neuroradiology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. Electronic address: daniela.prayer@meduniwien.ac.at.
authors.forename: D
authors.initials: D
authors.lastname: Prayer
authors.affiliation: Department of Neurology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. Electronic address: thomas.sycha@meduniwien.ac.at.
authors.forename: T
authors.initials: T
authors.lastname: Sycha
authors.affiliation: Department of Neurology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. Electronic address: gottfried.kranz@meduniwien.ac.at.
authors.forename: G
authors.initials: G
authors.lastname: Kranz
mesh_terms: D000328:Adult; D000368:Aged; D001905:Botulinum Toxins / Q000378:metabolism* / Q000627:therapeutic use; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000378:metabolism* / Q000627:therapeutic use; D013035:Spasm / Q000188:drug therapy / Q000473:pathology*; D055815:Young Adult
chemical_list: D009498:Neurotoxins; D001905:Botulinum Toxins
keywords: Botulinum toxin; Distribution; MRI; Spasticity