Comparison of Intramuscular Distribution of Different Injection Volumes Via Diffusion Tensor Imaging (DTI)
Condition: Healthy
Study type: Observational

Summary: 
      The purpose of this experimental pilot study is to assess a positive effect of higher
      injection volumes of fluid (physiological sodium) in the elbow-flection-muscle (M. biceps
      brachii) and elbow flexion and extension movements on fluid distribution in the muscle
      tissue.
    

Detailed description: 
      Background:

      Intramuscular application of Botulinum toxin is used as a successful therapy of many
      conditions (e.g. spasticity, movement disorders, hypersecretory disorders, ophthalmic
      disorders, painful conditions, pelvic floor and gastrointestinal disorders, cosmetic
      applications) Clinical practice shows that even with the use of special guidance techniques
      (electromyography (EMG), ultrasound, electrical stimulation) to increase accuracy of
      targeting, botulinum toxin may spread to adjacent sites by diffusion. Different therapy goals
      request variable diffusion of the toxin, depending on the number of muscles involved and loss
      of function in the affected area, respectively. There is some evidence that larger injection
      volume lead to greater distribution and a larger affected area. Thus, animal model showed
      increased efficacy and decreased systemic side effects of botulinum toxin A in the injected
      muscle after active or passive manipulation of muscle.

      Magnetic resonance imaging (MRI) has the potential to noninvasively probe the amount and
      motion of intracellular and extracellular water using different sequences. T2-weighted and
      diffusion tensor sequences are especially useful in the quantification and characterization
      of the chemical behaviour of water in different (animal) tissue types. To our knowledge there
      has been no systematically performed in vivo MR study using these imaging techniques in the
      visualization of intramuscular dilution of fluid in human subjects. However, the in vivo
      effect on tissue distribution of different injection volumes and active muscle movement in
      humans via DTI has never been observed.

      Hypothesis:

      Intramuscular distribution of common saline solutions can be non-invasively quantified by DTI
      in human subjects. DTI can be used to elucidate if:

        -  Intramuscular distribution is favoured by larger injection volumes and

        -  Intramuscular distribution is facilitated by active muscle activity.

      Rationale:

      The effect of large injection volumes and active muscle activity after injection on
      intramuscular toxin distribution and uptake remains unclear. Physiological sodium is the
      carrier material of all preparations of Botulinum toxin, suggesting that physiological sodium
      or natriumchlorid (NaCl) distribution is representative for toxin primary distribution.
      Dynamic T2-weighted sequences may monitor the inflow and regional distribution of the infused
      saline solution.

      DTI can non-invasively quantify the amount and directionality of motion of protons in human
      skeletal muscle and may therefore indirectly allow assumptions on the extra- and
      intracellular distribution of the infused solution/substance.

      Methods:

      In this exploratory, investigator blinded pilot study, 10 healthy subjects will be
      investigated by DTI of the musculi biceps brachii after randomised intramuscular injection of
      two different injection volumes of NaCl and randomisation to active flexion and extension in
      the elbow joints versus no active flexion and extension. During each injection dynamic T2
      weighted magnetic resonance tomographic sequences will be performed. Subsequently diffusion
      tensor sequences will be carried out at defined time points.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        healthy volunteer
      
Keywords: intramuscular; distribution; NaCl; botulinum toxin; muscle; volume; movement; biceps brachii; primary distribution of intramuscular NaCl representative for primary distribution of intramuscular botulinum toxin; shift from extracellular to intracellular viewed by DTI technology; effect of volume; effect of muscle movement