Intramuscular distribution of botulinum toxin—Visualized by MRI

Abstract

ObjectiveA 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. MethodsTo visualize distribution in muscle tissue, sagittal, dynamic, balanced fast field echo (BFFE) MRI imaging was performed during injection of 1ml BoNT/NaCl bolus in spastic biceps brachii muscles (SBB, n=4), and 1ml NaCl in the right and 2ml 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. ResultsBFFE indicated an immediate increase in hyperintensity, parallel to the muscle fibers, in the shape of a long (5.3±1.7cm) and thin (0.52±1.3cm) layer in HBB. The layer in SBB was shorter (3.25±0.6cm, p=0.01) and tended to be thicker (0.74±2.9cm, p=0.27). In HBB, an increase in volume (2ml) resulted in an increase in thickness (0.95±0.2cm, p=0.015), but a consistent length (5.67±1.3cm, p=0.54). DTI visualized a change of diffusion, which exceeded the bolus region by approximately 0.5cm. Redistribution occurred 10min after injection and was more prominent in HBB, compared to SBB. Additional muscle activity did not alter the diffusion pattern or bolus distribution. ConclusionInjecting 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.