Manganese-Enhanced MRI of the Brain in Healthy Volunteers

AJNR Am J Neuroradiol. 2019 Aug;40(8):1309-1316. doi: 10.3174/ajnr.A6152. Epub 2019 Aug 1.

Abstract

Background and purpose: The manganese ion is used as an intracellular MR imaging contrast agent to study neuronal function in animal models, but it remains unclear whether manganese-enhanced MR imaging can be similarly useful in humans. Using mangafodipir (Teslascan, a chelated manganese-based contrast agent that is FDA-approved), we evaluated the dynamics of manganese enhancement of the brain and glandular structures in the rostral head and neck in healthy volunteers.

Materials and methods: We administered mangafodipir intravenously at a rate of 1 mL/minute for a total dose of 5 μmol/kg body weight. Nine healthy adult volunteers (6 men/3 women; median age, 43 years) completed baseline history and physical examination, 3T MR imaging, and blood work. MR imaging also followed mangafodipir administration at various time points from immediate to 7 days, with delayed scans at 1-3 months.

Results: The choroid plexus and anterior pituitary gland enhanced within 10 minutes of infusion, with enhancement persisting up to 7 and 30 days, respectively. Exocrine (parotid, submandibular, sublingual, and lacrimal) glands also enhanced avidly as early as 1 hour postadministration, generally resolving by 1 month; 3 volunteers had residual exocrine gland enhancement, which resolved by 2 months in 1 and by 3 months in the other 2. Mangafodipir did not affect clinical parameters, laboratory values, or T1-weighted signal in the basal ganglia.

Conclusions: Manganese ions released from mangafodipir successfully enable noninvasive visualization of intra- and extracranial structures that lie outside the blood-brain barrier without adverse clinical effects, setting the stage for future neuroradiologic investigation in disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Brain / diagnostic imaging
  • Contrast Media / pharmacokinetics
  • Contrast Media / pharmacology*
  • Edetic Acid / analogs & derivatives*
  • Edetic Acid / pharmacokinetics
  • Edetic Acid / pharmacology
  • Female
  • Healthy Volunteers
  • Humans
  • Image Enhancement / methods
  • Magnetic Resonance Imaging / methods*
  • Male
  • Pyridoxal Phosphate / analogs & derivatives*
  • Pyridoxal Phosphate / pharmacokinetics
  • Pyridoxal Phosphate / pharmacology

Substances

  • Contrast Media
  • Pyridoxal Phosphate
  • Edetic Acid
  • N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid