Intrathecal administration of nitroxides as potential contrast agents for MR imaging

The diagnosis of various disorders of the cerebrospinal fluid (CSF) with magnetic resonance (MR) imaging may require the intrathecal administration of a paramagnetic contrast agent. Furthermore, the CSF route provides direct access to the brain, circumventing the blood-brain barrier. Three nitroxides, two charged and one uncharged, were administered intrathecally to dogs to assess their potential as contrast agents for MR imaging of the CSF. Nitroxide concentrations and proton T1 values were measured in samples of CSF removed at various times after nitroxide administration, and pharmacokinetic curves were constructed. The charged nitroxides had considerably longer half-lives than the uncharged compound. On in vivo MR imaging of the CSF (surrounding the upper cervical cord and brain stem) in one dog, use of a charged nitroxide as contrast agent led to considerably higher CSF signal intensity than was observed in the nonenhanced, baseline T1-weighted images. This effect was achieved at low doses (20 mumol) and sustained for at least 90 minutes. The intrathecal use of nitroxides as contrast agents for MR imaging warrants continued investigation.