A near-infrared probe for non-invasively monitoring cerebrospinal fluid flow by (18)F-positron emitting tomography and fluorescence

PURPOSE: Knowing the precise flow of cerebrospinal fluid (CSF) is important in the management of multiple neurological diseases. Technology for non-invasively quantifying CSF flow would allow for precise localization of injury and assist in evaluating the viability of certain devices placed in the central nervous system (CNS). METHODS: We describe a near-infrared fluorescent dye for accurately monitoring CSF flow by positron emission tomography (PET) and fluorescence. IR-783, a commercially available near-infrared dye, was chemically modified and radiolabeled with fluorine-18 to give [(18)F]-IR783-AMBF(3). [(18)F]-IR783-AMBF(3) was intrathecally injected into the rat models with normal and aberrant CSF flow and evaluated by the fluorescence and PET/MRI or PET/CT imaging modes. RESULTS: IR783-AMBF(3) was clearly distributed in CSF-containing volumes by PET and fluorescence. We compared IR783-AMBF(3) (fluorescent at 778/793 nm, ex/em) to a shorter-wavelength, fluorescein equivalent (fluorescent at 495/511 nm, ex/em). IR783-AMBF(3) was superior for its ability to image through blood (hemorrhage) and for imaging CSF-flow, through-skin, in subdural-run lumboperitoneal shunts. IR783-AMBF(3) was safe under the tested dosage both in vitro and in vivo. CONCLUSION: The superior imaging properties of IR783-AMBF(3) could lead to enhanced accuracy in the treatment of patients and would assist surgeons in non-invasively diagnosing diseases of the CNS.