A popular strategy for indicating CNS damage is to introduce a contrast agent into the CNS, but tracking small molecules deep within the CNS represents a particular challenge for multiple reasons: (1) Toxicity to structures within the CNS result in particularly morbid prognoses therefore, it is crucial that new contrast be useful at low concentrations to ensure non-toxicity. Unfortunately, CNS injuries can be difficult to identify, especially in patients who are unconscious or who have spontaneous or deep-tissue cerebrospinal fluid (CSF) leakage, where the anatomical CSF leak source is not obvious. ĭamage to the central nervous system (CNS) can significantly reduce a patient’s quality of life, especially if not promptly addressed. Therefore, by combining 18F-PET and fluorescent imaging modalities within a single molecule, we can transcend the molecular resolution limits of any one imaging modality. Moreover, while PET emissions can be non-invasively quantitated through a patient’s body, fluorescence imaging is ideal for visualizing submicron, histologic structure in superficial tissue. Both 18F-PET and fluorescence imaging allow the tracking of small molecules at sub-nanomolar concentration, making them among the most sensitive, and therefore also the potentially least toxic, of available imaging modalities. One good combination is positron emission tomography (PET) and fluorescence imaging. One popular strategy in the development of more universal contrast agents is to combine different imaging modalities with synergistic properties, where one modality will complement the resolution shortcomings of another imaging modality. Yet, no current single imaging modality is ideal, as each individual imaging modality is limited by unique temporal, spatial, and depth (through-tissue) resolutions. 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.Īdvances in molecular imaging have enhanced our ability to non-invasively track molecules in patients. IR783-AMBF 3 was safe under the tested dosage both in vitro and in vivo. 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. 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 clearly distributed in CSF-containing volumes by PET and fluorescence. 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. IR-783, a commercially available near-infrared dye, was chemically modified and radiolabeled with fluorine-18 to give -IR783-AMBF 3. We describe a near-infrared fluorescent dye for accurately monitoring CSF flow by positron emission tomography (PET) and fluorescence. 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). Knowing the precise flow of cerebrospinal fluid (CSF) is important in the management of multiple neurological diseases.
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