Magnetic resonance imaging provides evidence of glymphatic drainage from human brain to cervical lymph nodes

Sci Rep. 2018 May 8;8(1):7194. doi: 10.1038/s41598-018-25666-4.

Abstract

Pre-clinical research in rodents provides evidence that the central nervous system (CNS) has functional lymphatic vessels. In-vivo observations in humans, however, are not demonstrated. We here show data on CNS lymphatic drainage to cervical lymph nodes in-vivo by magnetic resonance imaging (MRI) enhanced with an intrathecal contrast agent as a cerebrospinal fluid (CSF) tracer. Standardized MRI of the intracranial compartment and the neck were acquired before and up to 24-48 hours following intrathecal contrast agent administration in 19 individuals. Contrast enhancement was radiologically confirmed by signal changes in CSF nearby inferior frontal gyrus, brain parenchyma of inferior frontal gyrus, parahippocampal gyrus, thalamus and pons, and parenchyma of cervical lymph node, and with sagittal sinus and neck muscle serving as reference tissue for cranial and neck MRI acquisitions, respectively. Time series of changes in signal intensity shows that contrast enhancement within CSF precedes glymphatic enhancement and peaks at 4-6 hours following intrathecal injection. Cervical lymph node enhancement coincides in time with peak glymphatic enhancement, with peak after 24 hours. Our findings provide in-vivo evidence of CSF tracer drainage to cervical lymph nodes in humans. The time course of lymph node enhancement coincided with brain glymphatic enhancement rather than with CSF enhancement.

MeSH terms

  • Adult
  • Aged
  • Arachnoid Cysts / cerebrospinal fluid
  • Arachnoid Cysts / diagnostic imaging*
  • Arachnoid Cysts / physiopathology
  • Cohort Studies
  • Contrast Media / administration & dosage
  • Female
  • Glymphatic System / diagnostic imaging*
  • Glymphatic System / metabolism
  • Glymphatic System / physiopathology
  • Humans
  • Hydrocephalus / cerebrospinal fluid
  • Hydrocephalus / diagnostic imaging*
  • Hydrocephalus / physiopathology
  • Injections, Spinal
  • Intracranial Hypertension / cerebrospinal fluid
  • Intracranial Hypertension / diagnostic imaging*
  • Intracranial Hypertension / physiopathology
  • Intracranial Hypotension / cerebrospinal fluid
  • Intracranial Hypotension / diagnostic imaging*
  • Intracranial Hypotension / physiopathology
  • Lymph Nodes / diagnostic imaging
  • Lymph Nodes / metabolism
  • Lymph Nodes / physiopathology
  • Lymphatic System / diagnostic imaging*
  • Lymphatic System / metabolism
  • Lymphatic System / physiopathology
  • Lymphatic Vessels / diagnostic imaging
  • Lymphatic Vessels / metabolism
  • Lymphatic Vessels / physiopathology
  • Lymphography
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Organometallic Compounds / administration & dosage
  • Parahippocampal Gyrus / diagnostic imaging
  • Parahippocampal Gyrus / metabolism
  • Parahippocampal Gyrus / physiopathology
  • Parenchymal Tissue / diagnostic imaging
  • Parenchymal Tissue / metabolism
  • Parenchymal Tissue / physiopathology
  • Pons / diagnostic imaging
  • Pons / metabolism
  • Pons / physiopathology
  • Prefrontal Cortex / diagnostic imaging
  • Prefrontal Cortex / metabolism
  • Prefrontal Cortex / physiopathology
  • Thalamus / diagnostic imaging
  • Thalamus / metabolism
  • Thalamus / physiopathology

Substances

  • Contrast Media
  • Organometallic Compounds
  • gadobutrol