Permeability of the windows of the brain: feasibility of dynamic contrast-enhanced MRI of the circumventricular organs

Fluids and Barriers of the CNS

Frans R. J. Verhey¹  Inge C. M. Verheggen¹  Martin P. J. van Boxtel¹  Joost J. A. de Jong²  Alida A. Postma²  Jacobus F. A. Jansen³  Walter H. Backes⁴ 

[1] Department of Psychiatry and Neuropsychology, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands;School for Mental Health and Neuroscience (MHeNs), Maastricht University, Maastricht, The Netherlands;Alzheimer Center Limburg, Maastricht, The Netherlands;School for Mental Health and Neuroscience (MHeNs), Maastricht University, Maastricht, The Netherlands;Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands;School for Mental Health and Neuroscience (MHeNs), Maastricht University, Maastricht, The Netherlands;Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands;Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands;School for Mental Health and Neuroscience (MHeNs), Maastricht University, Maastricht, The Netherlands;Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands;School for Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands;

关键词: Circumventricular organs;    Dynamic contrast-enhanced magnetic resonance imaging;    Permeability;    Pharmacokinetic modeling;   

DOI  :  10.1186/s12987-020-00228-x

来源: Springer

【 摘 要 】

BackgroundCircumventricular organs (CVOs) are small structures without a blood–brain barrier surrounding the brain ventricles that serve homeostasic functions and facilitate communication between the blood, cerebrospinal fluid and brain. Secretory CVOs release peptides and sensory CVOs regulate signal transmission. However, pathogens may enter the brain through the CVOs and trigger neuroinflammation and neurodegeneration. We investigated the feasibility of dynamic contrast-enhanced (DCE) MRI to assess the CVO permeability characteristics in vivo, and expected significant contrast uptake in these regions, due to blood–brain barrier absence.MethodsTwenty healthy, middle-aged to older males underwent brain DCE MRI. Pharmacokinetic modeling was applied to contrast concentration time-courses of CVOs, and in reference to white and gray matter. We investigated whether a significant and positive transfer from blood to brain could be measured in the CVOs, and whether this differed between secretory and sensory CVOs or from normal-appearing brain matter.ResultsIn both the secretory and sensory CVOs, the transfer constants were significantly positive, and all secretory CVOs had significantly higher transfer than each sensory CVO. The transfer constants in both the secretory and sensory CVOs were higher than in the white and gray matter.ConclusionsCurrent measurements confirm the often-held assumption of highly permeable CVOs, of which the secretory types have the strongest blood-to-brain transfer. The current study suggests that DCE MRI could be a promising technique to further assess the function of the CVOs and how pathogens can potentially enter the brain via these structures.Trial registration: Netherlands Trial Register number: NL6358, date of registration: 2017-03-24

【 授权许可】

CC BY