Permeability of the windows of the brain: feasibility of dynamic contrast-enhanced MRI of the circumventricular organs
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Fluids and Barriers of the CNS Open Access
RESEARCH
Permeability of the windows of the brain: feasibility of dynamic contrast‑enhanced MRI of the circumventricular organs Inge C. M. Verheggen1,2,3*† , Joost J. A. de Jong2,4†, Martin P. J. van Boxtel1,2,3, Alida A. Postma2,4, Frans R. J. Verhey1,2,3, Jacobus F. A. Jansen2,4,5 and Walter H. Backes2,4,6
Abstract Background: Circumventricular 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. Methods: Twenty 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. Results: In 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. Conclusions: Current 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 Keywords: Circumventricular organs, Dynamic contrast-enhanced magnetic resonance imaging, Permeability, Pharmacokinetic modeling Background The circumventricular organs
*Correspondence: [email protected] † Inge C. M. Verheggen and Joost J. A. de Jong contributed equally to this work 1 Department of Psychiatry and Neuropsychology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands Full list of author information is available at the end of the article
The circumventricular organs (CVOs) are structures located adjacent to the third and fourth ventricles of the brain [1–3]. An important characteristic of these structures is that they have extensive and highly permeable capillaries that lack a blood–brain barrier (BBB). The vessels in the CVOs branch into a network of fenestrated capillaries with loosely connected astrocytic endfeet
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