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

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.

SUBMITTER: Verheggen ICM

PROVIDER: S-EPMC7594295 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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

Verheggen Inge C M ICM de Jong Joost J A JJA van Boxtel Martin P J MPJ Postma Alida A AA Verhey Frans R J FRJ Jansen Jacobus F A JFA Backes Walter H WH

Fluids and barriers of the CNS 20201028 1

<h4>Background</h4>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 ...[more]

PMID: 33115484

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Project description:Background and purposePathological changes in the intracranial aneurysm wall may lead to increases in its permeability; however the clinical significance of such changes has not been explored. The purpose of this pilot study was to quantify intracranial aneurysm wall permeability (K(trans), VL) to contrast agent as a measure of aneurysm rupture risk and compare these parameters against other established measures of rupture risk. We hypothesized K(trans) would be associated with intracranial aneurysm rupture risk as defined by various anatomic, imaging, and clinical risk factors.Materials and methodsTwenty-seven unruptured intracranial aneurysms in 23 patients were imaged with dynamic contrast-enhanced MR imaging, and wall permeability parameters (K(trans), VL) were measured in regions adjacent to the aneurysm wall and along the paired control MCA by 2 blinded observers. K(trans) and VL were evaluated as markers of rupture risk by comparing them against established clinical (symptomatic lesions) and anatomic (size, location, morphology, multiplicity) risk metrics.ResultsInterobserver agreement was strong as shown in regression analysis (R(2) > 0.84) and intraclass correlation (intraclass correlation coefficient >0.92), indicating that the K(trans) can be reliably assessed clinically. All intracranial aneurysms had a pronounced increase in wall permeability compared with the paired healthy MCA (P < .001). Regression analysis demonstrated a significant trend toward an increased K(trans) with increasing aneurysm size (P < .001). Logistic regression showed that K(trans) also predicted risk in anatomic (P = .02) and combined anatomic/clinical (P = .03) groups independent of size.ConclusionsWe report the first evidence of dynamic contrast-enhanced MR imaging-modeled contrast permeability in intracranial aneurysms. We found that contrast agent permeability across the aneurysm wall correlated significantly with both aneurysm size and size-independent anatomic risk factors. In addition, K(trans) was a significant and size-independent predictor of morphologically and clinically defined high-risk aneurysms.

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Dataset Information

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

Publications

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

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