Application of Blood-Brain Barrier Permeability Imaging in Global Cerebral Edema

Abstract

Background and purpose: Blood-brain barrier permeability is not routinely evaluated in the clinical setting. Global cerebral edema occurs after SAH and is associated with BBB disruption. Detection of global cerebral edema using current imaging techniques is challenging. Our purpose was to apply blood-brain barrier permeability imaging in patients with global cerebral edema by using extended CT perfusion.

Materials and methods: Patients with SAH underwent CTP in the early phase after aneurysmal rupture (days 0-3) and were classified as having global cerebral edema or nonglobal cerebral edema using established noncontrast CT criteria. CTP data were postprocessed into blood-brain barrier permeability quantitative maps of PS (permeability surface-area product), K(trans) (volume transfer constant from blood plasma to extravascular extracellular space), Kep (washout rate constant of the contrast agent from extravascular extracellular space to intravascular space), VE (extravascular extracellular space volume per unit of tissue volume), VP (plasmatic volume per unit of tissue volume), and F (plasma flow) by using Olea Sphere software. Mean values were compared using t tests.

Results: Twenty-two patients were included in the analysis. Kep (1.32 versus 1.52, P < .0001), K(trans) (0.15 versus 0.19, P < .0001), VP (0.51 versus 0.57, P = .0007), and F (1176 versus 1329, P = .0001) were decreased in global cerebral edema compared with nonglobal cerebral edema while VE (0.81 versus 0.39, P < .0001) was increased.

Conclusions: Extended CTP was used to evaluate blood-brain barrier permeability in patients with SAH with and without global cerebral edema. Kep is an important indicator of altered blood-brain barrier permeability in patients with decreased blood flow, as Kep is flow-independent. Further study of blood-brain barrier permeability is needed to improve diagnosis and monitoring of global cerebral edema.

Fig 1.

Cytoarchitecture of the BBB and schematic representation of BBBP parameters derived from extended CTP. A, Non-GCE. At baseline, the BBB is composed of endothelial cells connected by tight junctions (as opposed to fenestrated endothelium outside of the CNS), the basement membrane, and the astrocyte processes. B, In the setting of GCE, there is an increase in EES as reflected by increased VE and decreased K_ep, indicating increased BBBP (indicated in the drawing by a more porous basement membrane and tight junctions). PS is also elevated, indicating increased BBBP. Importantly, K_ep is independent of F. In GCE, K_ep is the most reliable parameter to evaluate BBBP in the setting of flow impairment.

Fig 2.

BBBP quantitative maps of K_ep, K^trans, and VE in a representative patient from the GCE group (top panel) and a representative patient from the non-GCE group (bottom panel). NCCT images demonstrate loss of gray-white matter differentiation and presence of sulcal effacement in the patient with GCE. Corresponding BBBP maps reveal decreased K_ep, slightly decreased K^trans, and increased VE in the same patient compared with the patient without GCE.