Magnetic resonance imaging profile of blood-brain barrier injury in patients with acute intracerebral hemorrhage

Abstract

Background: Spontaneous intracerebral hemorrhage (ICH) is associated with blood-brain barrier (BBB) injury, which is a poorly understood factor in ICH pathogenesis, potentially contributing to edema formation and perihematomal tissue injury. We aimed to assess and quantify BBB permeability following human spontaneous ICH using dynamic contrast-enhanced magnetic resonance imaging (DCE MRI). We also investigated whether hematoma size or location affected the amount of BBB leakage.

Methods and results: Twenty-five prospectively enrolled patients from the Diagnostic Accuracy of MRI in Spontaneous intracerebral Hemorrhage (DASH) study were examined using DCE MRI at 1 week after symptom onset. Contrast agent dynamics in the brain tissue and general tracer kinetic modeling were used to estimate the forward leakage rate (K(trans)) in regions of interest (ROI) in and surrounding the hematoma and in contralateral mirror-image locations (control ROI). In all patients BBB permeability was significantly increased in the brain tissue immediately adjacent to the hematoma, that is, the hematoma rim, compared to the contralateral mirror ROI (P<0.0001). Large hematomas (>30 mL) had higher K(trans) values than small hematomas (P<0.005). K(trans) values of lobar hemorrhages were significantly higher than the K(trans) values of deep hemorrhages (P<0.005), independent of hematoma volume. Higher K(trans) values were associated with larger edema volumes.

Conclusions: BBB leakage in the brain tissue immediately bordering the hematoma can be measured and quantified by DCE MRI in human ICH. BBB leakage at 1 week is greater in larger hematomas as well as in hematomas in lobar locations and is associated with larger edema volumes.

Keywords: blood–brain barrier; dynamic contrast‐enhanced MRI; intracerebral hemorrhage; magnetic resonance imaging; stroke.

Figure 1.

Gadolinium (Gd) concentration vs time graphs. Vascular input function (VIF) plot, data points (squares), and model fit for (A) representative lesion regions of interest (ROI) in the perihematomal rim and (B) mirror contralateral control ROI. Negligible (in the noise range) contrast material uptake can be seen in the ROI measurements in the control ROI in the hemisphere opposite from the hematoma.

Figure 2.

A, Lesion regions of interest (ROI) (red) surrounding the hematoma and control ROI (blue) on the contralateral side. B, Blood–brain barrier (BBB) permeability map (C) “hot spot” ROI (red) outlined on permeability map. Color coded K^trans values are within the range of 0.005 to 0.500 min⁻¹, purple being 0.005 min⁻¹, blue 0.075 min⁻¹, light blue 0.150 min⁻¹, green 0.250 min⁻¹, light green 0.325 min⁻¹, yellow 0.400 min⁻¹, and red 0.500 min⁻¹.

Figure 3.

Admission brain CT, 1‐day FLAIR MRI and 1 week color coded permeability maps of a patient with a lobar hematoma (A, B, C), a patient with a small basal ganglionic (deep) hematoma (D, E, F), and a patient with a large basal ganglionic (deep) hematoma (G, H, I). BBB disruption around the hematoma at 1 week after symptom onset is readily visible on the permeability maps in all 3 patients. Color coded K^trans values are as described in the legend of Figure 2. CT indicates computed tomography; FLAIR, fluid attenuated inversion recovery; MRI, magnetic resonance imaging; BBB, blood–brain barrier.

Figure 4.

K^trans values including all magnetic resonance imaging (MRI) slices through the hematoma, by hematoma size and location. A, Large hematomas (≥30 mL) had higher blood–brain barrier (BBB) permeability surrounding the hematoma (P<0.005), and a wider range than small hemorrhages. B, BBB permeability around lobar hemorrhages was higher than permeability around deep hemorrhages (P<0.005). BBB permeability around cerebellar hemorrhages tended to be more similar to the lobar hemorrhages (P=0.57) than the deep hemorrhages (P=0.09). In the box plot, central horizontal lines are the medians, edges of the boxes are Q1 and Q3, whiskers extend to minimum and maximum values.

Figure 5.

Edema volume vs blood–brain barrier (BBB) permeability. Mean K^trans and edema volume are shown for each patient. Higher K^trans is associated with larger edema volumes (A) on day 1 (ρ=0.62) and (B) at 1 week after intracerebral hemorrhage (ICH) onset (ρ=0.35).