Distinct cerebral cortical perfusion patterns in idiopathic normal-pressure hydrocephalus

Abstract

The aims of the study are to evaluate idiopathic normal-pressure hydrocephalus (INPH)-related cerebral blood flow (CBF) abnormalities and to investigate their relation to cortical thickness in INPH patients. We investigated cortical CBF utilizing surface-based early-phase ¹⁸ F-florbetaben (E-FBB) PET analysis in two groups: INPH patients and healthy controls. All 39 INPH patients and 20 healthy controls were imaged with MRI, including three-dimensional volumetric images, for automated surface-based cortical thickness analysis across the entire brain. A subgroup with 37 participants (22 INPH patients and 15 healthy controls) that also underwent ¹⁸ F-fluorodeoxyglucose (FDG) PET imaging was further analyzed. Compared with age- and gender-matched healthy controls, INPH patients showed statistically significant hyperperfusion in the high convexity of the frontal and parietal cortical regions. Importantly, within the INPH group, increased perfusion correlated with cortical thickening in these regions. Additionally, significant hypoperfusion mainly in the ventrolateral frontal cortex, supramarginal gyrus, and temporal cortical regions was observed in the INPH group relative to the control group. However, this hypoperfusion was not associated with cortical thinning. A subgroup analysis of participants that also underwent FDG PET imaging showed that increased (or decreased) cerebral perfusion was associated with increased (or decreased) glucose metabolism in INPH. A distinctive regional relationship between cerebral cortical perfusion and cortical thickness was shown in INPH patients. Our findings suggest distinct pathophysiologic mechanisms of hyperperfusion and hypoperfusion in INPH patients.

Keywords: cerebral blood flow; idiopathic normal-pressure hydrocephalus; magnetic resonance imaging; positron emission tomography.

FIGURE 1

E‐FBB mean images of participant groups. Surface projections are presented for healthy controls and INPH patients. E‐FBB, early‐phase ¹⁸F‐florbetaben; INPH, idiopathic normal‐pressure hydrocephalus

FIGURE 2

Group differences in E‐FBB and cortical thickness. (a) T‐maps showing the results of cortical surface‐based E‐FBB PET analyses. Showing lower E‐FBB uptake in INPH patients when compared to healthy controls and higher E‐FBB uptake in INPH patients when compared to healthy controls (p <.05, corrected for multiple comparisons with false discovery rate). Mean (b) E‐FBB SUVR and (c) cortical thickness values for the brain regions with significant clusters obtained on the cortical surface‐based E‐FBB PET analyses in A. In clusters of higher CBF in INPH patients, INPH patients, when compared with healthy controls, showed a statistically significant increase in the average E‐FBB SUVR and cortical thickness values. In clusters of lower CBF in INPH patients, INPH patients, when compared with healthy controls, showed a statistically significant decrease only in the average E‐FBB SUVR values. See also Figure S2 for comparison between the L‐FBB‐positive and L‐FBB‐negative INPH cases in the average E‐FBB SUVR and cortical thickness for these brain regions. CBF, cerebral blood flow; E‐FBB, early‐phase ¹⁸F‐florbetaben; INPH, idiopathic normal‐pressure hydrocephalus; L‐FBB, late‐phase ¹⁸F‐florbetaben; SUVR, standardized uptake value ratio. *p <.05; **p <.01; ***p <.001

FIGURE 3

Correlations in INPH patients between mean E‐FBB SUVR and cortical thickness values for the brain regions with significant clusters obtained on the cortical surface‐based E‐FBB PET analyses in Figure 2a. In the INPH group, the average cortical thickness correlated with the average E‐FBB SUVR positively in clusters of higher CBF in INPH patients. CBF, cerebral blood flow; E‐FBB, early‐phase ¹⁸F‐florbetaben; INPH, idiopathic normal‐pressure hydrocephalus; SUVR, standardized uptake value ratio

FIGURE 4

Mean FDG SUVR values for the brain regions with significant clusters obtained on the cortical surface‐based E‐FBB PET analyses in Figure 2a. In clusters of higher CBF in INPH patients, INPH patients, when compared with healthy controls, showed a statistically significant increase in average FDG SUVR values. In clusters of lower CBF in INPH patients, INPH patients, when compared with healthy controls, showed a statistically significant decrease in the average FDG SUVR values. CBF, cerebral blood flow; E‐FBB, early‐phase ¹⁸F‐florbetaben; FDG, ¹⁸F‐fluorodeoxyglucose; SUVR, standardized uptake value ratio. *p <.05; **p <.01; ***p <.001