Cerebral Blood Flow with multi-delay Arterial Spin Labeling MRI Reveals Interictal Hypo- and Hyper-perfusion in epilepsy: A Proof of Concept

Abstract Background and Purpose Interictal cerebral blood flow (CBF) may be useful for seizure focus localization. However, its accuracy is debatable. Studies suggested interictal hypoperfusion at the seizure focus, yet others suggested hyperperfusion. This study aims to investigate the patterns of interictal perfusion in epilepsy subjects compared to healthy controls using multiple labeling-delays arterial spin labeling MRI, and to explore the accuracy of perfusion estimation using single post-labeling delay arterial-spin labeling MRI by comparing it to multiple post-labeling delays arterial-spin labeling MRI. Materials and Methods We analyzed CBF in 40 participants, 15 healthy (35.9 ± 9.5 years, 47% women) and 25 epilepsy (41.1 ± 10.5 years; 52% women). We acquired a multiple post-labeling delays arterial spin labeling MRI using Hadamard encoding, and structural MRI. Perfusion quantification was performed using in-house software and analyzed using surface-based method. Z-scores of CBF and its absolute value (|Z-score|) were calculated to evaluate abnormal perfusion. Results Brain perfusion showed interictal hypo- and/or hyper-perfusion in epilepsy compared to healthy participants involving focal to whole brain alterations. Epilepsy subjects had higher |Z-score| in most cortical regions compared to the healthy group. CBF generated from single post-labeling delay arterial-spin labeling MRI correlated with ones from multiple post-labeling delays in most cortical regions, yet the level of correlation was affected by regional arterial transit time and the labeling scheme. In regions with shorter arterial transit time, correlation peaked at shorter post-labeling delay (1300ms); whereas in regions with longer arterial transit time, correlation peaked at longer post-labeling delay (2250ms). Conclusions Our findings suggest that the interictal CBF may fluctuate between hypo- and hyper-perfusion, and the involvement of brain regions may extend well beyond the seizure focus. Additionally, while single-post-labeling delay is efficient and clinically feasible, the accuracy of its assessment of perfusion depends on brain regions and the labeling scheme. SUMMARY STATEMENT We observed interictal hypo-/hyper-perfusion, possibly extending beyond the seizure focus. Caution is warranted when interpreting single-post-labeling-delay perfusion MRI in epilepsy, as its reliability varies by brain region and labeling scheme. Key Results Epilepsy subjects showed larger fluctuation of CBF, yet the fluctuation may happen in either direction: hypo- or hyper-perfusion. The extent of fluctuation can be focal, regional, hemispheric, or global. CBF derived from single-PLD MRI largely correlates with the ones derived from more reliable multi-PLD method. However, the level of correlation varies spatially (i.e., brain regions) and temporally (i.e., different labeling and post-labeling schemes), and may be explained by regional variability of arterial transit times.