Authors :
Ning Hua, PhD – Boston Medical Center, BU Chobanian and Avedisian school of Medicine, Boston, MA USA
Lena Václavů, PhD – Leiden University Medical Center, Leiden, The Netherlands
Joseph Sisto, MPH – Boston Medical Center, BU Chobanian and Avedisian school of Medicine, Boston, MA USA
Shreeya Patel, High school student – Boston University RISE program/Del Norte High School
Leonie Petitclerc, PhD – Leiden University
Meher Juttukonda, PhD – Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
Mohammad Qureshi, MPH – Boston Medical Center, BU Chobanian and Avedisian school of Medicine, Boston, MA USA
Abrar Al-Faraj, MD – Boston Medical Center, BU Chobanian and Avedisian school of Medicine, Boston, MA USA
Maria Stefanidou, MD – Boston Medical Center, BU Chobanian and Avedisian school of Medicine, Boston, MA USA
Janine Barrett, RN, BSN – Boston Medical Center
Indrani Alagar, BA, MS – Boston University Chobanian and Avedisian School of Medicine
Sara Jacobellis, MD – Boston University/Boston Medical Center
Chad Farris, MD PhD – Boston Medical Center, BU Chobanian and Avedisian school of Medicine, Boston, MA USA
Osamu Sakai, MD PhD – MGB, Harvard University, Boston, MA USA
Lee Goldstein, MD, PhD – Boston Medical Center, BU Chobanian and Avedisian school of Medicine, Boston, MA USA
Sara Inati, PhD – National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland, USA
William Theodore, MD – National Institute of Neurological Disorders and Stroke, NIH
Bruce Rosen, MD, PhD – Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
Matthias van Osch, PhD – Leiden University Medical Center, Leiden, The Netherlands
Presenting Author: Myriam Abdennadher, MD – Boston Medical Center, BU Chobanian and Avedisian school of Medicine, Boston, MA USA
Rationale:
Although single post labeling delay (PLD) arterial spin labeling (ASL) MRI is widely available, multiple PLD ASL has shown better reliability of CBF measurements. To our knowledge, all previous studies utilized single PLD ASL with conflicting results. We aim to investigate distribution patterns of CBF in epilepsy, relative to healthy individuals, using multiple PLD ASL.
Methods:
All participants completed a questionnaire about MRI safety, seizure frequency and semiology, last time seizure, and current anti-seizure medications. Participants with active use of recreational substances (due to risk of affecting CBF), heart failure, and destructive brain lesions were excluded. We acquired a 30-minute Brain MRI including structural images with 3-D T1-weighted and fluid attenuated inversion recovery (FLAIR). We acquired a multiple-PLD ASL using Hadamard encoding and combining 9 pairs of labeling delays and PLDs. Quantification was performed using in-house software and analyzed using surface-based method. Normative values were generated in healthy volunteers and permitted calculation of absolute Z-scores in epilepsy participants. Study was approved by institutional review board. We obtained consent from all participants.
Results:
We recruited 15 healthy individuals (35.9 ± 9.5 years, 47% women) and 25 epilepsy (41.1 ± 10.5 years; 52% women) patients with 14 with drug-resistant epilepsy. Mean age at first seizure was 19.9 years (standard deviation 12.7 years). Presumed seizure focus was temporal in 18, frontal in 3, and parietal in 2. We found mesial temporal sclerosis in 9 (one had atrophy limited to hippocampus not involving the amygdala), focal cortical dysplasia in 2, heterotopias (adjacent to ipsilateral temporal horn) in 2, polymicrogyria in 1, and schizencephaly in1 (not included in group analysis). MRI lesions were ipsilateral to the seizure focus in all. In individual perfusion analysis, CBF Z-score surface maps showed lower (toward hypoperfusion) and higher (toward hyperperfusion) distribution relative to healthy subjects. In group analysis, epilepsy subjects had higher |Z-score| in most cortical regions compared to the healthy group, with extent varying from small areas limited to the presumed seizure focus, to regional, hemispheric, and even global (bilateral pattern). This pattern was not limited to drug-resistant epilepsy group.
Conclusions:
Our study showed interictal hypo- and hyper-perfusion, with variable extent of perfusion anomaly (focal to regional to global) in epilepsy patients. Our findings suggest that the interictal CBF has dynamic variability and may fluctuate between hypo- and hyper- perfusion. Multiple PLD perfusion measurements required longer acquisition time possibly capturing multiple “snapshots” of interictal brain activity. We speculate that these findings may reflect dynamic changes of interictal epileptiform discharges that our team is currently investigating.
Funding:
This work was funded by Boston University Clinical & Translational Science Institute 1UL1TR001430