Ronald I. Wolf
Complex partial seizures, often arising in the temporal lobe, are the most common etiology of medically intractable acquired epilepsy in adults, but seizure foci can be difficult to lateralize let alone localize. These patients typically undergo multimodality testing, including structural MRI, EEG, PET, fMRI and/or intracarotid amytal testing, and in some cases ictal or interictal SPECT and proton MR spectroscopy. When considering this project, hypometabolism on interictal [18F]-fluorodeoxyglucose PET (18FDG-PET) had been shown to contribute to seizure lateralization in temporal lobe epilepsy (TLE). Initial comparisons to interictal H215O-PET blood flow measurements showed that these were less successful in lateralizing seizures due to flow-metabolism uncoupling,1–3 but there was also evidence that coupling of flow and metabolism could be intact. Wu et al,4 for example, used DSC perfusion MRI to show decreased interictal rCBV (and increased ictal rCBV) in the mesial temporal lobe on the side of seizures, which correlated with 18FDG-PET predictions.
The intent of our work was to explore ASL perfusion MRI as a quantitative and completely noninvasive alternative for seizure lateralization in TLE as opposed to DSC perfusion MRI, which is semiquantitative and requires IV contrast administration as compared with 18FDG-PET, which requires IV radiotracer administration and has higher cost and less availability. Using an early multisection continuous ASL perfusion MRI approach,5 we found asymmetrically decreased interictal mesial temporal CBF in patients with TLE with lateralization of seizures correlating with 18FDG-PET hypometabolism, and also with hippocampal volumes and clinical evaluation. Global absolute CBF measurements were also decreased in seizure patients compared with controls. Close to the time of publication of our study, Liu et al6 compared a single-section PASL perfusion technique (FAIR-HASTE) to H215O-PET perfusion in patients with TLE, also showing interictal hypoperfusion on the side of seizures. Other studies confirm that coupling of flow and metabolism can be intact7–12 in this setting.
Perfusion imaging in seizure disorders like TLE has some challenges including small lesion volumes (also true for small subtle seizure foci associated with lesions such as focal cortical dysplasias), symmetric abnormalities such as bilateral mesial temporal sclerosis, and artifacts in mesial temporal or frontal regions due to the proximity of bone and air-containing structures. Innovations in implementation of ASL perfusion MRI address these challenges to an extent; for example, 3D background-suppressed pseudocontinuous ASL with GRASE or FSE readout strategies are now available with improved resolution and SNR as well as improved visualization of structures near the skull base.13–15 Analogous to strategies like ictal-postictal SPECT subtraction (SISCOM), coregistration of multiple modalities, including perfusion maps, can help in localizing subtle, previously undetected structural abnormalities,11,12,16—a promising application of state-of-the-art ASL perfusion methodology.
More challenging for MR perfusion techniques is ictal imaging, though this would be attractive for improved detection of lesional and nonlesional seizure foci. Ictal SPECT studies are better suited to this approach because the tracer can be injected as the patient begins a seizure and then scanned after the patient has recovered, a practice logistically difficult with MRI (though not impossible).12,17–19 In practice, the most likely clinical application for ictal MR perfusion imaging is in the acute or subacute setting for status epilepticus or other reversible disorders like eclampsia and post-CEA hyperperfusion syndrome.20,21