Abstracts

Rationale: The centromedian nucleus (CM) of the thalamus is a potential target for therapeutic deep brain stimulation (DBS) in patients with Lennox-Gastaut syndrome (LGS). Current opinion within the DBS community is that the CM is not directly visualizable using structural MRI (Epilepsia, 2017; 58(S1):80-4). Pre-surgical targeting is instead performed indirectly using stereotactic atlas coordinates (Neuropsychiatr Dis Treat, 2017; 13:2607-19), potentially failing to accommodate for inter-patient variability in the size/location of the CM. We aimed to develop an imaging approach for visualizing the CM. Methods: Six patients with LGS (five females; mean age=27 years) consented to undergo CM-DBS. For each patient, a Magnetization-Prepared 2 Rapid Gradient-Echoes (MP2RAGE) sequence (Neuroimage, 2010; 49(2):1271-81) was acquired pre-surgically using a Siemens Skyra 3T MRI scanner, yielding three whole-brain volumes: two volumes acquired with different inversion times (INV1, INV2) and a bias-field corrected ‘unified’ volume (UNI) derived from the combination of INV1 and INV2. To highlight thalamic substructure, a novel ‘edge-enhanced’ MP2RAGE image was calculated by (i) processing the INV1 volume using automated edge detection (Sobel filtering), and (ii) summing together the INV1, Sobel-filtered INV1, and UNI volumes. The CM’s location was compared to a histologically-informed thalamic MRI atlas (Neuroimage, 2010; 49(3):2053-62) by spatially warping the atlas to each patient’s edge-enhanced MP2RAGE image using nonlinear deformation. Results: Results are displayed in Fig. 1. Several key thalamic substructures bordering the CM were visualizable on the edge-enhanced MP2RAGE (for reference, thalamic visualization achieved by standard T1-weighted imaging is also shown for one patient). The CM appeared as a small, oval-shaped area of medium signal intensity approximately 10 mm lateral to the midline and located (i) immediately anterior and superior to the level of the posterior commissure; (ii) inferior to a larger region of lower signal intensity consistent with the mediodorsal nucleus, and (ii) anterior to a larger region of lower signal intensity consistent with the pulvinar nucleus. This location showed good correspondence with the CM’s position as determined from the thalamic MRI atlas (Fig. 1). Conclusions: The CM can be visualized in patients with LGS using MRI at clinically available magnetic field strength (3T). We anticipate that improved visualization of individual patient anatomy will increase implantation accuracy and maximize therapeutic response, as demonstrated by recent DBS studies in patients with movement disorders (J Neurol Surg A, 2015; 76(3):181-9). Funding: National Health and Medical Research Council of Australia (NHMRC) project grant #1108881Lennox-Gastaut syndrome Foundation postdoctoral research fellowship