title: Spectroscopic imaging of the pilocarpine model of human epilepsy suggests that early NAA reduction predicts epilepsy.
abstract: Reduced hippocampal N-acetyl aspartate (NAA) is commonly observed in patients with advanced, chronic temporal lobe epilepsy (TLE). It is unclear, however, whether an NAA deficit is also present during the clinically quiescent latent period that characterizes early TLE. This question has important implications for the use of MR spectroscopic imaging (MRSI) in the early identification of patients at risk for TLE. To determine whether NAA is diminished during the latent period, we obtained high-resolution (1)H spectroscopic imaging during the latent period of the rat pilocarpine model of human TLE. We used actively detuneable surface reception and volume transmission coils to enhance sensitivity and a semiautomated voxel shifting method to accurately position voxels within the hippocampi. During the latent period, 2 and 7 d following pilocarpine treatment, hippocampal NAA was significantly reduced by 27.5 +/- 6.9% (P < 0.001) and 17.3 +/- 6.9% (P < 0.001) at 2 and 7 d, respectively. Quantitative estimates of neuronal loss at 7 d (2.3 +/- 7.7% reduction; P = 0.58, not significant) demonstrate that the NAA deficit is not due to neuron loss and therefore likely represents metabolic impairment of hippocampal neurons during the latent phase. Therefore, spectroscopic imaging provides an early marker for metabolic dysfunction in this model of TLE.
authors.affiliation: Department of Radiology, Montefiore Medical Center, Bronx, New York 10467, USA. wgomes@montefiore.org
authors.forename: W A
authors.initials: WA
authors.lastname: Gomes
authors.forename: F A
authors.initials: FA
authors.lastname: Lado
authors.forename: N C
authors.initials: NC
authors.lastname: de Lanerolle
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: C
authors.initials: C
authors.lastname: Pan
authors.forename: H P
authors.initials: HP
authors.lastname: Hetherington
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D010862:Pilocarpine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D012815:Signal Processing, Computer-Assisted
chemical_list: D010862:Pilocarpine; D001224:Aspartic Acid; C000179:N-acetylaspartate