[Functional MRI employing diazepam; a proposal of neuropharmacological fMRI]

Employing the active benzodiazepine receptor (BZR) ligands, we have used BOLD fMRI to elucidate the effects of these drugs on brain function. The sequential MRI was performed with a 1.5T clinical scanner (Philips GYROSCAN) using a FLASH sequence with the following parameters: TR/TE, 100/45 msec; flip angle, 25 degrees; matrix size, 128*128; 2 averages; for 64 image acquisitions in 32 min. First, 2 mg of diazepam was administrated intravenously at the beginning of the 5th, 15th, 25th, and 35th acquisitions. Then, flumazenil was administrated at the beginning of the 45th (0.2 mg) and 55th (0.3 mg) acquisitions in order to reverse the effect of diazepam. Data processing was made employing Akaike Information Criterion to detect if there were intensity changes after the medication among the trends of intensity changes. Diazepam administration decreased the intensity for a while and flumazenil increased one. In the case of the left frontal glioma with focal epileptogenicity, intensity changes were detected around the tumor. Since the neuronal function consists of the trans-neuronal communications employing neurotransmitters, the result on the modulation of this passage depends on the neuronal function related to the transmitter: gamma-amino butyric acid (GABA) in this instance for the effects of these medications to epilepsy. The change in the local blood flow is the result of the local neuronal activity. Therefore, we speculate that this neuropharmacological functional MR image may reflect the neuronal function related to the GABAegic neurotransmitter system. In addition to elucidating basic neurotransmitter function mechanisms, we believe this technique may have clinical utility in the pre-surgical evaluation of patients with intractable seizure disorders. In this respect, this paper presents a new spectrum of fMRI that is capable to study a part of neurotransmitter function employing the BZR ligands, reversing the effect of the agonist with the competitive antagonist, for the first experience, to propose the neuropharmacological functional MR images to have clinical utility in patients with intractable epilepsy in the interictal state.