ro-16-0154 and Brain-Injuries

[(123)I] iomazenil (IMZ) single photon emission computed tomography (SPECT) has been reported to be a useful marker of neuronal integrity. We evaluated cortical damage following traumatic brain injury (TBI) with IMZ SPECT at the acute stage. After conventional therapy for a cranial trauma, an IMZ SPECT re-evaluation was performed at the chronic stage. A reduction in IMZ uptake in the location of cerebral contusions was observed during the TBI acute phase; however, images of IMZ SPECT obtained during the chronic phase showed that areas with decreased IMZ distribution were remarkably reduced compared with those obtained during the acute phase. As a result of in vivo microdialysis study, the extracellular levels of glutamate in the cortex, where decreased IMZ distribution was shown during the acute phase, were increased during the 168-h monitoring period. During the chronic phase, IMZ uptake in the region with the microdialysis probes was recovered. The results suggest that this reduction in IMZ uptake might not be a sign of irreversible tissue damage in TBI.

Topics: Brain Injuries; Cerebral Cortex; Female; Flumazenil; Humans; Middle Aged; Time Factors; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

In patients with higher brain dysfunction (HBD) after mild traumatic brain injury (MTBI), diagnostic imaging of cortical neuron loss in the frontal lobes was studied using SPECT with (123)I-iomazenil (IMZ), as a radioligand for central benzodiazepine receptor (BZR). Statistical imaging analysis using three-dimensional stereotactic surface projections (3D-SSP) for (123)I-IMZ SPECT was performed in 17 patients. In all patients with HBD defined by neuropsychological tests, cortical neuron loss was indicated in the bilateral medial frontal lobes in 14 patients (83 %). A comparison between the group of 17 patients and the normal database demonstrated common areas of cortical neuron loss in the bilateral medial frontal lobes involving the medial frontal gyrus (MFG) and the anterior cingulate gyrus (ACG). In an assessment of cortical neuron loss in the frontal medial cortex using the stereotactic extraction estimation (SEE) method (level 3), significant cortical neuron loss was observed within bilateral MFG in 9 patients and unilateral MFG in 4, and bilateral ACG in 12 and unilateral ACG in 3. Fourteen patients showed significant cortical neuron loss in bilateral MFG or ACG. In patients with MTBI, HBD seemed to correlate with selective cortical neuron loss within the bilateral MFG or ACG where the responsible lesion could be. 3D-SSP and SEE level 3 analysis for (123)I-IMZ SPECT could be valuable for diagnostic imaging of HBD after MTBI.

Topics: Adult; Aged; Brain; Brain Injuries; Brain Mapping; Cell Death; Female; Flumazenil; Humans; Male; Middle Aged; Neurons; Tomography, Emission-Computed, Single-Photon

Traumatic brain injuries demonstrate various symptoms, including the disturbance of higher brain function, which is not visualized as a morphological lesion on magnetic resonance (MR) imaging. We examined the use of iomazenil single photon emission computed tomography (SPECT) for patients with traumatic brain injury and evaluated its diagnostic value. The study population included patients who were admitted to our hospital for traumatic brain injuries. All patients survived and were discharged from our hospital. MR imaging and iomazenil SPECT were examined during the acute and/or chronic phases. MR images were acquired using a 1.5-T clinical instrument. The T1- and T2-weighted and fluid-attenuated inversion recovery (FLAIR) axial images were evaluated. SPECT images were acquired using a multi-detector SPECT machine 3 h after the intravenous injection of 740 MBq of iomazenil. Axial, statistically analyzed images and stereotactic extraction estimation images were reconstructed and evaluated statistically based on the Z-score for each cerebral cortex. Iomazenil SPECT showed various lesions that were not demonstrated by MR imaging. Some clinical symptoms correlated with the iomazenil SPECT findings. Iomazenil SPECT is thus considered to be valuable for evaluating both brain lesions and the brain function after traumatic brain injury.

Topics: Adolescent; Aged; Brain Injuries; Brain Mapping; Flumazenil; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Tomography, Emission-Computed, Single-Photon

We evaluated cortical damages following traumatic brain injury (TBI) in the acute phase with [(123)I] iomazenil (IMZ) single photon emission computed tomography (SPECT). In all, 12 patients with cerebral contusion following TBI were recruited. All patients underwent IMZ SPECT within 1 week after TBI. To investigate the changes in distribution of IMZ in the cortex in the chronic phase, after conventional treatment, patients underwent IMZ SPECT again. A decrease in the accumulation of radioligand for the central benzodiazepine receptor in the cortex corresponding to the contusion revealed with computed tomography (CT) scans and magnetic resonance imaging (MRI) were shown on IMZ SPECT in the acute phase in all patients. In 9 of 12 patients (75%), images of IMZ SPECT obtained in the chronic phase of TBI showed that areas with a decreased distribution of IMZ were remarkably reduced in comparison with those obtained in the acute phase. Both CT scans and MRI showed a normal appearance of the cortex morphologically, where the binding potential of IMZ recovered in the chronic phase. Reduced binding potential of radioligand for the central benzodiazepine receptor is considered to be an irreversible reaction; however, in this study, IMZ accumulation in the cortex following TBI was recovered in the chronic phase in several patients. [(123)I] iomazenil SPECT may have a potential to disclose a reversible vulnerability of neurons following TBI.

Topics: Adult; Aged; Brain; Brain Injuries; Cell Survival; Female; Flumazenil; Humans; Iodine Radioisotopes; Male; Middle Aged; Neurons; Receptors, GABA-A; Tomography, Emission-Computed, Single-Photon

In many brain disorders reduced binding of central benzodiazepine receptor ligands indicates irreversible neuronal damage. The data presented by Koizumi et al (2010) demonstrate that this is not the case in traumatic brain injury suggesting different pathogenetic mechanisms leading to tissue damage. The proof for this hypothesis requires further studies that should also consider thresholds of ligand binding as indicators of irreversible damage.

Topics: Brain Injuries; Flumazenil; Humans; Iodine Radioisotopes; Neurons; Receptors, GABA-A