ro-16-0154 and Chronic-Disease

Cerebral extraction of diffusively distributed substances like oxygen has been suggested to change according to the cerebral blood flow (CBF) and status of the microvasculature. The relationships between the cerebral extraction of diffusively distributed lipophilic tracers and the severity of cerebral ischemia has not yet been clarified. In the present study, we attempted to elucidate the association between the extraction fraction of the lipophilic tracer I-123 iomazenil (IMZ) (IMZ-EF) and the oxygen extraction fraction (OEF) derived from O-15 PET in patients with chronic steno-occlusive disease of internal carotid artery (ICA) or middle cerebral artery (MCA).. Seven patients with unilateral chronic severe stenosis or occlusion of the middle cerebral/internal cerebral artery were prospectively recruited for this study. All the patients underwent both O-15 PET and quantitative I-123 IMZ SPECT. Parametric images derived from the PET and SPECT scans were anatomically normalized and evaluated by automated image analysis based on the volume-of-interest template.. The asymmetry index (AI) of IMZ-EF was shown to be significantly correlated with the AI of OEF (r = 0.562, P < 0.001) in the internal carotid artery perfusion area. Strong and significant correlation between the AI of the influx rate constant K1 of IMZ and the AI of the cerebral metabolic rate of oxygen (r = 0.552, P = 0.001) was clarified.. Our results suggested that the transportation efficiency of I-123 IMZ into the brain tissue was an indicator for evaluating severity of cerebral ischemia in patients with chronic steno-occlusive disease of ICA or MCA. Cerebral metabolic state can possibly be estimated by I-123 IMZ SPECT without cyclotron.

Topics: Aged; Brain Ischemia; Cerebrovascular Circulation; Chronic Disease; Female; Flumazenil; Humans; Iodine Radioisotopes; Male

Clinical studies indicate that patients with acute schizophrenia may benefit from benzodiazepine treatment. Therefore we investigated the benzodiazepine receptor distribution and diazepam binding in 20 patients with DSM-III schizophrenia using single photon emission computed tomography (SPECT) with iomazenil as the ligand. In each patient, two SPECT images were obtained: SPECT 1 was obtained 2 h after intravenous injection of 200 MBq I-123-iomazenil. Following SPECT 1, patients received 10 mg diazepam intravenously. Twenty min later, SPECT 2 was started. The highest iomazenil uptake was found in the occipital cortex followed by the frontal and temporal cortices. Baseline iomazenil uptake in the medial frontal cortex was significantly (P < 0.05) correlated with the BPRS total score (r = 0.46). Diazepam injection led to a significant activity decrease in iomazenil binding which was greatest in the frontal regions of interest. With respect to the medial frontal cortex, this effect was significantly (P < 0.05) more pronounced in patients with a remitting than a chronic course of the disorder. These findings suggest that changes of the benzodiazepine receptor system in the frontal cortex may be associated with severity and chronicity of schizophrenia.

Topics: Adult; Benzodiazepines; Binding Sites; Chronic Disease; Diazepam; Flumazenil; Frontal Lobe; Growth Hormone; Humans; Hydrocortisone; Occipital Lobe; Receptors, GABA-A; Schizophrenia; Temporal Lobe; Tomography, Emission-Computed, Single-Photon

To investigate the utility of neuroreceptor imaging in ischaemic cerebrovascular disorders, dual-tracer autoradiography using 99Tcm-hexamethylpropyleneamine oxime (HMPAO) for the evaluation of cerebral blood flow and 125I-iomazenil for the evaluation of central-type benzodiazepine receptor density was performed in experimental brain ischaemia created by occlusion of the unilateral middle cerebral artery of the rat. In the acute phase of ischaemia, 125I-iomazenil accumulation showed less of a decrease than 99Tcm-HMPAO in the cerebral cortex of the lateral convexity and in the lateral segment of the caudate putamen in the lesioned cerebral hemisphere. In the sub-acute phase, both 125I-iomazenil and 99Tcm-HMPAO accumulation increased in the lesion compared with the acute phase. A large accumulation of 99Tcm-HMPAO and 125I-iomazenil in the lesion was considered to be due to luxury perfusion and penetration of 125I-iomazenil hydrophilic metabolites from the blood into the brain tissue through the altered blood-brain barrier. In the chronic phase, 125I-iomazenil accumulation showed a more marked decrease than 99Tcm-HMPAO in the lesion. Moreover, the ipsilateral thalamus, which is remote from the lesion, revealed decreased 125I-iomazenil accumulation despite normal 99Tcm-HMPAO accumulation. Since the central-type benzodiazepine receptors are principally located not on the glial cells but on the neurons, the receptor density may exhibit a change that parallels the neuron density. These results suggest that central-type benzodiazepine receptor imaging is useful for the evaluation of neuronal damage when used in conjunction with brain perfusion imaging in ischaemic cerebrovascular disorders, except in the sub-acute phase.

Topics: Acute Disease; Animals; Autoradiography; Brain; Brain Ischemia; Chronic Disease; Flumazenil; Functional Laterality; Iodine Radioisotopes; Male; Organ Specificity; Organotechnetium Compounds; Oximes; Radionuclide Imaging; Rats; Rats, Inbred Strains; Receptors, GABA-A; Technetium Tc 99m Exametazime

Double tracer autoradiography was performed to measure regional cerebral blood flow (rCBF) and the binding of central type benzodiazepine receptors (BZR) in infarction by means of permanent occlusion of the unilateral middle cerebral arteries (MCA) in rat. Iodine-125 Iomazenil and 99mTc-HMPAO was used to label BZR and rCBF respectively. In the chronic phase of infarction 21 to 28 days after occlusion (5 rats), rCBF in the left MCA territory was decreased to 62% of the sham control (4 rats), while BZR was more decreased to 45% of the control. In remote areas from the MCA lesion, the ipsilateral thalamus showed 28% decrease of BZR as compared to the control, though the decrease of rCBF was not significant. Iomazenil distribution may represent neuron density or BZR density on a neuron, since central type BZR is reported to be located on neurons. These results suggest that central type BZR imaging is more useful tool for the evaluation of brain tissue viability and transneuronal degeneration than rCBF imaging in brain infarction.

Topics: Animals; Autoradiography; Brain; Cerebral Infarction; Cerebrovascular Circulation; Chronic Disease; Flumazenil; Iodine Radioisotopes; Male; Organotechnetium Compounds; Oximes; Radionuclide Imaging; Rats; Rats, Inbred Strains; Receptors, GABA-A; Technetium Tc 99m Exametazime