Yasuomi Ouchi

Brain functional activity during gait in normal subjects : a SPECT study

The purpose of this study was to evaluate changes in brain activity during voluntary walking in normal subjects using technetium-99m-hexamethyl-propyleneamine oxime single photon emission computed tomography. This study included 14 normal subjects. Statistical parametric mapping analysis revealed that the supplementary motor area, medial primary sensorimotor area, the striatum, the cerebellar vermis and the visual cortex were activated. These results suggested that the cerebral cortices controlling motor functions, visual cortex, basal ganglia and the cerebellum might be involved in the bipedal locomotor activities in humans.

Altered energy metabolism in Alzheimer's disease

To evaluate the energy metabolic status of Alzheimers disease, we examined the cerebral arteriovenous differences of glucose, oxygen, lactate, pyruvate, ketone bodies, and free fatty acids and N-isopropyl-p-(123I) iodoamphetamine (IMP) single-photon emission computed tomography in 5 patients with Alzheimers disease (4 male and 1 female patients; mean age of 64.80 +/- 8.47 years). Compared with 5 age matched normal control subjects (4 males and 1 female; mean age of 63.20 +/- 10.76 years), the patients showed significantly decreased regional cerebral blood flow only in the parietotemporal region. The global cerebral glucose metabolic rate (CMRGlu) had significantly low value, whereas the global cerebral oxygen metabolic rate (CMRO2) was not changed. The metabolic ratio (CMRO2/CMRGlu) was significantly elevated to 9.73 in the patients with Alzheimers disease, compared with 5.50 in the normal controls. The cerebral metabolic rates of ketone bodies and free fatty acids were unchanged. The cerebral pyruvate output was significantly decreased. The cerebral lactate output became negative, but the decrease did not reach statistical significance. We concluded that the markedly elevated metabolic ratio suggests an altered energy metabolism in Alzheimers disease.

Scopolamine abolishes cerebral blood flow response to somatosensory stimulation in anesthetized cats: PET study

The effect of the cholinergic blocker, scopolamine on the cerebral blood flow (CBF) response to vibrotactile stimulation of a fore paw was studied using high-resolution positron emission tomography and H2 15O in 5 pentobarbital-anesthetized cats. Before scopolamine injection, the CBF response to the stimulation was found in the contralateral somatosensory cortex (mean ratio (contralateral/ipsilateral) control: stimulated 1.02 +/- 0.02: 1.17 +/- 0.05; P < 0.01). After intravenous injection of scopolamine (0.35 mg/kg), the CBF response was abolished. However, the cerebral metabolic rate of glucose (CMRGlu) response to the same stimulation was unchanged after scopolamine injection in the same cats. We concluded that scopolamine abolishes the CBF response but not neuronal response to stimulation. We suggest that cholinergic mechanisms may play an important role for mediating CBF coupling to neuronal activity during physiological stimulation.

Corpus callosum atrophy in amyotrophic lateral sclerosis

Recent studies have suggested widespread involvement of the cerebral regions other than the primary motor cortex in amyotrophic lateral sclerosis. To investigate atrophy of the corpus callosum as a measure of cerebral pathology, we studied 25 right-handed patients with sporadic amyotrophic lateral sclerosis using magnetic resonance imaging. Five patients had cognitive decline or emotional and personality changes. The ratios of mid-sagittal corpus callosum areas to the midline internal skull surface area on T1-weighted images were analysed. Compared with 25 age- and sex-matched right-handed control subjects, the patients had significantly decreased callosal/skull area ratio, with anterior predominance of the degree of atrophy. The patients with cognitive decline or psychiatric symptoms had substantial atrophy of the anterior fourth of the corpus callosum. These findings suggest that atrophy of the corpus callosum, especially in the anterior half, is present in amyotrophic lateral sclerosis, and that severe atrophy in the anterior fourth is associated with cognitive decline and psychiatric symptoms. Callosal atrophy may reflect the widespread distribution of pathological changes in the cerebral cortex, which are accentuated in the frontal cortex.

Cholinergic Projection from the Basal Forebrain and Cerebral Glucose Metabolism in Rats: A Dynamic PET Study

To investigate the influence of cholinergic projections from the basal forebrain on cerebral cortex metabolism, we evaluated the cerebral metabolic rate of glucose (CMRGlu) after selective inhibition of cholinergic neurons in the rat basal forebrain using the pyruvate dehydrogenase complex inhibitor 3-bromopyruvic acid (BPA), and compared the results with those obtained after lesioning the basal forebrain with ibotenic acid, as well as with those from a sham-operated control group. CMRGlu was measured using positron emission tomography (PET) with [18F]-2-fluoro-2-deoxy-D-glucose (FDG). Three days after surgery, CMRGlu and k3 (phosphorylation of FDG) were reduced similarly in the frontal cortex on the BPA-injected side and in the ibotenic acid-treated group, whereas K1 (transport rate of FDG from the plasma to brain) showed no marked changes. At 3 weeks postoperatively, the CMRGlu and k3 of the frontal cortex in both groups recovered to levels similar to those of the sham-operated group. The main difference between the BPA and ibotenic acid groups was that CMRGlu showed mild reduction on the side contralateral to the operation in the former, while such reduction was confined to the ipsilateral hemisphere in the latter. The present results indicate that the cholinergic system in the basal forebrain regulates cerebral cortex glucose metabolism through direct excitation of cortical neurons.

Callosal atrophy in patients with lacunar infarction and extensive leukoaraiosis. An indicator of cognitive impairment.

It is unclear why only some patients with lacunar infarction and radiological evidence of diffuse white matter abnormalities have dementia. The purpose of this study is to investigate the value of callosal atrophy as an indicator of cognitive impairment. Methods We used magnetic resonance imaging to evaluate 11 right-handed male patients with lacunar infarction and extensive white matter hypodensities on computed tomography (8 with dementia and 3 without dementia). The midsagittal corpus callosum area on T1-weighted images was compared with the IQ determined by the Wechsler Adult Intelligence Scale. The relation between these parameters and cerebral oxygen metabolism measured with positron emission tomography was also evaluated in the 8 patients with dementia. Results All patients showed diffuse high-intensity areas in the bilateral hemispheric white matter on T2-weighted images. Compared with 19 age-and sex-matched right-handed normal control subjects, the patients had a significantly smaller callosal area. The severity of callosal atrophy, which varied from mild to severe, was significantly related to the total IQ. In the 8 demented patients, the total callosal area was significantly correlated with the mean level of oxygen metabolism in the cerebral white matter. Conclusions In patients with lacunar infarction and diffuse white matter abnormalities, the presence of callosal atrophy may indicate cognitive impairment. Callosal atrophy may reflect the severity and extent of white matter damage associated with a decrease in oxygen metabolism, which may determine the severity of intellectual decline.

Focal Cortical Blood Flow Activation Is Regulated by Intrinsic Cortical Cholinergic Neurons

We evaluated the cholinergic mechanism underlying focal cortical vascular response to neuronal activation, using positron emission tomography for use on animals to measure cerebral blood flow and glucose metabolism activation upon vibrotactile stimulation in cats. Bromopyruvate, which blocks acetylcholine synthesis through inhibition of the production of acetyl CoA, was injected into the cerebral cortex and basal forebrain as well as the sphenopalatine ganglion, all of which have been confirmed to supply cholinergic terminals to the cerebral cortex. Although glucose metabolism was preserved, indicating that the neuronal activities were enhanced, cerebral blood flow increase during cortical neuronal activation was abolished by bromopyruvate injection into only the cerebral cortex and not other cholinergic systems. We conclude that the cholinergic intrinsic neurons control the focal cerebral blood flow increase in response to neuronal activation.

Hemodilution improves cerebral hemodynamics in internal carotid artery occlusion.

Background and Purpose Hemodilution may be a useful form of therapy for patients with carotid occlusive disease and hemodynamic ischemia. Accordingly, we evaluated the effects of hemodilution on cerebral hemodynamics and oxygen metabolism in patients with carotid artery occlusion. Methods Using positron emission tomography, we analyzed regional cerebral blood flow, oxygen extraction fraction, oxygen metabolic rate, and blood volume before and after isovolemic hemodilution in five patients with unilateral internal carotid artery occlusion and minor stroke. Hemodilution was accomplished by phlebotomy of 400 mL and infusion of 400 mL of hydroxyethyl starch. Results Before hemodilution, the patients had a significant decrease in blood flow and oxygen transport along with significantly elevated oxygen extraction fraction in the cerebral hemisphere with carotid artery occlusion compared with six control subjects. After hemodilution, the hematocrit and arterial oxygen content decreased from 41.2% and 18.6 mL/dL to 36.3% and 16.5 mL/dL, respectively. Both cerebral blood flow and oxygen transport were increased and oxygen extraction fraction was decreased without any change in oxygen consumption. The degree of increase in blood flow and oxygen transport was positively correlated with the ratio of oxygen extraction fraction to blood volume before hemodilution. Conclusions These findings indicate that hemodilution improves oxygen transport as well as blood flow in patients with internal carotid occlusion and decreased perfusion and that this improvement may be more prominent in patients with a severely compromised hemodynamic state. Thus, hemodilution may be useful in patients with hemodynamic ischemia.

Uncoupling between cortical glucose metabolism and blood flow after ibotenate lesion of the rat basal forebrain: a PET study.

We evaluated the cerebral metabolic rate of glucose (CMRGlu) and cerebral blood flow (CBF) after unilateral lesioning of the rat basal forebrain cholinergic projection system using ibotenic acid. Using positron emission tomography, we measured CMRGlu and CBF with [18F]-2-fluoro-2-deoxy-D-glucose (FDG) and with H2(15)O, respectively. Three days after surgery, CMRGlu and k3* (the rate constant for the phosphorylation of FDG) were reduced in the frontal cortex on the ibotenic acid-injected side, whereas CBF and K1* (the rate constant for the FDG transport from the plasma to brain) in the same rats remained in the normal range. It is concluded that the decreased cortical CMRGlu after the lesion of the cholinergic system projecting from the basal forebrain is due to the diminished neural activity rather than to decreased CBF.

Compartment analysis of cerebral glucose metabolism and in vitro glucose-metabolizing enzyme activities in the rat brain

To clarify the relationship between cerebral glucose metabolic rate constants and glucose-metabolizing enzyme activities in the cerebral cortex, we evaluated the cerebral metabolic rate of glucose (CMRGlu), metabolic rate constants of [18F]-2-fluoro-2-deoxy-D-glucose (FDG) and related enzyme activities in the frontal cortex under normal and glucose metabolism-suppressed conditions. Applying a three-compartment four-parameter model, metabolic rate constants were obtained by dynamic positron emission tomography with FDG, and CMRGlu was calculated based on these rate constants. The glycolytic enzyme activities were determined by in vitro biochemical assay. Three days after ibotenic acid injection into the basal forebrain, CMRGlu was decreased in the ibotenic acid-treated frontal cortex as well as k3* (phosphorylation), while K1* (plasma to brain) showed no remarkable change. No significant reductions of the enzyme activities except for hexokinase activity were found in the frontal cortex. Regression analysis showed a significant positive correlation between k3* and the hexokinase activity. These results suggested that k3* in the compartment analysis reflects hexokinase activity.