Kazuo Uemura

Reduction in regional cerebral metabolic rate of oxygen during human aging.

To investigate changes in cerebral circulation and oxygen metabolism during aging, regional cerebral blood flow (rCBF), regional oxygen extraction fraction (rOEF), regional cerebral metabolic rate of oxygen (rCMRO2) and regional cerebral blood volume (rCBV) were measured using the 15O labelled gas inhalation technique and a multi-slice positron emission tomograph (PET) in 22 healthy volunteers, aged from 26 to 64 years old. The measurements were performed with subjects at rest, without sensory deprivation. The values of rCBF, rOEF, rCMRO2 and rCBV in more than 40 anatomical structures of the brain were evaluated by studying a large series of scans in each region of interest after the functional PET image had been anatomically identified using x-ray computed tomographic images corresponding to the PET. In mean gray values, only CMRO2 showed significant reduction with age. rCMRO2 significantly decreased with age only in the supratentrium, and much more in the left hemisphere. Especially remarkable was rCMRO2 reduction in the left caudate region. Both CBF and OEF were variable and less age-dependent. It was concluded that CMRO2 could be reflecting healthy brain aging most properly.

Clinical Value of Pet with 18F-Fluorodeoxyglucose and L-Methyl-11C-Methionine for Diagnosis of Recurrent Brain Tumor and Radiation Injury

We studied 15 patients clinically suspected to have recurrent brain tumor or radiation injury, using positron emission tomography (PET) with 18F-fluorodeoxyglucose (18FDG) and L-methyl-11C-methionine (11C-Met). PET with 11C-Met (Met-PET) clearly delineated the extent of recurrent brain tumor as focal areas of increased accumulation of 11C-Met, and was useful for early detection of recurrent brain tumor. PET with 18FDG (FDG-PET) showed focal 18FDG-hypermetabolism in one patient with malignant transformation of low grade glioma, and demonstrated its usefulness for evaluation of malignant transformation. 18FDG-hypometabolism was observed in all patients with radiation injury, but was also found in one patient with recurrent malignant brain tumor. 11C-Met uptake in 3 patients with radiation injury was similar to that of the normal cortical tissue. FDG-PET can be used to initially exclude recurrent brain tumor which is seen as 18FDG-hypermetabolism. The combined use of Met-PET in addition to FDG-PET can improve the accuracy of differentiation of recurrent brain tumor with 18FDG-hypometabolism from radiation injury.

Regional cerebral blood flow, blood volume, oxygen extraction fraction, and oxygen utilization rate in normal volunteers measured by the autoradiographic technique and the single breath inhalation method

By means of a high resolution PET scanner, the regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), oxygen extraction fraction (rOEF), and metabolic rate of oxygen (rCMRO2) for major cerebral gyri and deep brain structures were studied in eleven normal volunteers during an eye-covered and ear-unplugged resting condition. Regional CBF was measured by the auto-radiographic method after intravenous administration of H215O. Regional OEF and rCMRO2 were measured by the single inhalation of15O2. With MR T1-weighted images as an anatomical reference, thirteen major cerebral gyri, caudate nucleus, lentiform nucleus, thalamus, midbrain, pons, cerebellum and vermis were defined on the CMRO2 images. Values were read by using circular regions of interest 16 mm in diameter. The posterior part of the cingulate gyri had the highest rCBF and rCMRO2 values among brain structures, followed by the lentiform nucleus, the cerebellum, the caudate nucleus, and the thalamus. Parahippocampal gyri had the lowest rCBF and rCMRO2 values amongthe cortical gyri.RegionalOEFforthepontinenuclei (0.34 ± 0.04), the midbrain (0.35 ± 0.05), the parahippocampal gyri (0.35 ± 0.04 for the right and 0.37 ± 0.05 for the left), and the thalami (0.37 ± 0.05 for the right and 0.36 ± 0.04 for the left) were significantly lower than the mean OEF for the cerebral cortices (0.42 ± 0.04) (p < 0.05 or less). The global CBF and CMRO2 were consistent with those obtained by the Kety-Schmidt method. Although several limitations to the quantification derived from an inadequate spacial resolution remain unsolved, the performance of the present PET scanner and the method for the quantification employed provide regional estimates of brain circulation and oxygen metabolism more acurately than the PET system and the steady state method previously used.

Oxygen Extraction Fraction at Maximally Vasodilated Tissue in the Ischemic Brain Estimated from the Regional CO2 Responsiveness Measured by Positron Emission Tomography

The oxygen extraction fraction (OEF) at maximally vasodilated tissue in patients with chronic cerebrovascular disease was evaluated using positron emission tomography. The vascular responsiveness to changes in PaCO2 was measured by the H215O autoradiographic method. It was correlated with the resting-state OEF, as estimated using the 15O steady-state method. The subjects comprised 15 patients with unilateral or bilateral occlusion and stenosis of the internal carotid artery or middle cerebral artery or moyamoya disease. In hypercapnia, the scattergram between the OEF and the vascular responsiveness to changes in PaCO2 revealed a significant negative correlation in 11 of 19 studies on these patients, and the OEF at the zero cross point of the regression line with a vascular responsiveness of 0 was 0.53 ± 0.08 (n = 11). This OEF in the resting state corresponds to exhaustion of the capacity for vasodilation. The vasodilatory capacity is discussed in relation to the lower limit of autoregulation.

MRI of acute cerebral infarction: a comparison of FLAIR and T2-weighted fast spin-echo imaging

Abstract Fluid-attenuated inversion-recovery (FLAIR) sequences have been reported to provide high sensitivity to a wide range of central nervous system diseases. To our knowledge, however, FLAIR sequences have not been used to study patients with acute cerebral infarcts. We evaluated the usefulness of FLAIR sequences in this context. FLAIR sequences were acquired on a 0.5 T superconducting unit within 8 h of the onset in 19 patients (aged 26–80 years) with a total of 23 ischaemic lesions. The images were reviewed retrospectively by three neuroradiologists, and the FLAIR images were compared with T2-weighted fast spin-echo images. All but one of the ischaemic lesions involving grey matter was clearly demonstrated on FLAIR images as increased signal intensity in cortical or central grey matter. FLAIR images were particularly useful for detecting the hyperacute cortical infarcts within 3 h of onset, which were not readily detected on the spin-echo images. In 9 of 11 patients with complete proximal occlusion, the distal portion of the cerebral artery was visible as an area of high signal intensity on FLAIR images.

Electroencephalographic correlates of blood flow and oxygen metabolism provided by positron emission tomography in patients with cerebral infarction

Quantitative EEG data were analyzed statistically with respect to cortical cerebral blood flow (CBF) and oxygen metabolism (CMRO2) measured by positron emission tomography in 47 patients with unilateral cerebral infarction. Relative value of the square root of average power was used as a percentage power fraction (PPF) for each frequency category. Power ratio index (PRI) was calculated by dividing the combined delta-PPF and theta-PPF by the combined alpha-PPF and beta-PPF. Delta-PPF, theta-PPF and PRI correlated negatively with regional CBF (rCBF) and CMRO2 (rCMRO2) whereas alpha-PPF and beta-PPF correlated positively. In the acute stage, delta-PPF, alpha-PPF and PRI correlated with rCBF at all but the frontopolar region whereas the correlation with rCMRO2 was poor. Alpha-PPF and PRI correlated also with rCMRO2 in the frontal, central, parietal and occipital regions while delta-PPF correlated with rCBF only in the parietal and occipital regions in the subacute stage. In the chronic stage, all EEG quotients correlated significantly with both rCBF and CMRO2 in the central and parietal regions. In the frontopolar region, only the theta-PPF correlated with rCBF throughout. In the comparison of hemispheric mean values, the correlations were always closer for the affected hemisphere than for the contralateral hemisphere. Although hemispheric mean CBF and CMRO2 were significantly lower in patients with cortical infarcts on CT than in those with small subcortical infarcts, there was no significant difference in the EEG data between the 2 groups.

Cerebrovascular CO2 reactivity in normotensive and hypertensive man.

Cerebrovascular reactivity to CO2 inhalation and voluntary hyperventilation was studied in seven normotensive subjects and nine hypertensive patients without clinical or angiographical signs of arteriosclerosis. Cerebral blood flow (CBF) was measured by the intracarotid 133Xe clearance method and calculated as the initial slope index. Three to five CBF measurements were made in each patient in the Paco2 range of 20 to 55 mm Hg. No difference was observed in reactivity between hypertensive and normotensive patients, either during CO, inhalation or during hyperventilation. The shape of the CBF:Paco2 curve suggested a decrease in reactivity below a Paco2 of 30 to 35 mm Hg in both groups. Above a Paco2 of 35 mm Hg, exponential regression analysis yielded a mean reactivity of 6 ± 2%, whereas below a Paco2 of 30 mm Hg it was about 2%. The rise in CBF during CO2 inhalation was not influenced by the intravenous infusion of a small dose of trimethaphan which blocked the concomitant rise in blood pressure.

Changes of cerebral blood flow, and oxygen and glucose metabolism following radiochemotherapy of gliomas: a PET study.

The effects of radiochemotherapy on blood flow, blood volume, and consumption of oxygen and glucose in tumor tissue and normal brain were studied by positron emission tomography. Thirteen patients with cerebral gliomas were included, and they were examined before, during, and within approximately 1 month after the therapy. The 15O-labeled gas steady state inhalation and the 18F-fluorodeoxyglucose methods were used. After the therapy, glucose consumption and blood volume decreased (p less than 0.03) in the tumoral tissue. In the structurally (CT) normal gray matter, blood flow, blood volume, and oxygen consumption did not show any significant changes; oxygen extraction fraction, glucose consumption, and glucose extraction fraction, however, decreased significantly (p less than 0.05, less than 0.02, and less than 0.03, respectively).

Photic Stimulation Study of Changing the Arterial Partial Pressure Level of Carbon Dioxide

To investigate the effect of the level of baseline cerebral blood flow (CBF) on local CBF augmentation by activation, we have used positron emission tomography to measure regional CBF (rCBF) in 12 normal volunteers with and without photic stimulation during hypocapnia, normocapnia, and hypercapnia. The increase in rCBF in the primary visual cortex by photic stimulation was 10.8 ± 3.1, 18.6 ± 9.3, and 19.5 ± 6.1 ml 100 ml−1 min−1 in hypo-, normo-, and hypercapnia, respectively. The increase was significantly smaller in hypocapnia than in normocapnia (p < 0.005). The fractional CBF increase caused by the photic stimulation was the same in all breathing conditions. This result indicates that the magnitude of the CBF increase induced by neuronal activity correlates proportionally with the level of baseline CBF.

Intracranial venous angiomas.

Publications in the scientific literature are controversial in regard to the clinical significance of intracerebral venous angiomas. The present study of 11 patients with venous angiomas underscores the clinical importance of these lesions as potential causes of cerebral hemorrhage and obstructive hydrocephalus. The clinical and radiographic manifestations in 9 of these 11 patients correlated well. In cases of venous angiomas, the venous phase of angiography must be carefully scrutinized, particularly in patients with subarachnoid or intracerebral hemorrhage. Some diagnostic problems related to the angiography of venous angiomas are discussed.