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Biomedical subjects

Y Imahori

Publications and source records attributed to Y Imahori.

At least 37 records · Page 2Linked to original sources
PubMed1996

Chronological positron emission tomographic study of severe diffuse brain injury in the chronic stage.

Cerebral blood flow and metabolism were investigated in five patients with severe diffuse brain injury in the chronic stage, using positron emission tomography (PET). Regional cerebral blood flow, regional oxygen extraction fraction, regional cerebral blood volume, regional cerebral metabolic rate for oxygen, and regional cerebral metabolic rate for glucose were measured bilaterally in the frontal, temporal, occipital, and parietal gray matter, as well as the white matter of the centrum semiovale. In 4 of 5 patients, a follow-up PET study was also performed. In three cases, below-normal regional cerebral blood flow and regional cerebral metabolic rate for oxygen values accompanied by above-normal regional oxygen extraction fraction values, as well as low metabolism, were demonstrated in the initial PET studies. In two of three cases, clinical improvements were observed, and follow-up PET data also improved. These findings suggest that chronological PET studies may be able to assess quantitatively clinical improvements in patients with diffuse brain injury.

Adult↗
PubMed1996

Irradiation effects on the metabolism of metastatic brain tumors: analysis by positron emission tomography and 1H-magnetic resonance spectroscopy.

To evaluate irradiation effects on the metabolism of metastatic brain tumors treated by Gamma Knife radiosurgery, positron emission tomography (PET) and 1H-magnetic resonance spectroscopy (MRS) studies were performed on five patients. The tumor origins were lung cancer in three patients and breast cancer in two. Treatment volume was 0.4-10.1 cm3 (mean: 5.5 cm3). The marginal dose to the tumor was 24-30 Gy (mean: 26.2 Gy). The follow-up period was 5-19 months (mean: 13.4 months). No patients had conventional whole-brain radiation therapy. 18F-fluoroboronophenylalanine (18FBPA) or 18F-fluorodeoxyglucose (18FDG) were used as tracers for the PET study. Using 1H-MRS, several metabolites were simultaneously measured in metastatic brain tumor and adjacent brain. In the PET study of the representative case, the uptake rate of 18FBPA that is actively transported to the tumor decreased markedly 15 days after radiosurgery and continued to decrease thereafter. In the 1H-MRS study, choline, which is characteristically high in metastatic brain tumors, also decreased over time. In two cases with suspected radiation injury, the enhanced region, which was decreased in size in early follow-up, enlarged progressively and was accompanied by edema. However, 18FBPA and 18FDG were not transported to the enhanced region. The peak of free lipid, which might show destruction of the cell membrane, was recognized in the enhanced region and adjacent brain in these cases. This study revealed that radiation effects on the metabolism of metastatic brain tumors occur at an early stage after radiosurgery and continue over several months. In particular, in the case of radiation injury, PET and 1H-MRS studies made it possible to distinguish between regrowth of the tumor and radiation injury.

Aged↗
PubMed1996

Spontaneous regression of intracranial arteriovenous malformation on PET.

We report a case of spontaneous regression of intracranial arteriovenous malformation (AVM) detected by PET in a 57-yr-old woman who had suffered repeated ruptures of the AVM at 28, 30 and 31 yr of age associated with pregnancy. The rupture at this hospitalization was the most critical, and after repeated ruptures for 1 mo, the AVM regressed spontaneously. The decreased cerebral blood volume (CBV) in the AVM indicated regression. The flow-to-volume (CBF/ CBV) ratios surrounding the AVM increased. The metabolic rate for oxygen (CMRO2) did not correlate with her improved neurological status, and an imbalance between CBF and CMRO2 was recognized.

Cerebrovascular Circulation↗
PubMed1996

Cerebral hemodynamics and metabolism of severe diffuse brain injury measured by PET.

Cerebral hemodynamics and metabolism in three patients with severe diffuse brain injury were measured 10 days after onset using PET. In this study, regional cerebral blood flow (rCBF), oxygen extraction fraction (rOEF), cerebral blood volume (rCBV), cerebral metabolic rate for oxygen (rCMRO2), cerebral metabolic rate for glucose (rCMRglc) and cerebral metabolic ratio (rCMRO2/rCMRglc) were measured. The Glasgow Coma Scale scores on admission were 4, 5 and 5, respectively, and CT on admission showed typical findings of diffuse brain injury. As a result, PET revealed misery perfusion and hyperglycolysis in Patient 1 and matching low perfusion and low glucose metabolism in Patients 2 and 3. Although Patient 1 died, Patients 2 and 3 had good recoveries. We speculate that a long-lasting anaerobic state, indicated by a high OEF value and low metabolic ratio, is an important undesirable factor related to the outcome.

Adolescent↗
PubMed1995

Rapid incorporation of carbon-11-labeled diacylglycerol as a probe of signal transduction in glioma.

We have synthesized and characterized a positron-emitting carbon-11-labeled 1,2-diacylglycerol to study phosphoinositide turnover in tumor cells. Rapid incorporation of the 1,2-diacylglycerol was observed in the C6 glioma cell line. The incorporated lipid fraction consisted chiefly of phosphoinositide pool and another phospholipid pool in the proliferative state. When the state was inhibited by (-)-3D-3-deoxy-3-fluoro-myo-inositol, incorporation into the phosphoinositide pool decreased selectively. This suggested that phosphoinositide turnover is the leading regulator of tumor proliferation potential. On the basis of the concept of carbon-11-labeled 1,2-diacylglycerol as a specific probe for visualizing the tumor signal transduction in vivo, we obtained proliferating images of implanted C6 glioma cells in the rat brain by autoradiography and visualized the proliferation signal in human glioma by positron emission tomography.

Animals↗
PubMed1995

[Carbon-11 labeled diacylglycerol for signal transduction imaging by positron CT: evaluation of the quality and safety for clinical use].

To elucidate the synaptic transmission in the neural system, we have been developing fundamental studies for intracellular signaling. For clinical application of carbon-11 labeled diacylglycerol (1-[1-11C]butyryl-2-palmitoyl-rac-glycerol: 11C-DAG) using positron emission computed tomography (PET), we evaluated the quality and the safety of 11C-DAG as the solution for injection. As a result, 11C-DAG was synthesized within 50 minutes, including the preparation step for injection. The half life time and energy spectrum of 11C-DAG were the same as the physical character of carbon-11, and other radioisotopes were not detected. In the quality control, 11C-DAG solution was negative in the examination of bacterial contamination and the pyrogen test in three successive synthesis procedures. In the acute toxicity test by administration of 11C-DAG and 100 mumol/kg of non-radioactive DAG to the rat intravenously, the systemic condition of the rat was not changed and no abnormalities were found in any organ 24 hours after administration. These findings indicated the safety of 11C-DAG solution. Clinical application of 11C-DAG using positron emission tomography may be useful to elucidate the dysfunction of intracellular signaling in disorders of higher cortical function such as Alzheimer disease.

Animals↗
PubMed1994

[Carbon-11 labeled diacylglycerol for signal transduction imaging: effect of the solubilizer on the distribution and radiation dosimetry].

Carbon-11 labeled diacylglycerol (11C-DAG) has been developed as a signal transduction imaging agent for the CNS, and it can visualize the second messenger. For clinical application by positron CT (PET), the 11C-DAG solution must be prepared for intravenous injection. However, the 11C-DAG does not dissolve in water because of its lipophilicity and requires a solubilizer such as human serum albumin (HSA) and Tween 80 (TW-80). We examined the influence of these solubilizers on the tissue distribution of 11C-DAG, and estimated the radiation dosimetry. In the brain, uptake of 11C-DAG dissolved with HSA was 1.3-1.8 times higher than that of dissolved with TW-80. On the other hand, the lung and spleen showed a higher uptake of 11C-DAG using TW-80 than when using HSA. Especially, the lungs showed 20-40 times higher uptake than when using HSA. Also, the washout of radioactivity from tissue was slower, and the dose of radiation exposure was estimated to be higher, with TW-80 than with HSA. Therefore, between TW-80 and HSA with different solubilizing mechanisms, the later was suggested to be a better solubilizer of 11C-DAG.

Animals↗
PubMed1993

Hemodynamic disturbances in cerebral ischemia: correlation between positron emission tomographic and angiographic findings.

Proper treatment of ischemic stroke requires better understanding of cerebral hemodynamic changes. The hemodynamic changes associated with ischemia were measured using positron emission tomography and related to angiographic findings in the subacute and chronic stages of 17 ischemia patients who showed symptoms of main trunk stenosis of the internal carotid artery system. The hemodynamic factors, cerebral blood flow, cerebral blood volume, cerebral metabolic rate for oxygen, oxygen extraction fraction, and flow/volume ratio, were measured in regions of interest determined from the angiographic stenosis (over 50%) and compared in each stage. The cerebral blood flow and flow/volume ratio in the territory downstream of the main trunk stenosis and cerebral metabolic rate for oxygen in the whole cortex were decreased in the subacute stage. In the chronic stage, cerebral blood flow and flow/volume ratio decreased mainly in borderzone areas.

Adult↗
PubMed1993

Phosphoinositide turnover imaging linked to muscarinic cholinergic receptor in the central nervous system by positron emission tomography.

Receptor-mediated membrane processing plays an essential role in neural function in the synapses. In such neurotransmission process, the phosphoinositide (PI) response, an effector in the production of second-messengers, can be used to assess in vivo signal transduction. Using in vivo autoradiography and positron emission tomography (PET), we attempted to visualize the PI response to muscarinic cholinergic receptor (mAChR)-stimulation in rats and monkeys, which were administered 1,2-[11C]diacylglycerol (DAG) intravenously. Enhancement of 1,2-[11C]DAG incorporation was observed in the rat ipsilateral hippocampus and cortex in which mAChR-agonist was administered by local injection, but this was in contrast to spreading cortical depression in the ipsilateral cortex using KCl. In monkey PET studies, dynamic brain scanning revealed increase in activity over time for about 15 min after a bolus injection of 1,2-[11C]DAG in an awake state. The activity then remained at a constant level. This finding documented the theoretical "membrane-trapping" mechanism. The systemic mAChR-stimulation accelerated incorporation in the cerebral cortices of the same monkey brain. Radioactivity uptake did not differ significantly between the mAChR-stimulated and nonstimulated early scan images. This suggested that cerebral blood flow does not greatly affect DAG incorporation. In sequential membrane processes of PI turnover, diacylglycerol kinase rapidly metabolizes DAG, included in PI turnover. In conclusion 1,2-[11C]DAG incorporation was limited by receptor-mediated PI turnover, which can represent real synaptic transmission in neural networks.

Animals↗
PubMed1993

Protein kinase C imaging using carbon-11-labeled phorbol esters: 12-deoxyphorbol 13-isobutyrate-20-[1-11C]butyrate as the potential ligand for positron emission tomography.

Protein kinase C plays a crucial role in signal transduction for a variety of biologically active substances which activates cellular functions and their proliferation. The actions are closely related to both normal and abnormal functions in the nervous system. Tumor-promoting phorbol esters can substitute for diacylglycerols which are important ligands that bind to protein kinase C. Three typical phorbol esters, phorbol 13-[1-11C]butyrate, phorbol 12,13-[1-11C]dibutyrate and 12-deoxyphorbol 13-isobutyrate-20-[1-11C]butyrate, were synthesized by using [11C]ethylketene with a high specific activity (186GBq/mumol). Their in vivo autoradiograms demonstrated a heterogenous distribution in rat brain. 12-deoxyphorbol 13-isobutyrate-20-[1-11C]butyrate was particularly suited for in vivo use due to its nontumor-promoting activity and its ready permeability to the blood-brain barrier. High optical density was observed in the cortex, amygdala and hippocampus. The in vivo binding properties of this compound to protein kinase C were confirmed by in vivo displacement studies with unlabeled 12-deoxyphorbol 13-isobutyrate-20-butyrate and unlabeled phorbol 12,13-dibutyrate. This suggests that 12-deoxyphorbol 13-isobutyrate-20-[1-11C] butyrate has a specific binding affinity for protein kinase C.

Animals↗
PubMed1992

Effect of hemodilution on cerebral hemodynamics and oxygen metabolism.

BACKGROUND AND PURPOSE: To evaluate the effects of hemodilution on cerebral hemodynamics and oxygen metabolism in the normal human brain, we measured regional cerebral blood flow, oxygen extraction fraction, oxygen metabolic rate, and regional cerebral blood volume in eight normal volunteers before and after hemodilution using positron emission tomography and oxygen-15-labeled gas inhalation technique. SUMMARY OF REPORT: Hemodilution was accomplished by phlebotomy of 400 ml and drip infusion of 500 ml low molecular weight dextran, which reduced hematocrit from 42.5% to 37.2% and arterial oxygen content from 19.1 to 16.9 ml/dl (both p less than 0.005). It also increased mean cerebral blood flow from 45.2 to 47.7 ml/100 ml/min (p less than 0.025), but decreased tissue oxygen delivery from 8.7 to 8.0 ml/100 ml/min (p less than 0.05) and cerebral blood volume from 4.9% to 4.6% (p less than 0.025) in the overall cortical gray matter. CONCLUSIONS: Our results indicate that hemodilution in the tested range does not improve oxygen transport or tissue oxygenation in the normal human brain, although it increases cerebral blood flow.

Adult↗
PubMed1992

Positron emission tomographic measurement of acute hemodynamic changes in primate middle cerebral artery occlusion.

Specific hemodynamic changes in acute ischemia were investigated using a middle cerebral artery occlusion primate model and positron emission tomography. The cerebral blood flow (CBF), cerebral blood volume, oxygen extraction fraction (OEF), and cerebral metabolic rate for oxygen were measured 1, 3, and 9 hours after occlusion. OEF showed an increase in ischemic areas, and especially where CBF was below 18 ml/100 gm/min 1 hour after occlusion the OEF increased significantly (0.69 +/- 0.20, p < 0.05). Nine hours after occlusion, the OEF values were lower compared to those 1 and 3 hours after occlusion. Areas where CBF ranged from 18 to 31 ml/100 gm/min showed an increase in OEF at all times (p < 0.05). Clearly, OEF changes remarkably in the acute stage.

Animals↗
PubMed1992

Membrane trapping of carbon-11-labeled 1,2-diacylglycerols as a basic concept for assessing phosphatidylinositol turnover in neurotransmission process.

The uptake mechanism of 1,2-[11C]diacylglycerols (DAG) was studied and its use as a probe for the measurement of phosphatidylinositol (PI) turnover was verified. A method of synthesis for producing rac-1,2-[11C]DAG using [11C]ethylketene was developed to label the 1- or 3-hydroxyl group of 2-monoacylglycerol. After intravenous injection, these tracers were metabolized rapidly in the rat brain cortex to phosphatidic acids, phosphatidylinositols and phosphatidylinositol phosphates. The brain cortex anesthetized by barbiturate, which represents inhibited state of synaptic transmission, did not produce differences in uptake values between sn-1,2-[11C]DAG and rac-1,2-[11C]DAG. However, in the liver, lung, and pancreas under the same conditions, the uptake values of rac-1,2-[11C]DAG were higher than those of sn-1,2-[11C] DAG, in which the labeling position was on the 2-hydroxyl group in the sn type. These findings suggest that the lipase activity in the brain should be disregarded because lipase predominantly hydrolyzes the 1- or 3-position of rac-1,2-[11C] DAG, which should be the main factor producing the differences in uptake values in other organs. Cholinergic stimulation prompted accumulation of 1,2-[11C]DAG in the conscious rat brain. In conclusion, sn-1,2-[11C]DAG, administered even in the racemic mixture, could serve as a tracer that becomes mixed with receptor-linked PI turnover and could accumulate in the brain based on the membrane trapping mechanism.

Animals↗
PubMed1991

[An evaluation of cerebral blood flow and metabolism of reconstructive vascular surgery using positron emission tomography--a report of 4 cases].

Changes in cerebral hemodynamics due to reconstructive cerebral vascular surgery were evaluated using positron emission tomography (PET). Three minor stroke cases and 1 TIA case, brought on by main trunk stenosis, were included. STA-MCA anastomoses was performed in two of the cases and carotid endarterectomy was performed in the remaining two cases. CBF, CBV, OEF, CMRO2 and CBF/CBV were investigated using PET with the ROIs fixed in both normal and stenosis areas. On the two cases of STA - MCA anastomosis, clear hemodynamic improvement was not demonstrated. On the two carotid endarterectomy cases, the hemodynamic factors showed improvement.

Aged↗
PubMed1991

No-carrier-added carbon-11-labeled sn-1,2- and sn-1,3-diacylglycerols by [11C]propyl ketene method.

This article describes the preparation of sn-1,2-[11C]diacylglycerols and sn-1,3-[11C]diacylglycerols by a no-carrier-added reaction based on a labeling method using [1-11C]propyl ketene, which is one of the most potent acylating agents. [1-11C]Propyl ketene was produced by pyrolytic decomposition of [1-11C]butyric acid and was trapped in pyridine containing L-alpha-palmitoyl-lysophosphatidylcholine, producing L-alpha-palmitoyl-2-[1-11C]butyryl-sn-glycero-3-phosphorylcholine. We adopted an enzymatic reaction to remove the phosphorylcholine, in which L-alpha-palmitoyl-2-[1-11C]butyryl-sn-glycero-3-phosphorylcholine was incubated with phospholipase C, hydrolyzing to produce 1-palmitoyl-sn-2-[1-11C]butyrylglycerol. Total synthesis time was about 50 minutes and the specific activity was estimated at 93 GBq/mumol (2.5 Ci/mumol) at end of synthesis. Radiochemical yield was 3.8% based on the trapped 11CO2. sn-1,3-[11C]Diacylglycerol was also synthesized by [1-11C]propyl ketene reaction with 1-palmitoyl-sn-glycerol in a single procedure. The regional brain tissue radioactivities obtained in sn-1,2-[11C]diacylglycerol were higher than those of sn-1,3-[11C]diacylglycerol, and the regional values varied widely. In autoradiography of brain slices from conscious rats, sn-1,2-[11C]diacylglycerol incorporation sites were discretely localized, especially in the amygdala, cerebral cortex, and hippocampus, suggesting that intensive neuronal processing occurred in these areas on the basis of phosphatidylinositol turnover.

Acylation↗
PubMed1990

Metabolic and hemodynamic aspects of peritumoral low-density areas in human brain tumor.

With the use of positron emission tomography, regional cerebral blood flow, oxygen utilization, and glucose utilization were measured in the peritumoral low-density areas on x-ray computed tomographic images in 23 patients with supratentorial brain tumors: 7 meningiomas, 11 malignant gliomas, and 5 metastatic brain tumors. Findings on positron emission tomography in these areas revealed characteristic patterns associated with the types of tumor and the degree of mass effect. It is likely that two different types of pathophysiological states exist in "peritumoral edema": 1) primary ischemia caused by mechanical compression by the tumor mass in meningiomas; and 2) primary metabolic suppression (mainly in oxygen metabolism) in malignant brain tumors.

Adult↗
PubMed1990

Positron emission tomographic studies on cerebral hemodynamics in patients with cerebral contusion.

Positron emission tomography is currently one of the most useful methods for measurements of cerebral hemodynamics and oxygen metabolism, because it facilitates accurate analysis of the local cerebral circulation in three-dimensional quantitative images. In this study, we performed positron emission tomography studies to measure cerebral circulation in a total of 11 patients who sustained head injuries with contusion. Several parameters were measured including regional cerebral blood flow, regional cerebral blood volume, permeability, and regional cerebral metabolic rate for oxygen. Data from brains both with and without contusion were analyzed for chronological changes, in the subacute stage from the 8th to 29th day and in the chronic stage until 360 days after the injury and compared with similar data in a group of normal subjects. It was concluded that in the subacute stage, regional cerebral blood flow decreased (26 +/- 7 and 39 +/- 10 ml/100 g/min) and regional cerebral blood volume increased (5.6 +/- 1.8 and 5.4 +/- 0.9 ml/100 g) both in areas of cerebral contusion and in areas remote from cerebral contusion and that permeability increased in areas of contusion but not in remote brain areas. In the chronic stage, these parameters showed a tendency for recovery.

Adolescent↗