scholarly journals Cerebral Oxygen Metabolism of Rats using Injectable 15O-Oxygen with a Steady-State Method

2011 ◽  
Vol 32 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Masato Kobayashi ◽  
Tetsuya Mori ◽  
Yasushi Kiyono ◽  
Vijay Narayan Tiwari ◽  
Rikiya Maruyama ◽  
...  

To develop a less-stressful and simple method for measurement of the cerebral metabolic rate of oxygen ( CMRO2) in small animals, the steady-state method was applied to injectable 15O2-PET (15O2-positron emission tomography) using hemoglobin-containing vesicles (15O2-HbV). Ten normal rats and 10 with middle cerebral arterial occlusion (MCAO) were studied using a small animal PET scanner. A series of 15O-PET scans with C15O-labeled HbV, H215O, and 15O2-HbV were performed with 10 to 15 minutes intervals to measure cerebral blood volume (CBV), cerebral blood flow (CBF), and CMRO2. Positron emission tomography scans were started with a tracer injection using a multiprogramming syringe pump, which provides a slowly increasing injection volume to achieve steady-state radioactivity for H215O and 15O2-HbV scans. The radioactivity concentration of 15O rapidly achieved equilibrium in the blood and whole brain at about 2 minutes after H215O and 15O2-HbV administration, which was stable during the scans. The whole brain mean values of CBF, CBV, and CMRO2 were 54.3 ± 2.0 mL per 100 g per minute, 4.9 ± 0.4 mL/100 g, and 2.8 ±0.2 μmoL per g per minute (6.2 ± 0.4 mL per 100 g per minute) in the normal rats, respectively. In the MCAO model rats, all hemodynamic parameters of the infarction area on the occlusion side significantly decreased. The steady-state method with 15O-labeled HbV is simple and useful to analyze hemodynamic changes in studies with model animals.

1988 ◽  
Vol 8 (1_suppl) ◽  
pp. S52-S60 ◽  
Author(s):  
Atsushi Inugami ◽  
Iwao Kanno ◽  
Kazuo Uemura ◽  
Fumio Shishido ◽  
Matsutaro Murakami ◽  
...  

The radioisotope distribution following intravenous injection of 99mTc-labeled hexamethylpropyleneamine oxime (HM-PAO) in the brain was measured by single photon emission computed tomography (SPECT) and corrected for the nonlinearity caused by differences in net extraction. The “linearization” correction was based on a three compartment model, and it required a region of reference to normalize the SPECT image in terms of regional cerebral blood flow distribution. Two different regions of reference, the cerebellum and the whole brain, were tested. The uncorrected and corrected HM-PAO images were compared with cerebral blood flow (CBF) image measured by the C15O2 inhalation steady state method and positron emission tomography (PET). The relationship between uncorrected HM-PAO and PET–CBF showed a correlation coefficient of 0.85 but tended to saturate at high CBF values, whereas it was improved to 0.93 after the “linearization” correction. The whole-brain normalization worked just as well as normalization using the cerebellum. This study constitutes a validation of the “linearization” correction and it suggests that after linearization the HM-PAO image may be scaled to absolute CBF by employing a global hemispheric CBF value as measured by the nontomographic 133Xe clearance method.


2001 ◽  
Vol 21 (7) ◽  
pp. 793-803 ◽  
Author(s):  
Hidehiko Okazawa ◽  
Hiroshi Yamauchi ◽  
Kanji Sugimoto ◽  
Masaaki Takahashi ◽  
Hiroshi Toyoda ◽  
...  

To evaluate a new simplified bolus method for measurement of cerebral perfusion and metabolism, the parametric images with that method were compared with those obtained from the conventional steady-state method with 15O-gas. The new method also provided images of arterial blood volume (V0), which is a different parameter from cerebral blood volume (CBV) obtained using a C15O technique. Seven healthy volunteers and 10 patients with occlusive cerebrovascular diseases underwent positron emission tomography (PET) scans with both methods. Three-weighted integration was applied to calculate regional cerebral blood flow (rCBF) and regional cerebral metabolic rate of oxygen (rCMRO2) in the bolus method. Global and regional CBF and CMRO2 in volunteers were compared between the two methods and used as control data. Regional values in patients also were evaluated to observe differences between the bilateral hemispheres. Both rCBF and rCMRO2 were linearly well correlated between the two methods, although global difference in CMRO2 was significant. The difference in each parametric image except for V0 was significant between the bilateral hemispheres in patients. The bolus method can simplify oxygen metabolism studies and yield parametric images comparable with those with the steady-state method, and can allow for evaluation of V0 simultaneously. Increase in CBV without a change in V0 suggested the increase might mainly be caused by venous dilatation in the ischemic regions.


1984 ◽  
Vol 4 (2) ◽  
pp. 224-234 ◽  
Author(s):  
Iwao Kanno ◽  
Adriaan A. Lammertsma ◽  
Jon D. Heather ◽  
Jeremy M. Gibbs ◽  
Christopher G. Rhodes ◽  
...  

This article describes a rapid method for the regional measurement of cerebral blood flow using a single breath of C15O2 and positron emission tomography. The technique is based on the bolus distribution principle and utilises a reference table for the calculation of flow. Seven subjects were studied using both this method and the C15O2 continuous inhalation steady-state technique. The single-breath method gave flow values 20% higher than those obtained using the steady-state method. A simulation study was performed in an attempt to define the reasons for the difference between the two techniques. Estimations were made of identified sources of error in the measurement of regional cerebral blood flow using the single-breath technique and compared with results from a similar study previously described for the steady-state technique. However, further comparative studies will be necessary to satisfactorily explain the difference between both techniques.


1988 ◽  
Vol 8 (2) ◽  
pp. 227-235 ◽  
Author(s):  
Iwao Kanno ◽  
Kazuo Uemura ◽  
Schuichi Higano ◽  
Matsutaro Murakami ◽  
Hidehiro Iida ◽  
...  

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.


2015 ◽  
Vol 35 (5) ◽  
pp. 743-746 ◽  
Author(s):  
Martin Bauer ◽  
Rudolf Karch ◽  
Markus Zeitlinger ◽  
Cécile Philippe ◽  
Kerstin Römermann ◽  
...  

As P-glycoprotein (Pgp) inhibition at the blood–brain barrier (BBB) after administration of a single dose of tariquidar is transient, we performed positron emission tomography (PET) scans with the Pgp substrate ( R)-[11C]verapamil in five healthy volunteers during continuous intravenous tariquidar infusion. Total distribution volume ( VT) of ( R)-[11C]verapamil in whole-brain gray matter increased by 273 ± 78% relative to baseline scans without tariquidar, which was higher than previously reported VT increases. During tariquidar infusion whole-brain VT was comparable to VT in the pituitary gland, a region not protected by the BBB, which suggested that we were approaching complete Pgp inhibition at the human BBB.


1998 ◽  
Vol 18 (10) ◽  
pp. 1130-1142 ◽  
Author(s):  
Richard E. Carson ◽  
Dale O. Kiesewetter ◽  
Elaine Jagoda ◽  
Margaret G. Der ◽  
Peter Herscovitch ◽  
...  

[18F]Fluoropropyl-TZTP (FP-TZTP) is a subtype-selective muscarinic cholinergic ligand with potential suitability for studying Alzheimer's disease. Positron emission tomography studies in isofluorane-anesthetized rhesus monkeys were performed to assess the in vivo behavior of this radiotracer. First, control studies (n = 11) were performed to characterize the tracer kinetics and to choose an appropriate model using a metabolite-corrected arterial input function. Second, preblocking studies (n = 4) with unlabeled FP-TZTP were used to measure nonspecific binding. Third, the sensitivity of [18F]FP-TZTP binding to changes in brain acetylcholine (ACh) was assessed by administering physostigmine, an acetylcholinesterase (AChE) inhibitor, by intravenous infusion (100 to 200 μg·kg−1·h−1) beginning 30 minutes before tracer injection (n = 7). Tracer uptake in the brain was rapid with K1 values of 0.4 to 0.6 mL·min−1·mL−1 in gray matter. A model with one tissue compartment was chosen because reliable parameter estimates could not be obtained with a more complex model. Volume of distribution ( V) values, determined from functional images created by pixel-by-pixel fitting, were very similar in cortical regions, basal ganglia, and thalamus, but significantly lower ( P < 0.01) in the cerebellum, consistent with the distribution of M2 cholinergic receptors. Preblocking studies with unlabeled FP-TZTP reduced V by 60% to 70% in cortical and subcortical regions. Physostigmine produced a 35% reduction in cortical specific binding ( P < 0.05), consistent with increased ACh competition. The reduction in basal ganglia (12%) was significantly smaller ( P < 0.05), consistent with its markedly higher AChE activity. These studies indicate that [18F]FP-TZTP should be useful for the in vivo measurement of muscarinic receptors with positron emission tomography.


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