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The serotonin agonist fenfluramine has been used widely in humans for studying neuronal activation. We carried out the present study in order to determine whether anesthetized pigs could be used for studying effects of fenfluramine on cerebral functions using positron emission tomography (PET). We obtained quantitative measures of regional cerebral blood flow (rCBF) and of glucose and oxygen utilization (rCMRglc and rCMR(O2)) during intravenous administration of fenfluramine, using [15O]water, [18F]FDG and [15O]oxygen, respectively. Fenfluramine (25 mg/h i.v.) caused a significant rise in rCBF and, to a lesser extent, in rCMR2(O2), but it failed to affect rCMRglc. The findings indicate that quantitative estimation of rCBF by repeated injection of [15O]water was more sensitive than either rCMRO2 or rCMRglc for detecting effects of fenfluramine on serotonin neurotransmission in living porcine brain.

Unlabelled: We propose a new method to quantify regional cerebral blood flow (rCBF) with continuous infusion of 99mTc-ethyl cysteinate dimer (ECD) and dynamic SPECT., Methods: Thirteen subjects were studied. Seven subjects had SPECT and PET studies, and the other six subjects were involved in the measurement of blood clearance of 99mTc-ECD. During constant infusion of 99mTc-ECD (740 MBq) over 10 min, dynamic SPECT scans were obtained every 1 min by means of a triple-head rotating SPECT camera. Intermittent arterial blood sampling with octanol extraction was performed every 1 min to estimate the arterial input function. Influx constant (Ku) obtained by Gjedde-Patlak graphical plot method was compared with rCBF measured by PET using 15O CO2 steady state method. In order to simplify the procedure, arterial input function in each subject was estimated by calibration of the arterial blood sampled at the end of the scan to the standard arterial input function estimated from the blood clearance rate in six subjects., Results: Ku was linearly correlated with rCBF (Ku = 0.09 + 0.62 rCBF, r = 0.85, p < 0.05). Ku calculated with the estimated input function (Ku') and rCBF also demonstrated a linear relationship (Ku' = 0.05 + 0.65 rCBF, r = 0.84, p < 0.05)., Conclusion: The proposed method with one-point arterial sampling is a simple, clinically feasible tool for quantitative measurement of rCBF with 99mTc-ECD.

Unlabelled: A one-day protocol with a double injection of 99mTc-ECD was introduced for the assessment of cerebral perfusion reserve with acetazolamide (ACZ). The purpose of this study was to investigate the feasibility and effectiveness of this protocol., Methods: Thirty subjects were given double injections of 99mTc-ECD (first dose 370 MBq; second dose 740 MBq) for consecutive brain perfusion studies. Serial dynamic SPECT scans (1 min x 50 frames) were performed with the first set of SPECT data obtained by totaling the data for the frames taken between 5 and 20 min, and the second by subtracting the decay and dose-corrected initial SPECT data from the sum of the data obtained between 35 and 50 min. To evaluate the feasibility and effectiveness of the procedure, 23 of the 30 subjects were injected with ACZ 14 min after the first dose. To evaluate the reproducibility, seven subjects were not given the ACZ. The washout rate (WR) was calculated for three stages (WR1 = from 6 to 14 min, WR2 = from 20 to 28 min, and WR3 = from 36 to 44 min). Regional count increase (percent increase) and the percent count difference between normal and affected side (percent difference) were also calculated., Results: Values for WR1, WR2 and WR3 did not show significant differences among the stages (WR1 = -1.43% +/- 6.09%, WR2 = -0.65% +/- 6.57%, and WR3 = -1.60% +/- 4.28%; F-value = 0.33, p-value = 0.72). Reproducibility was excellent (second SPECT = 0.964 x first SPECT; r = 0.997). Mean count increase after ACZ was 21.7%. In patients with unilateral cerebrovascular disease, the percent increase after ACZ loading was significantly greater on the normal side (26.6% +/- 13.0%) than on the affected side (19.3% +/- 13.2%) (p < 0.01), resulting in a significant increase in percent difference (control: 14.3% +/- 10.7%, ACZ: 19.2% +/- 11.5%; p < 0.01)., Conclusion: ECD washout was minimal during the first 50 min after injection and was not affected by ACZ, which supports the feasibility of this protocol. The simple procedure and short acquisition time of this method renders it clinically useful for measuring cerebral perfusion reserve.

Unlabelled: We evaluated quantitatively 62Cu-labeled pyruvaldehyde bis(N4-methylthiosemicarbazone) copper II (62Cu-PTSM) as a brain perfusion tracer for positron emission tomography (PET). For quantitative measurement, the octanol extraction method is needed to correct for arterial radioactivity in estimating the lipophilic input function, but the procedure is not practical for clinical studies. To measure regional cerebral blood flow (rCBF) by 62Cu-PTSM with simple arterial blood sampling, a standard curve of the octanol extraction ratio and a three-compartment model were applied., Methods: We performed both 15O-labeled water PET and 62 Cu-PTSM PET with dynamic data acquisition and arterial sampling in six subjects. Data obtained in 10 subjects studied previously were used for the standard octanol extraction curve. Arterial activity was measured and corrected to obtain the true input function using the standard curve., Results: Graphical analysis (Gjedde-Patlak plot) with the data for each subject fitted by a straight regression line suggested that 62Cu-PTSM can be analyzed by the three-compartment model with negligible K4. Using this model, K1-K3 were estimated from curve fitting of the cerebral time-activity curve and the corrected input function. The fractional uptake of 62Cu-PTSM was corrected to rCBF with the individual extraction at steady state calculated from K1-K3. The influx rates (Ki) obtained from three-compartment model and graphical analyses were compared for the validation of the model. A comparison of rCBF values obtained from 62Cu-PTSM and 150-water studies demonstrated excellent correlation., Conclusion: The results suggest the potential feasibility of quantitation of cerebral perfusion with 62Cu-PTSM accompanied by dynamic PET and simple arterial sampling.

The goal of this study was to develop a simple method for quantification of regional cerebral blood flow (rCBF) with 99mTc-ethyl cysteinate dimer (ECD) SPECT. Following an intravenous constant infusion of ECD for one minute, serial dynamic SPECT imaging was performed for 40 minutes in 6 healthy male volunteers with intermittent arterial blood sampling. PET scan with 15O-water was performed on the same day before the SPECT study for measurement of rCBF. Arterial blood data demonstrated rapid conversion of ECD to the hydrophilic metabolites, and most of the arterial input to the brain was completed within 5 minutes after the injection. Brain activity reached a peak value soon after the cessation of infusion, and was stable thereafter with very little washout. Net extraction of ECD in the brain calculated by arterial input of ECD and rCBF demonstrated a rapid decrease within a few minutes, reaching 42.7% at 5 minutes. The simulation study suggested that the arterial blood activity obtained by continuous drawing for 5 minutes and a single SPECT scan would provide a reasonable estimate of rCBF under the assumption of constant net extraction in the brain.

Balloon test occlusion (BTO) of the internal carotid artery (ICA) combined with cerebral blood flow (CBF) study has proved to be a sensitive test for prediction of the outcome of permanent vessel occlusion. In this study, we evaluated the acute changes in regional CBF during BTO under hypotension in order to examine the possible risk of cerebral ischaemia after surgical treatment. Eleven patients in whom surgical carotid sacrifice was planned underwent BTO combined with CBF studies using technetium-99m hexamethyl-propylene amine oxime single-photon emission tomography under hypotension by decreasing the systemic blood pressure by about 50 mm Hg using a ganglion blocking agent. All patients showed a mild to severe decrease in CBF in the ipsilateral ICA territory relative to the contralateral side. A decrease in CBF of greater than 20% was observed in nine patients (82%), and two of them showed a decrease exceeding 40%. However, no ischaemic symptoms were demonstrated during scanning with hypotensive BTO. Our results suggest that in many patients with negative normotensive BTO, a considerable reduction in CBF would occur during hypotension. This procedure may predict a possible risk of hypotensive accident during and/or after surgery.

Three patients with prelingual deafness and six patients with postlingual deafness using multichannel cochlear implants were examined by positron emission tomography using 15O-labeled water. Changes in regional cerebral blood flow (rCBF) were measured during three different sound stimuli: 1) with no sound stimulation, with the speech processor of the cochlear implant system switched off, 2) hearing white noise, and 3) hearing sequential Japanese sentences. In postlingually deaf patients, speech stimulation caused a significantly greater rCBF increase compared with noise stimulation in the left immediate auditory association area and the bilateral auditory association areas. In these patients, speech sound is thought to be processed by means of auditory cortices analogous to those in normal subjects. In contrast, in prelingually deaf patients, speech sound induced much less rCBF increase in auditory association cortices; this finding suggested underdevelopment of the neural network for complex sound analysis and speech sound recognition.

Unlabelled: To test the feasibility of applying N-isopropyl-[123I]p-iodoamphetamine (IMP) for sequential measurements of regional cerebral blood flow (rCBF) with injection of two separate doses in a single procedure, kinetic analysis based on a two-compartment model was done using dynamic SPECT data. A microsphere model analysis without consideration of IMP washout from the brain was also tested for clinical application., Methods: A dynamic SPECT scan consisting of fifty 1-min scans was obtained on 15 patients using a three-head rotating gamma camera with two separate doses of IMP (111 MBq each) at the beginning and 25 min after scan initiation. The reproducibility of two resting rCBF scans was tested in six patients and the cerebrovascular response shown by increased rCBF with acetazolamide (1 g) was assessed in nine patients., Results: Two-compartment model analysis showed excellent reproducibility of resting rCBF scans and significantly different cerebrovascular reactivity to acetazolamide between areas with and without ischemia. Microsphere model analysis showed smaller values in the first rCBF image by 3% and in the second by 10%, resulting in lower values for cerebrovascular reactivity. The difference in cerebrovascular reactivity between ischemic and nonischemic areas, however, is highly significant., Conclusion: The double-injection method for IMP is feasible for two sequential rCBF measurements in a single procedure and is applicable for acetazolamide challenge. Simple microsphere model analysis, as well as a two-compartment model analysis, provide reliable assessment for cerebrovascular reactivity despite the complex dynamics of IMP and are feasible for clinical application.

Unlabelled: Copper-62-pyruvaldehyde bis(N4-methylthiosemicarbazone) copper II (62Cu-PTSM) has been proposed as a generator-produced positron-emitting tracer for perfusion imaging. To evaluate the characteristics of 62Cu-PTSM as a cerebral perfusion tracer, brain PET images of 62Cu-PTSM were compared with cerebral blood flow (CBF)., Methods: Following an intravenous injection of 62Cu-PTSM, a serial dynamic PET scan was performed for 10 min with arterial sampling in 10 subjects. CBF was measured by 15O-labeled water before the 62Cu-PTSM study., Results: Dynamic PET scan with octanol-extracted arterial input function indicated the presence of significant back-diffusion of 62Cu-PTSM from the brain within 3 min after injection, followed by stable activity from 3 to 10 min. Comparison with 15O-water PET demonstrated less contrast between high- and low-flow regions in 62Cu-PTSM image and a nonlinear relationship of flow and 62Cu-PTSM uptake, which suggests the underestimation of CBF in high-flow regions due to the existence of back-diffusion., Conclusion: Although 62Cu-PTSM can be used widely for evaluation of brain perfusion with PET, kinetic analysis and correction may be needed to quantify regional CBF.