A multicenter validation of regional cerebral blood flow quantitation using [123I]iodoamphetamine and single photon emission computed tomography.

Recently, two methods have been proposed for regional cerebral blood flow (rCBF) quantitation using [123I]iodoamphetamine (IMP) and single-photon emission computed tomography (SPECT). The table look-up (TLU) method has been shown to provide both rCBF and volume of distribution, Vd, images from two SPECT scans, while a single-scan autoradiographic (ARG) technique provided rCBF using a fixed and assumed Vd. In both methods, a single blood sample was referred to calibrate the previously determined standard input function. The present multicenter project was designed to evaluate the accuracy of both methods for use as clinical investigative tools. Ten independent institutions performed [123I]IMP-SPECT studies according to both methods in 76 subjects (10 normal volunteers, 32 patients with cerebrovascular disease, and 34 patients with other diseases). Calculated rCBF values were compared with those obtained by the following reference methods available in the participating institutions; [15O] H2O positron emission tomography (PET) (five institutions), [133Xe]SPECT (four institutions), and the [123I]IMP microsphere method (three institutions). Both ARG and TLU methods provided rCBF values that were significantly correlated with those measured by the [15O] H2O PET technique (p < 0.001 for all subjects; overall regression equation, y = 15.14 + 0.54x) and those measured by the [123I]IMP-microsphere method (p < 0.001 for all subjects: y = 2.0 + 0.80x). Significant correlation (p < 0.05) was observed in 18 of 24 subjects studied with the [133Xe] SPECT reference technique (overall regression equation, y = 15.0 + 0.55x). Mean cortical gray matter rCBF in a group of normal subject was 43.9 +/- 3.3 and 43.4 +/- 2.0 ml/min/100 g for the ARG and TLU methods, respectively. Regional Vd of [123I]IMP estimated by the TLU method was 45 ml/ml +/- 20% in the normal cortical region. Close agreement between ARG and TLU rCBF values was observed (y = -3.21 + 1.07x, r = 0.97), confirming the validity of assuming a fixed Vd in the ARG method. Results of this study demonstrate that both the ARG and TLU methods accurately and reliably estimate rCBF in a variety of clinical settings.

A comparative study of simple methods to measure regional cerebral blood flow using iodine-123-IMP SPECT.

UNLABELLED: The aim of this study was to compare the accuracy and reliability of simple methods of quantifying regional cerebral blood flow (rCBF) with 123I-labeled N-isopropyl-p-iodoamphetamine (IMP) and SPECT and to determine which method was best. METHODS: Four methods were examined: (a) the microsphere method with continuous withdrawal of arterial blood, which was based on a microsphere model using the SPECT image obtained 5 min after tracer injection, (b) the microsphere method with one-point sampling, which was the same as the first method except that one-point sampling was used instead of continuous withdrawal, (c) the modified microsphere method with one-point sampling, which was the same as the second method except that a later SPECT image (30-min postinjection) with correction was used and (d) a table look-up method based on a two-compartment model with one-point arterial blood sampling and two SPECT scans obtained 40- and 180-min postinjection. The accuracy of these methods was validated by comparing the rCBF values with those obtained by nonlinear least squares fitting analysis based on the two-compartment model in 15 subjects. RESULTS: Regional cerebral blood flow values obtained by the first method correlated most closely with those obtained by nonlinear least squares fitting analysis (error, 6.8%). The second method estimated rCBF with a mean error of 10.4%. The third method estimated rCBF with a mean error of 13.1%, even though it tended to slightly overestimate rCBF. The fourth method was inclined to underestimate rCBF with a mean error of 17.1%, and it greatly overestimated regional distribution volume. CONCLUSION: The first method was the most accurate and reliable. For less invasiveness, the first method should be combined with one-point sampling instead of continuous withdrawal, which was used in the second method. When using a delayed SPECT image with a conventional SPECT scanner, the third method was considered to be superior to the fourth method.

Quantification of cerebral blood flow and partition coefficient using iodine-123-iodoamphetamine.

UNLABELLED: The aim of this study was to develop a simple, noninvasive method for quantifying both regional cerebral blood flow (rCBF) and the partition coefficient (lambda) using N-isopropyl-p[123I]iodoamphetamine and SPECT. METHODS: By employing a two-compartment model (influx, K1: outflux, k2), a new method was introduced that requires two serial SPECT scans at 30 min and 60 min, and a single arterial sample 5 min after tracer injection. The integral of the arterial input function is inferred from the sample by using the correlation obtained from 25 subjects. Two original mathematical functions, phi for K1 and gamma for lambda (= K1/k2), were obtained from the input functions of 12 subjects. The values of K1 and lambda are determined from the two scans and the single arterial sample by using these functions. The values obtained for K1 (= rCBF) and lambda were compared with those obtained by nonlinear least-squares fitting analysis and the 133Xe inhalation SPECT method. RESULTS: K1 and lambda were in good agreement with the values obtained by nonlinear least-squares fitting analysis (r = 0.873 in K1 and r = 0.825 in lambda), and rCBF values were closely correlated with those obtained by the 133Xe method (r = 0.843). CONCLUSION: The proposed method has three advantages: (a) accurate, simultaneous quantification of both rCBF and the partition coefficient; (b) simplicity and noninvasiveness; and (c) a relatively short period (approximately 70 min) for the study.

Noninvasive quantification of cerebral blood flow using 99mTc-ECD and SPECT.

UNLABELLED: The aim of this study was to develop a simple, noninvasive method for quantifying regional cerebral blood flow (rCBF) using 99mTc-ethyl cysteinate dimer (ECD) by a single SPECT scan and single venous sampling. METHODS: Using a three-compartment model, we introduced the regional brain fractionation index (BFI), Cb(Ts)/integral of 0-Ts Ca(tau)dtau [Ca(t), arterial input; Cb(t), brain activity]. Regional BFI obtained at the optimum time Ts (min) was converted to rCBF using an exponential function, which was obtained by analyzing the relationship between regional BFI and rCBF (= F) obtained by the standard 133Xe inhalation SPECT method. The integral of the concentration of 99mTc-ECD in arterial blood corrected for physical decay [Ca(t)] in BFI was estimated from a single venous blood sample obtained at the optimum time Tv using the regression line obtained by analyzing the relationship between the integral of Ca(t) and venous sample data. The data come from three groups of patients. The first group of patients (n = 16) underwent a complete 99mTc-ECD BFI study with measurement of Ca(t) and dynamic SPECT scanning, as well as a 133Xe inhalation study to measure rCBF The results were used to analyze the relationship between regional BFI and rCBF (obtained with 133Xe) and to determine the optimum time Ts for obtaining BFI. Data from the second group of patients (n = 15) were used to analyze the relationship between the integral of Ca(t) and venous sample data and to determine the optimum time Tv for one-point venous blood sampling. Finally, the third group of patients (8 patients, 10 studies) was used to validate the current method by comparing the results with 133Xe inhalation SPECT. RESULTS: Regional BFI obtained at time Ts = 20 min showed good agreement (r = 0.907; a = 0.552, b = 0.962) with rCBF. The venous sample data obtained at time Tv = 6 min showed a good correlation (r = 0.988) with BFI. In comparing rCBF values thus obtained and those obtained by the 133Xe method, we found a good correlation (r = 0.917, slope = 1.01). CONCLUSION: The proposed method has three advantages: (a) accurate quantification of rCBF without underestimation in the high flow range, (b) simplicity and noninvasiveness and (c) the ability to use any type of SPECT camera for the study.

Assessment of dopamine and its metabolites in the intracellular and extracellular compartments of the rat striatum after peripheral administration of L-[11C]dopa.

Success in the synthesis of L-3,4-[beta-11C]dihydroxyphenylalanine (L-[11C]DOPA) and its application to positron emission tomography encouraged us to perform radioactive metabolite analyses in rats in an early phase after peripheral injection of L-[11C]DOPA. Following intravenous injection of [11C]DOPA, the radioactivity associated with DOPA and its metabolites was determined in the striatum after decapitation and in striatal extracellular fluid using in vivo brain microdialysis. Without pretreatment, 70-80% of 11C-radioactivity taken up into the striatum was associated with acidic metabolites of dopamine (DA) from 2 to 30 min after administration of L-[11C]DOPA with or without 300 micrograms/kg of unlabelled L-DOPA. In contrast, 80-90% of 11C-radioactivity in the striatum was associated with DOPA and DA after pretreatment with benserazide (25 mg/kg, i.p.) followed by administration of L-[11C]DOPA with or without unlabelled L-DOPA. The radioactivity in the DOPA fraction decreased with time (from 35% of 11C-radioactivity in the striatum at 5 min to 10% at 30 min), but that in the DA fraction increased (from 57% to 68%). The 11C-radioactivity in the extracellular fluid determined by brain microdialysis was less than 0.4% of that in the whole striatum and no radioactivity was present in the DA fraction. These results suggest that, in an early phase after administration of L-[11C]DOPA, [11C]DA is the main metabolite and is localized exclusively in the intracellular compartment within this time frame.

Reduced density of NMDA receptors and increased sensitivity to dizocilpine-induced learning impairment in aged rats.

About 20 min prior to training in a shock-motivated 14-unit T-maze, young (3-4 months) and aged (24-25 months) male Fischer-344 rats were given s.c. injections of either saline or dizocilpine (MK-801, 0.02 or 0.04 mg/kg), a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor. The aged rats showed a dose-dependent impairment in maze performance. Deficiencies were manifested as increases in errors, in runtime from start to goal, and in the number and duration of shocks received. In contrast, young rats exhibited no detrimental effects of dizocilpine on maze performance. Analysis of [3H]glutamate binding in these rats revealed a marked age-related decline in NMDA receptor binding in hippocampus. A significant correlation was observed between errors in the maze and hippocampal [3H]-glutamate binding, but the correlation was positive, i.e., rats that made the most errors had the highest level of NMDA receptor binding. Thus, compared to young rats, aged rats were more sensitive to the behavioral effects of NMDA receptor antagonism and they showed a hippocampal loss of [3H]glutamate in binding, which may be related to the increased sensitivity to dizocilpine. The positive correlation between poor maze performance and NMDA receptor binding suggests that the behaviors assessed involve complex interactions between NMDA receptors and other neuronal systems in the hippocampus.

131I-beta 2-microglobulin scintigraphy in patients with dialysis amyloidosis.

The noninvasive detection of amyloid deposits has recently become possible using scintigraphy with radiolabelled amyloid precursor protein (131I-beta 2-M). We studied 131I-beta 2-M scintigraphy in 15 dialysis patients with special attention to the mechanism of the localized accumulation of tracer. Scintiscans were positive in 8 of the 15 patients. Those with histologically proved amyloid deposits had positive images at the large joints with a continuous accumulation of tracer after 48, 72 and 144 hours. The most significant accumulation occurred bilaterally in the hip joints, followed by the shoulders and knees. Mild uptake was observed in the hands, elbows and feet. No apparent uptake of tracer occurred in patients with secondary hyperparathyroidism, pseudo-gout or AA-type amyloidosis. Three patients were operated for CTS during this study. The radioactivity of tissue excised during the operation was 2-18 times higher than that of fat or plasma. Study of synovial tissue showed that some of the cells surrounding the amyloid deposits took up the radiolabelled tracer. The present study suggests that circulating 131I-beta 2-M is taken up by the cells surrounding the amyloid deposits and detected as a positive scan. It is not known whether these cells react secondarily to amyloid deposits, or whether they take up beta 2-M and form amyloid fibrils.

A new method of regional cerebral blood flow measurement using one-point arterial sampling based on the microsphere model with N-isopropyl-p-[123I]-iodoamphetamine SPECT.

We developed a new method for quantitative measurement of regional cerebral blood flow (rCBF) using one-point arterial sampling with N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP) and single photon emission computed tomography (SPECT) based on the microsphere model. Although the conventional microsphere method requires both the continuous withdrawal of arterial blood (integral of Ca(t)) and treatment of the blood with octanol to obtain the fraction of true tracer activity in the integral of Ca(t) (N), the new method does not require these two procedures. We examined 14 patients to analyse the correlation between the integral of Ca(t)N and a small arterial sample obtained at one time point [one-point Ca(t)] after the injection of 123I-IMP without octanol treatment. The integral of Ca(t)N was calculated from one point Ca(t) using the regression line of the correlation. An error of 8.1% in the calculated value compared to the actual value of the integral of Ca(t)N, could be inferred from one-point Ca(t) obtained at 6 min after the injection. Then regional cerebral blood flow was measured by the method and a significant correlation was obtained with rCBF measured using the 133Xe inhalation method (r = 0.773). The one-point Ca(t) method provides fast, easy, accurate and non-invasive measurement of rCBF without inserting catheters and without treatment of arterial blood with octanol.

Can the microsphere model by applied to cerebral blood flow measurement using N-isopropyl-p-[123I]iodoamphetamine with SPET regardless of washout from brain tissue?

The microsphere model and the continuous withdrawal of arterial blood have commonly been used in clinical studies when measuring regional cerebral blood flow (rCBF) by N-isopropyl-p-[123I]iodoamphetamine (IMP) single photon emission tomography. The method is considered to underestimate rCBF because of the washout of tracer from brain tissue; however, the extent of this underestimation is not known. To assess whether this underestimation can be determined quantitatively, we performed simulation analysis based on the microsphere model and the two-compartment model [influx, K1(rCBF); and outflux, k2(washout)] using the time-activity curves of 123I-IMP in arterial blood [Ca(t)] of 10 subjects. With the microsphere method, rCBF values fell as time post-injection increased. The extent of underestimation of rCBF was 4.7 +/- 0.28% (mean +/- S.D.) at 5 min, 10.2 +/- 0.42% at 10 min and 15.2 +/- 0.55% at 15 min. There was little variation in the extent of underestimation and it was not dependent on the Ca(t) of the subjects. We therefore considered the results to be generally applicable to various studies of the microsphere model. As 4.7% is considered to be negligible in clinical studies, we conclude that the microsphere model can be applied to obtain accurate measurement of rCBF up to 5 min regardless of washout.

A potential use of a 123I-labelled benzodiazepine receptor antagonist as a predictor of neuronal cell viability: comparisons with 14C-labelled 2-deoxyglucose autoradiography and histopathological examination.

In the treatment and therapy of patients suffering a stroke, it is very important to predict whether viable neurones, even those of poor function, remain intact in the lesions of the brain. To determine whether viable neurones of low functional activity are represented in in vivo neuroreceptor imaging, we undertook experiments in gerbils with cerebral infarction, in which we examined histological changes and the results of dual-tracer in vivo autoradiography of glucose utilization with 14C-labelled deoxyglucose and benzodiazepine receptor binding with 123I-labelled Ro 16-0154. The unrelated findings of cerebral glucose metabolism and benzodiazepine receptor binding were observed in the primary infarct lesion and in remote areas, including the ipsilateral striatum and thalamus. Our experiments showed that when viable neurones with low functional activity remain intact, normal in vivo binding to benzodiazepine receptors is demonstrated as hypometabolism of glucose utilization. This functional, contrast-enhanced technique with 123I-labelled Ro 16-0154 may have an important role to play in the prediction of neuronal cell viability after recent brain infarction in experimental animals and humans using single photon emission tomography (SPET).

A comparative study of simple methods to quantify cerebral blood flow with acetazolamide challenge by using iodine-123-IMP SPECT with one-point arterial sampling.

The aim of this study was to compare the accuracy of simplified methods for quantifying rCBF with acetazolamide challenge by using 123I-N-isopropyl-p-iodoamphetamine (IMP) and SPECT with one-point arterial sampling. After acetazolamide administration we quantified rCBF in 12 subjects by the following three methods: (a) the modified microsphere method, (b) the IMP-autoradiographic (ARG) method based on a two-compartment one-parameter model, and (c) the simplified method based on a two-compartment two-parameter model (functional IMP method). The accuracy of these methods was validated by comparing rCBF values with those obtained by the standard method: the super-early microsphere method with continuous withdrawal of arterial blood. On analyzing rCBF in each flow range (0-0.25, 0.25-0.5, 0.5-0.75 and more than 0.75 ml/g/min), rCBF values obtained by both methods (a) and (c) showed significant correlations (p < 0.01) with those obtained by the standard method in every range, but rCBF values obtained by method (b) did not significantly correlated in the high flow range (0.5-0.75 and more than 0.75 ml/g/min). Method (c) was found to be the most accurate, even though it needs two serial SPECT scans. When requiring one SPECT scan, method (a) was considered to be superior to method (b) because of its accuracy, especially in high flow regions loaded with acetazolamide.

125I-iomazenil binding shows stress- and/or diazepam-induced reductions in mouse brain: supporting data for 123I-iomazenil SPECT study of anxiety disorders.

Effects of repeated swim stress on the binding of 125I-iomazenil were examined in the brains of diazepam-treated and non-treated mice. The mice were orally administered diazepam or vehicle (0.5% ethylene glycol) and subjected to daily swim stress (at 20 degrees C for 10 min) for seven consecutive days. The distribution and the amount of 125I-iomazenil binding were analyzed autoradiographically after in vivo and in vitro binding experiments. Repeated swim stress decreased the in vivo binding in the hippocampus (p < 0.05) and cerebral cortex (p < 0.05) of vehicle-treated mice but caused no significant changes in diazepam-treated mice. Subchronic treatment with diazepam decreased the in vivo binding approximately 50% in all brain regions examined (p < 0.01). The in vitro experiment, however, revealed no significant changes except in the hippocampus, where a small but significant decrease in the binding was observed after subchronic treatment with diazepam (p < 0.01). The stress- or diazepam-induced reductions seem to represent alterations in the in vivo environment related to 125I-iomazenil binding. These results suggest that we can investigate the pathophysiology of stress and anxiety with 123I-iomazenil SPECT. Care must be taken concerning the effects of benzodiazepines.

Redistribution on I-123 IMP SPECT in children and adolescents with partial seizures.

To evaluate the redistribution phenomenon on delayed I-123 IMP SPECT images of children and adolescents with partial seizures, 25 patients were selected and investigated in the interictal state. Early and delayed SPECT were performed 15-20 minutes and 5 hours, respectively, after I-123 IMP injection. Redistribution patterns were classified into three groups: 1) redistribution (RD) (-) group (n = 5), in which a low-uptake area on the early image persisted or was enlarged on the delayed image, 2) RD (+) group (n = 14), in which a low-uptake area on the early image changed to normal distribution on the delayed image, and 3) marked redistribution (MRD) (+) group (n = 6), In which a low-uptake area on the early image changed to a high uptake area on the delayed image. Among the patients who were followed for at least 12 months after the SPECT scans, the short-term clinical outcome tended to be good in the RD (+) group, intermediate in the MRD (+) group, and poor in the RD (-) group. These results of our preliminary comparative study indicate that the redistribution pattern of I-123 IMP may be related to the clinical aspects in patients with partial seizures and that it may play an important role in predicting their short-term clinical outcome.

SPECT imaging in a case of primary respiratory tract amyloidosis.

SPECT findings in a very rare case of primary amyloidosis localized in the laryngotracheobronchial area are reported. SPECT using Tc-99m PYP revealed widespread uptake in the larynx and the entire tracheobronchial tree up to the subsegmental divisions; the areas corresponded to diffuse thickening and calcification of the walls on CT. SPECT using Ga-67 citrate also showed marked uptake in the same area, consistent with the findings shown by SPECT using Tc-99m PYP.

Regional cerebral blood flow measured with I-123 IMP SPECT in a case of subcortical arteriosclerotic encephalopathy (Binswanger's disease).

N-isopropyl-p-[I-123] iodoamphetamine (I-123 IMP) SPECT studies were performed on a 75-year-old patient who could be clinically classified as subcortical arteriosclerotic encephalopathy (Binswanger's disease). Regional cerebral blood flow (rCBF) was quantitatively measured by a microsphere model, and was diffusely decreased in the whole brain (mean rCBF: 36 ml/100 g/minute). After a ventriculoperitoneal shunt operation, his clinical symptoms were markedly improved, and the improvement was validated by a 32% increase of mean rCBF. However, MRI and CT images showed no significant interval changes before and after the shunt operation. Regional rCBF measurement by I-123 IMP SPECT should be performed and plays an important role in the evaluation of Binswanger's disease.

Evaluation of cerebral blood flow in patients with idiopathic orthostatic hypotension using Tc-99m HMPAO brain SPECT during postural testing.

To determine whether regional cerebral blood flow (rCBF) would change on standing in patients with idiopathic orthostatic hypotension (IOH), Tc-99m HMPAO SPECT studies were performed during postural testing in five patients with IOH. After 10 minutes of quiet rest on a bed, the patients arose quickly and, at the same time, the radiotracer was injected intravenously. SPECT data were obtained with a ring-type SPECT scanner. Another dose of Tc-99m HMPAO was injected with the subjects in the supine position, and SPECT was performed again. Image subtraction was used to evaluate the change in rCBF caused by postural testing. In all patients, the authors observed a decrease of rCBF ni the frontal cortex and basal ganglia. This preliminary study suggests that changes in rCBF occur in patients with IOH on standing, and Tc-99m HMPAO SPECT performed during postural testing may have an important role in evaluating these changes.

[A fundamental study of 99mTc-HMPAO double injection method and clinical application to stress scintigraphy in orthostatic hypotension].

Double injection method using brain perfusion 99mTc-HMPAO SPECT is popular one for evaluating stress scintigraphy. For appropriate evaluation of this method 555 MBq (15 mCi) of 99mTc-HMPAO was injected twice in sequence at the resting state. The first and second SPECT images were obtained 5 min after each injection. Twenty-five ROIs of 8 x 8 pixels were placed on in various regions of the first images, and calculate each counts (C1). Then the counts of the same region of the second scan were calculated (C2). One hundred and fifty ROIs/6 patients were examined. We derived the linear relationship as C2 = 1.66 x C1 + 106 (r = 0.97), where C1 and C2 represents counts of the first scan, and second scan, respectively. This results suggests that the counts of the second scan is derived from the counts of the first scan without second scanning if they are obtained in the same condition. When we applied this method to stress scintigraphy, it may be useful for evaluating the regional brain perfusion changes before and after loading instead of using subtraction technique.

[Quantifying regional cerebral blood flow with N-isopropyl-p-[123I]iodoamphetamine and SPECT by one-point sampling method].

We developed a new non-invasive technique; one-point sampling method, for quantitative measurement of regional cerebral blood flow (rCBF) with N-isopropyl-p-[123I]iodoamphetamine and SPECT. Although the continuous withdrawal of arterial blood and octanol treatment of the blood are required in the conventional microsphere method, the new technique does not require these two procedures. The total activity of 123I-IMP obtained by the continuous withdrawal of arterial blood is inferred by the activity of 123I-IMP obtained by the one point arterial sample using a regression line. To determine when one point sampling time was optimum for inferring integral input function of the continuous withdrawal and whether the treatment of sampled blood for octanol fraction was required, we examined a correlation between the total activity of arterial blood withdrawn from 0 to 5 min after the injection and the activity of one point sample obtained at time t, and calculated a regression line. As the results, the minimum % error for the inference using the regression line was obtained at 6 min after the 123I-IMP injection, moreover, the octanol treatment was not required. Then examining an effect on the values of rCBF when the sampling time was deviated from 6 min, we could correct the values in approximately 3% error when the sample was obtained at 6 +/- 1 min after the injection. The one-point sampling method provides accurate and relatively non-invasive measurement of rCBF without octanol extraction of arterial blood.

[A new method for measurement of both regional cerebral blood flow and distribution volume using N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) and SPECT].

We developed a new method (functional IMP SPECT) to quantitate both regional cerebral blood flow (rCBF) and distribution volume (Vd) using 123I-IMP and SPECT based on a 2- compartment model (influx; K1 =rCBF and outflux; k2). This method requires one arterial blood sampling at 5 min after injection of the tracer and two SPECT scans at 30 min and 60 min. It takes approximately 60 min for total measurements. The integration of arterial input function is estimated by one blood sample taken at 5 min after injection of the tracer without octanol treatment, by using the correlation between one blood sample and the integration, which was obtained from studies on 25 subjects. With the value of integration, K1 and Vd are calculated from the data of two SPECT scans by using the mathematical functions based on the 2-compartment model, which were obtained from studies on 12 subjects. In the practical range of K1 (0.3-0.7 ml/g/min) and Vd (15-35 ml/g) given in the 2-compartment model, statistical errors of K1 and Vd obtained by the functional IMP SPECT were evaluated at approximately 14.0% and 17.2%, respectively. In clinical studies for eight subjects including two healthy volunteers, three patients with cerebral infarction and three patients with degenerative disease, K1 and Vd values estimated by the functional IMP SPECT were significantly correlated with those estimated by non-linear least squares fitting analysis based on the 2-compartment model, and the mean errors of K1 and Vd estimated by the functional IMP SPECT were approximately 8.0% and 11.2% respectively, suggesting the validity of the new method. We conclude that the functional IMP SPECT is clinically useful because of the accuracy, less-invasiveness and convenience.

[A study on evaluation of CBF measurement based on microsphere model with N-isopropyl-p-[123I]iodoamphetamine (IMP) and SPECT--its correction with the value of PaCO2].

To evaluate the regional cerebral blood flow measurement with N-isopropyl-p-[123I]iodoamphetamine (IMP), we performed 123I-IMP SPECT and 133Xe inhalation method on 9 patients with mild cerebrovascular diseases and so on. A tracer dose of 123I-IMP (111 MBq) was injected i.v. and the data were obtained 15 min later. Regional CBF was measured by the microsphere model and arterial blood sampling method. However, mean cerebral blood flow values was not in agreement with both methods. We supposed the reason of the disagreement was due to the difference of PaCO2 when the studies were performed. Hence, CBF measurement with 123I-IMP was performed on the other patient's population with loading of hyperventilation before the IMP injection. Comparing with the control state with normal breathing, we calculated the rate of change of mean CBF between the state with normal breathing and the state with hyperventilation that was 1.02 ml/100 g/min/mmHg PaCO2. After the correction with the rate, we observed a much significant relation between the mean CBF measured with 123I-IMP SPECT and 133Xe inhalation method. When compared CBF values with loading studies or certain therapies, the correction of CBF with the rate of change of PaCO2 is one of the very important factors to be considered. Moreover, 133Xe inhalation method without the correction of PaCO2 can not be a golden standard method for rCBF measurement.