Use of the left ventricular time-activity curve as a noninvasive input function in dynamic oxygen-15-water positron emission tomography.

Noninvasive recording of arterial input functions using regions of interest (ROIs) in the left ventricular (LV) chamber obviates the need for arterial cannulation in PET, but it is compromised by the limited recovery coefficient of the LV chamber and by statistical noise. In the present study, a new mathematical model has been developed, which corrects for the spillover of radioactivity both from the myocardium into the LV ROI and the blood into the myocardial ROI. The method requires the measurement of a time-activity curve in the LV chamber during the dynamic H2(15)O PET study and the measurement of the recovery coefficient of the LV ROI using a 15O-carbon monoxide (C15O) scan and venous blood sampling. This approach was successfully validated against direct measurements of the arterial input function using an on-line beta detector in five greyhounds undergoing dynamic H2(15)O PET imaging. This technique also yielded myocardial blood flow (MBF) values which were not significantly different from those obtained with the beta-probe analyses (maximum difference less than 2%), provided that the LV ROIs were sufficiently large to provide good counting statistics. When this model was not applied for large ROIs (small recovery in LV ROI), systematic overestimations in MBF compared with beta-probe analysis (e.g., a factor by 40% for a recovery coefficient of 0.7) were observed. Thus, this technique enabled the prediction of an accurate input function using the LV time-activity curve, and hence, noninvasive quantification of MBF without arterial cannulation.     

Use of the abdominal aorta for arterial input function determination in hepatic and renal PET studies.

A method using the activity in the abdominal aorta of human and animal subjects to noninvasively estimate blood-pool input function in dynamic, abdominal PET scans is proposed and validated in this paper. Partial volume effects due to the aorta's dimensions are corrected by a semi-automated algorithm based on the transaxial resolution in the reconstructed images. The technique was validated by comparing PET measurements of abdominal aortic activity to well counter measurements of arterial blood samples (eight canine renal studies) and to PET measurements of left ventricular cavity activity (eight human hepatic studies). In renal studies, correlation analysis of the areas subtended by the two input functions yielded an essentially unitary slope (1.03 +/- 0.09), with high correlation (R2 greater than 0.95, p less than 0.001). In hepatic studies, similar values (0.99 +/- 0.03 and R2 greater than 0.85, p less than 0.001) were found. Correlation of the blood flow estimates based on the two input functions and a two-compartment model produced slopes of 1.07 +/- 0.16 and 1.03 +/- 0.07, and correlations of (R2 greater than 0.98, p less than 0.001) and (R2 greater than 0.97, p less than 0.001) for the renal and hepatic studies, respectively. We conclude that noninvasive, accurate measurements of the arterial input function by dynamic PET imaging are possible and represent a clinically viable alternative to arterial blood sampling.     

A tracer kinetic model for 18F-FHBG for quantitating herpes simplex virus type 1 thymidine kinase reporter gene expression in living animals using PET.

Reporter probe 9-(4-18F-fluoro-3-[hydroxymethyl]butyl)guanine (18F-FHBG) and reporter gene mutant herpes simplex virus type 1 thymidine kinase (HSV1-sr39tk) have been used for imaging reporter gene expression with PET. Current methods for quantitating the images using the percentage injected dose per gram of tissue do not distinguish between the effects of probe transport and subsequent phosphorylation. We therefore investigated tracer kinetic models for 18F-FHBG dynamic microPET data and noninvasive methods for determining blood time-activity curves in an adenoviral gene delivery model in mice. METHODS: 18F-FHBG (approximately 7.4 MBq [approximately 200 microCi]) was injected into 4 mice; 18F-FHBG concentrations in plasma and whole blood were measured from mouse heart left ventricle (LV) direct sampling. Replication-incompetent adenovirus (0-2 x 10(9) plaque-forming units) with the E1 region deleted (n = 8) or replaced by HSV1-sr39tk (n = 18) was tail-vein injected into mice. Mice were dynamically scanned using microPET (approximately 7.4 MBq [approximately 200 microCi] 18F-FHBG) over 1 h; regions of interest were drawn on images of the heart and liver. Serial whole blood 18F-FHBG concentrations were measured in 6 of the mice by LV sampling, and 1 least-squares ratio of the heart image to the LV time-activity curve was calculated for all 6 mice. For 2 control mice and 9 mice expressing HSV1-sr39tk, heart image (input function) and liver image time-activity curves (tissue curves) were fit to 2- and 3-compartment models using Levenberg-Marquardt nonlinear regression. The models were compared using an F statistic. HSV1-sr39TK enzyme activity was determined from liver samples and compared with model parameter estimates. For another 3 control mice and 6 HSV1-sr39TK-positive mice, the model-predicted relative percentage of metabolites was compared with high-performance liquid chromatography analysis. RESULTS: The ratio of 18F-FHBG in plasma to whole blood was 0.84 +/- 0.05 (mean +/- SE) by 30 s after injection. The least-squares ratio of the heart image time-activity curve to the LV time-activity curve was 0.83 +/- 0.02, consistent with the recovery coefficient for the partial-volume effect (0.81) based on independent measures of heart geometry. A 3-compartment model best described 18F-FHBG kinetics in mice expressing HSV1-sr39tk in the liver; a 2-compartment model best described the kinetics in control mice. The 3-compartment model parameter, k3, correlated well with the HSV1-sr39TK enzyme activity (r2 = 0.88). CONCLUSION: 18F-FHBG equilibrates rapidly between plasma and whole blood in mice. Heart image time-activity curves corrected for partial-volume effects well approximate LV time-activity curves and can be used as input functions for 2- and 3-compartment models. The model parameter k3 from the 3-compartment model can be used as a noninvasive estimate for HSV1-sr39TK reporter protein activity and can predict the relative percentage of metabolites.     

Quantification of regional myocardial blood flow using dynamic H2(15)O PET and factor analysis.

Because the use of factor analysis has been proposed for extracting pure physiologic temporal or spatial information from dynamic nuclear medicine images, factor analysis should be capable of robustly estimating regional myocardial blood flow (rMBF) using H2(15)O PET without additional C15O PET, which is a cumbersome procedure for patients. Therefore, we measured rMBF using time-activity curves (TACs) obtained from factor analysis of dynamic myocardial H2(15)O PET images without the aid of C15O PET. METHODS: H2(15)O PET of six healthy dogs at rest and during stress was performed simultaneously with microsphere studies using 85Sr, 46Sc, and 113SN: We performed factor analysis in two steps after reorienting and masking the images to include only the cardiac region. The first step discriminated each factor in the spatial distribution and acquired the input functions, and the second step extracted regional-tissue TACS: Image-derived input functions obtained by factor analysis were compared with those obtained by the sampling method. rMBF calculated using a compartmental model with tissue TACs from the second step of the factor analysis was compared with rMBF measured by microsphere studies. RESULTS: Factor analysis was successful for all the dynamic H2(15)O PET images. The input functions obtained by factor analysis were nearly equal to those obtained by arterial blood sampling, except for the expected delay. The correlation between rMBF obtained by factor analysis and rMBF obtained by microsphere studies was good (r = 0.95). The correlation between rMBF obtained by the region-of-interest method and rMBF obtained by microsphere studies was also good (r = 0.93). CONCLUSION: rMBF can be measured robustly by factor analysis using dynamic myocardial H2(15)O PET images without additional C15O blood-pool PET.     

Simple noninvasive quantification method for measuring myocardial glucose utilization in humans employing positron emission tomography and fluorine-18 deoxyglucose

To estimate regional myocardial glucose utilization (rMGU) with positron emission tomography (PET) and 2-[18F]fluoro-2-deoxy-D-glucose (FDG) in humans, we studied a method which simplifies the experimental procedure and is computationally efficient. This imaging approach uses a blood time-activity curve derived from a region of interest (ROI) drawn over dynamic PET images of the left ventricle (LV), and a Patlak graphic analysis. The spillover of radioactivity from the cardiac chambers to the myocardium is automatically removed by this analysis. Estimates of rMGU were obtained from FDG PET cardiac studies of six normal human subjects. Results from this study indicate that the FDG time-activity curve obtained from the LV ROI matched well with the arterial plasma curve. The rMGU obtained by Patlak graphic analysis was in good agreement with direct curve fitting results (r = 0.90). The average standard error of the estimate of the Patlak rMGU was low (3%). These results demonstrate the practical usefulness of a simplified method for the estimation of rMGU in humans by PET. This approach is noninvasive, computationally fast, and highly suited for developing parametric images of myocardial glucose utilization rate.     

Bringing physiology into PET of the liver

Several physiologic features make interpretation of PET studies of liver physiology an exciting challenge. As with other organs, hepatic tracer kinetics using PET is quantified by dynamic recording of the liver after the administration of a radioactive tracer, with measurements of time-activity curves in the blood supply. However, the liver receives blood from both the portal vein and the hepatic artery, with the peak of the portal vein time-activity curve being delayed and dispersed compared with that of the hepatic artery. The use of a flow-weighted dual-input time-activity curve is of importance for the estimation of hepatic blood perfusion through initial dynamic PET recording. The portal vein is inaccessible in humans, and methods of estimating the dual-input time-activity curve without portal vein measurements are being developed. Such methods are used to estimate regional hepatic blood perfusion, for example, by means of the initial part of a dynamic (18)F-FDG PET/CT recording. Later, steady-state hepatic metabolism can be assessed using only the arterial input, provided that neither the tracer nor its metabolites are irreversibly trapped in the prehepatic splanchnic area within the acquisition period. This is used in studies of regulation of hepatic metabolism of, for example, (18)F-FDG and (11)C-palmitate.     

Noninvasive quantitative measurement of cerebral blood flow with 123I-IMP--a study concerning the input function]

For the noninvasive quantitative measurement of cerebral blood flow (CBF) using N-isopropyl-[123I]p-iodoamphetamine (IMP), we studied the usefulness of the lung clearance curve obtained by a single probe detector as the input function for brain as an alternative to arterial blood activity. In four patients, we compared the time-activity curve of the lung and serial arterial blood activity for approximately 20 minutes following an IV bolus injection of IMP. Significant positive correlations were observed between lung clearance and the integral of arterial blood activity of IMP. In addition, a study to identify the best region for monitoring lung activity with the probe detector was performed in six patients using a gamma camera and region of interest (ROI) management. The central region of the right lung was found to be the best position for monitoring lung radioactivity. This study suggests that the lung clearance curve of IMP can be used as the input function for brain in the quantitative assessment of CBF.     

Minimally invasive method of determining blood input function from PET images in rodents.

For cardiovascular research on rodents, small-animal PET has limitations because of the inherent spatial resolution of the system and because of cardiac motion. A factor analysis (FA) technique for extracting the blood input function and myocardial time-activity curve from dynamic small-animal PET images of the rodent heart has been implemented to overcome these limitations. METHODS: Six Sprague-Dawley rats and 6 BALB/c mice underwent dynamic imaging with 18F-FDG (n = 6) and 1-11C-acetate (n = 6). From the dynamic images, blood input functions and myocardial time-activity curves were extracted by the FA method. The accuracy of input functions derived by the FA method was compared with that of input functions determined from serial blood samples, and the correlation coefficients were calculated. RESULTS: Factor images (right ventricle, left ventricle, and myocardium) were successfully extracted for both 18F-FDG and 1-11C-acetate in rats. The correlation coefficients for the input functions were 0.973 for 18F-FDG and 0.965 for 1-11C-acetate. In mice, the correlation coefficients for the input functions were 0.930 for 18F-FDG and 0.972 for 1-11C-acetate. CONCLUSION: The FA method enables minimally invasive extraction of accurate input functions and myocardial time-activity curves from dynamic microPET images of rodents without the need to draw regions of interest and without the possible complications of surgery and repeated blood sampling.     

Regions of interest in the venous sinuses as input functions for quantitative PET.

As clinical PET becomes increasingly available, quantitative methods that are feasible in busy clinical settings are becoming necessary. We investigated the use of intracranial blood pools as sources of an input function for quantitative PET. METHODS: We studied 25 patients after the intravenous injection of [18F]6-fluoro-L-m-tyrosine and compared sampled blood time-activity curves with those obtained in small regions of interest (ROIs) defined in the blood pools visible in the PET images. Because of the comparatively large dimensions of the blood pool at the confluence of the superior sagittal, straight and transverse sinuses, a venous ROI input function was chosen for further analysis. We applied simple corrections to the ROI-derived time-activity curves, deriving expressions for partial volume, spillover and partition of tracer between plasma and red blood cells. The results of graphic and compartmental analysis using both sampled [Cs(t)] and ROI [Cr(t)] venous input functions for each patient were compared. We also used an analytic approach to examine possible differences between venous and arterial input functions in the cerebral circulation. RESULTS: Cr(t) peaked significantly earlier and higher than Cs(t) in this patient population, although the total integral under the curves did not differ significantly. We report some apparent differences in the results of modeling using the two input functions; however, neither the graphically determined influx constant, Ki, nor the model parameter that reflects presynaptic dopaminergic metabolism, k3, differed significantly between the two methods. The analytic results suggest that the venous ROI input function may be closer to the arterial supply of radiotracer to the brain than arterialized venous blood, at least in some patient populations. CONCLUSION: We present a simple method of obtaining an input function for PET that is applicable to a wide range of tracers and quantitative methods and is feasible for diagnostic PET imaging.     

Noninvasive quantification of regional myocardial blood flow and ammonia extraction fraction using nitrogen-13 ammonia and positron emission tomography

This report describes the theoretical basis and a method to quantitate regional myocardial blood flow (RMBF) and ammonia extraction fraction (E) in man, noninvasively, with N-13 ammonia and positron emission tomography (PET). Two patients with hypertrophic cardiomyopathy, whose left ventricular (LV) walls were markedly thick, were employed in this study to avoid partial volume effects and cross contamination between LV walls and blood pool. RMBF and E were calculated from time-activity curves of myocardial tissue and left atrium derived from serial 6-second PET images of the heart. The time-activity curve of left atrium was used as an arterial input function. The results were RMBF = 67 +/- 4 ml/min/100 g, E = 80 +/- 13% and 65 +/- 10 ml/min/100 g, 81 +/- 16% for each patient. The validity of the present method was discussed.     

Measurement of input functions in rodents: challenges and solutions

INTRODUCTION: Tracer kinetic modeling used in conjunction with positron emission tomography (PET) is an excellent tool for the noninvasive quantification of physiological, biological and molecular processes and their alterations due to disease. Currently, complex multi-compartment modeling approaches are being applied in a variety of clinical studies to determine myocardial perfusion, viability and glucose utilization as well as fatty acid metabolism and oxidation in the normal and diseased heart. These kinetic models require two key measurements of tracer activity over time, tracer activity in arterial blood (input function) and its corresponding activity in the organ of interest. The alteration in the time course of tracer activity as it travels from blood to the organ of interest describes the kinetics of the tracer. To be able to implement these approaches in rodent models of disease using small-animal PET (microPET), it is imperative that the input function is measured accurately. METHODS: The blood input functions in rodent experiments were obtained by (1) direct blood sampling, (2) direct measurement of blood activity by a beta-detecting probe that counts the activity in the blood, (3) an arterial-venous bypass (A/V shunt), (4) factor analysis of dynamic structures from dynamic PET images and (5) measurement from region-of-interest (ROI) analysis of dynamic PET images. Direct blood sampling was used as the reference standard to which the results of the other techniques were compared. RESULTS: Beta probes are difficult to operate and may not provide accurate blood input functions unless they are used intravenously, which requires complicated microsurgery. A similar limitation applies to the A/V shunt. Factor analysis successfully extracts the blood input function for mice and rats. The ROI-based method is less accurate due to limited image resolution of the PET system, which results in severe partial volume effect and spillover from myocardium. CONCLUSION: The current reference standard, direct blood sampling, is more invasive and has limited temporal resolution. With current imaging technology, image-based extraction of blood input functions is possible by factor analysis, while forthcoming technological developments are likely to allow extraction of input function directly from the images. These techniques will reduce the level of complexity and invasiveness for animal experiments and are likely to be used more widely in the future.     

55Co-EDTA for renal imaging using positron emission tomography (PET): a feasibility study

The feasibility of imaging renal function with 55Co-ethylene diamine tetraacetic acid (EDTA) and dynamic positron emission tomography was investigated. A group of normal Wistar rats was injected intravenously with 55Co-EDTA and underwent dynamic positron emission tomography (PET) imaging in order to study the biodistribution. The time-activity curves of the heart (blood pool), both kidneys, liver, and bladder were observed. In two animals, blood and urinary clearances of 55Co-EDTA were compared with those for 51Cr-EDTA. In one animal, unilateral reduction in kidney function was induced and the right/left ratio for the kidneys was determined. The time-activity curves showed that 55Co-EDTA cleared rapidly from the blood pool (heart), whereas prompt and high target-to-background ratios for both kidneys were obtained. The entire tracer was cleared from the renal parenchyma by urinary excretion and collection of the activity in the bladder. No specific activity uptake was noticed in any other organ or tissue. The clearances of 55Co-EDTA and 51Cr-EDTA in blood were not significantly different, showing that the nature of the M++ has no influence on the in vivo behavior of EDTA. 55Co can be produced easily by cyclotron irradiation and 55Co-EDTA is a promising physiological tracer for nephrological research using PET.     

Quantitation of myocardial blood flow with H2 15O and positron emission tomography: assessment and error analysis of a mathematical approach

Quantitation of regional myocardial blood flow (MBF) in absolute terms with positron emission tomography (PET) has been difficult to achieve in part because of errors induced by the relatively low spatial resolution of current tomographic instruments. We previously demonstrated that MBF could be accurately measured over a wide range of flows after intravenous administration of H2 15O when the arterial input function and myocardial radiotracer content were measured directly. To extend this quantitative approach for noninvasive estimates of MBF with PET. We recently developed and implemented a novel mathematical approach whereby partial volume and spillover effects were estimated along with flow within the operational one-compartment flow equation. Noninvasive estimates of flow correlated closely with flow measured directly with radiolabeled microspheres. In the present study, with the use of a commercially available cardiac phantom, we assessed our ability to obtain true time-activity curves from observed PET data contaminated by partial volume and spillover effects. Computer simulations demonstrated that the approach developed is relatively insensitive to most potential sources of error, but is sensitive to timing discrepancies between the arterial input function and the tissue time-activity curve. Implementation of this approach provides accurate quantitation of regional MBF in absolute terms and should be useful in noninvasive evaluation of the efficacy of treatments designed to enhance nutritional perfusion in human subjects.     

Estimation of the 18F-FDG input function in mice by use of dynamic small-animal PET and minimal blood sample data.

Derivation of the plasma time-activity curve in murine small-animal PET studies is a challenging task when tracers that are sequestered by the myocardium are used, because plasma time-activity curve estimation usually involves drawing a region of interest within the area of the reconstructed image that corresponds to the left ventricle (LV) of the heart. The small size of the LV relative to the resolution of the small-animal PET system, coupled with spillover effects from adjacent myocardial pixels, makes this method reliable only for the earliest frames of the scan. We sought to develop a method for plasma time-activity curve estimation based on a model of tracer kinetics in blood, muscle, and liver. METHODS: Sixteen C57BL/6 mice were injected with (18)F-FDG, and approximately 15 serial blood samples were taken from the femoral artery via a surgically inserted catheter during 60-min small-animal PET scans. Image data were reconstructed by use of filtered backprojection with CT-based attenuation correction. We constructed a 5-compartment model designed to predict the plasma time-activity curve of (18)F-FDG by use of data from a minimum of 2 blood samples and the dynamic small-animal PET scan. The plasma time-activity curve (TACp) was assumed to have 4 exponential components (TAC(P)=A(1)e(lambda(1)t)+A(2)e(lambda(2)t)+A(3)e(lambda(3)t)-(A(1)+A(2)+A(3))e(lambda(4)t)) based on the serial blood samples. Using Bayesian constraints, we fitted 2-compartment submodels of muscle and liver to small-animal PET data for these organs and simultaneously fitted the input (forcing) function to early small-animal PET LV data and 2 blood samples (approximately 10 min and approximately 1 h). RESULTS: The area under the estimated plasma time-activity curve had an overall Spearman correlation of 0.99 when compared with the area under the gold standard plasma time-activity curve calculated from multiple blood samples. Calculated organ uptake rates (Patlak K(i)) based on the predicted plasma time-activity curve had a correlation of approximately 0.99 for liver, muscle, myocardium, and brain when compared with those based on the gold standard plasma time-activity curve. The model was also able to accurately predict the plasma time-activity curve under experimental conditions that resulted in different rates of clearance of the tracer from blood. CONCLUSION: We have developed a robust method for accurately estimating the plasma time-activity curve of (18)F-FDG by use of dynamic small-animal PET data and 2 blood samples.     

Non-invasive quantification of cerebral blood flow for rats by microPET imaging of 15O labelled water: the application of a cardiac time-activity curve for the tracer arterial input function

OBJECTIVE: In-vivo quantitative cerebral blood flow (CBF) measurement using positron emission tomography (PET) has typically employed invasive arterial blood sampling procedure to determine the arterial input function (AIF). The present study was performed to provide a non-invasive quantitative CBF measurement technique for rats using a dedicated animal PET. METHODS: CBF was measured in 10 male rats (Fischer 344, 247-290 g) under alpha-chloralose anesthesia (30 mg x kg . h, intravenous infusion) by dynamic PET imaging employing the intravenous bolus injection of H2(15)O. Unlike other conventional PET methods, no arterial blood sampling was employed. Instead, a cardiac time-activity curve (TAC) obtained from the dynamic PET imaging was used to determine the AIF. For the validation of this technique, CBF was also measured by calculating the washout rate of the tracer (H2(15)O) following an intracarotid bolus injection. CBF measurements by two independent methods were done while modulating and maintaining the body temperature at two different levels (32+/-1 and 37+/-1 degrees C by the rectal temperature). Two methods were compared by the linear regression analysis. RESULTS: CBF (ml x 100 g x min) values (mean+/-SD) were 45.2+/-6.05 (intravenous) and 47.4+/-8.64 (intracarotid) at the hypothermic condition (32 degrees C), and 55.1+/-4.88 (intravenous) and 54.4+/-4.60 (intracarotid) at the normothermic condition (37 degrees C). There was a good agreement between the two methods (r=0.70). CONCLUSIONS: Our cardiac TAC analysis technique for small animals can be used for the non-invasive quantification of CBF using the PET-based in-vivo imaging technique.     

Arterial input function measurement without blood sampling using a beta-microprobe in rats.

The evaluation of every new radiotracer involves pharmacokinetic studies on small animals to determine its biodistribution and local kinetics. To extract relevant biochemical information, time-activity curves for the regions of interest are mathematically modeled on the basis of compartmental models that require knowledge of the time course of the tracer concentration in plasma. Such a time-activity curve, usually termed input function, is determined in small animals by repeated blood sampling and subsequent counting in a well counter. The aim of the present work was to propose an alternative to blood sampling in small animals, since this procedure is labor intensive, exposes the staff to radiation, and leads to an important loss of blood, which affects hematologic parameters. METHODS: Monte Carlo simulations were performed to evaluate the feasibility of measuring the arterial input function using a positron-sensitive microprobe placed in the femoral artery of a rat. The simulation results showed that a second probe inserted above the artery was necessary to allow proper subtraction of the background signal arising from tracer accumulation in surrounding tissues. This approach was then validated in vivo in 5 anesthetized rats. In a second set of experiments, on 3 rats, a third probe was used to simultaneously determine 18F-FDG accumulation in the striatum. RESULTS: The high temporal resolution of the technique allowed accurate determination of the input function peak after bolus injection of 18F-FDG. Quantitative input functions were obtained after normalization of the arterial time-activity curve for a late blood sample. In the second set of experiments, compartmental modeling was achieved using either the blood samples or the microprobe data as the input function, and similar kinetic constants were found in both cases. CONCLUSION: Although direct quantification proved difficult, the microprobe allowed accurate measurement of arterial input function with a high temporal resolution and no blood loss. The technique, because offering adequate sensitivity and temporal resolution for kinetic measurements of radiotracers in the blood compartment, should facilitate quantitative modeling for radiotracer studies in small animals.     

Application of a beta microprobe for quantification of regional cerebral blood flow with15O-water and PET in rhesus monkeys

A beta microprobe was successfully applied to monitor arterial input function for quantification of regional cerebral blood flow (rCBF) in the monkey brain with¹⁵O-water and positron emission tomography (PET). The sensitivity of the probe was approximately 0.83 to 1.67 cps/kBq/ml depending on the studies. A preliminary study was performed to find a suitable use and to evaluate the performance of the system and data analysis procedure. The results showed that dispersion correction of measured input function was unnecessary if microprobes were connected directly to the arterial catheter. Then multiple CBF measurements were done in three monkeys under anesthesia. Identical regions of interest were placed with the aid of magnetic resonance imaging (MRI) of each monkey and rCBF values were estimated. Estimated rCBFs were reproducible for several measurements. The mean CBF value for a pentobarbital anesthetized monkey was 46.0 ml/ min/100 g (PaCO₂ = 46.3 mmHg). This shows that the use of the beta microprobe for quantification of rCBF with PET was validated. The lack of a need for dispersion correction of observed input function is an advantage with the beta microprobe system because the probes are small enough to be placed near the arterial sampling site.     

Measurement of skeletal muscle glucose utilization by dynamic 18F-FDG PET without arterial blood sampling

OBJECTIVE: Skeletal muscle glucose utilization (SMGU) can be measured by 18F-FDG PET to characterize insulin resistance. The aim of this study was to determine whether femoral muscle SMGU can be measured without arterial blood sampling by sequential PET imaging of the thoracic and femoral regions. METHODS: Ten patients with possible insulin resistance underwent dynamic 18F-FDG PET of the femoral region during hyperinsulinaemic euglycaemic clamping (group A), and femoral muscle SMGU was calculated using PET data of various time periods and measured arterial input. SMGU was also calculated using venous plasma activity, instead of arterial activity, as input during the late phase. Another five patients underwent sequential PET of the thoracic and femoral regions after single tracer injection (group B). The input function was estimated from aorta activity on thoracic images during the early phase and from venous activity during the late phase, and SMGU with this estimated input was compared with that with measured arterial input. RESULTS: In group A, exclusion of early dynamic PET data from analysis had essentially no effect on the calculated SMGU, and partial substitution of venous activity for arterial activity only marginally changed the estimates. The difference between SMGUs with measured and estimated inputs was minimal in group B. CONCLUSION: Femoral muscle SMGU can be calculated without femoral imaging early after tracer injection, and the input function can be assessed using data of thoracic imaging and venous blood samples. These results support the validity of measuring femoral muscle SMGU without arterial sampling, simultaneously with measurement of myocardial glucose utilization.     

Estimation of integral of input function for quantification of cerebral blood flow with N-isopropyl-p-[123I]iodoamphetamine using one-point venous blood sampling

The present study was designed to investigate a possibility of substitution of the venous blood radioactivity counts sampled 26 min post injection for the octanol-extracted arterial blood radioactivity counts obtained at 5 min after the injection of N-isopropyl-p-[123I]iodoamphetamine (123I-IMP). Furthermore, we investigated whether the integral of input function can be estimated from the venous blood radioactivity counts sampled 26 min post injection and the whole-brain time-activity curves early after 123I-IMP injection. There was a good correlation between the arterial blood radioactivity counts sampled 5 min post injection (y) and those obtained at 26 min (r = 0.902; n = 91; y = 2.348x - 867.063). There was also a good correlation between the arterial (x) and venous blood radioactivity counts (y) sampled 26 min post injection (r = 0.954; n = 14; y = 0.761x + 924.336). The venous blood radioactivity counts sampled at 26 min (x) correlated well with the octanol-extracted arterial blood radioactivity counts sampled at 5 min (y) (r = 0.964; n = 32; y = 0.173x - 21.598). There was a good correlation between the integrals of input function obtained from the regression equation obtained above and the whole-brain time-activity curves acquired during 7 min post injection (y) and those obtained by 5-min continuous arterial blood sampling (x) (r = 0.965; n = 41; y = 0.957x + 2665.208). These results indicate that this noninvasive and simple method can estimate the integral of input function for quantification of cerebral blood flow using 123I-IMP.     

Estimating the plasma time-activity curve during radionuclide renography

Quantitative analysis of the radionuclide renogram requires an estimate of the plasma time-activity curve. This estimate is usually obtained from an externally detected blood-pool curve that is calibrated with a single plasma sample. However, external probes detect activity in the extravascular as well as the intravascular space. This may lead to significant errors in estimating the plasma time-activity curve. A method for overcoming this problem by using a continuously varying calibration factor based upon multiple plasma samples was therefore evaluated. Externally detected blood-pool curves were used to estimate the plasma time-activity curves obtained from rabbits during radionuclide renography. Estimates obtained using the externally detected curves calibrated with a constant calibration factor were found to be significantly biased, while estimates obtained using the externally detected curves calibrated with the continuously varying calibration factor were not.