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.     

Distribution and kinetics of carbon-11-cocaine in the human body measured with PET.

The extent to which the toxic properties of cocaine are related to its accumulation in various organs is not known. This study investigates cocaine uptake in the human body using 11C-cocaine and PET in 14 healthy males. The rate of uptake and clearance of 11C-cocaine varied among organs: peak uptake occurred in the lungs at 45 sec, in the heart and kidneys at 2-3 min, in the adrenals at 7-9 min, and in the liver at 10-15 min. Half-peak clearances were 90 sec in the lungs, 10 min in the heart and kidneys and 22 min in the adrenals. Liver radioactivity plateaued 10-15 min after injection and remained constant thereafter (40 min). Lung radioactivity paralleled that of plasma. The average uptake at peak was 0.007% (s.d., 0.001) dose/cc in the heart, 0.014% (s.d., 0.002) dose/cc in the kidney, 0.014% (s.d., 0.002) dose/cc in the liver and 0.034% (s.d., 0.001) dose/cc in the adrenals. The significant accumulation of cocaine in human heart, kidneys, adrenals and liver could contribute to its toxicity.     

Tumor blood flow measured by PET dynamic imaging of first-pass 18F-FDG uptake: a comparison with 15O-labeled water-measured blood flow.

PET molecular imaging of 15O-labeled water is the gold standard for measuring blood flow in humans. However, this requires an on-site cyclotron to produce the short-lived 15O tracer, which is cost-prohibitive for most clinical PET centers. The purpose of this study was to determine if the early uptake of 18F-FDG could be used to measure regional blood flow in tumors in the absence of 15O-water. METHODS: PET scans were obtained in patients being evaluated for tumor perfusion and glucose metabolism in a phase I dose-escalating protocol for endostatin, a novel antiangiogenic agent. A 2-min perfusion scan was performed with a bolus injection of 2,220 MBq (60 mCi) of 15O-water, which was followed by a 370-MBq (10 mCi) dose of 18F-FDG. Four sequential scans of 18F-FDG uptake were acquired, consisting of an early 2-min uptake scan-or first-pass scan-and 3 sequential 15-min late 18F-FDG uptake scans. Regions of interest (ROIs) were drawn on 2 or more tumor sites and on back muscle, as a control ROI, for each patient. Arterial blood concentration was derived from the PET scans by drawing an ROI over a large artery in the field of view. Blood flow was computed with a simple 1-compartment blood flow model using the first 2 min of data after injection. RESULTS: Blood flow estimated from the early uptake of 18F-FDG was linearly correlated with 15O-measured blood flow, with an intercept of 0.01, a slope of 0.86, and an R2 regression coefficient of 0.74 (r = 0.86). The 18F-FDG tumor extraction fraction relative to 15O-water averaged 0.86. A preliminary case study of a patient with prostate cancer confirms the utility of the first-pass 18F-FDG blood flow analysis in tumor diagnosis. CONCLUSION: These results suggest that the first-pass uptake of 18F-FDG may provide an estimate of perfusion in a tumor within the limitations of incomplete extraction of 18F-FDG compared with 15O-water.     

Maternal and fetal 11C-cocaine uptake and kinetics measured in vivo by combined PET and MRI in pregnant nonhuman primates.

Cocaine use during pregnancy has been shown to be deleterious to the infant. This may reflect reduction of flow to placenta or effects on the fetal brain. Methods to assess pharmacokinetics of drugs of abuse in vivo would be useful to investigate the mechanisms underlying the fetal adverse effects. We recently reported that combined MRI and PET technology allows the measurement of radioisotope distribution in maternal and fetal organs in pregnant Macaca radiata. Here, we evaluate the utility of PET to measure the uptake and distribution of (11)C-cocaine in the third-trimester fetus. METHODS: Six pregnant M. radiata weighing 3.8-9.0 kg were anesthetized and MR images were acquired on a 4-T MRI instrument. In all 6 animals, dynamic PET scans were subsequently acquired using 148-259 MBq of (11)C-cocaine. Time-activity curves for both maternal and fetal organs were obtained simultaneously with the pregnant animal positioned transverse in the PET scanner. Distribution volume ratios for maternal and fetal brain for (11)C-cocaine were calculated. RESULTS: Coregistration of PET and MR images allowed identification of fetal organs and brain regions and demonstrated that (11)C-cocaine or its labeled metabolites readily cross the placenta and accumulate mainly in fetal liver and to a lesser extent in the brain. Time to reach peak (11)C uptake in brain was shorter for the mother than for the fetus. The distribution volume ratios of the maternal striatum were higher than those of the fetus. Placenta was clearly visible on the early time frames and showed more rapid uptake and clearance than other fetal tissues. CONCLUSION: The pregnant M. radiata model allows the noninvasive measurement of radioisotope pharmacokinetics in maternal and fetal brain and other organs simultaneously. Although the uptake of radioactivity into the fetal brain after the injection of (11)C-cocaine is lower and slower than in the maternal brain, a measurable quantity of (11)C-cocaine (or its labeled metabolites) accumulates in the fetal brain at early times after injection. The highest accumulation of (11)C occurs in the fetal liver. Rapid radioisotope accumulation and clearance in the placenta offer potential as an input function for kinetic modeling for future studies of binding site availability.     

PET measurement of cerebral acetylcholine esterase activity without blood sampling

Measurement of cerebral acetylcholine esterase (AChE) activity is of clinical interest for the differential diagnosis of memory disorders and dementia. We developed and tested a non-invasive method for quantitation of regional cortical AChE activity with carbon-11-labelled N-methyl-4-piperidyl acetate (11C-MP4A) that does not require arterial blood sampling. AChE activity was measured in terms of the rate constant for hydrolysis of 11C-MP4A (k3). The physiological model is based on the very high AChE activity in the basal ganglia, which are used as a reference structure. Non-invasive k3 was compared with k3 determined with a standard technique by fitting kinetic tissue and metabolite-corrected plasma data in nine subjects with and without dementia. Across all regional values, a very high correlation of 0.92 was found, with a tendency towards moderate underestimation of k3 by 5%-14% with the non-invasive technique as compared to the invasive technique. In addition to its advantages with respect to practicability, the new non-invasive technique overcomes problems of the invasive technique that are related to interindividual variation of delay times between cerebral and peripheral tracer arrival and measurement of very small amounts of non-hydrolysed tracer in plasma samples.     

PET measurement of cerebral acetylcholine esterase activity without blood sampling

Measurement of cerebral acetylcholine esterase (AChE) activity is of clinical interest for the differential diagnosis of memory disorders and dementia. We developed and tested a non-invasive method for quantitation of regional cortical AChE activity with carbon-11-labelled N-methyl-4-piperidyl acetate (¹¹C-MP4A) that does not require arterial blood sampling. AChE activity was measured in terms of the rate constant for hydrolysis of ¹¹C-MP4A (k₃). The physiological model is based on the very high AChE activity in the basal ganglia, which are used as a reference structure. Non-invasive k₃ was compared with k₃ determined with a standard technique by fitting kinetic tissue and metabolite-corrected plasma data in nine subjects with and without dementia. Across all regional values, a very high correlation of 0.92 was found, with a tendency towards moderate underestimation of k₃ by 5%-14% with the non-invasive technique as compared to the invasive technique. In addition to its advantages with respect to practicability, the new non-invasive technique overcomes problems of the invasive technique that are related to interindividual variation of delay times between cerebral and peripheral tracer arrival and measurement of very small amounts of non-hydrolysed tracer in plasma samples.     

Simplification for measuring input function of FDG PET: investigation of 1-point blood sampling method.

The current method for quantitative FDG PET study requires application of multiple arterial blood sampling for measuring the input function, but the procedure is invasive and complicated. The purpose of this study was to establish a 1-point blood sampling technique that gives data comparable with the data of more elaborate serial arterial sampling. METHODS: We established a time point for 1-point arterial sampling that exhibited the highest correlation between plasma radioactivity at the time point and the real integrated value (IV) of the measured input function obtained by multiple arterial sampling in 120 patients and the smallest coefficient of variation of the real IV divided by plasma radioactivity at the time point in 120 patients. Scaling factors for estimation at each sampling point were determined, and a reference table was established to make the supposed input function. RESULTS: The optimal time for 1-point arterial sampling was 12 min after FDG injection. A good correlation was observed between the real IVs and those estimated from 1-point arterial blood sampling at 12 min using the supposed input function (n = 120; P < 0.001). The time point at which the difference between values of arterial and venous blood disappeared was 40 min after FDG injection. The percentage errors of IV estimation by 1-point sampling were 1.70% (n = 120) for arterial blood at 12 min and 3.64% (n = 10) for venous blood at 40 min. CONCLUSION: We conclude that the simplified 1-point sample method works in a manner that is comparable with serial arterial sampling and should be useful for clinical PET.     

Measurement of cerebral glucose metabolic rates in the anesthetized rat by dynamic scanning with 18F-FDG, the ATLAS small animal PET scanner, and arterial blood sampling.

Rodent models and genetically altered mice have recently become available to study many human diseases. A sensitive and accurate PET scanner for small animals would be useful to evaluate treatment of these diseases in rodent models. To examine the feasibility of performing quantitative PET studies, we performed dynamic scans with arterial blood sampling in anesthetized rats with the ATLAS (Advanced Technology Laboratory Animal Scanner) small animal PET scanner developed at the National Institutes of Health and (18)F-FDG and compared activities determined by PET scanning with those obtained by direct tissue sampling. METHODS: Dynamic PET scans after a bolus of approximately 48 MBq (1.3 mCi) (18)F-FDG were performed in rats anesthetized with isoflurane. Arterial blood sampling was performed throughout the scanning period. At 60 min the rat was killed, and the brain was rapidly removed and dissected into 5 structures (thalamus [TH], cortex [CX], brain stem [BS], cerebellum [CB], and half brain). Activity in the tissue samples was compared with the mean activity of the last 5 min of calibrated PET data. RESULTS: Plasma activity peaked at approximately 0.2 min and then cleared rapidly. Brain activity initially rose rapidly; the rate of increase then progressively slowed until activity was approximately constant between 30 and 60 min. Recovery coefficients (MBq/mL in PET images)/(MBq/mL in tissue samples) were 0.99 +/- 0.04, 0.90 +/- 0.19, 1.01 +/- 0.24, 0.84 +/- 0.05, and 1.01 +/- 0.17, respectively, in TH, CX, BS, CB, and half brain (mean +/- SD, n = 6-9). Cerebral glucose utilization determined by Patlak analyses of PET data measured 30-60 min after injection of (18)F-FDG was 31.7 +/- 5.2, 23.9 +/- 4.8, 29.9 +/- 5.0, 39.3 +/- 7.3, and 28.1 +/- 4.6 micro mol/100 g/min (mean +/- SD, n = 9) in TH, CX, BS, CB, and whole brain, respectively. These results are consistent with a previous (14)C-deoxyglucose study of the isoflurane-anesthetized rat. CONCLUSION: Expected values for glucose metabolic rates and recovery coefficients near unity suggest that quantitatively accurate dynamic (18)F-FDG brain imaging can be performed in the rat with arterial blood sampling and the ATLAS small animal PET scanner.     

Performance evaluation of continuous blood sampling system for PET study: comparison of three detector-systems

OBJECTIVES: To measure cerebral blood flow with 15O'PET, it is necessary to measure the time course of arterial blood radioactivity. We examined the performance of three different types of continuous blood sampling system. METHODS: Three kinds of continuous blood sampling system were used: a plastic scintillator-based beta detector (conventional beta detector (BETA)), a bismuth germanate (BGO)-based coincidence gamma detector (Pico-count flow-through detector (COINC)) and a Phoswich detector (PD) composed by a combination of plastic scintillator and BGO scintillator. Performance of these systems was evaluated for absolute sensitivity, count rate characteristic, sensitivity to background gamma photons, and reproducibility for nylon tube geometry. RESULTS: The absolute sensitivity of the PD was 0.21 cps/Bq for 68Ga positrons at the center of the detector. This was approximately three times higher than BETA, two times higher than COINC. The value measured with BETA was stable, even when background radioactivity was increased. The count rate characteristic of the PD and COINC was linear up to 8 kcps. The reproducibility of sensitivity for nylon tube geometry of COINC was the smallest (C.V. = 1.00%) among the three. PD was the weights the least (3.5 kg) among the three, which is convenient for clinical use. CONCLUSIONS: Each detector has unique characteristics derived from its own structure. Although the performance of all three detectors meets clinical requirement, PD had the highest physical performance.     

Microliter-ordered automatic blood sampling system for fully quantitative analysis of small-animal PET

Annals of Nuclear Medicine - The objective of the present study was to develop a fully automated blood sampling system for kinetic analysis in mice positron emission tomography (PET) studies....     

Cerebral oxygen and glucose metabolism and blood flow in mitochondrial encephalomyopathy: a PET study

Cerebral blood flow (CBF), oxygen metabolism (CMRO₂), and glucose metabolism (CMRGlc) were measure using positron emission tomography in five patients diagnosed as having mitochondrial encephalomyopathy. The molar ratio between the oxygen and glucose consumptions was reduced diffusely, as CMRO₂ was markedly decreased and CMRGlc was slightly reduced. The CBF showed less changes. The CBF increase on hypercapnia was smaller than normal, though this was not significant. CBF with hypocapnia demonstrated a significant reduction compared with the normal. These results suggest that oxidative metabolism is imparied and anaerobic glycolysis relatively stimulated, due to a primary defect of mitochondrial function, and that mild lactic acidosis occurs in brain tissue because of impaired utilisation of pyruvate in the TCA cycle. As these findings appear to indicate directly a characteristic of this disease, such measurements may be a useful tool for assessment of the pathophysiology and for diagnosis of mitochondrial encephalomyopathy.     

Minimum blood vessel diameter measured by magnification angiography.

Visibility of small blood vessels was improved by magnification angiography of biologic specimens. Blood vessel diameter was determined for increasing magnifications by various screen-film combination. Significantly smaller vessels were recognized with the magnification technique in all screen combinations. Noisy screen-film combinations with better square wave transfer functions did not allow visualization of blood vessels as small as those screen-film combinations with poorer square wave transfer functions but less noise.     

Reliability of one-point blood sampling method for calculating input function in Na18F PET

OBJECTIVE: Conventional methods of quantitative Na18F positron emission tomography require multiple arterial blood sampling in order to obtain the input function, and the procedures are invasive and complicated. This study aims to establish a simplified and reliable technique for obtaining the input function. METHODS: Multiple arterial blood sampling was performed on 12 persons. The time point for one-point sampling was determined as the time when (1) the plasma radioactivity obtained showed the highest correlation to the real integrated value, which was calculated from the input function, and (2) the coefficient of variation of the real integrated value divided by plasma radioactivity obtained at each time point became the minimum. Scaling factors were obtained in order to estimate the plasma radioactivity at each time point, and a reference table was produced in order to estimate the input function. RESULTS: The optimal timing for one-point sampling was 12 min after intravenous injection of Na18F. The estimated integrated value obtained from arterial blood sampling at 12 min and the reference table was highly correlated with the real integrated value (P<0.001). Levels of plasma radioactivity of arterial blood and venous blood were almost the same at 12 and 40 min after Na18F injection. Percentage errors in the estimation of the integrated value were 2.63% (n=12) for the arterial blood collected at 12 min and 4.14% (n=12) for the venous blood collected at 30 min. CONCLUSIONS: This simplified method is clinically applicable and would replace traditional methods that require multiple blood sampling.     

血糖水平对18F-FDG PET/CT图像质量的影响

目的 研究血糖水平对18F-脱氧葡萄糖(FDG) PET/CT图像质量的影响.方法 80例行体格检查或评价肿瘤性质的受检者,按空腹血糖水平分为9组(组间距为1mmol/L),第1组为血糖正常组,即血糖＜6.0mmol/L(10例);第2～9组血糖水平高于正常,分别为6.0～6.9mmol/L(11例),7.0～7.9mmol/L(13例),8.0～8.9mmol/L(11例),9.0～9.9mmol/L(11例),10.0～10.9mmol/L(8例),11.0～11.9mmol/L(6例),12.0～12.9mmol/L(5例),≥13.0mmol/L(5例).受检者做完PET/CT检查后,图像质量由2位有经验的医师独立判断.同时根据肝不同层面的标准摄取值(SUV)最大值(SUVmax)及SUV平均值(SUVavg)分别计算肝图像噪声.采用SPSS 12.0软件进行统计学处理.结果 (1)9组之间图像质量评分、肝噪声差异有统计学意义(P均＜0.05).将第2～9组图像质量评分、肝噪声分别与第1组进行比较,第2～7组与第1组差异无统计学意义(P均＞0.05);第8,9组与第1组比较差异有统计学意义(P均＜0.05),且评分低于第1组.(2)血糖水平与图像质量评分呈负相关(r=-0.52,P＜0.05);血糖水平与肝噪声呈正相关(SUVmax、SUVavgr值分别为0.33和0.60,P均＜0.05);SUVavg所算噪声与血糖水平的相关性优于SUVmax.结论 图像质量随血糖水平的升高而下降,血糖＜12.0mmol/L时与血糖正常者PET/CT图像质量差异无统计学意义,但当血糖水平≥12.0mmol/L时图像质量将显著下降.     

Three-dimensional projection display of striatum dopamine function measured by PET

[(11)C]CFT and[(11)C]raclopride images obtained by positron emission tomography (PET) are used to evaluate pre-synaptic dopamine transporter availability and post-synaptic dopamine D(2) receptor binding, respectively. A combined study with these tracers is useful for the differential diagnosis of Parkinson's disease. We generated three-dimensional (3D) animations of striatum PET images for the diagnosis of Parkinson's disease. Brain images of a normal subject and a typical Parkinson's disease patient with[(11)C]CFT and[(11)C]raclopride were obtained using a PET camera. Three-dimensional animations were generated from serial maximum intensity projection (MIP) images created by gradually changing the projection angle. Furthermore, the striatum images extracted from brain data were superimposed over a brain surface magnetic resonance (MR) image that was created by the volume-rendering method, and 3D animations were similarly generated. The present 3D animations were clinically useful for the differential diagnosis of brain diseases, because we were able to observe distributions of[(11)C]CFT and[(11)C]raclopride from any angle and to grasp at a glance the regional differences of distributions in reference to anatomical landmarks.     

Accuracy of standardized uptake value measured by simultaneous emission and transmission scanning in PET oncology.

We assessed the accuracy of the standardized uptake value (SUV) measured by simultaneous emission and transmission scanning in cancer patients using FDG positron emission tomography (PET). Conventional, independent emission (E)/transmission (T) scans and simultaneous E/T scans were conducted consecutively in 30 patients who underwent FDG PET examinations. The SUVs of 35 mass lesions and 34 selected normal tissues were derived from the independent E/T scan and simultaneous E/T scan. Experimental studies using a cylindrical phantom were also conducted to evaluate the accuracy and reproducibility of the SUV derived from a simultaneous E/T scan. The SUVs of 18F solution in the phantom were estimated to be approximately 1, with high reproducibility in the range of total counts observed in the clinical examinations. There were no significant differences in the SUVs in 35 tumours derived from simultaneous E/T scans and those derived from independent scans, and there was a strong positive correlation between the two (r = 0.99, P < 0.01). There were also no significant differences in the SUVs in 34 normal tissue regions derived from simultaneous E/T scans and those derived from independent scans. In conclusion, simultaneous E/T scanning with FDG in patients with malignant tumours is a valid method, since the SUV derived from the simultaneous scan is accurate and reproducible.