Estimation of optimal number of gates in dual gated 18F-FDG cardiac PET.

Gating of positron emission tomography images has been shown to reduce the motion effects, especially when imaging small targets, such as coronary plaques. However, the selection of optimal number of gates for gating remains a challenge. Selecting too high number of gates results in a loss of signal-to-noise ratio, while too low number of gates does remove only part of the motion. Here, we introduce a respiratory-cardiac motion model to determine the optimal number of respiratory and cardiac gates. We evaluate the model using a realistic heart phantom and data from 12 cardiac patients (47-77 years, 64.5 on average). To demonstrate the benefits of our model, we compared it with an existing respiratory model. Based on our study, the optimal number of gates was determined to be five respiratory and four cardiac gates in the phantom and patient studies. In the phantom study, the diameter of the most active hot spot was reduced by 24% in the dual gated images compared to non-gated images. In the patient study, the thickness of myocardium wall was reduced on average by 21%. In conclusion, the motion model can be used for estimating the optimal number of respiratory and cardiac gates for dual gating.

NEMA NU 4-2008 and in vivo imaging performance of RAYCAN trans-PET/CT X5 small animal imaging system.

The RAYCAN Trans-PET/CT X5 is a preclinical positron emission tomography and computed tomography (PET/CT) system intended for in vivo imaging of rats and mice, featuring all-digital readout electronics for PET data acquisition. The National Electrical Manufacturers Association (NEMA) NU 4-2008 performance evaluation was conducted on the RAYCAN Trans-PET/CT X5 in addition to assessing in vivo imaging performance of the system on live animals. The performance characteristics of the system were evaluated, including system spatial resolution, count rate performance, sensitivity and image quality. The system imaging performance is assessed in dynamic in vivo PET imaging. The system resolution defined as full width half maximum (FWHM) was 2.07 mm, 2.11 mm and 1.31 mm for the tangential, radial and axial resolution, respectively, at the center of the field of view. The peak noise equivalent count rate (NECR) values measured were 61 kcps at 0.19 MBq ml-1 for the rat size phantom and 126 kcps at 1.53 MBq ml-1 for the mouse size phantom. Scatter fractions were 24% and 14% for the rat and mouse phantom. The measured peak sensitivity of the system was 1.70%. Image quality in static imaging was deemed sufficient based on the image quality phantom study, with average activity concentration of 155 ± 8.6 kBq ml-1 and image uniformity of 5.57% when using two-dimensional filtered backprojection algorithm (2D-FBP). Rods in the image quality phantom were visualized easily up to 2 mm in size. In dynamic in vivo PET imaging, time-activity-curves from several regions were successfully measured, characterizing the radioactivity distribution in myocardial blood pool, liver, left ventricle and the lung. In conclusion, the RAYCAN Trans-PET/CT X5 system can be considered a suitable option for basic imaging needs in preclinical imaging.

Validation of [18F]fluorodeoxyglucose and positron emission tomography (PET) for the measurement of intestinal metabolism in pigs, and evidence of intestinal insulin resistance in patients with morbid obesity.

AIMS/HYPOTHESIS: The role of the intestine in the pathogenesis of metabolic diseases is gaining much attention. We therefore sought to validate, using an animal model, the use of positron emission tomography (PET) in the estimation of intestinal glucose uptake (GU), and thereafter to test whether intestinal insulin-stimulated GU is altered in morbidly obese compared with healthy human participants. METHODS: In the validation study, pigs were imaged using [(18)F]fluorodeoxyglucose ([(18)F]FDG) and the image-derived data were compared with corresponding ex vivo measurements in tissue samples and with arterial-venous differences in glucose and [(18)F]FDG levels. In the clinical study, GU was measured in different regions of the intestine in lean (n = 8) and morbidly obese (n = 8) humans at baseline and during euglycaemic hyperinsulinaemia. RESULTS: PET- and ex vivo-derived intestinal values were strongly correlated and most of the fluorine-18-derived radioactivity was accumulated in the mucosal layer of the gut wall. In the gut wall of pigs, insulin promoted GU as determined by PET, the arterial-venous balance or autoradiography. In lean human participants, insulin increased GU from the circulation in the duodenum (from 1.3 ± 0.6 to 3.1 ± 1.1 µmol [100 g](-1) min(-1), p < 0.05) and in the jejunum (from 1.1 ± 0.7 to 3.0 ± 1.5 µmol [100 g](-1) min(-1), p < 0.05). Obese participants failed to show any increase in insulin-stimulated GU compared with fasting values (NS). CONCLUSIONS/INTERPRETATION: Intestinal GU can be quantified in vivo by [(18)F]FDG PET. Intestinal insulin resistance occurs in obesity before the deterioration of systemic glucose tolerance.

Cardiac positron emission tomography/computed tomography imaging accurately detects anatomically and functionally significant coronary artery disease.

BACKGROUND: Computed tomography (CT) is increasingly used to detect coronary artery disease, but the evaluation of stenoses is often uncertain. Perfusion imaging has an established role in detecting ischemia and guiding therapy. Hybrid positron emission tomography (PET)/CT allows combination angiography and perfusion imaging in short, quantitative, low-radiation-dose protocols. METHODS AND RESULTS: We enrolled 107 patients with an intermediate (30% to 70%) pretest likelihood of coronary artery disease. All patients underwent PET/CT (quantitative PET with (15)O-water and CT angiography), and the results were compared with the gold standard, invasive angiography, including measurement of fractional flow reserve when appropriate. Although PET and CT angiography alone both demonstrated 97% negative predictive value, CT angiography alone was suboptimal in assessing the severity of stenosis (positive predictive value, 81%). Perfusion imaging alone could not always separate microvascular disease from epicardial stenoses, but hybrid PET/CT significantly improved this accuracy to 98%. The radiation dose of the combined PET and CT protocols was 9.3 mSv (86 patients) with prospective triggering and 21.8 mSv (21 patients) with spiral CT. CONCLUSIONS: Cardiac hybrid PET/CT imaging allows accurate noninvasive detection of coronary artery disease in a symptomatic population. The method is feasible and can be performed routinely with <10 mSv in most patients. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00627172.

Low radiation dose imaging of myocardial perfusion and coronary angiography with a hybrid PET/CT scanner.

OBJECTIVES: To test the image quality and feasibility of a sequential low radiation dose protocol for hybrid cardiac PET/CT angiography (CTA). BACKGROUND: Multidetector computed tomography (MDCT) is a non-invasive method for coronary angiography. The negative predictive value of MDCT is high but perfusion imaging has a role in detecting functional significance of coronary lesions. This has encouraged combining these techniques. However, radiation dose is of concern. We report our first experiences with a low dose sequential CTA mode applicable to hybrid imaging. METHODS: In the first phase, 10 consecutive cardiac MDCT angiographies were performed with spiral acquisition and compared in terms of image quality and dose with the following 10 patients performed with a new sequential mode. In the second phase, feasibility and radiation dose of a combined (15)O-water rest-stress PET perfusion/sequential CTA protocol were assessed in another group of 61 consecutive patients. RESULTS: Mean effective radiation dose was 60% lower in the sequential group than in the spiral group (19.3 versus 7.6 mSv, P<0.001). In the second phase, the new sequential hybrid protocol proved possible in 87% of the patients given the preconditions determined by the manufacturer. Mean effective dose of the CT acquisition was 7.6 mSv and total dose from the PET/CTA hybrid study 9.5 mSv. CONCLUSION: Low dose PET/CT allows cardiac hybrid studies with <10 mSv. The protocol can be applied to almost nine out of 10 patients with CT image quality comparable to spiral acquisition.

Performance of the new generation of whole-body PET/CT scanners: Discovery STE and Discovery VCT.

PURPOSE: The new GE Discovery STE and Discovery VCT respectively combine 16-slice and 64-slice CT with PET. The PET scanner has a new BGO detector block of 8 x 6 matrix (6.3 x 4.7 x 30 mm(3)). The aim of this study was to test the performance of the new scanner. METHODS: The PET performance evaluation was done using NEMA methodology. Owing to improved front-end electronics, the system was tested with different energy window and coincidence timing settings. RESULTS: Transaxial resolution FWHM for 2D(3D) mode at 1 cm offset from the centre of the field of view (R1) was 4.87 mm (5.12 mm) and at 10 cm off centre (R10) radially 5.70 mm (5.89 mm) and tangentially 5.84 mm (5.47 mm). The axial resolutions were 4.4 mm (5.18 mm) (R1) and 5.99 mm (5.86 mm) (R10). The sensitivities were 2.3 cps/kBq (8.8 cps/kBq) (R0, centre of field of view) and 2.3 cps/kBq (8.9 cps/kBq) (R10). The system scatter fraction was 21.4% in 2D at an energy of 375 keV (33.9% in 3D mode at a higher energy of 425 keV). Peak noise equivalent count rates (k=1) were 84.9 kcps at 43.9 kBq/ml (2D) and 67.6 kcps at 12.1 kBq/ml (3D). In image quality measurement the hot sphere to background contrast with 10- to 22-mm diameter spheres varied from 14% to 68%, being slightly better in 3D than in 2D mode. Cold sphere contrast was 67% in 2D and 59% in 3D mode. CONCLUSION: GE's new STE and VCT PET/CT systems have improved spatial resolution without loss in sensitivity. When compared with the LYSO crystal-based GE Discovery RX, the resolution and scatter fraction are comparable, the count rate capability is lower but the sensitivity is higher.

Non-Gaussian smoothing of low-count transmission scans for PET whole-body studies.

A non-Gaussian smoothing (NGS) technique is developed for filtering low count transmission (TR) data to be used for attenuation correction (AC) of positron emission tomography (PET) studies. The method is based on a statistical technique known as the generalized linear mixed model that allows an inverse link function that avoids the inversion of the observed transmission data. The NGS technique has been implemented in the sinogram domain in one-dimensional mode as angle-by-angle computation. To make it adaptive as a function of the TR count statistics we also develop and validate an objective procedure to choose an optimal smoothing parameter. The technique is assessed using experimental phantoms, simulating PET whole-body studies, and applied to real patient data. Different experimental conditions, in terms of TR scan time (from 1 h to 1 min), covering a wide range of TR counting statistic are considered. The method is evaluated, in terms of mean squared error (MSE), by comparing pixel by pixel the distribution for high counts statistics TR scan (1 h) with the corresponding counts distribution for low count statistics TR scans (e.g., 1 min). The smoothing parameter selection is shown to have high efficiency, meaning that it tends to choose values close to the unknown best value. Furthermore, the counts distribution of emission (EM) images, reconstructed with AC generated using low count TR data (1 min), are within 5% of the corresponding EM images reconstructed with AC generated using the high count statistics TR data (1 h). An application to a real patient whole-body PET study shows the promise of the technique for routine use.

Implementation and evaluation of an ordered subsets reconstruction algorithm for transmission PET studies using median root prior and inter-update median filtering.

An ordered subsets (OS) reconstruction algorithm based on the median root prior (MRP) and inter-update median filtering was implemented for the reconstruction of low count statistics transmission (TR) scans. The OS-MRP-TR algorithm was evaluated using an experimental phantom, simulating positron emission tomography (PET) whole-body (WB) studies, as well as patient data. Various experimental conditions, in terms of TR scan time (from 1 h to 1 min), covering a wide range of TR count statistics were evaluated. The performance of the algorithm was assessed by comparing the mean value of the attenuation coefficient (MVAC) of known tissue types and the coefficient of variation (CV) for low-count TR images, reconstructed with the OS-MRP-TR algorithm, with reference values obtained from high-count TR images reconstructed with a filtered back-projection (FBP) algorithm. The reconstructed OS-MRP-TR images were then used for attenuation correction of the corresponding emission (EM) data. EM images reconstructed with attenuation correction generated by OS-MRP-TR images, of low count statistics, were compared with the EM images corrected for attenuation using reference (high statistics) TR data. In all the experimental situations considered, the OS-MRP-TR algorithm showed: (1) a tendency towards a stable solution in terms of MVAC; (2) a difference in the MVAC of within 5% for a TR scan of 1 min reconstructed with the OS-MRP-TR and a TR scan of 1 h reconstructed with the FBP algorithm; (3) effectiveness in noise reduction, particularly for low count statistics data [using a specific parameter configuration the TR images reconstructed with OS-MRP-TR(1 min) had a lower CV than the corresponding TR images of a 1-h scan reconstructed with the FBP algorithm]; (4) a difference of within 3% between the mean counts in the EM images attenuation corrected using the OS-MRP-TR images of 1 min and the mean counts in the EM images attenuation corrected using the OS-MRP-TR images of 1 h; (5) preservation of "good" image quality for both TR and EM reconstructed images. In conclusion, the OS-MRP-TR algorithm is particularly suitable for WB PET studies, allowing: (1) the acquisition of a very short TR scan (within 1 min), (2) the reconstruction of such TR data in low-noise TR images and (3) the use of the reconstructed OS-MRP-TR images for attenuation correction of corresponding EM data.

PET studies on the memory processing of word pairs in bilingual Finnish-English subjects.

This study examined the fundamental question whether verbal memory processing in two unrelated languages is mediated by a common neural system or by distinct cortical areas. Ten right-handed, male Finnish--English adult late bilinguals who had acquired the second language after the age of 10 were scanned whilst either encoding/retrieving word pairs in their mother tongue (Finnish) or in a foreign language (English). Within each language, subjects had to encode and retrieve four sets of 12 visually presented paired word associates which were not semantically related. Two sets consisted of highly imageable words (e.g. monkey-table; koira-lasi) and the other two sets of abstract word pairs (e.g. freedom-moral; uhka-suure). Presentation of pseudowords served as a reference condition. An emission scan was recorded after each intravenous administration of O-15 water. Encoding was associated with prefrontal and hippocampal activation. During memory retrieval, precuneus showed a consistent activation in both languages and for both highly imageable and abstract words. Although the brain mechanisms of the two languages share common components, differential activations were found in Broca's area and in the cerebellum as well as in the angular/supramarginal gyri according to the language used.

Implementation and evaluation of a 3D one-step late reconstruction algorithm for 3D positron emission tomography brain studies using median root prior.

A fully three-dimensional (3D) one-step late (OSL), maximum a posteriori (MAP) reconstruction algorithm based on the median root prior (MRP) was implemented and evaluated for the reconstruction of 3D positron emission tomography (PET) studies. The algorithm uses the ordered subsets (OS) scheme for convergence acceleration and data update during iterations. The algorithm was implemented using the software package developed within the EU project PARAPET (www.brunel.ac.uk/~masrppet). The MRP algorithm was evaluated using experimental phantom and real 3D PET brain studies. Various experimental set-ups in terms of activity distribution and counting statistics were considered. The performance of the algorithm was assessed by calculating figures of merit such as: contrast, coefficient of variation, activity ratio between two regions and full width at half of maximum for resolution measurements. The performance of MRP was compared with that of 3D ordered subsets-expectation maximisation (OSEM) and 3D re-projection (3DRP) algorithms. In all the experimental situations considered, MRP showed: (1) convergence to a stable solution, (2) effectiveness in noise reduction, particularly for low statistics data, (3) good preservation of spatial details. Compared with the OSEM and 3DRP algorithms, MRP provides comparable or better results depending on the parameters used for the reconstruction of the images.

Perfusion heterogeneity in human skeletal muscle: fractal analysis of PET data.

Muscle blood flow has been shown to be heterogeneous at the voxel by voxel level in positron emission tomography (PET) studies using oxygen-15 labelled water. However, the limited spatial resolution of the imaging device does not allow direct measurement of true vascular flow heterogeneity. Fractal dimension (D) obtained by fractal analysis describes the relationship between the relative dispersion and the size of the region studied, and has been used for the assessment of perfusion heterogeneity in microvascular units. This study was undertaken to evaluate fractal characteristics of PET perfusion data and to estimate perfusion heterogeneity in microvascular units. Skeletal muscle blood flow was measured in healthy subjects using [15O]water PET and the fractal characteristics of blood flow in resting and exercising skeletal muscle were analysed. The perfusion heterogeneity in microvascular units was estimated using the measured heterogeneity (relative dispersion, RD = SD/mean) and D values. Heterogeneity due to methodological factors was estimated with phantoms and subtracted from the flow data. The number of aggregated voxels was inversely correlated with RD both in phantoms (Pearson r = -0.96-0.97) and in muscle (Pearson r = -0.94) when both parameters were expressed using a logarithmic scale. Fractal dimension was similar between exercising (1.13) and resting (1.14) muscles and significantly lower than the values in the phantoms with different activity levels (1.27-1.29). Measured flow heterogeneity values were 20% +/- 6% (exercise) and 27% +/- 5% (rest, P < 0.001), whereas estimated flow heterogeneity values in microvascular units (1 mm3) were 35% +/- 14% (exercise) and 49% +/- 14% (rest, P < 0.01). In conclusion, these results show that it is feasible to apply fractal analysis to PET perfusion data. When microvascular flow heterogeneity is estimated using fractals, perfusion appears to be more heterogeneous in microvascular units than when obtained by routine spatial analysis of PET data. Analysis of flow heterogeneity using PET and fractals could provide new insight into physiological conditions and diseases associated with changes in peripheral vascular function.

The translating brain: cerebral activation patterns during simultaneous interpreting.

Brain activation was measured in professional interpreters during simultaneous interpreting (SI) vs. repetition (shadowing) of auditorily presented text by positron emission tomography (PET). SI into the native language (Finnish) elicited left frontal activation increases. SI into the non-native language (English) elicited much more extensive left-sided fronto-temporal activation increases. Our results indicate that SI activates predominantly left-hemispheric structures (particularly the left dorsolateral frontal cortex) previously related to lexical search, semantic processing and verbal working memory. Brain activation patterns were clearly modulated by direction of translation, with more extensive activation during translation into the non-native language which is often considered to a be more demanding task.

Radiotherapy treatment planning and long-term follow-up with [(11)C]methionine PET in patients with low-grade astrocytoma.

PURPOSE: To evaluate the feasibility of [(11)C]-methionine positron emission tomography (MET PET) in radiotherapy (RT) treatment planning and long-term follow-up in patients with low-grade glioma. PATIENTS: Thirteen patients with low-grade astrocytoma and 1 with anaplastic astrocytoma underwent sequential MET PET and magnetic resonance imaging (MRI) before and 3, 6, 12, and 21-39 months after RT, respectively. Ten patients were studied after initial debulking surgery or biopsy and 4 in the recurrence phase. METHODS: A total of 58 PET scans were performed. After transmission scanning, a median dose of 425 MBq of MET was injected intravenously and emission data was acquired 20 min after injection for 20 min. The uptake of MET in tumor area was measured as standardized uptake value (SUV) and tumor-to-contralateral brain SUV ratios were generated to assess irradiation effects on tumor metabolism. Functional imaging with PET was compared with concurrent MRI in designing the RT planning volumes and in assessment of response to RT during a median follow-up time of 33 months. RESULTS: In 12 patients (86%), tumor area was clearly discernible in the baseline PET study. In the remaining 2 patients with a suspected residual tumor in MRI, PET showed only a diffuse uptake of MET interpreted as negative in the original tumor area. In the dose planning of RT, MET PET was helpful in outlining the gross tumor volume in 3 of 11 cases (27%), whereas PET findings either coincided with MRI (46%) or were less distinctive (27%) in other cases. In quantitative evaluation, patients with a low tumor SUV initially had significantly better prognosis than those with a high SUV. Tumor-to-contralateral brain uptake ratios of MET discriminated well patients remaining clinically stable from those who have since relapsed or died of disease. CONCLUSION: Quantitative MET PET has prognostic value at the time of initial treatment planning of low-grade glioma. Some patients may benefit of RT volume definition with MET PET, which seems to disclose residual tumor better than MRI in selected cases. Stable or decreasing uptake of MET in tumor area after RT during follow-up seems to be a favorable sign.

Nodal staging of lymphoma with whole-body PET: comparison of.

UNLABELLED: Accurate staging is elementary for optimal management of malignant lymphoma. Advanced cases may be curable with multidrug chemotherapy combined with radiotherapy, whereas limited disease can sometimes be cured by local radiotherapy only. Recently, FDG imaging with whole-body PET (WB PET) has been introduced as an accurate method for staging lymphoma. We evaluated the usefulness of L-[methyl-11C]methionine (MET) in comparison with FDG as a tracer for nodal staging of lymphoma with WB PET. METHODS: Nineteen patients with untreated, histologically proven malignant lymphoma underwent WB PET imaging with MET and FDG within 1 wk before treatment. Fourteen patients had non-Hodgkin's lymphoma (NHL), and 5 had Hodgkin's disease (HD). Two of these 19 patients were excluded from the final analysis because of hyperglycemia. WB PET images using FDG and MET were visually compared by 3 independent interpreters, and the PET findings were correlated with the data on the basis of conventional staging studies. RESULTS: Fifty-five of 178 lymph node regions were classified as diseased both by FDG PET and by CT, and 54 of 178 were classified as diseased both by MET PET and by CT. In addition, 11 lymph node regions that CT showed to be normal avidly accumulated FDG. Ten of these lymph node regions also had clear uptake of MET. Another 4 and 5 lymph node regions were enlarged at CT but were judged to be normal by FDG and MET PET, respectively. In nodal staging, both FDG PET and MET PET would have upstaged the disease in 3 patients. MET PET would also have downstaged the disease in 1 patient. CONCLUSION: FDG and MET seem to be comparable in the detection of lymphoma by WB PET. However, visual interpretation of the images tends to be hampered more by physiologic accumulations of MET than by normal accumulations of FDG, and MET may be preferable to FDG in hyperglycemic patients undergoing staging studies with PET.

Cardiac positron emission tomography imaging with [11C]hydroxyephedrine, a specific tracer for sympathetic nerve endings, and its functional correlates in congestive heart failure.

The integrative mechanisms of autonomic dysfunction in congestive heart failure (CHF) remain poorly understood. We sought to study cardiac retention of [11C]hydroxyephedrine (HED), a specific tracer for sympathetic presynaptic innervation, and its functional correlates in CHF. Thirty patients with mild to moderate heart failure underwent resting cardiac HED positron emission tomography imaging, spectrum analysis testing of systolic pressure and heart rate variability in the resting supine and 70 degrees head-up tilt positions, and testing of baroreflex sensitivity. Compared with control subjects, global myocardial HED retention index was reduced by 30% (p <0.01) in patients with CHF. The HED retention index did not correlate significantly with heart rate variability. However, it correlated with baroreflex sensitivity at rest (r = 0.43, p = 0.05) and with systolic pressure low-frequency (0.03 to 0.15 Hz) variability at head-up tilt (r = 0.76, p <0.01), as well as with low-frequency systolic pressure variability response from baseline to tilt (r = 0.75, p <0.01). We conclude that cardiac HED retention is reduced in patients with CHF. This correlates with blunted vascular sympathetic effector responses during posture-induced reflex activation and baroreflex control of heart rate, suggesting an interdependence between cardiac presynaptic innervation abnormalities and neural mechanisms important to blood pressure maintenance in CHF.

Left hemisphere activation during processing of morphologically complex word forms in adults.

Functional neuroanatomy of the processing of morphologically complex words was studied by measuring regional brain activity by positron emission tomography (PET) during encoding of auditorily presented inflected versus monomorphemic Finnish nouns. Significant increases of activation occurred particularly in the left inferior posterior frontal lobe, corresponding to Broca's area. This suggests that besides their role in the production of grammatical morphology documented earlier, Broca's area and adjacent regions are important for the input processing of morphologically complex words.

Cerebral metabolic rate for glucose after neonatal hypoglycaemia.

OBJECTIVE: We studied the effect of neonatal hypoglycaemia on the local cerebral metabolic rate for glucose (LCMRglc). MATERIALS AND METHODS: Eight newborn infants with neonatal hypoglycaemia were studied. The LCMRglc in the whole brain, in five cerebral regions and in skeletal muscles were quantitated using positron emission tomography (PET) and 2-[18F]Fluoro-2-deoxy-D-glucose (FDG). The PET studies were performed at the age of 5.3 +/- 6.2 days during normoglycaemia. The LCMRglc of these infants were compared to the age-adjusted LCMRglc of eight infants with suspected hypoxic-ischaemic brain injury but with normal neurological development. RESULTS: After neonatal hypoglycaemia the age-adjusted LCMRglc in the whole brain was not lower than LCMRglc of the control infants (5.33 +/- 0.60 mumol/100 g/min vs. 6.71 +/- 0.60 mumol/100 g/min). Also the metabolic rate for glucose (MRglc) in the skeletal muscles was similar in hypoglycaemic and control infants (5.56 +/- 2.48 mumol/100 g/min vs. 6.99 +/- 2.41 mumol/100 g/min). CONCLUSION: MRglc in brain and in skeletal muscle seems to be normal after neonatal hypoglycaemia, although larger group of patients with more severe hypoglycaemia are needed to confirm this finding.

Quantitative blood flow measurement of skeletal muscle using oxygen-15-water and PET.

UNLABELLED: The aim of the present study was to evaluate quantitation of muscle blood flow using [15O]H2O and PET. METHODS: The autoradiographic (ARG) and the steady-state methods using PET were used to measure femoral muscle blood flow. A simulation study was performed to examine the errors due to contamination of radioactivity in the blood content in muscle tissue, statistical noise and delay and the dispersion of the input curve in the ARG method. Five separate paired muscle blood flow examinations were carried out for comparison of the ARG and the steady-state techniques, including measurement of muscle blood volume in each subject. To obtain the normal range for resting muscle blood flow, additional measurements with the ARG method were performed in 16 normal subjects. RESULTS: When the integration time in ARG was increased to 200-300 sec, the errors due to arterial blood volume, statistical noise, delay and dispersion of the input curve were significantly reduced. Muscle blood flow values in the ARG (200 sec) and the steady-state studies were in good agreement, and each provided an estimated accuracy of 5%. Resting muscle blood flow averaged 3.12 +/- 1.55 ml/min.100 g muscle (range 1.43-6.72 ml/min.100 g muscle, n = 18). CONCLUSION: The ARG and the steady-state methods provided consistent blood flow values for skeletal muscle when a long tissue integration time (> or = 200 sec) was applied in the ARG study. Based on the lower effective radiation dose and the shorter total scan duration, the ARG method is favored over the steady-state method in the measurement of muscle blood flow.

Transport of carbon-11-methionine is enhanced by insulin.

UNLABELLED: The anabolic effects of insulin are not restricted to carbohydrate and lipid metabolism but also include protein metabolism. However, the effects of insulin on protein metabolism have been difficult to demonstrate in vivo. Amino acid transport is partly regulated by insulin according to the experimental data. PET provides a way to measure fractional uptake rates of amino acids. The purpose of this study was to measure the effect of insulin on amino acid transport from the plasma to the human parotid glands. METHODS: We compared the uptake of L-[methyl-11C]methionine ([11C]methionine) into the parotid glands and cerebellum in seven healthy volunteers during the fasting state and euglycemic insulin clamp technique (1 mU/kg per minute). RESULTS: The fractional uptake rate of [11C]methionine was increased by 31% for the right parotid gland (p = 0.003) and by 29% for the left parotid gland (p = 0.009) during insulin clamp, while the increase was 19% for the cerebellum (p = 0.01). The concentration of amino acids typical for the hormone-sensitive transport system A was 11% lower during insulin infusion than in the fasting state. CONCLUSION: The uptake of methionine into brain tissue does not seem to be under major control by insulin, while the transport of methionine in the parotid glands is stimulated by insulin. PET provides a sophisticated method to study the transport system of amino acids in vivo.

Evidence for dissociation of insulin stimulation of blood flow and glucose uptake in human skeletal muscle: studies using [15O]H2O, [18F]fluoro-2-deoxy-D-glucose, and positron emission tomography.

We determined the effect of insulin on muscle blood flow and glucose uptake in humans using [15O]H2O, [18F]fluoro-2-deoxy-D-glucose ([18F]FDG), and positron emission tomography (PET). Femoral muscle blood flow was measured in 14 healthy volunteers (age 34 +/- 8 years, BMI 24.6 +/- 3.4 kg/m2 [means +/- SD]) before and at 75 min during a 140-min high-dose insulin infusion (serum insulin 2,820 +/- 540 pmol/l) under normoglycemic conditions. A dynamic scan of the femoral region was performed using PET for 6 min after injection of [15O]H2O to determine the 15O concentration in tissue. Regional femoral muscle blood flow was calculated using an autoradiographic method from the dynamic data obtained with PET and [15O]H2O. Femoral muscle glucose uptake was measured during hyperinsulinemia immediately after the flow measurement using PET-derived [18F]FDG kinetics and a three-compartment model. Whole-body glucose uptake was quantitated using the euglycemic insulin clamp technique. In the basal state, 84 +/- 8% of blood flow was confined to skeletal muscle. Insulin increased leg blood flow from 29 +/- 14 to 54 +/- 29 ml x kg-1 leg x min-1 (P < 0.001) and muscle flow from 31 +/- 18 to 58 +/- 35 ml x kg-1 muscle x min-1 (P < 0.005). Under insulin-stimulated conditions, 81 +/- 8% of blood flow was in muscle tissue (NS versus basal). Skeletal muscle explained 70 +/- 25% of the increase in leg blood flow. No correlation was observed between blood flow and glucose uptake when analyzed individually in identical regions of interest within femoral muscles. These data demonstrate that skeletal muscle accounts for most of the insulin-induced increase in blood flow. Insulin-stimulated rates of blood flow and glucose uptake do not colocalize in the same regions of muscle tissue, suggesting that insulin's hemodynamic and metabolic effects are differentially regulated.