Measurement of muscle protein synthesis by positron emission tomography with L-[methyl-11C]methionine.

Positron emission tomography (PET) with L-[methyl-11C]methionine was explored as an in vivo, noninvasive, quantitative method for measuring the protein synthesis rate (PSR) in paraspinal and hind limb muscles of anesthetized dogs. Approximately 25 mCi (1 Ci = 37 GBq) of L-[methyl-11C]methionine was injected intravenously, and serial images and arterial blood samples were acquired over 90 min. Data analysis was performed by fitting tissue- and metabolite-corrected arterial blood time-activity curves to a three-compartment model and assuming insignificant transamination and transmethylation in this tissue. PSR was calculated from fitted parameter values and plasma methionine concentrations. PSRs measured by PET were compared with arterio-venous (A-V) difference measurements across the hind limb during primed constant infusion (5-6 h) of L-[1-13C, methyl-2H3]methionine. Results of PET measurements demonstrated similar PSRs for paraspinal and hind limb muscles: 0.172 +/- 0.062 vs. 0.208 +/- 0.048 nmol-1.min-1.(g of muscle)-1 (P = not significant). PSR determined by the stable isotope technique was 0.27 +/- 0.050 nmol-1.min-1.(g of leg tissue)-1 (P < 0.07 from PET) and indicated that the contribution of transmethylation to total hind limb methionine utilization was approximately 10%. High levels of L-[methyl-11C]methionine utilization by bone marrow were observed. We conclude that muscle PSR can be measured in vivo by PET and that this approach offers promise for application in human metabolic studies.     

Noninvasive measurement of liver regeneration with positron emission tomography and [2-11C]thymidine

The feasibility of liver regeneration determination with [2-11C]thymidine and positron emission tomography was investigated in partially hepatectomized rats. Serial tomographic scans were performed over a 120-minute period after injection of [2-11C]thymidine together with tritium-labeled thymidine. Within 10 minutes after injection, positron emission tomography scans showed a twofold higher hepatic uptake in regenerating than in nonregenerating livers. Time-activity curves over the liver area indicated that the maximal uptake was followed by a faster decrease of 11C radioactivity in controls than in regenerating animals, so that total 11C activity remaining in the liver at 120 minutes accounted for 68% of maximum in regenerating and only 38% in controls. Tissue distribution studies performed at 120 minutes showed that total 11C radioactivity, expressed in percent injected dose per gram, was six times higher in regenerating livers than in controls (0.62% +/- 0.07% in regenerating livers and 0.10% +/- 0.03% in nonregenerating livers; P less than 0.001) and correlated with 3H radioactivity measured in the nuclear fraction (r = 0.92; P less than 0.001). When the hepatic uptake was expressed in percent of dose per organ, the difference between both groups increased (2.31% +/- 0.23% in regenerating livers and 0.29% +/- 0.02% in nonregenerating livers; P less than 0.001) because of higher weight of regenerating livers than of nonregenerating livers (3.83 +/- 0.11 g in regenerating livers and 2.96 +/- 0.16 g in nonregenerating livers; P less than 0.001). In other organs examined, no difference in 11C radioactivity was found between the two groups of rats. These results indicated the potential usefulness of [2-11C]thymidine and positron emission tomography for noninvasive measurement of liver regeneration.     

脑诱发电位与功能性脑成像在肠易激综合征研究中的应用

肠易激综合征(Irritablebowelsyndmme，IBS)是腹部不适或腹痛伴排便异常的一组肠功能障碍综合征，因其缺乏明显形态学及生化异常，病因及发病机制不甚清楚，给诊断及治疗带来了许多困难。近年来，IBS患者内脏感觉异常这一病理生理改变受到广泛关注，为深入了解内脏感觉异常的神经生物学机制，最近几种可客观评价IBS患者感觉传入通路及大脑信息处理过     

11C]metomidate positron emission tomography of adrenocortical tumors in correlation with histopathological findings

CONTEXT: Adrenal incidentalomas are common findings necessitating extensive laboratory work-up and repetitive radiological examinations. Positron emission tomography (PET) using (11)C-labeled metomidate (MTO) has previously been described as a tool for specific adrenocortical imaging. OBJECTIVE: We evaluated 212 MTO-PET examinations in 173 patients to identify its role in the management of adrenal tumors. DESIGN: Seventy-five histopathological examinations from 73 patients were retrospectively analyzed. SETTING: All examinations were performed at a referral center. PATIENTS: Patients who were operated or biopsied due to adrenal tumors had histopathological diagnoses of adrenocortical adenoma (n = 26), adrenocortical cancer (ACC; n = 13), adrenocortical hyperplasia (n = 8), pheochromocytoma (n = 6), metastasis (n = 3), and tumors of nonadrenal origin (n = 19). MAIN OUTCOME MEASURES: The main outcome measures were statistical analyses and findings while scrutinizing images. The hypothesis that MTO-PET is of value in the management of adrenal tumors, especially incidentaloma, was stated before data collection. RESULTS: Sensitivity was 0.89 and specificity was 0.96 for MTO-PET in proving adrenocortical origin of the lesions. Pheochromocytomas, metastases to the adrenal gland, and nonadrenal masses were all MTO negative. PET measurements using standardized uptake values (SUV) in pathological adrenocortical tissue could differentiate lesions larger than 1-1.5 cm from normal adrenocortical tissue. SUV was higher in aldosterone-hypersecreting adenomas, and the SUV ratio between the tumor and the contralateral gland was significantly higher in all hormonally hypersecreting adenomas as well as in ACC. CONCLUSION: MTO-PET is a specific and sensitive method for diagnosing adrenocortical tumors. MTO-PET is useful in the imaging work-up of adrenal incidentalomas and may be beneficial for the examination of patients with primary aldosteronism or ACC.     

Assessment of residual liver functional reserve after portal embolization with positron emission tomography usingl-[methyl-11C] methionine and computed tomography

Hepatic functional reserve after portal embolization was assessed in eight patients according to the functional volume index (FVI), a new index obtained using positron emission tomography (PET) withl-[methyl-¹¹C] methionine. FVI in residual liver was 1744–5252 (mean, 3441) (normal range, 3106–6211) before percutaneous transhepatic portal embolization (PTPE) and 2457–6906 (mean, 4590) after PTPE. FVI exceeded 4000 in five patients and did not reach 4000 in three patients after PTPE. Two patients with FVI values of more than 4000 survived after hepatectomy and one with FVI under 4000 died of liver failure. FVI is a useful criterion for determining indications for PTPE; a value exceeding 4000 is needed before major hepatectomy can be safely performed after PTPE.     

Endothelial dysfunction in patients with antiphospholipid syndrome assessed with positron emission tomography.

BACKGROUND: There is limited knowledge about endothelial dysfunction in patients with primary antiphospholipid syndrome (PAPS). The purpose of this study was to evaluate endothelial function in patients with PAPS assessed by positron emission tomography. METHODS AND RESULTS: A 3-phase protocol--rest, cold pressor test (CPT), and adenosine positron emission tomography with nitrogen 13 ammonia--was used in 18 patients with PAPS and 18 healthy volunteers (HVs). Myocardial blood flow (MBF) was measured in each phase, with calculation of the endothelial-dependent vasodilation index, the increase in the MBF in response to CPT, and the myocardial flow reserve. An important trend was found in the myocardial flow reserve (2.76 +/- 1.04 in PAPS group vs 3.27 +/- 0.72 in HV group, P > .05), in the endothelial-dependent vasodilation index (1.19 +/- 0.31 in PAPS group vs 1.55 +/- 0.37 in HV group, P < .05), and in the percent change in the MBF in response to CPT (from rest) (19% +/- 31% in PAPS group vs 55% +/- 37% in HV group, P < .05). CONCLUSION: The CPT results obtained in this study showed that the PAPS patients studied have endothelial dysfunction.     

Noninvasive quantitation of regional myocardial oxygen consumption in vivo with [1-11C]acetate and dynamic positron emission tomography

The usefulness of [1-11C]acetate as a tracer of overall myocardial oxidative metabolism for use with positron emission tomography has been investigated in 12 closed-chest dogs. Myocardial 11C activity clearance kinetics after intravenous administration of [1-11C]acetate in dogs have been determined noninvasively by positron emission tomography. Biexponential fitting of regional myocardial 11C time-activity curves was performed to give clearance half-times and fractional distribution. The rate constant k1 for the early rapid phase of 11C activity clearance was found to correlate linearly with myocardial oxygen consumption (y = 0.0156x + 0.039; SEE = 0.023; r = 0.95). k1 was approximately 7% lower in septal sectors compared with the left ventricular free wall, suggesting that regional oxygen consumption in the septum was lower; a concomitant regional attenuation of blood flow in the septum relative to the left ventricular free wall was also observed. In dogs using carbohydrates as the predominant fuel, k1 oxygen consumption was somewhat more than in dogs using predominantly free fatty acids (0.021 +/- 0.002 compared with 0.018 +/- 0.002, p less than 0.01), indicating that increased carbohydrate consumption is associated with a small increase in k1 at constant oxygen consumption. It is concluded that measurement of myocardial [1-11C]acetate kinetics allows noninvasive determination of cardiac oxygen consumption by positron emission tomography and that the technique is relatively insensitive to myocardial fuel selection.     

Vascular inflammation evaluated by [18F]-fluorodeoxyglucose positron emission tomography is associated with the metabolic syndrome.

OBJECTIVES: We investigated factors for carotid artery inflammation by [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography (PET). BACKGROUND: Inflammation is present in some atherosclerotic plaques. The FDG-PET is capable of identifying and quantifying vascular inflammation within atherosclerotic plaques. METHODS: The FDG-PET imaging was performed in 216 consecutive patients (63 +/- 9 years, men:women 147:69) for cancer screening. Vascular inflammation in carotid atherosclerosis was quantified by measuring the standardized uptake value (SUV) of FDG into the artery. RESULTS: Multiple stepwise regression analysis revealed significant relationships between SUV and waist circumference (p < 0.001), hypertensive medication (p < 0.001), carotid intima-media thickness (p < 0.001), high-density lipoprotein cholesterol (p < 0.01, inversely), homeostasis model assessment of insulin resistance (p < 0.05), or high sensitivity C-reactive protein (p < 0.05). Age- and gender-adjusted SUV of FDG was significantly higher (p < 0.0001) in proportion to the accumulation of the number of the components of the metabolic syndrome. Thus, the metabolic syndrome was associated with increased FDG uptake in carotid atherosclerosis. CONCLUSIONS: Our present study may suggest that the metabolic syndrome is associated with inflammation in carotid atherosclerosis. (Detection of Plaque Inflammation by Positron Emission Tomography (PET); http://www.clinicaltrials.gov/ct/show/NCT00114504; NCT00114504).     

[18F]-fluorodeoxyglucose positron emission tomography in patients with suspected recurrence of breast cancer

AIM: To evaluate the role of [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients presenting with a suspicion of breast cancer relapse after primary treatment. MATERIALS AND METHODS: Sixty consecutive female patients with clinical (n=35) or radiological (n=25) suspicion of breast cancer recurrence were evaluated by FDG-PET. Positive PET findings were further evaluated by histological examination or clinical and radiological follow-up. In 25 patients, the serum tumor marker (CA 15-3) status was compared to the PET results. RESULTS: Disease relapse was proven in 40 patients. Additionally, in three patients a second cancer was diagnosed with (n=1), and without (n=2) concomitant disease relapse. PET missed local recurrence in three patients, and was false positive in another four. In patient-based analysis, the overall sensitivity, specificity, and accuracy were 89%, 84%, and 87%, and 100%, 97%, and 98% for locoregional recurrence and distant metastases, respectively. FDG-PET was more sensitive than the serum tumor marker CA 15-3 in detecting relapsed breast cancer. CONCLUSION: FDG-PET is a valuable tool in the follow-up of patients with breast cancer.     

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.     

PET [11C]DASB imaging of serotonin transporters in patients with alcoholism

OBJECTIVE: Alcoholism and aggression have each been associated with neurochemical measurements suggestive of decreased serotonin synaptic transmission. We measured densities of the serotonin transporter (SERT) in a moderate-sized sample of alcoholic patients who were assessed for aggressive characteristics. METHODS: Thirty alcoholic inpatients and 18 healthy controls received a PET scan with [(11)C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile. The alcoholic inpatients were classified as aggressive or nonaggressive based on a comparison between the top third and bottom third scores on the Buss-Durkee Hostility Index. RESULTS: Using a pixel-wise comparison, no brain region showed significant alterations in SERT binding among the 3 groups of subjects (aggressive alcoholic subjects, nonaggressive alcoholic subjects, and healthy controls) or between the combined alcoholic group and healthy controls. None of the clinical measures (including measures of aggression) correlated with SERT binding in the alcoholic subjects. CONCLUSION: Contrary to prior imaging reports using the nonselective ligand [(123)I]beta-CIT, we found no significant alterations of SERT density in alcoholic patients.     

Appropriate use of positron emission tomography with [18F]fluorodeoxyglucose for staging of oncology patients

Positron emission tomography (PET) was developed in the mid-1970, and its initial applications were for heart and brain imaging research. Nowadays, this technology is aimed mainly at staging or restaging tumours as it allows the assessment of biochemical processes that are either specific or associated with tumour biology.The full appreciation of PET potentials and limitations among general practitioners and internists cannot be considered achieved and the appropriate use of PET especially when coupled to X-ray computed tomography (CT) is still suboptimal.The majority of PET studies rely on the use of fluorodeoxyglucose labelled with fluorine-18 (FDG), which is a radiopharmaceutical specific for glucose transport and metabolism.PET with FDG is amenable for studying most type of tumours, including those of the head and neck, lung, oesophagus, colo-rectal, gastrointestinal stromal tumours, pancreas, some types of lymphomas and melanoma, whereas in some tumours, including those of the reproductive system, brain, breast and bones, there is a limited role for PET and there is no substantial role for FDG-PET for the bronchoalveolar, hepatocellular, urinary system, testicular, neuroendocrine, carcinoids and adrenal tumours, differentiated thyroid cancers, and several subtypes of malignant lymphoma. Thus, the limits of FDG have stimulated the use and development of other radiopharmaceuticals. These tracers represent the opportunity for expanding the use of PET to other areas in oncology in the near future.     

Quantitative analysis of bowel gas using plain abdominal radiograph in patients with irritable bowel syndrome

OBJECTIVE: Ideally, the diagnosis of irritable bowel syndrome (IBS) would be achieved using a minimal number of procedures. It is presumed that bowel gas is related to IBS, and it is easily visualized by plain abdominal radiograph. In the present study, to clarify the relationship between IBS and the quantity of bowel gas, the measured bowel gas volume using plain abdominal radiographs was compared with the pathology of IBS. METHODS: Plain abdominal radiographs were digitized and transmitted to a computer (computed radiography) in 30 IBS patients and 30 normal controls. The quantity of bowel gas, determined as the pixel value on images and standardized by physique, was defined as the gas volume score (GVS). Using the mean +/- 2SD of GVS in the control group as the normal score, IBS patients were divided into three groups: high, normal, and low. To examine the sequential reproducibility of a similar quantity of bowel gas, a second plain abdominal radiography was performed about 2 months later, and the GVS were compared. The colonic transit time was determined using radiopaque markers. RESULTS: There was a strong correlation between the quantities of bowel gas measured by two independent gastroenterologists. The mean GVS of IBS patients was significantly higher than that in the control group (p < 0.001). The sequential reproducibility was recognized in all 10 IBS patients. There was no significance between colonic transit time and GVS, nor between symptoms and GVS. CONCLUSIONS: Abdominal gas was analyzed objectively by using GVS, and GVS was considered to represent a useful tool for the diagnosis of IBS.     

The sense of coherence index and the irritable bowel syndrome. A cross-sectional comparison among irritable bowel syndrome patients with and without coexisting fibromyalgia, irritable bowel syndrome non-patients, and controls

BACKGROUND: Sense of Coherence (SOC) is a global orientation that affects coping with stressors. A strong SOC is associated with better health outcomes. The purpose of this study was to evaluate SOC among patients with irritable bowel syndrome (IBS) and matched controls. METHODS: Seventy-nine IBS patients and 72 matched controls completed questionnaires and were tested for fibromyalgia (FS). The controls were subdivided into healthy controls (n = 49) or IBS non-patients (n = 23), and the patients into IBS only (n = 54) or IBS and FS (n = 25). RESULTS: The mean SOC score was higher for the controls than for the IBS patients (65.7+/-1.2 and 59.6+/-1.1, respectively; P = 0.003). There was no significant difference between the healthy controls and the IBS non-patients. The controls had a higher SOC than patients with IBS only and patients with IBS and FS (P = 0.0004). CONCLUSIONS: An association was found between IBS and SOC. No causality can be inferred from this study. Individuals with low SOC may be more likely to express symptoms in terms of psychologic distress and increased health care utilization because of poor coping skills. Conversely, the presence of IBS may affect SOC negatively. Further longitudinal studies could clarify the potential of SOC as a predictor variable (for example, for treatment results) or an outcome variable.     

Quantitative assessment of glucose transport in human skeletal muscle: dynamic positron emission tomography imaging of [O-methyl-11C]3-O-methyl-D-glucose

Insulin-stimulated glucose transport in skeletal muscle is regarded as a key determinant of insulin sensitivity, yet isolation of this step for quantification in human studies is a methodological challenge. One notable approach is physiological modeling of dynamic positron emission tomography (PET) imaging using 2-[18-fluoro]2-deoxyglucose ([(18)F]FDG); however, this has a potential limitation in that deoxyglucose undergoes phosphorylation subsequent to transport, complicating separate estimations of these steps. In the current study we explored the use of dynamic PET imaging of [(11)C]3-O-methylglucose ([(11)C]3-OMG), a glucose analog that is limited to bidirectional glucose transport. Seventeen lean healthy volunteers with normal insulin sensitivity participated; eight had imaging during basal conditions, and nine had imaging during euglycemic insulin infusion at 30 mU/min.m(2). Dynamic PET imaging of calf muscles was conducted for 90 min after the injection of [(11)C]3-OMG. Spectral analysis of tissue activity indicated that a model configuration of two reversible compartments gave the strongest statistical fit to the kinetic pattern. Accordingly, and consistent with the structure of a model previously used for [(18)F]FDG, a two-compartment model was applied. Consistent with prior [(18)F]FDG findings, insulin was found to have minimal effect on the rate constant for movement of [(11)C]3-OMG from plasma to tissue interstitium. However, during insulin infusion, a robust and highly significant increase was observed in the kinetics of inward glucose transport; this and the estimated tissue distribution volume for [(11)C]3-OMG increased 6-fold compared with basal conditions. We conclude that dynamic PET imaging of [(11)C]3-OMG offers a novel quantitative approach that is both chemically specific and tissue specific for in vivo assessment of glucose transport in human skeletal muscle.     

Multifocal, persistent cardiac uptake of [18-F]-fluoro-deoxy-glucose detected by positron emission tomography in patients with acute myocardial infarction

BACKGROUND: Inflammation appears to be important in the pathogenesis of acute myocardial infarction (AMI). METHODS AND RESULTS: Cardiac [18-F]-fluoro-deoxy-glucose (FDG) uptake by positron emission tomography/computed tomography (PET/CT)-scan was investigated in 12 fasting patients with first AMI (FAMI) single-vessel disease after successful primary percutaneous coronary intervention and at 9 weeks follow-up, and in 12 controls. The average FDG uptake (aFDGu) of the 28 left ventricular (LV) wall segments defined on the PET/CT images of the 12 FAMI patients was 1.28+/-0.57-fold higher than the activity present in the LV cavity. By contrast, the aFDGu of the 12 controls was 0.70+/-22 (p<0.001). The segmental aFDGu in the FAMI was multifocal in both the culprit and non-culprit segments; it was less than LV cavity activity in 38%, 1-2-fold greater in 51.8% and more than 2-fold greater in 10.2%. At follow-up, aFDGu was significantly increased in both culprit and non-culprit segments (1.69+/-1.15, p<0.001). Statistically significant differences between FAMI and controls patients were only found for interleukin-6 plasma levels on admission (11.3+/-7.7 pg/ml vs 2.2+/-1.3 pg/ml; p<0.004). CONCLUSION: Multifocal, non-infarct related, cardiac-FDG-uptake occurred immediately after AMI and persisted at follow-up. The cause of these striking and consistent findings is still speculative.     

Assessment of myocardial oxidative metabolism in aortic valve disease using positron emission tomography with C-11 acetate.

C-11 acetate has recently been introduced as a tracer of myocardial oxidative metabolism with the use of positron emission tomography. To evaluate this approach in the pressure- or volume-loaded heart, C-11 acetate clearance rate constants were determined in 22 patients with chronic aortic valve disease and in nine normal subjects. Global myocardial C-11 clearance was significantly higher in patients with predominant aortic stenosis (n = 11) or aortic regurgitation (n = 11) than in normal subjects (0.069 +/- 0.017 min-1 and 0.072 +/- 0.010 min-1 compared with 0.050 +/- 0.004 min-1, p less than 0.05) and correlated significantly with the rate-pressure product corrected for mean aortic valve gradient (r = 0.73, p = 0.0001) for all studies. However, analysis of patient subgroups demonstrated that this correlation held only for aortic stenosis (r = 0.79, p less than 0.005 for gradient-corrected rate-pressure product). Additionally, C-11 clearance was strongly correlated with the product of heart rate and mean wall stress in patients with aortic stenosis (r = 0.89, p less than 0.005) but not in patients with aortic regurgitation. Normalization of C-11 acetate clearance rate constants for gradient-corrected rate-pressure product were significantly lower in patients with loaded ventricles, particularly in the presence of a low ejection fraction, compared to normal subjects. Possible mechanisms include myocardial adaptation through hypertrophy or depressed contractility, which would both tend to reduce oxygen consumption under any given load. Serial comparison of C-11 acetate kinetics and noninvasive indexes of oxygen demand may provide assessment of disease progression in pathologic ventricular loading.