Evaluation of 18F-FDG uptake in lung parenchyma compensating for tissue fraction: Comparison between non-enhanced low dose CT and intravenous contrast-enhanced diagnostic CT.

AIM: To determine how the presence of intravenous (IV) contrast-enhanced CT influences SUV measurements corrected for both attenuation and tissue fraction. MATERIAL AND METHODS: Eighteen patients with different malignancies, free from lung disorders, lung cancer or metastasis, were prospectively recruited when referred for staging with combined 18F-FDG-PET/CT examination. A non-enhanced low-dose CT over the chest was immediately followed by a whole-body IV contrast-enhanced diagnostic CT and finally the PET acquisition. PET data were reconstructed with attenuation correction based on the two CT data sets. The lungs were segmented in the CT images and lung density was measured. Uptake of 18F-FDG in lung parenchyma was recorded using both non-enhanced and IV contrast-enhanced CT as well as with and without compensation for lung aeration. A comparison of SUV values of corrected and uncorrected PET images was performed. RESULTS: There was no significant difference between low dose PET/CT and IV contrast-enhanced PET/CT when removing the impact of air fraction (p = 0.093 for the right lung and p = 0.085 for the left lung). When tissue fraction was not corrected for, there was a significant difference between low dose PET/CT and IV contrast enhanced PET/CT used for attenuation correction (p = 0.006 for the right lung and p = 0.015 for the left lung). CONCLUSION: There was only a marginal effect on the assessement of SUV in the lung tissue when using IV contrast enhanced CT for attenuation correction when the air fraction was accounted for.

Measurement of airway inflammation in current smokers by positron emission tomography.

BACKGROUND: Accumulation of activated neutrophilic leucocytes is known to increase uptake of 18 F-fluorodeoxyglucose (18 F-FDG) into lung tissue. Available evidence suggests that smokers and subjects with chronic obstructive pulmonary disease (COPD) have neutrophilic inflammation in peripheral airways. The aim of this study was to examine whether current smokers have higher lung tissue uptake of 18 F-FDG than never-smokers when correcting for air fraction of the lungs. METHODS: We prospectively recruited 33 current smokers and 33 never-smokers among subjects referred for diagnosis or staging of cancer, other than lung cancer, with combined positron emission tomography/computed tomography (PET/CT) with 18 F-FDG. Subjects with focal 18 F-FDG uptake or focal CT abnormalities in the lungs were excluded. The lungs were segmented in the CT image, and lung density measured. 18 F-FDG uptake was measured in the corresponding volume and corrected for air fraction. RESULTS: Lung uptake of 18 F-FDG, corrected for air fraction, was 12·5 and 8 per cent higher in the right and left lungs, respectively, in current smokers than in never-smokers (P<0·05). Conclusion Abnormal lung tissue uptake of 18 F-FDG may be masked by reduced lung density if the uptake is not related to air fraction. Increased uptake of 18 F-FDG in lung tissue in current smokers relative to never-smokers may reflect inflammation in peripheral airways. Measurements of 18 F-FDG uptake in the lung tissue may be useful for animal and human studies of airways disease in COPD and the relation between airway and systemic inflammation.

Adding attenuation corrected images in myocardial perfusion imaging reduces the need for a rest study.

BACKGROUND: The American Society of Nuclear Cardiology and the Society of Nuclear Medicine conclude that incorporation of attenuation corrected (AC) images in myocardial perfusion scintigraphy (MPS) will improve diagnostic accuracy. The aim was to investigate the value of adding AC stress-only images for the decision whether a rest study is necessary or not. METHODS: 1,261 patients admitted to (99m)Tc MPS were studied. The stress studies were interpreted by two physicians who judged each study as "no rest study necessary" or "rest study necessary", by evaluating NC stress-only and NC + AC stress-only images. When there was disagreement between the two physicians, a third physician evaluated the studies. Thus, agreement between 2 out of 3 physicians was evaluated. RESULTS: The physicians assessed 214 more NC + AC images than NC images as "no rest study necessary" (17% of the study population). The number of no-rest-study-required was significantly higher for NC + AC studies compared to NC studies (859 vs 645 cases (p < 0.0001). In the final report according to clinical routine, ischemia or infarction was reported in 23 patients, assessed as "no rest study necessary" (22 NC + AC cases; 8 NC cases), (no statistically significant difference). In 11 of these, the final report stated "suspected/possible ischemia or infarction in a small area". CONCLUSIONS: Adding AC stress-only images to NC stress-only images reduce the number of unnecessary rest studies substantially.

Nuclear medicine technologists are able to accurately determine when a myocardial perfusion rest study is necessary.

BACKGROUND: In myocardial perfusion scintigraphy (MPS), typically a stress and a rest study is performed. If the stress study is considered normal, there is no need for a subsequent rest study. The aim of the study was to determine whether nuclear medicine technologists are able to assess the necessity of a rest study. METHODS: Gated MPS using a 2-day 99mTc protocol for 121 consecutive patients were studied. Visual interpretation by 3 physicians was used as gold standard for determining the need for a rest study based on the stress images. All nuclear medicine technologists performing MPS had to review 82 training cases of stress MPS images with comments regarding the need for rest studies, and thereafter a test consisting of 20 stress MPS images. After passing this test, the nuclear medicine technologists in charge of a stress MPS study assessed whether a rest study was needed or not or if he/she was uncertain and wanted to consult a physician. After that, the physician in charge interpreted the images and decided whether a rest study was required or not. RESULTS: The nuclear medicine technologists and the physicians in clinical routine agreed in 103 of the 107 cases (96%) for which the technologists felt certain regarding the need for a rest study. In the remaining 14 cases the technologists were uncertain, i.e. wanted to consult a physician. The agreement between the technologists and the physicians in clinical routine was very good, resulting in a kappa value of 0.92. There was no statistically significant difference in the evaluations made by technicians and physicians (P = 0.617). CONCLUSIONS: The nuclear medicine technologists were able to accurately determine whether a rest study was necessary. There was very good agreement between nuclear medicine technologists and physicians in the assessment of the need for a rest study. If the technologists can make this decision, the effectiveness of the nuclear medicine department will improve.

Evaluation of image reconstruction methods for (123)I-MIBG-SPECT: a rank-order study.

BACKGROUND: There is an opportunity to improve the image quality and lesion detectability in single photon emission computed tomography (SPECT) by choosing an appropriate reconstruction method and optimal parameters for the reconstruction. PURPOSE: To optimize the use of the Flash 3D reconstruction algorithm in terms of equivalent iteration (EI) number (number of subsets times the number of iterations) and to compare with two recently developed reconstruction algorithms ReSPECT and orthogonal polynomial expansion on disc (OPED) for application on (123)I-metaiodobenzylguanidine (MIBG)-SPECT. MATERIAL AND METHODS: Eleven adult patients underwent SPECT 4 h and 14 patients 24 h after injection of approximately 200 MBq (123)I-MIBG using a Siemens Symbia T6 SPECT/CT. Images were reconstructed from raw data using the Flash 3D algorithm at eight different EI numbers. The images were ranked by three experienced nuclear medicine physicians according to their overall impression of the image quality. The obtained optimal images were then compared in one further visual comparison with images reconstructed using the ReSPECT and OPED algorithms. RESULTS: The optimal EI number for Flash 3D was determined to be 32 for acquisition 4 h and 24 h after injection. The average rank order (best first) for the different reconstructions for acquisition after 4 h was: Flash 3D(32) > ReSPECT > Flash 3D(64) > OPED, and after 24 h: Flash 3D(16) > ReSPECT > Flash 3D(32) > OPED. A fair level of inter-observer agreement concerning optimal EI number and reconstruction algorithm was obtained, which may be explained by the different individual preferences of what is appropriate image quality. CONCLUSION: Using Siemens Symbia T6 SPECT/CT and specified acquisition parameters, Flash 3D(32) (4 h) and Flash 3D(16) (24 h), followed by ReSPECT, were assessed to be the preferable reconstruction algorithms in visual assessment of (123)I-MIBG images.

Semi-automatic analysis of standard uptake values in serial PET/CT studies in patients with lung cancer and lymphoma.

BACKGROUND: Changes in maximum standardised uptake values (SUVmax) between serial PET/CT studies are used to determine disease progression or regression in oncologic patients. To measure these changes manually can be time consuming in a clinical routine. A semi-automatic method for calculation of SUVmax in serial PET/CT studies was developed and compared to a conventional manual method. The semi-automatic method first aligns the serial PET/CT studies based on the CT images. Thereafter, the reader selects an abnormal lesion in one of the PET studies. After this manual step, the program automatically detects the corresponding lesion in the other PET study, segments the two lesions and calculates the SUVmax in both studies as well as the difference between the SUVmax values. The results of the semi-automatic analysis were compared to that of a manual SUVmax analysis using a Philips PET/CT workstation. Three readers did the SUVmax readings in both methods. Sixteen patients with lung cancer or lymphoma who had undergone two PET/CT studies were included. There were a total of 26 lesions. RESULTS: Linear regression analysis of changes in SUVmax show that intercepts and slopes are close to the line of identity for all readers (reader 1: intercept = 1.02, R2 = 0.96; reader 2: intercept = 0.97, R2 = 0.98; reader 3: intercept = 0.99, R2 = 0.98). Manual and semi-automatic method agreed in all cases whether SUVmax had increased or decreased between the serial studies. The average time to measure SUVmax changes in two serial PET/CT examinations was four to five times longer for the manual method compared to the semi-automatic method for all readers (reader 1: 53.7 vs. 10.5 s; reader 2: 27.3 vs. 6.9 s; reader 3: 47.5 vs. 9.5 s; p < 0.001 for all). CONCLUSIONS: Good agreement was shown in assessment of SUVmax changes between manual and semi-automatic method. The semi-automatic analysis was four to five times faster to perform than the manual analysis. These findings show the feasibility of using semi-automatic methods for calculation of SUVmax in clinical routine and encourage further development of programs using this type of methods.

Simultaneous quantification of myocardial perfusion, oxidative metabolism, cardiac efficiency and pump function at rest and during supine bicycle exercise using 1-11C-acetate PET--a pilot study.

BACKGROUND: PET using 1-(11)C-acetate (ACE-PET) applied at rest is used for measuring absolute myocardial blood flow (MBF) and oxidative metabolic rate (k(mono)). We evaluated the feasibility of quantitative ACE-PET during exercise. METHODS: Five endurance athletes underwent dynamic PET scanning at rest and during supine bicycle stress. Exercise was maintained at a workload of 120 Watt for 17 min. The rate-pressure product (RPP) was recorded repeatedly. MBF, k(mono) in left (LV) and right (RV) ventricular wall, cardiac output (CO), cardiac efficiency and a lung uptake value reflecting left heart diastolic pressures were calculated from the PET data using previously validated models. RESULTS: MBF increased from 0.71 +/- 0.17 to 2.48 +/- 0.25 ml min(-1) per ml, LV-k(mono) from 0.050 +/- 0.005 to 0.146 +/- 0.021 min(-1), RV-k(mono) from 0.023 + 0.006 to 0.087 + 0.014 min(-1), RPP from 4.7 +/- 0.8 to 13.2 +/- 1.4 mmHg x min(-1) x 10(3) and Cardiac Output from 5.2 +/- 1.1 to 12.3 +/- 1.2 l min (-1) (all P < 0.001). Cardiac efficiency was unchanged (P = 0.99). Lung uptake decreased from 1.1 +/- 0.2 to 0.6 +/- 0.1 ml g(-1) (P < 0.001). DISCUSSION: A number of important parameters related to cardiac function can be quantified non-invasively and simultaneously with a short scanning protocol during steady state supine bicycling. This might open up new opportunities for studies of the integrated cardiac physiology in health and early asymptomatic disease.

Right ventricular metastasis of leiomyosarcoma.

Metastatic presentation of leiomyosarcoma in the heart is very rare. We present transthoracic echocardiography and combined PET/CT images of a case with a large right ventricular metastasis of leiomyosarcoma. The patient was placed on cytostatic drugs for palliative purposes, but passed away one month later because of an untreatable ventricular tackycardia.

Primary lung tumour visualised by transthoracic echocardiography.

We present images of a rare case where a primary lung tumour was visualised by transthoracic echocardiography. The patient was a 78-year-old male where Chest X-ray had revealed a tumour-suspected structure in the left lung. Both transthoracic echocardiography and combined PET/CT images showed a large tumour located close to the heart. Fine-needle biopsy showed non-small cell lung cancer.

Sympathetic nerve dysfunction is common in patients with chronic intestinal pseudo-obstruction.

GOAL: To clarify whether disturbances in the autonomic nervous system, reflected in abnormal cardiovascular reflexes, could explain symptoms of impaired heat regulation in patients with intestinal pseudo-obstruction. BACKGROUND: Chronic intestinal pseudo-obstruction is a clinical syndrome characterized by diffuse, unspecific gastrointestinal symptoms due to damage to the enteric nervous system or the smooth muscle cells. These patients often complain of excessive sweating or feeling cold, suggesting disturbances in the autonomic nervous system. Earlier studies have pointed to a coexistence of autonomic disturbances in the enteric and cardiovascular nervous system. STUDY: Thirteen consecutive patients (age range 23 to 79, mean 44 y) fulfilling the criteria for chronic intestinal pseudo-obstruction were investigated. Six of them complained of sweating or a feeling of cold. Examination of autonomic reflexes included heart rate variation to deep-breathing (expiration/inspiration index), heart rate reaction to tilt (acceleration index, brake index), and vasoconstriction (VAC) due to indirect cooling by laser doppler (VAC-index; high index indicates impaired VAC). Test results in patients were compared with healthy individuals. RESULTS: Patients had significantly higher (more abnormal) median VAC-index compared with healthy controls [1.79 (interquartile ranges 1.89) vs. 0.08 (interquartile ranges 1.29); P=0.0007]. However, symptoms of impaired heat regulation were not related to the VAC-index. There were no differences in expiration/inspiration, acceleration index, or brake index between patients and controls. CONCLUSIONS: The patients with severe gastrointestinal dysmotility showed impaired sympathetic nerve function which, however, did not seem to be associated with symptoms of impaired heat regulation.

Automated interpretation of PET/CT images in patients with lung cancer.

PURPOSE: To develop a completely automated method based on image processing techniques and artificial neural networks for the interpretation of combined [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed tomography (CT) images for the diagnosis and staging of lung cancer. METHODS: A total of 87 patients who underwent PET/CT examinations due to suspected lung cancer comprised the training group. The test group consisted of PET/CT images from 49 patients suspected with lung cancer. The consensus interpretations by two experienced physicians were used as the 'gold standard' image interpretation. The training group was used in the development of the automated method. The image processing techniques included algorithms for segmentation of the lungs based on the CT images and detection of lesions in the PET images. Lung boundaries from the CT images were used for localization of lesions in the PET images in the feature extraction process. Eight features from each examination were used as inputs to artificial neural networks trained to classify the images. Thereafter, the performance of the network was evaluated in the test set. RESULTS: The performance of the automated method measured as the area under the receiver operating characteristic curve, was 0.97 in the test group, with an accuracy of 92%. The sensitivity was 86% at a specificity of 100%. CONCLUSIONS: A completely automated method using artificial neural networks can be used to detect lung cancer with such a high accuracy that the application as a clinical decision support tool appears to have significant potential.

Inhibition of carnitine-acyl transferase I by oxfenicine studied in vivo with [11C]-labeled fatty acids.

METHODS: Anesthetized pigs were studied with [(11)C]-labeled fatty acids (FAs) with carbon chain length ranging from 8 to 16 carbon atoms, during control conditions and during inhibition of carnitine-palmitoyl transferase I (CPT I) with oxfenicine. The myocardial uptake of [(11)C]-FAs from blood was measured together with the relative distribution of [(11)C]-acyl-CoA between rapid mitochondrial oxidation and incorporation into slow turnover lipid pools in the heart. RESULTS: During baseline conditions, the fractional oxidative utilization of palmitate was almost as high as that of carnitine-independent short-chain FAs, unless the carnitine shuttle was inhibited by high levels of lactate. Inhibition of CPT I almost completely blocked the oxidative pathway for palmitic acid and reduced the fractional oxidative utilization, while the rate of oxidative metabolism of acyl-CoA was unaffected. CONCLUSIONS: [(11)C]-Labeled FAs allow rapid oxidation to be well separated from esterification into slow turnover lipid pools in the heart of anaesthetized pigs. The fractional oxidative utilization of [(11)C]-palmitate serves well to characterize, in vivo, the carnitine-dependent transfer of long-chain FAs.

Sensed presence and mystical experiences are predicted by suggestibility, not by the application of transcranial weak complex magnetic fields.

Transcranial magnetic stimulation (TMS) with weak (micro Tesla) complex waveform fields have been claimed to evoke the sensed presence of a sentient being in up to 80% in the general population. These findings have had a questionable neurophysiological foundation as the fields are approximately six orders of magnitude weaker than ordinary TMS fields. Also, no independent replication has been reported. To replicate and extend previous findings, we performed a double-blind experiment (N=89), with a sham-field control group. Personality characteristics indicating suggestibility (absorption, signs of abnormal temporal lobe activity, and a "new age"-lifestyle orientation) were used as predictors. Sensed presence, mystical, and other somatosensory experiences previously reported from the magnetic field stimulation were outcome measures. We found no evidence for any effects of the magnetic fields, neither in the entire group, nor in individuals high in suggestibility. Because the personality characteristics significantly predicted outcomes, suggestibility may account for previously reported effects. Our results strongly question the earlier claims of experiential effects of weak magnetic fields.

Development of myocardial microcirculation and metabolism in acute ST-elevation myocardial infarction evaluated with positron emission tomography.

BACKGROUND: Early reperfusion is an established therapeutic objective in acute myocardial infarction (MI). The relationship of regional myocardial microcirculation and metabolism toward outcome in acute human MI is not well known. METHODS AND RESULTS: In 8 patients, positron emission tomography (PET) was performed with oxygen 15-labeled water at 3 hours, 24 hours, and 3 weeks after the start of fibrinolytic treatment, with carbon 11 acetate at 3 hours and with fluorine 18 fluorodeoxyglucose at 24 hours and 3 weeks. Absolute quantification of perfusion and water-perfusable tissue fraction (PTF), metabolic activity, and substrate extraction in 4 regions of interest was performed. Coronary angiography was performed at 24 hours. Short-term outcome at 3 weeks was evaluated by contractile reserve with dobutamine stress echocardiography and lung water measurements with PET. Early regional perfusion, PTF, and extraction and utilization of oxygen and glucose decreased closer to the infarct region ( P < .001 for all). Infarct-related oxygen utilization and extraction of oxygen and glucose were closely related to outcome ( P < .01 for all). PTF improved significantly in the infarct-related regions over time in proportion to early oxygen extraction and utilization. CONCLUSIONS: This pilot study indicates that PET might be useful in the evaluation of treatment efficacy and that restoration of oxidative metabolism is more closely related to myocardial damage recovery than perfusion in the early phase after MI.

Cerebral blood flow and metabolism after cardiopulmonary resuscitation. A pathophysiologic and prognostic positron emission tomography pilot study.

BACKGROUND: Prolonged coma is not an uncommon clinical problem following resuscitation from cardiac arrest. Early and precise prediction of outcome is highly desirable for ethical and economical reasons. The aims of this study were to use positron emission tomography (PET) to investigate the regional dynamic changes of cerebral blood flow and metabolism during the early period after cardiopulmonary resuscitation (CPR) in unconscious patients and to evaluate if PET may be a potential prognostic evaluator. METHODS AND RESULTS: PET and Glasgow Coma Scale examinations were sequentially performed on days 1, 3 and 7 in seven patients remaining comatose post CPR. Each PET included regional determinations of cerebral blood flow (rCBF), oxygen metabolism (rCMRO(2)), oxygen extraction ratio (rOER), and cerebral blood volume (rCBV). One patient was excluded due to complex trauma problems. Three patients remained unconscious until death and three woke up. All patients initially exhibited low CMRO(2) and CBF. Increased OER was only found exceptionally and when present was predominantly in focal areas. The comatose patients showed progressive depression of CMRO(2) and after 1 week had lower CMRO(2) than those patients who woke up. This difference was most pronounced in the putamen and occipital cortex. Two of the seven patients developed large focal infarcts. CONCLUSIONS: An initially low CMRO(2) was common to all patients. Early development of subclinical focal ischemic lesions was also common. The progressive depression of CMRO(2) over the first week in those patients remaining unconscious may be an indication of prolonged but not necessarily permanent coma. Further studies are required to identify pathophysiological features that can predict the long-term clinical outcome in patients who remain unconscious after 1 week.

Kinetics of lung macrophages monitored in vivo following particulate challenge in rabbits.

The ligand PK11195 binds specifically in macrophages. We have assessed the use of positron emission tomography (PET) of [(11)C]R-PK11195 to monitor macrophage disposition following particulate challenge to the lung. Repeated PET scanning was performed over 4 weeks following iv [(11)C]R-PK11195 in rabbits treated with 5-microm particles of either amorphous (aSiO(2)) or microcrystalline (xSiO(2)) silica instilled into right upper pulmonary lobes. aSiO(2) resulted in increased macrophages, few neutrophils, and no fibrosis, while xSiO(2) increased macrophages and neutrophils and caused fibrosis. After both stimuli, (11)C localized to the challenged area and correlated with macrophage numbers. Radioactive counts in challenged/control lung regions peaked at 4 days for aSiO(2) (2.88, n = 2) and 6 days for xSiO(2) (4.62, n = 2). The signal remained elevated throughout the study (aSiO(2), 2.33 +/- 0.77 SD, n = 14; xSiO(2), 3.99 +/- 1.29 SD, n = 9), as did macrophage accumulation. (11)C also localized to regions consistent with macrophage traffic through lymph ducts 6 days after aSiO(2) challenge, but not until 4 weeks after xSiO(2). Specific binding of R-PK11195 in macrophages was demonstrated by microautoradiography in lavage fluid from an inflamed rabbit knee-joint model. These data suggest that PET scanning after [(11)C]PK11195 provides a new noninvasive approach for the study of macrophage kinetics in the lung.