Michael N. Maisey

Detection of bone metastases in breast cancer by 18FDG PET: differing metabolic activity in osteoblastic and osteolytic lesions.

PURPOSE 99mTechnetium methylene diphosphonate (99mTc MDP) bone scintigraphy is currently the method of choice for the detection of bone metastases, but 18F-fluoro-deoxy-D-glucose positron emission tomography (18FDG PET) offers superior spatial resolution and improved sensitivity. We have compared 18FDG PET with 99mTc MDP bone scintigraphy in patients with skeletal metastases from breast cancer and have analyzed the data in subgroups based on radiographic characteristics of lesions. PATIENTS AND METHODS Twenty-three women with breast cancer and confirmed bone metastases were studied with both 99mTC MDP bone scintigraphy and 18FDG PET, and the number of lesions detected and the quantitation of uptake (standardized uptake values [SUVs]) of 18FDG in osteolytic and osteoblastic metastases were compared. Survival was compared for both lytic and blastic bone metastases and for patients with high and low accumulation of 18FDG. RESULTS 18FDG PET detected more lesions than 99mTc MDP scintigraphy (mean, 14.1 and 7.8 lesions, respectively; P < .01). However, 18FDG detected fewer bone metastases compared with 99mTc MDP scintigraphy in a subgroup of patients with osteoblastic disease (P < .05). Higher SUVs were observed for osteolytic than osteoblastic disease (mean, 6.77 and 0.95, respectively; P < .01). Survival was lower in patients with osteolytic disease compared with the remainder (P=.01). A difference in survival was not found for those patients with high SUVs (> 3.6; P=.4). CONCLUSION 18FDG PET is superior to bone scintigraphy in the detection of osteolytic breast cancer metastases, which led to a poorer prognosis. In contrast, osteoblastic metastases show lower metabolic activity and are frequently undetectable by PET. The biologic explanation for this observation remains to be elucidated.

Normal physiological and benign pathological variants of 18-fluoro-2-deoxyglucose positron-emission tomography scanning: Potential for error in interpretation

The use of positron-emission tomography in clinical practice is increasing, particularly with the use of 18-fluoro-2-deoxyglucose (FDG) for oncological studies. As in other imaging modalities, it is important to be aware of normal variants and benign diseases that may mimic more serious pathology. Uptake of FDG in a number of sites may be variable. Uptake of FDG may be seen normally in the skeletal muscle after exercise or under tension, in the myocardium, in parts of the gastrointestinal tract, especially the stomach and cecum, and in the urinary tract. Some causes of increased physiological uptake are avoidable, and measures can be taken to minimize accumulation, thus aiding study interpretation. Inflammatory lesions may cause an increase in FDG uptake, but not usually to the same degree as malignancy. Benign disease such as Pagets disease of bone, sarcoidosis, and tuberculosis may cause uptake that occasionally mimics that of malignancy. Typical examples of a number of physiological and benign variants are described and illustrated.

Normal variants, artefacts and interpretative pitfalls in PET imaging with 18-fluoro-2-deoxyglucose and carbon-11 methionine.

Abstract. Interpretation of studies from all imaging modalities requires a knowledge of the possible pitfalls that may occur due to normal variation, artefacts and processes which may mimic pathology. The applications and use of not only 18-fluoro-2-deoxyglucose but also l-[methyl-11C] methionine positron emission tomography (PET) are widening and it is timely that the currently recognised interpretative pitfalls are reviewed as the number of dedicated PET scanners and coincidence gamma cameras increases.

Evaluation of fluorine-18-fluorodeoxyglucose whole body positron emission tomography imaging in the staging of lung cancer

BACKGROUND Surgical resection of lung cancer remains the treatment of choice in appropriately staged disease, but conventional imaging techniques have limitations. Positron emission tomography (PET) may improve staging accuracy. METHODS We studied whole body and localized thoracic PET in staging lung cancer. Standardized uptake value was calculated for the primary lesion. Ninety-seven patients under consideration for surgical resection were included. PET, computed tomography, and clinical staging were compared to stage at operation, biopsy, or final outcome. Mean follow up was 17.5 months. RESULTS PET detected all primary lung cancers with two false-positive primary sites. Sensitivity and specificity for N2 and N3 mediastinal disease was 20% and 89.9% for computed tomography and 70.6% and 97% for PET. PET correctly altered stage in 26.8%, nodal stage in 13.4%, and detected distant metastases in 16.5%. PET missed 7 of 10 cerebral metastases. PET altered management in 37% of patients. PET staging (p<0.0001) and standardized uptake value (p<0.001) were the best predictors of time to death apart from operative staging. CONCLUSIONS PET provides significant staging and prognostic information in lung cancer patients considered operable by standard criteria. Routine use of PET will prevent unnecessary operation and may be cost effective.

Use of positron emission tomography in evaluation of brachial plexopathy in breast cancer patients

Summary18-Fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) has previously been used successfully to image primary and metastatic breast cancer. In this pilot study, 19 breast cancer patients with symptoms/signs referrable to the brachial plexus were evaluated with 18FDG-PET. In 11 cases computerized tomography (CT) scanning was also performed. Of the 19 patients referred for PET study, 14 had abnormal uptake of 18FDG in the region of the symptomatic plexus. Four patients had normal PET studies and one had increased FDG uptake in the chest wall that accounted for her axillary pain. CT scans were performed in 9 of the 14 patients who had positive brachial plexus PET studies; six of these were either normal or showed no clear evidence of recurrent disease, while three CTs demonstrated clear brachial plexus involvement. Of two of the four patients with normal PET studies, one has had complete resolution of symptoms untreated while the other was found to have cervical disc herniation on magnetic resonance imaging (MRI) scan. The remaining two patients almost certainly had radiation-induced plexopathy and had normal CT, MRI and PET study. These data suggest that 18FDG-PET scanning is a useful tool in evaluation of patients with suspected metastatic plexopathy, particularly if other imaging studies are normal. It may also be useful in distinguishing between radiation-induced and metastatic plexopathy.

Regional Differences in Cerebral Blood Flow and Glucose Utilization in Diabetic Man: The Effect of Insulin

To determine the effect of insulin on regional cerebral blood flow (rCBF) and glucose metabolism (CMRglu), we performed quantitative dynamic PET scanning of labeled water (H215O) and deoxyglucose (18FDG) using two protocols in 10 diabetic men. In protocol A, to test reproducibility of the technique, insulin was infused at 1.5 mU·kg−1·min−1 twice (n = 5). In protocol B, low (0.3 mU·kg−1·min−1) and high (3 mU·kg−1·min−1) dose insulin was given on separate occasions (n = 5). Euglycemia (5 mmol/L) was maintained by glucose infusion. In protocol A, CMRglu was 6% higher during the first infusion, and catecholamines were also increased, indicating stress. Blood flow was not different. Changing free insulin levels from 20.5 ± 4.8 to 191 ± 44.5 mU/L (P < 0.001, low versus high dose, protocol B) did not alter total or regional CMRglu (whole brain 36.6 ± 4.0 versus 32.8 ± 6.2 μmol·100 g−1·min−1, P = 0.32) or CBF (41.7 ± 5.1 and 45.6 ± 9.7 mL·100 g−1·min−1, P = 0.4) or rCBF. In cerebellum, CMRglu was lower than in cortex and the ratio between rate constants for glucose uptake and phosphorylation (K1 and k3) was reversed. There are regional differences in cerebral metabolic capacity that may explain why cerebral cortex is more sensitive to hypoglycemia than cerebellum. Brain glucose metabolism is not sensitive to insulin concentration within the physiologic range. This suggests that intracerebral insulin receptors have a different role from those in the periphery.

Significance of interictal bilateral temporal hypometabolism in temporal lobe epilepsy

Objective: To assess the clinical implications and the pathophysiologic determinants of interictal bitemporal hypometabolism (BTH) in temporal lobe epilepsy (TLE) not associated with bilateral MRI abnormalities or intracranial space-occupying lesions. Methods: The authors compared the clinical, interictal, and ictal EEG, Wada test, and neuropsychology data of 15 patients with intractable complex partial seizures of temporal lobe origin and BTH with those of 13 consecutive patients with unilateral TLE associated with unilateral temporal hypometabolism (UTH) who remained seizure free for more than 3 years after anterior temporal lobectomy. 18F-fluorodeoxyglucose PET scans were analyzed visually and semiquantitatively, and ratios of counts in individual temporal areas to the rest of the cerebrum were compared with the corresponding values from 11 normal control subjects and with the nonepileptogenic hemisphere of the 13 patients with UTH. BTH was defined as more than 2.5 SDs below control values for two or more temporal areas on each side irrespective of any asymmetry. Results: BTH reflected bilateral independent seizure onset in eight patients (53%). The topography of the metabolic depression was not a reliable predictor of epileptogenicity, but involvement of the inferior temporal gyrus was related specifically to ipsilateral seizure onset (70% sensitivity, 100% specificity). In patients with unilateral TLE, contralateral hypometabolism was associated with longer disease duration and worst memory performance during the Wada test, which amounted to global amnesia after ipsilateral injection in three patients, precluding surgical treatment. Contralateral seizure spread in the ictal EEG was significantly faster in patients with BTH. Conclusions: In TLE, symmetric or asymmetric BTH may signal bilateral independent seizure onset in approximately half the patients, especially when involving the inferior temporal gyrus. Alternatively, it may reflect an advanced stage of the disease process, characterized by a breakdown of the inhibitory mechanisms in the contralateral hemisphere, and secondary memory deficit associated with higher risk of postoperative memory decline. Patients with TLE and BTH but without bilateral MRI changes may still be operated on successfully, but surgical suitability should be proved by comprehensive intracranial EEG studies and Wada test.

Optimization of noise-equivalent count rates in 3D PET

We have used noise-equivalent count (NEC) rates to optimize count rate performance for 3D acquisition in PET in a wide range of situations, with particular reference to imaging of the torso. We have also compared NEC performance for 2D and 3D acquisition in order to establish the conditions under which 3D mode offers an improvement over 2D mode. Measurements were performed on four tissue-equivalent phantoms ranging in size from that of an infants head (13 cm diameter) to that of an obese adults chest (37 cm x 48 cm). Count rate data were acquired as a function of phantom size, activity in the field of view, lower energy discriminator level (LLD) and acquisition mode, and NEC rates were derived as a function of these variables. The LLD at which the highest NEC rate is obtained shows a dependence both on phantom size and on the activity in the field of view both for 2D and for 3D acquisition. The relative advantage of 3D mode over 2D mode, at the optimum LLD setting, is also strongly dependent both on activity in the field of view (FOV) and on the phantom size. The main limiting factors for 3D NEC rates are detector dead-time for small phantoms and random coincidences for large phantoms. The 3D NEC rate is more than twice as great as the 2D NEC rate when less than 60 MBq is present in the FOV for all phantoms except the largest, in which case a ratio of two is only achieved for activities less than 25 MBq. For the smallest phantom, 3D/2D NEC ratios of greater than 3.5 are obtained when the activity in the FOV falls below 10 MBq.

Interictal regional slow activity in temporal lobe epilepsy correlates with lateral temporal hypometabolism as imaged with 18FDG PET : neurophysiological and metabolic implications

OBJECTIVES The phenomenon of interictal regional slow activity (IRSA) in temporal lobe epilepsy and its relation with cerebral glucose metabolism, clinical data, MRI, and histopathological findings was studied. METHODS Interictal18F-fluorodeoxyglucose positron emission tomography (FDG PET) was performed under continuous scalp EEG monitoring in 28 patients with temporal lobe epilepsy not associated with intracranial foreign tissue lesions, all of whom subsequently underwent resective surgery. Regions of interest (ROIs) were drawn according to a standard template. IRSA was considered lateralised when showing a 4:1 or greater ratio of predominance on one side. RESULTS Sixteen patients (57%) had lateralised IRSA which was always ipsilateral to the resection and of maximal amplitude over the temporal areas. Its presence was significantly related to the presence of hypometabolism in the lateral temporal neocortex (p=0.0009). Logistic regression of the asymmetry indices for all measured cerebral regions confirmed a strong association between IRSA and decreased metabolism of the posterior lateral temporal neocortex only (p=0.009). No significant relation could be shown between slow activity and age at onset, duration of the epilepsy, seizure frequency, and MRI evidence for hippocampal atrophy. Furthermore, IRSA was not specifically related to mesial temporal sclerosis or any other pathology. CONCLUSIONS Interictal regional slowing in patients with temporal lobe epilepsy not associated with a mass lesion is topographically related to the epileptogenic area and therefore has a reliable lateralising, and possibly localising, value. Its presence is irrelevant to the severity or chronicity of the epilepsy as well as to lateral deactivation secondary to neuronal loss in the mesial temporal structures. Although slow EEG activity is generally considered as a non-specific sign of functional disturbance, interictal regional slowing in temporal lobe epilepsy should be conceptualised as a distinct electrographic phenomenon which is directly related to the epileptogenic abnormality. The strong correlation between interictal regional slowing and lateral temporal hypometabolism suggests in turn that the second may delineate a field of reduced neuronal inhibition which can receive interictal and ictal propagation.

Positron emission tomography in male violent offenders with schizophrenia

The FDG PET brain scans from 31 offenders with schizophrenia and schizoaffective disorder from a maximum security mental hospital were compared with those of normal controls (N = 6) in terms of relative FDG uptake in a range of regions covering frontal and temporal regions. The patient sample was divided into those who had a history of repetitive violent offending (RVO, N = 17) and those without a repetitive violent history (NRVO, N = 14) according to the violence rating of their pre-admission convictions. Reduced FDG uptake was noted at both the right and left anterior inferior temporal (R and L AIT) regions in NRVOs but only at LAIT in RVOs. NRVOs had significantly lower FDG uptake at RAIT than RVOs. The findings suggest that metabolic changes at AIT may be related to different patterns of violent offending in patients with schizophrenia.