Metabolic and hemodynamic evaluation of brain metastases from small cell lung cancer with positron emission tomography

Brain metastases from small cell lung cancer respond to chemotherapy, but response duration is short and the intracerebral concentration of chemotherapy may be too low because of the characteristics of the blood-brain barrier. Positron emission tomography has been applied in a variety of tumors for studies of metabolic and hemodynamic features. This study was performed to determine regional cerebral metabolic rate of glucose (rCMRglu), regional cerebral blood flow (rCBF), and regional cerebral blood volume (rCBV) in brain metastases from small cell lung cancer and the surrounding brain. Tumor rCMRglu, rCBF, and rCBV exerted a broad variability, but were higher than the corresponding values in white matter and higher than or similar to those of gray matter. Tumor rCMRglu and rCBF were highly correlated (P < 0.01, r = 0.79). No correlation between survival and metabolic or hemodynamic parameters could be demonstrated. After radiotherapy, mean tumor rCMRglu decreased from 0.40 to 0.31 micromol/g/min (not significant), and rCBF and rCBV remained unchanged. However, cortical rCBF demonstrated a trend of increased values after radiotherapy from 0.37 to 0.49 ml/g/min (P = 0.13). No change in rCMRglu was observed in gray or white matter after radiotherapy. Global CBF seems to be reversibly depressed by the metastases, but local hemodynamic changes in the tumor could not be detected with positron emission tomography in this study. An association between high tumor rCMRglu and rCBF as an indicator of hypoxia was not observed. Other methods for noninvasive in vivo analysis of tumor hemodynamics are needed, especially for discrimination between tumor necrosis and hypoxia.     

Fluorine-18 deoxyglucose positron emission tomography for the detection of bone metastases in patients with non-small cell lung cancer

Despite advances in morphological imaging, some patients with lung cancer are found to have non resectable disease at surgery or die of recurrence within a year of surgery. At present, metastatic bone involvement is usually assessed using bone scintigraphy, which has a high sensitivity but a poor specificity. We have attempted to evaluate the utility of the fluorine-18 deoxyglucose positron emission tomography (FDG PET) for the detection of bone metastasis. One hundred and ten consecutive patients with histological diagnosis of non-small cell lung cancer (NSCLC) who underwent both FDG PET and bone scintigraphy were selected for this review. In this group, there were 43 patients with metastatic disease (stage IV). Among these, 21 (19% of total group) had one or several bone metastases confirmed by biopsy (n = 8) or radiographic techniques (n = 13). Radionuclide bone scanning correctly identified 54 out of 89 cases without osseous involvement and 19 out of 21 osseous involvements. On the other hand, FDG PET correctly identified the absence of osseous involvement in 87 out of 89 patients and the presence of bone metastasis in 19 out of 21 patients. Thus using PET there were two false-negative and two false-positive cases. PET and bone scanning had, respectively, an accuracy of 96% and 66% in the evaluation of osseous involvement in patients with NSCLC. In conclusion, our data suggest that whole-body FDG PET may be useful in detecting bone metastases in patients with known NSCLC.     

Detection of cholangiocarcinoma in primary sclerosing cholangitis by positron emission tomography

Primary sclerosing cholangitis (PSC) predisposes to cholangiocarcinoma (CC), which usually is widespread in the liver at the time of the diagnosis and which has a median survival of approximately 6 months. Positron emission tomography (PET) is a noninvasive scanning method that allows the assessment of metabolism in vivo by means of positron-emitting radiolabeled tracers. [18F]Fluoro-2-deoxy-D-glucose (FDG) is a glucose analogue that accumulates in various malignant tumors because of their high glucose metabolic rates. The purpose of the study was to develop a PET method to detect small CC tumors in patients with PSC. PET scanning of the liver was performed after intravenous injection of 200 MBq FDG in 9 patients with PSC, 6 patients with PSC + CC, and 5 controls. The scanning was performed at successive time intervals for a total of 90 minutes with simultaneous successive arterial blood sampling for radioactivity concentration determination. In each of the PSC + CC patients, 2 to 7 "hot spots" were seen, with volumes of 1.0 to 45 mL (median, 4.4 mL). There were no hot spots in the two other patient groups. The localization of hot spots was confirmed by single-blind evaluation. Data were analyzed by the Gjedde-Patlak plot, yielding values of the net metabolic clearance of FDG, K [mL min(-1) 100 mL(-1) tissue]. In the CC hot spots, maximum K values were 1.59 to 4.17 (median, 2.34; n = 6); in the reference liver tissues of these patients, K values were 0.40 to 0.69 (median, 0.49); in PSC patients, they were 0.23 to 0.53 (median, 0.36); and in controls, they were 0.20 to 0.34 (median, 0.31). The difference between K in CC hot spots and the other groups was statistically significant (P < .001). We conclude that FDG-PET seems to be able to detect small CC tumors and may be useful in the therapeutic management of PSC.     

Detection of recurrent and metastatic colorectal cancer: comparison of positron emission tomography and computed tomography

BACKGROUND: This study evaluates the clinical value of positron emission tomography (PET) with 2-[F-18] fluoro-2-deoxy-D-glucose (FDG) as compared to computed tomography (CT) in patients with suspected recurrent or metastatic colorectal cancer (CRC). METHODS: A retrospective review of the records of 58 patients who had FDG-PET for evaluation of recurrent or advanced primary CRC was performed. FDG-PET results were compared with those of CT and correlated with operative and histopathologic findings, or with clinical course and autopsy reports. RESULTS: Recurrent or advanced primary CRC was diagnosed in 40 and 11 patients, respectively. The sensitivity and specificity of FDG-PET were 91% and 100% for detecting local pelvic recurrence, and 95% and 100% for hepatic metastases. These values were superior to CT, which had sensitivity and specificity of 52% and 80% for detecting pelvic recurrence, and 74% and 85% for hepatic metastases. FDG-PET correctly identified pelvic recurrence in 19 of 21 patients; CT was negative in 6 of these patients and equivocal in 4. FDG-PET was superior to CT in detecting multiple hepatic lesions and influenced clinical management in 10 of 23 (43%) patients. CONCLUSION: FDG-PET is more sensitive than CT in the clinical assessment of patients with recurrent or metastatic CRC, and provides an accurate means of selecting appropriate treatment for these patients.     

Detection of response to chemotherapy using positron emission tomography in patients with oesophageal and gastric cancer

BACKGROUND: The aim of the study was to determine whether 2-[18F]-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) could detect response to chemotherapy in patients with oesophageal and gastric cancer. METHODS: Fourteen patients underwent imaging before and after chemotherapy using FDG-PET. Computed tomography (CT), dysphagia scores and weight changes were used for comparison of evidence of response. Tumour to liver ratios (TLRs) and influx constants for FDG (K) were used for quantification purposes. RESULTS: Thirteen of 14 lesions were successfully imaged before therapy. Changes were seen in all follow-up scans, ranging from a complete response to a 15 per cent increase in tumour FDG uptake. Response was demonstrated by CT in four patients; all four had large reductions in FDG uptake after chemotherapy. Two patients with an increase in FDG uptake reported no improvement in dysphagia and continued to lose weight during therapy. CONCLUSION: Changes in tumour FDG uptake were seen in all tumours after chemotherapy. FDG-PET may have a role to play in the assessment of patients with upper gastrointestinal malignancy receiving chemotherapy.     

18F]fluorodeoxyglucose uptake in neonatal acute lung injury measured by positron emission tomography

PURPOSE: Our goal was to investigate the role of serial dynamic contrast-enhanced SPGR MRI in the nonsurgical follow-up of patients with temporomandibular joint (TMJ) pain. METHOD: Ten patients (10 joints) with internal derangement of the TMJ were imaged with T1-weighted SE and serial postgadolinium SPGR MR pulse sequences. RESULTS: On T1-weighted images prior to treatment, the disk position was normal in one joint and anteriorly displaced without reduction in nine joints. After treatment, the disk remained normally positioned in one joint, was anteriorly displaced without reduction in eight joints, and was anteriorly displaced with reduction in one joint. The dynamic study after treatment showed a decrease in contrast enhancement of the posterior disk attachment in 7 of 10 joints. These seven patients had resolution or reduction in joint pain. CONCLUSION: These results suggest an association between a decrease in contrast enhancement of the posterior disk attachment and resolution or reduction in joint pain. This association was much stronger than the association between the clinical findings and the anatomy of the disk.     

Assessment of pathophysiology of stroke by positron emission tomography

In stroke patients, multitracer positron emission tomography (PET) permits the assessment of acute changes in regional cerebral blood flow (rCBF), blood volume (rCBV), oxygen consumption (rCMRO2) and glucose metabolism (rCMRgl), which are the initial steps in the complex molecular and biochemical process leading to ischaemic cell damage. While early infarcts exhibit low flow and oxygen consumption, increased oxygen extraction fraction (OEF) due to preserved metabolism at reduced flow suggests viability of tissue. However, most initially "viable" tissue will be metabolically deranged and will become necrotic in the further course; only in a few instances do these tissue compartments recover to normal function. Increased glucose uptake at reduced oxygen supply induces non-oxidative glycolysis with noxious lactacidosis, whereas hyperperfusion beyond the metabolic demand is of controversial effect. In subacute or chronic states after ischaemia reduced flow can be compensated by increased blood volume; when perfusional reserve is exhausted, oxygen extraction increases. Such findings may guide therapeutic decisions and predict the severity of permanent deficits. Functional deactivation of tissue remote from the lesion is found regularly as a sign of damaged connecting pathways. Flow and metabolic studies during the performance of specific tasks help to detect alternative functional loops and may yield prognostic information. Repeat studies in the course of stroke are employed for the evaluation of therapeutic strategies targeted to improve reperfusion or to effect metabolic or biochemical alterations. In the future PET may gain additional clinical importance when patients are selected for elective treatment according to the prevailing pathophysiological pattern.     

Brain networks affected by synchronized sleep visualized by positron emission tomography

Nineteen lightly sleep-deprived healthy volunteers were examined with H2(15)O and positron emission tomography (PET). Scanning was performed during wakefulness and after the subjects had fallen asleep. Sleep stage was graded retrospectively from electroencephalogram (EEG) recordings, and scans were divided into two groups: wakefulness or synchronized sleep. Global flow was quantified, revealing no difference between sleep and wakefulness. A pixel-by-pixel-blocked one-way analysis of variance (ANOVA) was performed after correcting for differences in anatomy and global flow. The sum of squares of the z-score distribution showed a highly significant (P < 0.00001) omnibus difference between sleep and wakefulness. The z-score images indicated decreased flow in the thalamus and the frontal and parietal association cortices and increased flow in the cerebellum during sleep. A principal component (PC) analysis was performed on data after correction for global flow and block effects, and a multivariate analysis of variance (MANOVA) on all PC scores revealed significant (P = 0.00004) differences between sleep and wakefulness. Principal component's 2 and 5 correlated to sleep and revealed distinct networks consisting of PC 2, cerebellum and frontal and parietal association cortices, and PC 5, thalamus.     

Possible uses of positron emission tomography in breast carcinoma

The aetiology, biochemistry, clinical features and complications of histologically confirmed hepatic cirrhosis in 45 patients (26 females, 19 males) seen at the University Hospital of the West Indies, Jamaica, between 1984 and 1994 are presented. The age range was 1 to 72 years (mean 48 years). Abdominal swelling and weight loss were the commonest symptoms, occurring in 51% and 47% of patients, respectively. Jaundice was a presenting feature in 44%. Hepatomegaly was present in 71% of patients and splenomegaly in 33%. The aetiological factors were: alcohol (36%), bush tea (18%), chronic active hepatitis (11%), drugs (7%), and haemochromatosis (2%). Hepatitis B surface antigen was detected in 2 of 20 patients tested. 24% of the patients also had diabetes mellitus., 29% were anaemic, 29% were thrombocytopenic, 4% were leukopenic, and the prothrombin time was prolonged in 22%. The albumin/globulin ratio was reversed in 71% of the patients. The alkaline phosphatase was elevated in 56%, the aspartate aminotransferase was increased in 58% and the gamma glutamyl transpeptidase in 56%. 56% of the patients had macronodular cirrhosis; the liver showed a micronodular pattern in 18%; 7% had biliary cirrhosis; 7% chronic active hepatitis with cirrhosis; and 13% showed a mixed macro-micronodular pattern. Ascites and fluid overload developed in 44% of the patients. Hepatic encephalopathy occurred in 18% and upper gastrointestinal bleeding in 18%.     

The role of positron emission tomography in pharmacokinetic analysis

The physiological and biochemical measurements that can be performed noninvasively in humans with modern imaging techniques offer great promise for defining the precise state of a patient's disease and its response to therapy. In general, there are two critical points in drug development when PET measurements are likely to be particularly useful: (1) In preclinical studies, a new drug can be precisely compared to standard therapies or a series of analogs can be screened for further development on the basis of performance in appropriate animal models. (2) In phase I-II human studies, classic pharmacokinetic measurements can be coupled with imaging measurements (a) to define optimal dosing schedule; (b) to define the potential utility of interventions in particular clinical situations; and (c) to formulate the design of phase III studies that are crucial for drug licensure. In general, the types of measurements that are possible can be grouped into the following categories: 1. In those situations in which the drug can be radiolabeled, the time course of tissue delivery can be determined noninvasively in vivo in health and disease. Such information should be useful for determining dosing schedules, establishing efficacy, and predicting possible toxicity. 2. Ligand-receptor binding can be assessed in vivo in two ways. The ability of the drug to displace standard radiolabeled ligands from their receptors can be determined; alternatively, labeled drug can be used to more directly assess the distribution and time course of binding. These measurements are particularly useful for studying drugs that are active in the central nervous and cardiovascular systems. 3. Measurements of tissue metabolism will be useful in determining the effects of therapies aimed at particular metabolic abnormalities. In addition, these measurements may be useful in defining viability and function of tissues in such widely disparate clinical situations as cancer chemotherapy and cardiology. For example, effects of CNS or cardiovascular drugs can be monitored by observing 18FDG metabolism in brain and heart. We suggest that the joining of classic clinical pharmacology to exquisite imaging measurements will help form the basis for 21st-century clinical drug development.     

Current role of positron emission tomography in thoracic oncology

Continuing advances in PET imaging have resulted in an improved ability to evaluate thoracic malignancies. Published reports demonstrate that PET provides accurate, non-invasive detection and staging of thoracic malignancy. Preliminary studies suggest that PET may also be able to assess the therapeutic response accurately. The studies investigating PET have been relatively small but have shown statistically significant advantages over conventional non-invasive techniques in accuracy and possibly even cost/benefit performance in thoracic malignancies.     

Clinical use of positron emission tomography in cerebrovascular diseases

In this article the author reviews the state-of-the-art regarding the clinical applications of positron emission tomography (PET) in cerebrovascular diseases. First, the basic methodology and physiology of cerebral blood flow and metabolism as it pertains to cerebrovascular disease are summarized. The reader is then given an account of the main findings from this technique with respect to (1) the assessment of the hemodynamic and metabolic effects of carotid artery disease in the perspective of surgical versus medical management, (2) the changes in brain perfusion and metabolism in acute ischemic stroke as they relate to the issue of patient management, outcome predictability, and screening in therapeutic trials, and (3) mapping of the remote metabolic effects of stroke and their clinical relevance.     

Pre-processing variance reducing techniques in multispectral positron emission tomography

Stochastic fluctuations and systematic errors severely restrict the potential of multispectral acquisition to improve scatter correction by energy-dependent processing in high-resolution positron emission tomography (PET). To overcome this limitation, three pre-processing approaches which reduce stochastic fluctuations and systematic errors without degrading spatial resolution were investigated: statistical variance was reduced by smoothing acquired data in energy space, systematic errors due to nonuniform detector efficiency were minimized by normalizing the data in the spatial domain and the overall variance was further reduced by selecting an optimal pre-processing sequence. Selection of the best protocol to reduce stochastic fluctuations entailed comparisons between four smoothing algorithms (prior constrained (PC) smoothing, weighted smoothing (WS), ideal low-pass filtering (ILF) and mean median (MM) smoothing) and permutations of three pre-processing procedures (smoothing, normalization and subtraction of random events). Results demonstrated that spectral smoothing by WS, ILF and MM efficiently reduces the statistical variance in both the energy and spatial domains without observable spatial resolution loss. The ILF algorithm was found to be the most convenient in terms of simplicity and efficiency. Regardless of the position of subtraction of randoms in the sequence, reduction of the systematic errors by normalization followed by spectral smoothing to suppress statistical noise produced the best results. However, subtraction of random events first in the sequence reduces computation load by half since the need to pre-process this distribution before subtraction is removed. In summary, normalizing data in the spatial domain and smoothing data in energy space are essential steps required to reduce systematic errors and statistical variance independently without degrading spatial resolution of multispectral PET data.     

Computed tomography and positron emission tomography in the pre-operative staging of oesophageal carcinoma

Because patients with carcinoma of the oesophagus usually present with advanced disease and surgery has a high mortality with cure in less than 10% of patients, pre-operative staging to select appropriate patients is necessary. Computed tomography (CT) plays an important role in staging but has well recognized limitations. Positron emission tomography (PET) which provides physiological information may therefore be a better alternative. OBJECTIVE: To compare the findings of CT and positron emission tomography (PET) with 2-[18fluorine]-fluoro-2-deoxy-D-glucose (FDG) in the pre-operative staging of oesophageal carcinoma. MATERIALS AND METHODS: Twenty-five patients with biopsy proven oesophageal cancer had pre-operative staging using CT and FDG-PET. The studies were read independently and full histological confirmation was obtained in 19 patients. Four parameters were studied: the primary tumour, peri-oesophageal lymph nodes, liver metastases and left gastric lymph nodes. RESULTS: PET visualized all primary tumours; CT missed one. CT identified 4/8 patients with involved peri-oesophageal nodes and PET 3/8. CT identified 5/9 patients with left gastric adenopathy and PET 1/9. PET visualized a liver metastasis missed on CT and appeared to be better in assessing residual tumour. PET did identify distant metastases not seen on CT in seven patients. CONCLUSIONS: The two techniques are both effective in showing the primary tumour and about equally sensitive in the demonstration of peri-oesophageal nodes. PET is probably more sensitive than CT for the detection of distant metastases.     

The advantage of using positron emission tomography in drug research

A large problem in drug discovery is to find relevant in vitro or in vivo animal models and to be able to extrapolate the results obtained to humans. Drug research now benefits from the fast development of imaging technologies that trace radiolabelled molecules directly in the human brain. Positron emission tomography (PET) and allied techniques use molecules that are labelled with short-lived radioisotopes and injected intravenously. The most straightforward approach is to radiolabel a new potential drug and then to trace its anatomical distribution and binding in the brain. An indirect approach is to study how the unlabelled drug inhibits specific radioligand binding. The demonstration of quantitative relationships between drug binding in vivo and drug effects in patients is used to validate targets for drug action and to optimize clinical treatment.     

Imaging of delta- and mu-opioid receptors in temporal lobe epilepsy by positron emission tomography

The authors report the postoperative magnetic resonance (MR) imaging findings in 36 patients with advanced Parkinson's disease who underwent unilateral microelectrode-guided posteroventral pallidotomy. The lesions were placed within 1 mm of the ventral border of the globus pallidus internus (GPi) to include pallidothalamic outflow pathways. Sequential MR studies were obtained within 1 to 3 days postoperatively and at 6-month follow-up examination. Thirty-four (94%) of the 36 patients enjoyed sustained moderate or marked improvement of their parkinsonian symptoms 6 months postoperatively. Transient side effects occurred in five patients (14%), but there were no persistent complications. The pallidal radiofrequency lesions were prolate spheroid shaped and were composed of three concentric zones in the early postoperative studies. The mean volume of the middle zone, corresponding to the area of hemorrhagic coagulation necrosis, was 44.4 +/- 17.6 mm3; the mean lesion volume as defined by the outer zone, corresponding to perilesional edema, was 262.2 +/- 111.6 mm3. Additional edema spreading to the internal capsule was noted in 32 of 34 cases and to the optic tract in 11 of 34 cases. In two patients small ischemic infarctions involving the corona radiata were found, and in one a venous infarction was detected. Ischemic infarction resulted in mild transient Broca's aphasia in one patient, but there was no detectable neurological deficit in the other two. The mean volume of late-phase (6 months) lesions was 22 +/- 28.8 mm3. In three patients no lesion was identified despite sustained clinical improvement. The lesion was located in the posteroventral GPi in all cases except in one patient in whom it was confined to the GP externus (GPe). This 49-year-old woman did not experience sustained benefit. The authors found no consistent correlations between lesion size and location and clinical outcome as measured by a global outcome score, the Unified Parkinson's Disease Rating Scale motor, activities of daily living, and bradykinesia "off" scores or rating of dyskinesias. Lesioning of pallidal and subpallidal pathways may contribute to the sustained clinical benefit in this series. Magnetic resonance imaging analysis showed that intraoperative microelectrode recording facilitated accurate placement of the lesion in this critical area.     

Imaging of the dopaminergic neurotransmission system using single-photon emission tomography and positron emission tomography in patients with parkinsonism

Parkinsonism is a feature of a number of neurodegenerative diseases, including Parkinson's disease, multiple system atrophy and progressive supranuclear palsy. The results of post-mortem studies point to dysfunction of the dopaminergic neurotransmitter system in patients with parkinsonism. Nowadays, by using single-photon emission tomography (SPET) and positron emission tomography (PET) it is possible to visualise both the nigrostriatal dopaminergic neurons and the striatal dopamine D2 receptors in vivo. Consequently, SPET and PET imaging of elements of the dopaminergic system can play an important role in the diagnosis of several parkinsonian syndromes. This review concentrates on findings of SPET and PET studies of the dopaminergic neurotransmitter system in various parkinsonian syndromes.