Biomedical subjects

M E Phelps

Publications and source records attributed to M E Phelps.

At least 91 records · Page 5Linked to original sources

PubMed1997

Oral 18F-fluoro-2-deoxyglucose for primate PET studies without behavioral restraint: demonstration of principle.

We describe a method of orally administering 18F-fluoro-2-deoxyglucose (FDG) for positron emission tomography (PET) scans to determine local cerebral metabolic rates for glucose (LCMRGlc), normalized to that of whole brain, in fully conscious, non-restrained primates. Oral FDG-PET studies were performed in both non-restrained and chaired monkeys, and in one human where results could be compared with traditional intravenous FDG administration. The oral route of FDG administration gave images and whole brain-normalized PET LCMRGlc results comparable to those obtained by the intravenous route. This oral FDG-PET method may provide a useful means by which to obtain measures of LCMRGlcs for brain structures, relative to each other, in non-restrained, non-drugged primates in field and laboratory studies. This method might also have clinical applications for PET studies of children.

Administration, Oral↗

PubMed1997

PET in oncology: will it replace the other modalities?

Medical imaging technology is rapidly expanding and the role of each modality is being redefined constantly. PET has been around since the early sixties and gained clinical acceptance in oncology only after an extreme number of scientific publications. Although PET has the unique ability to image biochemical processes in vivo, this ability is not fully used as a clinical imaging tool. In this overview, the role of PET in relation to other tumor imaging modalities will be discussed and the reported results in the literature will be reviewed. In predicting the future of PET, technical improvements of other imaging modalities need to be dealt with. The fundamental physical principles for image formation with computed tomography (CT), ultrasound (US), magnetic resonance imaging (MRI), photon-emission tomography (PET), and single photon emission CT (SPECT) will not change. The potential variety of radiopharmaceuticals which may be developed is unlimited, however, and this provides nuclear imaging techniques with a significant advantage and adaptive features for future biologic imaging. The current applications of PET in oncology have been in characterizing tumor lesions, differentiating recurrent disease from treatment effects, staging tumors, evaluating the extent of disease, and monitoring therapy. The future developments in medicine may use the unique capabilities of PET not only in diagnostic imaging but also in molecular medicine and genetics. The articles discussed in this review were selected from a literature search covering the last 3 years, and in which comparisons of PET with conventional imaging were addressed specifically. PET studies with the glucose analogue fluorine-18-labeled deoxyglucose (FDG) have shown the ability of detecting tumor foci in a variety of histological neoplasms such as thyroid cancer, breast cancer, lymphoma, lung cancer, head and neck carcinoma, colorectal cancer, ovarian carcinoma, and musculoskeletal tumors. Also, the contribution of the whole body PET (WBPET) imaging technique in diagnosis will be discussed. In the current health care environment, a successful imaging technology must not only change medical management but also demonstrate that those changes improve patient outcome.

Adrenal Gland Neoplasms↗

PubMed1997

Ethological and 6-[18F]fluoro-L-DOPA-PET profiles of long-term vulnerability to chronic amphetamine.

A chronic 10-day amphetamine (Amp) protocol was used to induce significant long-term decrements of the striatal [18F]fluoro-L-DOPA influx rate constant (FDOPA Ki) in the vervet monkey. Longitudinal FDOPA-positron emission tomography (PET) assessment in Amp-treated subjects subsequently revealed a gradual recovery of striatal dopamine function: FDOPA Ki values were decreased by approximately 70% at 1 month, approximately 45% at 6 months, approximately 20% at 12 months and were similar to pre-Amp values at 24 months. Motoric and social behavioral measures were obtained on all subjects within a species-typical group setting. Behavioral observations were conducted during both basal and stressor-challenge conditions, the latter being created by placing a potential intruder-animal in an individual cage adjacent to the subject's group enclosure. During basal conditions, post-Amp stereotypies were present at 2 weeks and locomotor behaviors were increased throughout 1 month; both alterations occurred while FDOPA Ki values were significantly decreased. Social behaviors were also significantly affected; affiliative behavior was decreased up to 6 months while aggressive behavior was increased for 12 months. However, a different pattern of behavioral changes emerged under stressor-challenge conditions. Motoric and social changes were of greater magnitude and persisted longer than in basal settings while aggressive behavior remained elevated at 24 months. These results indicate that chronic Amp-induced decreases in FDOPA Ki values and behavioral alterations are reversible. Changes in striatal dopamine function as indexed with FDOPA-PET are not correlated with post-Amp alterations in behaviors and moreover, expression of those behaviors is context-dependent.

Aggression↗

PubMed1997

Cerebral hyperglycolysis following severe traumatic brain injury in humans: a positron emission tomography study.

Experimental traumatic brain injury studies have shown that cerebral hyperglycolysis is a pathophysiological response to injury-induced ionic and neurochemical cascades. This finding has important implications regarding cellular viability, vulnerability to secondary insults, and the functional capability of affected regions. Prior to this study, posttraumatic hyperglycolysis had not been detected in humans. The characteristics and incidence of cerebral hyperglycolysis were determined in 28 severely head injured patients using [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET). The local cerebral metabolic rate of glucose (CMRG) was calculated using a standard compartmental model. In six of the 28 patients, the global cerebral metabolic rate of oxygen (CMRO2) was determined by the simultaneous measurements of arteriovenous differences of oxygen and cerebral blood flow (xenon-133). Hyperglycolysis, defined as an increase in glucose utilization that measures two standard deviations above expected levels, was documented in all six patients in whom both FDG-PET and CMRO2 determinations were made within 8 days of injury. Five additional patients were found to have localized areas of hyperglycolysis adjacent to focal mass lesions. Within the 1st week following the injury, 56% of patients studied had presumptive evidence of hyperglycolysis. The results of this study indicate that the metabolic state of the traumatically injured brain should be defined differentially in terms of glucose and oxygen metabolism. The use of FDG-PET demonstrates that hyperglycolysis occurs both regionally and globally following severe head injury in humans. The results of this clinical study directly complement those previously reported in experimental brain-injury studies, indicating the capability of imaging a fundamental component of cellular pathophysiology characteristic of head injury.

Adolescent↗

PubMed1997

Whole-body FDG-PET imaging for staging of Hodgkin's disease and lymphoma.

UNLABELLED: Accurate staging of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) is important for treatment management. In this study, the utility of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) whole-body PET was evaluated as an imaging modality for initial staging or restaging of 7 HD and 11 NHL patients. METHODS: Whole-body PET-based staging results were compared to the patient's clinical stage based on conventional staging studies, which included combinations of CT of the chest, abdomen and pelvis, MRI scans, gallium scans, lymphangiograms, staging laparatomies and bone scans. RESULTS: Accurate staging was performed in 17 of 18 patients using a whole-body PET-based staging algorithm compared to the conventional staging algorithm in 15 of 18 patients. In 5 of 18 patients, whole-body PET-based staging showed additional lesions not detected by conventional staging modalities, whereas conventional staging demonstrated additional lesions in 4 of 18 patients not detected by whole-body PET. The total cost of conventional staging was $66,292 for 16 CT chest scans, 16 CT abdominal/pelvis scans, three limited MRI scans, four bone scans, five gallium scans, two laparotomies and one lymphangiogram. In contrast, scans cost $36,250 for 18 whole-body PET studies and additional selected correlative studies: one plain film radiograph, one limited CT, one bone marrow scan, one upper GI and one endoscopy. CONCLUSION: A whole-body FDG-PET-based staging algorithm may be an accurate and cost-effective method for staging or restaging HD and NHL.

Adolescent↗

PubMed1997

Effect of beta 1 adrenergic receptor blockade on myocardial blood flow and vasodilatory capacity.

UNLABELLED: The beta 1 receptor blockade reduces cardiac work and may thereby lower myocardial blood flow (MBF) at rest. The effect of beta 1 receptor blockade on hyperemic MBF is unknown. METHODS: To evaluate the effect of selective beta 1 receptor blockade on MBF at rest and during dipyridamole induced hyperemia, 10 healthy volunteers (8 men, 2 women, mean age 24 +/- 5 yr) were studied using 13N-ammonia PET (two-compartment model) under control conditions and again during metoprolol (50 mg orally 12 hr and 1 hr before the study). RESULTS: The resting rate pressure product (6628 +/- 504 versus 5225 +/- 807) and heart rate (63 +/- 6-54 +/- 5 bpm) declined during metoprolol (p < 0.05). Similarly, heart rate and rate pressure product declined from the baseline dipyridamole study to dipyridamole plus metoprolol (p < 0.05). Resting MBF declined in proportion to cardiac work by approximately 20% from 0.61 +/- 0.09-0.51 +/- 0.10 ml/g/min (p < 0.05). In contrast, hyperemic MBF increased when metoprolol was added to dipyridamole (1.86 +/- 0.27-2.34 +/- 0.45 ml/g/min; p < 0.05). The decrease in resting MBF together with the increase in hyperemic MBF resulted in a significant increase in the myocardial flow reserve during metoprolol (3.14 +/- 0.80-4.61 +/- 0.68; p < 0.01). CONCLUSION: The beta 1 receptor blockade increases coronary vasodilatory capacity and myocardial flow reserve. However, the mechanisms accounting for this finding remain uncertain.

Adrenergic beta-Antagonists↗

PubMed1997

Compartment model for measuring myocardial oxygen consumption using [1-11C]acetate.

UNLABELLED: Although [1-11C]acetate has been validated as a PET tracer for myocardial oxygen consumption (MVO2) in animals and humans, mono- and biexponential fitting of the tissue time-activity curve yields only estimates of MVO2. This study attempts to develop and validate a simple tracer kinetic model in vivo for estimation of regional MVO2. METHODS: Twenty-seven experiments were performed in 12 anesthetized dogs with [1-11C]acetate and serial PET images under different MBF and MVO2 (baseline, ischemia, xylazine, dobutamine and dipyridamole). Estimates of MVO2 were obtained from dynamic [1-11C]acetate PET and model fitting. MBF was measured by radiolabeled microspheres, and MVO2 was calculated by the Fick method using arterial and coronary blood samples. RESULTS: The proposed model fitted equally well for all study conditions with a multiple correlation coefficient of 0.985 +/- 0.026. Estimated MVO2 correlated linearly with measured MVO2 (y = 0.033 + 0.690x, r = 0.92, s.e. of estimates = 0.020). CONCLUSION: This study indicates that MVO2 can be assessed with PET and [1-11C]acetate over a wide range with a simple tracer kinetic model.

Acetates↗

PubMed1996

Early detection of Alzheimer's disease by combining apolipoprotein E and neuroimaging.

New treatments for Alzheimer's disease (AD) are more likely to slow or halt disease progression rather than to reverse existing neuronal damage. Identifying persons with mild cognitive complaints who are at risk for AD will allow investigators to apply anti-dementia treatments before extensive brain damage develops. The discovery of the apolipoprotein E epsilon 4 allele (APOE epsilon 4) as a major risk factor for AD offers promise of assisting in early detection and prediction of Alzheimer's disease, particularly when genetic assessments are combined with other biomarkers such as neuroimaging. Studies of relatives at risk for familial AD using neuroimaging (positron emission tomography [PET]) and genetic assessments of APOE suggest that at-risk relatives with APOE epsilon 4 have lower parietal metabolism than those without APOE epsilon 4. Additional techniques that might increase sensitivity and specificity include longitudinal assessment of clinical and brain functional change, pharmacological challenges of short-acting anticholinergic agents, and memory activation paradigms during functional scanning. Such strategies should eventually assist in early detection of AD and in vivo therapeutic monitoring of brain function during experimental anti-dementia treatment trials.

Adult↗

PubMed1996

Effects of dobutamine stimulation on myocardial blood flow, glucose metabolism, and wall motion in normal and dysfunctional myocardium.

BACKGROUND: This investigation examines the effects of inotropic stimulation on myocardial blood flow (MBF) and glucose metabolism (MRGlc) in dysfunctional myocardium through the use of positron emission tomography (PET). METHODS AND RESULTS: Nineteen patients with chronic coronary artery disease and 12 normal volunteers were studied with 13N-ammonia, 18F-deoxyglucose, and PET and with two-dimensional echocardiography at baseline and during intravenous dobutamine (5 to 10 micrograms/kg per minute). At rest, MBF in mismatch regions (n = 10) averaged 0.53 +/- 0.19 mL/g per minute and increased by 41.4 +/- 46.6% (P = .01) during dobutamine, whereas in match regions (n = 16) MBF was 0.28 +/- 0.09 mL/g per minute at rest without an increase during dobutamine (26.4 +/- 47.3%; NS). Myocardium with normal rest MBF was classified as normal remote (normal wall motion, n = 8) or abnormal remote (abnormal wall motion, n = 11). Dobutamine raised MBF similarly in normal subjects and in normal remote regions (by 82 +/- 85% and 84 +/- 42%, P < .01) but by only 33 +/- 34% in abnormal remote regions. MRGlc declined by 49 +/- 28% (P < .005) with dobutamine in the normal subjects, remained unchanged in normal and abnormal remote regions of the patients, but increased in mismatch and match regions (by 49 +/- 74% and 46 +/- 77%; P < .05). Wall motion improved with dobutamine only in mismatch and abnormal remote regions but not in match regions. CONCLUSIONS: Blood flow-metabolism mismatch patterns are not consistently associated with a fixed downregulation of MBF; the increased contractile work in response to dobutamine stimulation is associated with an increase in MBF and a greater reliance on glucose utilization, possibly reflecting acute ischemia or alterations in substrate selection by chronically dysfunctional myocardium. Importantly, functionally impaired though normally perfused myocardium frequently exists in chronic coronary artery disease patients and may represent repetitively stunned or, more likely, remodeled left ventricular myocardium.

Adult↗

PubMed1996

Systematic changes in cerebral glucose metabolic rate after successful behavior modification treatment of obsessive-compulsive disorder.

BACKGROUND: We sought to determine in a new patient sample whether symptomatic improvement in obsessive-compulsive disorder treated with behavior modification is accompanied by significant changes in glucose metabolic rates in the caudate nucleus, measured with positron emission tomography, as seen in a previous study. Second, by combining samples from this and the previous study, we also examined whether there were pathologic correlational relationships among brain activity in the orbital cortex, caudate nucleus, and thalamus that obtained before behavioral treatment of obsessive-compulsive disorder, but that decreased significantly with symptom improvement. METHODS: Nine patients with obsessive-compulsive disorder were studied with positron emission tomography before and after 10 weeks of structured exposure and response prevention behavioral and cognitive treatment. Results were analyzed both alone and combined with those from nine similar subjects from the previous study. RESULTS: Behavior therapy responders had significant (P < .05) bilateral decreases in caudate glucose metabolic rates that were greater than those seen in poor responders to treatment. Before treatment, there were significant correlations of brain activity between the orbital gyri and the head of the caudate nucleus and the orbital gyri and the thalamus on the right. These correlations decreased significantly after effective treatment. CONCLUSIONS: These results replicate and extend previous findings of changes in caudate nucleus function with behavior therapy for obsessive-compulsive disorder. A prefrontal cortico-striato-thalamic brain system is implicated in mediation of symptoms of obsessive-compulsive disorder.

Adult↗

PubMed1996

6-[18F]fluoro-L-DOPA-PET studies show partial reversibility of long-term effects of chronic amphetamine in monkeys.

The acute and long-term effects of chronic amphetamine administration on the striatal dopamine system in monkeys were assessed with 6-[18F]fluoro-L-DOPA (FDOPA) and positron emission tomography (PET). Vervet monkeys (Cerecopithecus aethiops) were administered amphetamine doses, i.m., that increased from 4 mg/kg/d to 18 mg/kg/d over a 10 day period. Post-amphetamine FDOPA-PET scans at 1-2, 3-4, and 6 week time points in individual subjects showed persistent decrements in dopamine synthesis capacity as reflected by FDOPA influx rate constant (Ki) values being approximately 30% that of pre-drug assessment. In other animals that were administered the same drug regimen, biochemical analysis of striatal regions at 1-2 weeks post-drug indicated that dopamine concentrations were decreased by approximately 95% throughout caudate and putamen regions, while the homovanillic acid/dopamine level ratio was increased 3-10-fold. Post-drug FDOPA-PET Ki values remained consistently low up to 6 weeks; however, at the 5-6 month time point, relative increases in FDOPA-Ki values (approximately 53% of pre-drug values) were observed for all subjects, indicative of partial recovery of striatal dopamine synthesis capacity. These results demonstrate that FDOPA-PET can reveal temporal activity changes within the striatal dopamine system of individual subjects. The apparent, partial reversibility of amphetamine's neurotoxic effects suggests a plasticity of dopaminergic function that may include regeneration of dopaminergic terminals and compensatory increases in residual dopamine synthesis rates. The persistence of the partial decrement in dopamine synthesis capacity, however, may indicate a long term component of amphetamine's toxic effects.

Amphetamine↗

PubMed1996

Longitudinal behavioral and 6-[18F]fluoro-L-DOPA-PET assessment in MPTP-hemiparkinsonian monkeys.

Biochemical and behavioral criteria were established to determine the long-term stability of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced unilateral striatal dopamine deficiency in the vervet monkey. At time points over a 12-month period, post-MPTP striatal dopamine synthesis capacity was indexed with 6-[18F]fluoro-L-DOPA (FDOPA)-positron emission tomography. For the MPTP-treated subjects (n = 4), an intrasubject FDOPA influx rate constant (Ki) ratio method of right (lesioned) striatum/left (unlesioned) striatum values was used to assess changes in striatal activity. Striatal FDOPA Ki ratios differed less than 5% between studies conducted at 1-2, 5-7, and 9-11 months post-MPTP; these results indicated a stable MPTP-induced striatal lesion over this time period. At the 5-7 and 9-11 month time points, behavioral indices of the MPTP-induced deficits were obtained within a species-typical group setting. For three of the four subjects, persistent decrements in motoric, affiliative, and vigilance behavior were observed while the frequency of aggression toward group members was increased. At the 9-11 month time point, one subject showed a 30% improvement in the social measures, indicative of a partial recovery from the MPTP-induced behavioral decrements although its striatal FDOPAKi ratio remained unchanged. Thus, behavioral and noninvasive biochemical methods can provide complementary indices to assess individual differences in sensitivity to MPTP-induced deficits. Both types of data are required to determine lesion stability and, subsequently, the efficacy of interventions designed to restore normal function in this primate Parkinsonian model.

Animals↗

PubMed1996

Automated image registration for FDOPA PET studies.

In this study, various image registration methods are investigated for their suitability for registration of L-6-[18F]-fluoro-DOPA (FDOPA) PET images. Five different optimization criteria including sum of absolute difference (SAD), mean square difference (MSD), cross-correlation coefficient (CC), standard deviation of pixel ratio (SDPR), and stochastic sign change (SSC) were implemented and Powell's algorithm was used to optimize the criteria. The optimization criteria were calculated either unidirectionally (i.e. only evaluating the criteria for comparing the resliced image 1 with the original image 2) or bidirectionally (i.e. averaging the criteria for comparing the resliced image 1 with the original image 2 and those for the sliced image 2 with the original image 1). Monkey FDOPA images taken at various known orientations were used to evaluate the accuracy of different methods. A set of human FDOPA dynamic images was used to investigate the ability of the methods for correcting subject movement. It was found that a large improvement in performance resulted when bidirectional rather than unidirectional criteria were used. Overall, the SAD, MSD and SDPR methods were found to be comparable in performance and were suitable for registering FDOPA images. The MSD method gave more adequate results for frame-to-frame image registration for correcting subject movement during a dynamic FDOPA study. The utility of the registration method is further demonstrated by registering FDOPA images in monkeys before and after amphetamine injection to reveal more clearly the changes in spatial distribution of FDOPA due to the drug intervention.

Animals↗

PubMed1996

Cerebral metabolism following neonatal or adult hemineodecortication in cats: I. Effects on glucose metabolism using [14C]2-deoxy-D-glucose autoradiography.

In the cat, cerebral hemispherectomy sustained neonatally results in a remarkable degree of recovery and/or sparing of function as compared with the effects of a similar lesion but sustained in adulthood. We have proposed that this effect is due to a combination of reduced neuronal loss within partially denervated structures and a lesion-induced reorganization of corticofugal projections arising from the remaining intact hemisphere in the neonatally lesioned animal. The current study was designed to assess the physiological consequences of these anatomical changes utilizing [14C]2-deoxy-D-glucose autoradiography. A total of 17 adult cats were studied. Seven animals served as intact controls, five received a left cerebral hemineodecortication as neonates (NH; mean age 11.4 days), and five sustained the same lesion in adulthood (AH). Histological analysis indicated that the lesion was very similar between the two age groups and essentially represented a unilateral hemineodecortication. Local CMRglc (LCMRglc; mumol 100 g-1 min-1) values were calculated for 50 structures bilaterally and indicated that in the remaining intact contralateral (right) cerebral cortex (including all areas measured), AH cats exhibited a significantly (p < 0.05) lower level of LCMRglc (ranging from 20 to 72 mumol 100 g-1 min-1) than NH (ranging from 49 to 81 mumol 100 g-1 min-1). In comparison, the rates of NH cats within the cerebral cortex were very similar to those seen in intact animals (ranging from 48 to 119 mumol 100 g-1 min-1). Ipsilateral to the lesion in AH cats, the structures spared by the resection, including the basal ganglia and thalamus, exhibited LCMRglc rates of between 23 and 69 mumol 100 g-1 min-1, which were significantly lower (p < 0.05) than in NH cats (range 47-72 mumol 100 g-1 min-1). Considering all structures, both age-at-lesion groups exhibited a lower level of metabolism compared with similar measurements for intact control animals (LCMRglc range 45-75 mumol 100 g-1 min-1). However, this depression of glucose metabolism was more pronounced in the AH cats (p < 0.05). These results indicate that following neonatal hemineodecortication, LCMRglc is maintained at a higher level in many regions of the brain than in animals that sustain the same resection in adulthood. This higher level of glucose metabolism in NH animals suggests that the lesion-induced anatomical reorganization of structures not directly injured by the lesion plays a functional role that is probably responsible for the greater degree of recovery and/or sparing of function in these early lesioned cats.

Aging↗

PubMed1996

Radiofluorinated L-m-tyrosines: new in-vivo probes for central dopamine biochemistry.

In this work, we introduce 6-[18F]fluoro-L-m-tyrosine (6-FMT) and compare its in-vivo kinetic and bio-chemical behaviors in monkeys and rodents with those of 4-FMT and 6-[18F]fluoro-L-3, 4-dihydroxyphenylalanine (DOPA) (FDOPA). These radiofluorinated m-tyrosine presynaptic dopaminergic probes, resistant to peripheral 3-O-methylation, offer a nonpharmacological alternative to the use of catechol-O-methyltransferase inhibitors. Like FDOPA, 4-FMT and 6-FMT are analogs that essentially follow the L-DOPA pathway of central metabolism. After i.v. administration in nonhuman primates and rodents, these new radiofluorinated m-tyrosine analogs accumulate selectively in striatal structures and allow for the detection of additional innervation sites (e.g., brain stem) rich in aromatic amino acid decarboxylase. Bio-chemical analyses in rodents and monkeys revealed the specificity of their central and peripheral metabolism. Molecular and enzymatic mechanisms involved in their retention in central brain structures are consistent with involvement of dopaminergic neurons. The high signal-to-noise ratios observed make these radiofluorinated m-tyrosine analogs outstanding candidates for probing the integrity of central dopaminergic mechanisms in humans.

Animals↗

PubMed1996

Quantification of serial tumor glucose metabolism.

UNLABELLED: We developed a method to improve the quantitative precision of FDG-PET scans in cancer patients. The total-lesion evaluation method generates a correlation coefficient (r) constrained Patlak parametric image of the lesion together with three calculated glucose metabolic indices: (a) the total-lesion metabolic index ("KT-tle", ml/min/lesion); (b) the total-lesion voxel index ("VT-tle", voxels/lesion); and (c) the global average metabolic index ("KV-tle", ml/min/voxel). METHODS: The glucose metabolic indices obtained from conventional region of interest (ROI) and multiplane evaluation were used as standards to evaluate the accuracy of the total-lesion evaluation method. Computer simulations and four patients with metastatic melanoma before and after chemotherapy were studied. RESULTS: Computer simulations showed that the total-lesion evaluation method has improved precision (% s.d. < 0.6%) and accuracy (approximately 10% error) compared with the conventional ROI method (% s.d. approximately 5%; approximately 25% error). The KT-tle and VT-tle indices from human FDG-PET studies using the total-lesion evaluation method showed excellent correlations with the corresponding values obtained from the conventional ROI methods and multiplane evaluation (r approximately 1.0) and CT lesion volume measurements. CONCLUSION: This method is a simple but reliable way to quantitatively monitor tumor FDG uptake. The method has several advantages over the conventional ROI method: (a) less sensitive to the ROI definition, (b) no need for image registration of serial scan data and (c) includes tumor volume changes in the global tumor metabolism.

Computer Simulation↗

PubMed1996

Decision tree sensitivity analysis for cost-effectiveness of FDG-PET in the staging and management of non-small-cell lung carcinoma.

UNLABELLED: Preliminary studies have shown that PET is more accurate than CT for the staging of non-small-cell lung carcinoma (NSCLC). However, the potential effect of PET on the management of these patients and its cost-effectiveness has not been rigorously studied. Thus, we have used decision tree sensitivity analysis to assess the cost-effectiveness of a PET based strategy for staging of NSCLC. METHODS: Two decision strategies for selection of potential surgical candidates were compared; thoracic CT alone or thoracic CT and thoracic PET. The first decision tree was conservatively constructed by requiring mediastinoscopy (biopsy) to confirm imaging results so that no patient with surgically curable disease would miss the opportunity for surgery in either strategy. A second less conservative tree in which only nonconcordant results are biopsied was also tested. The various paths of each strategy are dependent on numerous parameters which were determined from a review of the medical literature. Life expectancy was calculated using the declining exponential approximation of life expectancy and reduced based on procedural mortality. Costs were based on mean costs at our institution. For all possible outcomes of each strategy, the expected cost and projected life expectancy were determined. The effect of changing one or more parameters on the expected cost and life expectancy were studied using a sensitivity analysis. RESULTS: The CT + PET strategy in the conservative decision tree showed a saving of $1154 per patient without a loss of life expectancy (increase of 2.96 days) as compared to the alternate strategy of CT alone. Both these effects were the result of improved staging of lung carcinoma prior to the decision for surgery. The CT + PET strategy in the less conservative decision tree showed a savings of $2267 per patient but misses 1.7% of potentially operable patients. CONCLUSION: These results show through rigorous decision tree analysis, the potential cost-effectiveness of using FDG PET in the management of NSCLC. These results form a basis for detailed study of the results obtained from multicenter trials on the accuracy of PET in NSCLC management. Furthermore, the techniques utilized for decision tree analysis have broad range of applicability to the entire field of nuclear medicine.

Carcinoma, Non-Small-Cell Lung↗

PubMed1996

Reproducibility of measurements of regional resting and hyperemic myocardial blood flow assessed with PET.

UNLABELLED: PET with 13N-ammonia permits the noninvasive quantification of myocardial blood flow (MBF) in humans. The present study was done to assess the reproducibility of quantitative blood flow measurements at rest and during pharmacologically induced hyperemia in healthy individuals. METHODS: Thirty healthy volunteers (26 men, 4 women) were studied. Paired measurements of MBF at rest (n = 21), during adenosine (n = 15) and during dipyridamole (n = 7) were performed using a two-compartment model for 13N-ammonia PET. The mean difference between baseline and follow-up blood flow (% difference) was calculated to assess reproducibility. RESULTS: No significant difference was observed between resting blood flow at baseline or follow-up (15.8% +/- 15.8%; p = ns). Baseline and follow-up resting blood flow were linearly correlated (r = 0.63, p < 0.005). Normalization of resting blood flow to the rate pressure product improved the reproducibility significantly (15.8% +/- 15.8% versus 10.1% +/- 10.5%, p < 0.05). Baseline and follow-up hyperemic myocardial blood flow did not differ (11.8% +/- 9.4%; p = ns) and were linearly correlated (r = 0.69, p < 0.0005). CONCLUSION: MBF at rest can be measured reproducibly with 13N-ammonia PET. The individual response to pharmacologic stress appears to be relatively consistent. Thus, serial blood flow measurements with 13N-ammonia PET can be used to quantify the effect of various interventions on MBF and vasodilatory reserve.

Adenosine↗