Nuclear medicine in the new millennium.
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Algorithms↗
Biomedical subjects
M E Phelps
Publications and source records attributed to M E Phelps.
Effect of mental stress on myocardial blood flow and vasomotion in patients with coronary artery disease.
UNLABELLED: In patients with coronary artery disease (CAD), mental stress may provoke ischemic electrocardiograph changes and abnormalities in regional and global left ventricular function. However, little is known about the underlying myocardial blood flow response (MBF) in these patients. METHODS: We investigated the hemodynamic, neurohumoral, and myocardial blood flow responses to mental stress in 17 patients with CAD and 17 healthy volunteers of similar age. Mental stress was induced by asking individuals to solve mathematic subtractions in a progressively challenging sequence; MBF was quantified at rest and during mental stress using 13N ammonia PET. RESULTS: Mental stress induced significant (P < 0.01) and comparable increases in rate-pressure product, measured in beats per minute x mm Hg, in both patients (from 7826 +/- 2006 to 10586 +/- 2800) and healthy volunteers (from 8227 +/- 1272 to 10618 +/- 2468). Comparable increases also occurred in serum epinephrine (58% in patients versus 52% in healthy volunteers) and norepinephrine (22% in patients versus 27% in healthy volunteers). Although MBF increased in patients (from 0.67 +/- 0.15 to 0.77 +/- 0.18 mL/min/g, P < 0.05) and healthy volunteers (from 0.73 +/- 0.13 to 0.95 +/- 0.22 mL/min/g, P < 0.001), the magnitude of flow increase was smaller in patients (14% +/- 17%) than in healthy volunteers (29% +/- 14%) (P = 0.01). The increase in MBF during mental stress correlated significantly with changes in cardiac work in healthy volunteers (r = 0.77; P < 0.001) but not in patients. CONCLUSION: Despite similar increases in cardiac work and comparable sympathetic stimulation in CAD patients and healthy volunteers, CAD patients exhibit an attenuated blood flow response to mental stress that may contribute to mental stress-induced ischemic episodes in daily life.
Ammonia↗
PET: the merging of biology and imaging into molecular imaging.
PET and SPECT are molecular imaging techniques that use radiolabeled molecules to image molecular interactions of biological processes in vivo. PET imaging technologies have been developed to provide a pathway to the patient from the experimental paradigms of biological and pharmaceutical sciences in genetically engineered and tissue transplanted mouse models of disease. PET provides a novel way for molecular therapies and molecular diagnostics to come together in the discovery of molecules that can be used in low mass amounts to image the function of a target and, by elevating the mass, to pharmacologically modify the function of the target. In both cases, the molecules are the same or analogs of each other. PET can be used to titrate drugs to their sites of action within organ systems in vivo and to assay biological outcomes of the processes being modified in the mouse and the patient. The goal is to provide a novel way to improve the rates of discovery and approval of radiopharmaceuticals and pharmaceuticals. Extending this relationship into clinical practice can improve drug use by providing molecular diagnostics in concert with molecular therapeutics. Diseases are biological processes, and molecular imaging with PET is sensitive and informative to these processes. This sensitivity is exemplified by the detection of disease with PET without evidence of anatomic changes on CT and MRI. These biological changes are seen early in the course of disease, even in asymptomatic stages, as illustrated by the metabolic abnormalities detected with PET and FDG in Huntington's and familial Alzheimer's diseases 7 and 5 y, respectively, before symptoms appear. Differentiation of viable from nonviable tissue is fundamentally a metabolic question, as shown by the use of PET to differentiate patients with coronary artery disease who will benefit from revascularization from those who will not. Although beginning within a specific organ, cancer is a systemic disease the most devastating consequences of which result from metastases. Whole-body PET imaging with FDG enables inspection of glucose metabolism in all organ systems in a single examination to improve the detection and staging of cancer, selection of therapy, and assessment of therapeutic response. In lung and colorectal cancers, melanoma, and lymphoma, PET FDG improves the accuracy of detection and staging from 8% to 43% over conventional work-ups and results in treatment changes in 20%-40% of the patients, depending on the clinical question. Approximately 65% are upstaged because unsuspected metastases are detected, and 35% are downstaged because a structural diagnosis of lesions is changed from malignant to benign. Similar results are now being shown for other cancers. The main difference between CT, sonography, MRI, and PET or SPECT is not technologic but, rather, a difference between detecting and characterizing a disease by its anatomic features as opposed to its biology. The importance and success of developing new molecular imaging probes is increasing as PET becomes integral to the study of the integrative mammalian biology of disease and as molecular therapies targeting the biological processes of disease are developed.
Alzheimer Disease↗
A meta-analysis of the literature for whole-body FDG PET detection of recurrent colorectal cancer.
UNLABELLED: A meta-analysis of the literature for the use of FDG PET in the detection of recurrent colorectal cancer (CRC) was conducted to evaluate the quality of the reported studies. Overall values for the sensitivity and specificity of whole-body FDG PET and an overall FDG PET-directed percentage change in management were also determined through this analysis. METHODS: Guidelines to evaluate the articles were formulated on the basis of the U.S. medical payer source criteria for assessing studies that report information on usage of new medical technology. A metaanalysis was conducted using methodology described in the peer-reviewed literature. RESULTS: On the basis of the guidelines established for our review, the availability of necessary information for assessing the reliability of the FDG PET data for diagnosing recurrent CRC was less than ideal. Through a meta-analysis of 11 articles, we determined, within a 95% confidence level, an overall sensitivity of 97% (95% confidence level, 95%-99%) and an overall specificity of 76% (95% confidence level, 64%-88%) for FDG PET detecting recurrent CRC throughout the whole body. Furthermore, through pooling of the change-in-management data, an overall FDG PET-directed change in management was calculated to be 29% (95% confidence level, 25%-34%). CONCLUSION: Our review suggests that improvements can be made to more effectively report the results of these FDG PET studies. The overall values determined through the meta-analysis indicate the potential benefits of using FDG PET as a diagnostic or management tool. Furthermore, these values should prove to be useful to assess the cost-effectiveness of using FDG PET in the management of patients with recurrent CRC.
Colorectal Neoplasms↗
A review of the literature for whole-body FDG PET in the management of patients with melanoma.
BACKGROUND: A review and meta-analysis of the literature on the use of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in the detection of recurrent melanoma was conducted. The goals were to evaluate the quality of data reporting and to determine the overall values for the sensitivity and specificity of whole body FDG PET and management changes. METHODS: Guidelines to evaluate reporting within articles were formulated based on the United States medical payer source criteria for assessing studies reporting information on the utilization of new medical technology. A meta-analysis was conducted using methodology described in the peer reviewed literature. RESULTS: Our MEDLINE PLUS search resulted in a universe of 89 total articles. Within these 89, 19 were categorized in our targeted content area of which 13 were selected for analysis in our targeted subset, with the remaining 70 covering 24 different related content areas. Five of 13 (38%) articles in the target subset reported data which was adequate for incorporation into modeling objectives based on PET sensitivity and specificity values, with 1 of 13 (8%) in the same target subset reporting data adequate for modeling based on change-in-management data. Through a meta-analysis of the 13 target articles we determined, within a 95% confidence level, an overall sensitivity of 92% (95% confidence level 88.41%-95.82%) and an overall specificity of 90% (95% confidence level 83.26%-96.05%) as calculated by number of lesions, for FDG PET detecting recurrent melanoma throughout the whole body. Furthermore, limited data available for change-in-management suggests an overall FDG PET directed change-in-management value of 22%. CONCLUSIONS: Our review suggests that improvements can be made to more effectively report the results of these FDG PET studies. The overall values determined through the meta-analysis indicate the potential benefits of using FDG PET as a diagnostic/management tool. Furthermore, these values should prove useful to assessing the cost effectiveness of utilizing FDG PET in the management of recurrent melanoma.
Confidence Intervals↗
Evaluating dementia using PET: how do we put into clinical perspective what we know to date?
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Alzheimer Disease↗
Brain metabolic changes in major depressive disorder from pre- to post-treatment with paroxetine.
Functional brain imaging studies of subjects with Major Depressive Disorder (MDD) have suggested that decreased dorsolateral (DLPFC) and increased ventrolateral (VLPFC) prefrontal cortical activity mediate the depressed state. Pre- to post-treatment studies indicate that these abnormalities normalize with successful treatment. We performed [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) scans on 16 outpatients with MDD before and after treatment with paroxetine (target dose = 40 mg/day). Regions of interest (ROIs) for this analysis were drawn by a rater blind to subject identity on the magnetic resonance image of each subject and transferred onto their coregistered PET scans. We hypothesized that DLPFC metabolism would increase, while ventral frontal metabolism [in the VLPFC, the orbitofrontal cortex (OFC), and the inferior frontal gyrus (IFG)] would decrease with successful treatment. Treatment response was defined as a decrease in the Hamilton Depression Rating Scale of > 50% and a Clinical Global Improvement Scale rating of 'much' or 'very much' improved. By these criteria, nine of the subjects were classified as treatment responders. These responders had significantly greater decreases in normalized VLPFC and OFC metabolism than did non-responders. There were no significant effects of treatment response on change in the DLPFC or IFG in this sample. However, there was a positive correlation between change in HAM-D scores and change in normalized IFG and VLPFC metabolism. There were no significant interactions with laterality. On pre-treatment scans, lower metabolism in the left ventral anterior cingulate gyrus was associated with better treatment response. These findings implicate ventral prefrontal-subcortical brain circuitry in the mediation of response to serotonin reuptake inhibitors in MDD.
Adult↗
Prevalence of myocardial viability as detected by positron emission tomography in patients with ischemic cardiomyopathy.
BACKGROUND: Detection of myocardial viability is important in patients with ischemic cardiomyopathy. Restoration of blood flow to viable myocardium is associated with improved left ventricular function and improved patient prognosis. However, the prevalence of viable myocardium in patients with ischemic cardiomyopathy is unknown. METHODS AND RESULTS: To determine the prevalence of myocardial viability, clinical [13N]ammonia/18F-deoxyglucose PET studies performed in 283 patients (age, 63+/-10 years) with ischemic heart disease (mean ejection fraction, 26+/-8%) were visually analyzed for the presence and extent of viable and nonviable myocardium. The myocardium was divided into 19 segments. The extent of viable myocardium was considered "functionally" significant if >/=5 segments ( approximately 25% of the left ventricular myocardium) exhibited a blood flow/metabolism mismatch and "prognostically" significant if 1 to 4 left ventricular segments did so. Of all patients, 41% had no evidence of viable myocardium, 55% had viable myocardium, and 4% had normal blood flow and metabolism within an enlarged left ventricle. Functionally significant viability was found in 27% and prognostically significant viability in 28% of the patients. Multivariate analysis revealed the presence of angina to be the only clinical parameter associated with the presence of functionally significant viability. CONCLUSIONS: Revascularization might improve patient prognosis in 55% and result in improved left ventricular function in 27% of all patients with ischemic cardiomyopathy.
Aged↗
Application of positron emission tomography to determine cerebral glucose utilization in conscious infant monkeys.
Cerebral glucose metabolism has been used as a marker of cerebral maturation and neuroplasticity. In studies addressing these issues in young non-human primates, investigators have used positron emission tomography (PET) and [18F]2-fluoro-2-deoxy-D-glucose (FDG) to calculate local cerebral metabolic rates of glucose (1CMRG1c). Unfortunately, these values were influenced by anesthesia. In order to avoid this confounding factor, we have established a method that permits reliable measurements in young conscious vervet monkeys using FDG-PET. Immature animals remained in a conscious, resting state during the initial 42 min of FDG uptake as they were allowed to cling to their anesthetized mothers. After FDG uptake, animals were anesthetized and placed in the PET scanner with data acquisition beginning at 60 min post-FDG injection. FDG image sets consisted of 30 planes separated by 1.69 mm, parameters sufficient to image the entire monkey brain. Our method of region-of-interest (ROI) analysis was assessed within and between raters and demonstrated high reliability (P < 0.001). To illustrate that our method was sensitive to developmental changes in cerebral glucose metabolism, quantitative studies of young conscious monkeys revealed that infant monkeys 6-8 months of age exhibited significantly higher 1CMRG1c values (P < 0.05) in all regions examined, except sensorimotor cortex and thalamus, compared to monkeys younger than 4 months of age. This method provided high resolution images and 1CMRG1c values that were reliable within age group. These results support the application of FDG-PET to investigate questions related to cerebral glucose metabolism in young conscious non-human primates.
Age Factors↗
Imaging adenoviral-directed reporter gene expression in living animals with positron emission tomography.
We are developing quantitative assays to repeatedly and noninvasively image expression of reporter genes in living animals, using positron emission tomography (PET). We synthesized positron-emitting 8-[18F]fluoroganciclovir (FGCV) and demonstrated that this compound is a substrate for the herpes simplex virus 1 thymidine kinase enzyme (HSV1-TK). Using positron-emitting FGCV as a PET reporter probe, we imaged adenovirus-directed hepatic expression of the HSV1-tk reporter gene in living mice. There is a significant positive correlation between the percent injected dose of FGCV retained per gram of liver and the levels of hepatic HSV1-tk reporter gene expression (r2 > 0.80). Over a similar range of HSV1-tk expression in vivo, the percent injected dose retained per gram of liver was 0-23% for ganciclovir and 0-3% for FGCV. Repeated, noninvasive, and quantitative imaging of PET reporter gene expression should be a valuable tool for studies of human gene therapy, of organ/cell transplantation, and of both environmental and behavioral modulation of gene expression in transgenic mice.
Animals↗
Localized orbitofrontal and subcortical metabolic changes and predictors of response to paroxetine treatment in obsessive-compulsive disorder.
Previous positron emission tomography (PET) studies of patients with obsessive-compulsive disorder (OCD) have found elevated glucose metabolic rates in the orbitofrontal cortex (OFC) and caudate nuclei that normalize with response to treatment. Furthermore, OCD symptom provocation differentially activates specific subregions of the OFC, which have distinct patterns of connectivity and serve different functions. Therefore, we sought to determine the role of specific subregions of the OFC and associated subcortical structures in mediating OCD symptoms, by determining how glucose metabolism in these structures changed with paroxetine treatment of OCD patients. We also sought to determine whether pretreatment OFC metabolism would predict response to paroxetine, as it has for other OCD treatments. Twenty subjects with OCD received [18F]-fluorodeoxyglucose (FDG)-PET scans before and after 8 to 12 weeks of treatment with paroxetine, 40 mg/day. In patients who responded to paroxetine, glucose metabolism decreased significantly in right anterolateral OFC and right caudate nucleus. Lower pretreatment metabolism in both left and right OFC predicted greater improvement in OCD severity with treatment. These results add to evidence indicating that orbitofrontal-subcortical circuit function mediates the symptomatic expression of OCD. Specific subregions of the OFC may be differentially involved in the pathophysiology of OCD and/or its response to pharmacotherapy.
Cerebral Cortex↗
[18F]Fluoro-beta-fluoromethylene-m-tyrosine derivatives show stereo, geometrical, and regio specificities as in vivo central dopaminergic probes in monkeys.
Stereo (D and L), geometrical (E and Z), and regiospecific (2-, 4-, and 6-[18F]fluoro) analogs of beta-fluoromethylene-m-tyrosine (FMMT) have been investigated in adult vervet monkeys (Cercopithecus aethiops sabaeus, n = 12) in vivo with positron emission tomography (PET). Brain transport through the blood-brain barrier and central aromatic amino acid decarboxylase (AAAD)-mediated decarboxylation rates were established. Results show strict structural dependency of the kinetic behavior of radiofluorinated FMMT analogs, with the E-isomer exhibiting a higher specificity over the (Z) geometrical counterpart for central dopaminergic structures. The 6-[18F]fluoro substituted L-(E)-FMMT was also favored over the 2- and 4-[18F]fluorosubstituted isomers in terms of their ability to localize in the same brain areas. The role of PET in drug development is also exemplified in this work.
Animals↗
Assays for noninvasive imaging of reporter gene expression.
Repeated, noninvasive imaging of reporter gene expression is emerging as a valuable tool for monitoring the expression of genes in animals and humans. Monitoring of organ/cell transplantation in living animals and humans, and the assessment of environmental, behavioral, and pharmacologic modulation of gene expression in transgenic animals should soon be possible. The earliest clinical application is likely to be monitoring human gene therapy in tumors transduced with the herpes simplex virus type 1 thymidine kinase (HSV1-tk) suicide gene. Several candidate assays for imaging reporter gene expression have been studied, utilizing cytosine deaminase (CD), HSV1-tk, and dopamine 2 receptor (D2R) as reporter genes. For the HSV1-tk reporter gene, both uracil nucleoside derivatives (e.g., 5-iodo-2'-fluoro-2'-deoxy-1-beta-D-arabinofuranosyl-5-iodouracil [FIAU] labeled with 124I, 131I) and acycloguanosine derivatives [e.g., 8-[18F]fluoro-9-[[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]guanine (8-[18F]-fluoroganciclovir) ([18F]FGCV), 9-[(3-[18F]fluoro-1-hydroxy-2-propoxy)methyl]guanine ([18F]FHPG)] have been investigated as reporter probes. For the D2R reporter gene, a derivative of spiperone [3-(2'-[18F]-Fluoroethyl)spiperone ([18F]FESP)] has been used with positron emission tomography (PET) imaging. In this review, the principles and specific assays for imaging reporter gene expression are presented and discussed. Specific examples utilizing adenoviral-mediated delivery of a reporter gene as well as tumors expressing reporter genes are discussed.
Animals↗
Relationship between coronary function by positron emission tomography and temporal changes in morphology by intravascular ultrasound (IVUS) in transplant recipients.
BACKGROUND: Transplant coronary vasculopathy is one of the major causes of graft failure and death in cardiac transplant recipients. A non-invasive test of coronary function to predict the course of this disease would be desirable. METHODS: To determine whether the degree of abnormalities in endothelial dependent coronary vasomotion (cold pressor testing) or endothelial independent vasodilatory capacity (intravenous dipyridamole) as determined by positron emission tomography (PET) one to two years after heart transplantation is correlated with the course of transplant vasculopathy. Nineteen patients had baseline PET and intravascular ultrasound studies (IVUS) at 18 +/- 6 months after cardiac transplantation and a follow up IVUS study 15 +/- 5 months later. RESULTS: Myocardial blood flow was higher in patients than in healthy controls (p < 0.002) but increased during cold pressor testing only in controls (p < 0.005). Myocardial blood flow normalized to the rate pressure product declined in patients (p < 0.001). Dipyridamole-induced hyperemic blood flow and the flow reserve normalized to the resting rate pressure product were lower in patients than in controls (p < 0.001 and p < 0.01). The normalized flow reserve was correlated with changes in total vessel area (r = 0.55; p = 0.02) and lumen diameter (r = 0.52; p < 0.05). CONCLUSION: These findings suggest that the degree of abnormalities in endothelial independent myocardial flow as detected by PET one to two years after transplantation is associated with morphological indices of disease progression by IVUS.
Cold Temperature↗
A study on the cost effectiveness of sestamibi scintimammography for screening women with dense breasts for breast cancer.
The potential impact of Sestamibi scintimammography (SSMM) on the cost effective management of women with dense breasts is not known. This study addresses this issue quantitatively by examining the impact of SSMM based screening strategies on the approximately 3,000,000 women over 40 with very dense breasts (DY patterns) without palpable masses and who have had one or more prior mammograms, who undergo routine screening each year. Quantitative decision tree sensitivity analysis was used to compare the conventional mammography (MM) strategy (strategy A), which does not subject patients with negative mammograms to any further examination until their next screening, with two decision strategies for screening with SSMM; SSMM after a negative mammogram (strategy B) or SSMM as the only screening test for women already identified as having dense breasts by a previous mammogram (strategy C). Cost effectiveness was measured by calculating the incremental cost effectiveness ratio (ICER) of strategies B and C, which is the cost of achieving an additional year of life in the screening population by choosing a SSMM based decision strategy rather than the conventional strategy. Strategies B and C reduced the number of false negative diagnoses by 62% and 8%, respectively. The ICER was $632,000 and $3.18M per life year for strategy B and C, respectively. To be cost effective, the pre-test probability of cancer in the study population must be greater than 3% for strategy B or the cost of SSMM must be less than $50 for strategy C. These results show the ICER of an SSMM based breast cancer screening strategy in the management of patients with dense breasts is not currently within the range (approximately $50,000 per year life saved) of other commonly performed medical interventions that are considered cost effective.
Adult↗
Repetitive, non-invasive imaging of the dopamine D2 receptor as a reporter gene in living animals.
Reporter genes (e.g. beta-galactosidase, chloramphenicol-acetyltransferase, green fluorescent protein, luciferase) play critical roles in investigating mechanisms of gene expression in transgenic animals and in developing gene delivery systems for gene therapy. However, measuring expression of these reporter genes requires biopsy or death. We now report a procedure to image reporter gene expression repetitively and non-invasively in living animals with positron emission tomography (PET), using the dopamine type 2 receptor (D2R) as a reporter gene and 3-(2'-[18F]fluoroethyl)spiperone (FESP) as a reporter probe. We use a viral delivery system to demonstrate the ability of this PET reporter gene/PET reporter probe system to image reporter gene expression following somatic gene transfer. In mice injected intravenously with replication-deficient adenovirus carrying a D2R reporter gene, PET in vivo measures of hepatic [18F] retention are proportional to in vitro measures of hepatic FESP retention, D2R ligand binding and D2R mRNA. We use tumor-forming cells carrying a stably transfected D2R gene to demonstrate imaging of this PET reporter gene/PET reporter probe system in 'tissues'. Tumors expressing the transfected D2R reporter gene retain substantially more FESP than control tumors. The D2R/FESP reporter gene/reporter probe system should be a valuable technique to monitor, in vivo, expression from both gene therapy vectors and transgenes.
Adenoviridae↗
Performance evaluation of microPET: a high-resolution lutetium oxyorthosilicate PET scanner for animal imaging.
UNLABELLED: A new dedicated PET scanner, microPET, was designed and developed at the University of California, Los Angeles, for imaging small laboratory animals. The goal was to provide a compact system with superior spatial resolution at a fraction of the cost of a clinical PET scanner. METHODS: The system uses fiberoptic readout of individually cut lutetium oxyorthosilicate (LSO) crystals to achieve high spatial resolution. Each microPET detector consists of an 8 x 8 array of 2 x 2 x 10-mm LSO scintillation crystals that are coupled to a 64-channel photomultiplier tube by optical fibers. The tomograph consists of 30 detectors in a continuous ring with a 17.2-cm diameter and fields of view (FOVs) of 11.25 cm in the transaxial direction and 1.8 cm in the axial direction. The system has eight crystal rings and no interplane septa. It operates exclusively in the three-dimensional mode and has an electronically controlled bed that is capable of wobbling with a radius of 300 microm. We describe the performance of the tomograph in terms of its spatial, energy and timing resolution, as well as its sensitivity and counting-rate performance. We also illustrate its overall imaging performance with phantom and animal studies that demonstrate the potential applications of this device to biomedical research. RESULTS: Images reconstructed with three-dimensional filtered backprojection show a spatial resolution of 1.8 mm at the center of the FOV (CFOV), which remains <2.5 mm for the central 5 cm of the transaxial FOV. The resulting volumetric resolution of the system is <8 microL. The absolute system sensitivity measured with a 0.74 MBq (20 microCi) 68Ge point source at the CFOV is 5.62 Hz/kBq. The maximum noise equivalent counting rate obtained with a 6.4-cm diameter cylinder spanning the central 56% of the FOV is 10 kcps, whereas the scatter fraction is 37% at the CFOV for an energy window of 250-650 keV and the same diameter cylinder. CONCLUSION: This is the first PET scanner to use the new scintillator LSO and uses a novel detector design to achieve high volumetric spatial resolution. The combination of imaging characteristics of this prototype system (resolution, sensitivity, counting-rate performance and scatter fraction) opens up new possibilities in the study of animal models with PET.
Animals↗
Quantification of myocardial blood flow using 13N-ammonia and PET: comparison of tracer models.
UNLABELLED: Several tracer kinetic methods have been proposed for quantification of regional myocardial blood flow (MBF) with 13N-ammonia and PET. Merits and limitations specific to each approach, however, generally are not clear, because they have not been evaluated in the same experimental environment. Therefore, we compared six different commonly used methods (11 modifications) to characterize the accuracy of each approach. The methods included the two-parameter model (method 1), the modified two-parameter model (method 2), the four-parameter model (method 3), the graphical analysis (method 4), the first-pass extraction method (method 5) and the dose uptake index (DUI; method 6). METHODS: Eleven studies in four dogs, 16 studies in eight healthy human volunteers and 14 studies in seven patients were performed using 13N-ammonia and PET. MBF in dogs was varied with dipyridamole and coronary occlusions and was measured independently and simultaneously with microspheres. Volunteers and patients were studied at baseline and after dipyridamole. MBF and DUI were estimated using a time-activity curve (Qi[t]) derived from dynamic images and regions of interest (ROls) and using the six methods. DUI was defined as Qi(t = 2 min) x weight/dose. RESULTS: MBF estimated by methods 1-5 correlated well with microsphere MBF in dogs. MBF estimates by method 1 correlated well with those by methods 2, 4 and 5 and to a lesser degree with those by method 3 in both dog and human studies. DUI correlated poorly with MBF by microspheres and by methods 1-5 in both dog and human studies. MBF estimates by method 3 showed larger dispersion (SD/mean flow) and higher sensitivity to metabolites correction in arterial blood than those by methods 1, 2, 4 and 5. CONCLUSION: MBF can be measured accurately using 13N-ammonia PET and tracer kinetic methods. DUI is a poor indicator of MBF values. The results indicate that preference should be given to the two-parameter model, incorporating geometrical ROI representation (method 2) among the compartment models, and to the graphical analysis (method 4) among the noncompartmental approaches.
Adult↗