Biomedical subjects
Publications and source records attributed to J Maddahi.
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OBJECTIVES: Our purpose was to evaluate the long-term benefit of myocardial viability assessment for stratifying risk and selecting patients with low ejection fraction for coronary artery bypass grafting and to determine the relation between the severity of anginal symptoms, the amount of ischemic myocardium, and clinical outcome. METHODS: We studied 93 consecutive patients with severe coronary artery disease and low ejection fraction (median, 25%) who underwent positron emission tomography to delineate the extent of perfusion-metabolism mismatch (reflecting hibernating myocardium) for potential myocardial revascularization. Median follow-up was 4 years (range, 0 to 6.2 years). RESULTS: Fifty patients received medical therapy, and 43 patients underwent bypass grafting. In Cox survival models, heart failure class, prior myocardial infarction, and positron emission tomographic mismatch were the best predictors of survival. Patients with positron emission tomographic mismatch receiving bypass grafting had improved 4-year survival compared with those on medical therapy (75% versus 30%; P =.007) and a significant improvement in angina and heart failure symptoms. In patients without positron emission tomographic mismatch, bypass grafting tended to improve survival and symptoms only in those patients with severe angina (100% versus 60%; P =.085), whereas no survival advantage was apparent in patients with minimal or no anginal symptoms (63% versus 52%; P =.462). CONCLUSIONS: Patients with low ejection fraction and evidence of viable myocardium by positron emission tomography have improved survival and symptoms with coronary bypass grafting compared with medical therapy. In patients without evidence of viability, survival and symptom improvement with bypass grafting are apparent only among those patients with severe angina.
UNLABELLED: This study assessed the diagnostic accuracy of whole-body PET on a patient and lesion basis using 18F-fluorodeoxyglucose (FDG) for the detection of tumor foci in patients with suspected recurrent or metastatic lesions of breast carcinoma. METHODS: Whole-body FDG-PET imaging was performed on 57 patients with a previous history of breast carcinoma who were referred for a clinical suspicion of disease recurrence. Whole-body PET images were scored from 1 (definitely negative) to 5 (definitely positive) by three independent observers, and discrepancies were resolved by a fourth observer. Patients were clinically followed for up to 24 mo to assess the accuracy of PET diagnosis by biopsy, follow-up imaging and other diagnostic tests. RESULTS: PET scans showed that there were 41 sites indicating recurrent or metastatic disease in 29 patients. There were 38 sites in 28 patients that showed no evidence for malignant disease. On a patient basis, with scores 4 or 5 considered to be positive, sensitivity and specificity were 93% and 79%, respectively. The corresponding positive and negative predictive values were 82% and 92%. On a lesion basis, with scores 4 or 5 considered to be positive, the sensitivity was 85% and specificity 79%. The area index in receiver operating characteristic analysis was 0.91 for patient-based analysis and 0.88 for lesion-based analysis. To determine the cause for false-negative and false-positive findings more precisely, false-negative lesions with scores of 3 or lower and false-positive lesions with scores of 4 or higher were analyzed. Bone metastases had a significantly larger proportion of false-negative lesions than other nonosseous malignant sites (p < 0.05). False-positive lesions were due to muscle uptake (n = 5), inflammation (n = 4), blood pool activity in the great vessels (n = 2), bowel uptake (n = 1) and unknown causes (n = 6). CONCLUSION: The whole-body FDG-PET scan is a useful diagnostic test for detecting recurrent or metastatic lesions of breast carcinoma. However, the sensitivity for metastases to bone appears to be lower than that to other organs. Specificity may be improved by more strict attention to patient preparation and better recognition of physiologic skeletal muscle or artifactual uptakes.
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.
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.
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Rational management of patients with CAD and poor left ventricular function relies on proper identification of the subgroup at high risk and those who have the highest potential of benefiting from a particular type of treatment. It is now well recognized that patients with CAD and left ventricular dysfunction have a high but variable mortality rate while receiving medical therapy. Many of these patients who have intractable heart failure are considered candidates for cardiac transplantation. Despite favorable survival after cardiac transplantation, this procedure cannot be performed in 90% of the heart failure patients who are potentially eligible because of the shortage of donor hearts. Cardiac transplantation is also an expensive procedure. Perfusion-FDG metabolism PET imaging has become the gold-standard noninvasive imaging method to identify the presence and extent of hibernating myocardium. Positron emission tomography accurately predicts recovery of regional and global left ventricular dysfunction after revascularization. In patients with poor left ventricular function, the PET pattern of perfusion metabolism mismatch is also predictive of improvement in heart failure symptoms and survival benefit after myocardial revascularization. These data suggest that a rational approach may be developed for cost-effective management of patients with CAD and poor left ventricular function.
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.
BACKGROUND: Studies of patients with coronary artery disease and left ventricular dysfunction have shown that preoperative quantification of myocardial viability may be clinically useful to identify those patients who will benefit most from revascularization both functionally and prognostically. However, the relation between preoperative extent of viability and change in heart failure symptoms has not been documented carefully. We assessed the relation between the magnitude of improvement in heart failure symptoms after coronary artery bypass surgery (CABG) and the extent of myocardial viability as assessed by use of quantitative analysis of preoperative positron emission tomography (PET) images. METHODS AND RESULTS: We studied 36 patients with ischemic cardiomyopathy (mean left ventricular ejection fraction, 28 +/- 6%) undergoing CABG. Preoperative extent and severity of perfusion abnormalities and myocardial viability (flow-metabolism mismatch) were assessed by use of quantitative analysis of PET images with 13N ammonia and fluorine-18-deoxyglucose. Each patient's functional status was determined before and after CABG by use of a Specific Activity Scale. Mean perfusion defect size and severity were 63 +/- 13% and 33 +/- 12%, respectively. Total extent of a PET mismatch correlated linearly and significantly with percent improvement in functional status after CABG (r = .87, P < .0001). A blood flow-metabolism mismatch > or = 18% was associated with a sensitivity of 76% and a specificity of 78% for predicting a change in functional status after revascularization. Patients with large mismatches (> or = 18%) achieved a significantly higher functional status compared with those with minimal or no PET mismatch (< 5%) (5.7 +/- 0.8 versus 4.9 +/- 0.7 metabolic equivalents, P = .009). This resulted in an improvement of 107% in patients with large mismatches compared with only 34% in patients with minimal or no PET mismatch. CONCLUSIONS: In patients with ischemic cardiomyopathy, the magnitude of improvement in heart failure symptoms after CABG is related to the preoperative extent and magnitude of myocardial viability as assessed by use of PET imaging. Patients with large perfusion-metabolism mismatches exhibit the greatest clinical benefit after CABG.
OBJECTIVES: This study assessed the incremental prognostic value of exercise thallium-201 myocardial perfusion single-photon emission computed tomography (SPECT) performed > or = 5 years after coronary artery bypass surgery. BACKGROUND: Thallium-201 scintigraphy has shown significant prognostic value in a variety of populations with suspected and known coronary artery disease. However, its value in patients with previous bypass surgery remains unknown. METHODS: We studied 294 patients who were prospectively followed up. Cox proportional hazards models for prediction of "hard" events (cardiac death and nonfatal infarctions) were constructed, with variables considered for inclusion in hierarchic order: clinical and exercise data first, followed by scintigraphic information. RESULTS: Mean (+/- SD) follow-up duration after scintigraphy was 31 +/- 11 months. There were 20 cardiac deaths and 21 nonfatal acute myocardial infarctions. Twenty-nine patients had late (> 60 days after thallium-201 SPECT) revascularization procedures or underwent repeat bypass surgery or percutaneous transluminal angioplasty. Shortness of breath and peak exercise heart rate were the most important clinical predictors of hard events. Two scintigraphic variables added significant prognostic information to the clinical model: the thallium-201 summed reversibility score (summation of segmental differences between stress and redistribution scores) and the presence of increased lung uptake of the radiotracer. The global chi-square statistic for this model was twice as high as that for the clinical/exercise model alone (49.7 vs. 24.2). When a second multivariate Cox model was built adding "soft" events (i.e., late revascularization procedures) as outcomes of interest, the summed reversibility score was selected as an independent scintigraphic predictor of events. The global chi-square statistic for this model was 50.7, three times as high as that for the clinical/exercise model alone. CONCLUSIONS: After evaluation of treadmill and exercise data, thallium-201 myocardial perfusion SPECT provided incremental prognostic information in patients late after bypass.
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UNLABELLED: To evaluate the effects of hematopoietic cytokines on bone marrow glucose metabolism noninvasively, we studied serial quantitative FDG-PET images in 18 patients with metastatic melanoma and normal bone marrow who were undergoing granulocyte-macrophage colony-stimulating factor (GMCSF) or macrophage colony-stimulating factor (MCSF) administration as an adjunct to chemotherapy. METHODS: All patients received 14 days of cytokine therapy in three groups: four patients were treated with GMCSF (5 micrograms/kg/d SQ), eight patients were treated with GMCSF (5 micrograms/kg/d SQ) and monoclonal antibody (MAbR24) and six patients were treated with MCSF (80 micrograms/kg/d IVCI) and MAbR24. Dynamic FDG-PET imaging was performed over the lower thoracic or upper lumbar spine at four time points in each patient. RESULTS: Baseline glucose metabolic rates in the bone marrow of these three groups of patients were similar (5.2 +/- 0.7, 4.4 +/- 0.8 and 4.8 +/- 1.2 micrograms/min/g as mean value and standard deviations, respectively). In both GMCSF and GMCSF + R24 groups, rapid increases in bone marrow glucose metabolic rates were observed during therapy. After GMCSF was stopped, bone marrow glucose metabolic rates rapidly decreased in both groups. The glucose metabolic response in these two groups was not significantly different by pooled t-statistics (p = 0.105). In the MCSF+R24 group, the increase of glucose metabolic rate on Days 3 and 10 was 35% and 31% above baseline on the average, but was not significant. CONCLUSION: The results support the use of parametric FDG-PET imaging for noninvasive quantitation of bone marrow glucose metabolic changes to hematopoietic cytokines in vivo.
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BACKGROUND: The purpose of this study was to evaluate the utility of positron emission tomography- (PET) 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) imaging in extracranial head and neck cancers. METHODS: Sixty patients with biopsy-proven cancers were studied using PET-FDG. Thirty-four patients were studied before therapy (staging), of which 15 patients received primary radiotherapy and serial PET-FDG imaging (monitoring). Seven patients with advanced disease had laser excision (monitoring), and 19 patients were evaluated for recurrent disease (recurrence). RESULTS: Four patients had unknown primary lesions. PET-FDG imaging located the primary tumor in two of four patients, and magnetic resonance imaging (MRI) in none of four. In the remaining patients (staging), PET-FDG imaging detected the primary tumor in 29 of 30 patients, and MRI in 23 of 30. In the staging group, PET-FDG imaging identified the presence or absence of lymph node involvement in 32 of 34 patients, and MRI in 31 of 34. PET-FDG imaging was helpful in evaluating tumor response to radiation therapy or laser excision. Ten patients evaluated for recurrent disease had biopsy-confirmed recurrences, and 7 had no recurrence. PET-FDG imaging results were positive for primary tumor recurrence in 9 of 10 patients, and MRI results were positive in 6 of 10. MRI results were negative for lymph node disease in one of these patients with recurrent primary tumor where PET-FDG imaging and biopsy demonstrated nodal involvement. PET-FDG results were negative for recurrent disease in seven of seven patients, and MRI results were negative for recurrent disease in in four of seven. CONCLUSION: In this series, the authors found that PET-FDG is a useful diagnostic modality for evaluating the patient with an unknown primary, monitoring response to therapy, and in detecting recurrent tumors.
OBJECTIVES: This study aimed to determine whether angiographically visualized collateral vessels in patients with chronic coronary artery disease imply the presence of viable myocardium in asynergic regions subtended by completely occluded coronary arteries. BACKGROUND: Patients with chronic coronary artery disease who are being considered for revascularization frequently exhibit angiographically visualized collateral vessels to completely occluded coronary arteries supplying severely asynergic myocardial regions. However, little is known about the relation between angiographic collateral flow and myocardial viability in these patients. METHODS: We studied 42 patients with 78 completely occluded coronary arteries supplying asynergic territories. Angiographic collateral vessels were interpreted as absent (grade 1) in 14 patients, minimal (grade 2) in 27 and well developed (grade 3) in 37. Myocardial viability was determined with positron emission tomography using nitrogen-13 (N-13) ammonia and fluorine-18 (F-18) deoxyglucose for assessment of regional perfusion and glucose uptake, respectively. Positron emission tomographic patterns were interpreted as mismatch (perfusion defect with enhanced F-18 deoxyglucose uptake); transmural match (severe concordant reduction or absence of both perfusion and F-18 deoxyglucose uptake) or nontransmural match (mild to moderate concordant reduction of both perfusion and F-18 deoxyglucose uptake). RESULTS: There was no significant correlation (p = 0.14) between the severity of perfusion deficit assessed by positron emission tomography and the collateral grade. The extent of mismatch was unrelated to either the presence or the magnitude of collateral vessels. Conversely, with increasing collateral vessels from grade 1 to 3, the total extent of positron emission tomographic match remained similar, whereas the ratio of transmural to nontransmural match decreased. Myocardial viability was usually present in severely hypokinetic regions (82%). It was lower in akinetic-dyskinetic regions (49%). Of the 64 regions with angiographic collateral vessels, 37 (58%) (95% confidence interval [CI] 46% to 70%) showed positron emission tomographic mismatch. In contrast, 7 (50%) of 14 (95% CI 24% to 76%) regions without collateral vessels on angiography exhibited positron emission tomographic mismatch. The presence of angiographically visualized collateral vessels was a sensitive (84%) but not specific (21%) marker of viability. CONCLUSIONS: In patients with chronic coronary artery disease, angiographically visualized collateral vessels to asynergic myocardial regions subtended by occluded coronary arteries do not always imply the presence of viable myocardium, suggesting that revascularization may not always provide a functional benefit.
Positron emission tomography (PET) of the brain and heart has made important contributions in clinical and research applications in the fields of neurology and cardiology. The more recent applications of PET in tumor imaging has marked oncology as the next frontier in PET; however, the dilemma of rising health care cost will challenge the application of new technologies. This challenge can be approached by innovative and appropriate use of sophisticated technology in both the research and clinical realms. The current developments of PET imaging technology to accurately stage the extent of tumor, as well as monitor the effectiveness or ineffectiveness of new or current therapies will be an extremely valuable tool in research and in the cost effective management of cancer patients. In the future, the oncologist may be able to adjust the chemotherapy to the tumor response based on PET imaging. In other situations, PET may be able to predict that no existing therapy will elicit a durable response, resolving the patients' and families' uncertainty of whether extreme therapeutic measures would have made a significant difference. This paper reviews some of the recent developments and areas of research in tumor PET imaging, and describes some of the practical and technical aspects involved with FDG tumor quantitation and whole body PET imaging.
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Technetium-99m sestamibi is a new agent that offers several theoretical advantages over Tl-201 for myocardial perfusion imaging. The results of current clinical trials utilizing acquisition and processing parameters similar to those of Tl-201 and a separate 2-day injection protocol suggest that Tc-99m sestamibi and T1-201 SPECT provide similar information with respect to the detection of myocardial perfusion defects, the assessment of the pattern of defect reversibility, the overall detection of CAD, and the detection of disease in individual coronary arteries. Tc-99m sestamibi SPECT appears to be superior to Tc-99m planar imaging because it provides a higher defect contrast and is more accurate for the detection of disease in individual coronary arteries. Significant research is underway to address optimization of acquisition and processing of Tc-99m sestamibi studies and the development of quantitative algorithms for detection and localization of CAD and sizing of transmural and nontransmural myocardial perfusion defects. It is expected that with the implementation of the final results of these new developments, further significant improvement in image quality will be attained, which, in turn, will increase the confidence of image interpretation. The development of algorithms for analysis of diastolic myocardial images may allow better evaluation of small and nontransmural myocardial defects. Furthermore, gated studies may provide valuable information with respect to regional myocardial wall motion, wall thickening, and artifact identification. Simultaneous assessment of ventricular function by performing first-pass studies may provide important information additional to that obtained from analysis of myocardial perfusion, especially in relation to the prognostic significance of different myocardial perfusion patterns. With the implementation of algorithms for attenuation and scatter correction, the overall specificity of Tc-99m sestamibi SPECT should improve significantly because of a substantial decrease in the instances of attenuation-related image artifacts.