Components of professional competence for nuclear medicine physicians.
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Clinical Competence↗
Biomedical subjects
Heinrich R Schelbert
Publications and source records attributed to Heinrich R Schelbert.
The need for standardisation of cardiac FDG PET imaging in the evaluation of myocardial viability in patients with chronic ischaemic left ventricular dysfunction.
The evaluation of myocardial glucose utilisation with fluorine-18 fluorodeoxyglucose (FDG) and positron emission tomography is currently considered the most reliable tool for the identification of myocardial viability. However, the investigations using FDG imaging to predict improvement in left ventricular (LV) function after revascularisation have reported wide ranges for sensitivity (71%-100%) and, in particular, for specificity (33%-91%). The variable results may be related to differences in study populations but also to differences in the imaging protocols employed. Detailed analysis of the published studies has revealed differences in study populations, patient selection criteria, the methods for assessing changes in LV function post revascularisation and the timing of these assessments. Even more importantly, protocols have varied substantially with regard to imaging equipment, perfusion tracers, metabolic conditions, data analysis and interpretation of results. In addition, evaluation of patients with insulin resistance appears to represent a specific challenge. This review examines the different study protocols and methodologies used for myocardial FDG imaging in order to draw conclusions concerning optimal imaging protocols. It appears that the optimisation and standardisation of study protocols and analysis of FDG images for the assessment of myocardial viability are critical. In addition, multi-centre trials seem warranted on prediction of long-term function, congestive heart failure symptoms, survival and quality of life.
Fluorodeoxyglucose F18↗
Positron emission tomography imaging of cardiac reporter gene expression in living rats.
BACKGROUND: Imaging reporter gene expression is useful for noninvasive monitoring of gene therapy. In this study, we imaged cardiac reporter gene expression in living rats using micro positron emission tomography (microPET). METHODS AND RESULTS: Rats (n=10) underwent intramyocardial injection with 1x10(9) pfu of adenovirus carrying cytomegalovirus promoter-driving herpes simplex virus type 1 mutant thymidine kinase (Ad-CMV-HSV1-sr39tk) as PET reporter gene. Control rats (n=4) received 1x10(9) pfu of adenovirus carrying cytomegalovirus promoter-driving firefly luciferase (Ad-CMV-Fluc). On days 2 to 4, microPET images were obtained after a tail vein injection of nitrogen-13 ammonia ([13N]-NH3) as myocardial perfusion tracer, followed by 9-(4-[18F]-fluoro-3 hydroxymethylbutyl) guanine ([18F]-FHBG) to assess HSV1-sr39tk expression. After imaging, hearts were removed for ex vivo [18F] gamma counting and thymidine kinase enzyme assay. Results show homogenous myocardial distribution of [13N]-NH3 on all microPET images. Rats injected with Ad-CMV-HSV1-sr39tk have significant [18F]-FHBG uptake in the anterolateral wall compared with background signal in controls. Gamma counting shows 20.0+/-4.4-fold increase of radioactivity, whereas enzyme assay shows 22.1+/-6.1-fold increase of thymidine kinase activity in Ad-CMV-HSV1-sr39tk injected rats (P<0.05). CONCLUSIONS: Successful imaging of cardiac HSV1-sr39tk expression was performed in living rats with microPET. The presence of [18F]-FHBG uptake is confirmed by gamma counting and the presence of HSV1-sr39TK protein by thymidine kinase enzyme assay. Cardiac reporter gene imaging by PET may eventually be applied toward human gene therapy studies.
Adenoviridae↗
Noninvasive measurement of myocardial activity concentrations and perfusion defect sizes in rats with a new small-animal positron emission tomograph.
BACKGROUND: We explored the feasibility of measuring regional tracer activity concentrations and flow defects in myocardium of rats with a high spatial resolution small-animal PET system (microPET). METHODS AND RESULTS: Myocardial images were obtained after intravenous (18)F-fluorodeoxyglucose (18FDG) in 11 normal rats (group 1) and assembled into polar maps. Regional 18F activity concentrations were measured in 9 regions of interest and compared with tissue activity concentrations measured by well counting. In another 9 rats (group 2), myocardial perfusion images were acquired with 13N-ammonia at baseline and during coronary occlusion. On the polar maps recorded during coronary occlusion, the size of perfusion defects was measured as the myocardium with <50% of maximum activity and expressed as percent total myocardium and was correlated with the area at risk defined by postmortem staining. The diagnostic quality of 18FDG and 13N-ammonia microPET images was good to excellent; the images were easily assembled into polar maps. In group 1, regional (18)F concentrations by microPET and postmortem were correlated linearly (r=0.99; P<0.01 for average and r=0.97; P<0.01 for regional concentrations). In group 2, perfusion defect sizes by microPET and postmortem were correlated linearly (P<0.01; r=0.93). CONCLUSIONS: The findings indicate the feasibility of noninvasive studies of the myocardium in rats with a dedicated small-animal PET-imaging device.
Animals↗
Optical imaging of cardiac reporter gene expression in living rats.
BACKGROUND: Studies of cardiac gene transfer rely on postmortem analysis using histologic staining or enzyme assays. Noninvasive imaging of the temporal and spatial characteristics of cardiac gene expression in the same subject offers significant advantages. METHODS AND RESULTS: Rats underwent direct myocardial injection via left thoracotomy with adenovirus-expressing firefly luciferase (Ad-CMV-Fluc; n=30). The reporter substrate D-luciferin was injected intraperitoneally. Serial images were acquired by use of a cooled charged couple detector (CCD) camera. Results are expressed as relative light unit per minute (RLU/min). Rats transduced with 1x10(9) plaque-forming units show decremental cardiac luciferase activity over time: 152 070+/-21 170 (day 2), 195 806+/-62 630 (day 5), 7250+/-2941 (day 8), and 2040+/-971 RLU/min (day 14). To assess the detection sensitivity, serially diluted titers of Ad-CMV-Fluc were injected: 1x10(9) (195 393+/-14 896), 1x10(8) (33 777+/-18 179), 1x10(7) (417+/-91), 1x10(6) (185+/-64), 1x10(5) (53+/-1), and control (54+/-1) (P<0.05 for 1x10(9), 1x10(8), and 1x10(7) plaque-forming units versus control adenovirus-expressing mutant thymidine kinase [Ad-CMV-HSV1-sr39tk]; n=3). Finally, rats were euthanized, and in vitro luciferase activity correlated with in vivo CCD signals (r2=0.92). CONCLUSIONS: This study demonstrates for the first time the feasibility of imaging the location, magnitude, and time course of cardiac reporter gene expression in living rats. Cardiac gene therapy studies could be aided with wider application of this approach.
Adenoviridae↗
Noninvasive assessment of coronary microcirculatory function in postmenopausal women and effects of short-term and long-term estrogen administration.
BACKGROUND: Estrogen improves endothelial function in the coronary conduit vessels of animals; however, its effects on the coronary microcirculation have not been studied completely in humans. METHODS AND RESULTS: We measured myocardial blood flow (MBF) with a PET scan at rest, during cold pressor testing (CPT), and during dipyridamole hyperemia in 54 postmenopausal women without coronary artery disease. Of these, 23 were not and 31 women were taking long-term hormone replacement therapy (HRT) using estrogen either alone or with a progestogen. Each group was subdivided by coronary risk factors (RFs). Twelve young healthy women served as controls. In women not taking HRT, MBF measurements were repeated after 25 mg of conjugated equine estrogens IV. Neither short estrogen nor long-term HRT affected MBF at rest in women with and without RFs. Dipyridamole MBF was attenuated only in the women with RF who were not taking HRT. Short-term estrogen and long-term HRT did not reverse the abnormal response. MBF responses to CPT were abnormal in women not taking HRT, regardless of RFs (20+/-15% versus 32+/-21%) and remained unchanged after short-term estrogen administration. Long-term HRT normalized the response to CPT only in women without RF (53+/-22% versus 59+/-36% in the young women; NS). MBFs were similar for women on estrogen alone or estrogen plus a progestogen, regardless of presence or absence of RFs. CONCLUSION: Menopause is associated with abnormal CPT (an indirect measure of endothelial function), which can be reversed by long-term HRT only when RFs are absent. Progestogens do not antagonize this effect. Long-term HRT may therefore be useful in the primary prevention of coronary artery disease in women without RFs.
Adult↗
18F-deoxyglucose and the assessment of myocardial viability.
The glucose analogue 18F-deoxyglucose allowed for the first time the ability to noninvasively probe and characterize the regional metabolism of glucose as a major fuel substrate of the human heart. Used with positron emission tomography, it became the tool for demonstrating the operation of metabolic processes, long before established in invasive or destructive experiments in animals, directly in the human myocardium. Clinical investigations with 18F-deoxy-glucose, combined with other radiotracers of the myocardium's substrate metabolism, showed the dependency of the heart's substrate selection on circulating levels of glucose, free fatty acid and insulin, and the operation of Randle's cycle in the human myocardium. Regional responses in substrate metabolism to the myocardial ischemia were now visualized entirely noninvasively as, for example, decreases in fatty acid usage and oxidation and oxygen consumption, but foremost as an increase in glucose use. Regional 18F-deoxyglucose uptake markedly in excess of myocardial blood flow in dysfunctional myocardium of patients after a myocardial infarction, with chronic coronary artery disease or with ischemic cardiomyopathy, soon became recognized as a hallmark of myocardial viability or potentially reversible contractile dysfunction. Defined as blood flow metabolism mismatch, this particular regional glucose uptake pattern identifies patients to be at high risk for cardiac events and, at the same time, to benefit most from surgical revascularization. The patterns predict a postrevascularization improvement in global left ventricular function and, even more important, in symptoms related to congestive heart failure and in long-term survival. 18F-deoxyglucose is now widely used with positron emission tomography and, more recently, with single photon emission computed tomography and radiotracers of myocardial perfursion for stratifying ischemic cardiomyopathy patients to the most efficacious treatment.
Animals↗
Coronary vascular dysfunction in premenopausal women with diabetes mellitus.
BACKGROUND: Diabetes mellitus abolishes the sex differential in coronary artery disease morbidity and mortality in premenopausal women. This finding is independent of other diabetes-associated risk factors, suggesting that other mechanisms such as impaired coronary vascular function may contribute to the increased cardiovascular risk in women with diabetes. The objective of this study was to investigate the effect of diabetes on coronary vascular function in premenopausal women. METHODS: We studied 13 premenopausal women with diabetes (aged 41 +/- 10 years) who were free of overt cardiovascular complications, and 21 control women (12 age-matched and 9 postmenopausal [aged 56 +/- 8 years]). We used [13N]-ammonia as the flow tracer and positron emission testing to measure myocardial blood flow (MBF) at rest, during maximal hyperemia, and in response to cold pressor testing. RESULTS: Baseline MBF was lower in the postmenopausal controls, reflecting the differences in cardiac work and oxygen demand as assessed by the rate-pressure product. However, baseline MBFs were similar in the 3 groups after normalization for differences in the rate-pressure product. During hyperemia, MBF increased and coronary vascular resistance decreased significantly in the 3 groups. However, the increase (from baseline) in MBF in the women with diabetes (164% +/- 58%) was less than in the premenopausal controls (258% +/- 81%, P =.021), but not significantly different from the postmenopausal control women (204% +/- 104%, P =.51). Likewise, the increase in MBF in response to cold pressor testing in the women with diabetes (24% +/- 19%) was significantly lower than in the premenopausal controls (60% +/- 39%, P =.013), but similar to that in postmenopausal control women (27% +/- 15%, P =.97). These differences persisted after adjusting for age and diabetes-associated metabolic abnormalities. CONCLUSIONS: These results demonstrate reduced coronary vasodilator function and impaired response of resistance vessels to increased sympathetic stimulation in premenopausal women with diabetes, similar to those observed in healthy postmenopausal women in whom the sex differential in coronary artery disease morbidity and mortality is no longer present.
Adult↗
One additional year of training in nuclear medicine: will it help or hurt?
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Humans↗
Myocardial viability in patients with ischemic cardiomyopathy-evaluation by 3-D integration of myocardial scintigraphic data--and coronary angiographic data.
PURPOSE: To determine the prevalence of viable myocardium in patients with ischemic cardiomyopathy and, to evaluate the value of three-dimensional (3-D) fusion imaging of myocardial scintigraphic and angiographic data to assign coronary artery lesions to the corresponding viable and nonviable myocardial territory. PROCEDURES: In 105 patients, the combination of perfusion and metabolic imaging with (201)thallium ((201)TI) single-photon emission computed tomography (SPECT) and 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) positron emission tomography (PET) determined viability in dysfunctional myocardium. In addition, the value of 3-D scintigraphic fusion imaging was assessed in these patients. RESULTS: Based on the presence of viable dysfunctional myocardium, 54% of patients with ischemic cardiomyopathy may be considered for coronary revascularization. In 31 of 105 patients, the 3-D fusion imaging was estimated to be helpful in the diagnostic and interpretative process. CONCLUSION: In patients with end-stage coronary artery disease scintigraphic imaging is most important in the decision-making process. Three-dimensional fusion imaging may add important information in approximately 30% of these patients.
Aged↗
PET myocardial perfusion and glucose metabolism imaging: Part 2-Guidelines for interpretation and reporting.
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Coronary Circulation↗