PET/CT in cancer patient management. Introduction.
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Humans↗
Biomedical subjects
Heinrich R Schelbert
Publications and source records attributed to Heinrich R Schelbert.
Improvements in cancer staging with PET/CT: literature-based evidence as of September 2006.
PET/CT with 18F-FDG is increasingly being used for staging, restaging, and treatment monitoring for cancer patients. CT is still frequently used only for attenuation correction and lesion localization. However, increasing sales of high-end scanners that combine PET with 64-detector CT strongly suggest that the field is moving toward a comprehensive concept, whereby diagnostic CT studies during intravenous contrast material application are combined with the highest-quality PET studies. At many institutions, in-line PET/CT has replaced separately acquired PET and CT examinations for many oncologic indications. This replacement has occurred despite the fact that only a relatively small number of well-designed prospective studies have verified imaging findings against the gold standard of histopathologic tissue evaluation. However, a large number of studies have used acceptable reference standards, such as pathology, imaging, and other clinical follow-up findings, for validating PET/CT findings. From these data, we believe, has emerged reliable evidence in support of the notion that PET/CT offers diagnostic advantages over its individual components for the major cancers.
Clinical Trials as Topic↗
Determinants of myocardial blood flow response to cold pressor testing and pharmacologic vasodilation in healthy humans.
PURPOSE: Response of myocardial blood flow (MBF) to sympathetic stimulation with cold is modulated by endothelium-related factors and is typically altered in the presence of coronary risk factors. Determinants of flow response to cold pressor testing (CPT) in normal volunteers at low risk for CAD remain less well defined, especially relative to baseline conditions such as hemodynamics and MBF, plasma substrate and lipid levels, and total pharmacologically stimulated vasodilator capacity. METHODS: In 50 normal volunteers (42+/-13 years; 31 women) without coronary risk factors, insulin resistance, or family history of diabetes/premature CAD, MBF was measured with (13)N-ammonia and PET at baseline, during CPT, and during pharmacologic hyperemia. RESULTS: Sympathetic stimulation with CPT raised heart rate and blood pressure and thus MBF (Delta MBF=0.23+/-0.09 ml/min/g). MBF response, defined in absolute flow units as the difference between CPT and baseline, was independent of age, gender, heart rate, and blood pressure and rate-pressure product (RPP) at baseline as well as plasma substrate and lipid levels with the exception of an association with HDL cholesterol (rho=0.40, p=0.005) but depended on the change in RPP from rest (rho=0.33, p=0.019). Finally, changes in coronary vascular resistance in response to CPT were associated with changes in pharmacologic vasodilation (rho=0.56, p<0.0001). CONCLUSION: MBF response to sympathetic stimulation with cold (NO-mediated endothelium-dependent vasomotion), reflecting the functional state of the coronary endothelium, was independent of gender, age, and resting heart conditions. It was modulated by HDL cholesterol levels, even in healthy volunteers, and also related to pharmacologically stimulated vasodilator capacity at the coronary vascular resistance level.
Adult↗
PET-measured heterogeneity in longitudinal myocardial blood flow in response to sympathetic and pharmacologic stress as a non-invasive probe of epicardial vasomotor dysfunction.
PURPOSE: We investigated whether a myocardial perfusion gradient during pharmacologically induced hyperemia also occurred during sympathetic stimulation with cold pressor testing (CPT), which commonly induces a paradoxical coronary vasoconstriction in individuals with coronary risk factors. METHODS: Myocardial blood flow (MBF) was measured in absolute units (ml/g/min) with 13N-ammonia and PET at rest, during CPT, and during pharmacologic vasodilation in 59 participants with coronary risk factors ("at risk") and in 43 healthy individuals (controls). MBF was assessed globally as mean MBF, and in the mid and mid-distal myocardium of the left ventricle (LV). A decrease in MBF from mid to mid-distal LV myocardium was defined as MBF difference indicative of a perfusion gradient. RESULTS: The change in mean MBF to CPT (DeltaMBF) in the at-risk group was significantly reduced compared with controls (0.05+/-0.19 vs 0.31+/-0.20 ml/g/min, p<0.0001), whereas mean MBF during pharmacologic vasodilation in the at-risk group tended to be lower than in controls (1.72+/-0.71 vs 2.00+/-0.64 ml/g/min, p=NS). Absolute MBFs during CPT and pharmacologic vasodilation were significantly lower in the mid-distal than in the mid LV myocardium, resulting in a significant MBF difference in the at-risk group (0.15+/-0.06 and 0.27+/-0.12 ml/g/min, p<0.0001) that was not observed in controls (0.007+/-0.05 and 0.014+/-0.10 ml/g/min, p=NS). In the at-risk group there was a significant correlation between the difference of mid to mid-distal MBF during CPT and that during pharmacologic vasodilation (r=0.43, p<0.004), suggesting functional alterations of epicardial vessels as the predominant cause for the observed MBF difference. CONCLUSION: The relative decrease in MBF from the mid to the mid-distal left-ventricular myocardium suggests an intracoronary pressure decline during CPT and pharmacologic vasodilation, which is likely to reflect an impairment of flow-mediated epicardial vasomotor function.
Adult↗
Relationship between increasing body weight, insulin resistance, inflammation, adipocytokine leptin, and coronary circulatory function.
OBJECTIVES: We sought to evaluate effects of obesity, insulin resistance, and inflammation on coronary circulatory function and its relationship to leptin plasma levels. BACKGROUND: It is not known whether obesity, commonly paralleled by insulin resistance, inflammation, and leptin, is independently associated with coronary circulatory dysfunction. METHODS: Myocardial blood flow (MBF) responses to cold pressor test (CPT) and pharmacologic vasodilation was measured with positron emission tomography and 13N-ammonia. Study participants were divided into three groups based on their body mass index (BMI, kg/m2): control, 20 < or = BMI <25 (n = 19); overweight, 25 < or = BMI <30 (n = 21); and obese, BMI >30 (n = 32). RESULTS: Body mass index was significantly correlated to the Homeostasis Model Assessment Index of insulin resistance and C-reactive protein levels (r = 0.60 and r = 0.47, p < 0.0001). Compared with control subjects, endothelium-related change in MBF (DeltaMBF) to CPT progressively declined in overweight and obese groups (0.32 +/- 0.09 vs. 0.21 +/- 0.19 and 0.07 +/- 0.16 ml/g/min; p < 0.03 and p < 0.0001). The dipyridamole-induced total vasodilator capacity was significantly lower in obese than in control subjects (1.77 +/- 0.51 vs. 2.04 +/- 0.37 ml/g/min, p < 0.02). On multivariate analysis, BMI (p < 0.012) and age (p < 0.035) were significant independent predictors of DeltaMBF. Finally, only in the obese group leptin plasma levels significantly correlated with DeltaMBF (r = 0.37, p < 0.036). CONCLUSIONS: Increased body weight is independently associated with abnormal coronary circulatory function that progresses from an impairment in endothelium-related coronary vasomotion in overweight individuals to an impairment of the total vasodilator capacity in obese individuals. The findings that elevated leptin plasma levels in patients that are obese might exert beneficial effects on the coronary endothelium to counterbalance the adverse effects of increases in body weight on coronary circulatory function should be tested.
Adult↗
Task Force 5: training in nuclear cardiology: endorsed by the American Society of Nuclear Cardiology.
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Cardiology↗
Positron emission tomography myocardial perfusion and glucose metabolism imaging.
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Fluorodeoxyglucose F18↗
Coronary vasodilator reserve and Framingham risk scores in subjects at risk for coronary artery disease.
BACKGROUND: The relationship between coronary vasodilator reserve and risk of coronary heart disease (CHD) in subjects without coronary artery disease (CAD) is not well known. METHODS AND RESULTS: We studied 289 subjects (mean age, 58 +/- 10 years) without overt CAD and at low (< 10%) to intermediate risk (10%-20%) for CHD based on Framingham risk scores (RAMPART [Relative and Absolute Myocardial Perfusion changes as measured by Positron Emission Tomography to Assess the Effects of ACAT Inhibition: A Double-Blind, Randomized, Controlled, Multicenter Trial]). Coronary flow reserve (CFR) and coronary vascular resistance (CVR) were calculated from rest and adenosine nitrogen 13 ammonia positron emission tomography studies. Framingham-estimated CHD risk was used to as a surrogate for outcomes. Compared with subjects with low-risk scores (n = 150), those with intermediate-risk scores (n = 139) had a higher minimal CVR (49.3 +/- 17.41 mm Hg x mL(-1) x min(-1) x g(-1) vs 52.4 +/- 16.4 mm Hg x mL(-1) x min(-1) x g(-1), P = .05) and lower CFR (2.8 +/- 1.0 vs 2.5 +/- 0.8, P = .02). CFR was inversely related to CHD risk (R = -0.2, P = .006), and CVR was directly related to CHD risk (R = 0.2, P < .001). The mean CFR was significantly lower in patients in the first quartile of CHD risk compared with those in the fourth quartile (2.3 +/- 0.7 vs 2.8 +/- 1.0, P = .02), and the minimal CVR was significantly higher (44 +/- 15 mm Hg x mL(-1) x min(-1) x g(-1) vs 53 +/- 14 mm Hg x mL(-1) x min(-1) x g(-1), P < or = .05). CONCLUSIONS: In subjects without clinical CAD and at low to intermediate risk, CFR assessed by positron emission tomography is inversely related to estimated 10-year CHD risk.
Adenosine↗
Noninvasive measurement of cardiovascular function in mice with high-temporal-resolution small-animal PET.
UNLABELLED: The aim of this study was to explore the feasibility of determining parameters of cardiovascular function in mice noninvasively by high-temporal-resolution imaging with a dedicated small-animal PET system. METHODS: Twenty-five anesthetized mice (28.8 +/- 4.6 g) were injected via an intravenous catheter with a 30-microL bolus of (18)F-FDG (8-44 MBq). The first 9 s of data were reconstructed into 30 frames of 0.3 s using filtered backprojection. The time-activity curve derived from a left ventricle volume of interest was corrected for tracer recirculation and partial volume. Cardiac output was calculated by the Stewart-Hamilton method, in which cardiac output is total injected activity divided by the area under the left ventricle time-activity curve. Cardiac output divided by body weight was defined as cardiac index; cardiac output divided by heart rate yielded the stroke volume. In 5 mice, measurements were repeated 2-4 times to assess reproducibility. In 4 mice, the hemodynamic response to dobutamine was examined by measuring heart rate, cardiac output, and stroke volume. RESULTS: The cardiac output averaged 20.4 +/- 3.4 mL/min; in the repeated measurements, the parameter displayed a mean percentage SD per mouse of 10% +/- 6%. The cardiac index averaged 0.73 +/- 0.19 mL/min/g and the stroke volume 45.0 +/- 6.9 microL, and both correlated with heart rate (r = 0.53, P = 0.007, and r = 0.49, P = 0.01, respectively). During dobutamine stress, heart rate increased from 423 +/- 50 to 603 +/- 30 beats/min (P = 0.002) and cardiac output increased from 18.5 +/- 1.9 to 32.0 +/- 4.2 mL/min (P = 0.008). CONCLUSION: Parameters of cardiovascular function can be measured in mice noninvasively by radionuclide angiography using high-temporal-resolution small-animal PET. Measured values of cardiac output and stroke volume are reproducible and comparable to those obtained with MRI. The approach permits the monitoring of changes in cardiovascular function in response to pharmacologic intervention.
Animals↗
Myocardial perfusion reserve in adults with cyanotic congenital heart disease.
In patients with cyanotic congenital heart disease (CCHD), a right-to-left shunt results in systemic hypoxemia. Systemic hypoxemia incites a compensatory erythrocytosis, which increases whole blood viscosity. We considered that these changes might adversely influence myocardial perfusion in CCHD patients. Basal and hyperemic (intravenous dipyridamole) perfusion measurements were obtained with [13N]ammonia positron emission tomographic imaging in left (LV) and right (RV) ventricular and septal myocardium in 14 adults with CCHD [age: 34.1 yr (SD 6.5)]; hematocrit: 62.2% (SD 4.8)] and 10 healthy controls [age: 34.1 yr (SD 6.5)]. In patients, basal perfusion measurements were higher in LV [0.77 (SD 0.24) vs. 0.55 ml x min(-1) x g(-1) (SD 0.09), P < 0.02], septum [0.71 (SD 0.16) vs. 0.49 ml x min(-1) x g(-1) (SD 0.09), P < 0.001], and RV [0.77 (SD 0.30) vs. 0.38 ml x min(-1) x g(-1) (SD 0.09), P < 0.001]. However, basal measurements normalized for the rate-pressure product were similar to those of controls. Calculated oxygen delivery relative to rate-pressure product was higher in the patients [2.2 (SD 0.8) vs. 1.6 (SD 0.4) x 10(-5) ml O2 x min(-1) x g tissue(-1) x (beats x mmHg)(-1) in the LV, P < 0.05, and 2.0 (SD 0.7) vs. 1.4 (SD 0.3) x 10(-5) ml O2 x min(-1) x g tissue(-1) x (beats x mmHg)(-1) in the septum, P < 0.01]. Hyperemic perfusion measurements in CCHD patients did not differ from controls [LV, 1.67 (SD 0.60) vs. 1.95 ml x min(-1) x g(-1) (SD 0.46); septum, 1.44 (SD 0.56) vs. 1.98 ml x min(-1) x g(-1) (SD 0.69); RV, 1.56 (SD 0.56) vs. 1.65 ml x min(-1) x g(-1) (SD 0.64), P = not significant], and coronary vascular resistances were comparable [LV, 55 (SD 25) vs. 48 mmHg x ml(-1) x g x min (SD 16); septum, 67 (SD 35) vs. 50 mmHg x ml(-1) x g x min (SD 21); RV, 59 (SD 26) vs. 61 mmHg x ml(-1) x g x min (SD 27), P = not significant]. These findings suggest that adult CCHD patients have remodeling of the coronary circulation to compensate for the rheologic changes attending chronic hypoxemia.
Adult↗
Positron emission tomography-measured abnormal responses of myocardial blood flow to sympathetic stimulation are associated with the risk of developing cardiovascular events.
OBJECTIVES: We sought to assess prospectively whether patients with normal coronary angiograms but with impaired myocardial blood flow (MBF) increases to cold pressor testing (CPT) are at increased risk for cardiovascular events. BACKGROUND: Invasive angiographic assessments of coronary vasomotor function have demonstrated an impairment of endothelium-related coronary flow increases to independently predict future cardiovascular events. It is unknown whether noninvasive positron emission tomography (PET)-measured MBF alterations to sympathetic stimulation with CPT are associated with the risk of developing cardiovascular events. METHODS: A total of 72 patients (44 men, 28 women, age 58 +/- 8 years) referred for diagnostic cardiac catheterization were studied. Myocardial blood flow was measured in absolute units with (13)N-ammonia using PET, at baseline and during CPT in each patient. Cardiovascular events (cardiovascular death, acute coronary syndrome, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, ischemic stroke, or peripheral revascularization) were assessed as clinical outcome parameters over a mean follow-up period of 66 +/- 8 months. Patients were assigned to three groups: group 1, patients with >/=40% increase in MBF (%DeltaMBF), n = 22; group 2, patients with >0 and <40% increases in MBF, n = 32; and group 3, patients with decreases in MBF (</=0%), n = 18. RESULTS: During follow-up, one of the group 1 patients developed a cerebral stroke. In group 2, 15 cardiovascular events occurred in 9 patients and in group 3, 7 patients experienced 9 cardiovascular events (p </= 0.0001, univariate by log-rank test). Impaired MBF increases in group 2 and group 3 were associated with a significantly higher incidence of cardiovascular events by Kaplan-Meier analysis (p = 0.033, log-rank test). After adjusting for known coronary risk factors, MBF responses to CPT revealed a nonsignificant trend to be independently associated with a higher incidence for cardiovascular events (p = 0.065, multivariate by Cox regression model). CONCLUSIONS: Noninvasive PET-measured impaired MBF increases to sympathetic stimulation are associated with the risk of developing cardiovascular events.
Ammonia↗
Coronary circulatory dysfunction in insulin resistance, impaired glucose tolerance, and type 2 diabetes mellitus.
BACKGROUND: Abnormal coronary endothelial reactivity has been demonstrated in diabetes and is associated with an increased rate of cardiovascular events. Our objectives were to investigate the presence of functional coronary circulatory abnormalities over the full spectrum of insulin resistance and to determine whether these would differ in severity with more advanced states of insulin resistance. METHODS AND RESULTS: Myocardial blood flow (MBF) was measured with positron emission tomography and 13N-ammonia to characterize coronary circulatory function in states of insulin resistance without carbohydrate intolerance (IR), impaired glucose tolerance (IGT), and normotensive and hypertensive type 2 diabetes mellitus (DM) compared with insulin-sensitive (IS) individuals. Indices of coronary function were total vasodilator capacity (mostly vascular smooth muscle-mediated) during pharmacological vasodilation and the nitric oxide-mediated, endothelium-dependent vasomotion in response to cold pressor testing. Total vasodilator capacity was similar in normoglycemic individuals (IS, IR, and IGT), whereas it was significantly decreased in normotensive (-17%) and hypertensive (-34%) DM patients. Compared with IS, endothelium-dependent coronary vasomotion was significantly diminished in IR (-56%), as well as in IGT and normotensive and hypertensive diabetic patients (-85%, -91%, and -120%, respectively). CONCLUSIONS: Progressively worsening functional coronary circulatory abnormalities of nitric oxide-mediated, endothelium-dependent vasomotion occur with increasing severity of insulin-resistance and carbohydrate intolerance. Attenuated total vasodilator capacity accompanies the more clinically evident metabolic abnormalities in diabetes.
Adult↗
Quantitative relation between hemodynamic changes during intravenous adenosine infusion and the magnitude of coronary hyperemia: implications for myocardial perfusion imaging.
OBJECTIVES: The goal of this study was to determine the relationship between changes in cardiac hemodynamics during intravenous adenosine (ADO) infusion, and myocardial blood flow (MBF). BACKGROUND: The relationship between changes in MBF and the peripheral hemodynamic effects during peak adenosine infusion is unknown. METHODS: We studied 348 (age 57 +/- 11 years; 106 females) without evidence of obstructive coronary artery disease by positron emission tomography (PET). Patients underwent [(13)N]ammonia PET imaging to measure MBF and coronary vascular resistance (CVR) at rest and during a standard 6-min ADO infusion. Changes in heart rate (HR) and mean arterial pressure (MAP) were measured at baseline and during peak hyperemia. RESULTS: During ADO, HR increased (delta: 24 +/- 11 beats/min) and MAP decreased (delta: -2 +/- 10 mm Hg). Overall, delta HR correlated poorly with hyperemic MBF (R = 0.10, p = 0.06) and with CVR (R = 0.11, p = 0.04). Delta MAP also showed a weak correlation with hyperemic MBF (R = 0.04, p = 0.44) and with CVR (R = 0.11, p = 0.04). Patients in the lowest tertile for delta HR showed a 7% lower hyperemic MBF (1.84 +/- 0.6 ml/min/g vs. 1.98 +/- 0.6 ml/min/g, p = 0.022) and an 8% higher CVR (54 +/- 20 mm Hg/ml/min/g vs. 50 +/- 17 mm Hg/ml/min/g, p = 0.056) compared with those in the highest tertile. Patients in the lowest tertile for delta MAP (i.e., greatest decline) showed similar hyperemic MBF, and an 8% lower CVR compared with those in the highest tertile (p = NS for both). These small differences between tertiles remain, even after adjusting for differences in age, gender, smoking status, and lipid profile. CONCLUSIONS: Changes in cardiac hemodynamics during intravenous ADO are generally poor predictors of changes in MBF and CVR during peak hyperemia, and, thus, they should not be used to assess the effectiveness of vasodilator stress in myocardial perfusion imaging.
Adenosine↗
Chronic inflammation and impaired coronary vasoreactivity in patients with coronary risk factors.
BACKGROUND: The goal of this study was to examine a possible association between systemic microinflammation, as reflected by C-reactive protein (CRP) serum levels, and coronary vasomotion in patients with coronary risk factors but with angiographically normal coronary arteries. METHODS AND RESULTS: Coronary vasomotor function was studied in response to cold pressor testing (CPT) in 71 patients with normal angiograms. In all patients, CPT-induced changes in epicardial luminal area (LA; mm2) were assessed with quantitative angiography. Within 20 days, myocardial blood flow (MBF) responses to CPT were measured (mL x g(-1) x min(-1)) noninvasively with 13N-ammonia and PET imaging. The CPT-induced mean changes in LA and in MBF in patients with elevated CRP (> or =0.5 mg/dL) were significantly impaired compared with patients presenting with CRP levels within normal range (<0.5 mg/dL) (DeltaLA, -1.09+/-0.86 versus 0.45+/-0.63 mm2; DeltaMBF, 0.06+/-0.18 versus 0.44+/-0.31 mL x g(-1) x min(-1); P<0.0001, respectively). Coronary LA changes and MBF responses to CPT were inversely correlated with CRP serum levels (r=-0.84 and r=-0.63; P<0.0001). Lastly, regression analysis revealed a significant correlation between the changes in LA and MBF during CPT for patients with elevated CRP levels and those for patients with normal CRP levels (r=0.56 and r=0.66; P<0.001). CONCLUSIONS: These findings suggest a direct association between systemic microinflammation and altered coronary vasomotor function of both the epicardial conductance and the arteriolar resistance vessels.
Aged↗
PET-measured responses of MBF to cold pressor testing correlate with indices of coronary vasomotion on quantitative coronary angiography.
UNLABELLED: The aims of this study were to determine whether responses in myocardial blood flow (MBF) to the cold pressor testing (CPT) method noninvasively with PET correlate with an established and validated index of flow-dependent coronary vasomotion on quantitative angiography. METHODS: Fifty-six patients (57 +/- 6 y; 16 with hypertension, 10 with hypercholesterolemia, 8 smokers, and 22 without coronary risk factors) with normal coronary angiograms were studied. Biplanar end-diastolic images of a selected proximal segment of the left anterior descending artery (LAD) (n = 27) or left circumflex artery (LCx) (n = 29) were evaluated with quantitative coronary angiography in order to determine the CPT-induced changes of epicardial luminal area (LA, mm(2)). Within 20 d of coronary angiography, MBF in the LAD, LCx, and right coronary artery territory was measured with (13)N-ammonia and PET at baseline and during CPT. RESULTS: CPT induced on both study days comparable percent changes in the rate x pressure product (%DeltaRPP, 37% +/- 13% and 40% +/- 17%; P = not significant [NS]). For the entire study group, the epicardial LA decreased from 5.07 +/- 1.02 to 4.88 +/- 1.04 mm(2) (DeltaLA, -0.20 +/- 0.89 mm(2)) or by -2.19% +/- 17%, while MBF in the corresponding epicardial vessel segment increased from 0.76 +/- 0.16 to 1.03 +/- 0.33 mL x min(-1) x g(-1) (DeltaMBF, 0.27 +/- 0.25 mL x min(-1) x g(-1)) or 36% +/- 31% (P <or= 0.0001). However, in normal controls without coronary risk factors (n = 22), the epicardial LA increased from 5.01 +/- 1.07 to 5.88 +/- 0.89 mm(2) (19.06% +/- 8.9%) and MBF increased from 0.77 +/- 0.16 to 1.34 +/- 0.34 mL x min(-1) x g(-1) (74.08% +/- 23.5%) during CPT, whereas patients with coronary risk factors (n = 34) revealed a decrease of epicardial LA from 5.13 +/- 1.48 to 4.24 +/- 1.12 mm(2) (-15.94% +/- 12.2%) and a diminished MBF increase (from 0.76 +/- 0.20 to 0.83 +/- 0.25 mL x min(-1) x g(-1) or 10.91% +/- 19.8%) as compared with controls (P < 0.0001, respectively), despite comparable changes in the RPP (P = NS). In addition, there was a significant correlation (r = 0.87; P <or= 0.0001) between CPT-related percent changes in LA on quantitative angiography and in MBF as measured with PET. CONCLUSION: The observed close correlation between an angiographically established parameter of flow-dependent and, most likely, endothelium-mediated coronary vasomotion and PET-measured MBF further supports the validity and value of MBF responses to CPT as a noninvasively available index of coronary circulatory function.
Blood Flow Velocity↗
Nitrogen-13 ammonia cardiac positron emission tomography in mice: effects of clonidine-induced changes in cardiac work on myocardial perfusion.
We explored the feasibility of imaging myocardial perfusion and of demonstrating the flow changes in response to reduction of cardiac work non-invasively in anesthetized mice using high spatial resolution, dedicated small-animal positron emission tomography (microPET). In 31 C57BL/6 mice anesthetized with pentobarbital or isoflurane, (13)N-ammonia was injected intravenously and images were recorded with microPET from 4 to 20 min. Fifteen mice (group 1) were studied consecutively at baseline (BL) and after reduction of heart rate (HR) with intraperitoneal injection of clonidine (CLN) to investigate effects of CLN-induced reduction of cardiac work on myocardial (13)N-ammonia uptake. Eight mice (group 2) were imaged repeatedly at BL and eight mice (group 3) twice after CLN to examine reproducibility. Total myocardial (13)N-ammonia accumulation was determined from the transaxial images and normalized for injected dose (%ID). HR was 412+/-97 beats/min at BL and 212+/-44 beats/min after CLN (P<0.0001). In group 1, the %ID significantly decreased from 1.50%+/-0.27% at BL to 1.29%+/-0.28% after CLN (P<0.0001). In groups 2 and 3, reproducibility of %ID was good (y=0.96x+0.105, SEE=0.212%, r(2)=0.749, P<0.0001). In conclusion, (13)N-ammonia microPET imaging demonstrated non-invasively a reduction of myocardial perfusion induced by clonidine in mice. We believe this study is of importance as the first report on myocardial perfusion imaging and flow validation in in vivo mouse hearts with a left ventricular size of only 5 mm using (13)N-ammonia and PET. MicroPET will aid in elucidating cardiac pathophysiology in transgenic mice and monitoring effects of gene therapies on myocardial perfusion.
Ammonia↗
Myocardial perfusion and viability by positron emission tomography in infants and children with coronary abnormalities: correlation with echocardiography, coronary angiography, and histopathology.
OBJECTIVES: This study was designed to assess the feasibility and accuracy of positron emission tomography (PET) imaging in infants and children. BACKGROUND: Positron emission tomography is employed in adults for the evaluation of myocardial perfusion and the detection of myocardial viability. METHODS: Perfusion and metabolism findings on PET in infants and children with suspected coronary abnormalities (age 14 days to 12 years old, mean 3.3 +/- 4.0 years) were correlated with findings on coronary angiography, echocardiography, and myocardial histopathology. The segmental myocardial uptake of the flow tracer (13)N-ammonia and of the glucose tracer (18)F-deoxyglucose ((18)FDG) was graded on a five-point scale and compared with the angiographic perfusion score, with regional wall motion, and the presence of fibrosis. RESULTS: There was an agreement of r = 0.72 (p < 0.05) between regional myocardial perfusion and angiography. The correlation of histopathologic changes with normal, moderately, and severely reduced segmental (13)N-ammonia uptake was 87%, 60%, and 75%, respectively. Segmental myocardial (18)FDG uptake and histopathologic findings were concordant in 48 (79%) of 64 segments without fibrosis; absence of viability by perfusion and metabolism imaging correlated with the presence of fibrosis in 21 (84%) of 25 segments. CONCLUSIONS: The observed agreements between the findings on PET perfusion and metabolism imaging with those on coronary angiography, echocardiography, and histopathology support the utility and accuracy of PET for characterizing myocardial perfusion abnormalities and viability in pediatric patients.
Cardiovascular Abnormalities↗
Positron-emission tomography reporter gene expression imaging in rat myocardium.
BACKGROUND: This study examines the quantitative accuracy, detection sensitivity, and time course of imaging the expression of a mutant herpes simplex type-1 virus thymidine kinase (HSV1-sr39tk) PET reporter gene in rat myocardium by using the PET reporter probe 9-(4-[18F]-Fluoro-3-Hydroxymethylbutyl)-Guanine ([18F]-FHBG) and a small-animal PET (microPET). METHODS AND RESULTS: In 40 rats, adenovirus expressing HSV1-sr39tk driven by a cytomegalovirus promoter (Ad-CMV-HSV1-sr39tk, 1x10(6) to 1x10(9) pfu) was injected through a thoracotomy directly into the left ventricular myocardium. After 3 days, myocardial perfusion was imaged with [13N]-ammonia for delineating the left ventricular myocardium, followed by imaging the expression of the reporter gene with intravenous [18F]-FHBG. The total myocardial [18F]-FHBG accumulation was quantified in percent of injected dose (%ID). Immunohistochemistry and autoradiography demonstrated HSV1-sr39tk enzyme (HSV1-sr39TK) and accumulation of [18F]-FHBG in the inoculated myocardium in 3 rats each. In 24 rats with various viral titers, the %ID was correlated with ex vivo well counting (r2=0.981, P<0.0001) and myocardial HSV1-sr39TK activity by tissue enzyme activity assay (r2=0.790, P<0.0001). Myocardial [18F]-FHBG accumulation was identified at viral titers down to 1x10(7) pfu. In 6 rats serially imaged up to day 17, myocardial [18F]-FHBG accumulation on microPET peaked on days 3 to 5 and was no longer identified on days 10 to 17. CONCLUSIONS: HSV1-sr39tk reporter gene expression can be monitored with [18F]-FHBG and microPET in rat myocardium quantitatively and serially with high detection sensitivity. Cardiac PET reporter gene imaging offers the potential of monitoring the expression of therapeutic genes in cardiac gene therapy.
Adenoviridae↗