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Monitoring left-ventricular dilation in mice by high-resolution small-animal-PET: Validation study using MRI
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Abstracts Tuesday, May 10, 2005
10.16 Monitoring left-ventricular dilation in mice by high-resolution small-animal-PET: validation study using MRI. L. Lars Stegger1, K. Scha¨fers1, U. Flo¨gel2, J. Schrader2, O. Schober1, B. Levkau3, M. Scha¨fers.1 1University Hospital Mu¨nster, Nuclear Medicine, Mu¨nster, Germany, 2Hei-
nrich-Heine-University Du¨sseldorf, Department of Cardiovasc. Physiology, Du¨sseldorf, Germany, 3University Hospital Essen, Institute of Pathophysiology, Essen, Germany Background: Molecular imaging by small animal positron emission tomography (PET) is an important non-invasive means to phenotype transgenic mouse models in vivo. When investigating pathologies of the left ventricular (LV) myocardium (e.g. cardiomyopathies) the serial assessment of LV volumes is important. By this, the presence of left ventricular dilation as a sign of developing heart failure can be detected. Where PET imaging is usually used to derive biochemical/molecular information, the functional parameters such as ventricular volumes are generally measured by using morphological and functional imaging modalities such as echocardiography or magnetic resonance imaging. Here, a method to monitor left ventricular dilatation in mice with PET and thus obviating the need for a second imaging modality is presented and evaluated using cardiac MRI as the gold standard. Methods: The method uses a semiautomatic 3D-algorithm to delineate the left ventricular myocardial wall on static Small-Animal-PET images depicting myocardial glucose metabolism (F-18-fluoro-2-deoxy-glucosePET). The volume enclosed by the three-dimensional midmyocardial contour is calculated.
Data for twenty mice, ten wildtype mice and ten transgenic mice developing dilated cardiomyopathy, were obtained and compared to volumes measured by magnetic resonance imaging in the same animals. Results: Data obtained by PET and MRI correlated well (R⫽0.89). Graphical analysis according to Bland and Altman did not reveal a dependency on volume. Conclusion: Small animal PET imaging allows to monitor LV dilation in mice, thus obviating the need for a second imaging modality making serial measurements more efficient.
T U E T S U D E A S Y D A M Y A Y M A 10 Y 10
Journal of Nuclear Cardiology March/April 2005
10.18 Assessment of base-to-apex gradients of myocardial blood flow after statin therapy at different stages of coronary atherosclerosis. J.P. Peter Wielepp1, D. Baller2, E. Pulawski2, R. Weise1, E. Fricke1, D. Horstkotte2, W. Burchert.1 1Institute of Nuclear Medicine, Heart and Diabetes Center, Bad Oeynhausen, Germany, 2Clinic of Cardiology, Heart Center North Rhine-Westphalia, Bad Oeynhausen, Germany Diffuse coronary atherosclerosis is the common substrate for plaque rupture and cardiovascular events. Assessment of longitudinal, base-to-apex gradients (BAG) of myocardial perfusion abnormalities is a potential noninvasive marker for the functional integrity of the coronary endothelium. The aim of our study was the examination of reversibility of BAG after 6-month statin therapy. Methods: 31 pts (age 62.4 ⫾ 7.7 years; 22 males) with mild-to-moderate angina and LDL cholesterin (LDL-C) of 183 ⫾ 40 mg/dl at baseline were included. Coronary angiography revealed minimal disease in terms of wall irregularities or stenosis ⬍ 30% in 19 pts and moderate coronary artery disease (CAD) with stenosis ⬎50% in 11 pts. The reference group consists of 22 pts without detectable CAD. Absolute myocardial blood flow (MBF) was measured with ammonia PET under pharmacologic stress (adenosine). Basal mid (termed base) and mid-to-apex (apex) segments were analyzed. Minimal coronary resistance (MCR) was calculated as the ratio mean arterial pressure/ MBF-adenosine. Results: Before therapy BAG-MCR was significantly lower in pts (0.91 ⫾ 0.12) as compared to reference group (0.97 ⫾ 0.14; p⬍0.05). After statin therapy BAG-MCR increased from 0.91 ⫾ 0.12 to 0.95 ⫾ 0.12 (p⬍0.05). BAG-MBF decreased from 1.12 ⫾ 0.20 to 1.07 ⫾ 0.13 (p⬍0.05). Even in segments with normal MCR (⬍0.40 mmHg/(ml/min/100g) BAG-MCR increased from 0.90 ⫾ 0.10 to 0.96 ⫾ 0.11 (p⬍0.05). LDL-C decreased to 104 ⫾ 30 mg/dl at follow-up (p⬍0.001). Conclusions: These PET results demonstrate a short-term reversibility of base-to-apex gradients of myocardial perfusion disturbance at early or moderate coronary atherosclerosis after 6-month statin therapy. The pathophysiologic mechanism behind probably reflects healing endothelium with improved flow-dependent dilation of epicardial vessels prone to atherosclerosis and risk factors such as LDL-C.
Correlation
10.17
10.19
Myocardial blood flow and coronary vascular resistance are dependent on thyroid function-a quantitative study using positron emission tomography and oxygen-15labeled water. P. Peter Kies1, L. Stegger1, T. Wichter2, K.P. Scha¨fers1, O. Schober1, M. Scha¨fers.1 1 University Hospital Muenster, Nuclear Medicine, Muenster, Germany, 2University Hospital Muenster, Internal Medicine C, Cardiology, Muenster, Germany
Effect of spinal cord stimulation on myocardial blood flow in patients with therapy refractory angina pectoris. J.P. Peter Wielepp1, S. Eckert2, A. Dongas3, D. Horstkotte2, W. Burchert.1 1Institute of Nuclear Medicine, Heart and Diabetes Center, Bad Oeynhausen, Germany, 2Clinic of Cardiology, Heart and Diabetes Center, Bad Oeynhausen, Germany, 3Institute of Anesthesiology, Heart and Diabetes Center, Bad Oeynhausen, Germany
Introduction: Alterations of thyroid function are known to be associated with changes of the cardiovascular system. Aim of this study was to investigate the effects of an altered thyroid function on myocardial blood flow (MBF) and coronary vascular resistance (CVR). Methods: Twenty hypothyroid patients (4m,16f,38⫾9 years) with a history of differentiated thyroid carcinoma, eleven patients (4m,7f,48⫾15 years) during clinical or subclinical hyperthyroidism and ten euthyroid controls (6m,4f,32⫾4 years) were enrolled in this study. Entry criteria included the absence of coronary artery disease, risk factors and cardiac medication. MBF (ml/g/min) was quantified by dynamic PET and 15O-labeled water. MBF was measured at rest, during adenosine infusion to provoke maximal hyperaemic MBF and calculate the coronary flow reserve (CFR), and during cold pressor testing (CPT) to obtain maximal perfusion stimulated by the endothelial response. In addition, CVR (mmHg/ml/g/min) in the different settings was calculated dividing mean arterial blood pressure by the respective MBF. Rate pressure product (RPP) was calculated for each group to compare hemodynamic parameters during the scans. Results: Mean RPP at baseline were similar in the three groups excluding an effect of different cardiac work on MBF (Hypo:7660⫾1429,Eu:8131⫾2422,Hyper:8438⫾1101; p⫽ns). Baseline MBF was significantly higher in the hyperthyroid group (Hyper:1.15⫾0.23, Hypo:0.89⫾0.22, Eu:0.94⫾0.24; p⬍0.05). Absolute MBF during adenosine infusion and CFR were similar between the three groups (3.79⫾1.18, 3.66⫾1.26, 3.73⫾1.17; p⫽ns). MBF during CPT was significantly higher in the hyperthyroid group (Hyper: 1.57⫾0.39,Hypo:1.08⫾0.22, Eu:1.18⫾0.31; p⬍0.05). Baseline CVR was significantly lower in the hyperthyroid group (Hyper:78⫾12.2,Hypo: 105.7⫾27.6, Eu:99.9⫾20.0; p⬍0.05). CVR during adenosine infusion was not significantly different between the three groups (27.4⫾14.4, 29.6⫾18.6, 27.6⫾11.3; p⫽ns). CVR during CPT was significantly lower in the hyperthyroid group (62.1⫾15.9) than in the hypothyroid group (91.9⫾24.7, p⬍0.05). It was also lower compared to the euthyroid group (80.4⫾19.6), however this difference only reached borderline significance (p⫽0.058). Conclusion: Our results show an increased MBF at baseline and during CPT in patients with clinical and subclinical hyperthyroidism. Under the same conditions CVR is reduced in these patients. Adenosine infusion does not cause any significant changes, therefore our results strongly suggest an endothelium-mediated effect of clinical and subclinical hyperthyroidism on MBF and CVR.
Spinal cord stimulation (SCS) has proven to be a safe procedure in patients with symptomatic angina pectoris (AP) refractory to medical therapy and without any option for PCI or CABG. This technique has repeatedly demonstrated an antianginal effect by reducing AP symptoms. The mechanism, however, remains controversial. The aim of the study is the assessment of the effect of SCS on myocardial blood flow (MBF) and minimal coronary resistance (MCR). Methods: In 6 male patients (mean age 66 years) with multi-vessel disease which were scheduled for NS, perfusion at rest and during the maximum hemodynamic effect of intravenous adenosine were studied by ammonia PET (Siemens ECAT EXACT HR⫹) on two different occasions: directly before SCS and 13 ⫾ 0.5 months after SCS. The stimulator was active in all patients at 21 ⫾ 5 hours before PET scan was done. MBF and MCR were calculated for the most impaired myocardial segments at baseline (initial MBF stress ⬍ 190 ml/min/100g). We correlated these data with clinical CCS angina score and NYHA class. Results: Outpatients visits and hospitalization where significantly reduced in the 12 months post SCS compared to a 12 months interval before stimulation. Corresponding to the reduction in angina, the consumption of short-acting nitrates was also significantly reduced. There was an increased hyperemic myocardial blood flow (138.8 ⫾ 26.7 before SCS vs. 147.5 ⫾ 0.37 ml/min/100g during SCS; p⬍0.05) and decreased minimal coronary resistance (0.65 ⫾ 0.20 before SCS vs. 0.59 ⫾ 0.18 mmHg/(ml/min/100g) during SCS; p⬍0.05) in the initial most impaired myocardial segments. Conclusions: SCS has been shown to improve anginal status in patients with severe coronary artery disease. Our preliminary results suggest that the anti-anginal effect of SCS is associate with an improved regional MBF and vasodilator capacity in the most impaired myocardial segments.
Abstracts Tuesday, May 10, 2005
10.16 Monitoring left-ventricular dilation in mice by high-resolution small-animal-PET: validation study using MRI. L. Lars Stegger1, K. Scha¨fers1, U. Flo¨gel2, J. Schrader2, O. Schober1, B. Levkau3, M. Scha¨fers.1 1University Hospital Mu¨nster, Nuclear Medicine, Mu¨nster, Germany, 2Hei-
nrich-Heine-University Du¨sseldorf, Department of Cardiovasc. Physiology, Du¨sseldorf, Germany, 3University Hospital Essen, Institute of Pathophysiology, Essen, Germany Background: Molecular imaging by small animal positron emission tomography (PET) is an important non-invasive means to phenotype transgenic mouse models in vivo. When investigating pathologies of the left ventricular (LV) myocardium (e.g. cardiomyopathies) the serial assessment of LV volumes is important. By this, the presence of left ventricular dilation as a sign of developing heart failure can be detected. Where PET imaging is usually used to derive biochemical/molecular information, the functional parameters such as ventricular volumes are generally measured by using morphological and functional imaging modalities such as echocardiography or magnetic resonance imaging. Here, a method to monitor left ventricular dilatation in mice with PET and thus obviating the need for a second imaging modality is presented and evaluated using cardiac MRI as the gold standard. Methods: The method uses a semiautomatic 3D-algorithm to delineate the left ventricular myocardial wall on static Small-Animal-PET images depicting myocardial glucose metabolism (F-18-fluoro-2-deoxy-glucosePET). The volume enclosed by the three-dimensional midmyocardial contour is calculated.
Data for twenty mice, ten wildtype mice and ten transgenic mice developing dilated cardiomyopathy, were obtained and compared to volumes measured by magnetic resonance imaging in the same animals. Results: Data obtained by PET and MRI correlated well (R⫽0.89). Graphical analysis according to Bland and Altman did not reveal a dependency on volume. Conclusion: Small animal PET imaging allows to monitor LV dilation in mice, thus obviating the need for a second imaging modality making serial measurements more efficient.
T U E T S U D E A S Y D A M Y A Y M A 10 Y 10
Journal of Nuclear Cardiology March/April 2005
10.18 Assessment of base-to-apex gradients of myocardial blood flow after statin therapy at different stages of coronary atherosclerosis. J.P. Peter Wielepp1, D. Baller2, E. Pulawski2, R. Weise1, E. Fricke1, D. Horstkotte2, W. Burchert.1 1Institute of Nuclear Medicine, Heart and Diabetes Center, Bad Oeynhausen, Germany, 2Clinic of Cardiology, Heart Center North Rhine-Westphalia, Bad Oeynhausen, Germany Diffuse coronary atherosclerosis is the common substrate for plaque rupture and cardiovascular events. Assessment of longitudinal, base-to-apex gradients (BAG) of myocardial perfusion abnormalities is a potential noninvasive marker for the functional integrity of the coronary endothelium. The aim of our study was the examination of reversibility of BAG after 6-month statin therapy. Methods: 31 pts (age 62.4 ⫾ 7.7 years; 22 males) with mild-to-moderate angina and LDL cholesterin (LDL-C) of 183 ⫾ 40 mg/dl at baseline were included. Coronary angiography revealed minimal disease in terms of wall irregularities or stenosis ⬍ 30% in 19 pts and moderate coronary artery disease (CAD) with stenosis ⬎50% in 11 pts. The reference group consists of 22 pts without detectable CAD. Absolute myocardial blood flow (MBF) was measured with ammonia PET under pharmacologic stress (adenosine). Basal mid (termed base) and mid-to-apex (apex) segments were analyzed. Minimal coronary resistance (MCR) was calculated as the ratio mean arterial pressure/ MBF-adenosine. Results: Before therapy BAG-MCR was significantly lower in pts (0.91 ⫾ 0.12) as compared to reference group (0.97 ⫾ 0.14; p⬍0.05). After statin therapy BAG-MCR increased from 0.91 ⫾ 0.12 to 0.95 ⫾ 0.12 (p⬍0.05). BAG-MBF decreased from 1.12 ⫾ 0.20 to 1.07 ⫾ 0.13 (p⬍0.05). Even in segments with normal MCR (⬍0.40 mmHg/(ml/min/100g) BAG-MCR increased from 0.90 ⫾ 0.10 to 0.96 ⫾ 0.11 (p⬍0.05). LDL-C decreased to 104 ⫾ 30 mg/dl at follow-up (p⬍0.001). Conclusions: These PET results demonstrate a short-term reversibility of base-to-apex gradients of myocardial perfusion disturbance at early or moderate coronary atherosclerosis after 6-month statin therapy. The pathophysiologic mechanism behind probably reflects healing endothelium with improved flow-dependent dilation of epicardial vessels prone to atherosclerosis and risk factors such as LDL-C.
Correlation
10.17
10.19
Myocardial blood flow and coronary vascular resistance are dependent on thyroid function-a quantitative study using positron emission tomography and oxygen-15labeled water. P. Peter Kies1, L. Stegger1, T. Wichter2, K.P. Scha¨fers1, O. Schober1, M. Scha¨fers.1 1 University Hospital Muenster, Nuclear Medicine, Muenster, Germany, 2University Hospital Muenster, Internal Medicine C, Cardiology, Muenster, Germany
Effect of spinal cord stimulation on myocardial blood flow in patients with therapy refractory angina pectoris. J.P. Peter Wielepp1, S. Eckert2, A. Dongas3, D. Horstkotte2, W. Burchert.1 1Institute of Nuclear Medicine, Heart and Diabetes Center, Bad Oeynhausen, Germany, 2Clinic of Cardiology, Heart and Diabetes Center, Bad Oeynhausen, Germany, 3Institute of Anesthesiology, Heart and Diabetes Center, Bad Oeynhausen, Germany
Introduction: Alterations of thyroid function are known to be associated with changes of the cardiovascular system. Aim of this study was to investigate the effects of an altered thyroid function on myocardial blood flow (MBF) and coronary vascular resistance (CVR). Methods: Twenty hypothyroid patients (4m,16f,38⫾9 years) with a history of differentiated thyroid carcinoma, eleven patients (4m,7f,48⫾15 years) during clinical or subclinical hyperthyroidism and ten euthyroid controls (6m,4f,32⫾4 years) were enrolled in this study. Entry criteria included the absence of coronary artery disease, risk factors and cardiac medication. MBF (ml/g/min) was quantified by dynamic PET and 15O-labeled water. MBF was measured at rest, during adenosine infusion to provoke maximal hyperaemic MBF and calculate the coronary flow reserve (CFR), and during cold pressor testing (CPT) to obtain maximal perfusion stimulated by the endothelial response. In addition, CVR (mmHg/ml/g/min) in the different settings was calculated dividing mean arterial blood pressure by the respective MBF. Rate pressure product (RPP) was calculated for each group to compare hemodynamic parameters during the scans. Results: Mean RPP at baseline were similar in the three groups excluding an effect of different cardiac work on MBF (Hypo:7660⫾1429,Eu:8131⫾2422,Hyper:8438⫾1101; p⫽ns). Baseline MBF was significantly higher in the hyperthyroid group (Hyper:1.15⫾0.23, Hypo:0.89⫾0.22, Eu:0.94⫾0.24; p⬍0.05). Absolute MBF during adenosine infusion and CFR were similar between the three groups (3.79⫾1.18, 3.66⫾1.26, 3.73⫾1.17; p⫽ns). MBF during CPT was significantly higher in the hyperthyroid group (Hyper: 1.57⫾0.39,Hypo:1.08⫾0.22, Eu:1.18⫾0.31; p⬍0.05). Baseline CVR was significantly lower in the hyperthyroid group (Hyper:78⫾12.2,Hypo: 105.7⫾27.6, Eu:99.9⫾20.0; p⬍0.05). CVR during adenosine infusion was not significantly different between the three groups (27.4⫾14.4, 29.6⫾18.6, 27.6⫾11.3; p⫽ns). CVR during CPT was significantly lower in the hyperthyroid group (62.1⫾15.9) than in the hypothyroid group (91.9⫾24.7, p⬍0.05). It was also lower compared to the euthyroid group (80.4⫾19.6), however this difference only reached borderline significance (p⫽0.058). Conclusion: Our results show an increased MBF at baseline and during CPT in patients with clinical and subclinical hyperthyroidism. Under the same conditions CVR is reduced in these patients. Adenosine infusion does not cause any significant changes, therefore our results strongly suggest an endothelium-mediated effect of clinical and subclinical hyperthyroidism on MBF and CVR.
Spinal cord stimulation (SCS) has proven to be a safe procedure in patients with symptomatic angina pectoris (AP) refractory to medical therapy and without any option for PCI or CABG. This technique has repeatedly demonstrated an antianginal effect by reducing AP symptoms. The mechanism, however, remains controversial. The aim of the study is the assessment of the effect of SCS on myocardial blood flow (MBF) and minimal coronary resistance (MCR). Methods: In 6 male patients (mean age 66 years) with multi-vessel disease which were scheduled for NS, perfusion at rest and during the maximum hemodynamic effect of intravenous adenosine were studied by ammonia PET (Siemens ECAT EXACT HR⫹) on two different occasions: directly before SCS and 13 ⫾ 0.5 months after SCS. The stimulator was active in all patients at 21 ⫾ 5 hours before PET scan was done. MBF and MCR were calculated for the most impaired myocardial segments at baseline (initial MBF stress ⬍ 190 ml/min/100g). We correlated these data with clinical CCS angina score and NYHA class. Results: Outpatients visits and hospitalization where significantly reduced in the 12 months post SCS compared to a 12 months interval before stimulation. Corresponding to the reduction in angina, the consumption of short-acting nitrates was also significantly reduced. There was an increased hyperemic myocardial blood flow (138.8 ⫾ 26.7 before SCS vs. 147.5 ⫾ 0.37 ml/min/100g during SCS; p⬍0.05) and decreased minimal coronary resistance (0.65 ⫾ 0.20 before SCS vs. 0.59 ⫾ 0.18 mmHg/(ml/min/100g) during SCS; p⬍0.05) in the initial most impaired myocardial segments. Conclusions: SCS has been shown to improve anginal status in patients with severe coronary artery disease. Our preliminary results suggest that the anti-anginal effect of SCS is associate with an improved regional MBF and vasodilator capacity in the most impaired myocardial segments.