26 results on '"Seyfarth T"'
Search Results
2. Concentration of human cardiac31P-metabolites determined by SLOOP31P-MRS
- Author
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Landschütz, W., Meininger, M., Beer, M., Seyfarth, T., Horn, M., Pabst, T., Haase, A., Hahn, D., Neubauer, S., and von Kienlin, M.
- Published
- 1998
- Full Text
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3. 64‐slice Computed Tomography Assessment of Coronary Artery Stents: a Phantom Study.
- Author
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Mahnken, Andreas H., Mühlenbruch, G., Seyfarth, T., Flohr, T., Stanzel, S., Wildberger, J. E., Günther, R. W., and Kuettner, A.
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CORONARY arteries ,SCANNING systems ,CARDIAC imaging ,MEDICAL imaging systems ,MAGNETIC resonance imaging ,SURGICAL stents ,ANGIOGRAPHY ,HEART diseases ,MEDICAL radiography - Abstract
Purpose: To compare the use of a new 64-slice computed tomography (CT) scanner with 16-slice CT in the visualization of coronary artery stent lumen. Material and Methods: Eight different coronary artery stents, each with a diameter of 3 mm, were placed in a static chest phantom. The phantom was positioned in the CT gantry at an angle of 0° and 45° towards the z-axis and examined with both a 64-slice and a 16-slice CT scanner. Effective slice thickness was 0.6 mm with 64-slice CT and 1 mm with 16-slice CT. A reconstruction increment of 0.3 mm was applied in both scanners. Image quality was assessed visually using a 5-point grading scale. Stent diameters were measured and compared using paired Wilcoxon tests. Results: Artificial lumen reduction was significantly less with 64-slice than with 16-slice CT. Average visible stent lumen was 53.4% using 64-slice CT and 47.5% with 16-slice MSCT. Most severe artifacts were seen in stents with radiopaque markers. Using 64-slice CT, image noise increased by approximately 30% due to thinner slice thickness. Conclusion: Improved spatial resolution of 64-slice CT resulted in superior assessment of coronary artery stent lumen compared to 16-slice CT. However, a relevant part of the stent lumen is still not assessable with multi-slice CT. [ABSTRACT FROM AUTHOR]
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- 2006
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4. Untersuchungen des kardialen Energiestoffwechsels bei Herzvitien mit der 31P-MR-Spektroskopie.
- Author
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Beer, M., Viehrig, M., Seyfarth, T., Sandstede, J., Lipke, C., Pabst, T., Kenn, W., Harre, K., Horn, M., Landschütz, W., von Kienlin, M., Neubauer, S., and Hahn, D.
- Abstract
Copyright of Der Radiologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2000
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5. Concentration of human cardiac31P-metabolites determined by SLOOP31P-MRS.
- Author
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Landschütz, W., Meininger, M., Beer, M., Seyfarth, T., Horn, M., Pabst, T., Haase, A., Hahn, D., Neubauer, S., and Kienlin, M.
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- 1998
- Full Text
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6. Computer-aided detection of pulmonary nodules: influence of nodule characteristics on detection performance
- Author
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Marten, K., Engelke, C., Seyfarth, T., Grillhösl, A., Obenauer, S., and Rummeny, E.J.
- Subjects
- *
CHEST (Anatomy) , *DIAGNOSIS , *RADIOLOGISTS , *PHYSICIANS , *PATIENTS - Abstract
Aim: To evaluate prospectively the influence of pulmonary nodule characteristics on detection performances of a computer-aided diagnosis (CAD) tool and experienced chest radiologists using multislice CT (MSCT).Materials and Methods: MSCT scans of 20 consecutive patients were evaluated by a CAD system and two independent chest radiologists for presence of pulmonary nodules. Nodule size, position, margin, matrix characteristics, vascular and pleural attachments and reader confidence were recorded and data compared with an independent standard of reference. Statistical analysis for predictors influencing nodule detection or reader performance included chi-squared, retrograde stepwise conditional logistic regression with odds ratios and nodule detection proportion estimates (DPE), and ROC analysis.Results: For 135 nodules, detection rates for CAD and readers were 76.3, 52.6 and 52.6%, respectively; false-positive rates were 0.55, 0.25 and 0.15 per examination, respectively. In consensus with CAD the reader detection rate increased to 93.3%, and the false-positive rate dropped to 0.1/scan. DPEs for nodules < or = 5 mm were significantly higher for ICAD than for the readers (p < 0.05). Absence of vascular attachment was the only significant predictor of nodule detection by CAD (p = 0.0006-0.008). There were no predictors of nodule detection for reader consensus with CAD. In contrast, vascular attachment predicted nodule detection by the readers (p = 0.0001-0.003). Reader sensitivity was higher for nodules with vascular attachment than for unattached nodules (sensitivities 0.768 and 0.369; 95% confidence intervals = 0.651-0.861 and 0.253-0.498, respectively).Conclusion: CAD increases nodule detection rates, decreases false-positive rates and compensates for deficient reader performance in detection of smallest lesions and of nodules without vascular attachment. [ABSTRACT FROM AUTHOR]- Published
- 2005
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7. Concentration of human cardiac 31P-metabolites determined by SLOOP 31P-MRS
- Author
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Landschütz, W., Meininger, M., Beer, M., Seyfarth, T., Horn, M., Pabst, T., Haase, A., Hahn, D., Neubauer, S., and von Kienlin, M.
- Published
- 1998
8. Assessment of global right ventricular function on 64-MDCT compared with MRI.
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Plumhans C, Mühlenbruch G, Rapaee A, Sim KH, Seyfarth T, Günther RW, and Mahnken AH
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- Contrast Media, Coronary Artery Disease pathology, Electrocardiography, Female, Humans, Image Processing, Computer-Assisted, Iohexol analogs & derivatives, Magnetic Resonance Imaging, Cine, Male, Middle Aged, Prospective Studies, Reproducibility of Results, Stroke Volume, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease physiopathology, Tomography, X-Ray Computed methods, Ventricular Function, Right physiology
- Abstract
Objective: The aim of this study was to compare ECG-gated 64-MDCT with MRI for the assessment of global right ventricular (RV) function from coronary CT angiography data., Subjects and Methods: Thirty-eight patients (25 men, 13 women; mean age +/- SD, 55.0 +/- 8.8 years) with suspected coronary artery disease underwent contrast-enhanced 64-MDCT (64 x 0.6 mm, 120 kV, 770 mAs(eff)) and 1.5-T MRI (balanced fast-field echo; TR/TE, 3.3/1.6; flip angle, 60 degrees ; 50 phases). Double oblique short-axis MDCT and MR images were used for further analysis. End-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fraction (EF) were computed from manually drawn endocardial contours of the right ventricle. For statistical analysis, repeated-measures analysis of variance and Pearson's correlation coefficients were calculated. Bland-Altman plots were computed., Results: In general, RV volumes calculated from 64-MDCT agreed well with those calculated from MRI. The mean EF (+/- SD) calculated from MDCT and MRI was 51.0% +/- 7.8% and 51.4% +/- 7.3%, respectively. An excellent correlation was observed for EDV (r = 0.99), ESV (r = 0.98), SV (r = 0.98), and EF (r = 0.97). Bland-Altman plots showed no systematic variation between MDCT and MRI data. No statistically significant differences (p < or = 0.05) between the techniques were found., Conclusion: Although contrast injection is optimized for visualization of the coronary arteries, retrospectively ECG-gated 64-MDCT permits reliable assessment of global RV function.
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- 2008
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9. Diagnostic value of 64-slice multi-detector row cardiac CTA in symptomatic patients.
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Mühlenbruch G, Seyfarth T, Soo CS, Pregalathan N, and Mahnken AH
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- Calcinosis diagnostic imaging, Female, Heart Rate, Humans, Male, Middle Aged, Sensitivity and Specificity, Coronary Angiography methods, Coronary Artery Disease diagnostic imaging, Coronary Stenosis diagnostic imaging, Tomography, X-Ray Computed methods
- Abstract
Cardiac multi-detector-row computed tomography (MDCT) angiography has shown high levels of sensitivity and especially negative predictive value regarding the diagnosis of coronary artery disease (CAD). This study was designed to determine the value of a 64-slice-MDCT scanner in comparison to invasive coronary angiography for the detection of CAD in a population of symptomatic patients. Fifty-one patients with suspected CAD underwent conventional coronary angiography and ECG-gated cardiac 64-slice-MDCT angiography with a rotation time of 330 ms, a collimation of 64x0.6 mm and a slice thickness of 0.75 mm. Blinded patient- and segment-based analysis was performed for the detection of stenoses >or=70% of the vessel lumen. 95% of all coronary segments were assessable by MDCT angiography. Patient-based (segment-based) analysis revealed a sensitivity of 97.8% (86.7%), specificity of 50% (95.2%), positive predictive value of 93.6% (75.2%) and negative predictive value of 75% (97.7%). Inter-rater agreement revealed a kappa-value of 0.558 (0.722). In this symptomatic patient group a 64-slice-MDCT scanner shows good agreement on a segment-based analysis but only moderate agreement on a patient-based analysis. The diagnostic accuracy of 64-slice-MDCT coronary angiography is negatively influenced by the high pre-test probability of this symptomatic patient collective.
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- 2007
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10. Age and gender dependence of human cardiac phosphorus metabolites determined by SLOOP 31P MR spectroscopy.
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Köstler H, Landschütz W, Koeppe S, Seyfarth T, Lipke C, Sandstede J, Spindler M, von Kienlin M, Hahn D, and Beer M
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- Adult, Age Factors, Aged, Energy Metabolism, Female, Humans, Male, Middle Aged, Phosphorus Isotopes, Sex Factors, Statistics, Nonparametric, Adenosine Triphosphate metabolism, Magnetic Resonance Spectroscopy methods, Myocardium metabolism, Phosphates metabolism, Phosphocreatine metabolism
- Abstract
The aim of this study was to apply (31)P magnetic resonance spectroscopy (MRS) using spatial localization with optimal point spread function (SLOOP) to investigate possible age and gender dependencies of the energy metabolite concentrations in the human heart. Thirty healthy volunteers (18 males and 12 females, 21-67 years old, mean = 40.7 years) were examined with the use of (31)P-MRS on a 1.5 T scanner. Intra- and interobserver variability measures (determined in eight of the volunteers) were both 3.8% for phosphocreatine (PCr), and 4.7% and 8.3%, respectively, for adenosine triphosphate (ATP). High-energy phosphate (HEP) concentrations in mmol/kg wet weight were 9.7 +/- 2.4 (age < 40 years, N = 16) and 7.7 +/- 2.5 (age >or= 40 years, N = 14) for PCr, and 5.1 +/- 1.0 (age < 40 years) and 4.1 +/- 0.8 (age >or= 40 years) for ATP, respectively. Separated by gender, PCr concentrations of 9.2 +/- 2.4 (men, N = 18) and 8.0 +/- 2.8 (women, N = 12) and ATP concentrations of 4.9 +/- 1.0 (men) and 4.2 +/- 0.9 (women) were measured. A significant decrease of PCr and ATP was found for volunteers older than 40 years (P < 0.05), but the differences in metabolic concentrations between both sexes were not significant. In conclusion, age has a minor but still significant impact on cardiac energy metabolism, and no significant gender differences were detected.
- Published
- 2006
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11. Computer-assisted detection of pulmonary nodules: evaluation of diagnostic performance using an expert knowledge-based detection system with variable reconstruction slice thickness settings.
- Author
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Marten K, Grillhösl A, Seyfarth T, Obenauer S, Rummeny EJ, and Engelke C
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- Adult, Aged, Aged, 80 and over, Expert Systems, Female, Humans, Male, Middle Aged, Prospective Studies, ROC Curve, Radiography, Thoracic, Statistics, Nonparametric, Tomography, X-Ray Computed, Diagnosis, Computer-Assisted methods, Lung Neoplasms diagnostic imaging, Radiographic Image Interpretation, Computer-Assisted methods
- Abstract
The purpose of this study was to evaluate the performance of a computer-assisted diagnostic (CAD) tool using various reconstruction slice thicknesses (RST). Image data of 20 patients undergoing multislice CT for pulmonary metastasis were reconstructed at 4.0, 2.0 and 0.75 mm RST and assessed by two blinded radiologists (R1 and R2) and CAD. Data were compared against an independent reference standard. Nodule subgroups (diameter >10, 4-10, <4 mm) were assessed separately. Statistical methods were the ROC analysis and Mann-Whitney U test. CAD was outperformed by readers at 4.0 mm (Az = 0.18, 0.62 and 0.69 for CAD, R1 and R2, respectively; P<0.05), comparable at 2.0 mm (Az = 0.57, 0.70 and 0.69 for CAD, R1 and R2, respectively), and superior using 0.75 mm RST (Az = 0.80, 0.70 and 0.70 and sensitivity = 0.74, 0.53 and 0.53 for CAD, R1 and R2, respectively; P<0.05). Reader performances were significantly enhanced by CAD (Az = 0.93 and 0.95 for R1 + CAD and R2 + CAD, respectively, P<0.05). The CAD advantage was best for nodules <10 mm (detection rates = 93.3, 89.9, 47.9 and 47.9% for R1 + CAD, R2 + CAD, R1 and R2, respectively). CAD using 0.75 mm RST outperformed radiologists in nodules below 10 mm in diameter and should be used to replace a second radiologist. CAD is not recommended for 4.0 mm RST.
- Published
- 2005
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12. Flat-panel detector computed tomography for the assessment of coronary artery stents: phantom study in comparison with 16-slice spiral computed tomography.
- Author
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Mahnken AH, Seyfarth T, Flohr T, Herzog C, Stahl J, Stanzel S, Kuettner A, Wildberger JE, and Günther RW
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- Coronary Angiography instrumentation, Coronary Vessels surgery, Phantoms, Imaging, Stents, Tomography, Spiral Computed instrumentation
- Abstract
Purpose: The evaluation of coronary artery stents is a major limitation of cardiac multislice spiral computed tomography (MSCT). The development of flat-panel detector computed tomography (FPCT) with truly isotropic spatial resolution may overcome this limitation. Thus, we evaluated the use of FPCT in comparison to MSCT for the assessment of coronary artery stents., Material and Methods: Eight different coronary artery stents with a diameter of 3 mm each were placed in a static chest phantom. The phantom was positioned in the CT gantry at angles of 0 degrees , 45 degrees , and 90 degrees toward the z-axis and examined with the prototype of a FPCT (Siemens, Forchheim, Germany) and a commercially available 16-detector row MSCT (Sensation 16, Siemens). Slice thickness was 0.25 mm with FPCT whereas for MSCT, an effective slice thickness of 1 mm with a reconstruction increment of 0.5 mm was used. Image quality was assessed visually using a 5-point grading scale. Stent diameters were measured and compared using a repeated-measures analysis of variance., Results: When compared with MSCT, artificial lumen reduction was significantly less using FPCT. On average the visible stent lumen was reduced by 16.1% with FPCT, whereas the mean of the lumen reduction was 47.2% with 16-detector row MSCT. Visible lumen diameter as well as image noise significantly increased using FPCT (P < 0.001). With FPCT delineation of the different stent struts became possible., Conclusion: FPCT proved to be superior when compared with 16-detector row MSCT for the in vitro assessment of coronary artery stents. Improved spatial resolution allows for a detailed assessment of the coronary artery stent lumen.
- Published
- 2005
13. Computer-assisted detection of pulmonary nodules: performance evaluation of an expert knowledge-based detection system in consensus reading with experienced and inexperienced chest radiologists.
- Author
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Marten K, Seyfarth T, Auer F, Wiener E, Grillhösl A, Obenauer S, Rummeny EJ, and Engelke C
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- Adult, Aged, Aged, 80 and over, Contrast Media, Humans, Image Processing, Computer-Assisted, Middle Aged, Observer Variation, Pattern Recognition, Automated, Prospective Studies, ROC Curve, Sensitivity and Specificity, Single-Blind Method, Statistics, Nonparametric, Diagnosis, Computer-Assisted, Expert Systems, Iohexol analogs & derivatives, Lung Neoplasms diagnostic imaging, Radiology, Solitary Pulmonary Nodule diagnostic imaging, Tomography, X-Ray Computed methods
- Abstract
To evaluate the performance of experienced versus inexperienced radiologists in comparison and in consensus with an interactive computer-aided detection (CAD) system for detection of pulmonary nodules. Eighteen consecutive patients (mean age: 62.2 years; range 29-83 years) prospectively underwent routine 16-row multislice computed tomography (MSCT). Four blinded radiologists (experienced: readers 1, 2; inexperienced: readers 3, 4) assessed image data against CAD for pulmonary nodules. Thereafter, consensus readings of readers 1+3, reader 1+CAD and reader 3+CAD were performed. Data were compared against an independent gold standard. Statistical tests used to calculate interobserver agreement, reader performance and nodule size were Kappa, ROC and Mann-Whitney U. CAD and experienced readers outperformed inexperienced readers (Az=0.72, 0.71, 0.73, 0.49 and 0.50 for CAD, readers 1-4, respectively; P<0.05). Performance of reader 1+CAD was superior to single reader and reader 1+3 performances (Az=0.93, 0.72 for reader 1+CAD and reader 1+3 consensus, respectively, P<0.05). Reader 3+CAD did not perform superiorly to experienced readers or CAD (Az=0.79 for reader 3+CAD; P>0.05). Consensus of reader 1+CAD significantly outperformed all other readings, demonstrating a benefit in using CAD as an inexperienced reader replacement. It is questionable whether inexperienced readers can be regarded as adequate for interpretation of pulmonary nodules in consensus with CAD, replacing an experienced radiologist., (Copyright 2004 Springer-Verlag)
- Published
- 2004
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14. Cardiac beta-adrenoceptor changes in monocrotaline-treated rats: differences between membrane preparations from whole ventricles and isolated ventricular cardiomyocytes.
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Leineweber K, Seyfarth T, Abraham G, Gerbershagen HP, Heinroth-Hoffmann I, Pönicke K, and Brodde OE
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- Animals, Cell Membrane metabolism, Dose-Response Relationship, Drug, Heart Ventricles cytology, Heart Ventricles drug effects, Heart Ventricles metabolism, Male, Myocytes, Cardiac cytology, Myocytes, Cardiac metabolism, Norepinephrine pharmacology, Protein Binding drug effects, Protein Binding physiology, Rats, Rats, Wistar, Cell Membrane drug effects, Monocrotaline pharmacology, Myocytes, Cardiac drug effects, Receptors, Adrenergic, beta metabolism
- Abstract
In monocrotaline (MCT)-treated rats the beta-adrenoceptor-G-protein-adenylyl cyclase system-determined in crude membrane preparations from whole ventricular tissue-was desensitized not only in right (RV) but also in left ventricles (LV). This study aimed to assess the specific contribution of cardiomyocytes to these beta-adrenoceptor changes. Six-week-old male Wistar rats were treated with 60 mg/kg body weight MCT intraperitoneally; within 4-6 weeks, rats developed marked RV hypertrophy. Cardiomyocytes were isolated from RVs and LVs. In RV cardiomyocytes of MCT-treated rats, beta-adrenoceptor density was significantly reduced whereas it was unaltered in LV cardiomyocytes. Reduction of RV cardiomyocyte beta-adrenoceptors was due to a selective beta(1)-adrenoceptor reduction. Isoprenaline (100 microM)-induced cAMP increase was significantly reduced in RV but not in LV cardiomyocytes of MCT-treated rats. G protein-coupled receptor kinase activity was increased in RV but not in LV cardiomyocytes. alpha(1)-Adrenoceptor density and noradrenaline-induced increase in inositol phosphate formation were significantly reduced only in RV but not in LV cardiomyocytes from MCT-treated rats. It is concluded that in cardiomyocytes of MCT-treated rats, cardiac beta-adrenoceptors and alpha -adrenoceptors are chamber-specifically desensitized only in the RV. Thus, changes in cardiac beta-adrenoceptors determined in membrane preparations from whole tissue homogenates do not correctly reflect changes occurring in cardiomyocytes.
- Published
- 2003
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15. Absolute concentrations of high-energy phosphate metabolites in normal, hypertrophied, and failing human myocardium measured noninvasively with (31)P-SLOOP magnetic resonance spectroscopy.
- Author
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Beer M, Seyfarth T, Sandstede J, Landschütz W, Lipke C, Köstler H, von Kienlin M, Harre K, Hahn D, and Neubauer S
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- Adult, Aged, Aged, 80 and over, Aortic Valve Stenosis physiopathology, Bias, Cardiomyopathy, Dilated physiopathology, Case-Control Studies, Energy Metabolism, Female, Humans, Hypertrophy, Left Ventricular etiology, Hypertrophy, Left Ventricular physiopathology, Magnetic Resonance Imaging, Male, Middle Aged, Myocardium metabolism, Stroke Volume, Ventricular Function, Left, Adenosine Triphosphate analysis, Aortic Valve Stenosis diagnosis, Aortic Valve Stenosis metabolism, Cardiomyopathy, Dilated diagnosis, Cardiomyopathy, Dilated metabolism, Hypertension complications, Hypertrophy, Left Ventricular diagnosis, Hypertrophy, Left Ventricular metabolism, Imaging, Three-Dimensional methods, Magnetic Resonance Spectroscopy methods, Myocardium chemistry, Phosphocreatine analysis, Phosphorus Isotopes
- Abstract
Objective: The purpose of the present study was to measure absolute concentrations of phosphocreatine (PCr) and adenosine triphosphate (ATP) in normal, hypertrophied, and failing human heart., Background: Conflicting evidence exists on the extent of changes of high-energy phosphate metabolites in hypertrophied and failing human heart. Previous reports using phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) have quantified metabolites in relative terms only. However, this analysis cannot detect simultaneous reductions., Methods: Four groups of subjects (n = 10 each), were studied: volunteers and patients with hypertensive heart disease (HHD), aortic stenosis, and dilated cardiomyopathy (DCM). Left ventricular (LV) function and mass were measured by cine magnetic resonance imaging. Absolute and relative concentrations of PCr and ATP were determined by (31)P-MRS with spatial localization with optimum point spread function., Results: Left ventricular ejection fraction remained normal in HHD and aortic stenosis, but was severely reduced to 18% in DCM; LV mass was increased by 55%, 79%, and 68% respectively. In volunteers, PCr and ATP concentrations were 8.82 +/- 1.30 mmol/kg wet weight and 5.69 +/- 1.02 mmol/kg wet weight, and the PCr/ATP ratio was 1.59 +/- 0.33. High-energy phosphate levels were unaltered in HHD. In aortic stenosis, PCr was decreased by 28%, whereas ATP remained constant. In DCM, PCr was reduced by 51%, ATP by 35%, and reduction of the PCr/ATP ratio by 25% was of borderline significance (p = 0.06). Significant correlations were observed among energetic and functional variables, with the closest relations for PCr., Conclusions: In human heart failure due to DCM, both PCr and ATP are significantly reduced. Ratios of PCr to ATP underestimate changes of high-energy phosphate levels.
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- 2002
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16. Accidental small bowel perforation after antegrade femoral artery access for percutaneous thromboembolectomy and angioplasty.
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Seyfarth T, Baumgartner I, Triller J, and Dinkel HP
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- Aged, Female, Femoral Artery diagnostic imaging, Hernia, Femoral diagnostic imaging, Humans, Intestinal Perforation diagnostic imaging, Intestine, Small diagnostic imaging, Suction adverse effects, Thromboembolism diagnostic imaging, Tomography, X-Ray Computed, Angioplasty, Balloon adverse effects, Femoral Artery surgery, Hernia, Femoral etiology, Intestinal Perforation etiology, Intestine, Small injuries, Postoperative Complications, Thromboembolism surgery
- Abstract
Purpose: To report a rare complication of antegrade femoral access for percutaneous aspiration thromboembolectomy and transluminal angioplasty., Case Report: A 73-year-old obese woman underwent antegrade femoral aspiration thromboembolectomy for lower limb arterial embolism. Fifteen hours later, she presented with acute abdomen and decreased hemoglobin. Computed tomography showed small bowel obstruction, incarcerated femoral hernia, and free peritoneal air and fluid suggesting bowel perforation. Emergent laparotomy revealed an incarcerated, perforated femoral bowel loop and 4-quadrant peritonitis., Conclusions: Femoral hernia injury is an exceptional complication of vascular interventions. Knowledge of this potential hazard may help to avoid its occurrence.
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- 2002
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17. Changes in alpha(1)-adrenergic vascular reactivity in monocrotaline-treated rats.
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Dhein S, Giessler C, Heinroth-Hoffmann I, Leineweber K, Seyfarth T, and Brodde OE
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- Adrenergic alpha-1 Receptor Agonists, Adrenergic alpha-1 Receptor Antagonists, Adrenergic alpha-Agonists pharmacology, Adrenergic alpha-Antagonists pharmacology, Animals, Clonidine pharmacology, Hypertension, Pulmonary chemically induced, Hypertension, Pulmonary pathology, Hypertrophy, Right Ventricular chemically induced, Hypertrophy, Right Ventricular pathology, In Vitro Techniques, Male, Mesenteric Arteries drug effects, Mesenteric Arteries physiology, Piperazines pharmacology, Pulmonary Artery drug effects, Pulmonary Artery physiology, Rats, Rats, Wistar, Thoracic Arteries drug effects, Thoracic Arteries physiology, Clonidine analogs & derivatives, Hypertension, Pulmonary physiopathology, Hypertrophy, Right Ventricular physiopathology, Monocrotaline toxicity, Norepinephrine pharmacology, Receptors, Adrenergic, alpha-1 physiology, Vasoconstriction drug effects
- Abstract
In rats, injection of monocrotaline (MCT) causes pulmonary hypertension that leads to right ventricular failure. The aim of the present study was to characterize the responses of various vessels (the pulmonary artery, the thoracic aorta and small mesenteric arteries) to noradrenaline (NA; 10(-10)-10(-5) M) and carbachol (10 microM) in MCT-treated rats. For this purpose 6-week-old male Wistar rats ( n=13) were treated with 60 mg/kg MCT i.p. After 4-6 weeks the rats were killed and the heart, lungs and vessels removed and compared with those from age-matched saline-treated control rats ( n=47). First, the alpha(1)-adrenoceptor subtype(s) involved in the vascular NA-responses were characterized in normal rats using the alpha(1)-adrenoceptor subtype-selective antagonists 5-methylurapidil (5-MU; competitive alpha(1A)-adrenoceptor antagonist; 10(-8)-10(-6) M), BMY 7378 (competitive alpha(1D)-adrenoceptor antagonist; 10(-7)-10(-6) M) and chloroethylclonidine (CEC; irreversible alpha(1B)-adrenoceptor antagonist; 30 microM). In the pulmonary artery the pA(2) for BMY 7378 was 7.93, while that for 5-MU could not be calculated. CEC suppressed the NA-induced contraction significantly. In the thoracic aorta, the pA(2) for BMY 7378 was 8.06, while 5-MU was less effective (pA(2) 7.31). CEC again suppressed the NA-induced contraction significantly. In mesenteric arteries, CEC was ineffective whereas 5-MU induced a significant, rightwards shift of the concentration/response curve for NA (pA(2) 8.05). BMY 7378 had a lower pA(2) (6.6). MCT-treated rats developed an increased right ventricular pressure, obliteration of pulmonary vessels and inflammatory lung infiltration. In the pulmonary artery, but not in the thoracic aorta or mesenteric artery of MCT-treated rats NA-induced contraction was attenuated. In addition, carbachol-induced relaxation was reduced in the pulmonary and mesenteric arteries. In conclusion, NA-induced contraction is mediated predominantly by alpha(1A)-adrenoceptors in small mesenteric arteries, by alpha(1D)-adrenoceptors in the thoracic aorta (with a contribution from alpha(1A)- and alpha(1B)-adrenoceptors) and by alpha(1D)- and alpha(1B)-adrenoceptors in pulmonary arteries. MCT leads to reduced NA-responsiveness exclusively in the pulmonary artery that does not, however, account for the development of pulmonary hypertension, and to a more generalized endothelial dysfunction which may contribute to the pathogenesis of pulmonary hypertension in this model.
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- 2002
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18. Presence, distribution and physiological function of adrenergic and muscarinic receptor subtypes in the human heart.
- Author
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Brodde OE, Bruck H, Leineweber K, and Seyfarth T
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- Humans, Receptors, Adrenergic analysis, Receptors, Muscarinic analysis, Heart physiology, Myocardium chemistry, Receptors, Adrenergic physiology, Receptors, Muscarinic physiology
- Abstract
The sympathetic and parasympathetic nervous system play a powerful role in controlling cardiac function by activating adrenergic and muscarinic receptors. In the human heart there exist alpha1-, beta1- and beta2-adrenoceptors and M2-muscarinic receptors and possibly also (prejunctional) alpha2-adrenoceptors. Beta1- and beta2-adrenoceptors are quite evenly distributed in the human heart while M2-receptors are heterogeneously distributed (more receptors in atria than in ventricles). Stimulation of beta1- and beta2-adrenoceptors causes increases in heart rate and force of contraction while stimulation of M2-receptors decreases heart rate (directly in atria) and force of contraction (indirectly in ventricles). Pathological situations (such as heart failure) or pharmacological interventions (for example, beta-blocker treatment) can alter the distribution of beta1- and beta2-adrenoceptors in the human heart, while M2-receptors are only marginally affected. On the other hand, relatively little is known on distribution and functional role of alpha1- and alpha2-adrenoceptor subtypes in the human heart.
- Published
- 2001
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19. Noradrenaline-induced increase in protein synthesis in adult rat cardiomyocytes: involvement of only alpha1A-adrenoceptors.
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Pönicke K, Schlüter KD, Heinroth-Hoffmann I, Seyfarth T, Goldberg M, Osten B, Piper HM, and Brodde OE
- Subjects
- Adrenergic alpha-1 Receptor Antagonists, Animals, Cells, Cultured, Drug Interactions, Enzyme Inhibitors pharmacology, Flavonoids pharmacology, Heart drug effects, Inositol Phosphates biosynthesis, Male, Myocardium metabolism, Rats, Ribosomal Protein S6 Kinases antagonists & inhibitors, Sirolimus pharmacology, Norepinephrine pharmacology, Protein Biosynthesis, Receptors, Adrenergic, alpha-1 drug effects
- Abstract
Adult rat ventricular cardiomyocytes contain alpha1A- and alpha1B-adrenoceptors (ARs, 20%:80%, assessed by [3H]prazosin binding). We studied which alpha1-AR subtype mediates noradrenaline (NA)-induced increase in rate of protein synthesis, and which signalling pathway is involved. NA (10-9-10-4 M) concentration-dependently increased inositol phosphate (IP) formation (pEC50-value=6.1+/-0.1, n=5) and protein synthesis (assessed as [3H]phenylalanine incorporation; pEC50-value=6.6+/-0.1, n=6). NA-induced IP-formation was partly inhibited by the alpha1B-AR antagonist chloroethylclonidine (CEC, 30 microM; 33+/-9% inhibition, n=5); following CEC-treatment the alpha1A-AR-selective 5-methyl-urapidil (5-MU) inhibited NA-induced IP-formation with a pKi-value of 9.2+/-0.2 (n=6); the alpha1D-AR-selective BMY 7378 was only a weak antagonist (pKi-value <7). NA-induced increase in protein synthesis was insensitive to CEC whereas 5-MU inhibited it with a pKi-value of 9.1+/-0.2 (n=6). NA (1 microM)-induced increase in protein synthesis was inhibited by the protein kinase C (PKC) inhibitor bisindolylmaleimide (IC50-value: 206 nM), the PI 3-kinase inhibitors wortmannin (IC50=3.4 nM) and LY 294002 (IC50=10 microM), and p70s6-kinase inhibitor rapamycin (IC50=123 pM) but not by the p38 MAP-kinase inhibitor SB 203580 (10 microM) or the MEK-inhibitor PD 98059 (25 microM). Moreover, 5-MU (30 nM) but not CEC inhibited NA-induced activation of p70s6-kinase. We conclude that, in adult rat cardiomyocytes, alpha1A- and alpha1B-AR mediate NA-induced IP-formation but only alpha1A-ARs mediate increase in protein synthesis. Alpha1A-AR-mediated increase in protein synthesis involves activation of a PKC, PI 3-kinase and p70s6-kinase but not of ERK- or p38 MAP-kinase.
- Published
- 2001
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20. The cardiac beta-adrenoceptor-G-protein(s)-adenylyl cyclase system in monocrotaline-treated rats.
- Author
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Seyfarth T, Gerbershagen HP, Giessler C, Leineweber K, Heinroth-Hoffmann I, Pönicke K, and Brodde OE
- Subjects
- Animals, Blood Pressure drug effects, Blotting, Western, Body Weight drug effects, Disease Models, Animal, Dose-Response Relationship, Drug, Humans, Kinetics, Male, Myocardium enzymology, Myocardium metabolism, Rats, Rats, Wistar, Receptors, Muscarinic metabolism, Time Factors, Adenylyl Cyclases metabolism, Cardiomegaly metabolism, GTP-Binding Proteins metabolism, Monocrotaline pharmacology, Receptors, Adrenergic, beta metabolism
- Abstract
In rats, injection of the alkaloid monocrotaline (MCT) causes right ventricular hypertrophy and cardiac failure. In order to study whether, in MCT-treated rats, changes in the cardiac beta -adrenoceptor-G-protein(s)-adenylyl cyclase system might be comparable to those found in human primary pulmonary hypertension, we assessed in right and left ventricles from MCT-treated rats the components of the beta -adrenoceptor system: the receptor number and subtype distribution (by (-)-[(125)I]iodocyanopindolol binding), the G-proteins (by quantitative Western blotting), and the activity of adenylyl cyclase. A single injection of 60 mg/kg i.p. MCT caused in rats right ventricular hypertrophy (RVH); part of the rats developed cardiac failure (RVF). In these rats the cardiac beta -adrenoceptor-G-protein(s)-adenylyl cyclase system was markedly changed beta -adrenoceptors were desensitized due to a decrease in receptor number, an uncoupling of the receptor from the G(s)-adenylyl cyclase system, a decrease in G(s)and a decrease in the activity of the catalytic unit of adenylyl cyclase. In general, these changes were more pronounced in right ventricles v left ventricles, and in rats with RVF v rats with RVH. On the other hand, cardiac muscarinic receptors and G(i)appeared not to be altered. We conclude that in MCT-treated rats changes in the cardiac beta -adrenoceptor-G-protein(s)-adenylyl cyclase system occur that resemble those observed in human primary pulmonary hypertension. Thus, MCT-treated rat appears to be a suitable animal model to study in more detail the pathophysiology of the development of right heart failure, and to identify new therapeutic possibilities., (Copyright 2000 Academic Press.)
- Published
- 2000
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21. Chamber-specific alterations of noradrenaline uptake (uptake(1)) in right ventricles of monocrotaline-treated rats.
- Author
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Leineweber K, Seyfarth T, and Brodde OE
- Subjects
- Adrenergic Uptake Inhibitors pharmacology, Animals, Binding, Competitive drug effects, Cocaine pharmacology, Desipramine pharmacology, Dopamine Uptake Inhibitors pharmacology, Dose-Response Relationship, Drug, Fluoxetine analogs & derivatives, Fluoxetine metabolism, Fluoxetine pharmacology, Heart Failure chemically induced, Heart Failure metabolism, Heart Ventricles metabolism, Heart Ventricles pathology, Hypertrophy, In Vitro Techniques, Male, Membranes drug effects, Membranes metabolism, Norepinephrine antagonists & inhibitors, Piperazines pharmacology, Rats, Rats, Wistar, Tritium, Heart Ventricles drug effects, Monocrotaline pharmacology, Norepinephrine pharmacokinetics
- Abstract
1. In rats a single injection of the alkaloid monocrotaline (60 mg MCT kg(-1) body weight, i.p.) caused right ventricular hypertrophy and heart failure. The aim of this study was to find out whether, in these MCT-treated rats, the cardiac neuronal noradrenaline uptake (uptake(1)) might undergo chamber-specific alterations. 2. For this purpose we assessed in right and left ventricular slices, uptake(1) activity (by [(3)H]-noradrenaline accumulation), and in right and left ventricular membranes, uptake(1) carrier protein density (by [(3)H]-nisoxetine binding). 3. Uptake(1)-inhibitors blocked [(3)H]-noradrenaline accumulation in ventricular slices and [(3)H]-nisoxetine binding in ventricular membranes with the order of potency: desipramine > nisoxetine >> cocaine > or = GBR 12909, indicating that with both approaches noradrenaline uptake(1) was determined. 4. In right ventricular slices of MCT-treated rats uptake(1) activity was significantly lower than in control rats (84.7+/-8.2 vs 145.1+/-6.2 pmol noradrenaline mg(-1) tissue 15 min(-1); P<0.05). This was accompanied by a significant decrease in the density of [(3)H]-nisoxetine binding sites (73.7+/-14.4 vs 125.9+/-9.1 fmol mg(-1) protein; P:<0.05). 5. In left ventricular slices of MCT-treated rats uptake(1) activity was not significantly altered (131.2+/-10.5 vs 116.1+/-5.2 pmol noradrenaline mg(-1) tissue 15 min(-1)); similarly, also the density of [(3)H]-nisoxetine binding sites was unchanged (108+/-9.7 vs 123+/-7.7 fmol mg(-1) protein). 6. We conclude that in MCT-treated rats with right ventricular hypertrophy and heart failure uptake(1) activity is chamber-specifically reduced possibly due to a decrease in carrier protein density.
- Published
- 2000
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- View/download PDF
22. Absolute quantification of high energy phosphate metabolites in normal, hypertrophied and failing human myocardium.
- Author
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Neubauer S, Beer M, Landschütz W, Sandstede J, Seyfarth T, Lipke C, Köstler H, Pabst TKenn W, Meininger M, von Kienlin M, Horn M, Harre K, and Hahn D
- Subjects
- Adenosine Triphosphate metabolism, Aortic Valve Stenosis metabolism, Humans, Hypertension metabolism, Phosphocreatine metabolism, Cardiomyopathy, Dilated metabolism, Hypertrophy, Left Ventricular metabolism, Myocardium metabolism, Phosphates metabolism
- Published
- 2000
- Full Text
- View/download PDF
23. [Cardiac energy metabolism in heart valve diseases with 31P MR spectroscopy].
- Author
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Beer M, Viehrig M, Seyfarth T, Sandstede J, Lipke C, Pabst T, Kenn W, Harre K, Horn M, Landschütz W, von Kienlin M, Neubauer S, and Hahn D
- Subjects
- Adult, Aged, Aortic Valve Stenosis diagnosis, Aortic Valve Stenosis surgery, Female, Heart Valve Prosthesis Implantation, Humans, Magnetic Resonance Imaging, Cine, Male, Middle Aged, Postoperative Complications diagnosis, Postoperative Complications physiopathology, Reference Values, Treatment Outcome, Ventricular Function, Left physiology, Aortic Valve Stenosis physiopathology, Energy Metabolism physiology, Magnetic Resonance Spectroscopy, Myocardium metabolism, Phosphates metabolism
- Abstract
Purpose: Heart valve disease combined with left ventricular hypertrophy leads to derangements in cardiac energy metabolism, which can be detected non-invasively by 31P-MR-spectroscopy. The purpose of the present study was to examine whether the derangements in cardiac metabolism are reversible after surgical valve replacement., Patients and Methods: 10 healthy volunteers and 10 patients with aortic stenosis (pressure gradients > 60 mmHg) were included. For assessment of energy metabolism, 31P-MR spectra were obtained with a double oblique 3D-CSI technique (voxel size 25 cm3). In 5 of 10 patients, follow-up examination was performed 3 months after surgical valve replacement (SVR). Left ventricular (LV) function was analyzed by cine MRI., Results: Before SVR the myocardial phosphocreatine to adenosinetriphosphate (PCr-ATP) ratio was significantly (p = 0.0002) reduced to 0.80 +/- 0.25 in patients compared to 1.65 +/- 0.21 in volunteers. 3 months after SVR, LV mass had significantly (p = 0.04) decreased from 238 +/- 33 g to 206 +/- 47 g. At the same time a significant (p = 0.04) increase of the PCr-ATP ratio from 0.80 +/- 0.25 to 1.28 +/- 0.22 was observed. A slight, but not significant, reduction of the phosphodiester ATP ratio was observed before SVR, with a trend towards normalization after SVR., Conclusions: After SVR, the deranged energy metabolism shows a trend towards normalization. Further follow-up is necessary to determine whether complete normalization of the energetic derangement can be observed over longer periods of time following SVR.
- Published
- 2000
- Full Text
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24. [The quantification of energy-rich phosphates in healthy and damaged heart muscle by SLOOP 31P-MR spectroscopy. Spatial localization with optimal pointspread function].
- Author
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Beer M, Landschütz W, Meininger M, Seyfarth T, Viehrig M, Sandstede J, Pabst T, Kenn W, Horn M, Harre K, von Kienlin M, Neubauer S, and Hahn D
- Subjects
- Adenosine Triphosphate analysis, Electrocardiography, Energy Metabolism, Humans, Magnetic Resonance Spectroscopy instrumentation, Phosphocreatine analysis, Cardiomyopathy, Dilated metabolism, Hypertension metabolism, Hypertrophy, Left Ventricular metabolism, Magnetic Resonance Spectroscopy methods, Myocardial Ischemia metabolism, Myocardium metabolism, Phosphates analysis
- Abstract
Purpose: A quantitative 31P-MR-spectroscopic technique was used to assess the energy metabolism in healthy and diseased myocardium., Methods: 31P spectra were acquired on a 1.5 T scanner using a 3D-chemical shift imaging technique. Based on the anatomical information provided by 1H images, SLOOP (Spatial Localization with Optimal Pointspread Function) allows to obtain spectra from defined compartments. With SLOOP a free voxel shape with adaption to anatomic structures, e.g. the myocardium, is possible. Absolute values for phosphocreatine (PCr) and adenosine triphosphate (ATP) were determined using an external standard., Results: 31P-spectra showed only minimal contamination by surrounding tissue. The standard deviation for the determined values of healthy volunteers was low. Compared to healthy volunteers, reduced PCr and ATP concentrations were seen for dilative cardiomyopathies and coronary artery disease and unchanged concentrations were observed for hypertensive heart disease., Conclusion: 31P-MR spectroscopy with SLOOP allows a non-invasive, quantitative analysis of cardiac energy metabolism.
- Published
- 1999
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- View/download PDF
25. Concentrations of human cardiac phosphorus metabolites determined by SLOOP 31P NMR spectroscopy.
- Author
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Meininger M, Landschütz W, Beer M, Seyfarth T, Horn M, Pabst T, Haase A, Hahn D, Neubauer S, and von Kienlin M
- Subjects
- Adult, Humans, Phantoms, Imaging, Phosphorus Radioisotopes, Tissue Distribution, Adenosine Triphosphate analysis, Magnetic Resonance Spectroscopy methods, Myocardium chemistry, Phosphocreatine analysis
- Abstract
Human cardiac 31P nuclear magnetic resonance (NMR) spectra are usually quantified in relative terms, i.e., the ratio of metabolite signals is calculated. If 31P NMR spectroscopy of the heart is to emerge as a clinically relevant diagnostic modality, reliable quantification of absolute concentrations of 31P metabolites is required. We applied spectral localization with optimal point spread function (SLOOP) 31P NMR spectroscopy to measure absolute concentrations of phosphocreatine (PCr) and adenosine triphosphate (ATP) in human myocardium. The accuracy of the quantification was first validated in a phantom study. Seven healthy volunteers (aged 19-29 years) were then examined at 1.5 T using a nominal spatial resolution of 25 mL. SLOOP allowed us to obtain localized spectra from compartments anatomically matched to the left ventricular wall. The a priori knowledge of the anatomical structure was obtained from 1H images. The spatially varying effects of saturation, off-resonance, and sensitivity were considered during the reconstruction process. Metabolites were quantified with reference to an external 31P standard. Concentrations of 9.0 +/- 1.2 and 5.3 +/- 1.2 mmol/kg wet wt (mean +/- SD, n = 9) were determined for PCr and ATP in normal heart, respectively. The influence of nuclear Overhauser enhancement on metabolite quantification is discussed.
- Published
- 1999
- Full Text
- View/download PDF
26. Concentration of human cardiac 31P-metabolites determined by SLOOP 31P-MRS.
- Author
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Landschütz W, Meininger M, Beer M, Seyfarth T, Horn M, Pabst T, Haase A, Hahn D, Neubauer S, and von Kienlin M
- Subjects
- Adult, Humans, Phosphorus, Adenosine Triphosphate metabolism, Myocardium metabolism, Nuclear Magnetic Resonance, Biomolecular methods, Phosphocreatine metabolism
- Published
- 1998
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