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Publications (5)11.96 Total impact

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    ABSTRACT: Myocardial perfusion imaging with (99m)Tc-tetrofosmin is based on the assumption of a linear correlation between myocardial blood flow (MBF) and tracer uptake. However, it is known that (99m)Tc-tetrofosmin uptake is directly related to energy-dependent transport processes, such as Na(+)/H(+) ion channel activity, as well as cellular and mitochondrial membrane potentials. Therefore, cellular alterations that affect these energy-dependent transport processes ought to influence (99m)Tc-tetrofosmin uptake independently of blood flow. Because metabolism ((18)F-FDG)-perfusion ((99m)Tc-tetrofosmin) mismatch myocardium (MPMM) reflects impaired but viable myocardium showing cellular alterations, MPMM was chosen to quantify the blood flow-independent effect of cellular alterations on (99m)Tc-tetrofosmin uptake. Therefore, we compared microsphere-equivalent MBF (MBF_micr; (15)O-water PET) and (99m)Tc-tetrofosmin uptake in MPMM and in "normal" myocardium. Forty-two patients with severe coronary artery disease, referred for myocardial viability diagnostics, were examined using (18)F-FDG PET and (99m)Tc-tetrofosmin perfusion SPECT. Relative (18)F-FDG and (99m)Tc-tetrofosmin uptake values were calculated using 18 segments per patient. Normal myocardium and MPMM myocardium were classified using a previously validated (99m)Tc-tetrofosmin SPECT/(18)F-FDG PET score. In addition, (15)O-water PET was performed to assess kinetic-modeled MBF (MBF_kin), the water-perfusable tissue fraction (PTF), and the resulting MBF_micr (MBF_kin x PTF), which is comparable to tracer uptake values. (99m)Tc-tetrofosmin uptake and MBF_micr values were calculated for all normal and MPMM segments and averaged within their respective classifications. Mean relative (99m)Tc-tetrofosmin uptake was 86% +/- 1% in normal myocardium and 56% +/- 1% in MPMM, showing a significant difference (P < 0.001), as was expected from the classification. Contrary to these findings, mean MBF_micr in MPMM myocardium was 0.60 +/- 0.03 mL x min(-1) x mL(-1), which did not significantly differ from normal myocardium (0.64 +/- 0.01 mL x min(-1) x mL(-1)). All values are given as mean +/- SEM. Differences between reduced (99m)Tc-tetrofosmin uptake and the unchanged MBF_micr in MPMM myocardium suggest that the pathophysiologic basis of MPMM is not a blood flow reduction but cellular alterations that affect uptake and retention of (99m)Tc-tetrofosmin independently of blood flow. Therefore, it seems that perfusion deficits in MPMM myocardium are greatly overestimated by (99m)Tc-tetrofosmin and that it tends to give false-positive findings.
    Journal of Nuclear Medicine 01/2003; 44(1):33-9. · 5.77 Impact Factor
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    ABSTRACT: There is controversy about the role of decreased resting blood flow as the pathophysiologic correlate of hibernating myocardium. The aim of this study was an absolute quantification of volumetric myocardial blood flow (MBFvol) in dysfunctional myocardium with different viability conditions as defined by fluorine 18 deoxyglucose (FDG) positron emission tomography (PET) while taking into consideration the functional recovery after revascularization. The impact of MBFvol in the diagnosis of functional recovery was also investigated. Forty-two patients with severe coronary artery disease and dysfunctional myocardium underwent resting oxygen 15 water PET, as well as FDG PET and technetium 99m tetrofosmin single photon emission computed tomography, all attenuation-corrected. Relative FDG and Tc-99m tetrofosmin uptake (normalized to the segment with 100% Tc-99m tetrofosmin uptake), as well as MBFvol (myocardial blood flow multiplied by the water-perfusable tissue fraction to account for the flow to the entire segment volume), were determined in 18 myocardial segments per patient. Viability in dysfunctional segments (estimated by ventriculography) with reduced Tc-99m tetrofosmin uptake of 70% or lower was classified as viable (FDG >70%, mismatch) or nonviable (FDG < or =70%, match). Fifteen patients underwent revascularization and were followed up. Mismatch segments with improved function were classified as hibernating myocardium. Mean MBFvol in viable myocardium was slightly reduced (0.60 +/- 0.02 mL x min(-1) x mL(-1)) compared with that in normokinetic myocardium (0.64 +/- 0.01 mL x min(-1) x mL(-1)) (P = .036) and was significantly higher than in nonviable myocardium (0.36 +/- 0.01 mL x min(-1) x mL(-1)) (P < .001). Receiver operating characteristic analysis confirmed an FDG uptake greater than 70% as the optimal threshold to predict functional recovery (diagnostic accuracy [ACC], 76%). MBFvol in hibernating myocardium (0.62 +/- 0.04 mL x min(-1) x mL(-1)) was not significantly reduced compared with that in normokinetic myocardium (0.66 +/- 0.02 mL x min(-1) x mL(-1)) and was significantly higher than in persistently dysfunctional myocardium (0.51 +/- 0.04 mL x min(-1) x mL(-1)) (P < .05). The ACC of MBFvol greater than 0.40 mL x min(-1) x mL(-1) as the threshold to predict functional recovery was 61% but did not improve the accuracy of FDG PET by itself. In patients with severe coronary artery disease and dysfunctional myocardium, MBFvol as determined with O-15 water differs significantly between viable and nonviable myocardium as determined by FDG PET and is not significantly reduced in hibernating compared with normokinetic myocardium. Therefore chronically reduced resting blood flow appears unlikely to be the pathophysiologic correlate of the functional state of hibernation. However, MBFvol does not improve the ACC of FDG PET by itself.
    Journal of Nuclear Cardiology 01/2003; 10(1):34-45. · 2.85 Impact Factor
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    ABSTRACT: In the present study a new approach has been developed for comparative quantification of absolute myocardial blood flow (MBF), myocardial perfusion, and myocardial metabolism in short-axis slices. 42 patients with severe CAD, referred for myocardial viability diagnostics, were studied consecutively with 0-15-H2O PET (H2O-PET) (twice), Tc-99m-Tetrofosmin SPECT (TT-SPECT) and F-18-FDG PET (FDG-PET). All data sets were reconstructed using attenuation correction and reoriented into short axis slices. Each heart was divided into three representative slices (base, midventricular, apex) and 18 ROIs were defined on the FDG PET images and transferred to the corresponding H2O-PET and TT-SPECT slices. TT-SPECT and FDG-PET data were normalized to the ROI showing maximum perfusion. MBF was calculated for all left-ventricular ROIs using a single-compartment-model fitting the dynamic H2O-PET studies. Microsphere equivalent MBF (MBF_micr) was calculated by multiplying MBF and tissue-fraction, a parameter which was obtained by fitting the dynamic H2O-PET studies. To reduce influence of viability only well perfused areas (> 70% TT-SPECT) were used for comparative quantification. First and second mean global MBF values were 0.85 ml x min-1 x g-1 and 0.84 ml x min-1 x g-1, respectively, with a repeatability coefficient of 0.30 ml x min-1 x g-1. After sectorization mean MBF_micr was between 0.58 ml x min-1 x ml-1 and 0.68 ml x min-1 x ml-1 in well perfused areas. Corresponding TT-SPECT values ranged from 83% to 91%, and FDG-PET values from 91% to 103%. All procedures yielded higher values for the lateral than the septal regions. Comparative quantification of MBF, MBF_micr, TT-SPECT perfusion and FDG-PET metabolism can be done with the introduced method in short axis slices. The obtained values agree well with experimentally validated values of MBF and MBF_micr.
    Nuklearmedizin 10/2001; 40(5):164-71. · 1.67 Impact Factor
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    ABSTRACT: Aim of this study was a characterization of radioiodine therapy (RIT) failures in Graves' disease without simultaneous carbimazole. 226 patients with a confirmed diagnosis of Graves' disease received 686.8 +/- 376.4 MBq of iodine-131 orally for thyroid ablation. Target dose was 250 Gy. All patients were followed up for 6 months. Therapy failures were compared with successes regarding possible influencing variables initial thyroid volume, thyroid function, immune activity (TRAb), I-131 uptake, effective half-life, absorbed energy dose, age and gender. 212 of 226 patients (93.8%) were treated successfully, 14 (6.2%) showed a hyperthyroidism relapse within 6 months which required a second radioiodine therapy. A success rate of 92.5% (62/67) could also be achieved with 67 patients who were hyperthyroid at the time of RIT. Compared to the therapy successes, the 14 failures achieved significantly lower absorbed doses (223.8 +/- 76.6 Gy vs. 285.2 +/- 82.1 Gy, p < 0.005), but with no significant differences regarding age, thyroid volume, function or TRAb (all p > 0.2). Of the 14 failures, n = 8 reached an absorbed dose < 200 Gy and n = 1 a dose < 250 Gy, although 5 of the failures reached an absorbed dose of > 250 Gy. Stepwise logistic regression revealed only absorbed energy dose as a variable significantly influencing therapy success (p < 0.005), but no influence of initial thyroid volume, function, TRAb value, age (all p > 0.2) or gender (p = 0.13). Two-tailed Fisher's exact test showed no significant influence of gender on success rates (failures/successes: male 1/36, female 13/176, p = 0.48). Except for the absorbed energy dose, no other significant variable influencing the outcome of radioiodine therapy in Graves' disease without simultaneous carbimazole could be found. It should be noted, though, that 5 therapy failures (2.2%) reached an absorbed energy dose of > 250 Gy.
    Nuklearmedizin 03/2001; 40(1):1-6. · 1.67 Impact Factor
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    ABSTRACT: Radioactive stents have been proposed as endovascular irradiation device to prevent in-stent restenosis by inhibiting neointimal proliferation. 32P-stents have been used in several studies so far, but require large-scale labeling procedures and endovascular barotrauma for stent expansion supporting the development of edge restenosis. Purpose of this study was to establish dosimetry of a self-expanding nitinol stent for peripheral vascular disease, which was radiolabeled with 188rhenium (188Re) by a dip coating technique. The surface of nitinol Memotherm FLEXX stents was polymer-coated providing functional NH(2) groups for diethylenetriaminepentaacetic acid (DTPA) binding, providing the ligand for the complexation of 188Re onto the stent surface. Stability of radiolabeling was tested over 48 h using an in vitro blood circulation (Chandler Loop). Radial and longitudinal dose distributions of a radiolabeled stent were obtained with a plastic scintillator dosimetry system. Stents with a length of 30 mm and a diameter of 8 mm were labeled with up to 33 MBq 188Re. A total of 69+/-4% of the labeled 188Re remained stable on the stent surface after 48 h. Ninety-five percent of the infinitely accumulated dose was supplied to the target tissue within 72 h. Including correction for radioactivity washout from the stent, the infinitely accumulated dose at 1 mm radial distance from the stent surface was 1.85+/-0.19 Gy/MBq 188Re/cm stent length. We developed a technique for radiolabeling of self-expanding nitinol stents with 188Re by dip coating and formation of 188Re chelate complexes. We provide dosimetry data useful for application of this beta-emitting stent for endovascular brachytherapy in peripheral vascular occlusive disease.
    Cardiovascular Radiation Medicine 01/2001; 2(4):246-53.