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Biomedical subjects

Wolfgang M Schaefer

Publications and source records attributed to Wolfgang M Schaefer.

18 recordsLinked to original sources

Quantification of left ventricular volumes and ejection fraction from gated 99mTc-MIBI SPECT: validation of an elastic surface model approach in comparison to cardiac magnetic resonance imaging, 4D-MSPECT and QGS.

PURPOSE: The segmentation algorithm ESM based on an elastic surface model was validated for the assessment of left ventricular volumes and ejection fraction from ECG-gated myocardial perfusion SPECT. Additionally, it was compared with the commercially available quantification packages 4D-MSPECT and QGS. Cardiac MRI was used as the reference method. METHODS: SPECT and MRI were performed on 70 consecutive patients with suspected or proven coronary artery disease. End-diastolic (EDV) and end-systolic (ESV) volumes and left ventricular ejection fraction (LVEF) were derived from SPECT studies by using the segmentation algorithms ESM, 4D-MSPECT and QGS and from cardiac MRI. RESULTS: ESM-derived values for EDV and ESV correlated well with those from cardiac MRI (correlation coefficients R=0.90 and R=0.95, respectively), as did the measurements for LVEF (R=0.86). Both EDV and ESV were slightly overestimated for larger ventricles but not for smaller ventricles; LVEF was slightly overestimated irrespective of ventricle size. The above correlation coefficients are comparable to those for the 4D-MSPECT and QGS segmentation algorithms. However, results obtained with the three segmentation algorithms are not interchangeable. CONCLUSION: The ESM algorithm can be used to assess EDV, ESV and LVEF from gated perfusion SPECT images. Overall, the performance was similar to that of 4D-MSPECT and QGS when compared with cardiac MRI. Results obtained with the three tested segmentation methods are not interchangeable, so that the same algorithm should be used for follow-up studies and control subjects.

Adult↗

Indium-111 oxine labelling affects the cellular integrity of haematopoietic progenitor cells.

PURPOSE: Cell-based therapy by transplantation of progenitor cells has emerged as a promising development for organ repair, but non-invasive imaging approaches are required to monitor the fate of transplanted cells. Radioactive labelling with (111)In-oxine has been used in preclinical trials. This study aimed to validate (111)In-oxine labelling and subsequent in vivo and ex vivo detection of haematopoietic progenitor cells. METHODS: Murine haematopoietic progenitor cells (10(6), FDCPmix) were labelled with 0.1 MBq (low dose) or 1.0 MBq (high dose) (111)In-oxine and compared with unlabelled controls. Cellular retention of (111)In, viability and proliferation were determined up to 48 h after labelling. Labelled cells were injected into the cavity of the left or right cardiac ventricle in mice. Scintigraphic images were acquired 24 h later. Organ samples were harvested to determine the tissue-specific activity. RESULTS: Labelling efficiency was 75 +/- 14%. Cellular retention of incorporated (111)In after 48 h was 18 +/- 4%. Percentage viability after 48 h was 90 +/- 1% (control), 58 +/- 7% (low dose) and 48 +/- 8% (high dose) (p<0.0001). Numbers of viable cells after 48 h (normalised to 0 h) were 249 +/- 51% (control), 42 +/- 8% (low dose) and 32 +/- 5% (high dose) (p<0.0001). Cells accumulated in the spleen (86.6 +/- 27.0% ID/g), bone marrow (59.1 +/- 16.1% ID/g) and liver (30.3 +/- 9.5% ID/g) after left ventricular injection, whereas most of the cells were detected in the lungs (42.4 +/- 21.8% ID/g) after right ventricular injection. CONCLUSION: Radiolabelling of haematopoietic progenitor cells with (111)In-oxine is feasible, with high labelling efficiency but restricted stability. The integrity of labelled cells is significantly affected, with substantially reduced viability and proliferation and limited migration after systemic transfusion.

Animals↗

Assessment of reversible myocardial dysfunction in chronic ischaemic heart disease: comparison of contrast-enhanced cardiovascular magnetic resonance and a combined positron emission tomography-single photon emission computed tomography imaging protocol.

AIMS: The aim of the study was to compare, in patients with chronic ischaemic cardiomyopathy, contrast-enhanced cardiovascular magnetic resonance (ce-CMR) imaging and a combined (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and (99m)Tc-sestamibi single-photon emission computed tomography (SPECT) protocols for the prediction of functional recovery after revascularization, as assessed by cine CMR. METHODS AND RESULTS: Twenty-nine patients with ischaemic cardiomyopathy (ejection fraction 32 +/- 10%) were investigated with ce-CMR and PET/SPECT. For the assessment of global and regional functions, cine CMR was performed at baseline and at 6 months follow-up. For ce-CMR, the segmental extent of hyperenhancement (SEH) was quantitated, and for PET/SPECT, different viability categories were defined according to a validated quantitative protocol. Functional improvement was related to the SEH by ce-CMR, as well as to the viability categories by PET/SPECT. Sensitivity and specificity for the prediction of functional recovery at follow-up was 97 and 68% for ce-CMR and 87 and 76% for PET/SPECT. The positive predictive value was identical for both techniques (73%). However, ce-CMR achieved a higher negative predictive value (93 vs. 77%, respectively), indicating that ce-CMR may be superior to PET/SPECT for the identification of segments unlikely to recover function after revascularization. Both methods had a similar yield in the prediction of global functional improvement. CONCLUSION: ce-CMR is comparable with a PET/SPECT imaging protocol for the prediction of regional and global functional improvement after revascularization. However, ce-CMR may be superior to nuclear imaging for the identification of segments that are unlikely to recover function at follow-up.

Chronic Disease↗

Effect of catheter-based transendocardial delivery of stromal cell-derived factor 1alpha on left ventricular function and perfusion in a porcine model of myocardial infarction.

BACKGROUND: Myocardial regeneration after myocardial infarction can occur via stem cell recruitment. Stromal cell-derived factor 1alpha (SDF-1alpha) has been shown to be critical for stem cell homing to injured tissue. METHODS: Myocardial infarction was induced in pigs via microembolization of the distal left anterior descending artery. Two weeks after myocardial infarction animals underwent catheter-based transendocardial injection of SDF-1alpha into the periinfarct myocardium (18 injections, 5 ìg per injection) (n = 12) or sham-intervention (n = 8). Tc99m sestamibi single-photon emission computed tomography (SPECT) and electromechanical mapping (EMM) of the left ventricle were performed two and seven weeks after myocardial infarction. RESULTS: Infarct size by tetrazolium staining was similar in both groups (8.9 +/-1.2% of left ventricle vs. 8.9 +/- 2.6%). Vessel density in the periinfarct area was significantly higher in SDF-1alpha treated animals than in controls (349 +/- 17/mm2 vs. 276 +/- 21/mm2, p < 0.05). Myocardial perfusion (SPECT) did not change in either group. Ejection fraction and stroke volume (EMM) decreased in SDF-1alpha animals and increased in controls (difference between groups p = 0.05 for ejection fraction and p < 0.05 for stroke volume). Linear local shortening (EMM) did not change in controls (11.4 +/- 1.3% to 11.5 +/- 0.5%) but decreased significantly in SDF-1alpha treated animals (12.1 +/- 0.9% to 8.4 +/- 0.9%, p < 0.05, p < 0.05 for difference between groups). SDF-1 delivery was associated with a substantial loss of collagen in the periinfarct area (32+/-5% vs. 61+/-6% in control animals, p < 0.005). CONCLUSION: A strategy to augment stem cell homing by catheter-based transendocardial delivery of SDF-1alpha in experimental myocardial infarction increases periinfarct vessel density, fails to improve myocardial perfusion, is associated with loss of collagen in the periinfarct area and impairs left ventricular function.

Animals↗

Quantification of left ventricular volumes and ejection fraction from gated 99mTc-MIBI SPECT: MRI validation and comparison of the Emory Cardiac Tool Box with QGS and 4D-MSPECT.

UNLABELLED: The goal of this study was to validate the accuracy of the Emory Cardiac Tool Box (ECTB) in assessing left ventricular end-diastolic or end-systolic volume (EDV, ESV) and ejection fraction (LVEF) from gated (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) SPECT using cardiac MRI (cMRI) as a reference. Furthermore, software-specific characteristics of ECTB were analyzed in comparison with 4D-MSPECT and Quantitative Gated SPECT (QGS) results (all relative to cMRI). METHODS: Seventy patients with suspected or known coronary artery disease were examined using gated (99m)Tc-MIBI SPECT (8 gates/cardiac cycle) 60 min after tracer injection at rest. EDV, ESV, and LVEF were calculated from gated (99m)Tc-MIBI SPECT using ECTB, 4D-MSPECT, and QGS. Directly before or after gated SPECT, cMRI (20 gates/cardiac cycle) was performed as a reference. EDV, ESV, and LVEF were calculated using Simpson's rule. RESULTS: Correlation between results of gated (99m)Tc-MIBI SPECT and cMRI was high for EDV (R = 0.90 [ECTB], R = 0.88 [4D-MSPECT], R = 0.92 [QGS]), ESV (R = 0.94 [ECTB], R = 0.96 [4D-MSPECT], R = 0.96 [QGS]), and LVEF (R = 0.85 [ECTB], R = 0.87 [4D-MSPECT], R = 0.89 [QGS]). EDV (ECTB) did not differ significantly from cMRI, whereas 4D-MSPECT and QGS underestimated EDV significantly compared with cMRI (mean +/- SD: 131 +/- 43 mL [ECTB], 127 +/- 42 mL [4D-MSPECT], 120 +/- 38 mL [QGS], 137 +/- 36 mL [cMRI]). For ESV, only ECTB yielded values that were significantly lower than cMRI. For LVEF, ECTB and 4D-MSPECT values did not differ significantly from cMRI, whereas QGS values were significantly lower than cMRI (mean +/- SD: 62.7% +/- 13.7% [ECTB], 59.0% +/- 12.7% [4DM-SPECT], 53.2% +/- 11.5% [QGS], 60.6% +/- 13.9% [cMRI]). CONCLUSION: EDV, ESV, and LVEF as determined by ECTB, 4D-MSPECT, and QGS from gated (99m)Tc-MIBI SPECT agree over a wide range of clinically relevant values with cMRI. Nevertheless, any algorithm-inherent over- or underestimation of volumes and LVEF should be accounted for and an interchangeable use of different software packages should be avoided.

Adult↗

Prognostic value of endocardial electromechanical mapping in patients with left ventricular dysfunction undergoing percutaneous coronary intervention.

Endocardial electromechanical mapping (EEM) has been proposed as a method for myocardial viability assessment. However, the impact of EEM data on clinical outcome has not been studied before. We sought to assess the prognostic value of EEM in patients with left ventricular (LV) dysfunction undergoing percutaneous coronary intervention (PCI). Seventy-five patients with coronary artery disease and LV dysfunction (angiographic LV ejection fraction [EF] 49 +/- 15%) underwent LV EEM for myocardial viability assessment before coronary revascularization. EEM parameters included mean unipolar electrographic amplitude, mean local shortening, LV volumes, LVEF, number of regions with electrographic amplitudes <7.5 mV, number of electromechanical mismatch, and match regions. Cardiac death, nonfatal myocardial infarction, nonfatal stroke, and acute heart failure requiring hospitalization were defined as clinical events. During a follow-up of 3.6 +/- 1.8 years, 20 clinical events occurred. Event-free survival after coronary revascularization was significantly better in patients with a mean unipolar electrographic amplitude of >/=9.5 mV than in patients with a mean unipolar electrographic amplitude of <9.5 mV (88% vs 57%; p <0.005). Cox regression analysis revealed angiographic LVEF, mean electrographic amplitude, number of regions with electrographic amplitudes <7.5 mV, number of electromechanical match regions, and EEM EF as univariate predictors of clinical events. In a multivariate analysis, angiographic LVEF <40% (hazard ratio 4.78, p <0.005) and mean electrographic amplitude <9.5 mV (hazard ratio 2.92, p <0.05) were independent predictors of clinical events. Thus, EEM provides prognostic information in patients with LV dysfunction undergoing coronary revascularization.

Aged↗

Effects of cardiac resynchronization therapy on myocardial blood flow measured by oxygen-15 water positron emission tomography in idiopathic-dilated cardiomyopathy and left bundle branch block.

Regional and global myocardial blood flow and coronary vascular resistance were determined in patients with idiopathic-dilated cardiomyopathy and left bundle branch block before and during cardiac resynchronization therapy (CRT) using oxygen-15 water positron emission tomography. The investigated parameters did not exhibit regional heterogeneity and were not influenced by CRT. This implies that the beneficial effects of CRT do not require additional oxygen demand or regional reallocation of oxidative metabolism.

Blood Flow Velocity↗

Validation of 4D-MSPECT and QGS for quantification of left ventricular volumes and ejection fraction from gated 99mTc-MIBI SPET: comparison with cardiac magnetic resonance imaging.

The main aim of this study was to validate the accuracy of 4D-MSPECT in the assessment of left ventricular (LV) end-diastolic/end-systolic volumes (EDV, ESV) and ejection fraction (LVEF) from gated technetium-99m methoxyisobutylisonitrile single-photon emission tomography ((99m)Tc-MIBI SPET), using cardiac magnetic resonance imaging (cMRI) as the reference method. By further comparing 4D-MSPECT and QGS with cMRI, the software-specific characteristics were analysed to elucidate clinical applicability. Fifty-four patients with suspected or proven coronary artery disease (CAD) were examined with gated (99m)Tc-MIBI SPET (8 gates/cardiac cycle) about 60 min after tracer injection at rest. LV EDV, ESV and LVEF were calculated from gated (99m)Tc-MIBI SPET using 4D-MSPECT and QGS. On the same day, cMRI (20 gates/cardiac cycle) was performed, with LV EDV, ESV and LVEF calculated using Simpson's rule. Both algorithms worked with all data sets. Correlation between the results of gated (99m)Tc-MIBI SPET and cMRI was high for EDV [ R=0.89 (4D-MSPECT), R=0.92 (QGS)], ESV [ R=0.96 (4D-MSPECT), R=0.96 (QGS)] and LVEF [ R=0.89 (4D-MSPECT), R=0.90 (QGS)]. In contrast to ESV, EDV was significantly underestimated by 4D-MSPECT and QGS compared to cMRI [130+/-45 ml (4D-MSPECT), 122+/-41 ml (QGS), 139+/-36 ml (cMRI)]. For LVEF, 4D-MSPECT and cMRI revealed no significant differences, whereas QGS yielded significantly lower values than cMRI [57.5%+/-13.7% (4D-MSPECT), 52.2%+/-12.4% (QGS), 60.0%+/-15.8% (cMRI)]. In conclusion, agreement between gated (99m)Tc-MIBI SPET and cMRI is good across a wide range of clinically relevant LV volume and LVEF values assessed by 4D-MSPECT and QGS. However, algorithm-varying underestimation of LVEF should be accounted for in the clinical context and limits interchangeable use of software.

Adult↗

Validation of QGS and 4D-MSPECT for quantification of left ventricular volumes and ejection fraction from gated 18F-FDG PET: comparison with cardiac MRI.

UNLABELLED: The aim of this study was to validate Quantitative Gated SPECT (QGS) and 4D-MSPECT for assessing left ventricular end-diastolic and systolic volumes (EDV and ESV, respectively) and left ventricular ejection fraction (LVEF) from gated (18)F-FDG PET. METHODS: Forty-four patients with severe coronary artery disease were examined with gated (18)F-FDG PET (8 gates per cardiac cycle). EDV, ESV, and LVEF were calculated from gated (18)F-FDG PET using QGS and 4D-MSPECT. Within 2 d (median), cardiovascular cine MRI (cMRI) (20 gates per cardiac cycle) was done as a reference. RESULTS: QGS failed to accurately detect myocardial borders in 1 patient; 4D-MSPECT, in 2 patients. For the remaining 42 patients, correlation between the results of gated (18)F-FDG PET and cMRI was high for EDV (R = 0.94 for QGS and 0.94 for 4D-MSPECT), ESV (R = 0.95 for QGS and 0.95 for 4D-MSPECT), and LVEF (R = 0.94 for QGS and 0.90 for 4D-MSPECT). QGS significantly (P < 0.0001) underestimated LVEF, whereas no other parameter differed significantly between gated (18)F-FDG PET and cMRI for either algorithm. CONCLUSION: Despite small systematic differences that, among other aspects, limit interchangeability, agreement between gated (18)F-FDG PET and cMRI is good across a wide range of clinically relevant volumes and LVEF values assessed by QGS and 4D-MSPECT.

Aged↗

Comparison of regional myocardial blood flow and perfusion in dilated cardiomyopathy and left bundle branch block: role of wall thickening.

UNLABELLED: Heterogeneous perfusion in left bundle branch block (LBBB) has been demonstrated by (99m)Tc-methoxyisobutylisonitrile (MIBI) SPECT. Locally different contraction is also associated with LBBB. Quantitative analysis of myocardial SPECT is influenced by partial-volume effects depending on systolic wall thickening. Therefore, partial-volume effects may mimic perfusion heterogeneity in LBBB. METHODS: Fifteen patients with nonischemic dilated cardiomyopathy and LBBB underwent resting (15)O-water PET, (99m)Tc-MIBI SPECT, and gated (18)F-FDG PET for analysis of wall thickening. Myocardial blood flow corrected for rate-pressure product (corrMBF), (99m)Tc-MIBI uptake, and wall thickening were determined in 4 left ventricular wall areas. In 14 patients, M-mode echocardiographic recordings were available for comparison. RESULTS: Homogeneous distribution was found for corrMBF (1.09 +/- 0.41 to 1.19 +/- 0.31 mL x g(-1) x min(-1)). (99m)Tc-MIBI uptake and wall thickening were heterogeneous (P < 0.0001), with the lowest values septal ((99m)Tc-MIBI, 65% +/- 10%; wall thickening, 16% +/- 14%) and the highest lateral ((99m)Tc-MIBI, 84% +/- 5%; wall thickening, 55% +/- 17%). Similar relationships in systolic wall thickening were observed by M-mode echocardiography (anteroseptal, 20% +/- 11%; posterolateral, 37% +/- 18%; P < 0.001). CONCLUSION: Heterogeneity of (99m)Tc-MIBI uptake in LBBB corresponds to differences in wall thickening and does not reflect distribution of corrMBF. Supplementary analysis of wall thickening is recommended when assessing (99m)Tc-MIBI SPECT in LBBB.

Adult↗

Prone versus supine patient positioning during gated 99mTc-sestamibi SPECT: effect on left ventricular volumes, ejection fraction, and heart rate.

UNLABELLED: Gated myocardial perfusion SPECT allows assessment of left ventricular end-diastolic volume (EDV), left ventricular end-systolic volume (ESV), left ventricular stroke volume (SV), and left ventricular ejection fraction (LVEF). Acquiring images with the patient both prone and supine is an approved method of identifying and reducing artifacts. Yet prone positioning alters physiologic conditions. This study investigated how prone versus supine patient positioning during gated SPECT affects EDV, ESV, SV, LVEF, and heart rate. METHODS: Forty-eight patients scheduled for routine myocardial perfusion imaging were examined with gated (99m)Tc-sestamibi SPECT (at rest) while positioned prone and supine (consecutively, in random order). All parameters for both acquisitions were calculated using the commercially available QGS algorithm. RESULTS: Whereas EDV and SV were significantly lower (P < 0.0004) for prone acquisitions (EDV, 110.5 +/- 39.1 mL; SV, 55.9 +/- 13.3 mL) than for supine acquisitions (EDV, 116.9 +/- 36.2 mL; SV, 61.0 +/- 14.5 mL), ESV and LVEF did not differ significantly. Heart rate was significantly higher (P < 0.0001) during prone acquisitions (69.1 +/- 10.5 min(-1)) than during supine acquisitions (66.5 +/- 10.0 min(-1)). CONCLUSION: The observed position-dependent effect on EDV, SV, and heart rate might be explained by decreased arterial filling and increased sympathetic nerve activity. Hence, supine reference data should not be used to classify the results of prone acquisitions.

Adult↗

Cardiac resynchronization therapy homogenizes myocardial glucose metabolism and perfusion in dilated cardiomyopathy and left bundle branch block.

OBJECTIVES: We investigated whether cardiac resynchronization therapy (CRT) affects myocardial glucose metabolism and perfusion in dilated cardiomyopathy (DCM) and left bundle branch block (LBBB). BACKGROUND: Patients with DCM and LBBB present with asynchronous left ventricular (LV) activation, leading to reduced septal glucose metabolism. Cardiac resynchronization therapy recoordinates LV activation, but its effects on myocardial glucose metabolism and perfusion remain unknown. METHODS: In 15 patients (10 females; 61 +/- 13 years) with DCM and LBBB (QRS width 165 +/- 15 ms), gated (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and technetium-99m ((99m)Tc)-sestamibi single-photon emission computed tomography were performed before and after two weeks of CRT. Uptake of FDG and (99m)Tc-sestamibi was determined in four LV wall areas. Ejection fraction and volumes were calculated from gated PET. RESULTS: Baseline FDG uptake was heterogeneous (p < 0.0001), with lowest uptake in the septal region (56 +/- 12%) and highest uptake in the lateral region (89 +/- 6%). During CRT, septal and anterior increases (p < 0.01) and lateral decreases (p < 0.01) resulted in homogeneously distributed glucose metabolism. Baseline heterogeneity (p < 0.0001) in (99m)Tc-sestamibi uptake was modest (lowest septal 65 +/- 10%; maximum lateral 84 +/- 5%) and also reduced with CRT, although some heterogeneity (p < 0.05) remained. The septal-to-lateral ratio increased with CRT for FDG (0.62 +/- 0.12 to 0.91 +/- 0.26, p < 0.001) and (99m)Tc-sestamibi uptake (0.77 +/- 0.13 to 0.85 +/- 0.16, p < 0.01). The LV end-diastolic and end-systolic volumes decreased from 293 +/- 160 to 272 +/- 158 ml (p < 0.05) and from 244 +/- 164 to 220 +/- 160 ml (p < 0.01), respectively. Ejection fraction increased from 22 +/- 12% to 25 +/- 13% (p < 0.01). CONCLUSIONS: Glucose metabolism is reduced more than perfusion in the septal compared with LV lateral wall in patients with DCM and LBBB. Cardiac resynchronization therapy restores homogeneous myocardial glucose metabolism with less influence on perfusion.

Aged↗

Validation of an evaluation routine for left ventricular volumes, ejection fraction and wall motion from gated cardiac FDG PET: a comparison with cardiac magnetic resonance imaging.

The aim of this study was to validate the estimation of left ventricular end-diastolic and end-systolic volumes (EDV, ESV) and ejection fraction (LVEF) as well as wall motion analysis from gated fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in patients with severe coronary artery disease (CAD) using software originally designed for gated single-photon emission tomography (SPET). Thirty patients with severe CAD referred for myocardial viability diagnostics were investigated using a standard FDG PET protocol enhanced with gated acquisition (8 gates per cardiac cycle). EDV, ESV and LVEF were calculated using standard software designed for gated SPET (QGS). Wall motion was analysed using a visual four-point wall motion score on a 17-segment model. As a reference, all patients were also examined within a median of 3 days with cardiovascular cine magnetic resonance imaging (cMRI) (20 gates per cardiac cycle). Furthermore, all gated FDG PET data sets were reoriented in a second run with deliberately misaligned axes to test the quantification procedure for robustness. Correlation between the results of gated FDG PET and cMRI was very high for EDV and ESV ( R=0.96 and R=0.97) and for LVEF ( R=0.95). With gated FDG PET, there was a non-significant tendency to underestimate EDV (174+/-61 ml vs 179+/-59 ml, P=0.21) and to overestimate ESV (124+/-58 ml vs 122+/-60 ml, P=0.65), resulting in underestimated LVEF values (31.5%+/-9.4% vs 34.2%+/-12.4%, P<0.003). The results of reorientations 1 and 2 showed very high correlations (for all R>/=0.99). Segmental wall motion analysis revealed good agreement between gated FDG PET data and cMRI (kappa =0.62+/-0.03). In conclusion, despite small systematic differences which contributed mainly to the lower temporal resolution of gated FDG PET, agreement between gated FDG PET and cMRI was good across a wide range of volumes and LVEF values as well as for wall motion analysis. Therefore, gated FDG PET provides clinically relevant information on function and volumes, using the commercially available software package QGS.

Aged↗

Comparison of microsphere-equivalent blood flow (15O-water PET) and relative perfusion (99mTc-tetrofosmin SPECT) in myocardium showing metabolism-perfusion mismatch.

UNLABELLED: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Adult↗

201Tl, 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-furifosmin: relative retention and clearance kinetics in retrogradely perfused guinea pig hearts.

Myocellular kinetics of 201Tl, 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-furifosmin were investigated using retrogradely-perfused guinea-pig hearts. Relative retention decreased in the order 99mTc-MIBI ==> 99mTc-tetrofosmin ==> 99mTc-furifosmin. 201Tl and 99mTc-MIBI exhibited bi- (t1,t2), 99mTc-tetrofosmin and 99mTc-furifosmin triexponential (t1,t2,t3) time-activity-curves. Latest-phase elimination-half-life increased from 201Tl (t2) ==> 99mTc-MIBI (t2) ==> 99mTc-tetrofosmin (t3) ==> 99mTc-furifosmin (t3), showing a significant increase in deteriorating myocardium for all tracers but 99mTc-furifosmin. Delayed elimination in deteriorating myocardium explains at least partly the redistribution phenomenon of 201Tl, and suggests a similar phenomenon for 99mTc-MIBI and 99mTc-tetrofosmin.

Animals↗

Assessment of myocardial viability in dysfunctional myocardium by resting myocardial blood flow determined with oxygen 15 water PET.

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Adult↗