The quantification of dynamic FET PET imaging and correlation with the clinical outcome in patients with glioblastoma.

The PET tracer O-(2-[18F]Fluoroethyl)-l-tyrosine (FET) has been shown to be valuable for different roles in the management of brain tumours. The aim of this study was to evaluate several quantitative measures of dynamic FET PET imaging in patients with resected glioblastoma. We evaluated dynamic FET PET in nine patients with histologically confirmed glioblastoma. Following FET PET, all subjects had radiation and chemotherapy. Tumour ROIs were defined by a threshold-based region-growing algorithm. We compared several standard measures of tumour uptake and uptake kinetics: SUV, SUV/background, distribution volume ratio (DVR), weighted frame differences and compartment model parameters. These measures were correlated with disease-free and overall survival, and analysed for statistical significance. We found that several measures allowed robust quantification. SUV and distribution volume did not correlate with clinical outcome. Measures that are based on a background region (SUV/BG, Logan-DVR) highly correlated with disease-free survival (r = -0.95, p < 0.0001), but not overall survival. Some advanced measures also showed a prognostic value but no improvement over the simpler methods. We conclude that FET PET probably has a prognostic value in patients with resected glioblastoma. The ratio of SUV to background may provide a simple and valuable predictive measure of the clinical outcome. Further studies are needed to confirm these explorative results.

Cerebral A1 adenosine receptors (A1AR) in liver cirrhosis.

PURPOSE: The cerebral mechanisms underlying hepatic encephalopathy (HE) are poorly understood. Adenosine, a neuromodulator that pre- and postsynaptically modulates neuronal excitability and release of classical neurotransmitters via A(1) adenosine receptors (A(1)AR), is likely to be involved. The present study investigates changes of cerebral A(1)AR binding in cirrhotic patients by means of positron emission tomography (PET) and [(18)F]CPFPX, a novel selective A(1)AR antagonist. METHODS: PET was performed in cirrhotic patients (n = 10) and healthy volunteers (n = 10). Quantification of in vivo receptor density was done by Logan's non-invasive graphical analysis (pons as reference region). The outcome parameter was the apparent binding potential (aBP, proportional to B (max)/K (D)). RESULTS: Cortical and subcortical regions showed lower A(1)AR binding in cirrhotic patients than in controls. The aBP changes reached statistical significance vs healthy controls (p < 0.05, U test with Bonferroni-Holm adjustment for multiple comparisons) in cingulate cortex (-50.0%), precentral gyrus (-40.9%), postcentral gyrus (-38.6%), insular cortex (-38.6%), thalamus (-32.9%), parietal cortex (-31.7%), frontal cortex (-28.6), lateral temporal cortex (-28.2%), orbitofrontal cortex (-27.9%), occipital cortex (-24.6), putamen (-22.7%) and mesial temporal lobe (-22.4%). CONCLUSION: Regional cerebral adenosinergic neuromodulation is heterogeneously altered in cirrhotic patients. The decrease of cerebral A(1)AR binding may further aggravate neurotransmitter imbalance at the synaptic cleft in cirrhosis and hepatic encephalopathy. Different pathomechanisms may account for these alterations including decrease of A(1)AR density or affinity, as well as blockade of the A(1)AR by endogenous adenosine or exogenous xanthines.

SPECT imaging in the diagnosis of pulmonary embolism: automated detection of match and mismatch defects by means of image-processing techniques.

UNLABELLED: SPECT of ventilation/perfusion (V/Q) lung scans not only improves the diagnostic accuracy of the method but also facilitates the application of advanced image-processing techniques. On the basis of such techniques, our study aimed at developing a procedure that automatically analyzes V/Q lung scans with regard to match and mismatch defects. METHODS: Fifty-three patients with suspected pulmonary embolism had lung scans using the SPECT technique as well as 16-slice multidetector-row spiral CT within an interval of 48 h. After iterative image reconstruction and computerized linear registration of the V/Q scans, the ventilation was normalized to the perfusion. For the automated detection of mismatch defects, the perfusion was subtracted from the ventilation, whereas for the detection of match defects, the perfusion was subtracted from the inverted ventilation. Two experienced referees assessed all images. The final diagnosis was made at a consensus meeting while taking into account all of the imaging modalities, laboratory tests, clinical data, and evaluation of a follow-up period. RESULTS: The sensitivity, specificity, and accuracy of the conventional visual assessment were 0.91, 0.97, and 0.94, respectively, compared with 0.95, 0.84, and 0.89, respectively, for the automated algorithm. Artifacts imitating mismatch defects in the pulmonary recesses accounted for the relatively low specificity of the automated analysis. Artifacts of that kind were found in 15 patients and led to a false-positive diagnosis in 5 patients. However, by combining the visual and the automated approach, all artifacts could be easily identified leading to a sensitivity, specificity, and accuracy of 0.95, 1.0, and 0.98, respectively. Additionally, in all 12 patients of the cohort with highly heterogeneous ventilation and perfusion, the automated analysis made correct diagnoses. CONCLUSION: Because of the 3-dimensional properties of the SPECT data, the analysis of lung scans can be automated and objectified. The algorithm produces images that are easy to read and well suited for demonstration. Because of artifacts in the pulmonary recesses introduced by the automated approach, its diagnostic accuracy does not reach the level of the conventional analysis yet. Could these artifacts be overcome, the efficiency of the automated algorithm would be at least equivalent to that of conventional image interpretation. At present, best results can be achieved by combining both approaches.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.