Comparison of Microsphere-Equivalent Blood Flow (15O-Water PET) and Relative Perfusion (99mTc-Tetrofosmin SPECT) in Myocardium Showing Metabolism-Perfusion Mismatch

摘要

id="p-1">Myocardial perfusion imaging with 99mTc-tetrofosmin is based on the assumption of a linear correlation between myocardial blood flow (MBF) and tracer uptake. However, it is known that 99mTc-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 99mTc-tetrofosmin uptake independently of blood flow. Because metabolism (18F-FDG)-perfusion (99mTc-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 99mTc-tetrofosmin uptake. Therefore, we compared microsphere-equivalent MBF (MBF_micr; 15O-water PET) and 99mTc-tetrofosmin uptake in MPMM and in a€?normala€? myocardium. >Methods: Forty-two patients with severe coronary artery disease, referred for myocardial viability diagnostics, were examined using 18F-FDG PET and 99mTc-tetrofosmin perfusion SPECT. Relative 18F-FDG and 99mTc-tetrofosmin uptake values were calculated using 18 segments per patient. Normal myocardium and MPMM myocardium were classified using a previously validated 99mTc-tetrofosmin SPECT/18F-FDG PET score. In addition, 15O-water PET was performed to assess kinetic-modeled MBF (MBF_kin), the water-perfusable tissue fraction (PTF), and the resulting MBF_micr (MBF_kin?·PTF), which is comparable to tracer uptake values. 99mTc-tetrofosmin uptake and MBF_micr values were calculated for all normal and MPMM segments and averaged within their respective classifications. >Results: Mean relative 99mTc-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?·mina?’1?·mLa?’1, which did not significantly differ from normal myocardium (0.64 ?± 0.01 mL?·mina?’1?·mLa?’1). All values are given as mean ?± SEM. >Conclusion: Differences between reduced 99mTc-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 99mTc-tetrofosmin independently of blood flow. Therefore, it seems that perfusion deficits in MPMM myocardium are greatly overestimated by 99mTc-tetrofosmin and that it tends to give false-positive findings.