Accuracy and Reproducibility of Absolute Quantification of Myocardial Focal Tracer Uptake from Molecularly Targeted SPECT/CT: A Canine Validation

Accurate and reproducible SPECT quantification of myocardial molecular processes remains a challenge because of the complication of heterogeneous background and extracardiac activity adjacent to the heart, which causes errors in the estimation of myocardial focal tracer uptake. Our aim in this study was to introduce a heuristic method for the correction of extracardiac activity into SPECT quantification and validate the modified quantification method for accuracy and reproducibility using a canine model. Methods: Dual-isotope-targeted Tc-99m and (TI)-T-201 perfusion SPECT images were acquired using a hybrid SPECT/CT camera in 6 dogs at 2 wk after myocardial infarction. Images were reconstructed with and without CT-based attenuation correction, and the reconstructed SPECT images were filtered and quantified simultaneously with incorporation of extracardiac radioactivity correction, gaussian fitting, and total-count sampling. Absolute myocardial focal tracer uptake was quantified from SPECT images using 3 different normal limits (maximum entropy [ME], mean-squared-error minimization [MSEM], and global minimum [GM]). SPECT-quantified percentage injected dose (%ID) was calculated and compared with the well-counted radioactivity measured from the postmortem myocardial tissue. SPECT quantitative processing was performed by 2 different individuals with extensive experience in cardiac image processing, to assess reproducibility of the quantitative analysis. Results: Correlations between SPECT-quantified and well-counted %IDs using 3 different normal limits were excellent (ME: r = 0.82, y = 0.932x - 0.0102; MSEM: r = 0.73, y = 1.1413x - 0.0052; and GM: r = 0.7, y = 1.2147x - 0.0002). SPECT quantification using ME normal limits resulted in an underestimation of %ID, as compared with well-counted %ID. Myocardial focal tracer uptake quantified from SPECT images without CT-based attenuation correction was significantly lower than that with the attenuation correction. The %IDs quantified from attenuation-corrected SPECT images using MSEM and GM normal limits were not significantly different from well-counted %IDs. Reproducibility of the SPECT quantitative analysis was excellent (ME: r = 0.98, y = 0.9221x + 0.0001; MSEM: r = 0.97, y = 0.9357x + 0.0004; and GM: r = 0.96, y = 0.9026x + 0.001). Conclusion: Our SPECT/CT quantification algorithm for the assessment of regional radioactivity may allow for accurate and reproducible serial noninvasive evaluation of molecularly targeted tracers in the myocardium.