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

Abstract

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 99mTc and 201Tl 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.

Targeted Imaging of the Spatial and Temporal Variation of Matrix Metalloproteinase Activity in a Porcine Model of Postinfarct Remodeling

“…SPECT/CT transaxial images were reconstructed as described previously 14 . The 201 Tl images were used for reorientation of the heart into standard short and long axis views.…”

“…However, defining the spatial and temporal variation of MMP activation post MI in relationship to LV remodeling has been difficult because of the lack of a direct in vivo approach to assess MMP activity. Past studies demonstrated the feasibility of targeted non-invasive imaging with a 99m Tc-labeled MMP-targeted radiotracer ( 99m Tc-RP805) for the in vivo detection of regional myocardial MMP activation following MI 13, 14 . The current study extended these initial findings to a relevant pre-clinical post MI porcine model in order to test the central hypothesis that enhanced MMP activation occurs following MI, and is associated with altered regional myocardial deformation.…”

New Approach to Quantification of Molecularly Targeted Radiotracer Uptake from Hybrid Cardiac SPECT/CT: Methodology and Validation

“…Notice that the extracardiac activity correction expressed in Equation 3 is implemented only for the voxels within the epicardial edge determined by CT plus 1 voxel outward from the epicardial edge as illustrated in Figure 2A. With this correction scheme, voxels on the epicardial edge have a higher correction probability (r) than those inside the edge because of the gaussian property (2,14). However, the extracardiac activity correction is not implemented for the uncontaminated voxels determined above-that is, r 5 0 in Equation 3.…”

“…Figure 6 shows the correlations between SPECT-quantified and well-counted radioactivities with no correction (NC) and with the step-by-step corrections for tissue weight (TC); tissue weight plus extracardiac activity (TEC); and tissue weight, extracardiac activity, and partial-volume errors (TEPC). Without any correction (NC), the correlation was fair (R 2 19), whereas the correlations continued to improve with the accumulative step-by-step corrections for TC (R 2 5 0.84, y 5 1.82x 2 0.01, SEE 5 0.03, P , 0.001), TEC (R 2 5 0.85, y 5 1.54x 1 0.01, SEE 5 0.02, P , 0.001), and TEPC (R 2 5 0.86, y 5 1.68x 2 0.01, SEE 5 0.02, P , 0.001). Estimation errors (mean 6 SD) of SPECT-quantified myocardial radioactivities for NC, TC, TEC, and TEPC were 0.03 6 0.04, 0.03 6 0.04, 0.02 6 0.03, and 0.02 6 0.03 MBq, respectively.…”

“…201 Tl SPECT images were used to identify the position and orientation of the heart for SPECT image reconstruction and hot spot quantification. Our previous dual-isotope SPECT approach worked reasonably well for a cardiac phantom (3) and large animals (2). However, the crosstalk between the 2 radiotracers used in the dual-isotope imaging may be problematic and adversely affect the precision of this dualisotope quantitative approach.…”