Impact of Region of Interest Size on Semi-Quantification of Myocardial <sup>99m</sup>Tc-pyrophosphate Uptake in Suspected Transthyretin Cardiac Amyloidosis

<i>Background</i>: This study aimed to evaluate the optimal region of interest (ROI) size of the heart-to-contralateral (H/CL) ratio on planar imaging for detecting myocardial technetium-99m pyrophosphate (PYP) uptake in patients with suspected transthyretin cardiac amyloidosis (ATTR-CA) and to assess the impact of ROI size on intra- and interobserver variability in the H/CL ratio. <i>Methods</i>: We retrospectively analyzed 90 consecutive patients who underwent PYP imaging for ATTR-CA evaluation after excluding 20 patients without myocardial PYP uptake on planar images (i.e., Grade 0). The H/CL ratio was measured using three ROI sizes (4.5 cm, 3 cm, and 2 cm). Receiver operating characteristic (ROC) analysis was used to evaluate the performance of each ROI size in detecting positive PYP single-photon emission computed tomography (SPECT). Intra- and inter-observer variability was assessed using intraclass correlation coefficients (ICCs). <i>Results</i>: Grade 2-3 myocardial PYP uptake on SPECT was observed in 41 (46%) patients. ROC analysis revealed no significant differences in the area under the curve among the various ROI sizes at 1 hour (0.68, 0.71, and 0.71 for the 4.5-, 3-, and 2-cm ROIs, respectively; <i>P</i>=0.44) or 3 hours (0.71, 0.72, and 0.72 for the 4.5-, 3-, and 2-cm ROIs, respectively; <i>P</i>=0.86). The largest ROI (4.5 cm) demonstrated the highest reproducibility, with excellent intra-observer (ICC=0.949) and inter-observer (ICC=0.906) agreement. <i>Conclusions</i>: The size of the ROI used to calculate the H/CL ratio did not significantly affect the detection of myocardial PYP uptake in patients with suspected ATTR-CA. Using a larger ROI size that covers the entire heart may improve the reproducibility of the H/CL ratio measurement.