Software-Assisted Subtraction with Ultrasound-Correlated Interpretation Reduces Interpretive Ambiguity in Parathyroid Scintigraphy: A Preliminary Prospective Reporting Study

Background/Objectives: Parathyroid imaging is used for preoperative localization rather than biochemical diagnosis. Conventional planar and SPECT-based scintigraphy may yield equivocal reports when thyroid activity obscures lesion localization. This study evaluated whether combining software-assisted subtraction imaging with ultrasound-correlated interpretation improves reporting certainty and reduces ambiguity. Methods: This prospective reporting study included 96 consecutive patients referred for parathyroid scintigraphy because of biochemical or clinical suspicion of primary hyperparathyroidism. Each anonymized imaging dataset was evaluated by two independent consensus reader pairs using different interpretation strategies. The control arm (CTRL) used conventional dual-time-point Tc-99m sestamibi planar and SPECT images with Tc-99m pertechnetate thyroid images. The intervention arm (INT) additionally used software-assisted subtraction images and ultrasound-correlated interpretation. Endpoints included suspected parathyroid adenoma (PTA)-positive reporting, certainty, clinically actionable localization, high-confidence localization, and non-actionable reporting. Surgical/pathological reference localization was available in 22 operated patients. Results: INT increased PTA-positive reporting compared with CTRL [82/96 (85.4%) vs. 53/96 (55.2%), p < 0.001]. Median certainty increased from 1 (IQR, 0–2) to 3 (IQR, 1–3) (p < 0.001). Clinically actionable localization increased from 32/96 (33.3%) to 68/96 (70.8%) (p < 0.001), and high-confidence localization increased from 17/96 (17.7%) to 55/96 (57.3%) (p < 0.001). Non-actionable reporting decreased from 64/96 (66.7%) to 28/96 (29.2%). In the operated subgroup, correct localization was higher with INT [20/22 (90.9%) vs. 12/22 (54.5%), p = 0.008]. Conclusions: Software-assisted subtraction imaging, when combined with ultrasound-correlated interpretation, improved the clinical usability of conventional parathyroid scintigraphy by increasing reporting certainty, reducing ambiguity, and improving actionable localization. Reference-based findings were supportive, and ongoing follow-up is expected to provide surgical/pathological confirmation for robust diagnostic accuracy analyses.