Comparative Analysis of Heuron Brain PET and FreeSurfer Software in Automated Amyloid Quantification: Toward Reproducible and Clinically Applicable Brain PET Imaging

• Heuron Brain PET and FreeSurfer demonstrate strong agreement for amyloid PET SUVR quantification across two tracers ([¹¹C]PiB and [¹⁸F]Flutafuranol). • Heuron Brain PET achieves perfect computational reproducibility (ICC=1.00) in SUVR across brain regions, supporting robustness for clinical implementation. • Diagnostic accuracy of Heuron Brain PET is comparable to FreeSurfer for amyloid positivity classification. • Software specific SUVR cutoffs compensate for proportional bias, ensuring consistent amyloid-positive/negative classification. • Rapid processing and an integrated FDA approved workflow make Heuron Brain PET suitable for routine clinical use. Beta-amyloid (Aβ) plaque accumulation is a hallmark of Alzheimer’s disease (AD) and can be evaluated using positron emission tomography (PET). While visual assessment is standard in clinical settings, quantitative methods such as standardized uptake value ratios (SUVR) may improve diagnostic accuracy and reproducibility. This study aimed to compare the quantification and diagnostic performance of Heuron Brain PET, a recently developed clinical tool, with FreeSurfer, a well-validated research platform, in assessing Aβ deposition. A total of 205 amyloid PET scans (176 [¹¹C]PiB + 29 [¹⁸F]Flutafuranol) were analyzed using both Heuron Brain PET and FreeSurfer. SUVRs were calculated using cerebellar grey matter as the reference region. Diagnostic thresholds were determined, and regional/global SUVRs were compared using paired t-tests and correlation analysis. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. Reproducibility was assessed on a randomly selected subset (n=50) using intraclass correlation coefficients (ICC). For [¹¹C]PiB, Heuron Brain PET yielded slightly lower global SUVRs than FreeSurfer (1.32 ± 0.34 vs. 1.40 ± 0.41; p < 0.001), but showed very strong correlation (r = 0.960, p < 0.001). AUCs were comparable (Heuron: 0.988; FreeSurfer: 0.979; p = 0.401). ICC for reproducibility was perfect across all regions (ICC = 1.00, 95% CI [1.00, 1.00], p < 0.001). Results for [¹⁸F]Flutafuranol were less consistent due to small sample size. Heuron Brain PET demonstrates comparable SUVR quantification and diagnostic performance to FreeSurfer for [¹¹C]PiB PET, with excellent reproducibility and rapid analysis, supporting its potential for routine clinical application.