Evaluation of SCALE PET Software for Quantitative Brain PET Analysis in Alzheimer's Disease

• Study Overview This study is a single-center, retrospective, rater-blinded, crossover reader study. The primary objective is to evaluate the efficacy of 'Neurophet SCALE PET', a medical image analysis software, in assisting clinicians with the quantitative analysis of amyloid-beta (Aβ) positivity on brain PET scans. The study will compare the performance of readers when they use the software (SW-assisted) versus when they do not use it (unassisted).
• Data Collection and Reference Standard The investigators will retrospectively collect medical data from a total of 194 patients (97 Aβ-positive and 97 Aβ-negative cases).

Data Sources: De-identified data will be obtained from Ajou University Hospital and the Alzheimer's Disease Neuroimaging Initiative (ADNI) database.

• Study Procedures (Reader Study) The reader study consists of two main reading sessions separated by a 4-week washout period to minimize memory bias and order effects. Four readers will be randomly assigned to two groups (Reader Group 1 and Reader Group 2).

• Session 1: Reader Group 1 will evaluate Case Group A with SW assistance and Case Group B without assistance. Reader Group 2 will evaluate Case Group B with SW assistance and Case Group A without assistance.
• Washout Period: A 4-week interval will be implemented between sessions.
• Session 2: The conditions will be swapped following a crossover design. Readers will re-evaluate the same cases under the opposite condition (assisted vs. unassisted) compared to Session 1.

During each session, readers will rate Aβ positivity on a 5-point scale (1: Definitely negative, 2: Probably negative, 3: Equivocal, 4: Probably positive, 5: Definitely positive) and record their diagnostic confidence level on a 3-point scale (1: low confidence, 2: moderate confidence, 3: high confidence).

• Statistical Analysis The efficacy of the software will be assessed by comparing the diagnostic performance between the SW-assisted and unassisted conditions.

• Primary outcomes: Differences in readers' sensitivity and specificity for Aβ positivity classification.
• Secondary Outcomes: Differences in diagnostic accuracy (AUC), the number of cases rated as "equivocal," rater confidence levels, and inter-rater agreement.

Inclusion criteria

Medical imaging datasets meeting all of the following criteria will be eligible for inclusion in this study.

• Age ≥ 50 years at the time of brain magnetic resonance imaging (MRI)
• Participants who underwent amyloid brain PET imaging using one of the following tracers: 18F-Florbetaben, 18F-Florbetapir, 18F-Flutemetamol
• Availability of 3D T1-weighted brain MRI.
• The interval between amyloid PET and 3D T1-weighted MRI is within 1 year.
• Participants meeting one of the following predefined groups based on prior visual interpretation of amyloid PET:

• Aβ-positive group: Prior clinical interpretation of amyloid PET reported as Aβ positive.
• Aβ-negative group: Prior clinical interpretation of amyloid PET reported as Aβ negative.

Exclusion criteria

Medical imaging datasets meeting any of the following criteria will be excluded from the study.

• Poor image quality due to artifacts, motion, shading, or other technical issues that make visual interpretation difficult or prevent proper software processing.
• Presence of prior brain surgery resulting in significant structural changes, or presence of intracranial metallic implants.
• Contrast-enhanced 3D T1-weighted brain MRI.
• Presence of structural brain lesions other than cerebral infarction.
• Cases deemed inappropriate for study participation at the investigator's discretion.