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

A Single-Center, Retrospective, Rater-Blinded, Crossover Study to Evaluate the Efficacy of the Medical Image Analysis Software 'SCALE PET' for Quantitative Analysis of Brain PET Images in Patients With Alzheimer's Disease

The goal of this study is to learn if medical image analysis software, Neurophet SCALE PET, can enhance readers' amyloid beta positivity performance in people with Alzheimer's Disease. The main question it aims to answer is:

Does the use of medical image analysis software assistance result in a statistically significant difference in readers' sensitivity and specificity for the classification of amyloid-β (Aβ) positivity?

Four readers will interpret amyloid PET images in two sessions (with and without software assistance), separated by a 4-week washout period, and will record Aβ positivity and diagnostic confidence using predefined rating scales.

Study Overview

• Status: Completed
• Conditions: Mild Cognitive Impairment (MCI); Alzheimer's Disease (AD)
• Intervention / Treatment: Device: Neurophet SCALE PET

Detailed Description

1. 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).

2. 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.

3. 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).

4. 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.

• Study Type: Interventional
• Enrollment (Actual): 190
• Phase: Not Applicable

Contacts and Locations

Study Locations

• South Korea
  • Suwon, South Korea
    • Ajou University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

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

5. 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.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Reader group 1; In Session 1, readers in this group interpret Case Group A with software (SW) assistance and Case Group B without assistance (visual read). Following a 4-week washout period, the conditions are swapped for Session 2: readers interpret Case Group A without SW assistance and Case Group B with SW assistance.	Device: Neurophet SCALE PET; Neurophet SCALE PET is an artificial intelligence-based medical image analysis software designed for the quantitative analysis of brain PET images. It provides automated quantification of amyloid-beta (Aβ) deposition using standardized uptake value ratios (SUVR) and the Centiloid scale. In this study, the software is used as a diagnostic support tool to assist clinicians in evaluating Aβ positivity.
Experimental: Reader group 2; In Session 1, readers in this group interpret Case Group B with software (SW) assistance and Case Group A without assistance (visual read). Following a 4-week washout period, the conditions are swapped for Session 2: readers interpret Case Group B without SW assistance and Case Group A with SW assistance.	Device: Neurophet SCALE PET; Neurophet SCALE PET is an artificial intelligence-based medical image analysis software designed for the quantitative analysis of brain PET images. It provides automated quantification of amyloid-beta (Aβ) deposition using standardized uptake value ratios (SUVR) and the Centiloid scale. In this study, the software is used as a diagnostic support tool to assist clinicians in evaluating Aβ positivity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in readers' sensitivity in SW-assisted vs. unassisted classification of Aβ positivity	Comparison of the sensitivity for amyloid-beta positivity between the software-assisted and unassisted reading conditions, based on the expert-established reference standard.	At the completion of two reading sessions (approximately 3 months)
Difference in readers' specificity in SW-assisted vs. unassisted classification of Aβ positivity	Comparison of the specificity for amyloid-beta negativity between the software-assisted and unassisted reading conditions, based on the expert-established reference standard.	At the completion of the reading study (approximately 3 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in readers' diagnostic accuracy in SW-assisted vs. unassisted classification of Aβ positivity	The difference in diagnostic accuracy is evaluated using the Area Under the Receiver Operating Characteristic (ROC) Curve (AUC).	At the completion of the reading study (approximately 3 months)
Difference in number of cases rated as equivocal in SW-assisted vs. unassisted classification of Aβ positivity	Comparison of the frequency of cases rated as "3: Equivocal" on the 5-point scale between the software-assisted and unassisted conditions.	At the completion of the reading study (approximately 3 months)
Difference in confidence level of readers in SW-assisted vs. unassisted classification of Aβ positivity	Comparison of the readers' self-reported confidence levels when making a diagnosis	At the completion of the reading study (approximately 3 months)
Inter-rater Agreement	Evaluation of the consistency in amyloid-beta positivity ratings among the four readers	At the completion of the reading study (approximately 3 months)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of analysis failure cases	The number of cases where the 'Neurophet SCALE PET' software fails to complete the automated quantitative analysis or produces uninterpretable results due to technical errors, such as pre-processing failure or software crashes.	At the completion of the reading study (approximately 3 months)

Collaborators and Investigators

• Sponsor: NEUROPHET
• Collaborators: Ajou University Hospital, Suwon, South Korea
• Investigators: Principal Investigator: Soyoung Moon, Department of Neurology, Ajou University School of Medicine, Suwon, Republic of Korea

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2025
• Primary Completion (Actual): November 17, 2025
• Study Completion (Actual): November 17, 2025

Study Registration Dates

• First Submitted: February 11, 2026
• First Submitted That Met QC Criteria: February 11, 2026
• First Posted (Actual): February 18, 2026

Study Record Updates

• Last Update Posted (Actual): February 18, 2026
• Last Update Submitted That Met QC Criteria: February 11, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Alzheimer's Disease; quantification; AI software; Amyloid-β (Aβ); brain PET; reader study; Multi-Reader Multi-Case (MRMC); Centiloid Scale; SUVR
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Cognitive Dysfunction; Alzheimer Disease
• Other Study ID Numbers: AJOUIRB-DE-2025-195

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No