SWI and T2*-GRE Microhemorrhage Counts in Anti-Amyloid Therapy Eligibility: A Real-World-Calibrated Simulation Study

Area of Science:

• Neuroimaging
• Neurology
• Medical Imaging Analysis

Background:

• Patient eligibility for anti-amyloid therapies is limited by the presence of five or more cerebral microhemorrhages (CMHs).
• Current guidelines permit the use of either T2*-GRE or the more sensitive SWI sequence for CMH assessment.
• This discrepancy may lead to sequence-dependent variations in patient eligibility classification.

Purpose of the Study:

• To investigate the impact of different MRI sequences (SWI vs. T2*-GRE) on cerebral microhemorrhage (CMH) detection.
• To quantify the potential discrepancies in patient eligibility for anti-amyloid therapies based on CMH counts derived from SWI and T2*-GRE sequences.
• To evaluate the operational equivalence of CMH thresholds across SWI and T2*-GRE sequences.

Main Methods:

• A Bayesian right-censored zero-inflated Poisson model was fitted to real-world SWI-based CMH counts from 130 memory clinic patients.
• Simulations of T2*-GRE counts were performed using a directional binomial detection model.
• Key metrics P(T2* <5 | SWI ≥ 5) and P(SWI ≥ 5 | T2* <5) were estimated to assess eligibility discrepancies.

Main Results:

• The model indicated a zero-inflation probability of 0.57 and a Poisson mean of 2.29 in the susceptible subpopulation.
• In a scenario with 60% relative detection probability, nearly 80% of patients ineligible by SWI criteria were under-detected by T2*-GRE.
• Approximately 5% of patients eligible by T2*-GRE criteria would have been classified as ineligible by SWI.

Conclusions:

• A uniform numerical CMH threshold may not be operationally equivalent when using SWI and T2*-GRE sequences.
• Standardized studies comparing paired SWI and T2*-GRE sequences are necessary.
• Further research is needed to determine if SWI-defined and T2*-GRE-defined CMH thresholds correlate with equivalent ARIA risk.