MR Nano‐Radiomics for Detection of Amyloid Plaques in Alzheimer’s Disease

Abstract

AbstractBackgroundAmyloid plaques are a pathological hallmark of Alzheimer’s disease (AD). In a recent pre‐clinical study, we showed an amyloid‐targeted liposomal macrocyclic gadolinium (Gd) contrast agent, ADx‐001, for in vivo MRI‐based detection of amyloid plaques in mouse. Although ADx‐001 showed high sensitivity at a high dose (0.2 mmol Gd/kg), the performance was sub‐optimal (<70%) at lower doses (0.1 and 0.15 mmol Gd/kg). In this work, we investigated if nano‐radiomics (radiomic analysis of nanoparticle contrast‐enhanced images) would increase sensitivity of ADx‐001 at lower dose levels.MethodIn vivo studies were performed in the APP/PSEN1 mouse model of amyloid pathology. The efficacy of ADx‐001‐ enhanced MRI was studied at three dose‐levels: 0.10, 0.15, and 0.20 (mmol Gd/kg). Pre‐ and post‐contrast MRI was performed in transgenic (n = 6/dose) and wild‐type mice (n = 6/dose) using a T1‐weighted spin‐echo sequence. Semi‐automatic 3D segmentation of hippocampal and cortical regions was performed using a mouse brain MR atlas (Fig.1). Radiomic analysis was executed on the hippocampus and cortex regions of ADx‐001‐enhanced MR images 900 radiomic features (RFs). RF selection was completed using a non‐parametric neighborhood component method. 5‐fold cross‐validation was performed using a set of linear and non‐linear classifiers to confirm the accuracy of group separation.ResultSeven RFs (three RFs for cortex and four RFs for hippocampus) were identified that differentiated amyloid‐positive transgenic mice from amyloid‐negative wild‐type mice based on ADx‐001‐enhanced MRI. The best performing nearest‐neighbor classification model was trained simultaneously on all ADx‐001 dose groups. Nano‐radiomic analysis of ADx‐001‐enhanced MRI demonstrated 100% accuracy, specificity, and sensitivity for dose levels of 0.2 and 0.15 mmol Gd/kg. For low dose level (0.1 mmol Gd/kg), radiomics achieved accuracy of 91.6% and sensitivity of 83.3%, while maintaining specificity at 100%. The new results were superior when compared to previously reported results based on global signal enhancement analysis.ConclusionNano‐radiomic analysis of ADx‐001‐enhanced MRI improved sensitivity of ADx‐001 at lower dose levels for the detection of amyloid pathology and demonstrated excellent for intermediate and high dose. Our study demonstrates that radiomic analysis of contrast‐enhanced MR images could boost the performance of targeted molecular imaging agents for early detection of AD.