1. 2024;27;E557-E566A Multimodal Meta-Analysis of Structural and Functional Alterations in the Brain of Knee Osteoarthritis
   Systematic Review
   Shirui Cheng, MD, Xiaohui Dong, MD, Peng Lai, MM, Xingyao Chen, MM, Jun Zhou, MM, Zhengjie Li, MD, and Xi Wu, MD.

BACKGROUND: Abnormalities of structural and functional brain regions might influence the persistence of knee pain, the progression, and the response to treatments in knee osteoarthritis (KOA). These complex alterations present a challenge to the understanding of its mechanism.

OBJECTIVES: To meta-analyze the concurrence across structural and functional magnetic resonance imaging studies.

STUDY DESIGN: Systematic review and meta-analysis.

SETTING: This meta-analysis examined all voxel-based morphometric (VBM) and amplitude of low-frequency fluctuation (ALFF) studies involving the whole-brain alterations of KOA.

METHODS: VBM and ALFF studies published up to May 7, 2023, were searched in the Web of Science, PubMed, EMBASE, Cochrane Library (CENTRAL), China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database, Chongqing VIP, Wanfang Database. Two independent researchers carried out study screening, quality assessment, clinical data extraction, and neuroimaging data extraction. The whole-brain voxel-based gray matter (GM) and brain activity data of KOA were collected from eligible studies and meta-analyzed using the anisotropic effect size-signed differential mapping (AES-SDM).

RESULTS: Fourteen studies were included in this study. In VBM meta-analyses, a total of 481 patients were enrolled in this study (252 KOA and 229 healthy patients). In the ALFF meta-analysis, a total of 518 patients were enrolled in this study (265 KOA and 253 healthy patients). According to the meta-analysis, KOA had increased GM volume in the right inferior frontal gyrus and decreased GM volume in the bilateral superior frontal gyrus, as well as increased brain activity in the left inferior frontal gyrus and inferior temporal gyrus, and decreased brain activity in the left middle occipital gyrus, right supramarginal gyrus, right superior frontal gyrus, and right superior parietal gyrus compared with healthy patients.

LIMITATIONS: Most of the ALFF studies included in this meta-analysis were conducted in China. Our findings are exclusively addressed by the VBM and ALFF studies. The meta-regression between the duration of KOA, pain intensity and abnormal gray matter, and functional activity of brain regions in patients with KOA were unable to be analyzed.

CONCLUSION: The results of this meta-analysis indicate that patients with KOA present significant abnormalities in GM volume and functional activity. These findings contribute to a better understanding of the structural and functional abnormalities seen in patients with KOA.

KEY WORDS: Knee osteoarthritis, meta-analysis, signed differential mapping, voxel-based morphometry, amplitude of low frequency fluctuation