Matrix-assisted laser desorption/ionization mass spectrometry imaging as a new tool for molecular histopathology in epilepsy surgery.

IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY
Epilepsia Pub Date : 2024-10-05 DOI:10.1111/epi.18136
Cinzia Cagnoli, Dalia De Santis, Claudio Caccia, Italia Bongarzone, Giulia Capitoli, Laura Rossini, Michele Rizzi, Francesco Deleo, Laura Tassi, Marco de Curtis, Rita Garbelli
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引用次数: 0

Abstract

Objective: Epilepsy surgery is a treatment option for patients with seizures that do not respond to pharmacotherapy. The histopathological characterization of the resected tissue has an important prognostic value to define postoperative seizure outcome in these patients. However, the diagnostic classification process based on microscopic assessment remains challenging, particularly in the case of focal cortical dysplasia (FCD). Imaging mass spectrometry is a spatial omics technique that could improve tissue phenotyping and patient stratification by investigating hundreds of biomolecules within a single tissue sample, without the need for target-specific reagents.

Methods: An in situ proteomic technique called matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is here investigated as a potential new tool to expand conventional diagnosis on standard paraffin brain tissue sections. Unsupervised and region of interest-based MALDI-MSI analyses of sections from 10 FCD type IIb (FCDIIb) cases were performed, and the results were validated by immunohistochemistry.

Results: MALDI-MSI identified distinct histopathological features and the boundaries of the dysplastic lesion. The capability to visualize the spatial distribution of well-known diagnostic markers enabling multiplex measurements on single tissue sections was demonstrated. Finally, a fingerprint list of potential discriminant peptides that distinguish FCD core from peri-FCD tissue was generated.

Significance: This is the first study that explores the potential application of MALDI-MSI in epilepsy postsurgery fixed tissue, by utilizing the well-characterized FCDIIb features as a model. Extending these preliminary analyses to a larger cohort of patients will generate spectral libraries of molecular signatures that discriminate tissue features and will contribute to patient phenotyping.

基质辅助激光解吸电离质谱成像是癫痫手术中分子组织病理学的新工具。
目的:癫痫手术是药物治疗无效的癫痫患者的一种治疗选择。切除组织的组织病理学特征对于确定这些患者术后癫痫发作的预后具有重要价值。然而,基于显微镜评估的诊断分类过程仍具有挑战性,尤其是在局灶性皮质发育不良(FCD)的情况下。成像质谱是一种空间全息技术,可通过研究单个组织样本中的数百种生物大分子来改善组织表型和患者分层,而无需靶向特异性试剂:方法:本文研究了一种名为基质辅助激光解吸电离质谱成像(MALDI-MSI)的原位蛋白质组学技术,将其作为一种潜在的新工具来扩展标准石蜡脑组织切片的常规诊断。研究人员对10例FCD IIb型(FCDIIb)病例的切片进行了无监督和基于兴趣区域的MALDI-MSI分析,并通过免疫组化对结果进行了验证:结果:MALDI-MSI确定了不同的组织病理学特征和发育不良病变的边界。结果表明,MALDI-MSI能识别出明显的组织病理学特征和发育不良病变的边界,并能观察到知名诊断标记物的空间分布,从而实现对单个组织切片的多重测量。最后,还生成了一份潜在的鉴别肽指纹列表,用于区分 FCD 核心组织和 FCD 周围组织:这是第一项探索 MALDI-MSI 在癫痫术后固定组织中的潜在应用的研究,它利用了特征明确的 FCDIIb 特征作为模型。将这些初步分析扩展到更大的患者群,将生成可区分组织特征的分子特征光谱库,并将有助于患者的表型分析。
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来源期刊
Epilepsia
Epilepsia 医学-临床神经学
CiteScore
10.90
自引率
10.70%
发文量
319
审稿时长
2-4 weeks
期刊介绍: Epilepsia is the leading, authoritative source for innovative clinical and basic science research for all aspects of epilepsy and seizures. In addition, Epilepsia publishes critical reviews, opinion pieces, and guidelines that foster understanding and aim to improve the diagnosis and treatment of people with seizures and epilepsy.
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