Desorption Electrospray Ionization Mass Spectrometry Imaging in Clinical Diagnost

解吸电喷雾电离质谱成像在临床诊断中的应用

• 批准号: 8728229
• 负责人: Robert Graham Cooks
• 金额: $ 17.46万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8728229
• 关键词: Archives; Attention; Bioinformatics; Bladder; Cancerous; Chemicals; Classification; Classification Scheme; Clinic; Clinical; Collaborations; Complement; Data; Databases; Development; Diagnosis; Diagnostic; Discriminant Analysis; Discrimination; Disease; Electrospray Ionization; Environment; Evaluation; Future; Hematoxylin and Eosin Staining Method; Histocompatibility Testing; Histocytochemistry; Histologic; Histology; Histopathology; Human; Image; Imaging technology; Indiana; Ions; Kidney; Laboratories; Learning; Least-Squares Analysis; Lipids; Malignant Neoplasms; Malignant neoplasm of testis; Malignant neoplasm of urinary bladder; Mass Spectrum Analysis; Medical; Methodology; Methods; Molecular; Molecular Diagnosis; Molecular Profiling; Morphology; Operating Rooms; Operative Surgical Procedures; Optics; Organ; Pathologist; Pathology; Pattern; Performance; Positioning Attribute; Preparation; Procedures; Renal carcinoma; Resected; Resolution; Sampling; Series; Software Tools; Solvents; Source; Specialist; Spectrometry, Mass, Electrospray Ionization; Staging; Staining method; Stains; Statistical Methods; Surface; Surgeon; System; Technology; Testing; Time; Tissue Sample; Tissues; Training; Translations; Universities; Validation; Work; base; cancer diagnosis; cohort; imaging modality; improved; indexing; instrument; instrumentation; ionization technique; light microscopy; mass spectrometer; medical schools; miniaturize; molecular imaging; neoplastic; optical imaging; public health relevance; remediation; research study; tool; tumor

DESCRIPTION (provided by applicant): A method of tissue diagnosis based on mass spectrometry (MS) will be evaluated to distinguish the presence, type and grade of kidney, bladder and testicular cancers. The solvent-based method of desorption electrospray ionization (DESI) MS will be used to examine tissue directly and the resulting distribution of lipid-derived ions will be used to characterize the disease state of the tissue. This will be facilitated by building a data base of representative patterns of lipid ion intensities associated with tissue of different disease states and grades. Independent tissue characterization will be made by the standard methods of histopathology. Multivariate statistical tools will be used to evaluate the DESI-MS imaging data and software tools will be developed to correlate DESI molecular images with H&E stained optical images. (This aspect of the work will be led by Prof. Olga Vitek, a statistician and specialist in bioinformatics.) Special attention will be given to DESI solvents tht are morphologically non-destructive, so allowing DESI imaging to be inserted at any point in the surgical work-flow. The hypothesis underlying this effort is that the molecular information provided on lipid distributions in tissue is diagnostic of malignancy and complements the evaluation of tumor margins using histopathology. To test the capabilities of DESI-MS as a diagnostic tool for surgical applications, we will locate a DESI- equipped mass spectrometer in an Indiana University School of Medicine pathology laboratory. There, tests of the DESI method will be made in collaboration with a pathologist (Dr. Liang Cheng) using samples provided by a surgeon (Dr. Timothy Masterson). The experiments will occur in three stages: a) Off-line analysis of excised tissue without interfering with standard procedures used in surgical intervention. Tissue will be sprayed with a solvent and the mass spectra will be evaluated to reach a diagnosis (cancer, and its grade; or normal). These results will be compared with diagnoses obtained by standard histopathology. b) On-line tissue section imaging in parallel with standard pathology examination will be used to validate the capability of DESI-MS to yield pathological information on the time-scale of the surgery. These experiments will be used to validate/invalidate DESI-MS imaging as the primary step in clinical tissue- analysis workflow for tumor margin assessment. c) Rapid on-line DESI analysis of excised tissue during surgery will be used to check that the surface of resected tissue is clean of tumor margins. By using an indexing system the position of any incompletely removed cancerous tissue will be localized on a time scale suitable for surgical remediation. In preparation for future developments in which MS is utilized in the surgical suite, the performance of a small mass spectrometer will be improved to allow lipid analysis to mass 1000 Da at unit resolution.

描述（由申请方提供）：将评价基于质谱（MS）的组织诊断方法，以区分肾癌、膀胱癌和睾丸癌的存在、类型和分级。基于溶剂的解吸电喷雾电离（DESI）MS方法将用于直接检查组织，所得的脂质衍生离子分布将用于表征组织的疾病状态。这将通过建立与不同疾病状态和等级的组织相关的脂质离子强度的代表性模式的数据库来促进。将通过组织病理学标准方法进行独立的组织表征。将使用多变量统计工具来评估DESI-MS成像数据，并将开发软件工具来将DESI分子图像与H&E染色的光学图像相关联。(This这项工作将由Olga Vitek教授领导，他是一位统计学家和生物信息学专家。将特别注意DESI溶剂，其在形态上是非破坏性的，因此允许在手术工作流程的任何点插入DESI成像。这项工作的假设是，提供的脂质分布在组织中的分子信息是诊断恶性肿瘤，并补充使用组织病理学的肿瘤边缘的评价。 为了测试作为外科应用的诊断工具的质谱的能力，我们将在印第安纳州大学医学院病理实验室中定位配备DESI的质谱仪。在那里，将与病理学家（Liang Cheng博士）合作，使用外科医生（Timothy Masterson博士）提供的样本进行DESI方法的测试。实验将分三个阶段进行：a）在不干扰手术干预中使用的标准程序的情况下对切除组织进行离线分析。 将用溶剂喷洒组织，并评价质谱以达到诊断（癌症及其等级;或正常）。这些结果将与标准组织病理学诊断结果进行比较。 B）在线组织切片成像与标准病理学检查并行，将用于验证EST-MS在手术时间尺度上产生病理学信息的能力。这些实验将用于验证/无效作为临床组织分析工作流程中肿瘤边缘评估的主要步骤的HPLC-MS成像。c）在手术期间切除组织的快速在线DESI分析将用于检查切除组织的表面是否没有肿瘤边缘。通过使用索引系统，任何未完全移除的癌组织的位置将在适合于外科手术补救的时间尺度上被定位。 在准备未来的发展，其中MS在手术室中使用，一个小型质谱仪的性能将得到改善，使脂质分析质量1000 Da的单位分辨率。

项目成果

Analysis of human gliomas by swab touch spray-mass spectrometry: applications to intraoperative assessment of surgical margins and presence of oncometabolites.

• DOI: 10.1039/c7an01334e
• 发表时间: 2017-10-23
• 期刊: The Analyst
• 作者: Pirro V;Llor RS;Jarmusch AK;Alfaro CM;Cohen-Gadol AA;Hattab EM;Cooks RG
• 通讯作者: Cooks RG

Effect of lipid extraction and room temperature transportation of bovine oocytes determined by MRM profiling.

通过 MRM 分析确定牛卵母细胞脂质提取和室温运输的效果。

• DOI: 10.21203/rs.3.rs-3788683/v1
• 发表时间: 2023
• 期刊: Research square
• 作者: deLima,CamilaBruna;Milazzotto,MarcellaPecora;Vireque,AlessandraAparecida;Joaquim,DanielCarlino;Sobreira,TiagoJosePaschoal;Ferreira,ChristinaRamires
• 通讯作者: Ferreira,ChristinaRamires

Lipid characterization of individual porcine oocytes by dual mode DESI-MS and data fusion.

• DOI: 10.1016/j.aca.2014.08.001
• 发表时间: 2014-10-27
• 期刊: Analytica chimica acta
• 影响因子: 6.2
• 作者: Pirro V;Oliveri P;Ferreira CR;González-Serrano AF;Machaty Z;Cooks RG
• 通讯作者: Cooks RG

Differential Lipid Profiles of Normal Human Brain Matter and Gliomas by Positive and Negative Mode Desorption Electrospray Ionization - Mass Spectrometry Imaging.

• DOI: 10.1371/journal.pone.0163180
• 发表时间: 2016
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Jarmusch AK;Alfaro CM;Pirro V;Hattab EM;Cohen-Gadol AA;Cooks RG
• 通讯作者: Cooks RG

Ambient ionization mass spectrometric analysis of human surgical specimens to distinguish renal cell carcinoma from healthy renal tissue.

• DOI: 10.1007/s00216-016-9627-4
• 发表时间: 2016-08
• 期刊: Analytical and bioanalytical chemistry
• 影响因子: 4.3
• 作者: Alfaro CM;Jarmusch AK;Pirro V;Kerian KS;Masterson TA;Cheng L;Cooks RG
• 通讯作者: Cooks RG