Real-Time Stereotactic Mass Spectrometry Tissue Analysis for Intraoperative Neuro

术中神经的实时立体定向质谱组织分析

• 批准号: 7981836
• 负责人: Nathalie YR Agar
• 金额: $ 267.59万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7981836
• 关键词: Accounting; Brain Neoplasms; Clinical; Day Surgery; Detection; Environment; Epilepsy; Excision; Glioblastoma; Glioma; Goals; Histopathology; Image; Intervention; Intracranial Neoplasms; Malignant - descriptor; Mass Spectrum Analysis; Measurement; Modality; Molecular; Molecular Analysis; Neurologic; Neuronavigation; Neurosurgeon; Operating Rooms; Operative Surgical Procedures; Patients; Postoperative Period; Radiology Specialty; Residual Tumors; Risk; Specialized Center; Specificity; Time; Tissues; abstracting; brain tissue; improved; in vivo; intraoperative imaging; multimodality; novel; outcome forecast; tool; treatment strategy; tumor

DESCRIPTION (Provided by the applicant) Abstract: Real-Time Stereotactic Mass Spectrometry Tissue Analysis for Intraoperative Neurosurgical Guidance Clinical and Translational Research Abstract Gliomas account for 40% of intracranial tumors, with close to 70% of them being of anaplastic grade or higher. Their most malignant form, glioblastoma multiforme still resists elaborate treatment strategies with a median survival of 12-15 months, and 2 to 5 years for anaplastic gliomas. To this day, surgery remains the most important, and usually first treatment modality for the majority of brain tumors. The benefits of gross total tumor resection include relief of mass effect, decrease in risk for epilepsy, increase of time to progression, and increase survival time. It is now well accepted that a smaller volume of postoperative residual tumor is associated with an improved prognosis for the patient. The principal challenge and objective of neurosurgical intervention is therefore to maximize the resection of tumor, while minimizing the potential for neurological deficit by preserving critical tissue. Neurosurgeons must then have the capability during surgery to identify diseased tissue as well as critical brain tissue with the highest level of certitude. This project aims to integrate a combined mass spectrometry and neuronavigation platform into the clinical environment for in vivo measurement of tumor boundaries. Mass spectrometry derived signatures will be validated against standard histopathology and correlated to pre- and/or intra- operative radiology imaging. The molecular information could eventually be used to guide clinical decisions in the operating room. A further goal is to create portable tools that may be used in centers without the level of intraoperative imaging available in highly specialized centers. Combination of a novel mass spectrometry approach with a surgical probe will allow simultaneous surgical removal of tissue and in vivo molecular analysis. The proposed project will focus on glioma margin identification in real-time and integrate with a multimodality imaging platform to increase specificity in tumor boundaries detection, for the practice of personalized neurosurgical treatment. Public Health Relevance: In neurosurgical interventions for brain cancers, the principal challenge and objective is to maximize the resection of tumor, while minimizing the potential for neurological deficit by preserving critical tissue. This project aims to develop a real-time molecular analysis of the tissue at stake using mass spectrometry in combination with radiology imaging to guide neurosurgery. The platform being developed for such a complex system can be further adapted to other surgical interventions t in need of highly specific guidance.

描述（由申请人提供） 摘要：实时立体定向质谱组织分析用于术中神经外科指导临床和转化研究摘要胶质瘤占颅内肿瘤的40%，其中近70%为间变性或更高级别。它们最恶性的形式，多形性胶质母细胞瘤仍然抵抗复杂的治疗策略，中位生存期为12-15个月，间变性胶质瘤为2 - 5年。直到今天，手术仍然是大多数脑肿瘤最重要的，通常也是首选的治疗方式。肿瘤全切除术的益处包括减轻肿块效应、降低癫痫风险、延长疾病进展时间和延长生存时间。现在普遍认为，较小体积的术后残留肿瘤与患者预后的改善有关。因此，神经外科干预的主要挑战和目标是最大限度地切除肿瘤，同时通过保留关键组织来最大限度地减少神经功能缺损的可能性。然后，神经外科医生必须有能力在手术过程中识别病变组织以及具有最高水平确定性的关键脑组织。该项目旨在将联合质谱和神经导航平台整合到临床环境中，用于肿瘤边界的体内测量。将根据标准组织病理学验证质谱衍生特征，并将其与术前和/或术中放射学成像相关。这些分子信息最终可以用于指导手术室的临床决策。另一个目标是创建可在中心使用的便携式工具，而无需高度专业化中心的术中成像水平。一种新的质谱方法与手术探针的组合将允许同时手术切除组织和体内分子分析。拟议的项目将专注于实时胶质瘤边缘识别，并与多模态成像平台相结合，以提高肿瘤边界检测的特异性，用于个性化神经外科治疗的实践。 公共卫生相关性：在脑癌的神经外科干预中，主要的挑战和目标是最大限度地切除肿瘤，同时通过保留关键组织来最大限度地减少神经功能缺损的可能性。该项目旨在开发一种实时分子分析的组织在利害关系，使用质谱结合放射成像，以指导神经外科手术。为这种复杂系统开发的平台可以进一步适用于需要高度特定指导的其他外科手术。

项目成果

Molecular imaging of drug transit through the blood-brain barrier with MALDI mass spectrometry imaging.

• DOI: 10.1038/srep02859
• 发表时间: 2013-10-04
• 期刊: SCIENTIFIC REPORTS
• 影响因子: 4.6
• 作者: Liu, Xiaohui;Ide, Jennifer L.;Norton, Isaiah;Marchionni, Mark A.;Ebling, Maritza C.;Wang, Lan Y.;Davis, Erin;Sauvageot, Claire M.;Kesari, Santosh;Kellersberger, Katherine A.;Easterling, Michael L.;Santagata, Sandro;Stuart, Darrin D.;Alberta, John;Agar, Jeffrey N.;Stiles, Charles D.;Agar, Nathalie Y. R.
• 通讯作者: Agar, Nathalie Y. R.

Profiling of adrenocorticotropic hormone and arginine vasopressin in human pituitary gland and tumor thin tissue sections using droplet-based liquid-microjunction surface-sampling-HPLC-ESI-MS-MS.

使用基于液滴的液体微结S采样 - ESI-MS-MS-MS-MS-MS-MS在人垂体和肿瘤薄组织切片中，肾上腺皮质激素和精氨酸加压素的分析。

• DOI: 10.1007/s00216-015-8803-2
• 发表时间: 2015-08
• 期刊: Analytical and bioanalytical chemistry
• 影响因子: 4.3
• 作者: Kertesz V;Calligaris D;Feldman DR;Changelian A;Laws ER;Santagata S;Agar NY;Van Berkel GJ
• 通讯作者: Van Berkel GJ