MSACL 2016 US Abstract

Desorption Electrospray Ionization – Mass Spectrometry for Intraoperative Analysis of Brain Cancer Tissue

Alan Jarmusch (Presenter)
Purdue University

Bio: Alan K. Jarmusch obtained by B.S. in biochemistry from the University of North Carolina at Greensboro. He was mentored by Dr. Nadja Cech and performed 3 years of undergraduate research in LC-MS method development and applications in natural products. He joined the research group of Dr. Graham Cooks in 2011 at Purdue University working in biological applications of ambient mass spectrometry. During his Ph.D. study, he has used DESI-MS to study cancer and various other applications including natural products. He has also helped to develop new ambient ionization methods, namely swab touch spray ionization which generates ions directly from medical swabs with applications ranging from microbiology to illicit drug detection. His plan for the future is to continue in academia, researching and developing mass spectrometry in the areas of medicine and natural products.

Authorship: Alan K. Jarmusch(1) Valentina Pirro(1) Zane R. Baird(1) Clint M. Alfaro(1) Eyas M. Hattab(2) Aaron A. Cohen-Gadol(2) and R. Graham Cooks(1)
(1) Purdue University, West Lafayette, IN (2) Indiana School of Medicine, Indianapolis, IN

Short Abstract

Surgical intervention is a primary treatment option for brain tumors. The best patient outcomes are dependent on absolute tumor resection, ideally minimizing damage to adjacent normal tissue, and reducing surgery time. Ambient ionization MS provides molecular-based diagnostics on a timescale compatible with surgery. We have developed new DESI-MS methodology for the analysis of smeared neural tissue biopsies during tumor resection. MS data acquisition for each sample required <2 minutes, while providing rich lipid and metabolite MS profiles. Multivariate statistics and a DESI-MS spectral library, compiled with disease states as validated by traditional histopathology, was used in predicting disease state.

Long Abstract

Surgical intervention is a primary treatment option for brain tumors. The best patient outcomes are dependent on absolute tumor resection, ideally minimizing damage to adjacent normal tissue, and reducing surgery time. Ambient ionization MS provides molecular-based diagnostics on a timescale compatible with surgery. We have developed new DESI-MS methodology for the analysis of smeared neural tissue biopsies during tumor resection. MS data acquisition for each sample required <2 minutes, while providing rich lipid and metabolite MS profiles. Multivariate statistics and a DESI-MS spectral library, compiled with disease states as validated by traditional histopathology, was used in predicting disease state.

Banked human brain specimens (N=60) were analyzed by DESI-MS imaging, subsequently H&E stained, and evaluated by pathology. MS data were averaged based on pathology and used to create a classification system built using multivariate statistics. Lipids and additional biomolecules detected in the negative mode, including N-acetyl-aspartic acid, were important for differentiation of the pathological states evaluated. N-acetyl-aspartic acid was found to be particularly important in the differentiation of gliomas from normal brain tissue.

The new classification system expands upon our previous work which consisted primarily of gliomas. The critical addition of normal brain from healthy and cancer patients, meningiomas, and pituitary tumors, represents a significant expansion of information relevant to surgical treatment of brain tumors. Further, the WHO grade was determined and used in delineating low grade (I-II) and high grade (III-IV) gliomas. The classification system developed covers approximately 2/3 of all primary brain and CNS tumors (CBTRUS Report, 2007-2011), including the most prevalent types. The depth and breadth of the developed classifier is state of the art.

A custom designed cart allows transportation of the mass spectrometer and supporting equipment, e.g. pumps, gases, computer, to different operating rooms for intraoperative analysis. Instrument systems designed for this purpose are not commercially available and are uncommon. During surgery, residual tissue biopsies are evaluated by our new DESI methodology, classified, and compared with standard histopathology. Improvements to the tissue analysis process have eased implementation of DESI in the operation room and increased analysis speed, significantly decreasing the time required for pathological evaluation of neural tissue.


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