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.

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
NIH Director’s New Innovator Awards (DP2)
Project #
1DP2OD007383-01
Application #
7981836
Study Section
Special Emphasis Panel (ZGM1-NDIA-O (01))
Program Officer
Basavappa, Ravi
Project Start
2010-09-30
Project End
2015-06-30
Budget Start
2010-09-30
Budget End
2015-06-30
Support Year
1
Fiscal Year
2010
Total Cost
$2,675,875
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Kurreck, Annika; Vandergrift, Lindsey A; Fuss, Taylor L et al. (2018) Prostate cancer diagnosis and characterization with mass spectrometry imaging. Prostate Cancer Prostatic Dis 21:297-305
Jonas, Oliver; Calligaris, David; Methuku, Kashi Reddy et al. (2016) First In Vivo Testing of Compounds Targeting Group 3 Medulloblastomas Using an Implantable Microdevice as a New Paradigm for Drug Development. J Biomed Nanotechnol 12:1297-302
Lu, Fa-Ke; Calligaris, David; Olubiyi, Olutayo I et al. (2016) Label-Free Neurosurgical Pathology with Stimulated Raman Imaging. Cancer Res 76:3451-62
Pokorny, Jenny L; Calligaris, David; Gupta, Shiv K et al. (2015) The Efficacy of the Wee1 Inhibitor MK-1775 Combined with Temozolomide Is Limited by Heterogeneous Distribution across the Blood-Brain Barrier in Glioblastoma. Clin Cancer Res 21:1916-24
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Kertesz, Vilmos; Calligaris, David; Feldman, Daniel R et al. (2015) 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. Anal Bioanal Chem 407:5989-98
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Calligaris, David; Feldman, Daniel R; Norton, Isaiah et al. (2015) MALDI mass spectrometry imaging analysis of pituitary adenomas for near-real-time tumor delineation. Proc Natl Acad Sci U S A 112:9978-83
Santagata, Sandro; Eberlin, Livia S; Norton, Isaiah et al. (2014) Intraoperative mass spectrometry mapping of an onco-metabolite to guide brain tumor surgery. Proc Natl Acad Sci U S A 111:11121-6
Calligaris, David; Caragacianu, Diana; Liu, Xiaohui et al. (2014) Application of desorption electrospray ionization mass spectrometry imaging in breast cancer margin analysis. Proc Natl Acad Sci U S A 111:15184-9

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