BACKGROUND: Surgery remains the first and most important treatment modality for the majority of solid tumors. Across a range of brain tumor types and grades, postoperative residual tumor has a great impact on prognosis. The principal challenge and objective of neurosurgical intervention is therefore to maximize tumor resection while minimizing the potential for neurological deficit by preserving critical tissue. OBJECTIVE: To introduce the integration of desorption electrospray ionization mass spectrometry into surgery for in vivo molecular tissue characterization and intraoperative definition of tumor boundaries without systemic injection of contrast agents. METHODS: Using a frameless stereotactic sampling approach and by integrating a 3-dimensional navigation system with an ultrasonic surgical probe, we obtained image-registered surgical specimens. The samples were analyzed with ambient desorption/ionization mass spectrometry and validated against standard histopathology. This new approach will enable neurosurgeons to detect tumor infiltration of the normal brain intraoperatively with mass spectrometry and to obtain spatially resolved molecular tissue characterization without any exogenous agent and with high sensitivity and specificity. RESULTS: Proof of concept is presented in using mass spectrometry intraoperatively for real-time measurement of molecular structure and using that tissue characterization method to detect tumor boundaries. Multiple sampling sites within the tumor mass were defined for a patient with a recurrent left frontal oligodendroglioma, World Health Organization grade II with chromosome 1p/19q codeletion, and mass spectrometry data indicated a correlation between lipid constitution and tumor cell prevalence. CONCLUSION: The mass spectrometry measurements reflect a complex molecular structure and are integrated with frameless stereotaxy and imaging, providing 3-dimensional molecular imaging without systemic injection of any agents, which can be implemented for surgical margins delineation of any organ and with a rapidity that allows real-time analysis.
BACKGROUND: Surgery remains the first and most important treatment modality for the majority of solid tumors. Across a range of brain tumor types and grades, postoperative residual tumor has a great impact on prognosis. The principal challenge and objective of neurosurgical intervention is therefore to maximize tumor resection while minimizing the potential for neurological deficit by preserving critical tissue. OBJECTIVE: To introduce the integration of desorption electrospray ionization mass spectrometry into surgery for in vivo molecular tissue characterization and intraoperative definition of tumor boundaries without systemic injection of contrast agents. METHODS: Using a frameless stereotactic sampling approach and by integrating a 3-dimensional navigation system with an ultrasonic surgical probe, we obtained image-registered surgical specimens. The samples were analyzed with ambient desorption/ionization mass spectrometry and validated against standard histopathology. This new approach will enable neurosurgeons to detect tumor infiltration of the normal brain intraoperatively with mass spectrometry and to obtain spatially resolved molecular tissue characterization without any exogenous agent and with high sensitivity and specificity. RESULTS: Proof of concept is presented in using mass spectrometry intraoperatively for real-time measurement of molecular structure and using that tissue characterization method to detect tumor boundaries. Multiple sampling sites within the tumor mass were defined for a patient with a recurrent left frontal oligodendroglioma, World Health Organization grade II with chromosome 1p/19q codeletion, and mass spectrometry data indicated a correlation between lipid constitution and tumor cell prevalence. CONCLUSION: The mass spectrometry measurements reflect a complex molecular structure and are integrated with frameless stereotaxy and imaging, providing 3-dimensional molecular imaging without systemic injection of any agents, which can be implemented for surgical margins delineation of any organ and with a rapidity that allows real-time analysis.
Authors: Frank B Furnari; Tim Fenton; Robert M Bachoo; Akitake Mukasa; Jayne M Stommel; Alexander Stegh; William C Hahn; Keith L Ligon; David N Louis; Cameron Brennan; Lynda Chin; Ronald A DePinho; Webster K Cavenee Journal: Genes Dev Date: 2007-11-01 Impact factor: 11.361
Authors: A Aria Tzika; Leo Ling Cheng; Liliana Goumnerova; Joseph R Madsen; David Zurakowski; Loukas G Astrakas; Maria K Zarifi; R Michael Scott; Douglas C Anthony; R Gilberto Gonzalez; Peter McL Black Journal: J Neurosurg Date: 2002-06 Impact factor: 5.115
Authors: Manish Sud; Eoin Fahy; Dawn Cotter; Alex Brown; Edward A Dennis; Christopher K Glass; Alfred H Merrill; Robert C Murphy; Christian R H Raetz; David W Russell; Shankar Subramaniam Journal: Nucleic Acids Res Date: 2006-11-10 Impact factor: 16.971
Authors: David Calligaris; Isaiah Norton; Daniel R Feldman; Jennifer L Ide; Ian F Dunn; Livia S Eberlin; R Graham Cooks; Ferenc A Jolesz; Alexandra J Golby; Sandro Santagata; Nathalie Y Agar Journal: J Mass Spectrom Date: 2013-11 Impact factor: 1.982
Authors: David Calligaris; Daniel R Feldman; Isaiah Norton; Priscilla K Brastianos; Ian F Dunn; Sandro Santagata; Nathalie Y R Agar Journal: Int J Mass Spectrom Date: 2015-02-01 Impact factor: 1.986
Authors: Sandro Santagata; Livia S Eberlin; Isaiah Norton; David Calligaris; Daniel R Feldman; Jennifer L Ide; Xiaohui Liu; Joshua S Wiley; Matthew L Vestal; Shakti H Ramkissoon; Daniel A Orringer; Kristen K Gill; Ian F Dunn; Dora Dias-Santagata; Keith L Ligon; Ferenc A Jolesz; Alexandra J Golby; R Graham Cooks; Nathalie Y R Agar Journal: Proc Natl Acad Sci U S A Date: 2014-06-30 Impact factor: 11.205
Authors: Livia S Eberlin; Isaiah Norton; Allison L Dill; Alexandra J Golby; Keith L Ligon; Sandro Santagata; R Graham Cooks; Nathalie Y R Agar Journal: Cancer Res Date: 2011-12-02 Impact factor: 12.701
Authors: Alan K Jarmusch; Valentina Pirro; Zane Baird; Eyas M Hattab; Aaron A Cohen-Gadol; R Graham Cooks Journal: Proc Natl Acad Sci U S A Date: 2016-01-19 Impact factor: 11.205
Authors: Clint M Alfaro; Alan K Jarmusch; Valentina Pirro; Kevin S Kerian; Timothy A Masterson; Liang Cheng; R Graham Cooks Journal: Anal Bioanal Chem Date: 2016-05-20 Impact factor: 4.142