title: Guiding brain tumor resection using surface-enhanced Raman scattering nanoparticles and a hand-held Raman scanner.
abstract: The current difficulty in visualizing the true extent of malignant brain tumors during surgical resection represents one of the major reasons for the poor prognosis of brain tumor patients. Here, we evaluated the ability of a hand-held Raman scanner, guided by surface-enhanced Raman scattering (SERS) nanoparticles, to identify the microscopic tumor extent in a genetically engineered RCAS/tv-a glioblastoma mouse model. In a simulated intraoperative scenario, we tested both a static Raman imaging device and a mobile, hand-held Raman scanner. We show that SERS image-guided resection is more accurate than resection using white light visualization alone. Both methods complemented each other, and correlation with histology showed that SERS nanoparticles accurately outlined the extent of the tumors. Importantly, the hand-held Raman probe not only allowed near real-time scanning, but also detected additional microscopic foci of cancer in the resection bed that were not seen on static SERS images and would otherwise have been missed. This technology has a strong potential for clinical translation because it uses inert gold-silica SERS nanoparticles and a hand-held Raman scanner that can guide brain tumor resection in the operating room.
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center , New York, New York 10065, United States.
authors.forename: Hazem
authors.initials: H
authors.lastname: Karabeber
authors.forename: Ruimin
authors.initials: R
authors.lastname: Huang
authors.forename: Pasquale
authors.initials: P
authors.lastname: Iacono
authors.forename: Jason M
authors.initials: JM
authors.lastname: Samii
authors.forename: Ken
authors.initials: K
authors.lastname: Pitter
authors.forename: Eric C
authors.initials: EC
authors.lastname: Holland
authors.forename: Moritz F
authors.initials: MF
authors.lastname: Kircher
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000601:surgery*; D005909:Glioblastoma / Q000601:surgery*; D051379:Mice; D053758:Nanoparticles; D013059:Spectrum Analysis, Raman / Q000379:methods*
keywords: GBM; SERS nanoparticles; SERS-guided tumor resection; brain tumors; glioblastoma multiforme; hand-held Raman scanner; surface-enhanced Raman scattering (SERS)
references.citation: J Neurosurg. 2005 Apr;102(4):629-36
references.pmid: 15871504
references.citation: Lancet Oncol. 2006 May;7(5):392-401
references.pmid: 16648043
references.citation: Anal Bioanal Chem. 2010 Sep;398(1):477-87
references.pmid: 20577720
references.citation: Sci Transl Med. 2013 Sep 4;5(201):201ra119
references.pmid: 24005159
references.citation: Nat Med. 2012 Apr 15;18(5):829-34
references.pmid: 22504484
references.citation: Cancer Res. 1986 Dec;46(12 Pt 1):6387-92
references.pmid: 2946403
references.citation: PLoS One. 2009 Nov 13;4(11):e7752
references.pmid: 19915670
references.citation: Neuro Oncol. 2010 May;12(5):466-72
references.pmid: 20406897
references.citation: Lasers Surg Med. 2008 Apr;40(4):273-81
references.pmid: 18412229
references.citation: Magn Reson Imaging. 2000 Dec;18(10):1201-14
references.pmid: 11167040
references.citation: J Neurooncol. 2013 Jan;111(1):19-23
references.pmid: 23054563
references.citation: Mol Imaging Biol. 2010 Oct;12(5):500-8
references.pmid: 20012220
references.citation: Adv Drug Deliv Rev. 2013 Jan;65(1):71-9
references.pmid: 23088862
references.citation: Neurosurgery. 1994 Jan;34(1):45-60; discussion 60-1
references.pmid: 8121569
references.citation: J Neurol Surg A Cent Eur Neurosurg. 2012 Mar;73(2):73-8
references.pmid: 22467479
references.citation: Cancer Sci. 2013 Jul;104(7):779-89
references.pmid: 23495730
references.citation: J Neurosurg. 2012 Dec;117(6):1032-8
references.pmid: 23039151
references.citation: Oncologist. 2006 Feb;11(2):165-80
references.pmid: 16476837
references.citation: Cancer Cell. 2010 Jan 19;17(1):98-110
references.pmid: 20129251
references.citation: Cancer Res. 2012 Sep 15;72(18):4856-68
references.pmid: 22865458
references.citation: CA Cancer J Clin. 2013 Nov-Dec;63(6):395-418
references.pmid: 24114523
references.citation: J Nucl Med. 2011 Dec;52(12):1839-44
references.pmid: 21868625
references.citation: Childs Nerv Syst. 2012 Jan;28(1):101-9
references.pmid: 21927834
references.citation: Neuroimaging Clin N Am. 2010 Aug;20(3):409-24
references.pmid: 20708555
references.citation: Analyst. 2010 Dec;135(12):3042-7
references.pmid: 21046027
references.citation: Expert Opin Investig Drugs. 2009 Aug;18(8):1061-83
references.pmid: 19555299
references.citation: Cancer. 2004 Aug 15;101(4):817-24
references.pmid: 15305415
references.citation: Trends Immunol. 2012 Dec;33(12):579-89
references.pmid: 22926201
references.citation: PLoS One. 2011 Jan 18;6(1):e14545
references.pmid: 21267448
references.citation: Neurosurgery. 2005 Nov;57(5):1041-7; discussion 1041-7
references.pmid: 16284574
references.citation: J Cell Biol. 1996 Dec;135(6 Pt 1):1551-64
references.pmid: 8978822
references.citation: Neurosurgery. 2005 Oct;57(4 Suppl):382-91; discussion 382-91
references.pmid: 16234690
references.citation: J Neurooncol. 2009 Sep;94(3):399-408
references.pmid: 19330483
references.citation: Neuro Oncol. 2010 Mar;12(3):233-42
references.pmid: 20167811
references.citation: Clin Cancer Res. 2012 Oct 15;18(20):5731-40
references.pmid: 22914772
references.citation: N Engl J Med. 1994 Dec 1;331(22):1500-7
references.pmid: 7969301
references.citation: J Neurosurg. 2011 Jul;115(1):1-2; discussion 2
references.pmid: 21417711
references.citation: Can J Neurol Sci. 2011 Jul;38(4):621-5
references.pmid: 21672702
references.citation: Recent Results Cancer Res. 2009;171:67-81
references.pmid: 19322538
references.citation: J Neurosurg. 2011 Jul;115(1):3-8
references.pmid: 21417701
references.citation: Acta Neurochir (Wien). 2004 Apr;146(4):369-77; discussion 377
references.pmid: 15057531
references.citation: Nat Nanotechnol. 2014 Jun;9(6):481-7
references.pmid: 24727688
references.citation: J Neurosurg. 2003 Sep;99(3):597-603
references.pmid: 12959452
references.citation: Transl Oncol. 2009 May;2(2):89-95
references.pmid: 19412424
references.citation: AJNR Am J Neuroradiol. 1999 Sep;20(8):1547-53
references.pmid: 10512244
references.citation: Sci Transl Med. 2011 Apr 20;3(79):79ra33
references.pmid: 21508310
references.citation: Nat Mater. 2014 Feb;13(2):125-38
references.pmid: 24452356
references.citation: Neurosurgery. 2010 Apr;66(4):736-43
references.pmid: 20305495
references.citation: Cancer J. 2003 Mar-Apr;9(2):91-8
references.pmid: 12784874