Download PDF
J Neurol Surg A Cent Eur Neurosurg 2019; 80(06): 475-487
DOI: 10.1055/s-0039-1692976
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Markers for Identifying and Targeting Glioblastoma Cells during Surgery

Stephanie Schipmann 
1   Department of Neurosurgery, University Hospital Münster, Münster, Germany
,
Michael Schwake
1   Department of Neurosurgery, University Hospital Münster, Münster, Germany
,
Eric Suero Molina
1   Department of Neurosurgery, University Hospital Münster, Münster, Germany
,
Walter Stummer
2   NCH, UK Münster, Münster, Germany
› Author Affiliations
Further Information

Publication History

30 December 2018

04 March 2019

Publication Date:
29 August 2019 (online)

   Permissions and Reprints

Abstract

Glioblastoma is a highly malignant tumor with a poor prognosis. A factor influencing survival that can be affected by the surgeon is the extent of resection (EOR). Due to the infiltrative nature of the tumor, delineation of tumor from normal brain parenchyma is often challenging. To improve EOR and facilitate tumor visualization, several techniques have been developed over the last few years. This literature review presents an overview of current intraoperative strategies for identifying and targeting glioma cells and discusses the benefits and limitations of each technique. Along with conventional techniques such as neuronavigation and ultrasound, fluorescence-guided surgery with different fluorescent agents such as 5-aminolevulinc acid and fluorescein have been widely used. Recently, newer techniques have emerged and are being translated into the operating room, promising delineation of glioblastoma tissue using targeted approaches or identification on a microscopic level, for instance using Raman spectroscopy or confocal microscopy.

Keywords

glioma - interoperative MRI - 5-ALA - fluorescein - indocyanine green
 

  • References

  • 1 Koshy M, Villano JL, Dolecek TA. , et al. Improved survival time trends for glioblastoma using the SEER 17 population-based registries. J Neurooncol 2012; 107 (01) 207-212
    CrossrefPubMedGoogle Scholar
  • 2 Ostrom QT, Gittleman H, Truitt G, Boscia A, Kruchko C, Barnholtz-Sloan JS. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2011-2015. Neuro Oncol 2018; 20 (04) (Suppl. 04) iv1-iv86
    CrossrefPubMedGoogle Scholar
  • 3 Stupp R, Mason WP, van den Bent MJ. , et al; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005; 352 (10) 987-996
    CrossrefPubMedGoogle Scholar
  • 4 Lacroix M, Abi-Said D, Fourney DR. , et al. A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 2001; 95 (02) 190-198
    CrossrefPubMedGoogle Scholar
  • 5 Sanai N, Polley MY, McDermott MW, Parsa AT, Berger MS. An extent of resection threshold for newly diagnosed glioblastomas. J Neurosurg 2011; 115 (01) 3-8
    CrossrefPubMedGoogle Scholar
  • 6 Stupp R, Hegi ME, Mason WP. , et al; European Organisation for Research and Treatment of Cancer Brain Tumour and Radiation Oncology Groups; National Cancer Institute of Canada Clinical Trials Group. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 2009; 10 (05) 459-466
    CrossrefPubMedGoogle Scholar
  • 7 Desroches J, Jermyn M, Mok K. , et al. Characterization of a Raman spectroscopy probe system for intraoperative brain tissue classification. Biomed Opt Express 2015; 6 (07) 2380-2397
    CrossrefPubMedGoogle Scholar
  • 8 Kalkanis SN, Kast RE, Rosenblum ML. , et al. Raman spectroscopy to distinguish grey matter, necrosis, and glioblastoma multiforme in frozen tissue sections. J Neurooncol 2014; 116 (03) 477-485
    CrossrefPubMedGoogle Scholar
  • 9 Lyons SA, O'Neal J, Sontheimer H. Chlorotoxin, a scorpion-derived peptide, specifically binds to gliomas and tumors of neuroectodermal origin. Glia 2002; 39 (02) 162-173
    CrossrefPubMedGoogle Scholar
  • 10 Martirosyan NL, Cavalcanti DD, Eschbacher JM. , et al. Use of in vivo near-infrared laser confocal endomicroscopy with indocyanine green to detect the boundary of infiltrative tumor. J Neurosurg 2011; 115 (06) 1131-1138
    CrossrefPubMedGoogle Scholar
  • 11 Zhang RR, Swanson KI, Hall LT, Weichert JP, Kuo JS. Diapeutic cancer-targeting alkylphosphocholine analogs may advance management of brain malignancies. CNS Oncol 2016; 5 (04) 223-231
    PubMedGoogle Scholar
  • 12 Maciunas RJ, Berger MS, Copeland B, Mayberg MR, Selker R, Allen GS. A technique for interactive image-guided neurosurgical intervention in primary brain tumors. Neurosurg Clin N Am 1996; 7 (02) 245-266
    CrossrefPubMedGoogle Scholar
  • 13 Jung TY, Jung S, Kim IY. , et al. Application of neuronavigation system to brain tumor surgery with clinical experience of 420 cases. Minim Invasive Neurosurg 2006; 49 (04) 210-215
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Schulz C, Waldeck S, Mauer UM. Intraoperative image guidance in neurosurgery: development, current indications, and future trends. Radiol Res Pract 2012; 2012: 197364
    PubMedGoogle Scholar
  • 15 Wirtz CR, Albert FK, Schwaderer M. , et al. The benefit of neuronavigation for neurosurgery analyzed by its impact on glioblastoma surgery. Neurol Res 2000; 22 (04) 354-360
    CrossrefPubMedGoogle Scholar
  • 16 Orringer DA, Golby A, Jolesz F. Neuronavigation in the surgical management of brain tumors: current and future trends. Expert Rev Med Devices 2012; 9 (05) 491-500
    CrossrefPubMedGoogle Scholar
  • 17 Sæther CA, Torsteinsen M, Torp SH, Sundstrøm S, Unsgård G, Solheim O. Did survival improve after the implementation of intraoperative neuronavigation and 3D ultrasound in glioblastoma surgery? A retrospective analysis of 192 primary operations. J Neurol Surg A Cent Eur Neurosurg 2012; 73 (02) 73-78
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Rygh OM, Selbekk T, Torp SH, Lydersen S, Hernes TA, Unsgaard G. Comparison of navigated 3D ultrasound findings with histopathology in subsequent phases of glioblastoma resection. Acta Neurochir (Wien) 2008; 150 (10) 1033-1041 ; discussion 1042
    CrossrefPubMedGoogle Scholar
  • 19 Mursch K, Scholz M, Brück W, Behnke-Mursch J. The value of intraoperative ultrasonography during the resection of relapsed irradiated malignant gliomas in the brain. Ultrasonography 2017; 36 (01) 60-65
    CrossrefPubMedGoogle Scholar
  • 20 Mercier L, Del Maestro RF, Petrecca K. , et al. New prototype neuronavigation system based on preoperative imaging and intraoperative freehand ultrasound: system description and validation. Int J CARS 2011; 6 (04) 507-522
    CrossrefPubMedGoogle Scholar
  • 21 Liang D, Schulder M. The role of intraoperative magnetic resonance imaging in glioma surgery. Surg Neurol Int 2012; 3 (Suppl. 04) S320-S327
    CrossrefPubMedGoogle Scholar
  • 22 Jolesz FA. Intraoperative imaging in neurosurgery: where will the future take us?. Acta Neurochir Suppl (Wien) 2011; 109: 21-25
    PubMedGoogle Scholar
  • 23 Sutherland GR, Kaibara T, Louw D, Hoult DI, Tomanek B, Saunders J. A mobile high-field magnetic resonance system for neurosurgery. J Neurosurg 1999; 91 (05) 804-813
    CrossrefPubMedGoogle Scholar
  • 24 Senft C, Bink A, Franz K, Vatter H, Gasser T, Seifert V. Intraoperative MRI guidance and extent of resection in glioma surgery: a randomised, controlled trial. Lancet Oncol 2011; 12 (11) 997-1003
    CrossrefPubMedGoogle Scholar
  • 25 Hatiboglu MA, Weinberg JS, Suki D. , et al. Impact of intraoperative high-field magnetic resonance imaging guidance on glioma surgery: a prospective volumetric analysis. Neurosurgery 2009; 64 (06) 1073-1081 ; discussion 1081
    CrossrefPubMedGoogle Scholar
  • 26 Özduman K, Yıldız E, Dinçer A, Sav A, Pamir MN. Using intraoperative dynamic contrast-enhanced T1-weighted MRI to identify residual tumor in glioblastoma surgery. J Neurosurg 2014; 120 (01) 60-66
    CrossrefPubMedGoogle Scholar
  • 27 Moore GE. Fluorescein as an agent in the differentiation of normal and malignant tissues. Science 1947; 106 (2745): 130-131
    PubMedGoogle Scholar
  • 28 Stummer W, Stocker S, Wagner S. , et al. Intraoperative detection of malignant gliomas by 5-aminolevulinic acid-induced porphyrin fluorescence. Neurosurgery 1998; 42 (03) 518-525 ; discussion 525–526
    CrossrefPubMedGoogle Scholar
  • 29 Raabe A, Beck J, Gerlach R, Zimmermann M, Seifert V. Near-infrared indocyanine green video angiography: a new method for intraoperative assessment of vascular flow. Neurosurgery 2003; 52 (01) 132-139 ; discussion 139
    PubMedGoogle Scholar
  • 30 Colditz MJ, Leyen Kv, Jeffree RL. Aminolevulinic acid (ALA)-protoporphyrin IX fluorescence guided tumour resection. Part 2: theoretical, biochemical and practical aspects. J Clin Neurosci 2012; 19 (12) 1611-1616
    CrossrefPubMedGoogle Scholar
  • 31 Stummer W, Stepp H, Möller G, Ehrhardt A, Leonhard M, Reulen HJ. Technical principles for protoporphyrin-IX-fluorescence guided microsurgical resection of malignant glioma tissue. Acta Neurochir (Wien) 1998; 140 (10) 995-1000
    CrossrefPubMedGoogle Scholar
  • 32 Stummer W, Stocker S, Novotny A. , et al. In vitro and in vivo porphyrin accumulation by C6 glioma cells after exposure to 5-aminolevulinic acid. J Photochem Photobiol B 1998; 45 (2–3): 160-169
    CrossrefPubMedGoogle Scholar
  • 33 Kaneko S, Suero Molina E, Ewelt C, Warneke N, Stummer W. Fluorescence-based measurement of real-time kinetics of protoporphyrin IX after 5-Aminolevulinic acid administration in human in situ malignant gliomas. Neurosurgery. In press
    PubMedGoogle Scholar
  • 34 Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ. ; ALA-Glioma Study Group. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol 2006; 7 (05) 392-401
    CrossrefPubMedGoogle Scholar
  • 35 Teixidor P, Arráez MA, Villalba G. , et al. Safety and efficacy of 5-aminolevulinic acid for high grade glioma in usual clinical practice: a prospective cohort study. PLoS One 2016; 11 (02) e0149244
    CrossrefPubMedGoogle Scholar
  • 36 Eljamel S. 5-ALA fluorescence image guided resection of glioblastoma multiforme: a meta-analysis of the literature. Int J Mol Sci 2015; 16 (05) 10443-10456
    CrossrefPubMedGoogle Scholar
  • 37 Stummer W, Novotny A, Stepp H, Goetz C, Bise K, Reulen HJ. Fluorescence-guided resection of glioblastoma multiforme by using 5-aminolevulinic acid-induced porphyrins: a prospective study in 52 consecutive patients. J Neurosurg 2000; 93 (06) 1003-1013
    CrossrefPubMedGoogle Scholar
  • 38 Stummer W, Tonn JC, Goetz C. , et al. 5-Aminolevulinic acid-derived tumor fluorescence: the diagnostic accuracy of visible fluorescence qualities as corroborated by spectrometry and histology and postoperative imaging. Neurosurgery 2014; 74 (03) 310-319 ; discussion 319–320
    CrossrefPubMedGoogle Scholar
  • 39 Díez Valle R, Tejada Solis S, Idoate Gastearena MA, García de Eulate R, Domínguez Echávarri P, Aristu Mendiroz J. Surgery guided by 5-aminolevulinic fluorescence in glioblastoma: volumetric analysis of extent of resection in single-center experience. J Neurooncol 2011; 102 (01) 105-113
    CrossrefPubMedGoogle Scholar
  • 40 Nabavi A, Thurm H, Zountsas B. , et al; 5-ALA Recurrent Glioma Study Group. Five-aminolevulinic acid for fluorescence-guided resection of recurrent malignant gliomas: a phase ii study. Neurosurgery 2009; 65 (06) 1070-1076 ; discussion 1076–1077
    CrossrefPubMedGoogle Scholar
  • 41 Lau D, Hervey-Jumper SL, Chang S. , et al. A prospective Phase II clinical trial of 5-aminolevulinic acid to assess the correlation of intraoperative fluorescence intensity and degree of histologic cellularity during resection of high-grade gliomas. J Neurosurg 2016; 124 (05) 1300-1309
    CrossrefPubMedGoogle Scholar
  • 42 Schucht P, Beck J, Abu-Isa J. , et al. Gross total resection rates in contemporary glioblastoma surgery: results of an institutional protocol combining 5-aminolevulinic acid intraoperative fluorescence imaging and brain mapping. Neurosurgery 2012; 71 (05) 927-935 ; discussion 935–936
    CrossrefPubMedGoogle Scholar
  • 43 Della Puppa A, De Pellegrin S, d'Avella E. , et al. 5-aminolevulinic acid (5-ALA) fluorescence guided surgery of high-grade gliomas in eloquent areas assisted by functional mapping. Our experience and review of the literature. Acta Neurochir (Wien) 2013; 155 (06) 965-972 ; discussion 972
    CrossrefPubMedGoogle Scholar
  • 44 Schucht P, Seidel K, Beck J. , et al. Intraoperative monopolar mapping during 5-ALA-guided resections of glioblastomas adjacent to motor eloquent areas: evaluation of resection rates and neurological outcome. Neurosurg Focus 2014; 37 (06) E16
    PubMedGoogle Scholar
  • 45 Aldave G, Tejada S, Pay E. , et al. Prognostic value of residual fluorescent tissue in glioblastoma patients after gross total resection in 5-aminolevulinic Acid-guided surgery. Neurosurgery 2013; 72 (06) 915-920 ; discussion 920–921
    CrossrefPubMedGoogle Scholar
  • 46 Schucht P, Knittel S, Slotboom J. , et al. 5-ALA complete resections go beyond MR contrast enhancement: shift corrected volumetric analysis of the extent of resection in surgery for glioblastoma. Acta Neurochir (Wien) 2014; 156 (02) 305-312 ; discussion 312
    CrossrefPubMedGoogle Scholar
  • 47 Coburger J, Hagel V, Wirtz CR, König R. Surgery for glioblastoma: impact of the combined use of 5-aminolevulinic acid and intraoperative MRI on extent of resection and survival. PLoS One 2015; 10 (06) e0131872
    CrossrefPubMedGoogle Scholar
  • 48 Coburger J, Engelke J, Scheuerle A. , et al. Tumor detection with 5-aminolevulinic acid fluorescence and Gd-DTPA-enhanced intraoperative MRI at the border of contrast-enhancing lesions: a prospective study based on histopathological assessment. Neurosurg Focus 2014; 36 (02) E3
    PubMedGoogle Scholar
  • 49 Rabb MF, Burton TC, Schatz H, Yannuzzi LA. Fluorescein angiography of the fundus: a schematic approach to interpretation. Surv Ophthalmol 1978; 22 (06) 387-403
    CrossrefPubMedGoogle Scholar
  • 50 Shinoda J, Yano H, Yoshimura S. , et al. Fluorescence-guided resection of glioblastoma multiforme by using high-dose fluorescein sodium. Technical note. J Neurosurg 2003; 99 (03) 597-603
    CrossrefPubMedGoogle Scholar
  • 51 Diaz RJ, Dios RR, Hattab EM. , et al. Study of the biodistribution of fluorescein in glioma-infiltrated mouse brain and histopathological correlation of intraoperative findings in high-grade gliomas resected under fluorescein fluorescence guidance. J Neurosurg 2015; 122 (06) 1360-1369
    CrossrefPubMedGoogle Scholar
  • 52 Hamamcıoğlu MK, Akçakaya MO, Göker B, Kasımcan MO, Kırış T. The use of the YELLOW 560 nm surgical microscope filter for sodium fluorescein-guided resection of brain tumors: our preliminary results in a series of 28 patients. Clin Neurol Neurosurg 2016; 143: 39-45
    CrossrefPubMedGoogle Scholar
  • 53 Schebesch KM, Brawanski A, Hohenberger C, Hohne J. Fluorescein sodium-guided surgery of malignant brain tumors: history, current concepts, and future project. Turk Neurosurg 2016; 26 (02) 185-194
    PubMedGoogle Scholar
  • 54 Schebesch KM, Proescholdt M, Höhne J. , et al. Sodium fluorescein-guided resection under the YELLOW 560 nm surgical microscope filter in malignant brain tumor surgery—a feasibility study. Acta Neurochir (Wien) 2013; 155 (04) 693-699
    CrossrefPubMedGoogle Scholar
  • 55 Kuroiwa T, Kajimoto Y, Ohta T. Development of a fluorescein operative microscope for use during malignant glioma surgery: a technical note and preliminary report. Surg Neurol 1998; 50 (01) 41-48 ; discussion 48–49
    CrossrefPubMedGoogle Scholar
  • 56 Acerbi F, Broggi M, Eoli M. , et al. Is fluorescein-guided technique able to help in resection of high-grade gliomas?. Neurosurg Focus 2014; 36 (02) E5
    PubMedGoogle Scholar
  • 57 Chen B, Wang H, Ge P. , et al. Gross total resection of glioma with the intraoperative fluorescence-guidance of fluorescein sodium. Int J Med Sci 2012; 9 (08) 708-714
    CrossrefPubMedGoogle Scholar
  • 58 Francaviglia N, Iacopino DG, Costantino G. , et al. Fluorescein for resection of high-grade gliomas: a safety study control in a single center and review of the literature. Surg Neurol Int 2017; 8: 145
    CrossrefPubMedGoogle Scholar
  • 59 Koc K, Anik I, Cabuk B, Ceylan S. Fluorescein sodium-guided surgery in glioblastoma multiforme: a prospective evaluation. Br J Neurosurg 2008; 22 (01) 99-103
    CrossrefPubMedGoogle Scholar
  • 60 Stummer W. Poor man's fluorescence?. Acta Neurochir (Wien) 2015; 157 (08) 1379-1381
    CrossrefPubMedGoogle Scholar
  • 61 Schwake M, Stummer W, Suero Molina EJ, Wölfer J. Simultaneous fluorescein sodium and 5-ALA in fluorescence-guided glioma surgery. Acta Neurochir (Wien) 2015; 157 (05) 877-879
    CrossrefPubMedGoogle Scholar
  • 62 Acerbi F, Broggi M, Schebesch KM. , et al. Fluorescein-guided surgery for resection of high-grade gliomas: a multicentric prospective phase II study (FLUOGLIO). Clin Cancer Res 2018; 24 (01) 52-61
    CrossrefPubMedGoogle Scholar
  • 63 Suero Molina E, Wölfer J, Ewelt C, Ehrhardt A, Brokinkel B, Stummer W. Dual-labeling with 5-aminolevulinic acid and fluorescein for fluorescence-guided resection of high-grade gliomas: technical note. J Neurosurg 2018; 128 (02) 399-405
    CrossrefPubMedGoogle Scholar
  • 64 Cherrick GR, Stein SW, Leevy CM, Davidson CS. Indocyanine green: observations on its physical properties, plasma decay, and hepatic extraction. J Clin Invest 1960; 39: 592-600
    CrossrefPubMedGoogle Scholar
  • 65 Reinhart MB, Huntington CR, Blair LJ, Heniford BT, Augenstein VA. Indocyanine green: historical context, current applications, and future considerations. Surg Innov 2016; 23 (02) 166-175
    CrossrefPubMedGoogle Scholar
  • 66 Hänggi D, Etminan N, Steiger HJ. The impact of microscope-integrated intraoperative near-infrared indocyanine green videoangiography on surgery of arteriovenous malformations and dural arteriovenous fistulae. Neurosurgery 2010; 67 (04) 1094-1103 ; discussion 1103–1104
    CrossrefPubMedGoogle Scholar
  • 67 Raabe A, Nakaji P, Beck J. , et al. Prospective evaluation of surgical microscope-integrated intraoperative near-infrared indocyanine green videoangiography during aneurysm surgery. J Neurosurg 2005; 103 (06) 982-989
    CrossrefPubMedGoogle Scholar
  • 68 Lee JY, Thawani JP, Pierce J. , et al. Intraoperative near-infrared optical imaging can localize gadolinium-enhancing gliomas during surgery. Neurosurgery 2016; 79 (06) 856-871
    CrossrefPubMedGoogle Scholar
  • 69 Swanson KI, Clark PA, Zhang RR. , et al. Fluorescent cancer-selective alkylphosphocholine analogs for intraoperative glioma detection. Neurosurgery 2015; 76 (02) 115-123 ; discussion 123–124
    CrossrefPubMedGoogle Scholar
  • 70 Valdés PA, Roberts DW, Lu FK, Golby A. Optical technologies for intraoperative neurosurgical guidance. Neurosurg Focus 2016; 40 (03) E8
    PubMedGoogle Scholar
  • 71 Hilgard P, Klenner T, Stekar J, Unger C. Alkylphosphocholines: a new class of membrane-active anticancer agents. Cancer Chemother Pharmacol 1993; 32 (02) 90-95
    CrossrefPubMedGoogle Scholar
  • 72 Weichert JP, Clark PA, Kandela IK. , et al. Alkylphosphocholine analogs for broad-spectrum cancer imaging and therapy. Sci Transl Med 2014; 6 (240) 240ra75
    CrossrefPubMedGoogle Scholar
  • 73 Kuo JS, Zhang RR, Pinchuk AN, Clark PA, Weichert JP. Creation of a dual-labeled cancer-targeting alkylphosphocholine analog for dual modality quantitative positron emission tomography and intraoperative tumor visualization. Neurosurgery 2016; 63 (01) 208
    PubMedGoogle Scholar
  • 74 Parrish-Novak J, Byrnes-Blake K, Lalayeva N. , et al. Nonclinical profile of BLZ-100, a tumor-targeting fluorescent imaging agent. Int J Toxicol 2017; 36 (02) 104-112
    CrossrefPubMedGoogle Scholar
  • 75 Butte PV, Mamelak A, Parrish-Novak J. , et al. Near-infrared imaging of brain tumors using the Tumor Paint BLZ-100 to achieve near-complete resection of brain tumors. Neurosurg Focus 2014; 36 (02) E1
    PubMedGoogle Scholar
  • 76 Uematsu Y, Owai Y, Okita R, Tanaka Y, Itakura T. The usefulness and problem of intraoperative rapid diagnosis in surgical neuropathology. Brain Tumor Pathol 2007; 24 (02) 47-52
    CrossrefPubMedGoogle Scholar
  • 77 Foersch S, Heimann A, Ayyad A. , et al. Confocal laser endomicroscopy for diagnosis and histomorphologic imaging of brain tumors in vivo. PLoS One 2012; 7 (07) e41760
    CrossrefPubMedGoogle Scholar
  • 78 Hoffman A, Goetz M, Vieth M, Galle PR, Neurath MF, Kiesslich R. Confocal laser endomicroscopy: technical status and current indications. Endoscopy 2006; 38 (12) 1275-1283
    Article in Thieme ConnectPubMedGoogle Scholar
  • 79 Belykh E, Martirosyan NL, Yagmurlu K. , et al. Intraoperative fluorescence imaging for personalized brain tumor resection: current state and future directions. Front Surg 2016; 3: 55
    PubMedGoogle Scholar
  • 80 Raman C. A new type of secondary radiation. Nature 1928; 121: 501-502
    PubMedGoogle Scholar
  • 81 Hollon T, Lewis S, Freudiger CW, Sunney Xie X, Orringer DA. Improving the accuracy of brain tumor surgery via Raman-based technology. Neurosurg Focus 2016; 40 (03) E9
    PubMedGoogle Scholar
  • 82 Krafft C, Neudert L, Simat T, Salzer R. Near infrared Raman spectra of human brain lipids. Spectrochim Acta A Mol Biomol Spectrosc 2005; 61 (07) 1529-1535
    CrossrefPubMedGoogle Scholar
  • 83 Jermyn M, Mok K, Mercier J. , et al. Intraoperative brain cancer detection with Raman spectroscopy in humans. Sci Transl Med 2015; 7 (274) 274ra19
    CrossrefPubMedGoogle Scholar
  • 84 Desroches J, Jermyn M, Pinto M. , et al. A new method using Raman spectroscopy for in vivo targeted brain cancer tissue biopsy. Sci Rep 2018; 8 (01) 1792
    CrossrefPubMedGoogle Scholar
  • 85 Arbizu J, Tejada S, Marti-Climent JM. , et al. Quantitative volumetric analysis of gliomas with sequential MRI and 11C-methionine PET assessment: patterns of integration in therapy planning. Eur J Nucl Med Mol Imaging 2012; 39 (05) 771-781
    CrossrefPubMedGoogle Scholar
  • 86 Jaber M, Wölfer J, Ewelt C. , et al. The value of 5-aminolevulinic acid in low-grade gliomas and high-grade gliomas lacking glioblastoma imaging features: an analysis based on fluorescence, magnetic resonance imaging, 18F-fluoroethyl tyrosine positron emission tomography, and tumor molecular factors. Neurosurgery 2016; 78 (03) 401-411 ; discussion 411
    CrossrefPubMedGoogle Scholar
  • 87 Idoate MA, Díez Valle R, Echeveste J, Tejada S. Pathological characterization of the glioblastoma border as shown during surgery using 5-aminolevulinic acid-induced fluorescence. Neuropathology 2011; 31 (06) 575-582
    CrossrefPubMedGoogle Scholar
  • 88 Roberts DW, Valdés PA, Harris BT. , et al. Coregistered fluorescence-enhanced tumor resection of malignant glioma: relationships between δ-aminolevulinic acid-induced protoporphyrin IX fluorescence, magnetic resonance imaging enhancement, and neuropathological parameters. Clinical article. J Neurosurg 2011; 114 (03) 595-603
    CrossrefPubMedGoogle Scholar
  • 89 Valdés PA, Leblond F, Kim A. , et al. Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker. J Neurosurg 2011; 115 (01) 11-17
    CrossrefPubMedGoogle Scholar
  • 90 Valdés PA, Jacobs V, Harris BT. , et al. Quantitative fluorescence using 5-aminolevulinic acid-induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery. J Neurosurg 2015; 123 (03) 771-780
    CrossrefPubMedGoogle Scholar