Can Intraoperative Near-Infrared Fluorescence Imaging Improve Tumor Resection Margins in Glioblastoma Surgery? A Technical Note Review
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Abstract
Glioblastoma (GBM) is a highly aggressive brain tumor with limited treatment options, where achieving maximal safe resection is critical for improving patient outcomes. However, distinguishing tumor margins from surrounding healthy tissue intraoperatively remains challenging due to the infiltrative nature of GBM. Near-infrared (NIR) fluorescence imaging has emerged as a promising tool to enhance surgical precision by providing real-time visualization of tumor tissue during resection. This technical note evaluates the utility of intraoperative NIR fluorescence imaging in improving tumor resection margins in GBM. Current technical note review demonstrates that NIR fluorescence imaging significantly enhances the ability to achieve complete tumor resection while sparing normal brain tissue. This technique offers real-time guidance, improves accuracy, and integrates seamlessly with existing surgical workflows. Despite its promise, limitations such as variability in tumor metabolism and the inability to detect deeply infiltrative cells highlight the need for further refinements. Larger studies are warranted to validate these results and explore the long-term impact on survival. In conclusion, intraoperative NIR fluorescence imaging is a valuable adjunct in GBM surgery, offering the potential to improve resection margins and patient outcomes.
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This work is licensed under a Creative Commons Attribution 4.0 International License.
References
Kanderi T, Munakomi S, Gupta V. Glioblastoma Multiforme. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 [cited 2025 Jun 20]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK558954/
Patel V, Chavda V. Intraoperative glioblastoma surgery-current challenges and clinical trials: An update. Cancer Pathog Ther. 2024 Oct;2(4):256–67.
Dixon L, Lim A, Grech-Sollars M, Nandi D, Camp S. Intraoperative ultrasound in brain tumor surgery: A review and implementation guide. Neurosurg Rev. 2022 Aug;45(4):2503–15.
Kalisvaart GM, Meijer RPJ, Bijlstra OD, Galema HA, De Steur WO, Hartgrink HH, et al. Intraoperative Near-Infrared Fluorescence Imaging with Indocyanine Green for Identification of Gastrointestinal Stromal Tumors (GISTs), a Feasibility Study. Cancers. 2022 Mar 18;14(6):1572.
Handgraaf HJM, Verbeek FPR, Tummers QRJG, Boogerd LSF, Van De Velde CJH, Vahrmeijer AL, et al. Real-time near-infrared fluorescence guided surgery in gynecologic oncology: A review of the current state of the art. Gynecologic Oncology. 2014 Dec;135(3):606–13.
Mieog JSD, Hutteman M, Van Der Vorst JR, Kuppen PJK, Que I, Dijkstra J, et al. Image-guided tumor resection using real-time near-infrared fluorescence in a syngeneic rat model of primary breast cancer. Breast Cancer Res Treat. 2011 Aug;128(3):679–89.
Van Oosterom MN, Van Leeuwen SI, Mazzone E, Dell’Oglio P, Buckle T, Van Beurden F, et al. Click-on fluorescence detectors: using robotic surgical instruments to characterize molecular tissue aspects. J Robotic Surg [Internet]. 2022 Apr 9 [cited 2025 Jun 20]; Available from: https://link.springer.com/10.1007/s11701-022-01382-0
Pepper NB, Eich HT, Müther M, Oertel M, Rehn S, Spille DC, et al. ALA-RDT in GBM: protocol of the phase I/II dose escalation trial of radiodynamic therapy with 5-Aminolevulinic acid in patients with recurrent glioblastoma. Radiat Oncol. 2024 Jan 22;19(1):11.
Mansour HM, Shah S, Aguilar TM, Abdul-Muqsith M, Gonzales-Portillo GS, Mehta AI. Enhancing Glioblastoma Resection with NIR Fluorescence Imaging: A Systematic Review. Cancers (Basel). 2024 Nov 27;16(23):3984.
Rauf SA, Ahmed R, Hussain T, Saad M, Shah HH, Jamalvi SA, et al. Fluorescence in neurosurgery: its therapeutic and diagnostic significance - a comprehensive review. Ann Med Surg (Lond). 2024 Jul;86(7):4255–61.
Traylor JI, Pernik MN, Sternisha AC, McBrayer SK, Abdullah KG. Molecular and Metabolic Mechanisms Underlying Selective 5-Aminolevulinic Acid-Induced Fluorescence in Gliomas. Cancers (Basel). 2021 Feb 2;13(3):580.
Meijer RPJ, van Manen L, Hartgrink HH, Burggraaf J, Gioux S, Vahrmeijer AL, et al. Quantitative dynamic near-infrared fluorescence imaging using indocyanine green for analysis of bowel perfusion after mesenteric resection. J Biomed Opt. 2021 Jun;26(6):060501.
Fan X, Yang J, Ni H, Xia Q, Liu X, Wu T, et al. Initial Experience of NIR-II Fluorescence Imaging-Guided Surgery in Foot and Ankle Surgery. Engineering. 2024 Sep;40:19–27.
Ma L, Fei B. Comprehensive review of surgical microscopes: technology development and medical applications. J Biomed Opt. 2021 Jan;26(1):010901.
Ullah Z, Roy S, Gu J, Ko Soe S, Jin J, Guo B. NIR-II Fluorescent Probes for Fluorescence-Imaging-Guided Tumor Surgery. Biosensors. 2024 May 30;14(6):282.
Mazurek M, Szczepanek D, Orzyłowska A, Rola R. Analysis of Factors Affecting 5-ALA Fluorescence Intensity in Visualizing Glial Tumor Cells-Literature Review. Int J Mol Sci. 2022 Jan 15;23(2):926.
Unger J, Hebisch C, Phipps JE, Lagarto JL, Kim H, Darrow MA, et al. Real-time diagnosis and visualization of tumor margins in excised breast specimens using fluorescence lifetime imaging and machine learning. Biomed Opt Express. 2020 Mar 1;11(3):1216–30.
Kravchenko Y, Sikora K, Wireko AA, Lyndin M. Fluorescence visualization for cancer DETECTION: EXPERIENCE and perspectives. Heliyon. 2024 Jan;10(2):e24390.
Zhou Y, Tao L, Qiu J, Xu J, Yang X, Zhang Y, et al. Tumor biomarkers for diagnosis, prognosis and targeted therapy. Sig Transduct Target Ther. 2024 May 20;9(1):132.
Cheng H, Xu H, Peng B, Huang X, Hu Y, Zheng C, et al. Illuminating the future of precision cancer surgery with fluorescence imaging and artificial intelligence convergence. npj Precis Onc. 2024 Sep 9;8(1):196.
Main Article Content
Abstract
Glioblastoma (GBM) is a highly aggressive brain tumor with limited treatment options, where achieving maximal safe resection is critical for improving patient outcomes. However, distinguishing tumor margins from surrounding healthy tissue intraoperatively remains challenging due to the infiltrative nature of GBM. Near-infrared (NIR) fluorescence imaging has emerged as a promising tool to enhance surgical precision by providing real-time visualization of tumor tissue during resection. This technical note evaluates the utility of intraoperative NIR fluorescence imaging in improving tumor resection margins in GBM. Current technical note review demonstrates that NIR fluorescence imaging significantly enhances the ability to achieve complete tumor resection while sparing normal brain tissue. This technique offers real-time guidance, improves accuracy, and integrates seamlessly with existing surgical workflows. Despite its promise, limitations such as variability in tumor metabolism and the inability to detect deeply infiltrative cells highlight the need for further refinements. Larger studies are warranted to validate these results and explore the long-term impact on survival. In conclusion, intraoperative NIR fluorescence imaging is a valuable adjunct in GBM surgery, offering the potential to improve resection margins and patient outcomes.
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
References
Kanderi T, Munakomi S, Gupta V. Glioblastoma Multiforme. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 [cited 2025 Jun 20]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK558954/
Patel V, Chavda V. Intraoperative glioblastoma surgery-current challenges and clinical trials: An update. Cancer Pathog Ther. 2024 Oct;2(4):256–67.
Dixon L, Lim A, Grech-Sollars M, Nandi D, Camp S. Intraoperative ultrasound in brain tumor surgery: A review and implementation guide. Neurosurg Rev. 2022 Aug;45(4):2503–15.
Kalisvaart GM, Meijer RPJ, Bijlstra OD, Galema HA, De Steur WO, Hartgrink HH, et al. Intraoperative Near-Infrared Fluorescence Imaging with Indocyanine Green for Identification of Gastrointestinal Stromal Tumors (GISTs), a Feasibility Study. Cancers. 2022 Mar 18;14(6):1572.
Handgraaf HJM, Verbeek FPR, Tummers QRJG, Boogerd LSF, Van De Velde CJH, Vahrmeijer AL, et al. Real-time near-infrared fluorescence guided surgery in gynecologic oncology: A review of the current state of the art. Gynecologic Oncology. 2014 Dec;135(3):606–13.
Mieog JSD, Hutteman M, Van Der Vorst JR, Kuppen PJK, Que I, Dijkstra J, et al. Image-guided tumor resection using real-time near-infrared fluorescence in a syngeneic rat model of primary breast cancer. Breast Cancer Res Treat. 2011 Aug;128(3):679–89.
Van Oosterom MN, Van Leeuwen SI, Mazzone E, Dell’Oglio P, Buckle T, Van Beurden F, et al. Click-on fluorescence detectors: using robotic surgical instruments to characterize molecular tissue aspects. J Robotic Surg [Internet]. 2022 Apr 9 [cited 2025 Jun 20]; Available from: https://link.springer.com/10.1007/s11701-022-01382-0
Pepper NB, Eich HT, Müther M, Oertel M, Rehn S, Spille DC, et al. ALA-RDT in GBM: protocol of the phase I/II dose escalation trial of radiodynamic therapy with 5-Aminolevulinic acid in patients with recurrent glioblastoma. Radiat Oncol. 2024 Jan 22;19(1):11.
Mansour HM, Shah S, Aguilar TM, Abdul-Muqsith M, Gonzales-Portillo GS, Mehta AI. Enhancing Glioblastoma Resection with NIR Fluorescence Imaging: A Systematic Review. Cancers (Basel). 2024 Nov 27;16(23):3984.
Rauf SA, Ahmed R, Hussain T, Saad M, Shah HH, Jamalvi SA, et al. Fluorescence in neurosurgery: its therapeutic and diagnostic significance - a comprehensive review. Ann Med Surg (Lond). 2024 Jul;86(7):4255–61.
Traylor JI, Pernik MN, Sternisha AC, McBrayer SK, Abdullah KG. Molecular and Metabolic Mechanisms Underlying Selective 5-Aminolevulinic Acid-Induced Fluorescence in Gliomas. Cancers (Basel). 2021 Feb 2;13(3):580.
Meijer RPJ, van Manen L, Hartgrink HH, Burggraaf J, Gioux S, Vahrmeijer AL, et al. Quantitative dynamic near-infrared fluorescence imaging using indocyanine green for analysis of bowel perfusion after mesenteric resection. J Biomed Opt. 2021 Jun;26(6):060501.
Fan X, Yang J, Ni H, Xia Q, Liu X, Wu T, et al. Initial Experience of NIR-II Fluorescence Imaging-Guided Surgery in Foot and Ankle Surgery. Engineering. 2024 Sep;40:19–27.
Ma L, Fei B. Comprehensive review of surgical microscopes: technology development and medical applications. J Biomed Opt. 2021 Jan;26(1):010901.
Ullah Z, Roy S, Gu J, Ko Soe S, Jin J, Guo B. NIR-II Fluorescent Probes for Fluorescence-Imaging-Guided Tumor Surgery. Biosensors. 2024 May 30;14(6):282.
Mazurek M, Szczepanek D, Orzyłowska A, Rola R. Analysis of Factors Affecting 5-ALA Fluorescence Intensity in Visualizing Glial Tumor Cells-Literature Review. Int J Mol Sci. 2022 Jan 15;23(2):926.
Unger J, Hebisch C, Phipps JE, Lagarto JL, Kim H, Darrow MA, et al. Real-time diagnosis and visualization of tumor margins in excised breast specimens using fluorescence lifetime imaging and machine learning. Biomed Opt Express. 2020 Mar 1;11(3):1216–30.
Kravchenko Y, Sikora K, Wireko AA, Lyndin M. Fluorescence visualization for cancer DETECTION: EXPERIENCE and perspectives. Heliyon. 2024 Jan;10(2):e24390.
Zhou Y, Tao L, Qiu J, Xu J, Yang X, Zhang Y, et al. Tumor biomarkers for diagnosis, prognosis and targeted therapy. Sig Transduct Target Ther. 2024 May 20;9(1):132.
Cheng H, Xu H, Peng B, Huang X, Hu Y, Zheng C, et al. Illuminating the future of precision cancer surgery with fluorescence imaging and artificial intelligence convergence. npj Precis Onc. 2024 Sep 9;8(1):196.