Letter: Use of a Single-Fiber Optical Probe for the Detection of Tumor Fluorescence in High-Grade Glioma

To the Editor: We read with great interest the recent article by Dablouk et al1 published in Operative Neurosurgery in July 2025 on the use of a single-fiber optical probe for detecting tumor fluorescence in high-grade gliomas. We commend the authors for this innovative approach to a persistent challenge in neurosurgical oncology. For instance, fluorescence-guided surgery with 5-aminolevulinic acid is known to improve glioma resection and patient outcomes.2 Still, conventional microscope-based visualization of protoporphyrin IX fluorescence has well-documented limitations (eg, subjective intensity thresholds, difficult detection in deep surgical cavities).3 Dablouk et al demonstrated that a contact fiber-optic probe substantially outperformed the operating microscope in detecting protoporphyrin IX fluorescence, with an accuracy of 75.9% vs 56.6%. This represents a significant improvement in sensitivity (P < .001) and shows that the probe—which smoothly integrates into the surgical workflow—can detect tumor fluorescence imperceptible to the naked eye. Although the article provides a thorough and detailed overview, we would like to highlight additional modalities and visualization techniques for tumor assessment. An emerging technology is represented by the contact endoscopy (CE), which provides high-magnification (up to 150-fold), real-time visualization of superficial and deep brain tissue. Our group previously demonstrated that CE allows enhanced visualization of tumor-brain parenchyma interfaces by revealing distinctive microvascular patterns in the tissue that are not discernible with standard visualization tools.4,5 In our series of primary and metastatic brain lesions, CE was particularly useful in visualizing highly vascular tumors (eg, meningiomas, pituitary adenomas and high-grade gliomas) where abnormal microvasculature is prominent and could be immediately recognized. Another advanced adjunct in the modern neurosurgeon's armamentarium is provided by confocal laser endomicroscopy (CLE), which is based on a fiber-optic probe to provide histology-like images of brain tissue during surgery (with or without preoperative fluorescein administration).6,7 Studies have shown that CLE can differentiate tumor cells from normal brain in real time, reducing reliance on frozen-section analysis.8-11 Although CLE's field of view is limited (200-600 µm) and it requires steady contact with the tissue, its ability to provide immediate “optical biopsy” information makes it a powerful tool for guiding resection, especially in high-grade gliomas. Several other innovative tools are also being explored for intraoperative tumor delineation. Among them, Raman spectroscopy offers label-free molecular-level tissue identification by analyzing vibrational energy shifts of inelastic light scattering.12 Hollon et al13 combined a stimulated Raman microscopy platform with a neural network, achieving near real-time identification of glioma tissue with ∼94% diagnostic accuracy. Surpassing the limitation of 2-dimensional tissue visualization, intraoperative optical coherence tomography (OCT), provides cross-sectional imaging of tissue microstructure.14 A recent study investigating the application of microscope-integrated OCT reported an 85% accuracy in detecting residual tumor at resection margins by using machine-learning analysis of OCT signal differences between tumor and normal brain.15 Finally, mass spectrometry has been integrated into the operating room with the “intelligent knife” (iKnife), which analyzes electrocautery smoke derived from the coagulation of normal and pathological tissue to identify tissue type.16 In glioma surgeries, the iKnife technology enabled real-time molecular classification of tissue with approximately 88% overall accuracy, effectively distinguishing tumor from normal brain within seconds.17 These emerging tools are increasingly paired with machine learning algorithms to enhance their speed and diagnostic precision.15,18 Each technology provides a complementary perspective—CE and CLE enhancing in vivo visualization of vascular and cellular architecture, Raman and mass spectrometry revealing biochemical composition, and OCT mapping 3-dimensional tissue structure—while seamlessly integrating into the operative theater. This multimodal approach enriches intraoperative decision-making and supports more precise, personalized interventions. As these tools advance, their synergistic potential may redefine real-time surgical diagnostics. In conclusion, Dablouk et al's study exemplifies how technological innovation can improve intraoperative tumor visualization. Their fiber-optic probe significantly increases the detection of malignant tissue compared with the standard microscope, which could translate into more complete and safe glioma resections. This contribution, alongside advances in CE, CLE, Raman/OCT imaging, and machine learning-driven diagnostics, heralds a new era of precision neurosurgery. We anticipate that continued development and integration of these tools will refine surgical decision-making and ultimately improve outcomes by enabling maximal safe resection for patients with brain tumors.