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

To the Editor: We are grateful to Drs Carbone and de Notaris for their thoughtful and insightful letter1 regarding our publication, “Use of a Single-Fiber Optical Probe for the Detection of Tumor Fluorescence in High-Grade Glioma”.2 Their commentary highlights a shared commitment to enhancing intraoperative tumor detection and maximizing the safe resection of high-grade gliomas. We particularly appreciate their discussion of contact endoscopy (CE) and confocal laser endomicroscopy (CLE), both of which represent promising adjuncts in the neurosurgical toolkit. The ability of CE to highlight unique microvascular patterns and of CLE to provide near-histological resolution imaging aligns well with the central message of our article: that objective, real-time fluorescence detection can help overcome many of the limitations inherent to conventional microscope-based visualization of 5-aminolevulinic acid-induced protoporphyrin IX fluorescence. Our work specifically addressed several practical and sensitivity-related shortcomings of traditional fluorescence-guided surgery, such as subjective interpretation and poor performance in deep surgical fields. The optical probe we studied was designed to offer a more sensitive and objective assessment of protoporphyrin IX fluorescence, using spectral data to distinguish true fluorescence signals even when they are imperceptible to the naked eye. As noted in the letter, this complements the goals of CE, CLE, and other advanced modalities, including Raman spectroscopy and optical coherence tomography, which together are reshaping the intraoperative landscape. We agree with the authors that the future of neurosurgical oncology lies in a multimodal and integrative approach to real-time diagnostics. The various technologies described in their letter when used synergistically hold promise for achieving higher precision, improved tumor margin delineation, and ultimately better outcomes for patients. We also echo their call for greater international collaboration to explore how these tools can be integrated into clinical practice and refined through shared expertise. In conclusion, we are encouraged to see our work viewed within the broader context of advancing intraoperative imaging. We thank Drs Carbone and de Notaris for their collegial engagement and thoughtful contribution to this evolving conversation.