Researchers from the Marqués de Valdecilla Research Institute (IDIVAL), the Marqués de Valdecilla University Hospital (HUMV) and the University of Cantabria (UC) have studied the combination of two complementary optical technologies to differentiate tumour tissue from the brain tissue surrounding it in patients with glioblastoma. The findings, published in the scientific journal World Neurosurgery, open up a potential avenue for improving the identification of tumour margins during surgery.
Glioblastoma is one of the most aggressive brain tumours and presents a particular challenge during surgery due to its ability to progressively infiltrate the surrounding brain tissue. This characteristic makes it difficult to accurately delineate tumour margins and achieve maximal resection while maintaining patient safety.
In this context, the study explored the integration of a label-free nanoplasmonic biosensor and confocal laser endomicroscopy (CLE), two technologies that provide different and potentially complementary information about the tissue.
The study was conducted prospectively and exploratorily using 45 pairs of tissue samples obtained during surgery in patients with grade 4 glioblastoma according to the World Health Organization classification. In each case, samples from the tumour and peritumoural tissue were analysed, using histopathological diagnosis as the reference standard.
The nanoplasmonic biosensor enables tissue characterisation based on its refractive index, without the need for markers. The results showed significant differences between the two types of tissue: the tumour had a higher refractive index than the peritumoural tissue, with median values of 1.350 and 1.345, respectively.
Analysis of the biosensor’s performance showed an area under the ROC curve of 0.71. Using the refractive index threshold established in the study, the technology achieved a sensitivity of 88%, a specificity of 41% and an accuracy of 68% for identifying tumour tissue.
In addition, a subgroup of 14 pairs of samples underwent analysis using confocal laser endomicroscopy. This technology provides high-resolution images and enables assessment of the morphological characteristics of the tissue. The classification obtained using CLE was concordant with the histopathological diagnosis in 86% of the samples analysed.
One of the main aspects of interest in the study is the potential complementarity between the two technologies. While the nanoplasmonic biosensor provides quantitative information on the optical and biophysical properties of the tissue, confocal endomicroscopy provides morphological information about its microscopic structure.
The exploratory analysis conducted by the researchers suggests that the two approaches may have different strengths in tissue discrimination. CLE showed greater concordance in the identification of negative samples, while the biosensor performed better in identifying tumour tissue.
These findings therefore raise the possibility of combining quantitative and morphological information to improve the assessment of glioblastoma margins during surgery. However, the authors point out that these are preliminary results and that further studies will be needed to validate the findings in larger cohorts and to evaluate multimodal strategies under intraoperative conditions.
The study was conducted by Laura Bauluz, Víctor García-Milán, Sara Marcos, Rubén Martín-Láez, Dolores Ortiz, Fernando Moreno, José Luis Fernández-Luna, Alfredo Franco and Carlos Velásquez, in a multidisciplinary study bringing together expertise in neurosurgery, neuropathology, cell biology and photonic technologies.
Laura Bauluz played a prominent role in the neurosurgical aspects and analysis of the study, while Sara Marcos was centrally involved in the neuropathological assessment using confocal endomicroscopy. The project was coordinated by Alfredo Franco and Carlos Velásquez, integrating the development of the nanoplasmonic biosensor with its application to a clinical challenge such as the identification of glioblastoma margins.
