The role of potassium in depth profiling of the tumor border in bone-invasive oral cancer using laser-induced breakdown spectroscopy (LIBS): a pilot study

Abstract

Purpose Microscopic tumor spread beyond the macroscopically visible tumor mass in bone represents a major risk in surgical oncology, where the spatial complexity of bony resection margins cannot be countered with rapid bone analysis techniques. Laser-induced breakdown spectroscopy (LIBS) has recently been introduced as a promising option for rapid bone analysis. The present study aimed to use LIBS-based depth profiling based on electrolyte disturbance tracking to evaluate the detection of microscopic tumor spread in bone. Methods After en bloc resection, the tumor-infiltrated mandible section of a patient’s segmental mandibulectomy specimen was natively investigated using LIBS. Spectral and electrolytic depth profiles were analyzed across 30 laser shots per laser spot position in healthy bone and at the tumor border. For the histological validation of the lasered positions, the mandibular section was marked with a thin separating disc. Results Solid calcium (Ca) from hydroxyapatite and soluble Ca from dissolved Ca can be reliably differentiated using LIBS and reflect the natural heterogeneity of healthy bone. Increased potassium (K) emission values in otherwise typically healthy bone spectra are the first spectral signs of tumorous bone invasion. LIBS-based depth profiles at the tumor border region can be used to track tumor-associated changes within the bone with shot accuracy based on the distribution of K. Conclusion Depth profiling using LIBS might enable the detection of microscopic tumor spread in bone. In the future, direct electrolyte tracking using LIBS should be applied to other intraoperative challenges in surgical oncology to advance rapid bone analysis by spectroscopic–optical techniques.

Assessment of the Electrolyte Heterogeneity of Tissues in Mandibular Bone-Infiltrating Head and Neck Cancer Using Laser-Induced Breakdown Spectroscopy

“…In the present study, the tissue-specific discrimination of the human LIBS spectra was predominantly based on the LIBS emission values of Ca and K. The sufficient LIBS-based tissue separation is exciting, in that tumorous and nontumorous human tissues with comparable densities and consistency were differentiated in this study based on their LIBS signals. Healthy bone substances, whose LIBS spectra were characterized by high Ca and low K signals in our previous work [ 20 , 23 ], were not taken into account in this study for the identification of tissue-specific differences.…”

“…These included Ca with calcium oxide (CaO) and calcium hydroxide (CaOH) emission lines and K, while Na was less suitable for capturing tissue heterogeneity in this study. Further discussion regarding the wavelengths used in this study is already part of previous publications on calibration experiments with K on native sample material [ 19 ] and previous works on the use of LIBS as a rapid bone analysis technique [ 20 ] and LIBS-based depth profiling [ 23 ].…”

“…The results of the current study may contribute to a better understanding of the complexity in the dysregulation of Ca, K and Na ion channels in head and neck cancer cells [ 21 ]. While K and Na are involved in the invasiveness, progression and proliferation of head and neck cancer cells [ 21 , 34 ], Ca channels are involved in the differentiation of osteoblasts and osteoclasts [ 22 ] and thus, orchestrate the invasion of head and neck tumors into bone [ 22 , 35 ], as recently discussed [ 23 ]. Since the present study provides an indicative overview of electrolyte levels within tumorous and nontumorous tissues in mandibular bone-infiltrating head and neck cancer, future studies are needed to investigate the relationship of K, Na, and Ca levels in tumor tissues with more advanced statistical methods in more detail.…”

“…After optimizing the technical requirements of a LIBS-based experimental setup for instrumentation on native sample material and developing a robust method for the evaluation of LIBS spectra [ 19 ], we were able to describe the use of LIBS as a promising and innovative possibility for rapid bone analysis for the first time [ 20 ]. Subsequently, LIBS-based tracking of the electrolytes calcium (Ca), potassium (K), and sodium (Na), which are involved in the progression of head and neck tumors [ 21 ] and in the invasion of tumors into bone [ 22 ], was used to record depth profiles at the border of bone-infiltrating head and neck tumors [ 23 ]. The further development of LIBS-based rapid bone analysis as a feedback control of a laser surgical system requires algorithms for tissue recognition that can distinguish not only healthy bone but also nerve tissue and fibrosis from tumor stroma and cell-rich tumor areas.…”

“…As the next step of the research, the knowledge gained from our previous LIBS studies, which focused on healthy bone and bone-infiltrating oral cancer [ 20 , 23 ], needs to be transferred to other tumorous and nontumorous tissues from mandibular bone-infiltrating head and neck cancer. Accordingly, this study aimed to characterize the electrolyte composition of different tissues with LIBS in preparation for the development of LIBS-based tissue detection algorithms and to enable LIBS for the full-scale evaluation of segmental mandibulectomy specimens.…”