Functional Tumor Boundary and its Response to Short Mild Stimuli: First Dynamic 2D Electroimpedance Evidences of Dissipative Structures at Tissue Level

The Hanahan-Weinberg hallmarks of cancer framework conceptualizes cancer as a hostile ecosystem within the larger human system. The functional boundary of a tumor (FBT) can be characterized by the size and activity of the intermediate zone -a "battlefield"--driven by the interplay of cellular heterogeneity and environmental factors. The pioneering technology of functional imaging "Skin Electrodynamic Introscopy" has a unique combination of spatial and temporal resolution on a fairly large scanning area, which allowed dynamic visualization of the spectral impedance landscape (SEL), and thus to overlap and monitor the intermediate zone in our melanoma studies. A new class of SEL phenomena was discovered for the first time: the test-induced manifestation of coherent dynamic macroscopic structuring at the tissue level, thus reflecting the collective processes of intercellular interactions in parameters of the intra- and intercellular level. It turned out that these effects are highly sensitive to short weak stimuli like ischemia, non-thermal EMF and MF. Our primary objective was to identify general indicators of tumor functional boundary (FTB) manifestation within spectral electrical impedance parameters. Utilizing five datasets acquired through our innovative SEI technology, we aimed to evaluate the static and dynamic characteristics of the FTB in relation to its VB, contrasting them against the surrounding tissue. This study interprets observed effects through the lens of the theory of self-organization and dissipative structures. The findings provide the first empirical evidence of dissipative structuring at the tissue level, observed across the majority of the investigated phenomena- as transition from initially chaotic SEL to the tumor specific patterns and back upon cessation of the stimulus: - Initial impedance boundaries are significantly wider than visible ones, approximately repeating their shape. The stimulation leads to activation of intermediate zone and expansion of impedance boundaries, especially noticeable at the invasive fronts. - Relaxation of intermediate zone in the form of mobile clusters; - Emergence of antiphase structures/clusters as markers of the tumor invasive fronts, - Emergence of the tumor resistance zone to the influence as a post effect; - Significant spatial and temporal differences of FTB at the intra- and intercellular level, which is especially noticeable at the level of mitochondrial membranes; - Manifestation of stroma of pre-existing nevus at the mitochondrial fluctuation field; - Weakening or loss of the most phenomena in a case of X-rays exposure. Additionally, we report: - Informational significance of the ion imbalance maps; - Common features and differences found in a papillomatous nevus; - Antiphase structuring under stress in a plant leaf. The results demonstrate the potential of dynamic electrical impedance imaging to delineate tumor heterogeneity and offer novel insights into cancer-host interactions during targeted interventions in real time. Simple SummaryObjective assessment of tumor boundaries and its affected surrounding is a key and persistent problem for all types of cancer. Our previous in vivo experiments with melanoma firstly revealed: significant excess of impedance boundaries over visible ones and its increased sensitivity to weak and short stimuli (ischemia, electromagnetic and magnetic fields). This emerged e.g. as antiphase structuring at the visible tumor boundaries. Additional processing revealed a number of new phenomena like advance and reversal of impedance fronts in response to the stimuli. It is assumed that the revealed phenomena are the first registration of dissipative structuring at the tissue level. The results demonstrate potential of the dynamic electroimpedance imaging to delineate tumor functional boundaries and assess adaptive responses to external stimuli in real time.