Functional Tumor Boundaries Revealed by Dynamic Electroimpedance Imaging Under Weak Stimuli: Dissipative Structures in Melanoma Area
Authors: Babich Yuri F. 
Published: February 2025

AbstractReal-time imaging and monitoring of tumor boundaries are critical for understanding tumor growth dynamics and ensuring precise treatment. All physiological phenomena, specifically communicational, are inherently bioelectrical. Our original technology of “Skin Electrodynamic Introscopy” (SEI) firstly enabled time-lapse imaging of skin spectral electroimpedance landscape (SEL) with an unprecedented combination of temporal and spatial resolution. SEI enabled the revelation of several new phenomena in collective dynamics: the emergence of dynamic SEL structures in the melanoma region in response to weak short stimuli, such as ischemia and non-thermal EMF and MF.The main objective of this work was to identify criteria for assessing the functional boundaries of a tumor and its peritumor as a dynamic ecosystem. These boundaries are conceptualized as dissipative structures (DS)—self-organizing patterns that arise in nonequilibrium thermodynamic systems, with malignant tumors serving as a striking example. It is shown that the impedance boundaries of the tumor exceed its optical dimensions and can vary at different levels of the intra- and intercellular environment. It is proposed that the impedance boundaries are a quasi-stationary manifestation of entropy/negentropy flow from the tumor. The functional boundary can be assessed by revealing the pre-bifurcation zone of the tumor by measuring the increment of the impedance boundary in response to stimulation resulting from activation of the entropy/negentropy emitters. In this context, the invasive front of the tumor can be detected by the appearance of an antiphase impedance structure at its border.Thus, the previously discovered SEL phenomena, as well as a number of new ones, are considered the first demonstrations of DS at the tissue and cellular level. The tissue DS is determined primarily by increased group sensitivity/state of cells and their components, rather than by individual elements. Thus, insight into test-induced collective cellular behavior allows for a more nuanced (i.e. local and system) understanding of the tissue metabolism compared to traditional reductionist approaches. The dissipative nature of the observed phenomena is most effectively represented in fluctuation and correlation fields of the SEL, reflecting thus the fundamental concept of DS: the ‘Order from chaos’, which is especially relevant to tumor biology. In particular, this was demonstrated as:-Transition from initially chaotic SEL to the tumor specific patterns and back upon cessation of the stimulus;-Abrupt shift in magnitude and depth of the impedance front;-Manifestation of stroma of pre-existing nevus at the mitochondrial fluctuation field;-Emergence of the tumor resistance zone to the influence as a systemic post-effect, etc;Moreover, difference images of the SEL frames made it possible to trace the process of the DS emergence in the form of:-Wave-like dynamics around morphological boundaries of the tumor;-Expansion of initial functional microclusters at the tumor boundary;-Reverse migration of DS towards the negentropy emitters.From the ‘Order from chaos’ perspective, similarity was found between manifestations of weak information (EMF) and energy (ischemia) influence.Herewith we also attempted to estimate the information content of the spatio-temporal version of the ion balance index (as a ratio of the impedance modulus at 2 kHz and 1 MHz).In support of the DS hypothesis, the supplement presents analysis of two experiments:-Papillomatous nevus (as a relevant model for exploring the viral theory of cancer), which revealed similar and complementary effects of test-induced reorganization of the SEL;-Plant tissue (plant leaf), demonstrating the universal nature of the phenomenon of antiphase structuring.In summary, the SEL of melanoma, particularly in the context of the peritumor boundaries, reveals critical insights into how collective cellular dynamics influence tumor progression. The discovery of DS around tumors represents a significant advancement in our understanding of tumor biology. The developed approach and observed effects highlights new potential of advanced imaging techniques, it:-facilitates real-time monitoring and biofeedback in laboratory and clinical settings;-highlights the need for a paradigm shift in cancer research;-challenge traditional views on EMF exposure by demonstrating that non-thermal effects can induce significant biological responses at the tissue level;-calls for investigating tumors as dynamic entities shaped by their interactions with environmental factors, thereby opening up opportunities for innovative treatment approaches that target this adaptive behavior.