Estimation of the stable frozen zone volume and the extent of contrast for a therapeutic substance

Korpan, Nikolai N.; Chefranov, S. G.

doi:10.1371/journal.pone.0238929

Cited by 6 publications

(3 citation statements)

References 14 publications

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“…Their purpose was tumour modelling, but adaptation to using our model is relatively straightforward. In fact, there is much interest in modelling ice propagation in tissues and organs for the purposes of tumour ablation, known as cryosurgery [ 60 ]. Ice propagation in complex tissues is thought to occur first in the vasculature, followed by nucleation in capillaries where it then spreads throughout the tissue or organ [ 61 ].…”

Section: Resultsmentioning

confidence: 99%

A three-dimensional lattice-free agent-based model of intracellular ice formation and propagation and intercellular mechanics in liver tissues

Amiri,

Benson

2024

R. Soc. Open Sci.

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A successful cryopreservation of tissues and organs is crucial for medical procedures and drug development acceleration. However, there are only a few instances of successful tissue cryopreservation. One of the main obstacles to successful cryopreservation is intracellular ice damage. Understanding how ice spreads can accelerate protocol development and enable model-based decision-making. Previous models of intracellular ice formation in individual cells have been extended to one-cell-wide arrays to establish the theory of intercellular ice propagation in tissues. The current lattice-based ice propagation models do not account for intercellular forces resulting from cell solidification, which could lead to mechanical disruption of tissue structures during freezing. Moreover, these models have not been expanded to include more realistic tissue architectures. In this article, we discuss the development and validation of a stochastic model for the formation and propagation of ice in small tissues using lattice-free agent-based model. We have improved the existing model by incorporating the mechanical effects of water crystallization within cells. Using information from previous research, we have also created a new model that accounts for ice growth in tissue slabs, spheroids and hepatocyte discs. Our model demonstrates that individual cell freezing can have mechanical consequences and is consistent with earlier findings.

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Section: Resultsmentioning

confidence: 99%

A three-dimensional lattice-free agent-based model of intracellular ice formation and propagation and intercellular mechanics in liver tissues

Amiri,

Benson

2024

R. Soc. Open Sci.

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“…Their purpose was tumour modelling, but adaptation to using our model is relatively straightforward. In fact, there is much interest in modeling ice propagation in tissues and organs for the purposes of tumour ablation, known as cryosurgery [61]. Ice propagation in complex tissues is thought to occur first in the vasculature, followed by nucleation in capillaries where it then spreads throughout the tissue or organ [62].…”

Section: Resultsmentioning

confidence: 99%

An agent based model of intracellular ice formation and propagation in small tissues

Amiri

Benson

2022

Preprint

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Successful cryopreservation of tissues and organs would be a critical tool to accelerate drug discovery and facilitate myriad life saving and quality of life improving medical interventions. Unfortunately success in tissue cryopreservation is quite limited, and there have been no reports of successful long term organ cryopreservation. One principal challenge of tissue and organ cryopreservation is the propagation of damaging intracellular ice. Understanding the probability that cells in tissues form ice under a given cryopreservation protocol would greatly accelerate protocol design, enabling rational model-based decisions of all aspects of the cryopreservation procedure. Established models of intracellular ice formation (IIF) in individual cells have previously been extended to small linear (one-cell-wide) arrays to establish the theory of intercellular ice propagation in tissues. However these small-scale lattice-based tissue ice propagation models have not been extended to more realistic tissue structures, and do not account for intercellular forces that arise from the expansion water into ice that may cause mechanical disruption of tissue structures during freezing. To address these shortcomings, here we present the development and validation of a lattice-free agent-based stochastic model of ice formation and propagation in small tissues. We validate our Monte Carlo model against Markov chain models in the linear two-cell and four-cell arrays presented in the literature, as well as against new Markov chain results for 2 × 2 arrays. Moreover we expand the existing model to account for the solidification of water into ice in cells. We then use literature data to inform a model of ice propagation in hepatocyte disks, spheroids, and tissue slabs. Our model aligns well with previously reported experiments, and demonstrates that the mechanical effects of individual cells freezing can be captured.Author summaryThe widespread ability to successfully store, or cryopreserve, tissues and organs in liquid nitrogen temperatures would be game changing for human and animal medicine and drug discovery. However, success is limited to a select number of small tissues, and no organs can currently be stored in a frozen or solid state and survive thawing. One major contributor to damage during this process is the formation of intracellular ice, and its associated cell level damage. This ice formation is complicated in tissues by the number of intercellular connections facilitating intercellular ice propagation. Previous researchers have developed and experimentally validated simple one dimensional models of ice propagation in tissues, but these fail to capture complex tissue geometries, and have many fewer intercellular connections compared to three dimensional tissues. In this paper, we adopt previous models of ice formation and propagation to a model capable of capturing arbitrary cell orientations in three dimensions, allowing for realistic tissue structures to be modelled. We validated this tool on simple models and with experimental data, and then test it on three structures made of digital liver cells: disks, spheroids, and slabs. We show that we can capture new information about the interaction of cooling the tissue, the formation of intracellular ice, the movement of ice from one cell to another, and the mechanical disruption that occurs during this process. This allows for novel insights into a mechanism of damage during cryopreservation that is cooling rate and tissue structure dependent.

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“…Also, using the IRT method, we have monitored in real time the parameters of the freezing and thawing areas caused by exposure to low temperature in vivo [21,25]. The in vitro results [26] have demonstrated the hemispherical shape of the frozen volume under a point cryo-applicator. Based on this, we have assumed the equivalence of the radial temperature distribution on the surface and in the volume of the ice hemisphere.…”

Section: Studying Thermal Fields Of the Skin Exposed To Low Temperaturementioning

confidence: 99%

ТЕРМОГРАФІЧНЕ ДОСЛІДЖЕННЯ УРАЖЕННЯ М’ЯКИХ ТКАНИН ЛЮДИНИ ТА НИЗЬКОТЕМПЕРАТУРНОГО ВПЛИВУ НА БІОЛОГІЧНІ ТКАНИНИ in vivo

et al. 2022

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Вступ. Інфрачервона термографія на сьогодні використовується у клінічній практиці лише як додатковий метод через недостатні знання про патофізіологічні основи теплових зображень.Проблематика. Основним методом діагностики тяжкості ураження м’яких тканин є візуальна оцінка лікаря. Наразі не існує неінвазивного методу контролю динаміки температури в замороженій зоні в реальному часі кріовпливу.Мета. Оцінити можливості термографії для кількісної діагностики тяжкості ураження м’яких тканин при термічних та інших ушкодженнях, неінвазивного контролю стану рани під час лікування, поточного контролю динаміки теплового поля в замороженій зоні протягом кріовпливу на шкіру.Матеріали й методи. У дослідженні взяли участь 80 пацієнтів з ураженням м’яких тканин, яких обстежували оригінальним матричним термографом протягом періоду лікування. Контроль кріовпливу на м’які тканини 30 експериментальних тварин проводили за допомогою іншого оригінального термографу, розробленого для вимірювання низькотемпературних теплових полів.Результати. Запропоновано прогнозний метод оцінки категорії потенціалу загоєння опікової рани за середнімзначенням її відносної температури. Для оцінки прогностичної якості методу застосовано ROC-аналіз (Receiver Opera ting Characteristic): числовий показник площі під кривою чутливості та специфічності методу склав 0.79, що відповідає хорошій якості прогнозного методу. Встановлено, що співвідношення діаметрів зони первинного некрозу та замороженої зони становить 0,63 ± 0,3 при використаних параметрах низькотемпературного впливу. Під час відтавання спостерігалася тривала квазістабільна стадія розмірів і температур замороженої зони.Висновки. Показано можливість успішного використання термографії як для моніторингу уражень м’яких тканин на всіх етапах лікування, зокрема як для кількісної оцінки потенціалу загоєння опікових ран, так і для інтраопераційного контролю параметрів замороженої зони під час кріодеструкції тканин.

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Estimation of the stable frozen zone volume and the extent of contrast for a therapeutic substance

Cited by 6 publications

References 14 publications

A three-dimensional lattice-free agent-based model of intracellular ice formation and propagation and intercellular mechanics in liver tissues

A three-dimensional lattice-free agent-based model of intracellular ice formation and propagation and intercellular mechanics in liver tissues

An agent based model of intracellular ice formation and propagation in small tissues

ТЕРМОГРАФІЧНЕ ДОСЛІДЖЕННЯ УРАЖЕННЯ М’ЯКИХ ТКАНИН ЛЮДИНИ ТА НИЗЬКОТЕМПЕРАТУРНОГО ВПЛИВУ НА БІОЛОГІЧНІ ТКАНИНИ in vivo

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