Ultrasound-based geometric modeling of the human ovary with applications to cryopreservation.

Successful cryopreservation of the whole ovary outside of the body, while a woman undergoes cancer treatments, may help preserving fertility and regaining hormone balance during recovery. One of the key challenges in whole ovary cryopreservation is adequately loading the organ with cryoprotective agents (CPAs). Another notable challenge in developing the application is the lack of geometric data needed for designing matching thermal protocols.

Vitreous tissue cryopreservation using a blood vessel model and cryomacroscopy for scale-up studies: Observations and mathematical modeling.

Successful long-term cryobanking of multicellular tissues and organs at deep subzero temperatures calls for the avoidance of ice cryoinjury by reliance upon ice-free cryopreservation techniques. However, the quality of the cryopreserved material is the direct result of its ability to survive a host of harmful mechanisms, chief among which is overcoming the trifecta effects of ice crystallization, toxicity, and mechanical stress. This study aims at exploring improved conditions to scale-up ice-free cryopreservation by combining DP6 as a base cryoprotective agent (CPA) solution with an array of synthetic ice modulators (SIMs).

Thermomechanical stress analyses of nanowarming-assisted recovery from cryopreservation by vitrification in human heart and rat heart models.

This study investigates thermomechanical stress in cryopreservation by vitrification of the heart, while exploring the effects of nanowarming-assisted recovery from cryogenic storage. This study expands upon a recently published study, combining experimental investigation and thermal analysis of cryopreservation on a rat heart model. Specifically, this study focuses on scenarios with variable concentrations of silica-coated iron-oxide nanoparticles (sIONPs), while accounting for loading limitations associated with the heart physiology, as well as the properties of cryoprotective agent (CPA) solution and the geometry of the container.

Is isochoric vitrification feasible?

This study investigates the feasibility of ice-free isochoric vitrification for cryopreservation applications using mathematical modeling, computation tools, and the underlying principles of thermo-mechanics. This study is triggered by an increasing interest in the possibility of isochoric vitrification, following promising experimental results of isochoric cryopreservation. In general, isochoric cryopreservation is the preservation of biological materials in subzero temperatures in a rigid-sealed container, where some ice crystallization creates favorable pressure elevation due to the anomaly of water expansion upon ice Ih formation.

Large surface deformation due to thermo-mechanical effects during cryopreservation by vitrification - mathematical model and experimental validation.

This study presents a simplified thermal-fluids (TF) mathematical model to analyze large surface deformations in cryoprotective agents (CPA) during cryopreservation by vitrification. The CPA deforms during vitrification due to material flow caused by the combined effects of thermal gradients within the domain, thermal contraction due to temperature, and exponential increase in the viscosity of the CPA as it is cooled towards glass transition. While it is well understood that vitrification is associated with thermo-mechanical stress, which might lead to structural damage, those large deformations can lead to stress concentration, further intensifying the probability to structural failure.

Thermal Analyses of Nanowarming-Assisted Recovery of the Heart From Cryopreservation by Vitrification.

This study explores thermal design aspects of nanowarming-assisted recovery of the heart from indefinite cryogenic storage, where nanowarming is the volumetric heating effect of ferromagnetic nanoparticles excited by a radio frequency electromagnet field. This study uses computational means while focusing on the human heart and the rat heart models. The underlying nanoparticle loading characteristics are adapted from a recent, proof-of-concept experimental study.

Vitrification and Rewarming of Magnetic Nanoparticle-Loaded Rat Hearts.

To extend the preservation of donor hearts beyond the current 4-6 h, this paper explores heart cryopreservation by vitrification-cryogenic storage in a glass-like state. While organ vitrification is made possible by using cryoprotective agents (CPA) that inhibit ice during cooling, failure occurs during convective rewarming due to slow and non-uniform rewarming which causes ice crystallization and/or cracking. Here an alternative, "nanowarming", which uses silica-coated iron oxide nanoparticles (sIONPs) perfusion loaded through the vasculature is explored, that allows a radiofrequency coil to rewarm the organ quickly and uniformly to avoid convective failures.

Thermo-mechanics aspects of isochoric cryopreservation: A new modeling approach and comparison with experimental data.

A new mathematical model is proposed for the analysis of thermo-mechanics effects during isochoric cryopreservation. In that process, some ice crystallization in a fixed-volume container drives pressure elevation, which may be favorable to the preservation of biological material when it resides in the unfrozen portion of the same container. The proposed model is comprehensive, integrating for the first time concepts from the disparate fields of thermodynamics, heat transfer, fluid mechanics, and solid mechanics.

Analysis of crystallization during rewarming in suboptimal vitrification conditions: a semi-empirical approach.

Circumventing ice formation is critical to successful cryopreservation by vitrification of large organs. While ice formation during the cooling part of the cryogenic protocol is dictated by the evolving thermal conditions, ice formation during the rewarming part of the cryogenic protocol is also dependent on the history of cooling and storage conditions. Furthermore, while the exothermic effect of ice crystallization during cooling tends to adversely slow down the desired high cooling rates to ensure ice-free preservation, the same effect under some conditions tends to assist acceleration of rewarming during recovery of the specimen from cryogenic storage when limited crystallization does occur.

Mathematical modeling of surface deformation during vitrification.

Mathematical modeling of surface deformation during cryopreservation by vitrification is presented in this study. The specific problem under consideration is of a cryoprotective agent (CPA) solution vitrifying in a vial, following previously obtained cryomacroscopy observations. A multiphysics solution is proposed in this study, combining coupled effects associated with heat transfer, fluid mechanics, and solid mechanics.

Scaling Effects on the Residual Thermomechanical Stress During Ice-Free Cooling to Storage Temperature.

Cryopreservation via vitrification (glass formation) is a promising approach for long-term preservation of large-size tissues and organs. Unfortunately, thermomechanical stress, which is driven by the tendency of materials to change size with temperature, may lead to structural failure. This study focuses on analysis of thermomechanical stress in a realistic, pillow-like shape cryobag as it is cooled to cryogenic storage, subject to sufficiently high cooling rates to facilitate vitrification.

Thermomechanical stress analysis of rabbit kidney and human kidney during cryopreservation by vitrification with the application of radiofrequency heating.

This study presents a computational framework for thermomechanical stress analysis in a specimen undergoing cryopreservation, with emphasis on radiofrequency (RF) heating for recovering from cryogenic storage. In particular, this study addresses cryopreservation by vitrification, where the specimen is stored in the amorphous phase (vitreous means glassy). In broad terms, the relatively high cooling and rewarming rates necessary for vitrification result in differential thermal expansion in the specimen, which is the driving force for thermomechanical stress.

Thermal conductivity of cryoprotective agents loaded with nanoparticles, with application to recovery of preserved tissues and organs from cryogenic storage.

The objective of this study is to provide thermal conductivity data for CPA-based nanofluids for the benefit of the analyses of cryopreservation by vitrification. Thermal conductivity measurements were conducted using a hot-wire technique on an experimentation platform of the cryomacroscope, to correlate measurements with observed physical effects such as crystallization and fracturing. Tested materials in this study include the CPA cocktails M22, VS55, DP6, and DP6+sucrose.

Soft tissue deformation tracking by means of an optimized fiducial marker layout with application to cancer tumors.

Objective: Interventional radiology methods have been adopted for intraoperative control of the surgical region of interest (ROI) in a wide range of minimally invasive procedures. One major obstacle that hinders the success of procedures using interventional radiology methods is the preoperative and intraoperative deformation of the ROI. While fiducial markers (FM) tracing has been shown to be promising in tracking such deformations, determining the optimal placement of the FM in the ROI remains a significant challenge.

Thermal analysis of marginal conditions to facilitate cryopreservation by vitrification using a semi-empirical approach.

This study aims at the thermal analysis of marginal conditions leading to cryopreservation by vitrification, which appears to be the only alternative for indefinite preservation of large-size tissues and organs. The term "marginal conditions" here refers to cooling rates in close range with the so-called critical cooling rate, above which crystallization is avoided. The analysis of thermal effects associated with partial crystallization during vitrification is associated with the coupled phenomena of heat transfer and kinetics of crystallization.

Analysis of polarized-light effects in glass-promoting solutions with applications to cryopreservation and organ banking.

This study presents experimental results and an analysis approach for polarized light effects associated with thermomechanical stress during cooling of glass promoting solutions, with applications to cryopreservation and tissue banking in a process known as vitrification. Polarized light means have been previously integrated into the cryomacroscope-a visualization device to detect physical effects associated with cryopreservation success, such as crystallization, fracture formation, and contamination. The experimental study concerns vitrification in a cuvette, which is a rectangular container.

Vitrification tendency and stability of DP6-based vitrification solutions for complex tissue cryopreservation.

Vitrification tendency and stability of the amorphous state were analyzed by means of differential scanning calorimetry (DSC) for the vitrification solution DP6, with and without additional solutes to enhance ice suppression. This study is a part of an ongoing research effort to characterize the thermophysical and mechanical properties of DP6 and its derivatives, and their qualities as cryoprotective solutions. DP6 was determined to have a critical cooling rate necessary to ensure vitrification of 2.

Reconstruction of a Deformed Tumor Based on Fiducial Marker Registration: A Computational Feasibility Study.

Interstitial photodynamic therapy has shown promising results in the treatment of locally advanced head and neck cancer. In this therapy, systemic administration of a light-sensitive drug is followed by insertion of multiple laser fibers to illuminate the tumor and its margins. Image-based pretreatment planning is employed in order to deliver a sufficient light dose to the complex locally advanced head-and-neck cancer anatomy, in order to meet clinical requirements.

Defeating Cancers' Adaptive Defensive Strategies Using Thermal Therapies: Examining Cancer's Therapeutic Resistance, Ablative, and Computational Modeling Strategies as a means for Improving Therapeutic Outcome.

Background: Diverse thermal ablative therapies are currently in use for the treatment of cancer. Commonly applied with the intent to cure, these ablative therapies are providing promising success rates similar to and often exceeding "gold standard" approaches. Cancer-curing prospects may be enhanced by deeper understanding of thermal effects on cancer cells and the hosting tissue, including the molecular mechanisms of cancer cell mutations, which enable resistance to therapy.

The role of exposure time in computerized training of prostate cryosurgery: performance comparison of surgical residents with engineering students.

Purpose: This study aims at the evaluation of a prototype of a computerized trainer for cryosurgery-the controlled destruction of cancer tumors by freezing. The hypothesis in this study is that computer-based cryosurgery training for an optimal cryoprobe layout is essentially a matter of exposure time, rather than trainee background or the specific computer-generated planning target. Key geometric features under considerations are associated with spatial limitations on cryoprobes placement and the match between the resulted thermal field and the unique anatomy of the prostate.

Thermal Analyses of a Human Kidney and a Rabbit Kidney During Cryopreservation by Vitrification.

This study focuses on thermal analysis of the problem of scaling up from the vitrification of rabbit kidneys to the vitrification of human kidneys, where vitrification is the preservation of biological material in the glassy state. The basis for this study is a successful cryopreservation protocol for a rabbit kidney model, based on using a proprietary vitrification solution known as M22. Using the finite element analysis (FEA) commercial code ANSYS, heat transfer simulations suggest that indeed the rabbit kidney unquestionably cools rapidly enough to be vitrified based on known intrarenal concentrations of M22.

Computerized Planning of Prostate Cryosurgery and Shape Considerations.

The current study aims to explore possible relationships between various prostate shapes and the difficulty in creating a computer-based plan for cryosurgery. This research effort is a part of an ongoing study to develop computational means in order to improve cryosurgery training and education. This study uses a computerized planner-a key building block of a recently developed prototype for cryosurgery training.

A Computerized Tutor Prototype for Prostate Cryotherapy: Key Building Blocks and System Evaluation.

This paper focuses on the evaluation of a prototype for a computer-based tutoring system for prostate cryosurgery, while reviewing its key building blocks and their benchmark performance. The tutoring system lists geometrical constraints of cryoprobe placement, displays a rendered shape of the prostate, simulates cryoprobe insertion, enables distance measurements, simulates the corresponding thermal history, and evaluates the mismatch between the target region shape and a pre-selected planning isotherm. The quality of trainee planning is measured in comparison with a computer-generated plan, created for each case study by a previously developed planning algorithm, known as bubble-packing.

The promise of organ and tissue preservation to transform medicine.

The ability to replace organs and tissues on demand could save or improve millions of lives each year globally and create public health benefits on par with curing cancer. Unmet needs for organ and tissue preservation place enormous logistical limitations on transplantation, regenerative medicine, drug discovery, and a variety of rapidly advancing areas spanning biomedicine. A growing coalition of researchers, clinicians, advocacy organizations, academic institutions, and other stakeholders has assembled to address the unmet need for preservation advances, outlining remaining challenges and identifying areas of underinvestment and untapped opportunities.

Improved tissue cryopreservation using inductive heating of magnetic nanoparticles.

Vitrification, a kinetic process of liquid solidification into glass, poses many potential benefits for tissue cryopreservation including indefinite storage, banking, and facilitation of tissue matching for transplantation. To date, however, successful rewarming of tissues vitrified in VS55, a cryoprotectant solution, can only be achieved by convective warming of small volumes on the order of 1 ml. Successful rewarming requires both uniform and fast rates to reduce thermal mechanical stress and cracks, and to prevent rewarming phase crystallization.