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Yoed Rabin

Publications and source records attributed to Yoed Rabin.

17 recordsLinked to original sources

An efficient numerical technique for bioheat simulations and its application to computerized cryosurgery planning.

As a part of ongoing efforts to develop computerized planning tools for cryosurgery, the current study focuses on developing an efficient numerical technique for bioheat transfer simulations. Our long-term goal is to develop a planning tool for cryosurgery that takes a 3D reconstruction of a target region, and suggests the best cryoprobe layout. Toward that goal, a planning algorithm, termed "force-field analogy," has been recently presented, based on a sequence of bioheat transfer simulations, which are by far the most computationally expensive part of the planning method. The objective in the current study is to develop a finite difference numerical scheme for bioheat transfer simulations, which reduces the overall run time of computerized planning, thereby making it clinically relevant. While the general concept of variable grid size and time intervals is not new, its application to the phase change problem of cryosurgery is the unique contribution of the current study.

Computer Simulation↗

Analysis of the effect of partial vitrification on stress development in cryopreserved blood vessels.

Thermal stress development in blood vessels, during processes associated with vitrification (vitreous means glassy in Latin), is studied. This paper addresses the limiting case where the specimen completely crystallizes, while the cryoprotectant medium (CPA) completely vitrifies. This case is expected to provide upper boundary estimates for stresses for the more common problem of a partially vitrified sample. The CPA is modeled as a linear viscoelastic medium, with viscosity increasing exponentially with decreasing temperature; given the assumption of complete crystallization, the blood vessel is modeled as linear elastic below the freezing temperature. Consistent with previous observations, the CPA is found to behave linear elastically below a set-temperature, at which point the viscosity rises sufficiently quickly with further cooling. This observation reduces computational efforts and allows for parametric studies based on suitably chosen wholly elastic models. Both 2D concentric cylinder models of the blood vessel in a straight configuration and a 3D model of the vessel curled in a vial of CPA are studied; 2D models are shown to bound the results of the more general 3D problem. It is found that stress in the CPA decreases with increase in CPA volume, at least under conditions where the temperature can be viewed as uniform. Planar cracks are predicted to form transverse to the vessel axis, and to propagate right up to the blood vessel wall. Should such cracks propagate into the vessel, even over only a few mum, the mechanical damage to the lumen, or to endothelial cells, may cause the blood vessel to completely loose its functionality at the end of the cryopreservation protocol.

Animals↗

Fracture formation in vitrified thin films of cryoprotectants.

As a part of an ongoing effort to study the continuum mechanics effects associated with cryopreservation, the current report focuses on fracture formation in vitrified thin films of cryoprotective agents. The current study combines experimental observations with continuum mechanics analysis. Experimental results have been developed using a new imaging device, termed a "cryomacroscope", which has been recently presented by the current research team. A newly developed liquid nitrogen-based cooling stage is presented in this paper. The samples under investigation are 0.5 ml droplets of cryoprotective agents, having a characteristic diameter of 20 mm and a characteristic thickness of 1.5 mm. Tested samples included dimethyl sulfoxide (DMSO) in a concentration range from 6 to 8.4M, and the cryoprotectant cocktails VS55 and DP6. Some samples contained small bovine muscle segments, having a characteristic dimension of 1mm, in order to study stress concentration effects. Experimental results show that the onset of fracturing in vitrified films of cryoprotectants is very consistent, occurring over a small temperature range. Fracture pattern, however, was affected by the cooling rate. The presence of tissue segments did not affect the onset temperature of fracture, but affected the fracture pattern. The continuum mechanics analysis solidified the hypothesis that fracture is driven by thermal stress, not by temperature per se, and allowed fracture strain to be inferred from observed fracture temperature. In conjunction with the current report, additional photos of fracture formation in thin films are available at .

Cryoprotective Agents↗

Thermal expansion of blood vessels in low cryogenic temperatures, Part II: Vitrification with VS55, DP6, and 7.05 M DMSO.

As part of the ongoing effort to study the mechanical behavior of biological materials in cryopreservation processes, the current study focuses on thermal expansion during vitrification (vitreous in Latin means glassy). A new device is utilized in this study, which has been described in detail in the companion paper (Part I). The current study (Part II) focuses on measurements of vitrified blood vessels permeated with the cryoprotectants VS55, DP6, and DMSO. Data analysis in this study includes polynomial approximation of experimental results in the lower part of the cryogenic temperature range, where the material behaves as solid over a practical time scale. The study further includes a unified thermal expansion analysis throughout the entire cryogenic temperature range by compiling the current results with previously reported data. Finally, analysis of the glass transition temperature, based on thermal strain data is presented.

Blood Vessels↗

Thermal expansion of blood vessels in low cryogenic temperatures Part I: A new experimental device.

As part of the ongoing effort to study the mechanical behavior of biological material during cryopreservation processes, the current study focuses on thermal expansion of blood vessels at low cryogenic temperatures. The current paper (Part I) describes a new experimental device for thermal expansion measurements of blood vessels in typical conditions of vitrification, which are associated with rapid cooling rates. For validation purposes, the thermal strain of frozen arteries in the absence of cryoprotectants was measured, and found to be about 10% larger than that of polycrystalline water; this observation agrees with literature data. The companion paper (Part II) reports on experimental results of cryoprotectants permeated with VS55, DP6, and 7.05 M DMSO at high cooling rates applicable to vitrification.

Blood Vessels↗

Two-phase computerized planning of cryosurgery using bubble-packing and force-field analogy.

BACKGROUND: Cryosurgery is the destruction of undesired tissues by freezing, as in prostate cryosurgery, for example. Minimally invasive cryosurgery is currently performed by means of an array of cryoprobes, each in the shape of a long hypodermic needle. The optimal arrangement of the cryoprobes, which is known to have a dramatic effect on the quality of the cryoprocedure, remains an art held by the cryosurgeon, based on the cryosurgeon's experience and "rules of thumb." An automated computerized technique for cryosurgery planning is the subject matter of the current paper, in an effort to improve the quality of cryosurgery. METHOD OF APPROACH: A two-phase optimization method is proposed for this purpose, based on two previous and independent developments by this research team. Phase I is based on a bubble-packing method, previously used as an efficient method for finite element meshing. Phase II is based on a force-field analogy method, which has proven to be robust at the expense of a typically long runtime. RESULTS: As a proof-of-concept, results are demonstrated on a two-dimensional case of a prostate cross section. The major contribution of this study is to affirm that in many instances cryosurgery planning can be performed without extremely expensive simulations of bioheat transfer, achieved in Phase I. CONCLUSIONS: This new method of planning has proven to reduce planning runtime from hours to minutes, making automated planning practical in a clinical time frame.

Computer Simulation↗

Bubble packing application in computerized planning of cryosurgery.

Among many factors, the effectiveness of the cryoprocedure is determined by the quality of the cryoprobes layout. A computerized planning tool for optimizing this layout has the potential of improving the outcome of cryosurgery, reducing post-operative complications, and reducing the cost of the clinical operation. As part of an ongoing effort to develop planning tools for cryosurgery, the current study takes a novel approach, based on bubble-packing method. This study shows that the application of bubble-packing shortens runtime by an order of magnitude. In this study, the bubble-packing method is integrated with bioheat transfer simulations to demonstrate the quality of planning.

Algorithms↗

Thermal expansion of blood vessels and muscle specimens permeated with DMSO, DP6, and VS55 at cryogenic temperatures.

As part of an ongoing effort to characterize the continuum mechanics during cryopreservation via vitrification (vitreous in Latin means glass), the current study focuses on measuring the thermal expansion of cryoprotective agents in the presence and absence of biological samples of bovine muscle and goat arteries. The cryoprotectants under investigation are 7.05 M DMSO, DP6, and VS55, with permeation time of up to 48 h. This study focuses on the upper part of the cryogenic temperature range, where the cryoprotectant behaves like a liquid in all practical applications. The specific lower boundary of this range is unique to the cryoprotectant composition and to the applied cooling rate. The measurement device used in the current study is a modification of a prototype presented recently, in which modifications are made to accommodate biological samples. Based on thermal strain observations, it is concluded that the presence of tissue samples promotes crystallization (the tissue samples serve as potential nucleation sites). It is shown in this study that the thermal strain of tissue samples permeated with 7.05 M DMSO and DP6 is no greater than the thermal expansion of the same cryoprotectants in the absence of tissue samples, and in some cases it is significantly less. For a given cryoprotectant in comparable thermal conditions, experiments on bovine muscle samples show significantly higher scattered data than experiments on artery samples.

Animals↗

Cryomacroscopy of vitrification, Part I: A prototype and experimental observations on the cocktails VS55 and DP6.

A new imaging device, termed a "cryomacroscope", is presented in this report. This device is designed to assist in exploring thermal and mechanical effects associated with large-scale vitrification and crystallization, with the current setup aimed at the range of 50 μm to 2 cm. The cryomacroscope is not intended as a substitute for the cryomicroscope, but as a complementary tool for the cryobiologist. A combination of cryomacroscopy and cryomicroscopy is suggested as a basis for multi-scale cryobiology studies. This report presents initial results on vitrification, crystallization, and fracture formation in the cryoprotectant cocktails DP6 and VS55. These results show some inconsistency in the tendency to form crystals, based on critical cooling and rewarming rates measured by means of a differential scanning calorimetric device (DSC) in parallel studies. This research is in its early stages, and comparative studies on biological materials are currently underway. Part II of this report (the companion paper) presents results for fracture formation in the cryoprotectant and discusses the mechanical stresses which promote these fractures. In conjunction with these reports, additional photos of cryomacroscopy of vitrification, crystallization, and fracture formation are available at http://www.me.cmu.edu/faculty1/rabin/CryomacroscopyImages01.htm.

Journal Article↗

Cryomacroscopy of vitrification, Part II: Experimental observations and analysis of fracture formation in vitrified VS55 and DP6.

A new imaging device, termed a "cryomacroscope", was used to observe macrofractures in the cryoprotectant cocktails DP6 and VS55. Details of the design and construction of the cryomacroscope were presented in Part I of this report, which focused on describing the apparatus and observations of crystallization. Part I and the current paper (Part II) describe events that occur as 1 mℓ of cryoprotectant contained in a glass vial is cooled from room temperature down to cryogenic temperatures (∼ -135°C). The presence of cracking, as well as patterns in their position and orientation, are found to be dependent on the cooling rate and on the specific cryoprotectant cocktail. Cracks, if present, disappear upon rewarming, although they appear to be sites for later preferential crystallization. Computations which predict temperatures and mechanical stresses are used to explain observations of cracking. In conjunction with these reports, additional photos of cryomacroscopy of vitrification, crystallization, and fracture formation are available at http://www.me.cmu.edu/faculty1/rabin/CryomacroscopyImages01.htm.

Journal Article↗

Computerized planning for multiprobe cryosurgery using a force-field analogy.

Cryosurgery is the destruction of undesired biological tissues by freezing. For internal organs, multiple cryoprobes are inserted into the tissue with the goal of maximizing cryoinjury within a predefined target region, while minimizing cryoinjury to the surrounding tissues. The objective of this study is to develop a computerized planning tool to determine the best locations to insert the cryoprobes, based on bioheat transfer simulations. This tool is general and suitable for all available cooling techniques and hardware. The planning procedure employs a novel iterative optimization technique based on a force-field analogy. In each iteration, a single transient bioheat transfer simulation of the cryoprocedure is computed. At the end of the simulation, regions of tissue that would have undesired temperatures apply "forces" to the cryoprobes directly moving them to better locations. This method is more efficient than traditional numerical optimization techniques, because it requires significantly fewer bioheat transfer simulations for each iteration of planning. For demonstration purposes, 2D examples on cross sections typical of prostate cryosurgery are given.

Algorithms↗

Computerized planning of cryosurgery using cryoprobes and cryoheaters.

In a typical minimally invasive cryoprocedure, multiple cryoprobes are inserted into the tissue with the goal of maximizing cryoinjury within a predefined target region, while minimizing cryoinjury to the surrounding tissues. A temperature-controlled electrical heater has been developed recently by this research team, in order to assist in limiting the cryoinjury to the target region. The new device has been termed a 'cryoheater,' and it can work with any cryosurgical cooling technique. A prototype computerized planning tool has been presented recently by this research team, which helps to determine the best locations in which to insert the cryoprobes. This prototype was designed for cryoprobes only. The planning procedure utilized a novel iterative optimization technique, based on a force-field analogy. The combination of cryoheaters with computerized planning is the subject matter of this report. The current report includes a review of cryoheater development, and presents an improved cryosurgery planning tool which incorporates cryoheaters.

Computer Simulation↗

Cryoheater as a means of cryosurgery control.

A new concept for cryosurgery control is presented in this paper, a concept which has the potential to dramatically change the outcome of cryosurgery. Unlike other cryosurgery control techniques, which are based on controlling the thermal performance of the cryoprobe, this new concept is based on heating the treated tissue as a means of shaping the frozen region. The new controlling heater is termed a 'cryoheater'. The cryoheater is a complementary device to the cryoprobe and can work with any cryosurgery cooling technique. In the current pilot study, the new cryoheater is demonstrated in a gelatin solution and, using heat transfer simulations, it is studied in simulated cases of prostate cryosurgery. It is suggested that cryosurgery planning tools and optimization techniques must be developed before the concept of the cryoheater can be applied in its full capacity.

Body Temperature↗

A general model for the propagation of uncertainty in measurements into heat transfer simulations and its application to cryosurgery.

This report presents a technique for estimating the propagation of uncertainty in measurements into mathematical simulations of heat transfer. The motivation for this report is to show the dramatic uncertainty associated with estimating the value of the so-called "lethal temperature," even in a case where a perfect correlation appears to exist between histo-pathologic observations and a corresponding heat transfer simulation. Although the example presented in this report relates to cryosurgery, the technique proposed in this report is rather general and can be applied to any heat transfer problem. The uncertainty analysis presented in this report can be considered as an extension of the well-known concept of the rule of the square root of the sum of the square errors. A comparison of the new technique with the worst case scenario concept is also presented. In conclusion, it is recommended that the proposed technique be routinely applied when presenting simulated results, whether as a part of a theoretical study, or in comparison with experimental data.

Animals↗

Thermal expansion measurements of cryoprotective agents. Part II: measurements of DP6 and VS55, and comparison with DMSO.

As part of an ongoing effort to characterize the mechanical behavior of biological tissues in the cryogenic temperature range, the current study focuses on thermal expansion measurements of cryoprotective agents. Utilizing the experimental apparatus described in the previous report (Part I), the current report (Part II) includes thermal expansion measurements of the cryoprotectant mixtures DP6 and VS55, and comparison with available data from the literature on DMSO. In the temperature range in which the cryoprotectant mixture behaves like low viscosity liquid, results of this study show that the thermal expansion coefficient of VS55 and DP6 is 22% and 40% lower than that of 3M DMSO, respectively, where 3M DMSO is only one component of each cryoprotectant mixture. This significant difference is attributed to the presence of 3M formamide in VS55.

Cryoprotective Agents↗

Thermal expansion measurements of cryoprotective agents. Part I: a new experimental apparatus.

As part of an ongoing effort to characterize the mechanical behavior of biological tissues in the cryogenic temperature range, the current study focuses on the thermal expansion measurements of cryoprotective agents. This study focuses on the upper part of the cryogenic temperature range, where the cryoprotectant behaves like low viscous liquid at all practical cooling rates. For the purpose of this study, a new apparatus for thermal expansion measurements has been designed and constructed. Part I of this study (the current report) includes: a description of the new experimental apparatus, the techniques of operation, calibration, system validation, and a detailed uncertainty analysis. Part II of this study (the report following) includes thermal expansion measurements of the cryoprotectant mixtures DP6 and VS55, and comparison with data from the literature on DMSO solutions.

Cryopreservation↗

The thermal effect of urethral warming during cryosurgery.

The heating effect of urethral warming during cryosurgery has been investigated theoretically, via heat transfer simulations. Two warmer configurations have been considered: (i). the clinically available urethral warmer, which has a configuration of a counter flow fluid heat exchanger; (ii). a newly designed urethral warmer, based on a temperature controlled electrical heater, termed a "cryoheater". A dramatic effect of thermal resistance to heat transfer through the heat exchanger wall has been identified, which is absent in the cryoheater. It follows that the cryoheater is expected to be more efficient in generating an unfrozen region around the urethra. It is shown that the conventional heat exchanger may fail to prevent freezing around the urethra in a significant number of prostate cases, depending on the layout of cryoprobes around the urethra. On the other hand, clinical reports exist which suggest that the heat exchanger improves in many cases the outcome of cryosurgery, in terms of long term complications. It is speculated in the current report that the cryoheater can further improve the outcome of cryosurgery, by providing protection from freezing in a wider range of cases. It is suggested that a future study be conducted to examine the correlation between the layout of cryoprobes and surgical outcome.

Cryosurgery↗