Development of Gradient Smoothing Operations and Application to Biological Systems

Ph.DDOCTOR OF PHILOSOPH

An Approach to Improving Efficacy of Cryosurgery: Numerical and Experimental (Using Gel Phantoms) Studies

Freezing and ablating using cryosurgery is becoming a promising surgical tool for the treatment of tumours. For improving the efficiency of the cryosurgical procedure, different approaches have been implemented till now. Most of these techniques have focussed on the freezing process, without giving adequate attention to the damage to the surrounding healthy tissue. In this study, a novel concept is proposed which achieves the desired freezing while protecting the surrounding healthy tissue through the use of low thermal conductivity liquid layer (perfluorocarbons) around the interface of the tumour. Numerical modelling has been done to determine the location of the ice fronts in the presence of this perfluorocarbon layer around the boundary of the tumour. It is noticed that this method leads to a higher ablation rate substantially reducing the surgical time. Also, an optimal offset, i.e. the minimum distance between the tip of the cryoprobe and the boundary of the tumour, is identified for a given tumour radius and active length which gives maximum tumour necrosis in minimum time. It is also observed that for a 2 mm increase in the active length of the cryoprobe, the decrease in optimal offset is approximately 1 mm. Furthermore, for the tumour with different radii (between 10 mm and 15 mm), with same active length of the cryoprobe, the time taken for complete ablation of the larger tumour is nearly 2.7 times the time taken for the smaller one for every 2.5 mm increase in the tumour radius. The results also reveal that there exists an optimal thickness of the perfluorohexane layer around the tumour interface. It is also seen that among perfluorohexane, octafluoropropane and water, perfluorohexane acts as the best substitute for the formation of an insulating layer around the tumour interface. Experiments have been performed to prepare pefluorocarbon (perfluorohexane and perfluorodecalin) emulsions in varied concentration (i.e. 30%, 50%, 70% and 90% (w/v)) through probe sonication. Further, this study reports the particle size, emulsion stability, functional group analysis, thermophysical properties of both perfluorodecalin and perfluorohexane emulsions. With regard to thermal conductivity, it is observed that perfluorodecalin emulsions possess a marginally lower thermal conductivity than perfluorohexane emulsions. It is interesting to note that during cryosurgery of gel phantom in the presence of low thermal conductivity perfluorodecalin emulsion (90% (w/v)), it is observed that the freezing front is not able to penetrate the gel while in its absence, there is a temperature of 4oC at the same thermocouple location of 10 mm (in the axial direction).Cryosurgery of glycine-containing gels is carried out in presence and absence of perfluorohexane layer, and the thermal history is measured using K-type thermocouples connected to a data acquisition system. The presence of glycine causes rapid freezing during cryosurgery with an ice ball depth of 16 mm, while with a perfluorohexane layer at this gel interface, this depth is 13 mm, indicating the ability of this layer to limit freezing. In this study, alumina has also been utilised for the preparation of adjuvant containing gel phantoms. After cryosurgery, it is clearly evident that a temperature decrease is observed in the alumina consisiting gel phantoms when compared to the agarose gel phantoms. It is also noticed that with the increase in insertion depth of the cryoprobe (from 1 to 1.5 cm), there is a decrease in temperature at each thermocouple location in the gel phantoms. This study also demonstrates that in the presence of perfluorohexane layer, when the alumina consisting gel phantoms are cryosurgically cooled; even with the increase in insertion depth, the thermocouple placed axially at 10 mm which is inside the perfluorohexane solution layer indicates a temperature of 25oC. However, in its absence, the temperature is found to be 5:47oC at the same position, suggesting that the freezing is limited within the gel. Furthermore, this work also proposes a new approach that utilises glycine-alumina emulsions as an adjuvant. After cryosurgery of glycine-alumina containing gel, a substantial temperature decrease is observed at all thermocouples placed nearer to the probe, thus indicating an enhancement in freezing. In conclusion, this study proposes novel approaches to improve the cryosurgical procedure through numerical modelling and experiments in gel phantoms, thus, providing newer approaches to improve the cryosurgical outcome

Freezing processes in cell suspensions evaluated using cryomicroscopy

This thesis aims at evaluating the freezing response of three different cell types, Pacific Oyster embryos, Jurkats and Helas, using the technique of cryomicroscopy. The choice of cells was primarily based on supporting ongoing research work at the Bioengineering Laboratory, Department of Mechanical Engineering at Louisiana State University in Baton Rouge. On a secondary basis, the cells were chosen based on their contrasting nature. While Pacific Oyster being a favorite food in USA calls for successful techniques of cryopreservation of their embryos in order to keep up with the growing demand, Jurkat and HeLa are undesired malignant human cells that require successful cryosurgical techniques for their destruction. The fourth chapter of the thesis addresses the freezing experiments performed on Oyster embryos at freezing rates of 5 deg C/min and 10 deg C/min. During these experiments, embryos were investigated for either dehydration (water transport) or intracellular ice formation (IIF). The next two chapters address the freezing experiments performed on Jurkat cells and HeLa cells respectively. Freezing rates ranging from 1 deg C/min to 50 deg C/min were used for these cells. Once dehydration was observed, the cells were examined for their volume shrinkage. A graph of temperature against normalized volume was plotted using the experimental results. The key cell level parameters were: Reference permeability of cell membrane to water (Lpg), apparent activation energy (ELp), inactive cell volume (Vb), and the ratio of surface area for water transport to the volume of intracellular water (SA/WV). The values of ‘Vb’ for the chosen cells were known from earlier literature. The experimental data was fit into the water transport equation, using a numerical model, in order to obtain the values of the unknown cell level parameters i.e. Lpg and ELp. Finally, Generic Optimal Cooling Rate Equation (GOCRE) was used to determine the optimal cooling rate for the chosen variety of cells. Hence, higher freezing rates were used on the cells, which were investigated for IIF. IIF observed using cryomicroscopy, through darkening probably supported the results for optimal freezing rates, obtained using the water transport experiments and subsequent numerical simulations

Effective treatment of solid tumors via Cryosurgery

Ph.DDOCTOR OF PHILOSOPH

Finite element modeling of soft tissue deformation.

Computer-aided minimally invasive surgery (MIS) has progressed significantly in the last decade and it has great potential in surgical planning and operations. To limit the damage to nearby healthy tissue, accurate modeling is required of the mechanical behavior of a target soft tissue subject to surgical manipulations. Therefore, the study of soft tissue deformations is important for computer-aided (MIS) in surgical planning and operation, or in developing surgical simulation tools or systems. The image acquisition facilities are also important for prediction accuracy. This dissertation addresses partial differential and integral equations (PDIE) based biomechanical modeling of soft tissue deformations incorporating the specific material properties to characterize the soft tissue responses for certain human interface behaviors. To achieve accurate simulation of real tissue deformations, several biomechanical finite element (FE) models are proposed to characterize liver tissue. The contribution of this work is in theoretical and practical aspects of tissue modeling. High resolution imaging techniques of Micro Computed Tomography (Micro-CT) and Cone Beam Computed Tomography (CBCT) imaging are first proposed to study soft tissue deformation in this dissertation. These high resolution imaging techniques can detect the tissue deformation details in the contact region between the tissue and the probe for small force loads which would be applied to a surgical probe used. Traditional imaging techniques in clinics can only achieve low image resolutions. Very small force loads seen in these procedures can only yield tissue deformation on the few millimeters to submillimeter scale. Small variations are hardly to detect. Furthermore, if a model is validated using high resolution images, it implies that the model is true in using the same model for low resolution imaging facilities. The reverse cannot be true since the small variations at the sub-millimeter level cannot be detected. In this dissertation, liver tissue deformations, surface morphological changes, and volume variations are explored and compared from simulations and experiments. The contributions of the dissertation are as follows. For liver tissue, for small force loads (5 grams to tens of grams), the linear elastic model and the neo-Hooke\u27s hyperelastic model are applied and shown to yield some discrepancies among them in simulations and discrepancies between simulations and experiments. The proposed finite element models are verified for liver tissue. A general FE modeling validation system is proposed to verify the applicability of FE models to the soft tissue deformation study. The validation of some FE models is performed visually and quantitatively in several ways in comparison with the actual experimental results. Comparisons among these models are also performed to show their advantages and disadvantages. The method or verification system can be applied for other soft tissues for the finite element analysis of the soft tissue deformation. For brain tissue, an elasticity based model was proposed previously employing local elasticity and Poisson\u27s ratio. It is validated by intraoperative images to show more accurate prediction of brain deformation than the linear elastic model. FE analysis of brain ventricle shape changes was also performed to capture the dynamic variation of the ventricles in author\u27s other works. There, for the safety reasons, the images for brain deformation modeling were from Magnetic Resonance Imaging (MRI) scanning which have been used for brain scanning. The measurement process of material properties involves the tissue desiccation, machine limits, human operation errors, and time factors. The acquired material parameters from measurement devices may have some difference from the tissue used in real state of experiments. Therefore, an experimental and simulation based method to inversely evaluate the material parameters is proposed and compare

Subdomain BEM formulations for the solution of bio-heat problems in biological tissue with melanoma lesions

© 2017 Elsevier Ltd The main objective of the research presented in this paper is the development of efficient subdomain BEM solvers for the solution of steady-state and transient bio-heat problems in biological tissue, particularly involving melanoma of different sizes such as Clark II and IV. The short-term goal of the work is to investigate which of the numerical schemes implemented here produces the highest accuracy and efficiency, as a first step towards the long-term goal of solving inverse bio-heat problems for tumour diagnostics, i.e. the detection of tumour size and tumour parameters. The numerical results show that quadratic elements produce high accuracy with coarser meshes, and are thus more computationally efficient for this type of problem. It was also found that, for transient problems, a BEM formulation using the time-dependent fundamental solution of the diffusion equation was more efficient than the use of the fundamental solution of the Laplace equation with a finite difference time discretisation scheme, as much larger time steps could be used for the same accuracy. This work proposes that the subdomain BEM with quadratic elements and a time-dependent fundamental solution provides high accuracy and reduced computational time, and is thus indicated for the inverse analysis of bio-heat problems

Numerical Simulation of a Cryogenic Spray

Cryogenic sprays have many applications in modern engineering. Cooling of electronic equipment subject to high heat flows, surgical ablation of gastrointestinal mucosae or orbital maneuvering are a few examples of their versatility. However, the atomization of a cryogenic liquid is a complex process. During such an event, aerodynamic effects associated with secondary atomization are further affected by thermodynamic flashing. A better understanding of the characteristics of cryogenic sprays is then necessary to allow for improved design and optimization in applications. The overarching objective of this study is to document such characteristics. The numerical simulation was performed over cryogenic nitrogen spray using an Eulerian-Lagrangian approach. In other words, while the gas phase of the flow is treated as a continuum, the nitrogen droplets are tracked individually in a Lagrangian sense. Models for evaporation, atomization, and breakups capture the physical processes experienced by droplets along their pathways. In addition, turbulence in the flow is captured by the k-omega SST model. Simulations performed over a wide range of nozzle inlet pressure suggest that the spray cone angle tends to remain constant. In contrast, the diameter of droplets along the centerline of the spray reduces significantly. Finally, it was noticed that a higher concentration of liquid nitrogen is observed on a target plate as the nozzle inlet pressure increases

Numerical analysis of diaphragm type pulse tube refrigerator

In present study a new modeling approach for the performance of a pulse tube refrigerator is proposed. A single stage Stirling type diaphragm type pulse tube refrigerator is considered for CFD simulation using Fluent software. The two-dimensional geometry is taken for simulation. In this simulation the physical dimensions of all the components are kept constant and pressure input is generated from the different UDF (User Defined Function) for compressor and diaphragm. Generally, DC gas flow in pulse tube refrigerator created a crucial problem at the time of application, which will affect the cooling down performance because DC gas flow carries heat away from the HHX and deposits at the cold end reading an additional heat loss and unwanted thermal load to CHX , which degrades the cooling performance and doctorates the refrigeration stability of pulse tube cryocooler. For obtaining better temperature stability at CHX end, suppress the DC flow by eliminating the closed loop by using a diaphragm in between HHX and orifice valve. This simulation starts with an assumed uniform system temperature, and continued until steady periodic conditions are achieved by varying the pressure amplitude and getting the better stabilization temperature. The result shows that amplitude of 0.0045 produces a better cooling effect on the cold end of the pulse tube refrigerator

Small business innovation research. Abstracts of 1988 phase 1 awards

Non-proprietary proposal abstracts of Phase 1 Small Business Innovation Research (SBIR) projects supported by NASA are presented. Projects in the fields of aeronautical propulsion, aerodynamics, acoustics, aircraft systems, materials and structures, teleoperators and robots, computer sciences, information systems, data processing, spacecraft propulsion, bioastronautics, satellite communication, and space processing are covered