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Improvements in Total Hip Arthroplasty (THA) technology, methods of fixation, and cementing techniques of the prosthetic components have resulted in major problems when Revision Total Hip Arthroplasty (RTHA) is required, making the removal of well-fixed femoral stems a challenging and difficult surgical procedure. The promotion of osseointegration in cementless THA means removal of a cementless stem in RTHA is a particularly demanding task. Despite the numerous tools and methods that can be employed to remove the femoral component, the surrounding soft and osseous tissue can be severely damaged by the established revision techniques because no surgical procedure is able to remove a well-fixed femoral stem without causing any damage. This thesis investigates cooling the femoral prosthesis in order to lower the force required to extract the implant during RTHA of cementless femoral stems. Based on this concept, a new methodology was developed, consisting of cooling the neck of the femoral stem to a low temperature and immediately extracting the stem from the femur. As a proof of concept, to demonstrate the potential feasibility of the new method, experimental tests involving the removal of a cemented stem were considered; this was because, amongst other reasons, (i) the difficulty of simulating osseointegration in laboratory experimentation in a controlled and repeatable way, (ii) the favourable similarities of the mechanical and thermal properties of bone cement and bone, (iii) the fact that it has been determined that to pull-out cemented stems requires 60% to 70% of the pulling force to remove cementless stems, thus experimentation on cemented stems can provide a relatively good indication of the behaviour with cementless stems, (iv) the repeatability of the experimental procedure associated with the use of cemented stems. Three sets of in-vitro case studies were carried out with custom-made titanium stems cemented into a trapezoidal steel mould, a composite cylinder and a composite femur using polymethyl-methacrylate with a minimum cement mantle thickness of 3mm. First, a trapezoidal steel mould was employed for four case studies with the femoral neck stem cooled to temperatures of -76ᵒC, -58ᵒC, -49ᵒC, and -40ᵒC. Composite bones were used for the second set of case studies, in which stems were cemented into a) composite cylinders and b) composite femurs. Three case studies were performed for the cylindrical specimens: -76ᵒC, -49ᵒC, and -40ᵒC. Two case studies were considered for the composite femoral specimens: -76ᵒC, and -40ᵒC. In each of the tests, after reaching the temperature of interest, the specimen was immediately clamped in a materials testing machine, and the stem pulled out at a constant rate of 0.5 mm/min. Control tests were undertaken at room temperature for comparison purposes. Results from the first set of case studies showed that the force required to remove the titanium stem was reduced to 56.5% of the control force at a temperature of -76ᵒC, while for temperatures of -58ᵒC, -49ᵒC, and -40ᵒC the release force was reduced by 39%, 28%, and 31% respectively. Subsequent case studies with the cylindrical and femur composites also showed a reduction in the release force compared to their respective control force. The composite cylinder specimens exhibited reductions of 50%, 57% and 53% of the release force for temperatures of -76ᵒC, -49ᵒC, and -40ᵒC while, in the composite femur specimen the release force was reduced by 65% for a temperature of -40ᵒC. The results confirmed that the force required to remove a well-cemented femoral stem was reduced after cooling to temperatures below -40ᵒC allowing easier extraction of the stem. A finite element model was developed to analyse the thermal conditions in the femoral stem and surrounding material. The model can be used to ensure the required thermal balance can be obtained whilst avoiding conditions which may lead to tissue damage. The model was validated using the results of the experiments in which the temperature at strategic points on the stem was monitored during cooling. Furthermore, a concept design of a medical device based on the new methodology was developed.

Focal therapies (FT), including cryosurgery, thermal ablation and irreversible electroporation (IRE) have been widely used in the treatment of cancer and other diseases, with the aim to expose cells to extreme physical conditions, leading to cell death. The use of FT has increased recently due to advantages such as being minimally invasive and having lower costs, shorter recovery periods, and lower morbidity. The advent of imaging tools has also helped FT gain more attention among surgeons. However, limited understanding of the energy field around the FT probes might cause undertreatments, which would lead to recurrence of the disease, or overtreatment, which would lead to damages to the surrounding sensitive organs such as nerves and create severe side effects. Moreover, choosing the most suitable FT modality for treating a special organ target is essential.Our first objective for a successful focal therapy treatment is to have a clear understanding of the energy field distribution around the probes, both in clinical and preclinical applications. In preclinical cancer research, syngeneic tumors and xenograft tumors in rodent models are often used to define pre-clinical thresholds and outcomes for focal therapy modalities alone and with adjuvant approaches. Nevertheless, application of clinical-sized focal therapy probes in rodent tumor models can be difficult to control or characterize for this purpose. This, in turn, affects our understanding of the energy dose necessary to destroy diseased tissue. The fact that tumors in small animals come in different sizes and shapes and have thermal properties raises the need for a computational model capable of visualizing the temperature and electric field distribution within the tumor during the process of focal ablation. Understanding the interaction between the energy field and the tissue affects our understanding of the actual role of those ablation modalities in creating the tissue damage and enables us to predict and optimize the outcome of the procedure. Our second objective for a successful focal therapy treatment is to propose methods for preventing the damage to the surrounding organs, especially neural targets that are in close proximity to the treated area. In this work, we focus on preventing neural damage during prostate cancer cryosurgery. One major complication associated with prostate cancer cryosurgery is erectile dysfunction, caused by cryoinjury to the cavernous nerve in the neurovascular bundle, which is in close proximity to the prostate and is therefore directly exposed to freezing temperatures during cryosurgery. The use of cryoprotective agents (CPAs) to protect nerves against freezing temperatures is a method that has been used in nerve cryopreservation. While existing literature has established the idea of using CPAs to prevent nerve damage, there is still a lack of experimental data and quantitative models to study the effect of CPAs in preventing nerve cryoinjury during prostate cryosurgery. Moreover, no comprehensive study has assessed both the toxicity and the cryoprotective effectiveness of CPA exposure to the nerve within a repeatable and relevant biological model. Choosing a suitable FT modality is also crucial for a successful FT treatment. Certain modalities have better outcomes for specific organ targets than others. In this work, we propose a novel approach for renal denervation using Iron-oxide nanoparticle heating for treating hypertension. The most common ablation technique currently used in clinic for renal denervation is radiofrequency. However, this approach suffers from several disadvantages due to heating from inside of the renal artery which would result in damage to the artery wall, limited nerve ablation depth and inconsistent and unpredictable denervation. The use of iron-oxide nanoparticles, however, will alleviate some of the disadvantages mentioned by providing a repeatable treatment that can be used in combination with alcohol or other neurolytic agents as well. Using iron-oxide nanoparticles can also benefit from image guidance. This work will advance the application of FT by helping to better understand the energy field around the probe and helping to prevent unwanted damage to surrounding organs such as nerves.

Cryosurgery is a useful technique in the selective destruction of undesirable tissues, such as tumors, within the human body. Cryosurgery's primary benefit is that as a percutaneous method, it reduces the invasiveness and cost associated with traditional surgery. The objective of cryosurgery is to ensure complete destruction of the target tissue while simultaneously minimizing collateral damage to surrounding tissues. In addition to the problem of collateral damage, the nature of cryosurgery can make it difficult to ascertain the extent of cryoinjury during the surgical procedure. The scope of this work is to provide tools to minimize collateral damage, visualize cryoinjury following cryoinsult, and to better simulate cryosurgical outcomes.A method to counteract the collateral damage of cryosurgery was developed, which employs laser heating to thermally protect tissues surrounding a target tissue (e.g. tumor). A mouse hepatic tissue sample was cryogenically frozen with a cryoprobe on one side of the tissue, while freezing of the other side was prevented using selective laser heating. Tissue biopsies confirmed that this method can successfully protect regions of tissue from cryogenic damage through gentle laser heating.To visually characterize the regions of tissue damage following cryoinjury, Green Fluorescent Protein (GFP) transfected tissues were cryoinjured using a cryoprobe circulating liquid nitrogen. The long-term fluorescent yield of transfected tissues was observed in a controlled environment to determine the tissue's fluorescent response to cryoinjury. Other phenomena that impact fluorescent intensity were controlled and/or observed to eliminate these effects as the source of changing fluorescent intensity. It was observed that following cryoinjury, GFP fluorescence within tissues decays with a trend that follows Fick's second law of diffusion, suggesting that cryoinjury does not directly affect fluorescence, but allows the onset of GFP diffusion through and out of cryoinjured regions. Additional studies designed to account for the movement of all GFP within a closed system support this conclusion. It was determined that GFP-transfected tissues can effectively indicate cryoinjury, provided that conditions are favorable to diffusion.Emerging techniques that combine cryosurgery with laser heating need accurate methods to simulate the thermal response of a cryogenic tissue to optical irradiation. Light transport in tissue has been studied in great depth, and various computer programs and models currently exist that simulate light transport in simple systems. Light transport in tissues that undergo large changes in temperature, such as those encountered with laser-irradiated cryogenic tissues, cannot be accurately modeled with traditional methods, as those methods rely on simple geometries and optical properties which are constant with respect to temperature. A computer program and the supporting algorithms was developed which allows for the simulation of light transport in arbitrarily-shaped tissues which have temperature-dependent thermal and optical properties. The program first determines the optical distribution/deposition within the tissue, using a Monte Carlo photon heating simulation. The volumetric heating data is then used in determining heat transfer within the system. Optical properties based on the new thermal profile are interpolated and the optical distribution is repeated using these updated optical properties. This process repeats itself as necessary for the duration of the simulation. The simulation results compare favorably to established laser-tissue simulations, and to fundamental laws, validating the accuracy of the simulation outputs. The simulation can accurately predict the thermal response of a geometrically-complicated system to optical irradiation, including systems that undergo large changes in temperature and thus large changes in optical and thermal properties.

Non-thermal irreversible electroporation (IRE) is a new minimally invasive surgical technique that is part of the emerging field of molecular surgery which holds the potential to treat diseases with unprecedented accuracy. IRE utilizes electrical pulses delivered to a targeted area, producing irreversible damage to the cell membrane. While electroporation is not fully understood to date, evidence indicates that this damage is induced by the increased transmembrane potential due to high voltage pulses affecting the lipid bilayer. Because IRE does not cause thermal damage, the integrity of all other molecules and only effects cellular structures, collagen and elastin in the targeted area is preserved. Previous theoretical studies have only examined IRE in homogeneous tissues. However, tissues can be heterogeneous in two different capacities: 1) they can be intrinsically heterogeneous due to anatomy, and 2) they can be extrinsically heterogeneous due to external factors. This investigation of heterogeneous tissues studies both cases in order to expand the depth and breadth of the field of electroporation.Intrinsic Heterogeneous TissuesBecause biological structures are complex collections of diverse tissues it becomes imperative to consider intrinsic heterogeneities. In order to develop electroporation as a precise treatment in clinical applications, realistic models for pre-surgical planning are necessary. In this way, the study of heterogeneous tissues will enable refinement of electroporation as a treatment. In this chapter, three different intrinsic heterogeneous structures were taken into account: nerves, blood vessels and lactiferous ducts. The subsequent results made it clear that heterogeneities significantly impact both the temperature and electrical field distribution in surrounding tissues, indicating that heterogeneities should not be neglected. While the surrounding tissue experienced a high electrical field, the axon of the nerve, the interior of the blood vessel and the ducts experienced no electrical field. This indicates that blood vessels, nerves and lactiferous ducts adjacent to a tumor treated with electroporation have the potential to survive, while the cancerous lesion is ablated. This clearly demonstrates the importance of considering heterogeneity in IRE applications.Extrinsic Heterogeneous Tissues Extrinsic heterogeneous tissues can be induced by various external factors. One such factor is an applied temperature gradient. Two different temperature gradients were considered in this investigation: 1) subzero temperatures, induced by cryosurgery, and 2) cooling temperatures.Cryosurgery, tissue ablation by freezing, is a well-established minimally invasive surgical technique. The goal of this investigation was to study extrinsic heterogeneous tissues induced by externally applied subzero temperatures by combining cryosurgery and electroporation. Analysis of the electric field and temperature distribution during simultaneous tissue treatment with cryosurgery and irreversible electroporation (cryoIRE) was used to study the effect of tissue freezing on electric fields. The results indicate that this combination may resolve some of the major disadvantages that occur in each technology when used alone. Because of decreased electrical conductivity in the frozen tissue, this region experienced temperature induced magnified electric fields in comparison to IRE delivered to unfrozen tissue, the control case. This suggests that freezing confines and magnifies the electric fields to those regions; a targeting capability unattainable in traditional electroporation. This analysis also shows how temperature induced magnified and focused IRE can be used to ablate cells in the high subzero freezing region of a cryosurgical lesion, in which cells can be resistant to freezing damage.The next heterogeneous tissues that were studied were heterogeneities extrinsically produced by cooling. This chapter explores the hypothesis that non-subzero temperature dependent electrical parameters of tissue can also be used to modulate the outcome of IRE protocols, providing a new means for controlling and optimizing this minimally invasive surgical procedure. This chapter investigates two different applications of cooling temperatures applied during IRE. The first case utilizes an electrode which simultaneously delivers electric fields and cooling temperatures. The subsequent results demonstrate that changes in electrical properties due to temperature produced by this configuration can substantially magnify and confine the electric fields in the cooled regions while almost eliminating electric fields in surrounding regions. This method can be used to increase precision in IRE procedures, and eliminate muscle contractions and damage to adjacent tissues. The second configuration considered introduces a third probe that is not electrically active and only applies cooling boundary conditions. This second configuration demonstrates that with this probe geometry the temperature induced changes in electrical properties of tissue substantially reduce the electric fields in the cooled regions. This novel treatment can potentially be used to protect sensitive tissues from the effect of IRE.Perhaps the most important conclusion of this investigation is that temperature is a powerful and accessible mechanism to modulate and control electric fields in biological tissues and can therefore be used to optimize and control IRE treatments.

Micromachined Joule-Thomson (J-T) coolers have applications ranging from cryosurgery to cooling infrared detectors. With the absence of cold moving parts, the J-T coolers can be implemented with simple structures that are suitable for silicon/glass microfabrication. The investigation proposed in this thesis focuses on the development of micromachined Si/glass heat exchangers used in the J-T coolers that operate at 200-225K when the gas pressure is 1-2MPa. The heat exchangers must maintain good stream-to-stream heat conductance between the high- and low-pressure streams while restricting stream-wise conduction to achieve a high effectiveness. Two heat exchangers were designed, fabricated and tested. The first, a planar design, uses rows of high-conductivity silicon fins bonded onto a 100µm thick low-conductivity glass base plate. It was fabricated using a five-mask process including Si/glass/Si anodic bonding, two-step DRIE, and HF glass etching, etc. The second, a perforated-plate design, uses numerous silicon plates alternated with glass spacers. It was fabricated using a four-mask process including KOH on (110) silicon wafers, HF glass etching and anodic bonding. Platinum resistance temperature detectors were integrated into the heat exchanger for in-situ temperature sensing. Whereas the performance of the planar heat exchanger was limited by its ability to accommodate a pressure differential across the base plate, the perforated-plate heat exchangers demonstrated a high effectiveness (0.912) in at 237-252K in effectiveness tests and good robustness at high pressures (1MPa) in J-T self-cooling tests. The temperature distribution along the heat exchanger was measured by integrated resistance temperature detectors with sensitivities of 0.26-0.30%/K at 205-296K. A J-T system using the perforated-plate heat exchanger achieved 218.7K at steady state and 200.3K in a transient state. The system provided 200mW cooling power at 228K and 1W at 239K with an estimated parasitic heat load of 300-500mW. Finally, a flow-controlled J-T system using a perforated-plate heat exchanger and a piezoelectric microvalve was demonstrated. By modulating the flow, the microvalve could vary the cooling temperature by 5-8K around the operating points, which were 254.5K at 430kPa pressure difference in steady state, and 234K at 710kPa in transient state, without an added heat load.

Cryosurgery is a novel surgical technique using low temperature and tissue freezing to destroy undesired tissue, especially cancerous tissue. A numerical model of cryosurgery is highly desirable in clinic practice to predict target tissue thermal history, assess treatment outcome and optimize cryosurgical protocol. The present dissertation dedicates to develop an integrated model addressing multiple complex physics involved in cryosurgery, including fluid flow, bioheat transfer and tissue freezing. Extensive and in-depth numerical studies have been conducted for two typical yet distinct cryosurgeries: cutaneous cryosurgery (using liquid nitrogen spray) and hepatic cryosurgery (using liquid nitrogen cryoprobe). The modeling of cutaneous cryosurgery starts from treating target skin tissue as a homogeneous media. The anatomic structure of human skin tissue is then incorporated by considering three sub-layers: epidermis, dermis and subcutaneous fat. Bioheat transfer during the cryosurgery is described by classic Pennes Equation, while critical modifications are made on the thermal effects of blood perfusion and metabolism according to the physiological characteristics of each sub-layer. The model is then applied to study a general cutaneous cryosurgery and a specific clinic case: the cryosurgery on nodular basal cell carcinoma (BCC). A methodology for quantitatively determining the extent of intracellular ice formation (IIF) based on the tissue temperature and cooling rate (CR) is proposed, followed by systematic parametric study to investigate the effect of various protocol parameters on the final IIF zone. These results contribute to support dermatologists to estimate the treatment outcome in cryosurgery pretreatment planning. The modeling of hepatic cryosurgery emphasis the heat interaction between the fluid flow of LN2 within a cryoprobe and the surrounding tissue. Laminar flow model and turbulent flow model are all validated and applied to study the effect of LN2 flow on the heat transfer characteristic of the cryoprobe. A conjugate model is eventually developed, which simultaneously addresses the turbulent flow of LN2 within the cryoprobe, bioheat transfer in surrounding hepatic tissue and subsequent tissue freezing. Parametric study is also conducted to investigate the impact of LN2 flow on tissue freezing.