This PDF file contains the front matter associated with SPIE Proceedings Volume 6440, including the Title Page, Copyright information, Table of Contents, Introduction (if any), and the Conference Committee listing.

Volumetric conductive-convective heat sources, microwave and radiofrequency energy sources, high intensity focused ultrasound (HIFU), laser irradiation and other non-ionizing irradiation sources can be used to generate hyperthermic tissue injury in a variety of clinical settings with therapeutic temperature gradients ranging from 40 to over 90°C. On the opposite side, cryotherapy can be used to freeze tissues with negative therapeutic temperature gradients. The development of a successful thermal therapy using any one of these devices requires a precise understanding of the desired clinical end point in terms of 1) diagnosis vs. therapy, 2) cure vs. palliative intent, 3) dysfunctional vs. malignant tissue and 4) long-term monitoring issues. The effects of a specific thermal exposure depend on the architecture of the heat source and overall thermal history. During initial treatment before heat generation or cooling becomes dominant, tissue interactions with the delivered treatment may affect the geometry of the treatment effect and body's healing response. These two parameters are also affected by tissue anatomy, blood supply and protein vs. lipid content. The thermal lesion and final clinical outcome represent the sum of direct primary and secondary short and long term delayed injury. The latter occurs primarily from host responses producing ischemia, inflammation and wound healing followed by possible regeneration and/or scar formation. Once the thermal insult has been deployed, the resulting lesions can be broadly divided into two major zones: 1) a complete tissue ablation with lethal tissue injury closer to the device and 2) a peripheral transition zone of partial injury. Hyperthermic complete ablation zones can have two sub-regions: 1) thermal fixation from direct denaturation of cellular and tissue components and 2) coagulative necrosis due to direct injury and delayed secondary host responses. With a variety of special techniques, direct cellular injury can be studied at post-therapy intervals of less than 12 hours. At 1-5 days, the acute effects of direct and secondary injury can be assessed with hematoxylin and eosin staining and other techniques. While early healing changes can be studied around 7-10 days, chronic changes are best assessed at variable intervals between 1-9 months. A thorough understanding of the interval dynamics of direct and delayed tissue responses after treatment is critical when choosing appropriate post-treatment times to assess the results. Since many preclinical studies represent "snap shots" in time, care needs to be taken when using acute experimental results to develop mathematical models to predict chronic clinical outcomes. Recent collaborative studies indicate that many pathologic effects can act as direct markers of clinical efficacy when combined with various imaging modalities. In addition, both animal and human studies are performed to establish safety and efficacy; therefore, understanding species differences and the appropriate selection of pathology techniques is critical when designing these studies. In summary, effective biomedical instrument development requires close cooperation among engineers, physiologists, internists, pathologists and radiologists from conceptualization through instrument development, validation and refinement.

Many medical laser procedures require selecting laser operating parameters that minimize undesirable tissue damage. In this study, heat shock protein 70(hsp70) gene expression was used as a sensitive marker for laser-induced thermal damage. Wound repair and hsp70 expression were compared after surgery with the free electron laser(FEL) as a function of wavelength(&lgr;) and radiant exposure(H). Damage was assessed at &lgr; = 6.45, 6.10, and 2.94 &mgr;m using 8-20 J/cm². The FEL beam (&Vpgr;_r=200 &mgr;m,30Hz,&tgr;_p =5&mgr;s) was delivered to produce a 6.5 mm square wound. hsp70 expression was assessed using a transgenic mouse strain with the hsp70 promoter driving luciferase and eGFP expression. Bioluminescent imaging (BLI) was monitored non-invasively and in real time. Hsp70 protein was visualized with laser confocal imaging, blood velocity was measured with 2D-laser doppler, and depth of tissue damage was measured using histological methods. BLI verified the model's sensitivity and peak hsp70 expression was bi-phasic, with maxima occurring 12 and 24 hours after FEL irradiation. hsp70 expression exhibited wavelength-dependence, and it increased with radiant exposure. Histology indicated that tissue damage at 6.45 µm was ~2x deeper than 6.10 &mgr;m. Quantitative BLI with the Hsp70-luc transgene can be used to non-invasively measure gene expression in laser-tissue interaction studies.

The aim of this study was to determine the histopathologic effect on the skin of 2.0 &mgr;m wavelength laser with various exposure conditions 48 hours after irradiation. Histological sections of lesions were created at, below and beyond the threshold for grossly apparent thermal lesions. These lesions were studied to 1)identify and define the microscopically apparent threshold lesions, 2)determine the mechanisms producing the gross and microscopic threshold lesions in the skin, and 3)map the extent and severity of the lesions. Grossly apparent threshold lesion were defined as persistent surface redness at 48 hours. Histologically, these lesions showed relatively severe thermal damage in both the epidermis and the dermis. Damage included death and necrosis of the epidermal cells and endothelial necrosis, intravascular thrombosis as well as perivascular edema and inflammation in dermal blood vessels. The collagen bundles below the epidermis were slightly swollen but there was no change in birefringence image intensity. For each threshold lesion, three quantitative parameters were measured to map the extent of thermal damage: 1) the width of necrotic epidermis, 2) the depth measured from the epidermal/dermal junction to the deepest extent of thrombosis, and 3) the depth measured from the epidermal/dermal junction to the deepest extent of perivascular inflammation and edema. Birefringence change of dermal collagen which occurred at powers above threshold was another measurable damage marker which indicated coagulation of collagen bundles. These quantitative histopathologic data for skin damage associated with the transient temperature profiles and irradiation parameters provided important information to mathematically derive rate process coefficients for thermal damage and formulate mathematical tissue damage models for each cutaneous damage effect.

We demonstrate a method which incorporates state-of-the-art x-ray imaging with novel thermal therapy monitoring to enable improved minimally invasive thermal-therapy delivery for benign or malignant tumors. Thermal ablative techniques including RFA, microwave, and laser ablation are gaining acceptance. Incomplete treatments are common since there is no reliable method to monitor treatment zones during ablation. Treatment that doesn't encompass the entire tumor results in recurrence usually within one year. We describe a method to monitor tumor ablation zones during ablations performed under CT image guidance. This method allows the operator to predict necrosis while avoiding injury to critical structures. We validated the model using tissue and animal experiments. We also report on initial clinical results from patients receiving RFA treatments for primary or metastatic lesions. Following CT image-guidance to position RFA devices in a patient's tumor, intraprocedural CT data was acquired and processed offline. In this paper we describe the methods to monitor and provide feedback on the ablation during the study. By demonstrating the creation of accurate thermal maps in tissue and animal models, and extending this in preliminary treatment of tumors in patients, we hope to encourage the broader adoption of these methods by improving both safety and efficacy.

Magnetic Resonance Imaging (MRI) is a promising tool for visualizing the delivery of minimally invasive cancer treatments such as high intensity ultrasound (HUS) and cryoablation. We use an acute dog prostate model to correlate lesion histopathology with contrast-enhanced (CE) T1 weighted MR images, to aid the radiologists in real time interpretation of in vivo lesion boundaries and pre-existing lesions. Following thermal or cryo treatments, prostate glands are removed, sliced, stained with the vital dye triphenyl tetrazolium chloride, photographed, fixed and processed in oversized blocks for routine microscopy. Slides are scanned by Trestle Corporation at .32 microns/pixel resolution, the various lesions traced using annotation software, and digital images compared to CE MR images. Histologically, HUS results in discrete lesions characterized by a "heat-fixed" zone, in which glands subjected to the highest temperatures are minimally altered, surrounded by a rim or "transition zone" composed of severely fragmented, necrotic glands, interstitial edema and vascular congestion. The "heat-fixed" zone is non-enhancing on CE MRI while the "transition zone" appears as a bright, enhancing rim. Likewise, the CE MR images for cryo lesions appear similar to thermally induced lesions, yet the histopathology is significantly different. Glands subjected to prolonged freezing appear totally disrupted, coagulated and hemorrhagic, while less intensely frozen glands along the lesion edge are partially fragmented and contain apoptotic cells. In conclusion, thermal and cryo-induced lesions, as well as certain pre-existing lesions (cystic hyperplasia - non-enhancing, chronic prostatitis - enhancing) have particular MRI profiles, useful for treatment and diagnostic purposes.

The purpose of this study is to further investigate the approach of DWI to estimate the cell viability immediately after treatment. In this work, we reported the result from 12 canine prostate experiments underwent cryoablation or hyperthermic therapy. The lesion detected by diffusion-weighted imaging was evaluated through apparent diffusion coefficient (ADC) value, image contrast, and lesion contour compared to contrast enhanced imaging and histology.

Thermal therapy as a treatment for cancer is a dynamic treatment epicenter, with a variety of technologies available and undergoing continuous improvement. Recent advances in technology and applications for thermal therapy give clinicians more power to affect larger volumes of tissue in less time. New radiofrequency (RF) and microwave (MW) systems have appeared recently, giving powerful tools for cancer therapy. Novel therapeutic ultrasound (US) technologies are being explored, but are presently not commercialized. Thermal therapy applicators that deliver power to the target in the patient will be reviewed for shape, size, and features. The operation and performance of various applicators will be discussed. In the goal of performance increase, several features have been commercialized in the evolution of the technology, including cooling, multiple applicator arrays, power modulation, and applicator deployment and shape change. To place recent progress into perspective, a historical review of some RF and MW applicators will be given. The work will cover modeling and simulations, as well as in-vitro, in-vivo, and clinical results.

A larger percentage of small tumors in the breast are being detected due to effective screening programs and improved radiological diagnostic methods. For treatment, less invasive methods are preferred which are still radical but also provide a better aesthetic result. Recently, several ablation techniques have become available to locally ablate tumors in situ. In this study, the effectiveness of three ablation techniques was compared by imaging the thermal distribution and temperature mapping in vitro. The first system (KLS Martin, Trumpf, Germany) uses Nd:YAG laser light delivered through a single diffusing fiber tip which is positioned direct into the tissue or in a water-cooled needle. The second system (Olympus-Celon, Germany) uses bipolar Radio Frequency currents between electrodes in a water-cooled needle. The RF system has a temperature feedback based on tissue impedance to prevent tissue charring. The third system is a focused ultrasound system developed in the Hospital. For all three the techniques, the dynamics of temperature gradients around the probe or focus point are visualized using color Schlieren techniques in a transparent tissue model and recorded using thermocouples. The effective lesion size and tissue temperatures were determined in in vitro bovine mamma tissue. All systems were capable to heat tissue volumes up to 3 cm in diameter. The lesion growth dependent on the power input, temperature gradient around the initial power source and treatment time. Although the three systems are capable to ablate small mamma carcinoma in situ, they differ in precision, MR compatibility, invasiveness, practical use and treatment time. The real clinical effectiveness has to be proven in large patient studies with long term follow up.

Four types of transurethral applicators were devised for thermal ablation of prostate combined with MR thermal monitoring: sectored tubular transducer devices with directional heating patterns; planar and curvilinear devices with narrow heating patterns; and multi-sectored tubular devices capable of dynamic angular control without applicator movement. These devices are integrated with a 4 mm delivery catheter, incorporate an inflatable cooling balloon (10 mm OD) for positioning within the prostate and capable of rotation via an MR-compatible motor. Interstitial devices (2.4 mm OD) have been developed for percutaneous implantation with directional or dynamic angular control. In vivo experiments in canine prostate under MR temperature imaging were used to evaluate the heating technology and develop treatment control strategies. MR thermal imaging in a 0.5 T interventional MRI was used to monitor temperature and thermal dose in multiple slices through the target volume. Sectored tubular, planar, and curvilinear transurethral devices produce directional coagulation zones, extending 15-20 mm radial distance to the outer prostate capsule. Sequential rotation and modulated dwell time can conform thermal ablation to selected regions. Multi-sectored transurethral applicators can dynamically control the angular heating profile and target large regions of the gland in short treatment times without applicator manipulation. Interstitial implants with directional devices can be used to effectively ablate the posterior peripheral zone of the gland while protecting the rectum. The MR derived 52 °C and lethal thermal dose contours (t₄₃=240 min) allowed for real-time control of the applicators and effectively defined the extent of thermal damage. Catheter-based ultrasound devices, combined with MR thermal monitoring, can produce relatively fast and precise thermal ablation of prostate, with potential for treatment of cancer or BPH.

Previous studies have reported the computer modeling, CAD design, and theoretical performance of single and multiple antenna arrays of Dual Concentric Conductor (DCC) square slot radiators driven at 915 and 433 MHz. Subsequently, practical CAD designs of microstrip antenna arrays constructed on thin and flexible printed circuit board (PCB) material were reported which evolved into large Conformal Microwave Array (CMA) sheets that could wrap around the surface of the human torso for delivering microwave energy to large areas of superficial tissue. Although uniform and adjustable radiation patterns have been demonstrated from multiple element applicators radiating into simple homogeneous phantom loads, the contoured and heterogeneous tissue loads typical of chestwall recurrent breast cancer have required additional design efforts to achieve good coupling and efficient heating from the increasingly larger conformal array applicators used to treat large area contoured patient anatomy. Thus recent work has extended the theoretical optimization of DCC antennas to improve radiation efficiency of each individual aperture and reduce mismatch reflections, radiation losses, noise, and cross coupling of the feedline distribution network of large array configurations. Design improvements have also been incorporated into the supporting bolus structure to maintain effective coupling of DCC antennas into contoured anatomy and to monitor and control surface temperatures under the entire array. New approaches for non-invasive monitoring of surface and sub-surface tissue temperatures under each independent heat source are described that make use of microwave radiometry and flexible sheet grid arrays of thermal sensors. Efforts to optimize the clinical patient interface and move from planar rectangular shapes to contoured vest applicators that accommodate entire disease in a larger number of patients are summarized. By applying heat more uniformly to large areas of contoured anatomy, the CMA applicator resulting from these enhancements should expand the number of patients that can benefit from effective heating of superficial disease in combination with radiation or chemotherapy.

Uterine myomas (fibroids) are the most common pelvic tumors occurring in women, and are the leading cause of hysterectomy. Symptoms can be severe, and traditional treatments involve either surgical removal of the uterus (hysterectomy), or the fibroids (myomectomy). Interstitial ultrasound technologies have demonstrated potential for hyperthermia and high temperature thermal therapy in the treatment of benign and malignant tumors. These ultrasound devices offer favorable energy penetration allowing large volumes of tissue to be treated in short periods of time, as well as axial and angular control of heating to conform thermal treatment to a targeted tissue, while protecting surrounding tissues from thermal damage. The goal of this project is to evaluate interstitial ultrasound for controlled thermal coagulation of fibroids. Multi-element applicators were fabricated using tubular transducers, some of which were sectored to produce 180° directional heating patterns, and integrated with water cooling. Human uterine fibroids were obtained after routine myomectomies, and instrumented with thermocouples spaced at 0.5, 1.0, 1.5, 2.0, 2.5 and 3.0 cm from the applicator. Power levels ranging from 8-15 W per element were applied for up to 15 minute heating periods. Results demonstrated that therapeutic temperatures >50° C and cytotoxic thermal doses (t₄₃) extended beyond 2 cm radially from the applicator (>4 cm diameter). It is anticipated that this system will make a significant contribution toward the treatment of uterine fibroids.

Laser induced thermal therapy is used in conjunction with gold coated silica core nanoshells and magneticresonance temperature imaging (MRTI). The nanoshells are embedded in phantom or in vivo tumors and heat preferentially compared to surrounding tissue when the laser is applied. The tissues thermal response is varied by either the laser power or the nanoshell concentration. In this way precise control of the heating can be achieved. This results in the ability to quantitatively monitor therapeutic temperature changes that occur in a spatiotemporally controlled way. This provides an unprecedented means proscribing and monitoring a treatment in real time and the ability to make precise corrections when necessary.

Fe/Fe oxide nanoparticles, in which the core consists of metallic Fe and the shell is composed of Fe oxides, were obtained by reduction of an aqueous solution of FeCl₃ within a NaBH₄ solution, or, using a water-in-oil micro-emulsion with CTAB as the surfactant. The reduction was performed either in an inert atmosphere or in air, and passivation with air was performed to produce the Fe/Fe₃O₄ core/shell composite. Phase identification and particle size were determined by X-ray diffraction and TEM. Thermal analysis was performed using a differential scanning calorimeter. The quasistatic magnetic properties were measured using a VSM, and the specific absorption rates (SARs) of both Fe oxide and Fe/Fe₃O₄ composite nanoparticles either dispersed in methanol or in an epoxy resin were measured by Luxtron fiber temperature sensors in an alternating magnetic field of 150 Oe at 250 kHz. It was found that the preparation conditions, including the concentrations of solutions, the mixing procedure and the heat treatment, influence the particle size, the crystal structure and consequently the magnetic properties of the particles. Compared with Fe oxides, the saturation magnetization (MS) of Fe/Fe₃O₄ particles (100-190 emu/g) can be twice as high, and the coercivity (H_C) can be tunable from several Oe to several hundred Oe. Hence, the SAR of Fe/Fe₃O₄ composite nanoparticles can be much higher than that of Fe oxides, with a maximum SAR of 345 W/g. The heating behavior is related to the magnetic behavior of the nanoparticles.

The pharmacokinetics, tumor uptake, and biologic effects of inductively heating 111In-chimeric L6 (ChL6) monoclonal antibody (mAb)-linked iron oxide nanoparticle (bioprobes) by externally applied alternating magnetic fields (AMF) were studied in athymic mice bearing human breast cancer HBT 3477 xenografts. In addition, response was correlated with calculated total deposited heat dose. Methods: Using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide HCl, 111In-7,10-tetraazacyclododecane-N, N',N'',N'''-tetraacetic acid-ChL6 was conjugated to the carboxylated polyethylene glycol on dextran-coated iron oxide 20-nm particles, one to two mAbs per nanoparticle. After magnetic purification and sterile filtration, pharmacokinetics, histopathology, and AMF/bioprobe therapy were done using 111In-ChL6 bioprobe doses (20 mcg/2.2 mg ChL6/ bioprobe), i.v. with 50 mcg ChL6 in athymic mice bearing HBT 3477; a 153 kHz AMF was given 72 hours postinjection for therapy with amplitudes of 1,300, 1,000, or 700 Oe. Weights, blood counts, and tumor size were monitored and compared with control mice receiving nothing, or AMF, or bioprobes alone. Results: 111In-ChL6 bioprobe binding in vitro to HBT 3477 cells was 50% to 70% of that of 111In-ChL6. At 48 hours, tumor, lung, kidney, and marrow uptakes of the 111In-ChL6 bioprobes were not different from that observed in prior studies of 111In-ChL6. Significant therapeutic responses from AMF/bioprobe therapy were shown compared with no treatment. In addition, greatest therapeutic benefit was observed for the 700 Oe treatment cohort. Toxicity was only seen in the 1,300 Oe AMF cohort, with 4 of 12 immediate deaths associated with skin erythema and petechiae. Conclusion: This study shows that mAb-conjugated nanoparticles (bioprobes), when given i.v., escape into the extravascular space and bind to cancer cell membrane antigen.Thus, bioprobes can be used in concert with externally applied AMF to deliver thermoablative cancer therapy. Therapeutic benefit was observed with increasing calculated heat dose deposited in tumors.

Thermotherapy, particularly magnetic nanoparticle hyperthermia, is a promising modality both as a direct cancer cell killing and as a radiosensitization technique for adjuvant therapy. Dextran-coated iron oxide nanoparticles were mixed with multiple tumor cell lines in solution and exposed to varying magnetic field regimes and combined with traditional external radiotherapy. Heating of cell lines by water bath in temperature patterns comparable to those achieved by nanoparticle hyperthermia was conducted to assess the relative value of nano-magnetic thermotherapy compared with conventional bulk heating techniques and data.

The potential synergism and benefit of combined hyperthermia and radiation for cancer treatment is well established, but has yet to be optimized clinically. Specifically, the delivery of heat via external arrays /applicators or interstitial antennas has not demonstrated the spatial precision or specificity necessary to achieve appropriate a highly positive therapeutic ratio. Recently, antibody directed and possibly even non-antibody directed iron oxide nanoparticle hyperthermia has shown significant promise as a tumor treatment modality. Our studies are designed to determine the effects (safety and efficacy) of iron oxide nanoparticle hyperthermia and external beam radiation in a murine breast cancer model. Methods: MTG-B murine breast cancer cells (1 x 106) were implanted subcutaneous in 7 week-old female C3H/HeJ mice and grown to a treatment size of 150 mm3 +/- 50 mm3. Tumors were then injected locally with iron oxide nanoparticles and heated via an alternating magnetic field (AMF) generator operated at approximately 160 kHz and 400 - 550 Oe. Tumor growth was monitored daily using standard 3-D caliper measurement technique and formula. specific Mouse tumors were heated using a cooled, 36 mm diameter square copper tube induction coil which provided optimal heating in a 1 cm wide region in the center of the coil. Double dextran coated 80 nm iron oxide nanoparticles (Triton Biosystems) were used in all studies. Intra-tumor, peri-tumor and rectal (core body) temperatures were continually measured throughout the treatment period. Results: Preliminary in vivo nanoparticle-AMF hyperthermia (167 KHz and 400 or 550 Oe) studies demonstrated dose responsive cytotoxicity which enhanced the effects of external beam radiation. AMF associated eddy currents resulted in nonspecific temperature increases in exposed tissues which did not contain nanoparticles, however these effects were minor and not injurious to the mice. These studies also suggest that iron oxide nanoparticle hyperthermia is more effective than non-nanoparticle tumor heating techniques when similar thermal doses are applied. Initial electron and light microscopy studies of iron oxide nanoparticle and AMF exposed tumor cells show a rapid uptake of particles and acute cytotoxicity following AMF exposure.

The cornea may be reshaped to correct hyperopia by selective shrinkage of collagen in the stroma using radio Frequency (RF) current from a needle electrode. Continuous sine wave current at constant power has proven very effective to achieve repeatable results by thermally shrinking corneal collagen. Post-treatment relaxation of the collagen may be moderated by creating a larger zone of lesser damage over a longer heating time; rather than using a smaller zone of greater damage created in a shorter time. Finite difference numerical models of the electric fields and resulting thermal events were used to study the process parameters and to identify advantageous treatment strategies. The models include temperature- and water-dependent electrical and thermal properties.

Knowledge of heat transfer in biological bodies has many therapeutic applications involving either increasing or lowering tissue temperature. Radio-Frequency (RF) energy deposition is a method for increasing the temperature of diseased tissue above 55°C to thermally ablate it. The resulting elevated tissue temperature is due to RF energy deposition as well as tissue thermodynamics. However, it is difficult to separate these two processes on any lab bench or in vivo model, hence computer simulation is a valuable tool for the separation and examination of these two phenomena. Classically, the Pennes' bio-heat equation coupled with electrical field equations in a finite element analysis (FEA) environment provides the governing structure for computer simulations that model energy deposition in biological tissues. In the present work we have modified the computer simulation to allow an artificial partitioning of RF energy deposition and tissue thermal diffusion. An internal cooled RF electrode (CoolTip^TM) is analyzed using this partitioning method. This method provides useful knowledge for optimizing the control of RF energy delivery to target tissue.

Radiofrequency ablation (RFA) has been used for a variety of clinical treatments including treatment of non-resectable liver tumors with good clinical success. Liver pretreatment with injected saline increases the volume of the RFA treatment and is a potential tool for strategically treating larger tumors. Understanding the electrical conductivity of the affected tissue is required to improve the applicator performance and to accurately control the ablation area. We have developed a micro two-electrode probe capable of measuring the local electrical conductivity of tissues at different temperature levels and recording the transient change of electrical conductivity with saline pretreatment. An optical temperature sensor was attached on the probe tip for real-time temperature monitoring to capture the dynamic effects of temperature changes. Three methods which were implemented by water bath and a commercial RF ablation applicator (Cool-tip RF ablation system) were used to heat the hepatic tissues. The results show that at elevated temperatures the electrical conductivity increases by a factor of two compared to the values at the body temperature and different heating methods cause different levels of electrical conductivity change. The preliminary measurements of the local electrical conductivity after the saline injection indicate a dynamic pattern in electrical conductivity. The results serve to provide guidance for accurate prediction of RFA area when using saline injection pretreatment.

A micro thin-film thermal conductivity probe is developed to measure thermal conductivity of biological tissues based on the principle of traditional hot-wire method. The design of this new micro probe consists of a resistive line heating element on a substrate and a RTD based temperature sensor. The transient time response of the heating element depends on the thermal conductivity of the surrounding medium and the substrate. A theoretical analysis of the transient conduction for this configuration where the heater source is sandwiched between two materials (the substrate and the surrounding medium) shows that the composite thermal conductivity calculated from the temperature versus time response is simply the average of the thermal conductivity of the two materials. The experiments conducted to measure thermal conductivity of Crisco and agar gel show a good match with the theoretical and numerical analyses. The technique demonstrates the potential of the microprobe for in vivo measurements of thermal conductivity of biological tissues.

Early work utilizing MW energy for thermal treatment or ablation of tissues such as liver using coherent phased arrays began in 1979. This early work involved the use of multiple interstitial antennas driven with the same phase and equal power at 915 MHz through the use of a power splitter. Early models of the antenna utilized a hypodermic needle that was transformed into an antenna by the deployment of an insulated coaxial central wire beyond the end of the needle. Early unpublished treatments of tissue phantoms and swine liver demonstrated the feasibility of such a design for selective tissue damage, but sufficient image and targeting methods had not been sufficiently developed to support such applications. MW therapeutic technology was subsequently commercialized in combination with invasive radiation therapy called brachytherapy. For this application coherent arrays of coaxial antennas were inserted into cancerous tumors. Initial investigators would deploy these into the tumor through 14 gauge plastic angiocatheters. In later procedures, the antennas were inserted into the same closed-end plastic catheters used for insertion of the radiation sources. MW energy delivery through the walls of closed-end plastic catheters and numerical pretreatment planning has been in clinical practice since 1984. Recent development of numerical models, split tissue equivalent phantoms with IR imaging, and tissue ablation studies have led to new insights in microwave ablation applications. Current research will improve ablative heat therapy with increased temperatures and power to improve stand alone thermal treatments.

Ablation therapy is used as an alternative to surgical resection of hepatic tumors. In ablation, tumors are destroyed through heating by RF current, high intensity focused ultrasound (HIFU), or other energy sources. Ablation can be performed with a linear array transducer delivering unfocused intense ultrasound (<10 W/cm²). This allows simultaneous treatment and imaging, a feature uncommon in RF ablation. Unfocused ultrasound can also enable faster bulk tissue ablation than HIFU. In the experiments reported here, a 32-element linear array transducer with a 49 mm aperture delivers 3.1 MHz continuous wave unfocused ultrasound at amplitudes 0.7-1.4 MPa during the therapy cycle. It also operates in pulse-echo mode to capture B-scan images. Ex-vivo fresh bovine liver tissue placed in degassed saline is exposed to continuous wave ultrasound interleaved with brief pulsed ultrasound imaging cycles. Tissue exposures range between 5 to 20 minutes. The following measurements are made at intervals of 1 to 3 seconds: tissue temperature with a needle thermocouple, acoustic emissions with a 1 MHz passive unfocused detector, and tissue echogenicity from image brightness. Passively detected acoustic emissions are used to quantify cavitation activity in the ablation experiments presented here. As severity and extent of tissue ablation are related to temperature, this paper will statistically model temperature as a function of tissue echogenicity and cavitation. The latter two quantities can potentially be monitored noninvasively and used as a surrogate for temperature, enabling improved image guidance and control of ultrasound ablation.

Devices delivering energy to biological tissues (eg lasers, RF and ultrasound) can induce surgical smoke consisting of particles, vapor, gasses and aerosols. Besides interfering with the view of the surgeon, the smoke is a risk for the health of both the users and patients. In literature, it has been shown that surgical smoke can contain carcinogenic and harmful biological agents. However, the impact on health of the users and patients is widely debated. The use of smoke evacuation systems in the OR is usually governed by economical reason instead of safety issues. A special image enhancement technique is used to study the behavior of smoke and aerosols and the effectiveness of smoke evacuation systems. A back scatter illumination technique using 1 &mgr;s light flashes at video rate was applied to image the smoke production of various surgical devices without and with smoke evacuation while ablating biological tissues. The effectiveness of various smoke evacuation devices and strategies were compared. The ablative thermal devices produced smoke but also aerosols. If the thermal energy was delivered in high peak pulses, the presence of aerosols was more significant. Ultrasound based devices produce mainly aerosols. The distance to the target, the opening of the evacuation nozzle and the dimension of aerosols were leading for the effectiveness of the smoke evacuation. The smoke visualization technique has proven an effective tool for study the effectiveness of smoke and aerosols evacuation. The results can contribute to the necessity to use evacuation systems in the OR.

Successful application of laser cartilage reshaping (LCR) for the in-situ treatment of structural deformities in the nasal septum, external ear and trachea requires a better understanding of the evolution of cartilage mechanical properties with temperature. We develop a method of Radio Frequency (RF) heating for reliable evaluation of mechanical changes in septal cartilage undergoing heating and used obtained data to model the mechanical changes in cartilage at steady state following laser heating. Cartilage specimens harvested from porcine septum were secured between two flat parallel copper platens connected to a surgical radiofrequency source. The current was user-selectable and controlled to achieve any desired heating rate mimicking heating rate obtained during laser irradiation. Surface and internal temperatures were monitored by an IR camera and embedding a small electrically insulated thermocouple inside the specimen. Cylindrical and rectangular samples were fashioned from the heated specimens and their equilibrium elastic modulus was measured in a step unconfined compression and tension experiments, respectively. Functional dependencies of the elastic modulus and maximum temperature were interpolated from the measurements. The calculated elastic modulus profiles were incorporated into a numerical model of uniaxial unconfined compression and tension of laser irradiated samples. The reaction force to a 0.1 strain was calculated and compared with the reaction force obtained in analogous mechanical measurements experiment. The results of the numerical simulation of uniaxial compression of laser heated samples demonstrate good correlation with experimentally obtained reaction force. Generalization of this methodology to incorporate orthogonal mechanical properties may aid in optimizing clinical LCR procedures.

A method of control of the absorbed dose of radiation during low-level laser therapy is proposed. It is based on registration of both the reflected part of energy and part of energy spent on local heating of epidermis. Results of theoretical and experimental studies of heating process at pulse action are presented. As a device controlling the absorbed dose a therapeutic machine is proposed. The intensity of its action can be adjusted depending on optical and thermophysical properties of the biological tissue.

Magnetic iron oxide nanoparticles have intrinsic advantages over other nanoparticles for various biomedical applications. These advantages include visualization, heating, and movement properties. There are now numerous efforts underway to expand the applications of these particles for non-invasive magnetic targeting/localization, drug/adjuvant delivery and release, cellular imaging and cellular therapies. In order to move these applications forward it is necessary to define new assays and methods to visualize, move and heat these particles and define their interactions with cellular systems. Our studies of the movement and heating of these nanoparticles in solutions and gels suggest a strong response of these properties to the size and coating of the particles, the suspending medium and the field parameters. Additionally, cellular association is a strong function of the coating and concentration of the nanoparticles and the time of incubation. X-ray computed tomography (CT) can be used to image at least two orders of concentration (1-40 mg Fe/ml) higher than that by 1.5 T Magnetic Resonance (MR) (0.01-0.4 mg Fe/ml) and could prove to be useful for image-guided treatments in vivo.