B. Stuart Trembly

The Effects of Driving Frequency and Antenna Length on Power Deposition Within a Microwave Antenna Array Used for Hyperthermia

The theory of the linear, insulated antenna embedded in an electrically dense medium is applied to microwave antennas used for hyperthermia cancer therapy. The pattern of power deposition is computed for a square array of four antennas with a side length of 3 cm under the assumption of no coupling among antennas. The driving frequency is set to seven values between 300 and 915 MHz, and the antenna halflength is set to three values: 3 cm, 6 cm, and the resonant value.

Brain hyperthermia: I. interstitial microwave antenna array techniques—the Dartmouth experience

PURPOSE Microwave antennas of various designs were inserted into arrays of nylon catheters implanted in brain tumors with the goal of raising temperatures throughout the target volume to 43.0 degrees C. METHODS AND MATERIALS All antennas were flexible, and included dipole, choke dipole, modified dipole, and helical designs driven at 915 or 2450 MHz. Antennas were tested in brain-equivalent phantom in arrays. Phase shifting and phase rotation techniques were incorporated into the treatment system to steer power in the tumor, assisted by a treatment planning computer that predicted power deposition patterns and temperature distributions. Choke antennas were designed and tested to reduce a dependence of the central power location on depth of insertion into tissue. Temperature data analysis used only central and orthogonal axes mapping data measured at 2.0 mm intervals. RESULTS A total of 23 patients were treated, using from one to six microwave antennas. Minimum tumor temperatures, averaged over the 60 min treatment, ranged from 37.2-44.3 degrees C (mean 40.0 degrees C) and maximum average tumor temperatures ranged from 46.5-60.1 degrees C (mean 49.1 degrees C). The percentage of all measured temperatures reaching therapeutic levels (> or = 43.0 degrees C) was 70.9. T90, the temperature at which 90% of all measured temperatures equaled or exceeded, was 40.8 degrees C, and T50 was 44.2 degrees C. CONCLUSION Patient data analysis showed that the array of four dipole antennas spaced 2.0 cm apart were capable of heating a volume of 5.9 cm (along the central array axis) x 2.8 cm x 2.8 cm.

Comparison of magnetic nanoparticle and microwave hyperthermia cancer treatment methodology and treatment effect in a rodent breast cancer model

Abstract Purpose: The purpose of this study was to compare the efficacy of iron oxide/magnetic nanoparticle hyperthermia (mNPH) and 915 MHz microwave hyperthermia at the same thermal dose in a mouse mammary adenocarcinoma model. Materials and methods: A thermal dose equivalent to 60 min at 43 °C (CEM60) was delivered to a syngeneic mouse mammary adenocarcinoma flank tumour (MTGB) via mNPH or locally delivered 915 MHz microwaves. mNPH was generated with ferromagnetic, hydroxyethyl starch-coated magnetic nanoparticles. Following mNP delivery, the mouse/tumour was exposed to an alternating magnetic field (AMF). The microwave hyperthermia treatment was delivered by a 915 MHz microwave surface applicator. Time required for the tumour to reach three times the treatment volume was used as the primary study endpoint. Acute pathological effects of the treatments were determined using conventional histopathological techniques. Results: Locally delivered mNPH resulted in a modest improvement in treatment efficacy as compared to microwave hyperthermia (p = 0.09) when prescribed to the same thermal dose. Tumours treated with mNPH also demonstrated reduced peritumoral normal tissue damage. Conclusions: Our results demonstrate similar tumour treatment efficacy when tumour heating is delivered by locally delivered mNPs and 915 MHz microwaves at the same measured thermal dose. However, mNPH treatments did not result in the same type or level of peritumoral damage seen with the microwave hyperthermia treatments. These data suggest that mNP hyperthermia is capable of improving the therapeutic ratio for locally delivered tumour hyperthermia. These results further indicate that this improvement is due to improved heat localisation in the tumour.

A theoretical model for input impedance of interstitial microwave antennas with choke

PURPOSE Two important characteristics for interstitial microwave antennas used in clinical hyperthermia are: (1) a good impedance match to minimize reflected power; and (2) a good power deposition pattern which is independent of insertion depth. A major problem of the miniature coaxial dipole antennas used for interstitial hyperthermia is the fact that the impedance and power deposition patterns of these antennas change with insertion depth. One possible solution is the addition of a coaxial choke. A theoretical model for calculating the input impedance of interstitial microwave antennas having a coaxial choke is presented, which may serve as the first step in the design of such antennas. METHODS AND MATERIALS A theoretical model for calculating the input impedance of coaxial microwave antennas with and without a choke is presented using insulated antenna theory. The theoretical model was used to calculate the input impedance of several prototype antennas having various choke and feedline dimensions, and comparison was made with experimentally measured impedance measurements in tissue-equivalent phantom. RESULTS The choke section of the antenna is not ideal if conventional plastic insulation is used as the choke dielectric, because the desired radiating length of the antenna is significantly shorter than the quarter-wavelength in the choke dielectric. Impedance calculations based on the theoretical model correlate reasonably well with experimentally measured impedance. Based on these calculations, the effect of parameters such as choke layer thickness and choke dielectric constant are discussed for a 915 MHz antenna with choke. CONCLUSION The theoretical model can serve as a design aid for optimizing choked microwave antenna designs, as well as predicting the impedance match of a given antenna design at a given insertion depth. The model allows the effect of some variables not accessible experimentally such as termination impedance to be studied, which may also be useful in the understanding of these antennas. Calculations are easily performed on a desktop computer.

Comparison of a Single Optimized Coil and a Helmholtz Pair for Magnetic Nanoparticle Hyperthermia

Magnetic nanoparticles in a tumor can induce therapeutic heating when energized by an alternating magnetic field from a current-carrying coil outside the body. We analyzed a single-turn, air-core coil carrying a filamentary current to quantify the power absorbed by: a) magnetic nanoparticles at depth in tissue and b) superficial tissue in response to induced eddy currents; we defined this quotient as power ratio (PR). Given some limit on the eddy current heating tolerated by an alert patient, maximizing the PR maximizes the power absorbed in the tumor; all else being equal, this increases the thermal dose delivered to the tumor. The mean eddy current heating rate tolerated in four clinical studies we reviewed equaled 12.5 kW/m 3. We differentiated our analytical expression for PR with respect to the radius of the coil to find the value of radius that maximizes PR. Under reasonable simplifying assumptions, the optimal value of coil radius equaled 1.187 times the depth of the nanoparticle target below the body surface. We also derived the PR of two coils surrounding the body configured as a Helmholtz pair. We computed PR for combinations of nanoparticle depths below the surface and axial locations with respect to the coils. At depths less than 4.6 cm, the optimized single coil had a higher PR than that of the Helmholtz pair and furthermore produced less total ohmic heating within the coil. These results were independent of driving frequency, nanoparticle concentration, tissue electrical conductivity, and magnetic nanoparticle heating rate, provided the latter is assumed to be proportional to the product of frequency and the square of the local magnetic field. This paper supports the clinical application of current-carrying coils to deliver efficacious hyperthermia therapy to tumors injected with magnetic nanoparticles.

Imaging magnetic nanoparticles using the signal's frequency spectrum

Current methods of magnetic particle imaging generate a signal by cyclically saturating nanoparticles creating measurable harmonics in the induced magnetization. The sensitivity promises to be competitive with SPECT so molecular imaging is possible. The signal was localized by saturating the nanoparticles outside a voxel using a strong static magnetic field and sweeping the voxel across the sample to form an image. However, in applications where enough nanoparticles are present, signal can be detected at several higher harmonic frequencies and we show that the distribution of signal between those frequencies contributes localizing information. We tested one-dimensional implementations but the methods can be generalized to three dimensions. Spatial encoding was accomplished by using multiple drive frequencies that varied spatially. Two drive coils tuned to different drive frequencies and mounted on the same axis were used to explore the method. The response was measured from a single sample of iron oxide nanoparticles at eight positions along that axis to estimate response function for the reconstruction. Then two identical samples were placed at pairs of locations to test the method. The sample positions were reconstructed from the measured spectrum of the signal generated. The number of independent parameters is limited but four independent parameters can be achieved with very good conditioning and eight independent parameters can be achieved with reasonable conditioning.

Comparison of iron oxide nanoparticle and microwave hyperthermia alone or combined with cisplatinum in murine breast tumors

Surgery, radiation and chemotherapy are currently the most commonly used cancer therapies. Hyperthermia has been shown to work effectively with radiation and chemotherapy cancer treatments. The major obstacle faced by previous hyperthermia techniques has been the inability to deliver heat to the tumor in a precise manner. The ability to deliver cytotoxic hyperthermia to tumors (from within individual cells) via iron oxide magnetic nanoparticles (mNP) is a promising new technology that has the ability to greatly improve the therapeutic ratio of hyperthermia as an individual modality and as an adjuvant therapy in combination with other modalities. Although the parameters have yet to be conclusively defined, preliminary data suggests mNP hyperthermia can achieve greater cytotoxicity (in vitro) than conventional water bath hyperthermia methods. At this time, our theory is that intracellular nanoparticle heating is more effective in achieving the combined effect than extracellular heating techniques.1 However, understanding the importance of mNP association and uptake is critical in understanding the potential novelty of the heating modality. Our preliminary data suggests that the mNP heating technique, which did not provide time for particle uptake by the cells, resulted in similar efficacy to microwave hyperthermia. mNP hyperthermia/cisplatinum results have shown a tumor growth delay greater than either modality alone at comparable doses.

Evaluation and comparison of five experimental BPH/prostate cancer treatment modalities

Five non-pharmacological, experimental, prostate (benign hyperplasia/cancer) treatment modalities including transurethral radiofrequency thermotherapy (TURT); transurethral microwave thermotherapy (TUMT); transurethral and transrectal microwave thermotherapy (TUMT/TRMT); interstitial laser coagulation (ILC); and interstitial cryotherapy (IC), are evaluated. These and other similar techniques are currently in various stages of development and clinical use. Most of these modalities produce relatively similar effects in tissue; however, each has pathophysiologic features and potential complications which may preference its use in a specific anatomical and/or disease situation. All treatments were performed using the canine prostate model, by the same investigators. Our studies have shown that although the canine prostate does not respond to injury exactly as the human prostate does, the effects are similar enough to be conceptually, and often specifically, valuable from efficacy and safety standpoints. Two of the five treatments evaluated (TURT, TUMT/TRMT) resulted in marked dilation of the prostatic urethra without significant parenchymal effect. Three of the treatments (IC, ILC, TUMT) resulted in parenchymal ablation with only minor dilation of the urethra. Although each technique has encouraging experimental findings, ultimate success will be determined by further definition of the instrumentation technique and appropriate clinical implementation.

Separation of Solid Stress From Interstitial Fluid Pressure in Pancreas Cancer Correlates With Collagen Area Fraction

Elevated total tissue pressure (TTP) in pancreatic adenocarcinoma is often associated with stress applied by cellular proliferation and hydrated hyaluronic acid osmotic swelling; however, the causal roles of collagen in total tissue pressure have yet to be clearly measured. This study illustrates one direct correlation between total tissue pressure and increased deposition of collagen within the tissue matrix. This observation comes from a new modification to a conventional piezoelectric pressure catheter, used to independently separate and quantify total tissue pressure, solid stress (SS), and interstitial fluid pressure (IFP) within the same tumor location, thereby clarifying the relationship between these parameters. Additionally, total tissue pressure shows a direct correlation with verteporfin uptake, demonstrating the impediment of systemically delivered molecules with increased tissue hypertension.

Is penile electrocautery safe?: I. Histological and computational temperature assessment in an animal model

The purpose of this study was to evaluate the thermal and tissue changes associated with the use of electrocautery hemostasis on dependent tissues such as the penis. Circumcision was performed on twelve male sheep using a Gomco clamp and surgical removal. Electrocautery was then applied circumferentially to 6 separate sites along the circumcision incision for a duration of 2 seconds per application, with a 10-second interval between applications. Coagulation electrocautery power was set at either 25 or 50 Watts. Temperature changes were monitored by fiber-optic temperature probes placed immediately beneath the circumcision site in the penile urethra and at the base of the penis. Three animals were sacrificed acutely while the remaining 15 animals were sacrificed one month post-procedure. Penises were assessed by gross and histologic observation. Immediately post-procedure, epidermal and superficial dermal necrosis was observed at the cautery sites. By 32-days postprocedure, primary tissue change at the cautery site consisted of scarring and mild inflammation. Energy level (25 vs 50 Watts) did not significantly affect the level of tissue damage. Penile tissue subadjacent or distant to the cautery sites showed no gross or histologic change at the acute or chronic assessment period. During electrocautery, a maximum increase of 7°C (1-2 mm from the site of electrocautery) was observed regardless of the energy level. Temperature elevations commonly returned to near baseline within 5 minutes post-application. Smaller increases in temperature (range 1-2°C) occurred at the base of the penis. Our results document the long-held perception that electrocautery hemostasis can be safely employed in penile surgery, if the appropriate technique is used. Significant temperature and tissue changes are confined to very small/localized regions immediately adjacent to the cautery applicator.