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Ginsenoside Rg3 is a natural active ingredient that is extracted from Korean red ginseng root. It elevates the therapeutic effect of radiotherapy and chemotherapy, but previous studies found that the application of Rg3 is heavily limited by its low bioavailability and poor absorption via oral administration. To overcome these problems, Rg3-loaded PEG-PLGA-NPs (Rg3-NPs) were prepared by the modified spontaneous emulsification solvent diffusion (SESD) method, and the physicochemical characteristics of Rg3-NPs were investigated. We treated primary glioblastoma with 50 mM Rg3-NPs for 48h. We then used gene expression arrays (Illumina) for genome-wide expression analysis and validated the results for genes of interest by means of real-time PCR. Functional annotations were then performed using the DAVID and KEGG online tools. The results showed that the Rg3-NPs are slick and uniform, the average diameter of the nanoparticles is 75-90 nm, and their entrapment efficiency is 89.7+1.7%. MTT showed that the growth of cells can be significantly inhibited by Rg3-NPs in a dose-dependent manner. FCM testing showed Rg3-NPs can be released from the conjugate nanoparticle and react with the genes in the cell nuclei, causing changes in the gene molecules. We also found that cancer cells treated with Rg3-NPs undergo cell-cycle arrest at different checkpoints. This arrest was associated with a decrease in the mRNA levels of core regulatory genes BUB1, CDC20, TTK, and CENPE, as determined by microarray analysis and verified by real-time PCR. Furthermore, Rg3-NPs induced the expression of the apoptotic and antimigratory protein p53 in cell lines. The results of the present study, together with the results of earlier studies, show that Rg3-NPs target genes involved in theprogressionoftheM-phaseofthecellcycle.Itisassociatedwithseveralimportant pathways, which include apoptosis (p53). Rg3-NPs may be a potent cell-cycle regulation drug targeting the M-phase in glioblastoma cell lines.

The 16th Annual Scientific Meeting of the Society for Neuro-Oncology in Conjunction with the AANS/CNS Section on Tumors, Orange County, California, USA, 17-20 November 2011. In Neuro-Oncology, 2011, v. 13 n. Suppl. 3, p. iii111, abstract no. ET-18

Assess the accuracy, precision, and sources of error using a preclinical MR-guided focused ultrasound system.A preclinical focused ultrasound system, described previously [Chopra et al., Med. Phys. 36(5), 1867-1874 (2009)], was tested on a benchtop and with 3T GE, 3T Philips, and 7 T Bruker MR scanners for spatial targeting accuracy and precision. Randomly distributed water-filled holes drilled into a polystyrene plate were imaged using MRI and targeted using treatment planning software. The ultrasound focus of a 72 mm, f-number 0.8, 1.16 MHz transducer was aimed at the target locations, and 1-2 s continuous-wave sonications were performed on clear polystyrene plates to create localized spots of melted plastic. The distance between target and observed locations was measured and analyzed. Retrospective analysis of targeting accuracy was performed on preclinical data obtained from other experiments at their institution using the same system.The results suggest that the sources of targeting error under MR guidance can be roughly separated into three components--normally distributed random error; constant shift from inaccuracy in detection of the initial ultrasound focus; and angular misalignment between MR and focused ultrasound (FUS) coordinates. The lower bound on the targeting error was estimated to be 0.25 ± 0.13 mm, while the maximum observed targeting error did not exceed 2 mm. Measures required to reduce errors and improve targeting were developed to reduce the registration and misalignment errors such that maximum error was reduced to 0.36 ± 0.14 mm. Retrospective in vivo analysis indicated that the error was 1.02 ± 0.43 mm, including error extrinsic to the system.The FUS system, as described, is capable of precise and accurate sonications. The largest source of error--misregistration of the coordinate systems of the scanner and ultrasound system--was addressed which reduced the error to 0.36 ± 0.14 mm, sufficient for many preclinical applications.

BACKGROUND The current study was conducted to evaluate the combination of external beam radiation therapy and hyperthermia in the treatment of patients with locally advanced prostate carcinoma. METHODS Twenty-six patients were treated on a Phase I/II protocol between June 1990 and April 1993. The median age of the patients was 69 years. Nine patients had well differentiated adenocarcinoma, ten patients had moderately differentiated adenocarcinoma, and six patients had poorly differentiated adenocarcinoma. All patients had American Urologic Society Stage C2-D1 adenocarcinoma. The median pretreatment prostate specific antigen (PSA) level was 29 ng/mL (range, 6–104 ng/mL). All patients received external beam radiation therapy using a four-field technique. The median radiation dose was 6800 centigrays (cGy) given in 200-cGy fractions. Hyperthermia was administered concurrently with radiation therapy to temperatures of 42.5 °C for 30 minutes using a transrectal ultrasound applicator with 3 thermometry probes, given as either a single treatment (9 patients) or as two treatments (17 patients). Overall survival (OS) and biochemical no evidence of disease (bNED) status were calculated using Kaplan–Meier analysis. A consensus conference definition of PSA failure was used. The Cox proportional hazards model was used for multivariate analysis. The median follow-up for all patients was 71 months. RESULTS The median time to PSA nadir was 15 months with a median PSA nadir value of 1.0 ng/mL. The median and 5-year OS was 88 months and 73%, respectively, and the median and 5-year bNED survival was 36 months and 35%, respectively. Multivariate analysis revealed only the pretreatment PSA level (P = 0.03) and the PSA nadir reached (P < 0.01) to be significant predictors of bNED survival. The duration of hyperthermia therapy showed a trend toward significance for OS (P = 0.06). CONCLUSIONS The current Phase I/II protocol evaluating the combination of prostate hyperthermia and external beam radiation therapy for the treatment of patients with locally advanced prostate carcinoma suggests prostate hyperthermia to be feasible with no apparent significant increased toxicity, although there was no significant improvement in treatment outcome when compared with other studies reported in the literature evaluating external beam radiation therapy with or without androgen suppression. However, further investigation into the duration as well as the temperature of the hyperthermia with a greater number of patients is warranted. Cancer 2000;89:399–403. © 2000 American Cancer Society.

A 256-element phased array has been designed, constructed, and tested for ablative treatment of large focal volumes of deep seated tissue. The array was constructed from a 1.1-MHz, 1-3 composite piezoelectric spherical shell with a 10-cm radius of curvature and a 12-cm diameter. The array was tested to determine its electroacoustic efficiency and inter-element coupling under high acoustic power conditions. A series of in vivo porcine experiments demonstrated the ability to produce deep seated tissue lesions in thigh muscle using the large scale phased array. The array was used to heat and coagulate tissue volumes >5 cm/sup 3/ in a single ultrasound exposure using multiple foci and temporally scanned power deposition patterns. The spatial and temporal experimental results for large, heated focal volumes correlated very well with the simulated temperature response model for homogeneous tissue. A 25-cm/sup 3/ tissue volume was coagulated in a 90-min period using overlapping large ultrasound exposures.

Ultrasound has been used for therapeutics for over 70 years, but it has seen a rapid expansion in clinical applications over the last two decades. Ultrasound uses the mechanical energy of pressure waves to induce a number of biological effects in tissue. These effects can range from the annihilation of tissue to the activation of cell surface receptors. The development of new materials and technology has allowed the construction of precise and powerful ultrasound transducers, and combined in particular with advances in magnetic resonance and ultrasound imaging, ultrasound is being applied throughout the body with promising results.

Ultrasound activated contrast agents inside microvessels induce mechanical effects on the vessel wall. It is important to use the bubbles safely and avoid rupturing the vessels. The objective of this work was to develop a three dimensional model of a bubble, blood and micro‐vessels in order to investigate the mechanical effects (mainly the fluid shear stress and the circumferential stress) by a non‐inertial microbubble on the vessel wall. A finite element method was used to solve for this model numerically. The blood vessel was simulated as having a viscoelastic, elastic or a rigid wall. Acoustic pressure and frequency were varied and the values for fluid shear stress and circumferential stress on the vessel wall were calculated. The circumferential stress could exceed the vascular strength in rigid microvessels if the applied acoustic pressure is above 260 kPa. Also the values for fluid shear stress are large enough to induce hemolysis or damage the cell membrane close to the oscillating bubble. Next, the streamlines and stagnation points are obtained for a rigid and a flexible vessel.

A commercial diagnostic ultrasound scanner (Octoson) was modified for performing hyperthermia treatments. The temperature elevations were induced in tissues by four large, focused ultrasonic transducers whose common focal zone was scanned along a computer controlled path as determined from B-scan images. The system is described and the results of preliminary tests demonstrating some of its capabilities are given. Extensive tests with canine thighs and kidneys were performed. The blood flow to the kidneys was controllable, and thus tumours having different blood perfusion rates could be simulated. The results showed that the system is capable of inducing a local temperature maximum deep in tissues (up to 10 cm was tested) and that tissues with high perfusion rates could be heated.

Non-uniform thermal deposition in skull during transcranial focused ultrasound thermal ablation of brain tumors may cause undesired temperature elevation and produce adverse effects in scalp, skull and the adjacent normal brain tissues. Instead of using continuous wave (CW) sonication scheme, a pulsed wave (PW) sonication scheme was proposed, intending to allow extra cooling between sonicating pulses so that the accumulated heat in skull would dissipate from the skull surface to the surrounding low temperature coupling water. Using a 0.6 MHz, 500-elemnt and 300-mm-diameter hemispherical phased array and taking into account of the speed of sound and acoustic attenuation coefficient variations in skull bone, the specific absorption rate distribution and the resulting thermal behaviors in the brain and skull were simulated from a large-scale 3D finite- difference time-domain (FDTD) acoustic and thermal simulation with distributed client/server computing techniques. An active exchange of 15°C chilling water was used to cool the skull. The CW case had a 20-s sonication followed by a 20-s cooling time. Two PW cases were simulated, with five identical pulses of 4-s period with 50% and 25% duty cycle respectively, and followed by a 20-s cooling time. To reach a 70°C peak temperature at focus in the brain tissue, the CW and two PW cases had peak temperatures of 51.5°C, 48.9°C and 48.5°C in the skull bone, respectively. The peak cumulative equivalent minutes at 43°C in the skull bone of the CW and PW cases were 13.5, 0.76 and 0.32 min, respectively. The peak thermal dose in skull of the PW cases were significantly lower than that of the CW case. The results suggest that the pulsed sonication scheme may be useful in reducing thermal deposition in the skull bone during the noninvasive transcranial focused ultrasound surgery of brain tumors.

This study shows that an electrically focussed intracavitary ultrasound array can be constructed for the application of intracavitary hyperthermia. An experimental prototype 0.5 MHz array was tested in water, and was in good agreement with the corresponding theoretical simulations.

Blood brain barrier (BBB) is a major barrier for delivering therapeutic agents in the brain. In this study we investigated the feasibility of open the BBB by using focused ultrasound. Rabbit brains were exposed to pulsed focused ultrasound while injecting ultrasound contrast agent containg microbubbles intravenously. The BBB opening was measured after the sonications by injecting MRI contrast agent i.v. and evaluating the local enhancement in the brain. Low ultrasound powers and pressure amplitudes were found to cause focal enhancement. Before sacrificing the animals trypan blue was also injected i.v.. After the sacrifice of the animals blue spots were found in the brain in the sonicated locations. This method may have potential for targeted delivery of macromolecules in the brain.

Temperature monitoring is most important during the application of thermal treatment, such as in the case of Focused Ultrasound Surgery (FUS). Currently, Magnetic Resonance Imaging (MRI) is the predominant method for temperature mapping of FUS. However, its high cost, low temporal resolution and limited availability and applicability often result in its restricted use. In this paper, a new device for temperature mapping is introduced that only uses focused ultrasound to both apply and monitor the treatment temporally and spatially. By utilizing the principle of the recently introduced Ultrasound-Stimulated Acoustic Emission (USAE) as well as the phased array capability of steering the beam, the temperature distribution at various instants during the application of the treatment could be assessed. The target used here was a silicone gel with tissue-mimicking properties. The temperature spot could be detected during the application of the treatment and the temperature elevation could be both mapped spatially and monitored temporally. In conclusion, an all ultrasound-based system could serve as a more applicable alternative to MR techniques for thermal therapy monitoring. Our plan is to use the same array for the therapy sonication and monitoring of the treatment in the focal zone. This could provide a potential for realizing the ultimate clinical goal: an economic, fully integrated closed loop feedback system for therapy control.

This paper presents a consistent methodology to assess the effect of variable-frequency operation on the dynamics of DC/DC converters, which are commonly used in power-factor-correction and low-cost battery-charger applications. The self-oscillation is typically implemented using peak-current control in boundary mode operation with a deterministic delay. The modeling is based on the proper derivation of cycle-time and on-time constraints leading to full-order small-signal models predicting accurately the dynamical behavior of a converter. The effect of switching delay is found to be insignificant in the load level of concern both by predictions and experiments.

A 16 element, spherically sectioned array has been constructed for application in ultrasound surgery guided by magnetic resonance imaging. To reduce the peak temperature and cooling time interval, a treatment based on rapid switching between multiple focus fields during a ten second sonication has been investigated. First, a simulation study for the array was performed to determine an optimal treatment from a set of multiple focus fields. These fields were generated using the mode scanning technique with power levels determined numerically using a direct weighted gradient search to create an optimally uniform thermal dose over a 0.6/spl times/0.6/spl times/1.0 cm/sup 3/ volume. Second, the simulated results were experimentally tested using MRI to non-invasively monitor temperature elevations and predict lesion size in rabbit thigh muscle in vivo.

To meet two of the requirements for MRI Guided Ultrasound Surgery, namely small surgical equipment and large focal volumes, a combined array encompassing the design parameters of the concentric-ring array and the sector-vortex array has been proposed. Simulations will show that the sectored annular array is capable of producing larger necrosed tissue volumes than the concentric-ring alone, while maintaining the ability of the concentric-ring array to move the focal volume in the axial direction of the array. These simulations are verified by measurements of the acoustic fields produced by an experimental array in water. In addition, the constructed array produced the necessary power required to coagulate tissue in rabbit thigh in vivo, while the temperature elevation was monitored using MRI.

Contingent with previous studies, the transskull ultrasound field is reexamined numerically by utilizing the maximum available skull surface area. The source is assumed to be right on the outer skull surface and phase correction is adopted to obtain a sharp focus at a desired location. A digitized skull profile was obtained from MR images of a volunteer. With no phase correction, there is no apparent transskull focus. With phase correction, a sharp transskull focus is obtained at the desired location. Both pressure and SAR gains are examined, and it is shown that the skull over heating problem can be well overcome. Maximum pressure and SAR gains of above 70 and 800 are observed at 625 kHz. By specifying the phase correction for different locations, the focus can be successfully moved inside most part of the brain volume.

A custom built 512 channel system was designed to drive therapeutic ultrasound phased arrays. The system was used to drive a newly constructed 256 element phased array in a series of MR guided in vivo porcine experiments to coagulate deep seated tissue in the thigh, kidney, and liver. Thermal coagulation lesions greater than 5 cm/sup 3/ in thigh and greater than 2 cm/sup 3/ in the liver were generated using a single 20 second sonication. The feasibility of MR guided phased array ultrasound surgery to coagulate in vivo liver tissue in a large animal model has been shown.

A simple model is presented to illustrate the focal limitations of a spherically sectioned array designed for the treatment of deep seated liver tumors. The design is optimized using the acoustic dose as a function of the focal depth and available acoustic aperture. A quantitative measure of the possible region of focal necrosis is presented as a function of array parameters with the limiting criteria being near field heating. The maximum distance to produce continuous necrosis between foci in a multiple focus pattern and in a temporally multiplexed pattern is approximately 50% larger than the distance needed between sequential foci.

A 57 element aperiodic linear phased array was designed and constructed to investigate the feasibility of using transrectal ultrasound for thermal therapeutic treatment of diseases of the prostate. A method of reducing grating lobe levels by using optimized random distributions of unequally sized elements was used, which made it feasible to use larger elements and hence fewer elements and amplifier channels, while still achieving acceptable power field patterns. The heating capabilities of this array were investigated using an ex vivo perfused kidney for hyperthermia and fresh bovine liver for thermal surgery. The experiments demonstrated that the aperiodic array was capable of generating and controlling adequate power for the purposes of hyperthermia and thermal surgery.

The aim of the study was to test the hypothesis that fast spin echo T(1)-weighted images can be used to quantify the temperature in fat during thermal therapy in vivo. An MR compatible positioning device was used to manipulate focused ultrasound transducers in an MRI scanner. This system was used to sonicate fat tissue around the kidneys of 12 rabbits at various power levels for 10 to 20 sec. The scan parameters of T(1)-weighted fast spin echo (FSE) sequence were varied to optimize signal intensity characteristics while maintaining short scan times. An invasive optical probe was used to calibrate the temperature related signal intensity changes. For the T(1)-weighted FSE sequence, the signal intensity decreased with the temperature elevation at the rate of 0.97+/-0.02%/ degrees C. The single focused transducer produced a contrast-to-noise ratio more than 10 at power levels below the tissue damage threshold. The signal intensity was linearly dependent on the power, despite the measured temperatures being well above the coagulation threshold. This study demonstrates that T(1)-weighted FSE MRI sequences can be used to quantify the temperature elevation in fat in vivo during short focused ultrasound exposures. This can be very important for breast tumor surgery, fat ablation, and for treating deep seated tumors through superficial fat layers. Magn Reson Med 43:901-904, 2000.

An echo-planar spectroscopic imaging method of temperature mapping is proposed. This method is sufficiently faster than the so-called 3D magnetic resonance spectroscopic imaging (3D-MRSI) method and does not require image subtractions, unlike the conventional phase mapping method when an internal reference signal is detectable. The water proton chemical shift measured by using the tissue lipid as an internal reference clearly visualized the temperature change in a porcine liver sample in vitro. It was also demonstrated that the internally referenced echo-planar spectroscopic imaging method could markedly reduce a temperature error caused by a simple, translational motion between scans compared with the phase-mapping method.

The aim of this study was to investigate a potential technique for image-guided minimally invasive neurosurgical interventions. Focused ultrasound (FUS) delivers thermal energy without an invasive probe, penetrating the dura mater, entering through the cerebrospinal fluid (CSF) space, or harming intervening brain tissue. We applied continuous on-line monitoring by MRI to demonstrate the effect of the thermal intervention on the brain tissue. For this, seven rabbits had a part of their skull removed to create access for the FUS beam into the brain through an acoustic window of 11 mm in diameter. Dura was left intact and skin was sutured. One week later, the rabbits were sonicated for 3 seconds with 21 W acoustic power, and the FUS focus was visualized with a temperature-sensitive T1-weighted MRI pulse sequence. The tissue reaction was documented over 7 days with T2-weighted images of the brain. The initial area of the central low signal intensity in the axial plane was .4+/-.3 mm2, and for the bright hyperintensity surrounding the lesion, it was 2.3+/-.6 mm2 (n = 7). In the coronal plane, the corresponding values were .4+/-.1 mm2 and 3.4+/-.9 mm2 (n = 5). The developing brain edema culminated 48 hours later and thereafter diminished during the next 5 days. Histology revealed a central necrosis in the white matter surrounded by edematous tissue with inflammatory cells. In summary, the image-guided thermal ablation technique described here produced a relatively small lesion in the white matter at the targeted location. This was accomplished without opening the dura or the need for a stereotactical device. MRI allowed on-line monitoring of the lesion setting and the deposition of thermal energy and demonstrated the tissue damage after the thermal injury.

Noninvasive magnetic resonance temperature maps that are used to monitor thermal ablation of tissue are described. In magnetic resonance images, thermally induced proton nuclear magnetic resonance frequency shifts, and changes in the longitudinal relaxation time produce both phase and magnitude changes in the MR signal. Temperature maps with improved sensitivity are derived from the complex-difference nuclear magnetic resonance signal. Bovine muscle specimens were heated with focused ultrasound to model thermal surgery and create a known thermal distribution to test the method. Resulting MR images acquired in 2 s produce temperature maps with 1 min resolution and 2 degrees C temperature sensitivity. The temperature sensitivity was increased by extending the acquisition to 5 s, by decreasing the receiver bandwidth, and increasing the echo time.

Ultrasound has several characteristics which make it well suited for the induction of thermal therapy. These include the feasibility of constructing applicators of virtually any shape and size, and the good penetration of ultrasound at frequencies where the wavelengths are on the order of millimeters. The small wavelengths allow the beams to be focused and controlled. The major disadvantages of ultrasound are high absorption in bone and reflection from gas interfaces, which make treatments difficult to execute. These competing features require that ultrasound therapy systems be fairly complex in order to execute a treatment optimally. Only a few clinical systems have attempted to utilize the flexibility of ultrasound and thus, it has not yet been widely tested. Moreover, there are no clinical systems which are fully optimized for treatment of a given tumor.

Preliminary clinical results indicate that some tumors can be heated well utilizing cylindrical ultrasound sources placed in body cavities. In this paper a simple method for measuring the acoustic power from cylindrical intracavitary transducers will be described. The radially propagating acoustic field was converted to a beam with a single propagation direction by a brass reflector, and the radiation force generated by this beam on an absorbing target was measured. The power output of several clinical intracavitary arrays varied significantly between identically shaped transducer elements. The results show that it is important to measure the acoustic power output from each element prior to its clinical use. The radiation force technique is simple and sensitive and can be easily adapted to be used as a routine clinical quality assurance method.

In this study, the feasibility of using magnetic resonance imaging (MRI) to detect tissue necrosis induced by focussed ultrasound beams was investigated. It was shown that lesions produced in dog's thigh muscle in vivo were clearly visible in T2-weighted images and that the lesion dimensions measured from the images correlated with the postmortem measurements of the visible tissue damage. It was also shown that the sonications can be done in the magnet and that the lesions are visible immediately after the sonications with increasing image contrast as a function of time. These results showed that MRI can be used to direct and monitor on-line noninvasive ultrasound surgery. This may have a major impact in future patient treatments.

The performance of several different types of multisensor thermocouple probes have been tested to determine the feasibility of each type for use in the hyperthermia clinic. All of the probes tested were manufactured in-house, and a detailed description of the construction process will be presented. The overall performance of the probes in terms of robustness, calibration, conduction errors, and response time will be described. In particular, this study describes our experience with in-house manufactured thermocouples over the past several years. The results indicate that when strict quality assurance guidelines are followed, in-house manufactured thermocouples perform satisfactorily--thereby providing an alternative to purchasing probes and measurement systems from commercial vendors if the proper resources are available.

In this study the feasibility of utilizing nonlinear ultrasound propagation to control the power deposition patterns during ultrasound hyperthermia treatments of malignant tumors was investigated. From the in vivo results it appears that the power deposition pattern and the temperature distributions can be significantly altered by increasing the temporal peak power of the source while reducing the duty cycle to maintain the same acoustic time average power. The maximum temperature gains obtained during hyperthermia sonication (between 1.5 and 2) were significantly less than one could obtain by varying the frequency and the other parameters of transducers and thus, the linear characteristics of the ultrasound fields should be used when hyperthermia systems are designed and treatments are planned. Then during the treatment nonlinear propagation can be used to provide on-line control of the power deposition patterns. The transducer characteristics determined the magnitude of the temperature gain and the nonlinear propagation region could not be reached when sharply focused (F number = 1) transducers were used at the frequencies between 0.25 to 1.68 MHz due to the high pressure amplitudes that exceeded the transient cavitation threshold.

Maintenance of the controlled temperatures at their target levels in the face of disturbances, a uniform temperature distribution within the treatment region, an acceptable temperature rise outside that volume, a fast temperature rise, and stability are desirable characteristics of an optimal hyperthermia treatment control system. This paper presents a proportional-integral-derivative plus bang-bang (power on at either a maximum value or at zero) feedback control system designed to meet the above requirements for a scanned focused ultrasound hyperthermia system. Treatment stimulations and analytical results for a first-order approximation of a tumor show that the controller is stable for a wide range of gains and sampling times. It was also found that there is an optimal controller gain which minimizes the peak temperature overshoot and the settling time when a step function input is applied to the system. Both the simulation results and experimental animal results show that the controlled region can be rapidly heated to the target temperature with a small overshoot and maintained at that level in the face of disturbances. The effects of temperature fluctuations due to both the periodic changes caused by the scanning and due to measurement noise can be reduced by the use of an auto regressive moving average approach. In vitro dog kidney model and in vivo dog thigh experiments show that the controller works well in practice, and verify that it can compensate for spatial and temporal blood perfusion variations. As shown in both these experiments and in simulations the controller can be used for controlling a single temperature or multiple temperature points simultaneously, thus allowing relatively uniform temperature fields to be created.

This study investigated the design concepts and development of a multielement intracavitary ultrasound applicator for use in hyperthermia. A necessary condition imposed on these applicators is that each transducer element be separately powered and produce collimated beams. This way, the power deposition within the target volume can be controlled by varying the power to each element. Theoretical computer simulations (acoustic and thermal) and bench experiments were used to determine the constraints on the transducer element size and the spacing between them. These have shown that the length of the cylindrical segments (or subsections of) must be greater than approximately 10 lambda for proper collimation and that the spacing between them must be less than approximately 1.5 mm for uniform heating. With these design principles in mind, applicators were constructed using sections of cylindrical transducers (wall-thickness resonance). These were surrounded by temperature-controlled circulating water which was enclosed by a latex membrane. This allowed for acoustic coupling and additional control over the depth of the maximum temperature from the cavity wall. This depth could be varied between the cavity surface and up to 1.5 cm for circulating water temperatures between 5 and 42 degrees C, respectively. These applicators were tested in vivo and were able to induce controlled transrectal heating, at depths of 2-3 cm, in the canine rectum and prostate gland.

Blood units (59) were warmed with the Haemotherm microwave blood warmer and seven units were warmed in a water bath for comparison. The influence of the final blood temperature, the size and the hematocrit of the units on the erythrocyte lesion was studied. Extracellular hemoglobin and potassium, hematocrit, osmotic fragility and mean cellular volume were used as indicators of red cell damage. Warming in the water bath caused no erythrocyte damage at temperatures below +46.8 degrees C. Higher temperatures caused progressive morphological changes and hemolysis. Units of red cells in saline warmed to temperatures above +46.3 degrees C with the Haemotherm showed intense hemolysis and changes in all parameters used. Below this temperature no erythrocyte damage occurred. When the amount of blood warmed was less than 300 g or when the hematocrit exceeded 0.70, the blood mixing mechanism became insufficient, leading to local overheating and hemolysis. Therefore, erythrocyte concentrates in a Fenwal blood bag should never be warmed by the Haemotherm. The mean plasma hemoglobin increase of the ten whole blood units warmed by the Haemotherm to +36.0-36.8 degrees C was 123 mg/l. The results of the present study indicate that microwaves per se are not harmful to erythrocytes but that poor penetrance of microwaves, together with insufficient blood mixing during warming, are the critical factors leading to hemolysis.

focused fields, was used to investigate the effect of nonlinear a bsorption during heat treatments. this study, 56 thermocouples were implanted in dogs' thighs. The temperature distributions were measured during s onication with different intensities while the total acoustical power was kept constant by changing the duty c ycle. The effect of non1 i near absorption was demonstrated both during stationary and scanned field heting. The enhancement of the temperature elevation was significant, and it may be useful during ultrasound hyperthermia treatments.

A series of calculations and tests were performed on polyethylene, polystyrene, acrylic, and a commercially available polymethyl methacrylate cranioplastic to determine which material would best serve as an acoustical window in the skull. The purpose of the window is to transmit focused ultrasound to treat brain tumors with hyperthermia. Each material was evaluated based on its ability to transmit power and to protect the brain. The results revealed that, of the four materials tested, polyethylene transmitted the largest percentage of incident power and is the toughest and best suited material to protect the brain. Further physical tests showed that a polyethylene plate does not significantly distort the sound field. Finally, acute and chronic dog tests (supported by theoretical calculations) using the polyethylene as an acoustical window through the skull showed that it will not reach temperatures greater than the target hyperthermia temperature (42 degrees C) at the required intensity levels unless the tumor is near the skull and the skin surface is not cooled. Since polyethylene effectively transmits power without distorting the sound field of overheating in dog tests, it may now be used in Phase 1 clinical ultrasound hyperthermia tests on human patients. However, the chronic animal studies indicated that the collagen which composes the dura thickens under the cranioplasty and absorbs increasingly greater amounts of power with time. A thick layer of organized fibrous tissue also formed on the external surface of the cranioplasty, filling in the cavity formed by the exterior surface of the cranioplasty and by the excision of the temporalis muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

When inducing localized hyperthermia for superficial cancer therapy with microwaves there has often been question about the total power output from the applicator. Although specific absorption rates and thermograms are used to obtain localized power distributions and heating patterns, these provide, at best, only an approximation of the total power applied to tissues or phantoms. In this paper a calorimetric technique for obtaining total microwave output power from applicators is described. An experimental apparatus was constructed and it was found to be accurate to approximately +/- 5 W. The power output from four clinical microwave applicators as a function of applied electric power was measured and the efficiency was found to be 40% in average. Along with enhancing quality assurance, the areas of hyperthermia research which may benefit the most from this calorimetric technique are computer modeling and patient treatment planning.

In this study the ultrasonic field distortions and the temperature measurement errors caused by temperature sensing probes were investigated. It was found that probes with diameters equal to or greater than 1/2 of the square root of the wavelength (lambda) scatter and reflect the waves, and thus distort the field significantly. Smaller probes down to lambda 1/2/5 in diameter had a detectable effect which was very local and, therefore, will probably not have a significant effect on the overall temperature distribution. When the temperature measurement errors were studied, even the smallest probes showed some self-heating artifact and its magnitude depended on the probe size, material, structure, orientation, and the operating frequency. This error was small with most of the nonultrasound absorbing probes (such as bare wires or stainless steel needle probes), but significant with plastic shielded thermocouples. The energy absorption associated with plastic coated probes can be reduced by orienting the probe parallel to the beam, by scanning the focus in such a manner that the focus is not passing on the sensor, and by inserting the probe in a stainless steel catheter. The temperature measurement error can also be reduced by covering the plastic probe with a high- (or low-) acoustical impedance material around the sensor. This would scatter the sound around the probe, thus preventing energy absorption in the plastic. This arrangement can preserve the desirable properties of plastic probes (mainly flexibility, strength, and electrical isolation from the patient) while at the same time allowing fairly absorption artifact free measurements.

Using the combined concentric-ring sector-vortex phased array concept, the present work explores the viability of the design to treat regions of various sizes and depths. Several large-scale phased arrays were constructed to verify the array design for treatment of large deep-seated tumors. MRI guided in-vivo and ex-vivo experiments were performed to verify the extent to which the array's power absorption pattern could be tailored for treatment of deep tissue. It is shown that the array design is able to target volumes of tissue at various distances from the transducer surface by electronically phasing the annular concentric ring elements. Furthermore, it is demonstrated that it is possible to increase the heated area in the radial plane by applying radial-sector phase rotation. Results are presented for a 12 cm diameter f/1.3 phased-array for ex-vivo and in-vivo experiments guided by MRI.