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Biomedical subjects

K Hynynen

Publications and source records attributed to K Hynynen.

At least 127 records · Page 7Linked to original sources

Feasibility and patient tolerance of a novel transrectal ultrasound hyperthermia system for treatment of prostate cancer.

This report describes patient tolerance and toxicity of a transrectal ultrasound hyperthermia system used with external beam radiation therapy in treatment of locally advanced prostate cancer. Nine patients with clinical T2B-T3B (4th edition AJCC criteria) disease received external beam radiation therapy, with two hyperthermia treatments scheduled at least 1 week apart during the first 4 weeks of radiation. Five patients also received hormonal therapy. Interstitial and anterior rectal wall thermometry were performed. Median temperature for each treatment (T50) was 40.8 degrees C and mean CEM T90 = 43 degrees C was 3.4 min. Rectal wall temperature was maintained at < or = 40 degrees C. Treatment duration was limited in three of 17 sessions due to positional discomfort which was alleviated with light IV sedation and use of a 'New Life' mattress (Comfortex, Inc. Winoba, MN, USA). Acute toxicity was limited to NCI common toxicity criteria grade 1 and no excess toxicity was noted with full course radiation therapy +/- hormonal therapy. These findings are consistent with those reported in a previous phase I trial assessing this device. Given the favourable toxicity profile demonstrated to date, modification of treatment parameters for this ongoing phase II study have been instituted that should further the efficacy of transrectal ultrasound hyperthermia for treatment of prostate cancer.

Aged↗

MR-guided focused ultrasound surgery.

Magnetic resonance guided focused ultrasound surgery provides a minimally invasive controlled method for selectively destroying deep-lying tissue. A thermal analysis of focused ultrasound provides an estimate of the time-dependent temperature distribution and thermal dose required for ultrasound surgery. The temperature distribution is estimated by accumulating heat sources, considering the effects of thermal conductivity, heat content, and perfusion. In this study, both gel phantoms and excised in vitro bovine muscle specimens were imaged in a 1.5 T MR system while heated with a 5 cm diameter, 10 cm focal length, 1.1 MHz transducer. During sonication, the thermal effects were observed with T1-weighted pulse sequences. Below a critical temperature, the heat zone appeared as a dark spot that moved with the focal spot. Above a critical thermal dose, the in vitro tissue was irreversibly altered and the focal lesion was observed on both the MR image and the specimen slice.

Absorption↗

An ultrasound window to perform scanned, focused ultrasound hyperthermia treatments of brain tumors.

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)

Acrylic Resins↗

The efficiency of clinical microwave applicators measured by a calorimetric method.

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.

Calorimetry↗

Temperature measurements during ultrasound hyperthermia.

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.

Animals↗

Theoretical and experimental evaluation of a temperature controller for scanned focused ultrasound hyperthermia.

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.

Animals↗

The development of intracavitary ultrasonic applicators for hyperthermia: a design and experimental study.

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.

Animals↗

The role of nonlinear ultrasound propagation during hyperthermia treatments.

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.

Animals↗

The feasibility of interstitial ultrasound hyperthermia.

One of the most promising ways to increase the efficacy of brachytherapy is to combine it with hyperthermia. In this paper, the feasibility of using ultrasound transducers as interstitial hyperthermia sources was investigated. The ultrasound output of eight cylindrical transducers (diameter 1 mm and length 25 mm) was studied. It was found that many of these transducers were able to generate between 2 and 3 W of acoustic energy at the frequency of 9.5 MHz. The ultrasound field emitted radially was well collimated and extended the full length of the transducer. In vitro perfused liver and kidney experiments showed that an array of four transducers placed in brachytherapy catheters up to a maximum spacing of 20 mm in a square pattern could induce therapeutic temperatures. Also, the effect of flow rate into the organs and catheter cooling were investigated. These results showed that interstitial ultrasound sources are potentially the most promising way of generating therapeutic temperatures through standard interstitial radiation therapy catheters.

Animals↗

Thermocouples--the Arizona experience with in-house manufactured probes.

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.

Feasibility Studies↗

MRI-guided noninvasive ultrasound surgery.

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.

Animals↗

Acoustic power calibrations of cylindrical intracavitary ultrasound hyperthermia applicators.

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.

Acoustics↗

A scanned, focused, multiple transducer ultrasonic system for localized hyperthermia treatments.

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.

Animals↗

Temperature elevation at muscle-bone interface during scanned, focused ultrasound hyperthermia.

The effect of a muscle-bone interface on the temperature distribution during scanned, focused ultrasound hyperthermia was studied in vivo in dogs' thighs. The detailed temperature maps showed a sharp temperature maximum at the interface. The magnitude of the temperature elevation was between two and four times as large as obtained in resting muscle with similar intensities. The muscle tissue close to the bone could be heated to a therapeutic temperature level without overheating the bone when higher frequency or multiple-focused beams were used. The results showed that bone pain associated with ultrasound hyperthermia treatments is probably caused by extreme temperatures in bone, which can be avoided by sonicating the tumour in such a manner that the intensities at the bone surface are low enough so as not to cause large temperature elevations. Therefore, treatment planning which takes into account the location of bones is necessary for successful, clinical utilization of scanned, focused ultrasound hyperthermia.

Animals↗

The effect of blood perfusion rate on the temperature distributions induced by multiple, scanned and focused ultrasonic beams in dogs' kidneys in vivo.

The effect of blood perfusion rate on the temperature distribution during scanned, focused ultrasound hyperthermia was investigated using an in vivo dog kidney model. The results showed that the ultrasound beams could penetrate through the body wall without severe distortion, and that they could be used to induce controlled temperature elevations in the target volume. The blood perfusion rate of the heated tissue significantly modified the temperature distribution and the temperatures achieved in the kidney with no flow were about five times higher than in the case with full flow for the same applied acoustic power. It was also demonstrated that the power deposition pattern produced by scanned focused ultrasonic fields could be modified to give an acceptable temperature distribution in different perfusion situations. Similar trends were also obtained by using the bioheat transfer equation to simulate the experiment. Both the magnitude of the temperature elevations and the effect of perfusion on the temperature distributions obtained in the experiments were in agreement with the simulations. The main difference occurred at high perfusion rates where the experiments showed significant temperature elevation outside of the scanned volume and the simulation results predicted hardly any temperature increase 5 mm outside the scan. These observations indicate that both the theoretical power calculation programme and the temperature simulations will have value in the design of optimal heating systems, treatment planning and in the retrospective of the achieved temperature distributions.

Animals↗

The CDRH Helix: an in vivo evaluation.

The Helix is an electromagnetic heating device used to induce regional/systemic hyperthermia for cancer therapy. It is a resonant device operating at about 82 MHz with an aperture size of 60 cm x 40 cm (elliptical) x 40 cm long. The Helix deposits power in tissues (or phantoms) by producing a predominantly axial electric field within its radiating aperture. Five pig experiments were performed to provide in vivo verification of specific absorption rate (SAR) measurements and electric field measurements which were obtained earlier in tissue-equivalent phantom and 0.9% saline, respectively. In addition to verifying the power deposition patterns found in phantoms, the pig experiments provided valuable insight into the capabilities and limitations of electromagnetic regional heating. For example, a kidney with limited blood flow, simulating a necrotic tumor, heated very well-although the highest temperature was not always measured there. Also, fat heating may be a problem, since excessive temperatures in the fat were observed in approximately 20% of the heatings. This paper compares the in vivo temperature measurements in pigs with SARs and electric field measurements obtained in phantoms, and also provides a brief overview of results of the Helix in clinical situations.

Adipose Tissue↗

Temperature distributions during clinical scanned, focused ultrasound hyperthermia treatments.

In this study a scanned focused ultrasound (SFUS) system was used to heat 66 tumours at various anatomical locations in 52 patients. A total of 160 treatments were given. On average, temperatures were measured in 14 or 15 locations in the scanned volume. The time-averaged temperatures over the 30 min treatment period in the best treatment of each tumour were 44.0 +/- 2.4 degrees C (mean +/- SD) and 39.6 +/- 1.5 degrees C at the location of the highest and lowest sensor, respectively. On average, 39% of the sensors were above 42.5 degrees C. When only the cases that were judged to be good candidates for the hyperthermia device were analysed, 64% of the sensors reached a temperature over 42.5 degrees C with the highest temperature achieved being 45.9 +/- 2.3 degrees C and the lowest 40.7 +/- 1.4 degrees C. Although the system tested has many technical limitations (for example, fixed frequency, beam geometry and power during the scan cycle), the results demonstrate that therapeutic temperatures can be achieved in many tumours. Significantly better temperatures are expected when all of the theoretical potential of scanned focused ultrasound systems has been used.

Body Temperature↗

Hot spots created at skin-air interfaces during ultrasound hyperthermia.

It is well known that ultrasound beams will be completely reflected at a soft-tissue-gas interface. The reflected beam is contributing to the power absorption at the tissue interface and may cause a hot spot which could prevent therapeutic temperatures at the treatment volume. In this study the temperature elevation caused by a reflected ultrasound beam at the skin surface has been investigated in dogs' thighs in vivo. The magnitude of the hot spot was quantified and the effect of entrance angle was also investigated. In addition, the possibility of eliminating the hot spot by coupling the beam out of the tissue was studied. The results showed that the temperature elevation can be up to four times larger at the skin-air surface than in resting muscle under similar exposure. The geometry of the reflecting surface had a significant effect on the temperature distribution. When the sound was coupled out of the tissue the magnitude of the temperature elevation at the skin reduced to less than half (depending on the geometry) but was still larger than temperatures measured in muscle. These results suggest the need for computerized treatment planning for scanned focused ultrasound treatments.

Air↗