Robert B. Roemer

Effects of physical parameters on high temperature ultrasound hyperthermia

The purpose of this research was to investigate the feasibility of inducing perfusion independent, predictable therapeutic thermal dose using high power ultrasonic pulses. Computer simulations were used to study the effects of blood perfusion, tissue properties, transducer characteristics, and treatment geometry on the temperature elevation and thermal dose delivered by short ultrasonic pulses. Experiments were conducted in vitro and in vivo to investigate the effects of blood perfusion changes. Results show that short pulse lengths (less than or equal to 2 s) and small focal diameters (approximately 3 mm) give temperature elevations and thermal doses which are nearly perfusion independent. Normal fluctuations in tissue properties should not have a significant effect on the treatment provided that proper choice of transducer is made for each individual application.

Observations on the Use of Ferromagnetic Implants for Inducing Hyperthermia

Magnetic induction heating of ferromagnetic implants can be used to produce highly localized hyperthermia in deep seated tumors. We discuss the physical parameters which characterize this method and give illustrations from initial clinical investigations in animals. The physical parameters studied include magnetic field strength, frequency, load size, field uniformity, coil designs, and the heating potential of implant materials and configurations. Calculations consistent with our experimental results predict a maximum heating frequency of the order of 500 kHz for large cross-sectional loads, such as the human abdomen, and 1.9 MHz for smaller loads, such as the human brain. An experlhnental technique is introduced for accurate quantitative evaluation of the heating potentials of ferromagnetic materials in a gelled phantom medium. These data are analyzed in terms of heating efficiency per unit implant length (¿L), which is itself a function of implant length, diameter, annealed state, and orientation with respect to the magnetic field. A spiral sheet coil design is described and recommendations are given for proper E-Field shielding of induction coils for clinical applications. A brief discussion of techniques of implanting the ferromagnetic materials is also given. Finally, several in vivo animal studies are presented to illustrate the use of the technique for treating tumors in pelvis, thorax, oral-pharynx, and brain.

Treatment of malignant brain tumors with focused ultrasound hyperthermia and radiation: results of a phase I trial

SummaryHyperthermia delivered by scanned focused ultrasound was combined with external beam radiation to treat 15 patients with primary malignant tumors of the brain. A preliminary craniectomy was performed to avoid attenuation of the ultrasound beam by the skull, and multiple thermal sensors were employed to ascertain intratumoral temperatures. The target temperature was 42.5°C at the tumor boundary. This was attained at more than one point during every complete treatment, while a mean temperature in excess of 42°C was achieved within the scanned tumor volume during at least 1 treatment in 11 patients. Technical problems and toxicities are described.

Obtaining local SAR and blood perfusion data from temperature measurements: steady state and transient techniques compared

A series of analyses and experiments was performed to determine the extent that SAR and blood perfusion information can be extracted from steady state temperature values and from transient temperature measurements following a step change in applied power. Multiple local temperature measurements were made in canine thighs heated by 2450 MHZ microwaves to evaluate two parameters: the local absorbed power in the tissue, and the local effective blood perfusion. The theoretical bases for these calculations are presented in order to identify their underlying assumptions and to obtain a unified basis for comparison of the various calculation methods used by previous investigators. From energy balance considerations it can be shown that the local absorbed power can be obtained from either the rate of increase of temperature following a step increase in power, or from the rate of decrease in temperature immediately following a step decrease in power. These theoretical observations are verified experimentally by comparing the SAR results at fixed positions in canine thighs as calculated from both increasing and decreasing power steps. For decreasing power steps, the resulting decreasing temperature curves can also be used to calculate an effective blood perfusion rate if thermal conduction is included. Alternatively, this same effective blood perfusion rate can be calculated from steady state data. (These two approaches have been used by previous investigators to determine blood perfusion values. We have added the modifier effective to specifically denote the presence of thermal conduction effects in such perfusion calculations.) From our experimental results and theoretical calculations it appears that differences between the predictions of the two calculation methods arise from changing thermal conduction values during the cooling period of the thermal clearance method. The steady state calculation approach is easier to apply than the washout method, but it requires the additional knowledge of the local SAR value. It is important to realize that effective blood perfusion values calculated using thermal techniques are subject to large errors under conditions where thermal conduction is important, unless this conduction is explicitLy included in the calculation. Such effective blood perfusion values should not be quantitatively compared to values calculated from non-thermal techniques that are not affected by thermal conduction. Unless such conduction effects are known to be negligible, effective perfusion values are only qualitative indicators of the presence of changes in blood perfusion.

A Survey of Computer Simulations of Hyperthermia Treatments

This paper is a review of the state-of-the-art of-a new-area in hyperthermia: computerized simulations of hyperthermia treatments. One of the more difficult problems in hyperthermia is the determination of the complete temperature field throughout both tumor and normal tissue. Theoretical methods, of estimating temperature distributions are needed to help address this problem. In this paper we divide this field into four areas: comparative, prospective, concurrent, and retrospective. We then summarize the mathematical formulations of both the electromagnetic and ultrasonic power deposition problems and the heat transfer problem. This is followed by a review of the numerical techniques available for calculating the power deposition in the tissue and then finding the resulting temperature distribution. The paper concludes with a description of a series of applications drawn from the current literature.

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.

Development of scanned focussed ultrasound hyperthermia: Clinical response evaluation clinical response evaluation

Selective heating of irregularly shaped tumors at depth can now be accomplished through focussing and controlled scanning of energy deposition patterns by ultrasound. A scanned focussed ultrasound (SFUS) hyperthermia system developed at the University of Arizona has been used to deliver 220 treatments to 87 tumors in 71 patients with extracranial malignancies between October 1986 and May 1990. Patients received an average of three SFUS hyperthermia treatments, spaced weekly, during ongoing fractionated radiotherapy. The most common anatomic sites treated were the pelvis (22 patients), chest wall or breast (14), neck (8), and axilla (7), while the most common histologies were adenocarcinoma (36), squamous cell carcinoma (11), and melanoma (10). Concurrent radiotherapy was delivered (range 1000-7640 cGy, mean 4320 cGy) to 67 SFUS hyperthermia patients; 4 received concomitant chemotherapy. Tumor volumes ranged from 1-2100 cubic centimeters (mean 325 cc), and 75% were located at depths greater than 3 cm from skin. A 62% overall response rate was observed, with 22% of treated tumors demonstrating a complete response (defined as complete disappearance of treated tumor), and 40% exhibiting a partial response (defined as greater than or equal to 50% reduction in tumor volume). Dramatic local pain reduction was achieved in 42% of the tumors treated. The acute tolerance of SFUS hyperthermia was quite good, and chronic toxicities (persistent skin blisters/burns) were identified in two patients. The versatility of the SFUS system is discussed, as well as its future potential for improving control of advanced loco-regional malignancies treated with curative intent.

Experimental evaluation of two simple thermal models using hyperthermia in muscle in vivo

The predictions from two simple field equation models for calculating temperature distributions in tissue, namely, the Pennes bioheat transfer equation (BHTE) and an effective thermal conductivity equation (ETCE), were compared to in vivo experimental temperature measurements made under hyperthermic conditions generated by scanned focused ultrasound. The models were kept simple (i.e. homogenous isotropic properties, no separate blood vessels included) in order to concentrate attention on the predictive abilities of these field equations using a minimum number of free parameters. Simulated results were fitted to the experimental data (multiple, linear temperature profiles in the thigh muscles of greyhound dogs) by minimizing a performance index using a golden section searth. This search determined a value for the single free parameter in each model (blood perfusion in the BHTE, and effective thermal conductivity in the ETCE) which minimized the square error difference between the experimental and simulated temperatures. The results showed that (a) the simple BHTE model could qualitatively reproduce the major features of the temperature patterns seen experimentally better than the ETCE model could, and (b) the simple BHTE model produced better quantitative fits to the experimental data than did the simple ETCE model. In addition, blood perfusion predictions from the BHTE model compared well to measurements done with coloured microspheres. Finally, the experimental results showed that individual, large blood vessels appeared to have a major influence in producing asymmetries in the experimental data in 21% of the measured temperature profiles.

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.

Scanned focussed ultrasound hyperthermia: initial clinical results☆

Between November 1986 and July, 1987, a preliminary study to determine the feasibility of scanned focussed ultrasound for clinical hyperthermia at various sites was conducted. Fourteen patient (17 tumors) have been treated using a microprocessor-controlled apparatus developed at the University of Arizona by modifying a commercially available diagnostic ultrasound unit. We have treated nine pelvic tumors, four extremity tumors, two brain tumors, and two extracranial head and neck tumors for a total of 42 treatments. Multipoint thermometry was achieved for all patients, with 2-25 (mean = 10) points monitored during each treatments within the scanned tumor volume. Average maximum temperature within the scanned tumor volume was 44.2, 44.7, 44.8, and 42.0 degrees C for pelvic, extremity brain, and extracranial head and neck tumors, respectively; similarly, 55%, 45%, 71%, and 0 of monitored points exceeded 42.5 degrees C. Pain limited applied power in 15 of 42 treatments, and bone pain with a periodicity similar to the scanning periodicity was seen in 11 treatments. A non-randomized comparison of temperatures achieved using scanned focussed ultrasound to those achieved using the microwave annular array and the CDRH Helix suggests that scanned focussed ultrasound may have promise and potential advantages in heating selected pelvic tumors.