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Biomedical subjects

J W Hunt

Publications and source records attributed to J W Hunt.

98 records · Page 6Linked to original sources

The development of improved ultrasound heaters suitable for superficial tissue heating.

The acoustical fields generated by several ultrasound heaters have been measured to determine their suitability for heating superficial lesions in cancer patients. Three different acoustical sensors were used in the study, and one sensor, consisting of a thermocouple embedded in a sound-absorbing plastic, proved to be the most practical device for routine use. The method employed to mount the piezoelectric crystal in the heater was found to have a profound effect on the acoustical field generated by the heater. Clamping the crystal close to its edge resulted in a field with a prominent acoustical maxima on the crystal axis. A flexible attachment at the very edge of the crystal resulted in a much more uniform field which could be further improved by rapidly sweeping the frequency of the signal used to excite the piezoelectric crystal. A heater in which the rear electrode of the piezoelectric crystal is sectioned into a series of concentric rings has also been developed. This heater can deposit more acoustical energy at the edges of a treatment volume than at the center, and the diameter of the ultrasound beam can also be adjusted. The results demonstrate that (i) the acoustical fields of ultrasound heaters must be accurately measured before using the heaters clinically, and that (ii) by careful design, both uniform or controlled nonuniform acoustical fields can be generated.

Hot Temperature↗

Development of an inductive, non-invasive RF applicator for studying hyperthermia in a rat brain tumour model.

A non-invasive inductive RF applicator has been designed specially for local heating of 6 mm diameter tumours growing in the brains of F344 rats (144-148 MHz). It is shown that an inductive applicator is the choice for this particular case. The power deposition pattern is analysed by modelling the applicator with a three-dimensional array of magnetic dipoles. The total hyperthermia system is briefly described and results of phantom and in vivo experimental measurements are presented. These confirm the theoretical analysis.

Animals↗

Rapid heating: critical theoretical assessment of thermal gradients found in hyperthermia treatments.

There is increasing evidence that many hyperthermia failures are closely related to the large variability of temperatures found in the treatment field. These are linked to thermal gradients near the treatment boundary, vascular perfusion differences, localized cooling, and poor distribution of energy deposition in the tissues. One way of reducing the temperature gradients is to replace traditional heating treatments of 30-60 min by a rapid heating technique, in which the treatment time is a few seconds combined with higher treatment temperatures. The purpose of this paper is to model potential advantages of using various rapid heating protocols, and to compare them with traditional treatments. Theoretical models (in agreement with clinical treatments) suggest that traditional hyperthermia treatments often do not produce the necessary temperature homogeneity needed to kill the last malignant cells in the tumour due to cooler regions in the field. The simulations presented in this paper suggest that much shorter treatment times (1-10 s) should give significant improvements in the treatment field for both the temperature homogeneity and equivalent thermal doses.

Hyperthermia, Induced↗

Observations of thermal gradients in perfused tissues during water bath heating.

Actual thermal gradients in perfused tissues are difficult to observe using thermocouples because of thermal conduction along the probes. We have used fine type-K (chromel-alumel) probes, which have a much lower thermal conductivity than equivalent-sized type-T (copper-constantan) thermocouples, to examine thermal gradients in two mouse tumour systems during water bath heating. The results indicate substantial heterogeneity in temperature distribution even in tumours transplanted in the foot and immersed to a depth of 2 cm in a 44 degrees C water bath for 20 min, i.e. thermal gradients greater than 1 degree C/mm were observed in KHT fibrosarcomas. The temperature heterogeneity for water bath heating is primarily a result of blood flow and appears to be tumour-specific. Temperature measurements using an excised perfused canine kidney demonstrate that increased perfusate volume flow increases the range of tissue temperatures. Consistent with theory, an artifactual improvement in temperature homogeneity resulted when temperature was measured using type-T thermocouples instead of type-K probes. These results emphasize the difficulties in obtaining accurate temperature measurements during experimental and clinical hyperthermia. Even extensive measurements of temperature in tissues may underestimate the true range of heterogeneity unless factors such as thermal smearing are controlled.

Animals↗

Differential thermal sensitivity of tumour and normal tissue microvascular response during hyperthermia.

The goal of this study was to investigate the heat sensitivity of the microcirculation in normal C3H murine leg muscle and a variety of transplanted tumour lines (KHT, SCC-VII, RIF-1, C3H mouse mammary carcinoma, two human mammary carcinomas MDA-468 and S5). Clearance rate of a radioactive tracer monitored following an intra-tissue injection was used as a measurement of microvascular integrity during heat treatment. Clearance rate in all tumours studied was significantly lower after 1 h of heating at 44 degrees C than the initial pretreatment clearance rate. Response of normal muscle differed from that of tumours in that the clearance rate after 1 h of heating at 44 degrees C was similar to the initial clearance rate. Vasculature in the KHT fibrosarcoma was more sensitive to heat treatment than that in other tumours. In response to a heat treatment at 43, 44, 45 and 46 degrees C the same level of microvascular damage occurred in half the time in KHT fibrosarcoma than in normal muscle. Furthermore, vascular damage in both muscle and KHT tumour followed the same relative isoeffect relationship, a 1 degree C change in temperature was equivalent to a change in heating time by a factor of two.

Animals↗

Effect of vascular occlusion on tumour temperatures during superficial hyperthermia.

Tumour temperature heterogeneity during hyperthermia has been attributed to irregular tumour vascular perfusion. We have compared temperature distributions in human tumours subjected to superficial hyperthermia under conditions of normal and occluded blood flow. Three patients with recurrent malignant melanoma on the leg were treated with radiation followed by hyperthermia 60-90 min later on days 1, 8 and 22. Heating (15-30 min) with normal blood flow was followed by 15 min of heating with tourniquet occlusion, although the tourniquet had to be intermittently released when the patients complained of discomfort. Hyperthermia was delivered using either a 1.4 MHz ultrasound or 915 MHz microwave applicator. Temperatures were monitored using superficial and interstitial thermometers in tumour and normal tissues. When the tourniquet was applied, the amount of power required to maintain peak temperatures was decreased by a factor of 3-10. With normal blood flow, there was a significant degree of temperature heterogeneity within the treatment volume, both within normal and tumour tissues, which improved with tourniquet application. The T90 and T50 indices increased both in normal tissues and tumour following the tourniquet occlusion, with the temperature increments being greater for normal tissues. Temperatures at depth were increased despite the reduction in applied power and the temperature profiles were smoother when the tourniquet was applied. No cutaneous, vascular or neuromuscular side effects were observed amongst these three subjects either acutely or at 1 month follow-up. These studies demonstrate directly that the temperature heterogeneity which exists in human tumours subjected to external heating can be reduced by occluding the blood supply.

Aged↗

The potential role of HSP70 as an indicator of response to radiation and hyperthermia treatments for recurrent breast cancer.

Twenty-three patients with recurrent breast cancer participating in a Phase III trial evaluating radiotherapy (XRT) with or without hyperthermia (HT) were included in a parallel study of heat shock protein (hsp) expression. The patients had core biopsies and/or fine needle aspirates (FNA) performed on their tumours, before and after treatment. These were analysed for hsp content using immunohistochemical staining with a monoclonal antibody to the inducible form of hsp 70. The proportion of samples containing identifiable cancer cells was greater for the core biopsy specimens (80%) than with FNA (60%). Staining intensity was analysed using either the majority score, i.e. the staining intensity (on a relative scale from 0 to 3) for the largest proportion of tumour cells, or the arithmetic score, which is the sum of the product of percentage of tumour cells and their staining intensity. The staining intensity for hsp's after treatment correlated inversely with the probability of attaining a complete response (CR). Specifically, the median and maximum scores for the biopsy specimens were significantly inversely related to the probability of attaining CR. The results suggest that this technique may be useful in predicting for thermotolerance development, though more data is needed to confirm the utility of the technique. Results from this study corroborate data from other clinical studies which suggest that tumours with elevated hsp levels may demonstrate resistant biologic behaviour.

Biopsy↗

The effects of artery occlusion on temperature homogeneity during hyperthermia in rabbit kidneys in vivo.

To investigate the role of arterial occlusion on temperature homogeneity during hyperthermia for deep seated tissue, a renal hyperthermia animal model has been established using New Zealand white rabbits. The effects of ultrasound-induced renal hyperthermia, with or without continuous and intermittent renal artery occlusion, were compared and analysed. Both continuous and intermittent occlusion showed certain protection of surrounding tissue and demonstrated improved temperature homogeneity and heating efficiency. The benefits of continuous vs. intermittent occlusion are compared and discussed as well.

Animals↗