Ultrasound properties of human prostate tissue during heating.

Changes in the ultrasound (US) properties of tissue during heating affect the delivery of US thermal therapy and may provide a basis for US image monitoring of thermal therapy. The US attenuation coefficient and backscatter power of fresh human prostate tissue were measured as the tissue was heated. Samples of human prostate were obtained directly from autopsies and heated rapidly to final temperatures of 45 degrees C, 50 degrees C, 55 degrees C, 60 degrees C and 65 degrees C. A 5.0-MHz transducer was scanned in a raster pattern over the tissue and radiofrequency (RF) data were collected at 36 uncorrelated positions. Both attenuation and backscatter were measured over the frequency range 3.5 to 7.0 MHz at each min of a 30-min heating. Little change was observed in attenuation or backscatter at 55 degrees C or less. The attenuation coefficient and backscatter power increased by factors of 1.25 and 5, respectively, during the 60 degrees C heating. During the 65 degrees C heating, the same properties showed increases by factors of 2.7 and 9.

Changes in ultrasound properties of porcine kidney tissue during heating.

Changes in the ultrasound (US) attenuation and backscatter of fresh pig kidney were measured as the tissue was heated. The objective was to use these changes to predict how an US image would change in real-time with a view to its use as a monitoring tool for minimally invasive thermal therapy (MITT). Separate samples of fresh pig kidney were heated from 37 degrees C to temperatures of 45 degrees, 50 degrees, 55 degrees, 60 degrees and 65 degrees with warm water. Measurements were made over the frequency range from 3.5 MHz to 7.0 MHz during 30-min heating experiments. A general increase in attenuation magnitude (dB/cm) and slope (dB/cm-MHz) was observed at temperatures of 55 degrees C or greater. Little change in backscatter power was observed during heating to 45 degrees C. At higher temperatures, the changes in backscatter showed a more complex pattern throughout the experiments, but still showed a trend of increase to a greater value at the end of heating than at the start. This backscatter increase was greater at higher temperatures. The net effect of the changes in US properties suggests that it may be possible to use diagnostic US to monitor, in real-time, MITT in kidney.

An investigation of the flow dependence of temperature gradients near large vessels during steady state and transient tissue heating.

Temperature distributions measured during thermal therapy are a major prognostic factor of the efficacy and success of the procedure. Thermal models are used to predict the temperature elevation of tissues during heating. Theoretical work has shown that blood flow through large blood vessels plays an important role in determining temperature profiles of heated tissues. In this paper, an experimental investigation of the effects of large vessels on the temperature distribution of heated tissue is performed. The blood flow dependence of steady state and transient temperature profiles created by a cylindrical conductive heat source and an ultrasound transducer were examined using a fixed porcine kidney as a flow model. In the transient experiments, a 20 s pulse of hot water, 30 degrees C above ambient, heated the tissues. Temperatures were measured at selected locations in steps of 0.1 mm. It was observed that vessels could either heat or cool tissues depending on the orientation of the vascular geometry with respect to the heat source and that these effects are a function of flow rate through the vessels. Temperature gradients of 6 degrees C mm(-1) close to large vessels were routinely measured. Furthermore, it was observed that the temperature gradients caused by large vessels depended on whether the heating source was highly localized (i.e. a hot needle) or more distributed (i.e. external ultrasound). The gradients measured near large vessels during localized heating were between two and three times greater than the gradients measured during ultrasound heating at the same location, for comparable flows. Moreover, these gradients were more sensitive to flow variations for the localized needle heating. X-ray computed tomography data of the kidney vasculature were in good spatial agreement with the locations of all of the temperature variations measured. The three dimensional vessel path observed could account for the complex features of the temperature profiles. The flow dependences of the transient temperature profiles near large vessels during the pulsed experiments were consistent with the temperature distributions measured in the steady state experiments and provided unique insights into the process of convective heat transfer in tissues. Finally, it was shown that even for very short treatment times (3-20 s), large vessels had significant effects on the tissue temperature distributions.

Experimental evaluation of two simple thermal models using transient temperature analysis.

Thermal models are used to predict temperature distributions of heated tissues during thermal therapies. Recent interest in short duration high temperature therapeutic procedures necessitates the accurate modelling of transient temperature profiles in heated tissues. Blood flow plays an important role in tissue heat transfer and the resultant temperature distribution. This work examines the transient predictions of two simple mathematical models of heat transfer by blood flow (the bioheat transfer equation model and the effective thermal conductivity equation model) and compares their predictions to measured transient temperature data. Large differences between the two models are predicted in the tissue temperature distribution as a function of blood flow for a short heat pulse. In the experiments a hot water needle, approximately 30 degrees C above ambient, delivered a 20 s heating pulse to an excised fixed porcine kidney that was used as a flow model. Temperature profiles of a thermocouple that primarily traversed the kidney cortex were examined. Kidney locations with large vessels were avoided in the temperature profile analysis by examination of the vessel geometry using high resolution computed tomography angiography and the detection of the characteristic large vessel localized cooling or heating patterns in steady-state temperature profiles. It was found that for regions without large vessels, predictions of the Pennes bioheat transfer equation were in much better agreement with the experimental data when compared to predictions of the scalar effective thermal conductivity equation model. For example, at a location r approximately 2 mm away from the source, the measured delay time was 10.6 +/- 0.5 s compared to predictions of 9.4 s and 5.4 s of the BHTE and ETCE models, respectively. However, for the majority of measured locations, localized cooling and heating effects were detected close to large vessels when the kidney was perfused. Finally, it is shown that increasing flow in regions without large vessels minimally perturbs temperature profiles for short exposure times; regions with large vessels still have a significant effect.

Ultrasound imaging of thermal therapy in in vitro liver.

The objective of this work was to image liver tissue heated to temperatures below the vaporization threshold as a function of time, to test the feasibility of real-time ultrasound monitoring to control lesion size during minimally invasive thermal therapy (MITT). Two experiments were devised. In one experiment, a thermal gradient was established in a rectangular volume of tissue to correlate changes in ultrasound image echogenicity (B-mode image brightness) with tissue temperature. In the other, a thermal lesion was produced in a rectangular volume of tissue by an interstitial microwave antenna, and the progression of the lesion was monitored by ultrasound. In both experiments, the echogenicity of the tissue increased slightly for tissue temperatures up to 40 degrees C, but became lower than that of unheated tissue for temperatures above 40 degrees C. In the second experiment, images of the lesion were compared with a photograph of the lesion taken after the experiment was complete. The final lesion was composed of two concentric regions--an inner region of heavily coagulated tissue and an outer region of less-damaged tissue. These two damaged regions indicated that increased ultrasound attenuation was largely responsible for the decreased echogenicity observed in the ultrasound images, and the increase in echogenicity of tissue heated to temperatures up to 40 degrees C is thought to be due to decreased ultrasound attenuation at these temperatures.

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.

Mechanism of ultrasound enhanced porphyrin cytotoxicity. Part I: A search for free radical effects.

Intense ultrasound beams may have the potential to treat malignant tumours when combined with sensitizers, often called sonodynamic agents. Some of these agents, e.g., the porphyrins, are currently used for photodynamic therapy. However, the experimental evidence for ultrasound activation of sensitizers is inconsistent. This paper attempts to discover whether they yield of free radicals such as .OH and .H, which are produced by transient cavitation, could explain the killing of Chinese hamster ovary (CHO) cells in vitro with and without sonodynamic agents. CHO cells were irradiated with ultrasound beams in phosphate-buffered saline or in growth medium, and the immediate cell lysis and loss of cell colony forming ability were measured. Under our specific conditions, in which the standing wave patterns were minimized, a general correlation was observed between the transient cavitation, free radical production, and cytotoxicity. However, the yield of free radicals was much too small to explain the cell killing observed. We conclude that cytotoxicity is not linked to attack from free radicals formed outside the cells. In our experiments, immediate cell lysis is closely linked to the transient cavitation, which is known to produce shear forces that disrupt cellular membranes. We hypothesize that the loss of cell colony forming ability is also linked to damage of cellular membranes.

The subtleties of ultrasound images of an ensemble of cells: simulation from regular and more random distributions of scatterers.

Significant differences in the backscatter amplitudes which are correlated with different tissue morphology have been observed in ultrasound images of tissue. While many factors could be linked to subtle changes in the images, the purpose of this paper is to explore the possibility that backscatter signals are linked to the organization of the spatial distribution of individual cells that produce an ensemble of scattering sources. Simple one- and two-dimensional simulations of backscatter signals produced by weak scatters separated by << lambda to < lambda in regular, random, and pseudo-random distributions in a "sample" are performed. Both regular and pseudo-random distributions produce large boundary signals, and in the central regions of the sample, the square root of the backscatter power is directly related to the amount of randomization, R, over a large range. Large changes in backscattering intensities are predicted for the same density of scatterers with differing R in different regions of the same sample. Thus, the subtle differences in the scattering distribution should show significant changes in the backscatter images.

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.