Arthur E. Worthington

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.

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.

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.

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.

Determination of the optical properties of turbid media using relative interstitial radiance measurements: Monte Carlo study, experimental validation, and sensitivity analysis.

Interstitial quantification of the optical properties of tissue is important in biomedicine for both treatment planning of minimally invasive laser therapies and optical spectroscopic characterization of tissues, for example, prostate cancer. In a previous study, we analyzed a method first demonstrated by Dickey et al., [Phys. Med. Biol. 46, 2359 (2001)] to utilize relative interstitial steady-state radiance measurements for recovering the optical properties of turbid media. The uniqueness of point radiance measurements were demonstrated in a forward sense, and strategies were suggested for improving performance under noisy experimental conditions. In this work, we test our previous conclusions by fitting the P3 approximation for radiance to Monte Carlo predictions and experimental data in tissue-simulating phantoms. Fits are performed at: 1. a single sensor position (0.5 or 1 cm), 2. two sensor positions (0.5 and 1 cm), and 3. a single sensor position (0.5 or 1 cm) with input knowledge of the samples effective attenuation coefficient. The results demonstrate that single sensor radiance measurements can be used to retrieve optical properties to within approximately 20%, provided the transport albedo is greater than approximately 0.9. Furthermore, compared to the single sensor fits, employing radiance data at two sensor positions did not significantly improve the accuracy of recovered optical properties. However, with knowledge of the effective attenuation coefficient of the medium, optical properties can be retrieved experimentally to within approximately 10% for an albedo greater or equal to 0.5.

Towards understanding the nature of high frequency backscatter from cells and tissues: an investigation of backscatter power spectra from different concentrations of cells of different sizes

During cell death, a series of structural changes occur within the cell. We have shown that cell ensembles and tissues undergoing structural changes associated with various cell death pathways can be detected using high-frequency ultrasound. In our effort to understand better the nature of backscatter from collections of cells (which emulate tissues), we have collected raw RF backscatter data from cells of two different sizes (human acute myeloid leukemia, AML, cells and transformed prostate cells) in solutions for a series of concentrations or in pellet form. It was found that the backscatter power (as measured by the mid-band fit) increased by /spl sim/3 dB for both cell types in dilute solutions for which the volumetric concentration was doubled for a specific range of cell concentrations (which was dependent on cell size). In pellet form, the backscatter power from the prostate cell pellets was /spl sim/12-14 dB greater than the AML cell pellets. A comparison of the spectral slopes also strongly suggests a change in the scattering source contributions when the cells are in pellets: the spectral slope was negative for all concentrations for prostate cells imaged at 40 MHz, but positive when measured in pellets. This is consistent with an increased contribution to the backscatter of smaller sized scatterers (such as the cell nucleus) that manifests itself only when the cells are in pellets but not in solution. These data are compared to theoretical predictions and their significance discussed.

Ultrasound drug targeting to tumors with thermosensitive liposomes

Induction of local tissue hyperthermia is emerging as a valuable tool in cancer therapy, as temperatures between 39-43°C are sufficient to trigger release of drug from thermosensitive liposomes (TSL), but is not harmful to normal tissue. Despite significant advances in spatial and dynamic control of ultrasound, temperature profiles in heated tissues are never homogenous, and an ideal TSL should achieve complete local release over the entire hyperthermia range. We have developed a TSL exhibiting a sensitive temperature release profile (39-43°C) with excellent stability at 37°C. We prepared a TSL composed of DPPC lipid and Brij78 surfactant, and loaded this hyperthermia-activated-cytotoxic (HaT) TSL with doxorubicin (DOX). EMT-6 breast tumors located on a Balb/c mouse footpad were instantaneously heated to 42-43°C using a 3.9 MHz planar transducer: body temperature did not elevate above 37°C, and complete remission of the EMT-6 breast cancer tumors was observed. Mice treated with standard DOX chemotherapy (at same 10 mg/kg dose as HaT) did not exhibit any tumor inhibition effects compared to control mice. By histological examination, no physiological damage to normal tissues was induced by ultrasound heating, and mice treated with HaT DOX regained normal tissue appearance and function posttreatment. This study confirms the benefit of coupling ultrasound induced hyperthermia with a sensitive TSL formulation.

A high-resolution transrectal ultrasonographic system

Abstract The design of a transrectal echographical ultrasound system is described in this paper. This system produces high-quality, gray-scale images of the prostate, seminal vesicles and the bladder. A light, hand-held probe is inserted into the rectum. The probe is covered with a thin latex sheath which is filled with water to obtain excellent acoustic coupling with the wall of the rectum. The transducer, which is placed in the tip, rotates continuously, and this generates an ultrasound beam at 90° to the probe. A balanced arm can be coupled to the probe during this procedure to obtain better position stability and patient comfort. The transducer can be detached. Most of the work has been done for a 5 MHz transducer, but sometimes a 3.5 MHz transducer is used for greater penetration (≈ 9 cm). The transmitting and receiving systems contain unusual circuits. This includes a novel high-voltage pulser that generates the ultrasound pulse, and a simple but flexible variable time-gain control that adjusts the gain in echoes from different depths. A unique gray-scale phantom, that contains a mixture of lossy gel and reflecting objects, has been used routinely to check the performance of the transrectal scanner. This help is achieving excellent images of the prostate and seminal vesicles.

Characterization of changes in therapeutic ultrasound transducer performance over time using the angular spectrum method

Strongly focused large aperture transducers used in high-intensity focused ultrasound treatments are prone to manufacturing defects and degradation. Current methods for evaluating transducer quality measure only bulk physical changes of transducers. We have determined the pressure distribution at the transducer surface, using the angular spectrum method, to detect defects of the transducer. Three therapeutic transducers were investigated. The pressure distribution at the focal plane of each transducer was measured and input into a back-projection algorithm to calculate the pressure distribution at the transducer surface. A number of scan window sizes were used for the pressure distribution measurement at the focal plane to determine the effect on the resolution of the calculated pressure distribution at the transducer surface. Results showed that one transducer might have suffered manufacturing defects. The second transducer degraded over 1 year of use with one half of the transducer suffering a partial loss of efficiency. The third transducer remained unchanged over 1 year. The scan window of 40 mm times 40 mm at the focal plane was required to identify defects 6 mm in diameter on the transducer surface. The results demonstrate that the angular spectrum method could be a useful tool for evaluating transducer quality